shuttle arylation by rh(i) catalyzed reversible carbon

doi.org/10.26434/chemrxiv.13122830.v1

Shuttle Arylation by Rh(I) Catalyzed Reversible Carbon–Carbon BondActivation of Unstrained AlcoholsMarius D. R. Lutz, Valentina C. M. Gasser, Bill Morandi

Submitted date: 21/10/2020 • Posted date: 22/10/2020Licence: CC BY-NC-ND 4.0Citation information: Lutz, Marius D. R.; Gasser, Valentina C. M.; Morandi, Bill (2020): Shuttle Arylation byRh(I) Catalyzed Reversible Carbon–Carbon Bond Activation of Unstrained Alcohols. ChemRxiv. Preprint.https://doi.org/10.26434/chemrxiv.13122830.v1

The advent of transfer hydrogenation and borrowing hydrogen reactions paved the way to manipulate simplealcohols in previously unthinkable manners and circumvent the need for hydrogen gas. Analogously, transferhydrocarbylation could greatly increase the versatility of tertiary alcohols. However, this reaction remainsunexplored because of the challenges associated with the catalytic cleavage of unactivated C–C bonds.Herein, we report a rhodium(I)-catalyzed shuttle arylation cleaving the C(sp2)–C(sp3) bond in unstrainedtriaryl alcohols via a redox-neutral β-carbon elimination mechanism. A selective transfer hydrocarbylation ofsubstituted (hetero)aryl groups from tertiary alcohols to ketones was realized, employing benign alcohols aslatent C-nucleophiles. All preliminary mechanistic experiments support a reversible β-carbonelimination/migratory insertion mechanism. In a broader context, this novel reactivity offers a new platform forthe manipulation of tertiary alcohols in catalysis.

File list (2)

download fileview on ChemRxivLutzetal_MS_new.pdf (1.22 MiB)

download fileview on ChemRxivLutzetal_SI.pdf (6.21 MiB)

http://doi.org/10.26434/chemrxiv.13122830.v1

https://chemrxiv.org/authors/Bill_Morandi/6724526

https://chemrxiv.org/ndownloader/files/25186484

https://chemrxiv.org/articles/preprint/Shuttle_Arylation_by_Rh_I_Catalyzed_Reversible_Carbon_Carbon_Bond_Activation_of_Unstrained_Alcohols/13122830/1?file=25186484



1

Shuttle Arylation by Rh(I) Catalyzed Reversible Carbon–Carbon Bond Activation

of Unstrained Alcohols

Authors:

Marius D. R. Lutz1, Valentina C. M. Gasser1 & Bill Morandi1*

1Laboratory of Organic Chemistry, Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich,

Switzerland.

*Corresponding author. Email: [email protected]

Abstract

The advent of transfer hydrogenation and borrowing hydrogen reactions paved the way to manipulate simple alco-

hols in previously unthinkable manners and circumvent the need for hydrogen gas. Analogously, transfer hydro-

carbylation could greatly increase the versatility of tertiary alcohols. However, this reaction remains unexplored

because of the challenges associated with the catalytic cleavage of unactivated C–C bonds. Herein, we report a

rhodium(I)-catalyzed shuttle arylation cleaving the C(sp2)–C(sp3) bond in unstrained triaryl alcohols via a redox-

neutral β-carbon elimination mechanism. A selective transfer hydrocarbylation of substituted (hetero)aryl groups

from tertiary alcohols to ketones was realized, employing benign alcohols as latent C-nucleophiles. All preliminary

mechanistic experiments support a reversible β-carbon elimination/migratory insertion mechanism. In a broader

context, this novel reactivity offers a new platform for the manipulation of tertiary alcohols in catalysis.

Main text

Catalytic reversible reactions have found widespread use in the chemical community, as highlighted by the broad

range of applications that alkene metathesis offers across the molecular sciences1–4. Another prominent example is

the transfer hydrogenation reaction, in which primary and secondary alcohols and ketones are interconverted by

formally shuttling a molecule of hydrogen, in lieu of using the hazardous gas (Fig. 1a, top)5. Many variants of this

concept have been developed over the years, including borrowing hydrogen reactions that transiently dehydrogen-

ate alcohols to construct new C–C bonds6–11. The analogous transfer hydrocarbylation reaction using tertiary alco-

hols would provide exciting new avenues for the synthesis and modification of these species; however, reversibly

cleaving and reforming a strong C–C bond represents a far more considerable challenge (Fig. 1a, bottom).

Methods to directly activate C–C bonds are attractive, as the substrates of interest can be functionalized without

the need to introduce reactive functional handles, such as halides, and some have been strategically used in total

synthesis12. When compared to the significant progress made in the functionalization of inert C–H bonds, catalytic

2

reactions to cleave strong C–C bonds selectively are scarce13,14. Reasons for their low reactivity compared to C–H

bonds can be found in their kinetic inertness, as the σ-orbital is highly directional and does not allow for significant

overlap with the d-orbitals of transition metals15,16.

Recently, several strategies to oxidatively cleave unstrained C–C bonds using directing groups have been de-

vised14,15,17–20, however, there are few reports of unbiased systems that proceed via redox-neutral β-carbon elimina-

tion16,18,21,22. While strategies to activate propargylic and allylic alcohols are well known, the activation of an un-

strained C(sp2)–C(sp3) bond remains challenging. We and others have reported cross-couplings of α,α-disubstituted

arylmethanols with alkene electrophiles via directed C–C bond activation forging new C–C bonds23–28. Despite

these, reports of selective C(sp2)–C(sp3) bond cleavage of alcohols without using a directing group are rare and

limited to specific substrate scaffolds designed to relieve internal strain or gain aromaticity29,30. A notable exception

is a Pd-catalyzed biaryl coupling of α,α-disubstituted arylmethanols and aryl bromides reported by Miura31,32.

Continuing our interest in developing catalytic reversible reactions33–37, we sought to develop a shuttle catalysis

reaction to interconvert tertiary alcohols and ketones via reversible C–C bond cleavage (Fig. 1a, bottom). Such a

reaction would parallel the widely employed transfer hydrogenation reaction between alcohols and ketones, with

the key difference being that a C–C bond would be cleaved and reformed instead of a C–H bond.

Besides the inherent challenge of catalyzing the cleavage of a C–C bond in a traditionally inert alcohol substrate

(Fig. 1b, top), it is worth noting that there are only a few examples of transition metal-catalyzed aryl additions onto

unactivated (i.e., aliphatic) ketones, even when employing traditional organoboron nucleophiles (Fig. 1b, bottom)38–

45. Reasons for the limited reports of insertions of ketones into late transition metal-carbon bonds include the high

bond strength of the C=O π-bond, increased steric hinderance compared to terminal monosubstituted α-olefins, and

the less favorable interaction between a soft late transition metal center and an alkoxide46. Thus, the development

of a shuttle catalysis approach to ketone arylation is contingent upon addressing two significant challenges in or-

ganometallic chemistry, namely the activation of unbiased C‒C bonds and the productive migratory insertion of a

M‒R species into ketone substrates. A shuttle arylation protocol overcoming these challenges would open new

research avenues that take advantage of reversible β-carbon elimination to parallel the ingenious reactions devel-

oped in the area of transfer hydrogenation and borrowing hydrogen reactions5–7,11. It would also pave the way for

catalytic alternatives to highly reactive stoichiometric Grignard and organolithium additions. Crucial to unlocking

the desired reactivity is the identification of a suitable catalyst that can lower the activation barrier of the key

transition state for C–C bond cleavage, which is identical to the one for C–C bond formation by virtue of the

microscopic reversibility principle (Fig. 1b, right).

Herein, we describe a reversible catalytic shuttle arylation reaction between triaryl alcohols and aliphatic ketones,

by cleaving and reforming strong C–C bonds (Fig. 1c). The reaction does not require directing groups or destabili-

zation of the alcohol substrates and proceeds in the presence of a range of polar functional groups. Various aliphatic

cyclic and linear ketones, including pharmaceuticals, could be arylated in good yields using this method.

3

Fig. 1. Context of this work. a, Transfer hydrogenation is a widely employed reaction to interconvert 1° and 2°

alcohols and carbonyl compounds. An analogous transfer hydrocarbylation of 3° alcohols is unknown. b, Two main

challenges, namely activation of the C(sp2)–C(sp3) bond in the alcohol and productive insertion into the ketone,

have to be overcome to unlock the desired reactivity. Our strategy is to lower the barrier of the key transition state

that occurs during both key steps. c, This work: Development of a catalytic shuttle arylation reaction between 3°

alcohols and ketones.

Results

Catalyst evaluation and reaction development. Inspired by stoichiometric β-carbon elimination studies from

rhodium(I) alkoxide complexes by Hartwig and co-workers47–49, we envisaged that tuning the steric environment

around the metal center to stabilize reactive, low coordinated complexes could unlock a catalytic transfer arylation

tolerating a range of unbiased scaffolds. We began our studies with triphenylmethanol (1a) and 4,4'-difluorobenzo-

phenone (2) as model substrates in the presence of [Rh(cod)Cl]2 and a weak base in toluene at 110 °C. Initially, a

panel of ligands was evaluated, and several conditions promoted benzophenone (3a) formation by β-carbon elimi-

nation but only trace amounts of alcohol product 4 were observed. After extensive reaction optimization, suitable

conditions for the transfer of the phenyl group were identified (see Supplementary Information section 2 'Reaction

4

development' for details). NHC ligands effected β-carbon elimination of 1a towards benzophenone (3a) and facili-

tated productive insertion of the aryl group into ketone 2. Among all NHC ligands tested, the electron-rich and

sterically demanding ligand IPr*OMe was identified as the optimal ligand for this transformation (Fig. 2a)50. Inter-

estingly, the major product was not triaryl alcohol 4, but diaryl ketone 5, which is formed through subsequent β-

aryl elimination of the more electron-withdrawing group from the transiently generated alcohol 4 over the course

of the reaction. After 48 h nearly full conversion of both alcohols 1a and 4 towards the ketones 3a and 5, and

(fluoro)benzene was observed.

In an effort to avoid downstream reactions of the desired alcohol product, we next sought ways to take advantage

of this unique reactivity to develop a synthetically attractive reaction. We reasoned that using an aliphatic ketone

as acceptor would be beneficial because: 1) the tertiary alcohol product would likely not have the ability to scramble

through cleavage of a strong C(sp3)–C(sp3) bond, preventing undesired crossover reactions; 2) the overall transfer

reaction would likely be exothermic due to the formation of a conjugated ketone by-product as driving force (DFT

predicts ΔG = −4.0 kcal mol-1), while no deconjugation of the acceptor substrate (aliphatic ketone) would take place

(see Supplementary Information section 7 'Computational studies' for details). Indeed, the reaction of 1a and 4,4-

dimethylcyclohexanone (6a) worked efficiently and reached full conversion with only marginal excess (1.5 equiv.)

of the donor (Fig. 2b). The desired alcohol product 7a was obtained in excellent yield, while 1a was converted into

ketone 3a and benzene as a side product (by protodemetalation). Control experiments confirmed the essential role

of the catalyst and a weak base. Sterically encumbered NHC ligands resulted in the highest yield, but other ligands

also effected product formation. Notably, the reaction could even be conducted at 0.5 mol% catalyst loading, albeit

with prolonged reaction time.

5

Fig. 2. Reaction development. a, Proof of concept of a catalytic reversible shuttle arylation reaction. Reaction

conditions: 1a (0.10 mmol), 2 (0.10 mmol), [Rh(cod)Cl]2 (2.5 mol%), IPr*OMe ∙ HBF4 (5 mol%), KOtBu (5 mol%)

and K3PO4 (1 equiv.) in toluene (0.2 M) at 125 °C for 24 h. GC-FID yields using n-dodecane as an internal standard.

b, Catalytic aryl transfer to aliphatic ketones. Reaction conditions: 1a (0.15 mmol), 6a (0.10 mmol), [Rh(cod) Cl]2

(2.5 mol%), IPr*OMe ∙ HBF4 (5 mol%), KOtBu (5 mol%) and K3PO4 (1 equiv.) in toluene (0.2 M) at 125 °C for 24 h. aGC-FID yields using n-dodecane as an internal standard. bIsolated yield after purification. c72 hours.

Substrate scope. After finding the optimal conditions, we investigated the generality and utility of this transfor-

mation. A range of cyclic (6a-b) and linear (6d-e) aliphatic ketones were efficiently arylated to afford the corre-

sponding tertiary alcohols in good yields (Fig. 3a). Acetophenone could also be arylated, albeit the formation of

product 7c was reversible, leading to a diminished yield. Several functional groups were found to be compatible

with the reaction conditions, such as acetal-protected ketones (7f), protected amines (7g), ethers (7h), and sulfones

(7i). Notably, both carboxylic esters (7k-l) and amides (7m) remained untouched. Cross-coupling handles such as

aryl silanes (7j) and chlorides (7n) remained unchanged, offering the potential for orthogonal synthetic manipula-

tion. The arylation also proved to be effective in the presence of a heterocyclic residue (7o). Drug molecules, such

as nabumetone and pentoxifylline, underwent arylation in good yields (7p-q), demonstrating the potential for late-

stage derivatization of bioactive compounds. Sterically hindered ketones were unreactive under the reaction condi-

tions, which might indicate that bulky ketones are unable to approach the sterically encumbered catalyst (Supple-

mentary Table S12).

Subsequently, we turned our focus to the alcohol scope. We first investigated several symmetrical triaryl alcohols

1 (Fig. 3b). A range of alkyl-substituted alcohols (8a-c) and a 2-naphthyl group (8d) were suitable donor molecules,

affording the desired alcohols in good to excellent yield. Moreover, several common functional groups were toler-

ated, such as fluoro (8e), chloro (8f), methoxy (8g), trifluoromethyl (8h, 8j), and trifluoromethoxy (8i) groups. The

reaction was efficient with both electron-rich and -deficient donors, albeit the yield of 8g and 8j was limited due to

fast consumption of the alcohol starting material via protodemetalation. Notably, heterocyclic scaffolds were well

tolerated under the reaction conditions and allowed the transfer of 1,3-benzodioxolane (8k), benzofurane (8l-m),

and morpholine (8n) moieties.

Beyond triaryl alcohols, we investigated the propensity of other alcohols to undergo β-carbon elimination (Fig. 3c).

1,1-Diphenylethanol (1p) afforded product 9a in moderate yield, because the formation of the by-product aceto-

phenone is reversible (7c, vide supra). Excitingly, a 2° alcohol (1q) could be engaged to afford the product 9b in a

promising yield, showing potential for productive β-carbon elimination in the presence of a competing β-hydride.

We surmise that rapid and reversible β-hydride elimination occurs under the reaction conditions, yet the final for-

mation of the desired tertiary alcohol kinetically traps the occasionally formed β-carbon elimination intermediate,

hence slowly driving the mixture towards the desired product. This result thus suggests the possibility to merge

complex sequences of reversible β-hydride and β-carbon eliminations, opening new avenues for the manipulation

of alcohols in catalysis.

To further showcase the scalability and robustness of this reaction, the transfer arylation of 1a and 6d was conducted

on 10 mmol scale with a reduced catalyst loading of 1 mol% (Fig. 3d). The alcohol product 7d' was obtained in

6

70% yield after purification. The second product, benzophenone (3a'), was recovered in 77% with respect to 1a, or

116% based on the limiting reagent 6d.

8

Fig. 3. Substrate scope of the shuttle arylation. a, Scope of ketones. b, Scope of symmetric alcohols. c, Scope of

asymmetric alcohols. d, Scale-up at reduced catalyst loading. aRatio determined by 1H NMR of the crude reaction

mixture.

Preliminary mechanistic studies. After demonstrating the synthetic versatility of this protocol, we performed ex-

periments to investigate the reaction's reversibility. To confirm that β-carbon elimination is reversible for triaryl

alcohols 1, diaryl ketone 3b was added to the reaction mixture of 1a and 6a (Fig. 4a). Incorporation of both the

phenyl group (red) and the p-tolyl group (blue) into 6a was observed in a 4.9 : 1 ratio, together with a mixture of

all three possible diaryl ketones, confirming that addition into diaryl ketone 3b is reversible and has a similar rate

to the addition into aliphatic ketone 6a.

To evaluate the reversibility of the reaction in the case of (dialkyl)aryl alcohols 7, alcohol trans-7b and benzophe-

none (3a) were subjected to the reaction conditions (Fig. 4b). Notably, isomerization to the more stable cis-isomer

and small amounts of ketone 6b were observed, highlighting that β-aryl elimination from (dialkyl)aryl alcohols also

takes place, albeit the reaction rate is much lower than for triaryl alcohols.

To gain insight into the electronic preference of β-aryl elimination, intermolecular competition experiments with

two symmetrical triaryl alcohols were carried out (Fig. 4c). Interestingly, both electron-rich and -deficient substi-

tuted aryl groups were preferentially cleaved compared to phenyl, with no correlation between the electronic char-

acter and the observed selectivity. Notably, a similar trend was observed in Pd-catalyzed β-aryl elimination51. The

interpretation of these results is, however, complicated by the partial reversibility of the addition of one aryl group

to another diaryl ketone by-product leading to crossover products (see Fig. 4a).

We next independently synthesized the complex [Rh(IPr*OMe)(cod)Cl] (10) that is presumedly formed in situ (Fig.

4d). The complex was catalytically competent, effectively giving the same yield of product (Supplementary Table

S6). The crystal structure obtained by X-ray diffraction of the air-stable complex illustrates the steric encumbrance

of the NHC ligand around the substrate binding site. The steric influence of the ligand was parameterized by its

buried volume (Vbur)52. While the buried volume of IPr*OMe is slightly larger than that of IPr at 3.5 Å radius (Vbur =

37.2% versus 33.6%), its reach extends further in the periphery (Vbur = 46.4% versus 38.6% at 5.5 Å).

Based on these preliminary observations, we propose the following reversible catalytic cycle (Fig. 4e). Ligand

exchange of complex I (10) with the alcohol substrate followed by dissociation of a cod ligand creates the presumed

catalytically active species II. As in the case of β-hydride elimination, an empty coordination site is a requisite for

β-carbon elimination to occur. The coordinatively unsaturated Rh center in II likely interacts with one of the aryl

rings in a η2-fashion, as has been shown in X-ray structures of related complexes47, thereby facilitating the C–C

bond cleavage. Aryl complex III then undergoes reversible ketone exchange to form complex IV that in turn un-

dergoes migratory insertion into the ketone to form alkoxide complex V. Every step in the catalytic cycle is reversi-

ble according to our findings. Finally, alcohol exchange closes the cycle.

9

Fig. 4. Preliminary mechanistic experiments and proposed catalytic cycle. a, β-Aryl elimination from triaryl

alcohols is reversible, resulting in two alcohol products via scrambling. b, β-Aryl elimination from di(alkyl)aryl

alcohols is feasible but occurs at a low rate. c, Intermolecular competition experiments show no correlation between

the electronic character of the cleaved aryl group and product selectivity. d, The catalytically active complex 10

was independently synthesized and characterized by X-ray crystallography. The NHC ligand displays a large buried

volume in the periphery. e, Proposed catalytic cycle.

10

Conclusions

In summary, we have developed a catalytic shuttle arylation reaction that cleaves unactivated C(sp2)–C(sp3) bonds

in unstrained alcohols and arylates unactivated aliphatic ketones. This is the first example of a reversible transfer

hydrocarbylation reaction that parallels the ubiquitous transfer hydrogenation reaction of secondary alcohols and

carbonyl acceptors. Using this method, triaryl alcohols can be used as latent nucleophilic aryl sources for tradition-

ally challenging catalytic additions to ketones. Preliminary mechanistic studies point towards reversible C–C bond

activation as a key factor in enabling this process. In a broader context, this novel reactivity offers numerous op-

portunities for the creative use of tertiary alcohols in synthesis which parallel major achievements made in transfer

hydrogenation and borrowing hydrogen.

Data availability

Materials and methods, experimental procedures, detailed optimization studies, mechanistic studies and NMR spec-

tra are available in the Supplementary Information or from the corresponding author upon reasonable request. Crys-

tallographic data for compounds 7a, cis-7b and 10 are available free of charge from the Cambridge Crystallographic

Data Centre under deposition numbers 2035749, 2035750 and 2035751. Copies of the data can be obtained free of

charge via https://www.ccdc.cam.ac.uk/structures/.

References

1. Grubbs, R. H. Handbook of Metathesis. (Wiley-VCH, 2003).

2. Fürstner, A. Olefin Metathesis and Beyond. Angew. Chem. Int. Ed. 39, 3012–3043 (2000).

3. Schrock, R. R. & Hoveyda, A. H. Molybdenum and tungsten imido alkylidene complexes as efficient olefin-

metathesis catalysts. Angew. Chem. Int. Ed. 42, 4592–4633 (2003).

4. Ogba, O. M., Warner, N. C., O’Leary, D. J. & Grubbs, R. H. Recent advances in ruthenium-based olefin

metathesis. Chem. Soc. Rev. 47, 4510–4544 (2018).

5. Wang, D. & Astruc, D. The Golden Age of Transfer Hydrogenation. Chem. Rev. 115, 6621–6686 (2015).

6. Hamid, M. H. S. A., Slatford, P. A. & Williams, J. M. J. Borrowing hydrogen in the activation of alcohols.

Adv. Synth. Catal. 349, 1555–1575 (2007).

7. Corma, A., Navas, J. & Sabater, M. J. Advances in One-Pot Synthesis through Borrowing Hydrogen

Catalysis. Chem. Rev. 118, 1410–1459 (2018).

8. Dobereiner, G. E. & Crabtree, R. H. Dehydrogenation as a substrate-activating strategy in homogeneous

transition-metal catalysis. Chem. Rev. 110, 681–703 (2010).

9. Zbieg, J. R., Yamaguchi, E., McInturff, E. L. & Krische, M. J. Enantioselective C-H crotylation of primary

alcohols via hydrohydroxyalkylation of butadiene. Science 336, 324–327 (2012).

10. Goldman, A. S. et al. Catalytic alkane metathesis by tandem alkane dehydrogenation-olefin metathesis.

Science 312, 257–261 (2006).

11. Gunanathan, C. & Milstein, D. Applications of acceptorless dehydrogenation and related transformations in

chemical synthesis. Science 341, 257–261 (2013).

12. Wang, B., Perea, M. A. & Sarpong, R. Transition‐Metal‐Mediated Cleavage of C−C Single Bonds: Making

the Cut in Total Synthesis. Angew. Chem. Int. Ed. 59, 2–24 (2020).

13. Miura, M. & Satoh, T. Catalytic Processes Involving β-Carbon Elimination. Palladium in Organic

Synthesis. Topics in Organometallic Chemistry (Springer, 2005).

14. Dong, G. C-C Bond Activation. (Springer, 2014).

15. Rybtchinski, B. & Milstein, D. Metal Insertion into C−C Bonds in Solution. Angew. Chem. Int. Ed. 38, 870–

883 (1999).

16. Lutz, M. D. R. & Morandi, B. Metal-Catalyzed Carbon–Carbon Bond Cleavage of Unstrained Alcohols.

11

Chem. Rev. http://dx.doi.org/10.1021/acs.chemrev.0c00154 (2020).

17. Jun, C.-H. Transition metal-catalyzed carbon–carbon bond activation. Chem. Soc. Rev. 33, 610–618 (2004).

18. Chen, F., Wang, T. & Jiao, N. Recent Advances in Transition-Metal-Catalyzed Functionalization of

Unstrained Carbon–Carbon Bonds. Chem. Rev. 114, 8613–8661 (2014).

19. Souillart, L. & Cramer, N. Catalytic C-C Bond Activations via Oxidative Addition to Transition Metals.

Chem. Rev. 115, 9410–9464 (2015).

20. Xia, Y. & Dong, G. Temporary or removable directing groups enable activation of unstrained C–C bonds.

Nature Reviews Chemistry 1–15 (2020).

21. Murakami, M. Cleavage of Carbon-Carbon Single Bonds by Transition Metals. (Wiley-VCH, 2015).

22. Song, F., Gou, T., Wang, B.-Q. & Shi, Z.-J. Catalytic activations of unstrained C–C bond involving

organometallic intermediates. Chem. Soc. Rev. 47, 7078–7115 (2018).

23. Li, H. et al. Pyridinyl directed alkenylation with olefins via Rh(III)-catalyzed C-C bond cleavage of

secondary arylmethanols. J. Am. Chem. Soc. 133, 15244–15247 (2011).

24. Chen, K. et al. Direct oxidative arylation via rhodium-catalyzed C-C bond cleavage of secondary alcohols

with arylsilanes. Chem. Sci. 3, 1645–1649 (2012).

25. Zhang, X.-S. et al. Rh-Catalyzed C-C Cleavage of Benzyl/Allylic Alcohols to Produce Benzyl/Allylic

Amines or other Alcohols by Nucleophilic Addition of Intermediate Rhodacycles to Aldehydes and Imines.

Chem. Eur. J. 18, 16214–16225 (2012).

26. Ozkal, E., Cacherat, B. & Morandi, B. Cobalt(III)-Catalyzed Functionalization of Unstrained Carbon-

Carbon Bonds through β-Carbon Cleavage of Alcohols. ACS Catal. 5, 6458–6462 (2015).

27. Wang, H., Choi, I., Rogge, T., Kaplaneris, N. & Ackermann, L. Versatile and robust C–C activation by

chelation-assisted manganese catalysis. Nat. Catal. 1, 993–1001 (2018).

28. Qiu, Y., Scheremetjew, A. & Ackermann, L. Electro-Oxidative C–C Alkenylation by Rhodium(III)

Catalysis. J. Am. Chem. Soc. 141, 2731–2738 (2019).

29. Nishimura, T., Katoh, T. & Hayashi, T. Rhodium-catalyzed aryl transfer from trisubstituted aryl methanols

to α,β-unsaturated carbonyl compounds. Angew. Chem. Int. Ed. 46, 4937–4939 (2007).

30. Deng, R., Xi, J., Li, Q. & Gu, Z. Enantioselective Carbon-Carbon Bond Cleavage for Biaryl Atropisomers

Synthesis. Chem 5, 1834–1846 (2019).

31. Terao, Y., Wakui, H., Satoh, T., Miura, M. & Nomura, M. Palladium-Catalyzed Arylative Carbon−Carbon

Bond Cleavage of α,α-Disubstituted Arylmethanols. J. Am. Chem. Soc. 123, 10407–10408 (2001).

32. Terao, Y. et al. Palladium-catalyzed arylation of α,α-disubstituted arylmethanols via cleavage of a C-C or a

C-H bond to give biaryls. J. Org. Chem. 68, 5236–5243 (2003).

33. Bhawal, B. N. & Morandi, B. Catalytic transfer functionalization through shuttle catalysis. ACS Catal. 6,

7528–7535 (2016).

34. Lian, Z., Bhawal, B. N., Yu, P. & Morandi, B. Palladium-catalyzed carbon-sulfur or carbon-phosphorus

bond metathesis by reversible arylation. Science 356, 1059–1063 (2017).

35. Xianjie, F., Yu, P. & Morandi, B. Catalytic reversible alkene-nitrile interconversion through controllable

transfer hydrocyanation. Science 351, 832–836 (2016).

36. Bhawal, B. N. & Morandi, B. Catalytic Isofunctional Reactions—Expanding the Repertoire of Shuttle and

Metathesis Reactions. Angew. Chem. Int. Ed. 58, 10074–10103 (2019).

37. Bhawal, B. N., Reisenbauer, J. C., Ehinger, C. & Morandi, B. Overcoming Selectivity Issues in Reversible

Catalysis: A Transfer Hydrocyanation Exhibiting High Kinetic Control. J. Am. Chem. Soc. 142, 10914–

10920 (2020).

38. Liu, Y.-L. & Lin, X.-T. Recent Advances in Catalytic Asymmetric Synthesis of Tertiary Alcohols via

Nucleophilic Addition to Ketones. Adv. Synth. Catal. 361, 876–918 (2019).

39. Ueura, K., Miyamura, S., Satoh, T. & Miura, M. Rhodium-catalyzed addition of arylboron compounds to

nitriles, ketones, and imines. J. Organomet. Chem. 691, 2821–2826 (2006).

40. Liao, Y.-X., Xing, C.-H. & Hu, Q.-S. Rhodium(I)/Diene-Catalyzed Addition Reactions of Arylborons with

Ketones. Org. Lett. 14, 1544–1547 (2012).

41. White, J. R., Price, G. J., Plucinski, P. K. & Frost, C. G. The rhodium-catalysed 1,2-addition of arylboronic

acids to aldehydes and ketones with sulfonated S-Phos. Tetrahedron Lett. 50, 7365–7368 (2009).

42. Huang, L. et al. Highly Enantioselective Rhodium-Catalyzed Addition of Arylboroxines to Simple Aryl

Ketones: Efficient Synthesis of Escitalopram. Angew. Chem. Int. Ed. 55, 4527–4531 (2016).

43. Gallego, G. M. & Sarpong, R. Rh(I)-catalyzed enantioselective intramolecular hydroarylation of unactivated

ketones with aryl pinacolboronic esters. Chem. Sci. 3, 1338–1342 (2012).

44. Korenaga, T., Ko, A., Uotani, K., Tanaka, Y. & Sakai, T. Synthesis and application of 2,6-

12

bis(trifluoromethyl)-4-pyridyl phosphanes: The most electron-poor aryl phosphanes with moderate

bulkiness. Angew. Chem. Int. Ed. 50, 10703–10707 (2011).

45. Hatano, M. & Ishihara, K. Recent progress in the catalytic synthesis of tertiary alcohols from ketones with

organometallic reagents. Synth. 1647–1675 (2008).

46. Krug, C. & Hartwig, J. F. Reactions of an arylrhodium complex with aldehydes, imines, ketones, and

alkynones. New classes of insertion reactions. Organometallics 23, 4594–4607 (2004).

47. Zhao, P., Incarvito, C. D. & Hartwig, J. F. Direct observation of β-aryl eliminations from Rh(I) alkoxides.

J. Am. Chem. Soc. 128, 3124–3125 (2006).

48. Zhao, P., Incarvito, C. D. & Hartwig, J. F. Carbon-oxygen bond formation between a terminal alkoxo ligand

and a coordinated olefin. Evidence for olefin insertion into a rhodium alkoxide. J. Am. Chem. Soc. 128,

9642–9643 (2006).

49. Zhao, P. & Hartwig, J. F. Insertions of ketones and nitriles into organorhodium(i) complexes and β-

hydrocarbyl eliminations from rhodium(I) alkoxo and iminyl complexes. Organometallics 27, 4749–4757

(2008).

50. Meiries, S., Speck, K., Cordes, D. B., Slawin, A. M. Z. & Nolan, S. P. [Pd(IPr*OMe)(acac)Cl]: Tuning the

N-Heterocyclic Carbene in Catalytic C–N Bond Formation. Organometallics 32, 330–339 (2013).

51. Bour, J. R., Green, J. C., Winton, V. J. & Johnson, J. B. Steric and electronic effects influencing β-aryl

elimination in the Pd-catalyzed carbon-carbon single bond activation of triarylmethanols. J. Org. Chem. 78,

1665–1669 (2013).

52. Clavier, H. & Nolan, S. P. Percent buried volume for phosphine and N-heterocyclic carbene ligands: steric

properties in organometallic chemistry. Chem. Commun. 46, 841 (2010).

Acknowledgements

We thank the European Research Council (ERC Grant 757608 ShuttleCat), the Swiss National Science Foundation

(SNF 184658) and the ETH Zürich for financial support. M.D.R.L. is grateful for funding from the German Aca-

demic Scholarship Foundation. We thank the NMR service, the Molecular and Biomolecular Analysis Service (Mo-

BiAS) and X-ray departments of ETH Zürich for technical assistance. We thank the Morandi group members for

critical proof reading of the manuscript.

Author contributions

M.L. and B.M. conceived the project. M.L. discovered and developed the reaction; M.L. and V.G. conducted the

synthetic studies. All authors contributed to the writing and editing of the manuscript.

Competing interests

The authors declare no competing interests.

download fileview on ChemRxivLutzetal_MS_new.pdf (1.22 MiB)



Supporting Information

Shuttle Arylation by Rh(I) Catalyzed Reversible

Carbon–Carbon Bond Activation of Unstrained

Alcohols

Marius D. R. Lutz, Valentina C. M. Gasser, Bill Morandi∗

ETH Zürich, Vladimir-Prelog-Weg 3, HCI, 8093, Zürich, Switzerland

*Corresponding author. Email: [email protected]

Contents

Supplementary Methods S4

1 General information S4

2 Reaction development S5

2.1 Optimization of transfer arylation between an aromatic alcohol and an aromatic ketone . . . S5

2.2 Optimization of transfer arylation between an aromatic alcohol and an aliphatic ketone . . S10

2.3 Evaluation of other alcohol donors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . S15

3 Synthesis and characterization of starting materials S15

3.1 Synthesis of ketone starting materials . . . . . . . . . . . . . . . . . . . . . . . . . . . . S15

3.2 Synthesis of alcohol starting materials . . . . . . . . . . . . . . . . . . . . . . . . . . . . S20

4 Substrate scope S29

4.1 Ketone side . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . S30

4.2 Alcohol side . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . S36

4.3 Unsymmetrical alcohols . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . S41

4.4 Scale-up . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . S42

4.5 Substrate limitations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . S43

4.6 Not isolated products . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . S44

S1

[email protected]

Contents Supporting Information

5 Mechanistic investigation S45

5.1 Intermolecular competition experiments . . . . . . . . . . . . . . . . . . . . . . . . . . . S45

5.2 Reversibility experiments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . S46

5.2.1 Triaryl alcohol + dialkyl ketone + diaryl ketone cross-over . . . . . . . . . . . . . S46

5.2.2 Reverse reaction: dialkyl alcohol + diaryl ketone . . . . . . . . . . . . . . . . . . S48

5.2.3 Aryl scrambling by reversible β -carbon elimination . . . . . . . . . . . . . . . . . S51

5.3 Synthesis and characterization of organometallic compounds . . . . . . . . . . . . . . . . S53

5.3.1 Preparation of complex 10 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . S53

6 X-ray data S54

6.1 Compound 7a . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . S56

6.2 Compound cis-7b . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . S57

6.3 Complex 10 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . S58

6.3.1 Structure discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . S59

6.3.2 Space-Filling Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . S60

6.3.3 Calculations of Percent Buried Volume (%Vbur) . . . . . . . . . . . . . . . . . . . S60

7 Computational studies S61

7.1 Cartesian Coordinates and Energies of Structures . . . . . . . . . . . . . . . . . . . . . . S63

8 References S67

Appendix S71

A NMR spectra S71

S2

List of Supplementary Tables Supporting Information

List of Supplementary Figures

S1 Cross-over between diaryl ketone and alkyl ketone. . . . . . . . . . . . . . . . . . . . . . . S46

S2 GC chromatogram after reaction of alcohol 1a with alkyl ketone 6a and diaryl ketone 3b. . . S47

S3 Reversibility of β -aryl elimination from an dialkyl alcohol. . . . . . . . . . . . . . . . . . . S48

S4 GC chromatogram after reaction of alcohol trans-7b and ketone 3a. . . . . . . . . . . . . . S49

S5 Reversibility of β -aryl elimination from an dialkyl alcohol. . . . . . . . . . . . . . . . . . . S49

S6 GC chromatogram after reaction of alcohol cis-7b and ketone 3a. . . . . . . . . . . . . . . . S50

S7 Scrambling of triaryl alcohols and diaryl ketones. . . . . . . . . . . . . . . . . . . . . . . . S51

S8 GC chromatogram after reaction between alcohol 1b and ketone 3c. . . . . . . . . . . . . . S52

S9 GC chromatogram after reaction between alcohol 1c and ketone 3b . . . . . . . . . . . . . . S52

S10 Displacement ellipsoid plot of 10. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . S59

S11 Space-Filling Model of [Rh(IPr*OMe)(cod)Cl] (10). . . . . . . . . . . . . . . . . . . . . . . S60

S12 Steric Maps of L24 and L30 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . S61

S13 Gibbs free energy change for the transfer arylation between 1a and 2. . . . . . . . . . . . . S62

S14 Gibbs free energy change for the cleavage of 4 to 5 and fluorobenzene. . . . . . . . . . . . . S62

S15 Gibbs free energy change for the overall reaction of 1a and 2 to 5 and fluorobenzene. . . . . S62

S16 Gibbs free energy change for the transfer arylation between 1a and 6a. . . . . . . . . . . . . S62

S17 Gibbs free energy change for the transfer arylation between PhMe2COH and 6a. . . . . . . . S62

List of Supplementary Tables

S1 Initial ligand screening. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . S6

S2 Base screening. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . S8

S3 NHC ligand screening. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . S9

S4 NHC ligand screening at higher temperature. . . . . . . . . . . . . . . . . . . . . . . . . . S10

S5 Ligand screening. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . S11

S6 Ligand screening at higher temperature. . . . . . . . . . . . . . . . . . . . . . . . . . . . . S12

S7 Rh-precursor screening. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . S13

S8 Base screening. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . S13

S9 Temperature screening. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . S14

S10 Catalyst loading screening. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . S14

S11 Donor screening. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . S15

S12 Incompatible acceptor substrates. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . S44

S13 Incompatible donor substrates. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . S44

S14 Not isolated substrates. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . S45

S15 Intermolecular competition. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . S46

S3

1 General information Supporting Information

1 General information

General methods All air- and moisture-sensitive manipulations were carried out using Schlenk techniques

under nitrogen or in an MBraun LABmaster Pro SP glovebox under an argon atmosphere with a Teflon-coated

magnetic stirring bar unless otherwise noted. Nitrogen was dried using a drying tube equipped with Drierite™

unless otherwise noted. All glassware was stored in a pre-heated oven prior to use. For the reactions carried

out at elevated temperature, an aluminum heating block was used. Yields refer to chromatographically and

spectroscopically (1H-NMR) homogeneous material, unless otherwise stated. Reactions were monitored by

GC/MS, and thin layer chromatography (TLC).

Chemicals Chemicals were purchased from common suppliers and used without further purification, unless

noted else. Chloro(1,5-cyclooctadiene)rhodium(I) dimer ([Rh(cod)Cl]2) was purchased from ABCR and was

stored in a Glovebox. Anhydrous potassium phosphate tribasic (K3PO4) was purchased from Sigma-Aldrich

and stored in a Glovebox. NHC ligands SIPrMe (L21)1, SIPrPh (L22)2, IPrMe (L25)2, CAAC-5 (L28)3,

IPr* (L29)4, IPr*OMe (L30)5 were prepared as previously reported. All other ligands were purchased from

commercial sources.

Solvents The solvents used for air and moisture-sensitive manipulations were dried and deoxygenated us-

ing literature procedures.6 Toluene (PhMe), tetrahydrofuran (THF), dichloromethane (CH2Cl2), and hexane

were obtained by passing the previously degassed solvents through an activated alumina column. The sub-

strates and reagents for catalytic reactions were degassed and stored in the glovebox over activated molecular

sieves. Deuterated organic solvents were distilled over sodium (toluene-d8) or CaH2 (CD2Cl2) before use.

Liquid Chromatography Analytical thin layer chromatography (TLC) was performed on Merck silica

gel 60 F254 glass-backed plates and alcohol coupling products were mainly visualized by UV light or

staining with cerium ammonium molybdate (CAM) stain. Other products were visualized under UV light

or by potassium permanganate stain (KMnO4). For purification via flash column chromatography, silica

gel (SiliCycle, 40–63 µm or Sigma Aldrich, 40–60 µm), solvents of technical grade and an air pressure of

0.3–0.5 bar was applied.

NMR spectroscopy 1H,13C and 19F-NMR spectra were recorded at 25 °C on machines from Bruker

(Bruker Avance III 400 MHz, Bruker Neo 400 MHz and Bruker Neo 500 MHz, all equipped with BBFO

smart Probe). 1H-NMR chemical shifts are reported relative to chloroform-d (CDCl3, δ = 7.26 ppm), toluene-

d8 (δ = 2.08 ppm), or CD2Cl2 (δ = 5.32 ppm).7 Spectral data are reported as followed: chemical shift δ/ppm,

multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, br = broad, m = multiplet, app = apparent; or

combinations thereof. 13C-NMR chemical shifts are reported relative to chloroform-d (CDCl3, δ = 77.16

ppm), or toluene-d8 (δ = 20.43 ppm).7 13C and 19F signals are singlets unless stated else.103Rh signals were

detected indirectly in a 1H-103Rh HMBC experiment. JRh–H was set to 51 Hz.

S4

2 Reaction development Supporting Information

Gas chromatography (GC) GC measurements were conducted on a Shimadzu GC-2025 Series GC system.

A quartz capillary column Macherey-Nagel OPTIMA 5 (30.0m×0.25mm×0.25µm, carrier gas: hydrogen)

was used. The carrier gas rate was 68.6 cm s−1 and the injection temperature 250 °C. A flame ionization

detector (FID) with an inlet temperature of 250 °C was used. To determine GC yields, calibration curves

were generated using n-dodecane as an internal standard.

High resolution mass spectrometry (HRMS) HRMS data was obtained using electron ionisation (EI) on a

Thermo scientific Q Exactive GC Orbitrap with direct Probe, electrospray ionisation (ESI) on a Bruker maXis

– ESI-Qq-TOF-MS or matrix-assisted laser desorption/ionisation (MALDI) on Bruker solariX – MALDI-

FTICR-MS and are reported in m/z. All published data are within a range of m/z ± 3 ppm of theoretical

values.

2 Reaction development

2.1 Optimization of transfer arylation between an aromatic alcohol and an aromatic ketone

General procedure for screening of the conditions

In a glovebox, an oven-dried 4 mL vial equipped with a magnetic stirring bar under argon was charged with

rhodium complex, ligand (additional base for salts of NHC ligands) and solvent. The resulting mixtures were

stirred for 5 to 10 min, before 1a, 2 and the base were added. The reaction mixture was sealed with a screw

cap, taken out of the glovebox and placed in a preheated heating block for the indicated time and temperature.

After cooling to room temperature again, n-dodecane (11.0 µL, 0.0485 mmol) was added as internal standard

and the reaction was then analyzed by gas chromatography.

S5


Supplementary Table S1: Initial ligand screening.

OH

PhPh

Ph+

Ph Ph

O

[Rh(cod)Cl]2 (5 mol%)ligand (5 or 10 mol%)

Cs2CO3 (1 equiv.)PhMe, 110 °C, 3-17 h

Ph

O

ArFArF

O OH

ArFArF

Ph+

ArF = 4-fluorophenyl

ArF

1a 2 43a 5

+

P

Ph2PPPh2

Ph2P Ph2PPPh2

L13

L1 L2 L4

PPh2 FePPh2

PPh2

L3

PPh2

PPh2

L5

O

PPh2 PPh2

L6

O

PPh2 PPh2

L7

OPh2P PPh2

L8

O

PtBu2 PtBu2

L9

O

PCy2 PCy2

L10

HN

O

PPh2 PPh2

L11(oTol)3P

P

L12

P

L14

P

L15

F5

F5F5

SPhos

PAr2

PAr2

(S)-DBTM-Segphos

tBu

tBu

OMe

O

O

O

O

L17

MeO OMe

PCy2

L16

FePtBu2

PtBu2

L18

N N N N

L19 L20

dppe dppp dppf dppb (rac)-BINAP

Xantphos DPEphos DBFphos tBu-Xantphos Cy-Xantphos

Nixantphos

P(C6F5)3 DTBPF

IMes SIPr

PCy3 PAd2Bn

S6


Entrya Ligand (mol%)b Time (h) Yield 3a (%)c Yield 4 (%)c Yield 5 (%)c

1 L1 (10) 3 4 0 0

2 L2 (10) 3 8 1 0

3 L3 (10) 16 7 2 0

4 L4 (10) 23 17 2 0

5 L5 (10) 16 5 1 0

6 L5 (20) 17 10 4 0

7 L6 (10) 16 18 2 3

8 L7 (10) 16 10 2 0

9 L8 (10) 15 6 1 0

10 L9 (10) 15 54 5 9

11 L10 (10) 15 33 6 3

12 L11 (10) 17 24 7 0

13 L12 (20) 16 1 0 3

14 L13 (20) 15 19 1 0

15 L14 (20) 9 23 3 0

16 L15 (20) 9 29 8 3

17 L16 (10) 9 22 5 0

18 L17 (20) 9 30 2 0

19 L18 (10) 16 7 1 0

20d L19 (10) 16 57 3 4

21d L20 (10) 17 74 4 5a Reactions were performed on 0.100 mmol scale of 2.b 10 mol% for bidentate phosphine and NHC ligands and 20 mol% for monodentate phosphine ligands.c Product yield was determined by GC analysis.d Ligand used as protonated salt with cat. amount of KOtBu.

S7


Supplementary Table S2: Base screening.

OH

PhPh

Ph+

Ph Ph

O

[Rh(cod)Cl]2 (x mol%)SIPr · HCl (L20) (2x mol%)

KOtBu (2x mol%)

base (X equiv.)PhMe, 110 °C, 24 h

Ph

O

ArFArF

O OH

ArFArF

Ph+


ArF

1a 2 43a 5

+

Entrya,b Base (equiv.) x (mol%) Yield 3a (%)c Yield 4 (%)c Yield 5 (%)c

1 Cs2CO3 (1.0) 5 74 4 5

2 Cs2CO3 (1.0) 2.5 33 7 3

3 Cs2CO3 (2.0) 2.5 47 10 7

4 K3PO4 (1.0) 2.5 27 13 55 K2CO3 (1.0) 2.5 2 0 0

6 KOtBu (1.0) 2.5 0 0 0

7 KHMDS (1.0) 2.5 0 0 0

8 LDA (1.0) 2.5 0 0 0

9 NaH (1.0) 2.5 9 0 16

10 DABCO (1.0) 2.5 0 0 0a Reactions were performed on 0.100 mmol scale of 2.b Ligand used as protonated salt with cat. amount of KOtBu.c Product yield was determined by GC analysis.

S8


Supplementary Table S3: NHC ligand screening.

OH

PhPh

Ph+

Ph Ph

O

[Rh(cod)Cl]2 (2.5 mol%)ligand (5 mol%)

(KOtBu (5 mol%))

K3PO4 (1 equiv.)PhMe, 110 °C, 24 h

Ph

O

ArFArF

O OH

ArFArF

Ph+


ArF

1a 2 43a 5

+

N N

L20SIPr

N

L28CAAC-5

N N

L21(rac)-SIPrMe

N N

L23SIMes

N N

IPr

N N

IPrMe

N

PhPh

PhPh

N

PhPh

Ph

Ph

L30IPr*OMe

OMeMeO

N N

L22(S,S)-SIPrPh

Ph Ph

N N

L26IAd

N N

IPentL27L24 L25

N

PhPh

PhPh

N

PhPh

Ph

Ph

L29IPr*

Entrya Ligand Yield 3a (%)b Yield 4 (%)b Yield 5 (%)b

1 L20 · HClc 27 13 5

2 L21 · HBF4c 18 6 3

3 L22 · HBF4c 64 11 10

4 L23 · HClc 67 8 10

5 L24 · HClc 67 8 17

6 L25 · HClc 68 10 407 L26 · HBF4

c 26 5 4

8 L27 · HClc 79 3 24

9 L28 · HBF4c 79 5 12

10 [Rh(L28)Cl(cod)]d 62 13 14

11 L30 · HBF4c 26 6 23

a Reactions were performed on 0.100 mmol scale of 2.b Product yield was determined by GC analysis.c Ligand used as protonated salt with cat. amount of KOtBu.d In place of rhodium precursor.

S9


Supplementary Table S4: NHC ligand screening at higher temperature.

OH

PhPh

Ph+

Ph Ph

O


(KOtBu (5 mol%))


Ph

O

ArFArF

O OH

ArFArF

Ph+


ArF

1a 2 43a 5

+

Entrya Ligand Yield 3a (%)b Yield 4 (%)b Yield 5 (%)b

1 L20 · HClc 66 3 20

2 [Rh(L20)(cod)Cl]d 88 0 40

3 L21 · HBF4c 41 12 5

4 L23 · HClc 98 4 38

5 L24 82 8 35

6 L25 · HClc 108 0 18

7 L28 · HBF4c 94 3 36

8 L29 · HBF4c 66 11 59

9 L30 87 6 53

10 L30 · HBF4c 75 7 58

11 [Rh(IPr*OMe)(cod)Cl] (10)d 86 0 82a Reactions were performed on 0.100 mmol scale of 2.b Product yield was determined by GC analysis.c Ligand used as protonated salt with cat. amount of KOtBu.d In place of rhodium precursor and KOtBu.

2.2 Optimization of transfer arylation between an aromatic alcohol and an aliphatic ketone

General procedure for screening of the conditions

In a glovebox, an oven-dried 4 mL vial equipped with a magnetic stirring bar under argon was charged with

rhodium complex, ligand (additionally KOtBu to deprotonate NHC ligand salts) and solvent. The resulting

mixtures were stirred for 5 to 10 min, before 1a, 6a and the base were added. The reaction mixture was

sealed with a screw cap, taken out of the Glovebox and placed in a preheated heating block for the indicated

time and temperature. After cooling to room temperature again, n-dodecane (11.0 µL, 0.0485 mmol) was

added as internal standard and the reaction was then analyzed by gas chromatography.

S10


Supplementary Table S5: Ligand screening.

OH

PhPh

Ph+

Ph Ph

O


(KOtBu (5 mol%))


+

1a 6a 3a 7a

OOH

Ph

1.5 equiv. 1.0 equiv.

Entrya Ligand Yield 3a (%)b Yield 7a (%)b

1 None 133 50

2 L2 60 36

3 L4 71 44

4 L5 37 27

5 L6 4 0

6 L19 · HClc 105 607 L20 · HClc 6 3

8 L24 91 56

9 L27 · HClc 100 55

10 L30 · HBF4c 57 39

a Reactions were performed on 0.100 mmol scale of 6a.b Product yield was determined by GC analysis.c Ligand used as protonated salt with cat. amount of KOtBu.

S11


Supplementary Table S6: Ligand screening at higher temperature.

OH

PhPh

Ph+

Ph Ph

O


(KOtBu (5 mol%))


+

1a 6a 3a 7a

OOH

Ph


Entrya Ligand Yield 3a (%)b Yield 7a (%)b

1 None 106 49

2 L2 80 48

3 L4 69 49

4 L5 40 31

5 L6 0 0

6 L13c 84 19

7 L19 · HCld 121 71

8 L20 · HCld 102 64

9 L24 126 69

10 L27 · HCld 130 80

11 L30d 149 8612 [Rh(IPr*OMe)(cod)Cl]e 142 79a Reactions were performed on 0.100 mmol scale of 6a.b Product yield was determined by GC analysis.c 10 mol% for monodentate phosphine ligands.d Ligand used as protonated salt with cat. amount of KOtBu.e In place of rhodium precursor and KOtBu.

S12


Supplementary Table S7: Rh-precursor screening.

OH

PhPh

Ph+

Ph Ph

O

[Rh] (5 mol%)IPr*OMe · HBF4 (L30) (5 mol%)

KOtBu (5 mol%)


+

1a 6a 3a 7a

OOH

Ph


Entrya Rhodium source Yield 3a (%)b Yield 7a (%)b

1 [Rh(cod)Cl]2 149 862 [Rh(cod)(OH)]2 98 62

3 [Rh(coe)2Cl]2 6 5

4 [Rh(C2H4)2Cl]2 16 13

5 [Rh(CO)2Cl]2 135 886 RhCl3 3 2a Reactions were performed on 0.100 mmol scale of 6a.b Product yield was determined by GC analysis.

Supplementary Table S8: Base screening.

OH

PhPh

Ph+

Ph Ph

O

[Rh(cod)Cl]2 (2.5 mol%)IPr*OMe · HBF4 (L30) (5 mol%)

KOtBu (5 mol%)

base (x equiv.)PhMe, 125 °C, 24 h

+

1a 6a 3a 7a

OOH

Ph


Entrya Base (equiv.) Yield 3a (%)b Yield 7a (%)b

1 K3PO4 (1.0) 149 862 K3PO4 (2.0) 110 80

3 K3PO4 (0.25) 45 36

4 None 0 0

5 Cs2CO3 (1.0) 108 77

6 KOtBu (1.0) 5 4

7 NaH (1.0) 70 57

8 KHMDS (1.0) 10 5a Reactions were performed on 0.100 mmol scale of 6a.b Product yield was determined by GC analysis.

S13


Supplementary Table S9: Temperature screening.

OH

PhPh

Ph+

Ph Ph

O


KOtBu (5 mol%)

K3PO4 (1 equiv.)PhMe, temp, 24 h

+

1a 6a 3a 7a

OOH

Ph


Entrya Temperature (°C) Yield 3a (%)b Yield 7a (%)b

1 125 149 862 110 37 26

3 80 1 1

4 60 0 0a Reactions were performed on 0.100 mmol scale of 6a.b Product yield was determined by GC analysis.

Supplementary Table S10: Catalyst loading screening.

OH

PhPh

Ph+

Ph Ph

O

[Rh(cod)Cl]2 (x mol%)IPr*OMe · HBF4 (L30) (2x mol%)

KOtBu (2x mol%)


+

1a 6a 3a 7a

OOH

Ph


Entrya x (mol%) Yield 3a (%)b Yield 7a (%)b

1 5 120 82

1 2.5 149 86

2 0.5 97 70

3 0.25 47 35

4c 0.25 84 65

5d 0.25 125 84

6 0 (only L30) 0 0

7 0 0 0a Reactions were performed on 0.100 mmol scale of 6a.b Product yield was determined by GC analysis.c 48 hours.d 72 hours.

S14

3 Synthesis and characterization of starting materials Supporting Information

2.3 Evaluation of other alcohol donors

Supplementary Table S11: Donor screeninga,b.

HOOH

18%

HO

Me

53%

HO

25% 37%

HO

Me

2%

Me

OH

RR

Ph+

R R

O


KOtBu (5 mol%)


+

6a 7a

OOH

Ph


HO

22%

H HO

H

0%

H

31

a Reactions were performed on 0.100 mmol scale of 6a.b Product yield was determined by GC analysis.

3 Synthesis and characterization of starting materials

3.1 Synthesis of ketone starting materials

Ketones 3a, 3b, 6a, 6b, 6d, 6c, 6f, 6g, 6p and 6q were purchased from commercial suppliers.

General Procedure A: Conjugate arylation of α ,β -unsaturated ketones with boronic acids

+

[Rh(cod)Cl]2 (3 mol%)K3PO4 (1 equiv., 3 M aq.)

Dioxane/H2O (6:1)60 °C, 15-20 h

1.5 equiv.

OOB(OH)2

RR

In the Glovebox, a 8 mL vial was charged with [Rh(cod)Cl]2 (29.6 mg, 3 mol%) and arylboronic acid (2.00

mmol, 1.0 equiv.). The vial was closed with a septum cap and 1,4-dioxane (4 mL), degassed aq. 3 M K3PO4

S15


solution (0.67 mL, 2.00 mmol, 1.0 equiv.) and methyl vinyl ketone (0.25 mL, 3.00 mmol, 1.5 equiv.) were

added thereto. The mixture was degassed by sparging with N2 and heated for 15–20 h at 60 °C. After cooling

to room temperature, the reaction mixture was extracted with ethyl acetate and dried over Na2SO4. The filtrate

was concentrated in vacuo and further purified by flash column chromatography over silica (hexane/ethyl

acetate) to give the product.

bis(4-(tert-butyl)phenyl)methanone (3c)

O

Cl

O

AlCl3 (1.2 equiv.)

neat, 80 °C, 3 h

+

According to a literature procedure,8 a 100 mL two-necked round-bottom flask equipped with a magnetic stir-

ring bar under nitrogen was charged with aluminum chloride (4.10 g, 30.7 mmol, 1.2 equiv.). The apparatus

was evacuated and back-filled with nitrogen three times. Then, tert-butylbenzene (9.9 mL, 64.0 mmol, 2.5

equiv.) was added. To the resulting suspension was added 4-(tert-butyl)benzoyl chloride (5.0 mL, 25.6 mmol,

1.0 equiv.) dropwise at 25 °C via syringe over the course of 5 min. During the addition of 4-tert-butylbenzoyl

chloride, the reaction turned from a yellow suspension to a dark reddish brown solution. After the addition

was complete, the reaction was warmed at 80 °C for 3 h. Vigorous bubbling was observed throughout the

reaction. The reaction was allowed to reach rt (25 °C) and was quenched with 1 M aq. HCl solution (20 mL).

A yellow solid formed in an exothermic reaction. The crude was dissolved in EtOAc (50 mL) and the phases

were separated. The aq. layer was extracted with EtOAc (3 × 20 mL), dried over sodium sulfate and concen-

trated to yield an orange oil. Recrystallisation from hexane afforded 1.80 g (24 %) of the title compound as

light yellow solid.

1H-NMR (500 MHz, CDCl3): δ 7.77 (d, J = 8.8Hz, 4 H), 7.49 (d, J = 8.7Hz, 4 H), 1.37 (s, 18 H). 13C{1H}-NMR (126 MHz, CDCl3): δ 196.3, 156, 135.3, 130.2, 125.3, 35.2, 31.3. TLC (hexane/EtOAc 20:1): Rf =

0.45. HRMS (m/z): [M+Na]+ calcd. for C21H26NaO, 317.1876; found, 317.1877.

The spectroscopic data matched the reported literature.8

O

4-([1,1’-biphenyl]-4-yl)butan-2-one (6e)

Following General Procedure A with [1,1’-biphenyl]-4-ylboronic acid at 2.00 mmol

scale. Purification by column chromatography (50:1 to 20:1 to 10:1 hexane:EtOAc)

afforded 303 mg (68 %) of the title compound as off-white solid.

S16


1H-NMR (400 MHz, CDCl3): δ 7.61 – 7.54 (m, 2 H), 7.52 (d, J = 8.2Hz, 2 H), 7.43 (t, J = 7.5Hz, 2 H),

7.36 – 7.31 (m, 1 H), 7.28 – 7.25 (m, 2 H), 2.95 (t, J = 7.4Hz, 2 H), 2.81 (t, J = 7.7Hz, 2 H), 2.17 (s, 3 H).13C{1H}-NMR (101 MHz, CDCl3): δ 208.0, 141.1, 140.2, 139.2, 128.9, 128.9, 127.4, 127.2, 127.1, 45.2,

30.3, 29.4. HRMS (m/z): [M+Na]+ calcd. for C16H16NaO, 247.1093; found, 247.1092.


4-(4-methoxyphenyl)butan-2-one (6h)

O

HO

O

O

MeI

K2CO3 (2 equiv.)

acetonert, 24 h

+

According to a literature procedure,10 a 100 mL round-bottom flask equipped with a magnetic stirring bar

under nitrogen was charged with 4-(4-hydroxyphenyl)butan-2-one (2.20 g, 13.4 mmol, 1.0 equiv.) and K2CO3

(3.7 mg, 26.8 mmol, 2.0 equiv.). The apparatus was evacuated and back-filled with nitrogen three times.

Then, acetone (60 mL) was added. To the resulting suspension was added methyl iodide (1.0 mL, 16.1

mmol, 1.2 equiv.) dropwise at 25 °C via syringe and the resulting mixture was stirred at 25 °C for 24 h. The

reaction mixture was concentrated and partitioned between water and EtOAc (50 mL each). The phases were

separated, and the aq. phase was extracted with EtOAc (2 × 50 mL). The combined organic phases were

dried over Na2SO4 and concentrated under reduced pressure to afford a yellow oil. Purification by column

chromatography (10:1 to 5:1 to 4:1 hexane:EtOAc) afforded 1.46 g (61 %) of the title compound as colorless

oil.

1H-NMR (500 MHz, CDCl3): δ 7.10 (d, J = 8.8Hz, 2 H), 6.82 (d, J = 8.7Hz, 2 H), 3.78 (s, 3 H), 2.84 (t,

J = 7.2Hz, 2 H), 2.72 (t, J = 7.4Hz, 2 H), 2.13 (s, 3 H). 13C{1H}-NMR (126 MHz, CDCl3): δ 208.3, 158.1,

133.1, 129.3, 114, 55.4, 45.6, 30.2, 29.0. TLC (hexane/EtOAc 5:1): Rf = 0.39. HRMS (m/z): [M+Na]+

calcd. for C11H14NaO2, 201.0886; found, 201.0886.


O

S

O O

4-(4-(methylsulfonyl)phenyl)butan-2-one (6i)

Following General Procedure A with (4-(methylsulfonyl)phenyl)boronic acid at 2.00

mmol scale. Purification by column chromatography (1:1 hexane:EtOAc) afforded

379 mg (84 %) of the title compound as white solid.

1H-NMR (500 MHz, CDCl3): δ 7.85 (d, J = 8.4Hz, 2 H), 7.39 (d, J = 8.5Hz, 2 H), 3.03 (s, 3 H), 2.98 (t,

J = 7.4Hz, 2 H), 2.80 (t, J = 7.4Hz, 2 H), 2.16 (s, 3 H). 13C{1H}-NMR (126 MHz, CDCl3): δ 206.9, 147.9,

S17


138.6, 129.5, 127.8, 44.7, 44.4, 30.2, 29.5. TLC (hexane/EtOAc 1:1): Rf = 0.23. HRMS (m/z): [M+Na]+

calcd. for C11H14NaO3S, 249.0556; found, 249.0555.

O

Me3Si

4-(4-(trimethylsilyl)phenyl)butan-2-one (6j)

Following General Procedure A with (4-(trimethylsilyl)phenyl)boronic acid at 2.00

mmol scale. Purification by column chromatography (20:1 hexane:EtOAc) afforded

368 mg (84 %) of the title compound as yellow oil.

1H-NMR (500 MHz, CDCl3): δ 7.45 (d, J = 8.1Hz, 2 H), 7.18 (d, J = 8.2Hz, 2 H), 2.89 (t, J = 7.7Hz, 2 H),

2.81 – 2.73 (m, 2 H), 2.15 (s, 3 H), 0.25 (s, 9 H). 13C{1H}-NMR (126 MHz, CDCl3): δ 208.0, 141.7, 138.0,

133.7, 127.9, 45.2, 30.2, 29.8, -1.0. TLC (hexane/EtOAc 20:1): Rf = 0.15. HRMS (m/z): [M+Na]+ calcd.

for C13H20NaOSi, 243.1176; found, 243.1178.


O

O

O

methyl 3-(3-oxobutyl)benzoate (6k)

Following General Procedure A with (3-(methoxycarbonyl)phenyl)boronic acid

at 2.00 mmol scale. Purification by column chromatography (5:1 hexane:EtOAc)

afforded 307 mg (88 %) of the title compound as light yellow oil.

1H-NMR (400 MHz, CDCl3): δ 7.89 – 7.82 (m, 2 H), 7.41 – 7.31 (m, 2 H), 3.91 (s, 3 H), 2.94 (t, J = 7.6Hz,

2 H), 2.78 (t, J = 7.4Hz, 2 H), 2.14 (s, 3 H). 13C{1H}-NMR (101 MHz, CDCl3): δ 207.6, 167.3, 141.5,

133.2, 130.5, 129.4, 128.7, 127.6, 52.2, 45.0, 30.2, 29.5. TLC (hexane/EtOAc 5:1): Rf = 0.3. HRMS (m/z):[M+Na]+ calcd. for C12H14NaO3, 229.0835; found, 229.0836.


O

O

O

tert-butyl 3-(3-oxobutyl)benzoate (6l)

Following General Procedure A with (3-(tert-butoxycarbonyl)phenyl)boronic

acid at 2.00 mmol scale. Purification by column chromatography (10:1 hex-

ane:EtOAc) afforded 444 mg (89 %) of the title compound as yellow oil.

1H-NMR (500 MHz, CDCl3): δ 7.83 – 7.79 (m, 2 H), 7.37 – 7.30 (m, 2 H), 2.97 – 2.90 (m, 2 H), 2.78 (ddt,

J = 7.8,7.4,0.6Hz, 2 H), 2.15 (s, 3 H), 1.59 (s, 9 H). 13C{1H}-NMR (126 MHz, CDCl3): δ 207.7, 165.9,

141.2, 132.7, 132.4, 129.3, 128.5, 127.4, 81.2, 45.1, 30.2, 29.6, 28.3. TLC (hexane/EtOAc 10:1): Rf = 0.15.

HRMS (m/z): [M+Na]+ calcd. for C15H20NaO3, 271.1305; found, 271.131.

S18


O

N

O

N,N-diethyl-4-(3-oxobutyl)benzamide (6m)

Following General Procedure A with (4-(diethylcarbamoyl)phenyl)boronic acid

at 2.00 mmol scale. Purification by column chromatography (1:1 hexane:EtOAc)

afforded 220 mg (45 %) of the title compound as a colorless oil.

1H-NMR (400 MHz, CDCl3): δ 7.28 (d, J = 8.5Hz, 2 H), 7.19 (d, J = 8.4Hz, 2 H), 3.39 (br d, 4 H, NEt2rotamers), 2.90 (m, 2 H), 2.75 (m, 2 H), 2.14 (s, 3 H), 1.17 (br d, 6 H, NEt2 rotamers). 13C{1H}-NMR (126MHz, CDCl3): δ 207.7, 171.4, 142.3, 135.3, 128.5, 126.7, 45, 43.4 (NEt2 rotamer A), 39.4 (NEt2 rotamer

B), 30.3, 29.6, 14.4 (NEt2 rotamer A), 13.1 (NEt2 rotamer B). TLC (hexane/EtOAc 1:1): Rf = 0.21. HRMS(m/z): [M+Na]+ calcd. for C15H21NNaO2, 270.1464; found, 270.1466.


O

Cl

4-(4-chlorophenyl)butan-2-one (6n)

Following General Procedure A with (4-bromophenyl)boronic acid at 2.00 mmol scale.

Purification by column chromatography (10:1 hexane:EtOAc) afforded 365 mg (100

%) of the title compound as light yellow oil.

1H-NMR (500 MHz, CDCl3): δ 7.24 (d, J = 8.4Hz, 2 H), 7.11 (d, J = 8.7Hz, 2 H), 2.86 (t, J = 7.6Hz, 2 H),

2.74 (t, J = 7.2Hz, 2 H), 2.14 (s, 3 H). 13C{1H}-NMR (126 MHz, CDCl3): δ 207.6, 139.6, 132, 129.8, 128.7,

45.1, 30.3, 29.1. TLC (hexane/EtOAc 10:1): Rf = 0.27. HRMS (m/z): [M+Na]+ calcd. for C10H11ClNaO,

205.0391; found, 205.0391.


O

O

4-(furan-3-yl)butan-2-one (6o)

Following General Procedure A with furan-3-ylboronic acid at 2.00 mmol scale. Purifica-

tion by column chromatography (10:1 hexane:EtOAc) afforded 118 mg (43 %) of the title

compound as yellow oil.

1H-NMR (400 MHz, CDCl3): δ 7.33 (t, J = 1.7Hz, 1 H), 7.21 (s, 1 H), 6.25 (dd, J = 1.9,0.9Hz, 1 H), 2.72

- 2.67 (m, 4 H), 2.15 (s, 3 H). 13C{1H}-NMR (101 MHz, CDCl3): δ 208.0, 143.0, 139.1, 123.9, 111.0, 44.0,

30.2, 19.1. TLC (hexane/EtOAc 10:1): Rf = 0.18. HRMS (m/z): [M+H]+ calcd. for C8H11O2, 139.07544;

found, 139.0753.


S19


3.2 Synthesis of alcohol starting materials

Alcohols triphenylmethanol (1a), 2-phenyl-2-propanol (1p) and benzhydrol (1q) were purchased from com-

mercial suppliers.

General Procedure B1: Grignard addition to diaryl ketones

+Br

O

OHTHF

0 °C to rt

R1 R1

R1

R1

R1

R1

Mg

BrBr

To an oven-dried two-necked Schlenk flask equipped with a magnetic stirring bar was added magnesium

(1.1 equiv.). The flask was sealed and evacuated/back-filled with nitrogen three times before THF (1.0 M) was

added via syringe. 1,2-Dibromoethane (0.05 equiv.) was added and the suspension was stirred for 5 min.

10 % of a solution of bromoarene (1.1 equiv.) in THF (final reaction concentration 0.2 M) was then added

via syringe and the suspension heated at 36–40 °C (can be done by hand or using a heating bath) until an

exotherm was observed. The vessel was then removed from heat and the rest of the bromoarene solution

was added dropwise. Once addition was complete, the reaction mixture had developed a yellow to brown

color of a Grignard reagent. It was then heated to 60 °C for 1 h before cooling to room temperature and

subsequently to 0 °C in an ice bath. Then, a solution of diaryl ketone (1.0 equiv.) in THF was added dropwise

via syringe. The reaction mixture was allowed to warm back to room temperature (25 °C) before stirring

overnight (14–18 h). It was then quenched through dropwise addition of sat. aq. NH4Cl solution at 0 °C (ice

bath). EtOAc was added and the layers were separated. The aqueous layer was extracted twice with EtOAc.

The combined organics were washed with aq. sat. NaCl solution and dried over Na2SO4, and filtered. The

filtrate was concentrated under reduced pressure at 40 °C to obtain the crude product which was purified by

column chromatography or recrystallization.

General Procedure B2: Grignard addition to aryl esters

+Br

O

O

OHTHF

0 °C to rt

R1 R1

R1

R1

R1

Mg

BrBr

S20










subsequently to 0 °C in an ice bath. Then, a solution of diaryl ester (1.0 equiv.) in THF was added dropwise

via syringe. The reaction mixture was allowed to warm back to room temperature (25 °C) before stirring

overnight (14–18 h). It was then quenched through dropwise addition of sat. aq. NH4Cl solution at 0 °C (ice

bath). EtOAc was added and the layers were separated. The aqueous layer was extracted twice with EtOAc.

The combined organics were washed with aq. sat. NaCl solution and dried over Na2SO4, and filtered. The

filtrate was concentrated under reduced pressure at 40 °C to obtain the crude product which was purified by

column chromatography or recrystallization.

General Procedure B3: Grignard addition to diethyl carbonate

+Br

O

O O

OHTHF

0 °C to rt

R1

R1

R1

R1

Mg

BrBr









subsequently to 0 °C in an ice bath. Then, a solution of diethyl carbonate (1.0 equiv.) in THF was added

dropwise via syringe. The reaction mixture was allowed to warm back to room temperature (25 °C) before

stirring overnight (14–18 h). It was then quenched through dropwise addition of sat. aq. NH4Cl solution at

0 °C (ice bath). EtOAc was added and the layers were separated. The aqueous layer was extracted twice with

EtOAc. The combined organics were washed with aq. sat. NaCl solution and dried over Na2SO4, and filtered.

The filtrate was concentrated under reduced pressure at 40 °C to obtain the crude product which was purified

by column chromatography or recrystallization.

S21


General Procedure C1: Organolithium addition to diaryl ketones

+

Br

OHTHF

-78 °C to rt

R1

R1

R1

R1

nBuLiO

R1 R1

To an oven-dried Schlenk flask equipped with a magnetic stirring bar was added bromoarene (1.1 equiv.).

The flask was sealed and evacuated/back-filled with nitrogen three times before THF (0.2 M) was added

via syringe. The reaction was cooled to −78 °C and n-butyllithium (1.6 M in hexane, 1.1 equiv.) was added

dropwise at this temperature. The resulting reaction mixture was stirred at −78 °C for 30 min. Then, a solution

of diaryl ketone (1.0 equiv.) in THF was dropwise added at −78 °C. After complete addition the reaction was

stirred and allowed to reach room temperature (25 °C) overnight (14–18 h). It was then quenched through

dropwise addition of sat. aq. NH4Cl solution at 0 °C (ice bath). EtOAc was added and the layers were

separated. The aqueous layer was extracted twice with EtOAc. The combined organics were washed with aq.

sat. NaCl solution and dried over Na2SO4, and filtered. The filtrate was concentrated under reduced pressure

at 40 °C to obtain the crude product which was purified by column chromatography or recrystallization.

General Procedure C2: Organolithium addition to aryl esters

+

Br

OHTHF

-78 °C to rt

R1

R1

R1

R1

nBuLiO

OR1




dropwise at this temperature. The resulting reaction mixture was stirred at −78 °C for 30 min. Then, a solution

of aryl ester (1.0 equiv.) in THF was dropwise added at −78 °C. After complete addition the reaction was

stirred and allowed to reach room temperature (25 °C) overnight (14–18 h). It was then quenched through

dropwise addition of sat. aq. NH4Cl solution at 0 °C (ice bath). EtOAc was added and the layers were

separated. The aqueous layer was extracted twice with EtOAc. The combined organics were washed with aq.

sat. NaCl solution and dried over Na2SO4, and filtered. The filtrate was concentrated under reduced pressure

at 40 °C to obtain the crude product which was purified by column chromatography or recrystallization.

S22


General Procedure C3: Organolithium addition to methyl chloroformate

+

BrO

O Cl

OHTHF

-78 °C to rt

R1

R1

R1

R1

nBuLi




dropwise at this temperature. The resulting reaction mixture was stirred at −78 °C for 30 min. Then, a

solution of methyl chloroformate (1.0 equiv.) in THF was dropwise added at −78 °C. After complete addition

the reaction was stirred and allowed to reach room temperature (25 °C) overnight (14–18 h). It was then

quenched through dropwise addition of sat. aq. NH4Cl solution at 0 °C (ice bath). EtOAc was added and

the layers were separated. The aqueous layer was extracted twice with EtOAc. The combined organics were

washed with aq. sat. NaCl solution and dried over Na2SO4, and filtered. The filtrate was concentrated under

reduced pressure at 40 °C to obtain the crude product which was purified by column chromatography or

recrystallization.

OH

tri-p-tolylmethanol (1b)

Following General Procedure B1 with di-p-tolylmethanone (5.80 g, 27.6 mmol, 1.0

equiv.) and 4-bromotoluene (4.0 mL, 33.1 mmol, 1.2 equiv.). Recrystallization from

hexane afforded 8.26 g (99 %) of the title compound as white solid.

1H-NMR (400 MHz, CDCl3): δ 7.19 – 7.15 (m, 6 H), 7.14 – 7.10 (m, 6 H), 2.70 (s, 1 H), 2.35 (s, 9 H).13C{1H}-NMR (101 MHz, CDCl3): δ 144.4, 136.9, 128.7, 127.9, 81.7, 21.2. HRMS (m/z): [M+Na]+ calcd.

for C22H22NaO, 325.1563; found, 325.1562.


OH

tris(4-(tert-butyl)phenyl)methanol (1c)

Following General Procedure B1 with bis(4-(tert-butyl)phenyl)methanone (3c)

(1.00 g, 3.40 mmol, 1.0 equiv.) and 1-bromo-4-(tert-butyl)benzene (0.71 mL, 4.08

mmol, 1.2 equiv.). Purification by column chromatography (100:1 to 50:1 to 20:1

hexane:EtOAc) afforded 1.12 g (77 %) of the title compound as white solid.

S23


1H-NMR (500 MHz, CDCl3): δ 7.32 (d, J = 8.8Hz, 6 H), 7.19 (d, J = 8.8Hz, 6 H), 2.72 (s, 1 H), 1.31

(s, 27 H). 13C{1H}-NMR (126 MHz, CDCl3): δ 150.0, 144.3, 127.7, 124.8, 81.7, 34.6, 31.5. TLC (hex-ane/EtOAc 20:1): Rf = 0.56. HRMS (m/z): [M+Na]+ calcd. for C31H40NaO, 451.2971; found, 451.2969.


OH

tris(3,5-dimethylphenyl)methanol (1d)

Following General Procedure B2 with methyl 3,5-dimethylbenzoate (0.750 g, 4.57

mmol, 1.0 equiv.) and 1-bromo-3,5-dimethylbenzene (1.8 mL, 13.4 mmol, 2.9 equiv.).

Purification by recrystallization from hexane afforded 1.13 g (72 %) of the title com-

pound as white solid.

1H-NMR (500 MHz, CDCl3): δ 6.91 (s, 3 H), 6.89 (s, 6 H), 2.68 (s, 1 H), 2.28 (s, 18 H). 13C{1H}-NMR(126 MHz, CDCl3): δ 147.2, 137.3, 128.9, 125.9, 82.0, 21.7. TLC (hexane/EtOAc 99:1): Rf = 0.31. HRMS(m/z): [M+Na]+ calcd. for C25H28NaO, 367.2032; found, 367.2038.


OH

tri(naphthalen-2-yl)methanol (1e)

Following General Procedure C2 with methyl 2-naphthoate (0.500 g, 2.69 mmol,

1.0 equiv.) and 2-bromonaphthalene (1.17 g, 5.64 mmol, 2.1 equiv.). Purification

by column chromatography (19:1 to 9:1 hexane:EtOAc) afforded 813 mg (74 %)

of the title compound as white solid.

1H-NMR (400 MHz, CDCl3): δ 7.87–7.85 (m, 3 H), 7.84 – 7.82 (m, 3 H), 7.80-7.80 (m, 3 H), 7.76 - 7.74 (m,

3 H), 7.57 (dd, J = 8.7,1.9Hz, 3 H), 7.52 - 7.46 (m, 6 H), 3.13 (s, 1 H). 13C{1H}-NMR (126 MHz, CDCl3):δ 143.9, 133.0, 132.8, 128.6, 128.0, 127.7, 126.9, 126.5, 126.4, 126.3, 82.7. TLC (hexane/EtOAc 9:1): Rf

= 0.29. HRMS (m/z): [M+Na]+ calcd. for C31H22NaO, 433.1563; found, 433.1565.


OH

F

F

F

tris(4-fluorophenyl)methanol (1f)

Following General Procedure B1 with bis(4-fluorophenyl)methanone (0.702 g, 3.22

mmol, 1.0 equiv.) and (4-fluorophenyl)magnesium bromide (1.8 mL, 2 M in THF,

3.54 mmol, 1.1 equiv.). Recrystallization from DCM/hexane afforded 816 mg (81 %)

of the title compound as light yellow solid.

S24


1H-NMR (400 MHz, CDCl3): δ 7.25 – 7.18 (m, 6 H), 7.07 – 6.94 (m, 6 H), 2.70 (s, 1 H). 13C{1H}-NMR(101 MHz, CDCl3): δ 162.2 (d, 1JCF = 247.1Hz), 142.5 (d, 4JCF = 3.3Hz), 129.7 (d, 3JCF = 8.2Hz), 115.1

(d, 2JCF = 21.4Hz), 81.1. 19F{1H}-NMR (376 MHz, CDCl3): δ -114.92. HRMS (m/z): [M+Na]+ calcd. for

C19H13F3NaO, 337.0811; found, 337.0808.


OH

Cl

Cl

Cl

tris(4-chlorophenyl)methanol (1g)

Following General Procedure B1 with bis(4-chlorophenyl)methanone (1.88 g, 7.48

mmol, 1.0 equiv.) and 1-bromo-4-chlorobenzene (1.0 mL, 8.23 mmol, 1.1 equiv.).

Recrystallization from hexane afforded 2.34 g (86 %) of the title compound as

white solid.

1H-NMR (500 MHz, CDCl3): δ 7.30 (d, J = 8.9Hz, 6 H), 7.19 (d, J = 8.9 Hz, 6 H), 2.69 (s, 1 H). 13C{1H}-NMR (126 MHz, CDCl3): δ 144.6, 133.9, 129.3, 128.5, 81.1. TLC (hexane/EtOAc 10:1): Rf = 0.44.

HRMS (m/z): [M+Na]+ calcd. for C19H13Cl3NaO, 384.9924; found, 384.9926.

OH

O

O

O

tris(4-methoxyphenyl)methanol (1h)

Following General Procedure B1 with bis(4-methoxyphenyl)methanone (1.01 g,

4.17 mmol, 1.0 equiv.) and (4-methoxyphenyl)magnesium bromide (5.0 mL, 1.0

M in THF, 5.00 mmol, 1.2 equiv.). Purification by column chromatography (5:1

hexane:EtOAc) afforded 1.42 g (97 %) of the title compound as white solid.

1H-NMR (400 MHz, CDCl3): δ 7.17 (d, J = 9.0Hz, 6 H), 6.83 (d, J = 9.0Hz, 6 H), 3.80 (s, 9 H), 2.69 (s,

1 H). 13C{1H}-NMR (101 MHz, CDCl3): δ 158.7, 139.8, 129.2, 113.3, 81.3, 55.4. TLC (hexane/EtOAc5:1): Rf = 0.15. HRMS (m/z): [M+Na]+ calcd. for C22H22NaO4, 373.1410; found, 373.1405.


OH

CF3

CF3

CF3

tris(4-(trifluoromethyl)phenyl)methanol (1i)

Following General Procedure B2 with methyl 4-(trifluoromethyl)benzoate (1.0

mL, 6.17 mmol, 1.0 equiv.) and 1-bromo-4-(trifluoromethyl)benzene (1.9 mL,

13.6 mmol, 2.2 equiv.). Purification by column chromatography (20:1 hexane:EtOAc)

and afforded a light yellow solid that was further triturated with hexane to afford


S25


1H-NMR (500 MHz, CDCl3): δ 7.62 (dd, J = 8.9,0.7Hz, 6 H), 7.42 (dd, J = 8.9,0.7Hz, 6 H), 2.85 (s, 1 H).13C{1H}-NMR (126 MHz, CDCl3): δ 149.2, 130.4 (q, 2JCF = 32.6Hz), 128.3, 125.6 (q, 3JCF = 3.8Hz),

124.0 (q, 1JCF = 272.2Hz), 81.5. 19F{1H}-NMR (471 MHz, CDCl3): δ -62.68. TLC (hexane/EtOAc 20:1):Rf = 0.15. HRMS (m/z): [M]+ calcd. for C22H13F9O, 464.0817; found, 464.0805.


OH

O

O

OCF3

CF3

CF3

tris(4-(trifluoromethoxy)phenyl)methanol (1j)

Following General Procedure B2 with methyl 4-(trifluoromethoxy)benzoate

(0.40 mL, 2.27 mmol, 1.0 equiv.) and 1-bromo-4-(trifluoromethoxy)benzene

(1.0 mL, 6.81 mmol, 3.0 equiv.). Purification by column chromatography (19:1

to 9:1 hexane:EtOAc) afforded 0.914 g (79 %) of the title compound as yellow

solid.

1H-NMR (400 MHz, CDCl3): δ7.33–7.27 (m, 6 H), 7.22–7.16 (m, 6 H), 2.76 (s, 1 H). 13C{1H}-NMR (126MHz, CDCl3): δ 148.8 (app d, 3JCF = 1.9Hz), 144.6, 129.4, 120.7 (app d, 4JCF = 1.0Hz), 120.6 (q, 1JCF =

257.6Hz), 81.0. 19F{1H}-NMR (471 MHz, CDCl3): δ -57.82. TLC (hexane/EtOAc 19:1): Rf = 0.47.

HRMS (m/z): [M]+ calcd. for C22H13F9O4, 512.0665; found, 512.0662.


OH

CF3

CF3

CF3 CF3

CF3

CF3

tris(3,5-bis(trifluoromethyl)phenyl)methanol (1k)

Following General Procedure B1 with bis(3,5-bis(trifluoromethyl)phenyl)metha-

none (3.59 g, 7.90 mmol, 1.0 equiv.) and 1-bromo-3,5-bis(trifluoromethyl)ben-

zene (1.5 mL, 8.70 mmol, 1.1 equiv.). Purification by column chromatography

(40:1 to 20:1 hexane:EtOAc) and afforded a light yellow solid that was further

recrystallized from hexane to afford 541 mg (10 %) of the title compound as

light yellow solid.

1H-NMR (500 MHz, CDCl3): δ 7.94 (s, 3 H), 7.77 (s, 6 H), 3.22 (s, 1 H). 13C{1H}-NMR (126 MHz, CDCl3):δ 146.5, 132.8 (q, 2JCF = 33.8Hz), 127.7 (app d, 3JCF = 2.5Hz), 123.2 (sept, 3JCF = 3.9Hz), 123.0 (q, 1JCF =

273Hz), 80.8. 19F{1H}-NMR (471 MHz, CDCl3): δ -63.10. TLC (hexane/EtOAc 20:1): Rf = 0.29.


S26


OH

O

O

O

O

O

O

tris(benzo[d][1,3]dioxol-5-yl)methanol (1l)

Following General Procedure B3 with 5-bromobenzo[d][1,3]dioxole (2.0 mL,

16.8 mmol, 3.3 equiv.) and diethyl carbonate (0.61 mL, 5.08 mmol, 1.0 equiv.). Pu-

rification by column chromatography (19:1 to 9:1 hexane:EtOAc) afforded 1.21 g

(61 %) of the title compound as light brown solid.

1H-NMR (500 MHz, CDCl3): δ 6.78 (d, J = 1.7Hz, 3 H),6.74 – 6.68 (m, 6 H), 5.95 (s, 6 H), 2.66 (s, 1 H).13C{1H}-NMR (126 MHz, CDCl3): δ 147.5, 146.9, 141.3, 121.5, 108.9, 107.5, 101.3, 81.8. TLC (hex-ane/EtOAc 4:1): Rf = 0.40. HRMS (m/z): [M+Na]+ calcd. for C22H16NaO7, 415.0788; found, 415.0785.


OH

O

O

O

tri(benzofuran-2-yl)methanol (1m)

Following General Procedure B3 with 2-bromobenzofuran (0.991 g, 5.03 mmol,

3.3 equiv.) and diethyl carbonate (0.19 mL, 1.52 mmol, 1.0 equiv.). Purification by

column chromatography (19:1 to 9:1 hexane:EtOAc) afforded 0.440 g (76 %) of

the title compound as beige solid.

1H-NMR (500 MHz, CDCl3): δ 7.58 (ddd, J = 7.7,1.4,0.7Hz, 3 H), 7.51 (dd, J = 8.2,0.9Hz, 3 H), 7.33

(ddd, J = 8.4,7.3,1.4Hz, 3 H), 7.28 – 7.24 (m, 3 H), 6.83 (d, J = 1.0Hz, 3 H), 3.70 (s, 1 H). 13C{1H}-NMR(126 MHz, CDCl3): δ 155.3, 155.1, 127.9, 125.1, 123.3, 121.7, 111.8, 106.2, 71.8. TLC (hexane/EtOAc5:1): Rf = 0.15. HRMS (m/z): [M+Na]+ calcd. for C25H16NaO4, 403.0941; found, 403.0938.

OH

O

O

O

tri(benzofuran-5-yl)methanol (1n)

Following General Procedure B3 with 5-bromobenzofuran (1.4 mL, 11.2 mmol,

3.3 equiv.) and diethyl carbonate (0.41 mL, 3.39 mmol, 1.0 equiv.). Purification by

column chromatography (19:1 to 9:1 hexane:EtOAc) afforded 0.430 g (33 %) of

the title compound as off-white solid.

1H-NMR (500 MHz, CDCl3): δ 7.62 (d, J = 2.2Hz, 3 H), 7.50 (d, J = 2.0Hz, 3 H), 7.47 – 7.43 (m, 3 H), 7.32

(dd, J = 8.7,2.0Hz, 3 H), 6.70 (dd, J = 2.2,1.0Hz, 3 H), 3.01 (s, 1 H). 13C{1H}-NMR (126 MHz, CDCl3):δ 154.2, 145.6, 142.6, 127, 125, 121, 110.9, 107.1, 82.7. TLC (hexane/EtOAc 5:1): Rf = 0.15. HRMS(m/z): [M+Na]+ calcd. for C25H16NaO4, 403.0941; found, 403.0938.


S27


4-(4-bromobenzyl)morpholine (11)

O

NH+

Br

BrO

N

BrKOH

EtOH

25 °C, 24 h

The compound was synthesized according to a literature procedure.24 A 100 mL round-bottom flask equipped

with a magnetic stirring bar under air was charged with p-bromobenzyl bromide (1.25 g, 5.0 mmol, 1.0

equiv.) and ethanol (10 mL). To the resulting solution was added morpholine (0.43 mL, 5.0 mmol, 1.0 equiv.)

dropwise at 25 °C via syringe and the resulting mixture was stirred at 25 °C for 24 h. A white suspension

formed within minutes. The reaction mixture was concentrated and partitioned between water and EtOAc

(30 mL each). The phases were separated, and the aq. phase was extracted with EtOAc (3 × 20 mL). The

combined organic phases were dried over MgSO4 and concentrated under reduced pressure. Purification by

column chromatography (hexane/EtOAc/Et3N 85:14:1) afforded 1.24 g (97 %) of the title compound as a

white solid.

1H-NMR (400 MHz, CDCl3): δ 7.44 (d, J = 8.4Hz, 2 H), 7.21 (d, J = 8.3Hz, 2 H), 3.74 – 3.67 (app t, 4 H),

3.44 (s, 2 H), 2.46 – 2.39 (m, 4 H). 13C{1H}-NMR (101 MHz, CDCl3): δ 137.0, 131.5, 130.9, 121.1, 67.1,

62.8, 53.7.


OHN

N

N

O

O

O

tris(4-(morpholinomethyl)phenyl)methanol (1o)

Following General Procedure C3 with 4-(4-bromobenzyl)morpholine

(11) (1.24 g, 4.86 mmol, 3.3 equiv.) and methyl chloroformate (0.11

mL, 1.47 mmol, 1.0 equiv.). Purification by column chromatography

(1:1 hexane/(3:1 EtOAc/EtOH) to EtOAc/EtOH 3:1) afforded 505 mg

(62 %) of the title compound as white solid.

1H-NMR (500 MHz, CDCl3): δ 7.26 (d, J = 8.3Hz, 6 H), 7.21 (d, J = 8.4Hz, 6 H), 3.70 (app t, J = 4.7Hz,

12 H), 3.49 (s, 6 H), 2.85 (s, 1 H), 2.44 (s, 12 H). 13C{1H}-NMR (126 MHz, CDCl3): δ 146.0, 136.9, 128.9,

127.9, 81.8, 67.2, 63.2, 53.8. TLC (hexane/(EtOAc/EtOH 3:1) 1:1): Rf = 0.07. HRMS (m/z): [M+H]+

calcd. for C34H44N3O4, 558.3326; found, 558.3325.

S28

4 Substrate scope Supporting Information

4 Substrate scope

General Procedure D1: Catalytic arylation of ketones with alcohols

OH

R1R1

Ar+

R1 R2

O

[RhCl(cod)]2 (2.5 mol%)IPr*OMe · HBF4 (5 mol%)

KOtBu (5 mol%)

K3PO4 (1 equiv)PhMe, 125 °C, 24 h

+

1 6 3 7

R4

O

R4R3

OHAr

1.5 equiv.

R3

1.0 equiv.

A 8 mL vial under air was charged with alcohol 1 (0.750 mmol, 1.5 equiv.), ketone 6 (0.500 mmol, 1.0 equiv.)

and a magnetic stirring bar. A second 4 mL vial was charged with L30 · HBF4 (25.9 mg, 25 µmol, 5 mol%),

and both vials were transferred into the Glovebox. [Rh(cod)Cl]2 (6.2 mg, 12.5 µmol, 2.5 mol%), KOtBu

(2.8 mg, 25 µmol, 5 mol%), and toluene (1.0 mL) were added into the ligand-containing vial and the resulting

yellow almost homogeneous mixture was stirred for about 5 min. The substrate-containing vial was charged

with K3PO4 (106 mg, 0.500 mmol, 1.0 equiv.), toluene (1.5 mL) and the catalyst solution. The vial was sealed

with a screw cap, taken out of the Glovebox, placed in a preheated heating block at 125 °C and stirred for 24 h.

After cooling to room temperature, the reaction mixture was exposed to air, concentrated and further purified

by flash column chromatography over silica (hexane/ethyl acetate) to give the product.

General Procedure D2: Catalytic arylation of ketones with alcohols, followed by derivatization of

remaining starting material from the crude

To aid separation of the product from remaining starting material 6, the remaining ketone was reduced with

NaBH4 after the reaction.

The reaction was set up and run as described in General Procedure D1. The crude reaction mixture was

concentrated, dissolved in methanol (2.5 mL, 0.2 M) and cooled to 0 °C. NaBH4 (18.9 mg, 0.250 mmol, 1.0

equiv.) was added in one portion and the reaction mixture was stirred at 0 °C for 5 min and at rt for 1 h.

The resulting mixture was treated with water, concentrated and extracted with ethyl acetate three times. The

combined organic extracts were washed dried over Na2SO4, filtered, and concentrated. The residue was

purified by column chromatography eluting with hexane/EtOAc.

General Procedure D3: Catalytic arylation of ketones with alcohols, followed by derivatization of

remaining starting material after initial purification

To aid separation of the product from remaining starting material 6, the remaining ketone was reduced with

NaBH4 after initial purification.

S29


The reaction was set up, run, and purified as described in General Procedure D1. All fractions containing

product, including impure fractions were combined and concentrated. The residue was dissolved in methanol

(2.5 mL, 0.2 M) and cooled to 0 °C. NaBH4 (9.5 mg, 0.250 mmol, 0.5 equiv.) was added in one portion and

the reaction mixture was stirred at 0 °C for 5 min and at rt for 1 h. The resulting mixture was treated with

water, concentrated and extracted with ethyl acetate three times. The combined organic extracts were washed

dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography eluting

with hexane/EtOAc.

4.1 Ketone side

OH

4,4-dimethyl-1-phenylcyclohexan-1-ol (7a)

Following General Procedure D1 with 1a and 4,4-dimethylcyclohexan-1-one (6a). Pu-

rification by column chromatography (40:1 to 20:1 hexane:acetone, then 20:1 hexane:EtOAc,

then 20:1 hexane:acetone) afforded 82.9 mg (81 %) of the title compound as a white solid.

1H-NMR (500 MHz, CDCl3): δ 7.54 – 7.50 (m, 2 H), 7.39 – 7.32 (m, 2 H), 7.29 – 7.22 (m, 1 H), 2.06 – 1.97

(m, 2 H), 1.75 – 1.63 (m, 4 H), 1.51 (s, 1 H), 1.34 – 1.28 (m, 2 H), 1.01 (s, 3 H), 0.99 (s, 3 H). 13C{1H}-NMR(126 MHz, CDCl3): δ 149.4, 128.4, 126.9, 124.7, 73, 35.2, 35.0, 32.5, 29.5, 24.2. TLC (hexane/EtOAc10:1): Rf = 0.38. HRMS (m/z): [M+Na]+ calcd. for C14H20NaO, 227.1406; found, 227.1402.


OH

OH

+

cis trans

cis and trans-4-(tert-butyl)-1-phenylcyclohexan-1-ol (7b)

Following General Procedure D1 with 1a and 4-(tert-butyl)cy-

clohexan-1-one (6b). Purification by column chromatography

(20:1 to 10:1 hexane:EtOAc) afforded 58.0 mg (50 %) of trans-

4-(tert-butyl)-1-phenylcyclohexan-1-ol as colorless plates and

27.7 mg (24 %) of cis-4-(tert-butyl)-1-phenylcyclohexan-1-ol as

off-white solid (d.r. crude: 5.4:1 (1H-NMR); isolated: 2.1:1).

The assignment of the two regioisomers was confirmed by the X-ray structure of cis-7b (see Section 6.2).

cis-isomer:

1H-NMR (500 MHz, CDCl3): δ 7.57 – 7.51 (m, 2 H), 7.41 – 7.34 (m, 2 H), 7.31 – 7.23 (m, 1 H), 1.93

– 1.81 (m, 4 H), 1.78 – 1.71 (m, 2 H), 1.63 – 1.51 (m, 3 H), 1.13 (tt, J = 12.1,3.2Hz, 1 H), 0.94 (s, 9 H).13C{1H}-NMR (126 MHz, CDCl3): δ 149.7, 128.3, 126.8, 124.6, 72.9, 47.7, 39.6, 32.6, 27.8, 23.0. TLC(hexane/EtOAc 10:1): Rf = 0.52. HRMS (m/z): [M+Na]+ calcd. for C16H24NaO, 255.1719; found, 255.172.

S30


trans-isomer:

1H-NMR (500 MHz, CDCl3): δ 7.56 (dd, J = 8.5,1.2Hz, 2 H), 7.40 – 7.35 (m, 2 H), 7.32 – 7.25 (m, 1 H),

2.57 – 2.51 (m, 2 H), 1.74 (dddd, J = 13.7,12.2,9.4,6.1Hz, 5 H), 1.17 (tt, J = 11.9,3.1Hz, 1 H), 1.07 – 0.95

(m, 2 H), 0.78 (s, 9 H). 13C{1H}-NMR (126 MHz, CDCl3): δ 144.5, 128.7, 127.5, 126.5, 73.6, 47.9, 39.0,

32.4, 27.7, 25.1. TLC (hexane/EtOAc 10:1): Rf = 0.26. HRMS (m/z): [M+Na]+ calcd. for C16H24NaO,

255.1719; found, 255.172.

The spectra of both isomers and the assigned stereochemistry of 7b is consistent with literature data.27,28

HO

1,1-diphenylethan-1-ol (7c)

Following General Procedure D1 with 1a and acetophenone (6c). Purification by column

chromatography (20:1 hexane:EtOAc) afforded 50.4 mg (51 %) of the title compound as

light yellow needles.

1H-NMR (500 MHz, CDCl3): δ 7.44 – 7.42 (m, 4 H), 7.35 – 7.31 (m, 4 H), 7.27 – 7.23 (m, 2 H), 2.14 (br

s, 1 H), 1.97 (s, 3 H). 13C{1H}-NMR (126 MHz, CDCl3): δ 148.1, 128.3, 127.1, 126, 76.4, 31.0. TLC (hex-ane/EtOAc 20:1): Rf = 0.15. HRMS (m/z): [M+Na]+ calcd. for C14H14NaO, 221.0937; found, 221.0934.


HO

2,4-diphenylbutan-2-ol (7d)

Following General Procedure D1 with 1a and 4-phenylbutan-2-one (6e). Purification by

column chromatography (20:1 to 10:1 to 5:1 hexane:EtOAc) afforded 98.0 mg (87 %)

of the title compound as yellow oil.

1H-NMR (400 MHz, CDCl3): δ 7.50 – 7.46 (m, 2 H), 7.40 – 7.35 (m, 2 H), 7.31 – 7.22 (m, 1 H), 7.25 –

7.22 (m, 2 H), 7.18 – 7.15 (m, 1 H), 7.14 – 7.10 (m, 2 H), 2.63 (ddd, J = 13.6,10.9,6.5Hz, 1 H), 2.45 (ddd,

J = 13.6,10.9,5.7Hz, 1 H), 2.14 (ddd, J = 11.6,5.8,5.1Hz, 2 H), 1.74 (s, 1 H), 1.62 (s, 3 H). 13C{1H}-NMR(101 MHz, CDCl3): δ 147.7, 142.4, 128.5, 128.5, 128.4, 126.8, 125.9, 124.9, 74.9, 46.1, 30.7, 30.6. TLC(hexane/EtOAc 10:1): Rf = 0.16. HRMS (m/z): [M+Na]+ calcd. for C16H18NaO, 249.125; found, 249.1249.


S31


HO

4-([1,1’-biphenyl]-4-yl)-2-phenylbutan-2-ol (7e)

Following General Procedure D1 with 1a and 6e. Purification by column chro-

matography (hexane to 8:1 hexane:EtOAc) afforded 119 mg (79 %) of the title

compound as yellow oil.


7.34 (m, 1 H), 7.34 – 7.30 (m, 1 H), 7.25 – 7.22 (m, 2 H), 2.72 (ddd, J = 13.7,11.1,6.2Hz, 1 H), 2.54 (ddd,

J = 13.7,11.1,5.6Hz, 1 H), 2.27 – 2.16 (m, 2 H), 1.88 (s, 1 H), 1.67 (s, 3 H). 13C{1H}-NMR (126 MHz,CDCl3): δ 147.6, 141.5, 141.2, 138.8, 128.8, 128.8, 128.4, 127.2, 127.1, 127.1, 126.8, 124.9, 74.8, 46.1,

30.7, 30.2. TLC (hexane/EtOAc 10:1): Rf = 0.13. HRMS (m/z): [M+Na]+ calcd. for C22H22NaO, 325.1563;

found, 325.1561.

HO

O O

8-phenyl-1,4-dioxaspiro[4.5]decan-8-ol (7f)

Following General Procedure D1 with 1a and 1,4-dioxaspiro[4.5]decan-8-one (6f). Purification

by column chromatography (5:1 to 3:1 to 2:1 hexane:EtOAc) afforded 100 mg (85 %) of the

title compound as an off-white solid.


4.02 – 3.96 (m, 4 H), 2.26 – 2.04 (m, 4 H), 1.86 – 1.78 (m, 2 H), 1.72 – 1.65 (m, 2 H), 1.53 (s, 1 H). 13C{1H}-NMR (126 MHz, CDCl3): δ 148.6, 128.4, 127.1, 124.7, 108.6, 72.6, 64.5, 64.4, 36.8, 30.9.1 TLC (hex-ane/EtOAc 2:1): Rf = 0.24. HRMS (m/z): [M+Na]+ calcd. for C14H18NaO3, 257.1148; found, 257.1147.


HO

NBn

1-benzyl-4-phenylpiperidin-4-ol (7g)

Following General Procedure D1 with 1a and 1-benzylpiperidin-4-one (6g). Purification by

column chromatography (1:1 hexane:EtOAc + 2% (v/v) NEt3) afforded 52.8 mg (40 %) of the

title compound as light yellow oil.

1H-NMR (400 MHz, CDCl3): δ 7.55 – 7.50 (m, 2 H), 7.39 – 7.31 (m, 6 H), 7.30 – 7.23 (m, 2 H), 3.60 (s,

2 H), 2.80 (dd, J = 11.2,2.9Hz, 2 H), 2.49 (td, J = 12.0,2.5Hz, 2 H), 2.18 (td, J = 13.5,4.5Hz, 2 H), 1.75

(dd, J = 14.2,2.9Hz, 2 H). 13C{1H}-NMR (101 MHz, CDCl3): δ 148.6, 138.5, 129.4, 128.5, 128.4, 127.2,

1The two signals 64.5 and 64.4 ppm likely stem from two magnetically inequivalent carbons on the six-membered ring.

S32


127.1, 124.7, 71.5, 63.4, 49.6, 38.6. TLC (hexane/EtOAc 1:1 + 2% (v/v) NEt3): Rf = 0.32. HRMS (m/z):[M+Na]+ calcd. for C18H21NNaO, 290.1515; found, 290.1519.


HO

MeO

4-(4-methoxyphenyl)-2-phenylbutan-2-ol (7h)

Following General Procedure D1 with 1a and 4-(4-methoxyphenyl)butan-2-one

(6h). Purification by column chromatography (10:1 to 5:1 hexane:EtOAc) af-

forded 84.5 mg (66 %) of the title compound as yellow oil.


7.03 (d, J = 8.8Hz, 2 H), 6.80 (d,J = 8.6Hz, 2 H), 3.77 (s, 3 H), 2.56 (ddd, J = 13.8,11.1,6.2Hz, 1 H),

2.40 (ddd, J = 13.8,11.1,5.5Hz, 1 H), 2.17 – 2.05 (m, 2 H), 1.73 (s, 1 H), 1.61 (s, 3 H). 13C{1H}-NMR(126 MHz, CDCl3): δ 157.9, 147.8, 134.4, 129.3, 128.4, 126.8, 124.9, 114.0, 74.9, 55.4, 46.3, 30.7, 29.7.

TLC (hexane/EtOAc 10:1): Rf = 0.18. HRMS (m/z): [M+Na]+ calcd. for C17H20NaO2, 279.1356; found,

279.136.

HO

S

OO

4-(4-(methylsulfonyl)phenyl)-2-phenylbutan-2-ol (7i)

Following General Procedure D1 with 1a and 6i. Purification by column chroma-

tography (1:1 hexane:EtOAc) afforded 82.5 mg (54 %) of the title compound as

off-white oil.

1H-NMR (500 MHz, CDCl3): δ 7.83 (d, J = 8.4Hz, 2 H), 7.49 (dd, J = 8.5,1.2Hz, 2 H), 7.42 – 7.38 (m, 2 H),

7.33 – 7.29 (m, 3 H), 3.04 (s, 3 H), 2.77 (ddd, J = 13.8,10.8,6.4Hz, 1 H), 2.54 (ddd, J = 13.8,10.9,6.0Hz,

1 H), 2.14 (ddd, J = 11.2,5.7,4.5Hz, 2 H), 1.76 (s, 1 H), 1.67 (s, 3 H). 13C{1H}-NMR (126 MHz, CDCl3):δ 149.3, 147.2, 138.1, 129.4, 128.5, 127.6, 127, 124.8, 74.6, 45.8, 44.7, 30.8, 30.7. TLC (hexane/EtOAc1:1): Rf = 0.36. HRMS (m/z): [M+Na]+ calcd. for C17H20NaO3S, 327.1025; found, 327.102.

HO

Me3Si

2-phenyl-4-(4-(trimethylsilyl)phenyl)butan-2-ol (7j)

Following General Procedure D1 with 1a and 4-(4-(trimethylsilyl)phenyl)butan-

2-one (6j). Purification by column chromatography (10:1 hexane:EtOAc) af-

forded 115 mg (77 %) of the title compound as yellow oil.

1H-NMR (400 MHz, CDCl3): δ 7.52 – 7.45 (m, 2 H), 7.44 – 7.33 (m, 4 H), 7.31 – 7.22 (m, 1 H), 7.12 (d,

J = 8.2Hz, 2 H), 2.62 (ddd, J = 13.5,10.9,6.5Hz, 1 H), 2.44 (ddd, J = 13.6,11.0,5.8Hz, 1 H), 2.14 (ddd,

S33


J = 11.6,5.7,5.1Hz, 2 H), 1.74 (s, 1 H), 1.62 (s, 3 H), 0.24 (s, 9 H). 13C{1H}-NMR (101 MHz, CDCl3): δ

147.7, 143.1, 137.5, 133.6, 128.4, 127.9, 126.8, 124.9, 74.9, 46.0, 30.8, 30.5, -0.9. TLC (hexane/EtOAc10:1): Rf = 0.18. HRMS (m/z): [M+Na]+ calcd. for C19H26NaOSi, 321.1645; found, 321.1645.

HO

O

O

methyl 3-(3-hydroxy-3-phenylbutyl)benzoate (7k)

Following General Procedure D2 with 1a and methyl 3-(3-oxobutyl)benzoate

(6k). Purification by column chromatography (5:1 hexane:EtOAc) afforded 103

mg (73 %) of the title compound as yellow oil.


(m, 2 H), 7.32 – 7.29 (m, 2 H), 7.30 – 7.25 (m, 1 H), 3.90 (s, 3 H), 2.69 (dddd, J = 13.7,11.1,5.9,0.6Hz,

1 H), 2.48 (dddd, J = 13.6,11.7,5.5,0.6Hz, 1 H), 2.20 – 2.06 (m, 2 H), 1.75 (s, 1 H), 1.63 (s, 3 H). 13C{1H}-NMR (126 MHz, CDCl3): δ 167.4, 147.5, 142.8, 133.2, 130.3, 129.5, 128.5, 128.5, 127.2, 126.9, 124.9, 74.7,

52.2, 46, 30.7, 30.4. TLC (hexane/EtOAc 5:1): Rf = 0.23. HRMS (m/z): [M+Na]+ calcd. for C18H20NaO3,

307.1305; found, 307.1303.

HO

O

O

tert-butyl 3-(3-hydroxy-3-phenylbutyl)benzoate (7l)

Following General Procedure D1 with 1a and tert-butyl 3-(3-oxobutyl)benzo-

ate (6l). Purification by column chromatography (10:1 hexane:EtOAc) af-

forded 109 mg (67 %) of the title compound as colorless oil.

1H-NMR (400 MHz, CDCl3): δ 7.78 (ddd, J = 6.3,2.8,1.8Hz, 1 H), 7.74 (s, 1 H), 7.50 – 7.46 (m, 2 H), 7.37

(t, J = 7.6Hz, 2 H), 7.29 – 7.24 (m, 3 H), 2.68 (ddd, J = 13.7,11.0,6.3Hz, 1 H), 2.48 (ddd, J = 13.7,11.0,5.7

Hz, 1 H), 2.13 (dt, J = 11.7,5.5Hz, 2 H), 1.74 (s, 1 H), 1.63 (s, 3 H), 1.59 (s, 9 H). 13C{1H}-NMR (101MHz, CDCl3): δ 166.1, 147.6, 142.6, 132.6, 132.2, 129.4, 128.5, 128.3, 127.1, 126.9, 124.9, 81.1, 74.8, 46.1,

30.7, 30.4, 28.4. TLC (hexane/EtOAc 10:1): Rf = 0.24. HRMS (m/z): [M+Na]+ calcd. for C21H26NaO3,

349.1774; found, 349.1772.

HO

N

O

N,N-diethyl-4-(3-hydroxy-3-phenylbutyl)benzamide (7m)

Following General Procedure D1 with 1a and 6m. Purification by column

chromatography (1:1 hexane:EtOAc) afforded 125 mg (77 %) of the title com-

pound as off-white oil.


7.12 (dd, J = 7.9,0.6Hz, 2 H), 3.38 (br d, 4 H, NCH2CH3), 2.64 (ddd, J = 13.7,11.2,6.1Hz, 1 H), 2.44 (ddd,

J = 13.7,11.2,5.5Hz, 1 H), 2.18 – 2.03 (m, 2 H), 1.82 (s, 1 H), 1.62 (s, 3 H), 1.16 (br d, 6 H, NCH2CH3).

S34


13C{1H}-NMR (126 MHz, CDCl3): δ 171.5, 147.6, 143.7, 134.9, 128.4, 128.4, 126.9, 126.6, 124.9, 74.7,

46, 43.4 (NEt2 rotamer A), 39.3 (NEt2 rotamer B), 30.7, 30.5, 14.4 (NEt2 rotamer A), 13.1 (NEt2 rotamer B).

TLC (hexane/EtOAc 1:1): Rf = 0.24. HRMS (m/z): [M+Na]+ calcd. for C21H27NNaO2, 348.1934; found,

348.1936.

HO

Cl

4-(4-chlorophenyl)-2-phenylbutan-2-ol (7n)

Following General Procedure D1 with 1a and 4-(4-chlorophenyl)butan-2-one (6n)

with a reaction time of 48 h. Purification by column chromatography (10:1 hex-

ane:EtOAc) afforded 66.6 mg (51 %) of the title compound as yellow oil.

1H-NMR (500 MHz, CDCl3): δ 7.50 – 7.44 (m, 2 H), 7.41 – 7.34 (m, 2 H), 7.31 – 7.23 (m, 1 H), 7.20 (d, J =

8.4Hz, 2 H), 7.04 (d, J = 8.7Hz, 2 H), 2.60 (ddd, J = 13.8,11.1,6.2Hz, 1 H), 2.40 (ddd, J = 13.8,11.1,5.7

Hz, 1 H), 2.15 – 2.03 (m, 2 H), 1.72 (s, 1 H), 1.62 (s, 3 H). 13C{1H}-NMR (126 MHz, CDCl3): δ 147.5,

140.9, 131.6, 129.8, 128.6, 128.5, 126.9, 124.9, 74.8, 46.1, 30.7, 30.0. TLC (hexane/EtOAc 10:1): Rf =

0.13. HRMS (m/z): [M+Na]+ calcd. for C16H17ClNaO, 283.0860; found, 283.0860.

HO

O

4-(furan-3-yl)-2-phenylbutan-2-ol (7o)

Following General Procedure D1 with 1a and 4-(furan-3-yl)butan-2-one (6o). Purifica-

tion by column chromatography (hexane to 10:1 to 5:1 hexane:EtOAc) afforded 83.3 mg

(77 %) of the title compound as brown oil.

1H-NMR (500 MHz, CDCl3): δ 7.49 – 7.43 (m, 2 H), 7.39 – 7.34 (m, 2 H), 7.32 (t, J = 1.7Hz, 1 H), 7.30 –

7.22 (m, 1 H), 7.15 (dd, J = 1.6,0.9Hz, 1 H), 6.22 (dd, J = 1.8,0.9Hz, 1 H), 2.44 (dddd, J = 14.7,10.8,6.2,1.1

Hz, 1 H), 2.31 – 2.20 (m, 1 H), 2.17 – 1.99 (m, 2 H), 1.71 (br s, 1 H), 1.61 (s, 3 H). 13C{1H}-NMR (126MHz, CDCl3): δ 147.6, 142.9, 138.7, 128.4, 126.8, 125.0, 124.9, 111.0, 74.8, 44.3, 30.6, 19.7. TLC (hex-ane/EtOAc 9:1): Rf = 0.20. HRMS (m/z): [M+Na]+ calcd. for C14H16NaO2, 239.1043; found, 239.1044.

O

HO

4-(6-methoxynaphthalen-2-yl)-2-phenylbutan-2-ol (7p)

Following General Procedure D3 with 1a and nabumetone (6p). Purifica-

tion by column chromatography (9:1 to 4:1 hexane:EtOAc) afforded mixed

fractions of the product and starting material 6p. After derivatization, the

crude was purified by column chromatography (5:1 hexane:EtOAc) to afford


1H-NMR (500 MHz, CDCl3): δ 7.63 (d, J = 8.4Hz, 2 H), 7.53 – 7.49 (m, 2 H), 7.49 – 7.47 (m, 1 H), 7.45 –

7.34 (m, 2 H), 7.32 – 7.26 (m, 1 H), 7.23 (dd, J = 8.4,1.8Hz, 1 H), 7.14 – 7.07 (m, 2 H), 3.90 (s, 3 H), 2.76

S35


(ddd, J = 13.7,11.1,6.1Hz, 1 H), 2.58 (ddd, J = 13.8,11.2,5.5Hz, 1 H), 2.28 – 2.14 (m, 2 H), 1.77 (s, 1 H),

1.65 (s, 3 H). 13C{1H}-NMR (126 MHz, CDCl3): δ 157.3, 147.8, 137.5, 133.1, 129.3, 129.0, 128.4, 127.9,

126.9, 126.8, 126.2, 125.0, 118.8, 105.8, 74.9, 55.4, 46.1, 30.8, 30.6. TLC (hexane/EtOAc 10:1): Rf = 0.08.

HRMS (m/z): [M+Na]+ calcd. for C21H22NaO2, 329.1512; found, 329.1513.

N

N

N

N

O

OHO Me

1-(5-

hydroxy-5-phenylhexyl)-3,7-dimethyl-3,7-dihydro-1H-purine-2,6-dione

(7q)

Following General Procedure D1 with 1a and pentoxifylline (6q) with a reac-

tion time of 48 h. Purification by column chromatography (EtOAc) afforded

115 mg (64 %) of the title compound as off-white solid.


7.15 (m, 1 H), 3.95 – 3.91 (m, 5 H), 3.52 (s, 3 H), 2.42 (br s, 1 H), 1.89 – 1.83 (m, 2 H), 1.59 (p, J = 7.4Hz,

2 H), 1.52 (s, 3 H), 1.39 – 1.27 (m, 1 H), 1.22 – 1.12 (m, 1 H). 13C{1H}-NMR (126 MHz, CDCl3): δ 155.5,

151.6, 148.8, 148.2, 141.5, 128.1, 126.4, 124.9, 107.7, 74.4, 43.5, 40.9, 33.6, 30.3, 29.8, 28.0, 21.1. TLC(EtOAc): Rf = 0.20. HRMS (m/z): [M+Na]+ calcd. for C19H24N4NaO3, 379.1741; found, 379.1739.

4.2 Alcohol side

HO

4-phenyl-2-(p-tolyl)butan-2-ol (8a)

Following General Procedure D1 with tri-p-tolylmethanol (1b) and 4-phenylbutan-2-

one (6d). Purification by column chromatography (20:1 to 10:1 hexane:EtOAc) af-

forded 81.4 mg (68 %) of the title compound as yellow oil.

1H-NMR (500 MHz, CDCl3): δ 7.37 (d, J = 8.3Hz, 2 H), 7.29 – 7.21 (m, 2 H), 7.20 – 7.15 (m, 3 H), 7.15

– 7.11 (m, 2 H), 2.62 (ddd, J = 13.7,11.0,6.3Hz, 1 H), 2.46 (ddd, J = 13.7,11.0,5.6Hz, 1 H), 2.36 (s, 3 H),


129.1, 128.5, 128.5, 125.9, 124.8, 74.8, 46.1, 30.7, 30.7, 21.1. TLC (hexane/EtOAc 10:1): Rf = 0.10. HRMS(m/z): [M+Na]+ calcd. for C17H20NaO, 263.1406; found, 263.1404.

HO

2-(4-(tert-butyl)phenyl)-4-phenylbutan-2-ol (8b)

Following General Procedure D1 with tris(4-(tert-butyl)phenyl)methanol (1c) and

4-phenylbutan-2-one (6d). Purification by column chromatography (10:1 hexane:EtOAc)

afforded 72.4 mg (51 %) of the title compound as off white solid.

S36


1H-NMR (500 MHz, CDCl3): δ 7.46 – 7.34 (m, 4 H), 7.29 – 7.19 (m, 2 H), 7.19 – 7.09 (m, 3 H), 2.64 (ddd,

J = 13.6,11.1,6.2Hz, 1 H), 2.51 (ddd, J = 13.6,11.0,5.7Hz, 1 H), 2.20 – 2.07 (m, 2 H), 1.75 (s, 1 H), 1.62

(s, 3 H), 1.35 (s, 9 H). 13C{1H}-NMR (126 MHz, CDCl3): δ 149.6, 144.7, 142.5, 128.5, 128.5, 125.8, 125.3,


calcd. for C20H26NaO, 305.1876; found, 305.1881.

HO

2-(3,5-dimethylphenyl)-4-phenylbutan-2-ol (8c)

Following General Procedure D3 with tris(3,5-dimethylphenyl)methanol (1d) and

4-phenylbutan-2-one (6d). Purification by column chromatography (20:1 to 10:1

hexane:EtOAc) afforded mixed fractions of the product and starting material 6d.

After derivatization, the crude was purified by column chromatography (10:1 hex-

ane:EtOAc) afforded 89.4 mg (70 %) of the title compound as colorless oil.


7.08 (m, 2 H), 6.93 – 6.90 (m, 1 H), 2.64 (ddd, J = 13.7,11.2,6.2Hz, 1 H), 2.48 (ddd, J = 13.7,11.1,5.6Hz,

1 H), 2.35 (app d, 6 H), 2.18 – 2.04 (m, 2 H), 1.72 (s, 1 H), 1.60 (s, 3 H). 13C{1H}-NMR (126 MHz, CDCl3):δ 147.8, 142.6, 137.9, 128.5, 128.5, 128.4, 125.9, 122.7, 74.8, 46.0, 30.7, 30.6, 21.7. TLC (hexane/EtOAc10:1): Rf = 0.20. HRMS (m/z): [M+Na]+ calcd. for C18H22NaO, 277.1563; found, 277.1565.

HO

2-(naphthalen-2-yl)-4-phenylbutan-2-ol (8d)

Following General Procedure D1 with tri(naphthalen-2-yl)methanol (1e) and 4-

phenylbutan-2-one (6d). Purification by column chromatography (20:1 to 10:1

hexane:EtOAc) afforded 120 mg (87 %) of the title compound as pale oil.

1H-NMR (500 MHz, CDCl3): δ 7.97 (s, 1 H), 7.91 – 7.81 (m, 3 H), 7.57 (dd, J = 8.6,1.8Hz, 1 H), 7.54 – 7.44

(m, 2 H), 7.25 – 7.21 (m, 2 H), 7.18 – 7.13 (m, 1 H), 7.12 (d, J = 6.9Hz, 2 H), 2.66 (ddd, J = 13.8,11.6,5.7Hz,

1 H), 2.46 (ddd, J = 13.8,11.8,5.0Hz, 1 H), 2.32 – 2.16 (m, 2 H), 1.88 (br s, 1 H), 1.71 (s, 3 H). 13C{1H}-NMR (126 MHz, CDCl3): δ 145.0, 142.4, 133.4, 132.4, 128.5, 128.5, 128.3, 128.2, 127.6, 126.3, 125.9,


calcd. for C20H20NaO, 299.1406; found, 299.1405.

HO

F

2-(4-fluorophenyl)-4-phenylbutan-2-ol (8e)

Following General Procedure D1 with tris(4-fluorophenyl)methanol (1f) and 4-phenylbutan-

2-one (6d). Purification by column chromatography (10:1 hexane:EtOAc) afforded

83.3 mg (68 %) of the title compound as brown oil.

S37




1 H), 2.18 – 2.05 (m, 2 H), 1.71 (s, 1 H), 1.61 (s, 3 H). 13C{1H}-NMR (126 MHz, CDCl3): δ 161.7 (d,1JCF = 244.8Hz), 143.3 (d, 4JCF = 3.1Hz), 142.1, 128.4, 128.3, 126.5 (d, 3JCF = 8.0Hz), 125.9, 115.0 (d,2JCF = 21.1Hz), 74.5, 46.1, 30.7, 30.5. 19F{1H}-NMR (471 MHz, CDCl3): δ -116.79 TLC (hexane/EtOAc10:1): Rf = 0.14. HRMS (m/z): [M+Na]+ calcd. for C16H17FNaO, 267.1156; found, 267.1156.

HO

Cl

2-(4-chlorophenyl)-4-phenylbutan-2-ol (8f)

Following General Procedure D1 with tris(4-chlorophenyl)methanol (1g) and 4-phenylbutan-

2-one (6d). Purification by column chromatography (20:1 to 10:1 hexane:EtOAc)

afforded 98.7 mg (76 %) of the title compound as brown oil.


(m, 1 H), 7.14 – 7.08 (m, 2 H), 2.62 (ddd, J = 13.6,10.5,6.8Hz, 1 H), 2.42 (ddd, J = 13.7,10.5,6.1Hz, 1 H),


128.6, 128.5, 128.4, 126.5, 126.0, 74.6, 46.1, 30.8, 30.5. TLC (hexane/EtOAc 10:1): Rf = 0.15. HRMS(m/z): [M+Na]+ calcd. for C16H17ClNaO, 283.0860; found, 283.0858.

HO

OMe

2-(4-methoxyphenyl)-4-phenylbutan-2-ol (8g)

Following slightly modified General Procedure D3 with tris(4-methoxyphenyl)-

methanol (1h) and 4-phenylbutan-2-one (6d). Purification by column chromatogra-

phy (10:1 to 5:1 hexane:EtOAc) afforded mixed fractions of the product and the di-

arylketone byproduct. The concentrated suspension of a solid in an oil was extracted

with hexane to remove most of the diarylketone. After derivatization, the crude was

purified by column chromatography (5:1 hexane:EtOAc) afforded 60.6 mg (47 %)

of the title compound as colorless oil.

1H-NMR (500 MHz, CDCl3): δ 7.43 (d, J = 8.9Hz, 2 H), 7.27 (t, J = 7.4Hz, 2 H), 7.22 – 7.16 (m, 1 H), 7.16

– 7.14 (m, 2 H), 6.93 (d, J = 8.8Hz, 2 H), 3.84 (s, 3 H), 2.63 (ddd, J = 13.7,10.5,6.9Hz, 1 H), 2.49 (ddd, J =

13.6,10.4,6.3Hz, 1 H), 2.19 – 2.08 (m, 2 H), 1.82 (s, 1 H), 1.62 (s, 3 H). 13C{1H}-NMR (126 MHz, CDCl3):δ 158.4, 142.5, 139.9, 128.5, 128.4, 126.1, 125.9, 113.7, 74.5, 55.4, 46.2, 30.7, 30.6. TLC (hexane/EtOAc5:1): Rf = 0.22. HRMS (m/z): [M+Na]+ calcd. for C17H20NaO2, 279.1356; found, 279.1357.


S38


HO

CF34-phenyl-2-(4-(trifluoromethyl)phenyl)butan-2-ol (8h)

Following General Procedure D1 with tris(4-trifluoromethyl)methanol (1i) and 4-

phenylbutan-2-one (6d). Purification by column chromatography (10:1 hexane:EtOAc)

afforded 118 mg (80 %) of the title compound as brown oil.

1H-NMR (500 MHz, CDCl3): δ 7.65 – 7.59 (app q, 4 H), 7.26 (t, J = 7.5Hz, 2 H), 7.20 – 7.15 (app t, 1 H),

7.13 – 7.10 (app d, 2 H), 2.65 (ddd, J = 13.7,11.1,6.1Hz, 1 H), 2.42 (ddd, J = 13.7,11.1,5.5Hz, 1 H), 2.22

– 2.09 (m, 2 H), 1.80 (s, 1 H), 1.63 (s, 3 H). 13C{1H}-NMR (126 MHz, CDCl3): δ 151.7, 141.9, 129.1 (q,

J = 32.4Hz), 128.6, 128.4, 126.1, 125.4, 125.4 (q, J = 3.8Hz), 124.6 (q, J = 272.2Hz), 74.8, 46.0, 30.8,

30.4. 19F{1H}-NMR (471 MHz, CDCl3): δ -62.35. TLC (hexane/EtOAc 10:1): Rf = 0.10. 0.10 HRMS(m/z): [M−H2+Na]+ calcd. for C17H15F3NaO, 315.0967; found, 315.0968.

HO

OCF3

4-phenyl-2-(4-(trifluoromethoxy)phenyl)butan-2-ol (8i)

Following General Procedure D1 with tris(4-(trifluoromethoxy)phenyl)methanol

(1j) and 4-phenylbutan-2-one (6d). Purification by column chromatography (10:1

hexane:EtOAc) afforded 116 mg (75 %) of the title compound as beige solid.



1 H), 2.18 – 2.08 (m, 2 H), 1.76 (s, 1 H), 1.62 (s, 3 H). 13C{1H}-NMR (126 MHz, CDCl3): δ 148.1 (q,3JCF = 1.6Hz), 146.4, 142.1, 128.6, 128.4, 126.5, 126.0, 120.7 (q, 1JCF = 256.9Hz), 120.8 (m), 74.6, 46.1,

30.7, 30.5. 19F{1H}-NMR (471 MHz, CDCl3): δ -57.82. TLC (hexane/EtOAc 10:1): Rf = 0.11. HRMS(m/z): [M+Na]+ calcd. for C17H17F3NaO2, 333.1073; found, 333.1082.

HO

CF3

CF3

2-(3,5-bis(trifluoromethyl)phenyl)-4-phenylbutan-2-ol (8j)

Following General Procedure D3 with tris(3,5-bis(trifluoromethyl)phenyl)methanol

(1k) and 4-phenylbutan-2-one (6d). Purification by column chromatography (20:1

to 10:1 hexane:EtOAc) afforded mixed fractions of the product and starting ma-

terial 6d. After derivatization, the crude was purified by column chromatography

(10:1 hexane:EtOAc) afforded 70.5 mg (39 %) of the title compound as brown oil.



1 H), 2.24 – 2.11 (m, 2 H), 1.83 (s, 1 H), 1.66 (s, 3 H). 13C{1H}-NMR (126 MHz, CDCl3): δ 150.5, 141.4,

131.7 (q, 2JCF = 33.1Hz), 128.7, 128.4, 126.3, 125.6 – 125.3 (m), 123.6 (q, 1JCF = 272.8Hz), 120.9 (sept,

S39


3JCF = 3.9Hz), 74.6, 45.9, 30.8, 30.4. 19F{1H}-NMR (471 MHz, CDCl3): δ -62.72.TLC (hexane/EtOAc10:1): Rf = 0.24. HRMS (m/z): [M+Na]+ calcd. for C18H16F6NaO, 385.0998; found, 385.1000.


HO

OO

2-(benzo[d][1,3]dioxol-5-yl)-4-phenylbutan-2-ol (8k)

Following General Procedure D2 with tris(benzo[d][1,3]dioxol-5-yl)methanol (1l) and

4-phenylbutan-2-one (6d). Purification by column chromatography (10:1 to 5:1 hex-

ane:EtOAc) afforded 62.1 mg (46 %) of the title compound as colorless oil.

1H-NMR (500 MHz, CDCl3): δ 7.29 – 7.22 (m, 2 H), 7.19 – 7.11 (m, 3 H), 6.99 (d, J = 1.7Hz, 1 H), 6.94

(dd, J = 8.1,1.9Hz, 1 H), 6.80 (d, J = 8.1Hz, 1 H), 5.96 (s, 2 H), 2.61 (ddd, J = 13.7,10.4,6.9Hz, 1 H), 2.47

(ddd, J = 13.6,10.4,6.3Hz, 1 H), 2.16 – 2.02 (m, 2 H), 1.72 (s, 1 H), 1.58 (s, 3 H). 13C{1H}-NMR (126 MHz,CDCl3): δ 147.8, 146.3, 142.4, 142, 128.5, 128.4, 125.9, 118.0, 108.0, 106.1, 101.1, 74.8, 46.2, 30.8, 30.6.

TLC (hexane/EtOAc 5:1): Rf = 0.24. HRMS (m/z): [M+Na]+ calcd. for C17H18NaO3, 293.1148; found,

293.1151.

HO O

2-(benzofuran-2-yl)-4-phenylbutan-2-ol (8l)

Following General Procedure D1 with tri(benzofuran-2-yl)methanol (1m) and 4-phenylbutan-

2-one (6d). Purification by column chromatography (10:1 hexane:EtOAc, then 10:1

hexane:acetone) afforded 90.5 mg (68 %) of the title compound as yellow oil.

1H-NMR (500 MHz, CDCl3): δ 7.56 (ddd, J = 7.5,1.5,0.7Hz, 1 H), 7.49 – 7.46 (m, 1 H), 7.31 – 7.20 (m,

4 H), 7.19 – 7.15 (m, 3 H), 6.65 (d, J = 0.9Hz, 1 H), 2.72 – 2.57 (m, 2 H), 2.34 – 2.19 (m, 2 H), 2.14 (s, 1 H),

1.70 (s, 3 H). 13C{1H}-NMR (126 MHz, CDCl3): δ 162.3, 154.9, 141.9, 128.6, 128.5, 128.4, 126, 124.1,

122.9, 121.1, 111.3, 101.7, 72.2, 43.4, 30.7, 27.3. TLC (hexane/EtOAc 10:1): Rf = 0.10. HRMS (m/z):[M+Na]+ calcd. for C18H18NaO2, 289.1199; found, 289.1203.

HO

O

2-(benzofuran-5-yl)-4-phenylbutan-2-ol (8m)

Following General Procedure D1 with tri(benzofuran-5-yl)methanol (1n) and 4-phenylbutan-

2-one (6d). Purification by column chromatography (10:1 hexane:EtOAc, then 10:1

hexane:acetone) afforded 73.7 mg (55 %) of the title compound as light yellow oil.

S40


1H-NMR (500 MHz, CDCl3): δ 7.76 – 7.74 (m, 1 H), 7.64 (d, J = 2.2Hz, 1 H), 7.51 – 7.48 (m, 1 H), 7.41

(dd, J = 8.7,1.9Hz, 1 H), 7.24 (d, J = 7.7Hz, 2 H), 7.15 (t, J = 7.4Hz, 1 H), 7.12 (d, J = 7.6Hz, 2 H),

6.78 (dd, J = 2.2,0.9Hz, 1 H), 2.64 (ddd, J = 13.6,11.3,6.0Hz, 1 H), 2.46 (ddd, J = 13.5,11.2,5.4Hz,

1 H), 2.25 – 2.13 (m, 2 H), 1.81 (s, 1 H), 1.68 (s, 3 H). 13C{1H}-NMR (126 MHz, CDCl3): δ 154.0, 145.5,

142.4, 128.5, 128.4, 127.4, 125.9, 121.6, 117.5, 111.1, 106.9, 75.0, 46.5, 31.2, 30.7.2 1H-NMR (500 MHz,CD2Cl2): δ 7.75 (dd, J = 1.9,0.7Hz, 1 H), 7.65 (d, J = 2.2Hz, 1 H), 7.48 (dt, J = 8.7,0.8Hz, 1 H), 7.42 (ddd,

J = 8.7,1.9,0.4Hz, 1 H), 7.25 – 7.21 (m, 2 H), 7.16 – 7.09 (m, 3 H), 6.80 (dd, J = 2.2,1.0Hz, 1 H), 2.61 (ddd,

J = 13.7,11.6,5.7Hz, 1 H), 2.41 (ddd, J = 13.6,11.6,5.2Hz, 1 H), 2.15 (td, J = 11.4,5.3Hz, 2 H), 1.87 (s,

1 H), 1.65 (s, 3 H). 13C{1H}-NMR (126 MHz, CD2Cl2): δ 154.4, 146.0, 143.1, 143.1, 128.8, 128.8, 127.8,

126.2, 122.2, 118.0, 111.3, 107.3, 75.2, 47.1, 31.4, 31.1. TLC (hexane/EtOAc 10:1): Rf = 0.09. HRMS(m/z): [M+Na]+ calcd. for C18H18NaO2, 289.1199; found, 289.1199.

HO

N O

2-(4-(morpholinomethyl)phenyl)-4-phenylbutan-2-ol (8n)

Following General Procedure D1 with tris(4-(morpholinomethyl)phenyl)me-

thanol (1o) and 4-phenylbutan-2-one (6d). Purification by column chromato-

graphy (1:1 to 1:2 hexane:EtOAc to pure EtOAc) afforded 112 mg (69 %) of

the title compound as yellow oil.

1H-NMR (500 MHz, CDCl3): δ 7.43 (d, J = 8.4Hz, 2 H), 7.32 (d, J = 8.5Hz, 2 H), 7.27 – 7.21 (m, 2 H), 7.17

– 7.13 (m, 1 H), 7.13 – 7.11 (m, 2 H), 3.76 – 3.66 (app t, 4 H), 3.51 (s, 2 H), 2.62 (ddd, J = 13.7,11.2,6.1Hz,

1 H), 2.49 – 2.41 (m, 5 H), 2.19 – 2.06 (m, 2 H), 1.78 (br s, 1 H), 1.61 (s, 3 H). 13C{1H}-NMR (126 MHz,CDCl3): δ 146.7, 142.4, 136.2, 129.3, 128.5, 128.4, 125.9, 124.9, 74.8, 67.2, 63.2, 53.8, 46.1, 30.6, 30.6.

TLC (hexane/EtOAc 1:1): Rf = 0.16. HRMS (m/z): [M+Na]+ calcd. for C21H27NNaO2, 348.1934; found,

348.1932.

4.3 Unsymmetrical alcohols

HO

2,4-diphenylbutan-2-ol (9a)

Following General Procedure D1 with 1,1-diphenylethan-1-ol (1p) and 4-phenylbutan-

2-one (6d) with a reaction time of 48 h. Purification by column chromatography (10:1

hexane:EtOAc) afforded 61.6 mg (54 %) of the title compound as light yellow oil.


(m, 1 H), 7.14 – 7.11 (m, 2 H), 2.63 (ddd, J = 13.6,11.2,6.1Hz, 1 H), 2.45 (ddd, J = 13.6,11.2,5.5Hz, 1 H),


2Two signals are overlapping.

S41


128.5, 128.4, 126.8, 125.9, 124.9, 74.9, 46.1, 30.7, 30.6. TLC (hexane/EtOAc 10:1): Rf = 0.16. HRMS(m/z): [M+Na]+ calcd. for C16H18NaO, 249.1250; found, 249.1250.


OH

4,4-dimethyl-1-phenylcyclohexan-1-ol (9b)

Following General Procedure D1 with diphenylmethanol (1q) and 4,4-dimethylcyclohe-

xan-1-one (6a) with a reaction time of 48 h. Purification by column chromatography (20:1

to 10:1 hexane:EtOAc, then 10:1 hexane:EtOAc, then 20:1 hexane:acetone) afforded

26.9 mg (26 %) of the title compound as a light yellow semicrystalline solid. Trace

amounts (1 % by GC-FID) of Ph3COH (1a) could not be removed during purification.

The yield reflects the purity.


(m, 2 H), 1.74 – 1.65 (m, 4 H), 1.52 (s, 1 H), 1.35 – 1.24 (m, 2 H), 1.01 (s, 3 H), 0.99 (s, 3 H). 13C{1H}-NMR(126 MHz, CDCl3): δ 149.4, 128.4, 126.9, 124.7, 73.0, 35.2, 35.0, 32.5, 29.5, 24.1. TLC (hexane/EtOAc10:1): Rf = 0.38. HRMS (m/z): [M+Na]+ calcd. for C14H20NaO, 227.1406; found, 227.1408.


4.4 Scale-up

[Rh(cod)Cl]2 (0.5 mol%)

IPr*OMe ⋅ HBF4 (1 mol%)

KOtBu (1 mol%)

K3PO4 (1 equiv.)

PhMe

125 °C, 72 h

OH

PhPh

+

1.5 equiv.

O

PhOH

Ph

70% (1.57 g)10 mmol

Ph Ph

O+

116%1a 6d 7d' 3a'

An oven-dried 100 mL Schlenk round-bottom flask equipped with a magnetic stirring bar was charged with

triphenylmethanol (1a) (3.91 g, 15.0 mmol, 1.5 equiv.) and K3PO4 (2.12 g, 10.0 mmol, 1.0 equiv.) and placed

under nitrogen. Then, toluene (45 mL) and 4-phenylbutan-2-one (6d) (1.5 mL, 10.0 mmol, 1.0 equiv.) were

added via syringe. In the Glovebox, a 10 mL Schlenk round-bottom flask was charged with [Rh(cod)Cl]2

(24.7 mg, 50 µmol, 0.5 mol%), L30 · HBF4 (103 mg, 100 µmol, 1 mol%) and KOtBu (11.2 mg, 100 µmol, 1

mol%). The flask was sealed and removed from the Glovebox, connected to the Schlenk line and toluene

(5.0 mL) was added. The resulting yellow almost homogeneous mixture was stirred for 15 min at 25 °C.

The catalyst solution was transferred into the reaction mixture via cannula. The reaction vessel was sealed

(closed system) and the light yellow reaction mixture was stirred at 125 °C for 72 h. Over the course of

S42


the reaction, the color changed from yellow to orange to brown. After cooling to room temperature, the

reaction mixture was exposed to air, and partitioned between water and EtOAc (50 mL each). The phases

were separated, and the aqueous layer was extracted with EtOAc (2 × 50 mL). The combined organic phases

were dried over Na2SO4 and concentrated under reduced pressure to afford a crude brown oil. Purification

by column chromatography (10:1 hexane:EtOAc) afforded 2,4-diphenylbutan-2-ol (7d’) (1.57 g, 70 %)3 as

yellow oil and benzophenone (3a’) (2.11 g, 116 %, 77 % with respect to 1a) as colorless needles.

2,4-diphenylbutan-2-ol (7d’) 1H-NMR (500 MHz, CDCl3): δ 7.51 – 7.48 (m, 2 H), 7.38 (dddd, J =

8.0,6.3,1.4,0.6Hz, 2 H), 7.29 – 7.26 (m, 1 H), 7.25 (d, J = 7.6Hz, 2 H), 7.18 – 7.14 (m, 1 H), 7.14 – 7.11

(m, 2 H), 2.64 (ddd, J = 13.7,11.2,6.2Hz, 1 H), 2.46 (ddd, J = 13.7,11.2,5.5Hz, 1 H), 2.21 – 2.07 (m, 2 H),

1.76 (br s, 1 H), 1.63 (s, 3 H). 13C{1H}-NMR (126 MHz, CDCl3): δ 147.7, 142.4, 128.5, 128.5, 128.4, 126.8,

125.9, 124.9, 74.9, 46.1, 30.7, 30.6. TLC (hexane/EtOAc 10:1): Rf = 0.16. HRMS (m/z): [M+Na]+ calcd.

for C16H18NaO, 249.125; found, 249.1248.


benzophenone (3a’) 1H-NMR (500 MHz, CDCl3): δ 7.84 – 7.76 (m, 4 H), 7.62 – 7.57 (m, 2 H), 7.53 –

7.45 (m, 4 H). 13C{1H}-NMR (126 MHz, CDCl3): δ 196.9, 137.8, 132.6, 130.2, 128.4. TLC (hexane/EtOAc10:1): Rf = 0.43. HRMS (m/z): [M+H]+ calcd. for C13H11O, 183.0804; found, 183.0807.


4.5 Substrate limitations

The following substrates were examined under the standard reaction conditions (see Section 4). However,

low conversion of the alcohol donor or acceptor ketone4 were noted.

3After column chromatography purification 1.34 g (59 %) of the alcohol product was isolated directly in addition to mixed fractionswith remaining starting material ketone. After purification of the mixed fractions by column chromatography a second crop ofproduct was obtained (0.230 g, 10 %).

4While conversion of the ketone was low, oftentimes formation of benzophenone and benzene was observed.

S43


O

R

H2N

O

Bpin HO

O

O

O

S

O

O

O

(a) low conversion

(b) decomposition

O

NBoc

O O

Br I

O

O2N

O

O

OH

O

TfO

Supplementary Table S12: Incompatible acceptor substrates.

(a) low conversion

(b) β−carbon elimination but no ketone addition

N

N

Ph

OH

PhCF3 CF3

OH

PhPh

OHPh

PhOH

FF

H3CH3C

OH

Ph

iPriPr

OH

TIPS

MeMe

OH

R

Me

OMe

N

MeMe

OH

FF

OMe

(c) decomposition

oToloTol

OH

OHAr

Ar

OH

TIPS

Supplementary Table S13: Incompatible donor substrates.

4.6 Not isolated products

The following substrates could be arylated using the general procedure (see Section 4) but could not be

isolated due to co-elution with either remaining starting materials or ketone byproduct.

S44

5 Mechanistic investigation Supporting Information

HOCH3

HO

OH

Ph

Ph

Ph

HO

O

Ph

OH

Ph

medium conversion 51% isolated(65% purity)

high conversion

medium conversion

high conversion

O

F

MeO

full conversion

PhPh

OH

OMe

OH

from

HO Ph

high conversion

medium conversion

46% isolated (90% purity)

612

F

PhPh

OH

F

OH

from

48% isolated(95% purity)

O

F

from

F

O

OMeMeO

O

CF3

CF3CF3

CF3

fromO

MeO

fromO

CF3

CF3

high conversion

high conversion

Ph

OH

Supplementary Table S14: Not isolated substrates.

5 Mechanistic investigation

5.1 Intermolecular competition experiments

Procedure A 4 mL vial under air was charged with 1a (130 mg, 0.500 mmol, 5.0 equiv.), 1x (0.500 mmol,

5.0 equiv.), 6a (12.6 mg, 0.100 mmol, 1.0 equiv.) and a magnetic stirring bar. A second 4 mL vial was charged

with L30 · HBF4 (5.2 mg, 5 µmol, 5 mol%), and both vials were transferred into the Glovebox. [Rh(cod)Cl]2

(1.2 mg, 2.5 µmol, 2.5 mol%), KOtBu (0.6 mg, 5 µmol, 5 mol%), and toluene (0.50 mL) were added into the

ligand-containing vial and the resulting yellow almost homogeneous mixture was stirred for about 5 min. The

substrate-containing vial was charged with K3PO4 (21.2 mg, 0.100 mmol, 1.0 equiv.), n-dodecane (22.0 µL,

0.0970 mmol) as internal standard, and the catalyst solution. The vial was sealed with a screw cap, taken out

of the Glovebox, placed in a preheated heating block at 125 °C and stirred for 24 h. After cooling to room

temperature again, the reaction was analyzed by gas chromatography.

S45


Supplementary Table S15: Intermolecular competition.



KOtBu (5 mol%)

K3PO4 (1 equiv.)

PhMe

125 °C, 24 h

OH

PhPh

+5.0 equiv.

OOH

OH

ArAr

5.0 equiv.

OH

Ph Ph

O

Ar Ar

O+R

R

1a

1x

3a 3ax

7a 7x

1.0 equiv.6a

Ph Ar

O

3x

+

++

Entrya R Yield 7a (%)b 7x (%)b Ratio 7a/7x

1 4-Me 36 64 1.75

2 4-tBu 42 56 1.33

3 4-OMe 16 79 4.90

4 4-CF3 21 79 3.75a Reactions were performed on 0.100 mmol scale of 6a.b Product yield was determined by GC analysis.

5.2 Reversibility experiments

5.2.1 Triaryl alcohol + dialkyl ketone + diaryl ketone cross-over



KOtBu (5 mol%)

K3PO4 (1 equiv.)

PhMe

125 °C, 24 h

OH

PhPh

+

Ph Ph

O+

1.5 equiv.

O

OH

+

O

Me Me

OH

Me

+

pTol Ph

O+

HO

pTolpTol

Ph

via

1.5 equiv.

68% 14%6a1a

3b

7a 7r

3a 3x

1.0 equiv.

Supplementary Figure S1: Cross-over between diaryl ketone and alkyl ketone.

Procedure A 4 mL vial under air was charged with 1a (39.1 mg, 0.150 mmol, 1.5 equiv.), 6a (12.6 mg,

0.100 mmol, 1.0 equiv.), 3b (31.5 mg, 0.150 mmol, 1.5 equiv.) and a magnetic stirring bar. A second 4 mL

vial was charged with L30 · HBF4 (5.2 mg, 5 µmol, 5 mol%), and both vials were transferred into the Glovebox.

[Rh(cod)Cl]2 (1.2 mg, 2.5 µmol, 2.5 mol%), KOtBu (0.6 mg, 5 µmol, 5 mol%), and toluene (0.50 mL) were

S46


added into the ligand-containing vial and the resulting yellow almost homogeneous mixture was stirred for

about 5 min. The substrate-containing vial was charged with K3PO4 (21.2 mg, 0.100 mmol, 1.0 equiv.) and

the catalyst solution. The vial was sealed with a screw cap, taken out of the Glovebox, placed in a preheated

heating block at 125 °C and stirred for 24 h. After cooling to room temperature again, n-dodecane (11.0 µL,

0.0485 mmol) was added as internal standard and the reaction was then analyzed by gas chromatography.

Supplementary Figure S2: GC chromatogram after reaction of alcohol 1a with alkyl ketone 6a and diaryl ketone 3b.The cross-over product 7r and mixed ketone (pTol)COPh (3x) were detected.

Both products 7a and 7r were detected, as well as three biaryl ketones (Ph2CO (3a), (pTol)COPh (3x),

(pTol)2CO (3b)) were observed. Small amounts of the four possible triaryl alcohols (Ph3COH (1a), (pTol)Ph2COH,

(pTol)2PhCOH, and (pTol)3COH (1b)) were also detected.

S47


5.2.2 Reverse reaction: dialkyl alcohol + diaryl ketone

Procedure A 4 mL vial under air was charged with cis-7b or trans-7b (23.2 mg, 0.100 mmol, 1.0 equiv.),

3a (18.2 mg, 0.100 mmol, 1.0 equiv.) and a magnetic stirring bar. A second 4 mL vial was charged with L30 ·

HBF4 (5.2 mg, 5 µmol, 5 mol%), and both vials were transferred into the Glovebox. [Rh(cod)Cl]2 (1.2 mg,

2.5 µmol, 2.5 mol%), KOtBu (0.6 mg, 5 µmol, 5 mol%), and toluene (0.50 mL) were added into the ligand-

containing vial and the resulting yellow almost homogeneous mixture was stirred for about 5 min. The

substrate-containing vial was charged with K3PO4 (21.2 mg, 0.100 mmol, 1.0 equiv.) and the catalyst solution.

The vial was sealed with a screw cap, taken out of the Glovebox, placed in a preheated heating block at 125 °C

and stirred for 24 h. After cooling to room temperature again, n-dodecane (11.0 µL, 0.0485 mmol) was added

as internal standard and the reaction was then analyzed by gas chromatography.

+



KOtBu (5 mol%)

K3PO4 (1 equiv.)

Ph

O

PhPh

OHO+

OH

Ph

6b

7%3a

1.0 equiv.cis-7b

26%trans-7b

1.0 equiv.

PhMe125 °C, 24 h

+Ph

HO

Ph

Ph

1a

3%

isomerization by reversible β−carbon elimination takes place

Supplementary Figure S3: Reversibility of β -carbon elimination from dialkyl alcohol trans-7b. Formation of ketone6b and the more stable cis-isomer were observed, highlighting that β -aryl eliminationfrom dialkyl alcohols occurs under the reaction conditions.

S48


Supplementary Figure S4: GC chromatogram after reaction of alcohol trans-7b and ketone 3a. Formation of themore stable cis-isomer, ketone 6b and 1a was observed.

Formation of ketone 6b and the more stable cis-isomer was observed, highlighting that β -aryl elimination

from dialkyl alcohols is feasible, albeit the reaction rate is low.

+



KOtBu (5 mol%)

K3PO4 (1 equiv.)

Ph

O

PhOH

PhO+

Ph

OH

6b

5%3a

1.0 equiv.trans-7b

3%cis-7b

1.0 equiv.

PhMe125 °C, 24 h

+Ph

HO

Ph

Ph

1a

2%

β−carbon elimination from dialkyl alcohol 7b takes place, albeit at low rate

Supplementary Figure S5: Reversibility of β -carbon elimination from dialkyl alcohol cis-7b. Traces of ketone 6band the trans-isomer were observed, highlighting that β -aryl elimination from dialkylalcohols is feasible, albeit the reaction rate is low.

S49


Supplementary Figure S6: GC chromatogram after reaction of alcohol cis-7b and ketone 3a. Traces of the trans-isomer, ketone 6b and 1a were detected.

Trace amounts of isomerized alcohol trans-7b and ketone 6b were observed, highlighting that β -aryl elimi-

nation from dialkyl alcohols is feasible, albeit the reaction rate is low.

S50


5.2.3 Aryl scrambling by reversible β -carbon elimination



KOtBu (5 mol%)

K3PO4 (1 equiv.)

PhMe, 125 °C, 24 h

OH

R1R1

R1

+O

R2R2

O

R1R1



KOtBu (5 mol%)

K3PO4 (1 equiv.)

PhMe, 125 °C, 24 h

OH

R2R2

R2

+O

R1R1

O

R2R2

O

R2R1+ +

OH

R1R1

R1 OH

R2R2

R2OH

R1R1

R2 OH

R2R2

R1

O

R2R2

O

R1R1

O

R2R1

O

R1R1

O

R2R2

O

R2R1+ +

R1 =

R2 =

HR2H

R1+ +

HR2H

R1+ +

1.06

0.431b 3c

1c 3b

3c3b 3x

3c3b 3x

Supplementary Figure S7: Scrambling of triaryl alcohols and diaryl ketones.

Procedure A 4 mL vial under air was charged with 1 (0.100 mmol, 1.0 equiv.), 3 (0.100 mmol, 1.0 equiv.)

and a magnetic stirring bar. Another 4 mL vial was charged with L30 · HBF4 (5.2 mg, 5 µmol, 5 mol%),

and both vials were transferred into the Glovebox. [Rh(cod)Cl]2 (1.2 mg, 2.5 µmol, 2.5 mol%), KOtBu (0.6

mg, 5 µmol, 5 mol%), and toluene (0.50 mL) were added into the ligand-containing vial and the resulting

yellow almost homogeneous mixture was stirred for about 5 min. The substrate-containing vial was charged

with K3PO4 (21.2 mg, 0.100 mmol, 1.0 equiv.) and the catalyst solution. The vial was sealed with a screw

cap, taken out of the Glovebox, placed in a preheated heating block at 125 °C and stirred for 24 h. After

cooling to room temperature again, n-dodecane (11.0 µL, 0.0485 mmol) was added as internal standard and

the reaction was then analyzed by gas chromatography.

The reaction was set up two times in parallel using

a) 1b (30.2 mg, 0.100 mmol, 1.0 equiv.) and 3c (29.4 mg, 0.100 mmol, 1.0 equiv.)

b) 1c (42.9 mg, 0.100 mmol, 1.0 equiv.) and 3b (21.0 mg, 0.100 mmol, 1.0 equiv.)

S51


Supplementary Figure S8: GC chromatogram after reaction between alcohol 1b and ketone 3c. The major productsare a mixture of the three ketones.

Supplementary Figure S9: GC chromatogram after reaction between alcohol 1c and ketone 3b. The major productsare a mixture of the three ketones.

S52


A mixture of all three ketones was obtained when conducting the reaction starting from both sides of the

reaction arrow. At the same time, only trace amounts of the four possible alcohols were present at the end of

the reaction. While the same products were formed approaching from either side, full equilibration was not

reached. This might be explained with the observation that a significant amount of the protonated arenes (i. e.,

toluene and tert-butylbenzene) were formed by protodemetalation. Therefore, the alcohols 1 are depleted

over the course of the reaction and an equilibrium cannot be reached.

5.3 Synthesis and characterization of organometallic compounds

5.3.1 Preparation of complex 10

B-

FF

F

F

Rh(IPr*OMe)(cod)Cl

Rh

OO

NN

Ph

PhPh

Ph

Ph

Ph

Ph

Ph

Rh

Cl

IPr*OMe · HBF4

1. KOtBu THF, rt, 2 h

2. [Rh(cod)Cl]2 rt, 2 h

Ph

Ph

O N N+O

Ph

Ph

Ph

Ph

Ph

Ph

In the Glovebox, a 25 mL Schlenk round bottom flask equipped with a magnetic stirring bar under argon was

charged with L30 · HBF4 (826 mg, 800 µmol, 1.0 equiv.) and KOtBu (94.3 mg, 840 µmol, 1.05 equiv.), and

was brought out of the Glovebox and cycled onto the Schlenk line. A 10 mL Schlenk tube was charged

with [Rh(cod)Cl]2 (197 mg, 400 µmol, 1.0 equiv.), and was brought out of the Glovebox and cycled onto the

Schlenk line. THF (8.0 mL) was added to the ligand and the off white nearly homogeneous mixture was

stirred at 25 °C for 2 h. Likewise, THF (2.0 mL) was added to the rhodium-containing vessel. At this point,

the solution of [Rh(cod)Cl]2 was syringed into the carbene solution and the vessel was washed with THF

(2 × 2 mL). The yellow reaction mixture was stirred at 25 °C for 2 h to give a yellow solution. The reaction

mixture was exposed to air and concentrated. The yellow orange residue was taken up in DCM and filtered

through a pad of Celite (eluent CH2Cl2). Evaporation of the filtrate gave a yellow orange gel which was

triturated with pentane resulting in a yellow solid. The solid was filtered, washed with pentane and dried

under high vacuum to yield [Rh(IPr*OMe)(cod)Cl] (10) (924 mg, 97 %) as a yellow solid.

1H-NMR (500 MHz, CDCl3): δ 7.55 (d, J = 7.2Hz, 4 H, HPh), 7.31 – 7.10 (m, 16 H, CHAr), 7.10 – 6.96

(m, 12 H, CHAr), 6.87 – 6.66 (m, 12 H, CHAr), 6.60 (s, 2 H, CHPh2), 5.27 (s, 2 H, CHPh2), 5.00 (s, 2 H,

=CHcod), 4.72 (s, 2 H, H4,5Im), 3.65 (d, J = 3.1Hz, 2 H, =CHcod), 3.61 (s, 6 H, OMe), 2.15 – 2.05 (m, 2 H,

Hallyl cod), 1.83 – 1.67 (m, 4 H, Hallyl cod), 1.61 – 1.50 (m, 2 H, Hallyl cod). 13C{1H}-NMR (126 MHz,CDCl3): δ 184.7 (d, 1JC Rh = 52.1Hz, Rh-C), 158.9 (ArC), 146.2 (ArC), 144.7 (ArC), 144.7 (ArC), 144.2

(ArC), 144.1 (ArC), 143.1 (ArC), 142.4 (ArC), 132.0 (ArCH), 131.0 (ArCH), 130.3 (ArCH), 129.8 (ArCH),

129.3 (ArCH), 128.3 (ArCH), 128.1 (ArCH), 127.9 (ArCH), 126.8 (ArCH), 126.6 (ArCH), 126.1 (ArCH),

S53

6 X-ray data Supporting Information

126.0 (ArCH), 123.9 (N(CH)2N), 115.4 (ArCH), 114.5 (ArCH), 96.8 (d, 1JC Rh = 7.4Hz, COD CH), 69.1

(d, 1JC Rh = 14.0Hz, COD CH), 55.3 (OMe), 51.9 (CHPh2), 51.1 (CHPh2), 32.7 (COD CH2), 28.6 (COD

CH2). 1H-NMR (600 MHz, toluene d8): δ 7.95 (d, J = 7.7Hz, 4 H, HPh), 7.35 (d, J = 7.1Hz, 6 H, CHAr),

7.23 (t, J = 7.6Hz, 4 H, CHAr), 7.04 - 6.93 (m, 10 H, CHAr), 6.92 – 6.76 (m, 22 H, CHAr + CHPh2),

5.44 (s, 2 H, CHPh2), 5.33 (dt, J = 5.3,2.0Hz, 2 H, =CHcod), 4.82 (s, 2 H, H4,5Im), 3.93 (dd, J = 5.2,2.4

Hz, 2 H, =CHcod), 3.17 (s, 6 H, OMe), 2.06 – 2.00 (m, 2 H, Hallyl cod), 1.92 (ddd, J = 11.5,7.0,3.8Hz,

2 H, Hallyl cod), 1.64 – 1.53 (m, 4 H, Hallyl cod). 13C{1H}-NMR (151 MHz, toluene d8): δ 186.2 (d,1JC Rh = 51.8Hz, Rh-C), 159.7 (ArC), 147.4 (ArC), 145.5 (ArC), 144.8 (app d, J = 4.5Hz, ArC), 143.6

(ArC), 143.0 (ArC), 132.3 (ArC), 131.7 (ArC), 130.7 (ArCH), 130.3 (ArCH), 129.7 (ArCH), 129.2 (ArCH),

128.5 (ArCH), 128.4 (ArCH), 128.3 (ArCH), 127.1 (ArCH), 126.8 (ArCH), 126.5 (ArCH), 126.2 (ArCH),

125.4 (ArCH), 124.0 (N(CH)2N), 115.5 (ArCH), 114.9 (ArCH), 97.0 (d, 1JC Rh = 6.8Hz, COD CH), 68.9

(d, 1JC Rh = 13.7Hz, COD CH), 54.6 (OMe), 52.5 (CHPh2), 51.6 (CHPh2), 33.1 (COD CH2), 28.9 (COD

CH2). 103Rh-NMR (16 MHz, toluene d8): δ -7530.3, -7535.7. IR (ATR) ν̃ = 2940.2 (w), 1598.2 (m),

1493.8 (m), 1463.3 (m), 1439.1 (m), 1299.5 (m), 1235 (m), 1207.3 (m), 1146.9 (m), 1087.6 (m), 1050.9 (m),

1031.4 (m), 959.6 (w), 850.7 (w), 760.3 (m), 738.8 (m), 698.2 (s), 649.8 (w), 602.7 (m), 583 (w), 472.6 (w)

cm−1. HRMS (m/z): [M−Cl]+ calcd. for C77H68N2O2Rh, 1155.4330; found, 1155.4255. analysis (calcd.,

found for C77H68ClN2O2Rh): C (77.60, 77.63), H (5.75, 5.67), N (2.35, 2.58).

Single crystals suitable for X-ray diffraction analysis were obtained by slow diffusion of hexane into a

toluene solution (vide infra).

6 X-ray data

General information

Single crystalline samples were measured on the following instruments:

• Bruker/Nonius Kappa APEX-II diffractometer with microfocus sealed tube Mo-Kα radiation using

mirror optics (λ = 0.710 73 Å, 7a).

• Rigaku Oxford Diffraction XtaLAB Synergy-S Dualflex kappa diffractometer equipped with a Dectris

Pilatus 300 HPAD detector and using microfocus sealed tube Cu-Kα radiation with mirror optics (λ =

1.541 78 Å, cis-7b, 10).

All measurements were carried out at 100 K (unless otherwise noted) using an Oxford Cryosystems Cryostream

800 sample cryostat. Data collected on Bruker instruments were integrated using SAINT from the Bruker

Apex-II program suite and corrected for absorption effects using the multi-scan method (SADABS).36 Data

collected on the Rigaku instrument were integrated using CrysAlisPro and corrected for absorption effects

S54


using a combination of empirical (ABSPACK) and numerical corrections.5 The structures were solved using

SHELXT37 or SHELXS38 and refined by full-matrix least-squares analysis (SHELXL)39, using the program

package OLEX2.40 Unless otherwise indicated below, all non-hydrogen atoms were refined anisotropically

and hydrogen atoms were constrained to ideal geometries and refined with fixed isotropic displacement

parameters (in terms of a riding model).

Organic compounds: 7a (CCDC 2035749), cis-7b (CCDC 2035751).

Metallorganic compounds: 10 (CCDC 2035750).

These data can be obtained free of charge from The Cambridge Crystallographic Data Centre, 12 Union

Road, Cambridge CB2 1EZ, UK (fax: +44(1223)-336-033; e-mail: [email protected]), or via https:

//www.ccdc.cam.ac.uk/getstructures.

5CrysAlisPro and ABSPACK. Rigaku Oxford Diffraction (2016).

S55

[email protected]

https://www.ccdc.cam.ac.uk/getstructures

https://www.ccdc.cam.ac.uk/getstructures


6.1 Compound 7a

Experimental. Single crystals were isolated at 25 °C

vacuum sublimation of solid 7a.

A suitable crystal was selected and analysed on a

Bruker APEX-II Duo (Mo) diffractometer. The crystal

was kept at 100.0(1) K during data collection. Using

Olex240, the structure was solved with the ShelXT37

structure solution program using Intrinsic Phasing and

refined with the ShelXL39 refinement package using

Least Squares minimization.

Note: The absolute structure was not determined.

Identification code CCDC 2035749Empirical formula C14H20O

Formula weight 204.30

Temperature/K 100.0(1)

Crystal system monoclinic

Space group Cc (9)

a/Å 15.205(2)

b/Å 15.190(2)

c/Å 22.088(3)

α/◦ 90

β /◦ 98.676(3)

γ/◦ 90

Volume/Å3 5043.3(13)

Z 16

ρcalc/g cm−3 1.076

µ/mm−1 0.065

F(000) 1792

Crystal size/mm3 0.34×0.26×0.1

Crystal color clear colorless

Crystal shape block

Radiation Mo Kα (λ=0.71073)

2θ range/° 3.73 to 56.86

Index ranges -20 ≤ h ≤ 19

-20 ≤ k ≤ 20

-29 ≤ l ≤ 29

Reflections collected 44457

Independent reflections 12341

Rint = 0.0542

Rsigma = 0.0529

Data / Restraints / Param. 12341/2/553

Goodness-of-fit on F2 1.107

Final R indexes R1 = 0.0856

[I ≥ 2σ(I)] wR2 = 0.2297


[all data] wR2 = 0.2387

Largest peak/hole /eÅ3 0.50/-0.39

Flack x parameter -0.6(4)

S56


6.2 Compound cis-7b


by slow evaporation of a concentrated CH2Cl2 solu-

tion.

A suitable crystal was selected and analysed on a Xta-

LAB Synergy, Dualflex, Pilatus 300K diffractometer.

The crystal was kept at 100.0(1) K during data col-

lection. Using Olex240, the structure was solved with

the ShelXS38 structure solution program using Direct

Methods and refined with the ShelXL39 refinement

package using Least Squares minimization.

Note: Pseudo-merohedral twinning.

Identification code CCDC 2035751Empirical formula C16H24O



Crystal system monoclinic

Space group P/c (13)

a/Å 10.52380(10)

b/Å 13.07400(10)

c/Å 21.2571(2)

α/◦ 90

β /◦ 104.3040(10)

γ/◦ 90

Volume/Å3 2834.05(5)

Z 8


µ/mm−1 0.496

F(000) 1024

Crystal size/mm3 0.161×0.11×0.082

Crystal color clear colorless

Crystal shape block

Radiation Cu Kα (λ=1.54184)

2θ range/° 4.29 to 159.44


-16 ≤ k ≤ 16

-26 ≤ l ≤ 27



Rint = 0.0643

Rsigma = 0.0247




[I ≥ 2σ(I)] wR2 = 0.0978


[all data] wR2 = 0.0993


S57


6.3 Complex 10


by slow diffusion of hexane into a saturated toluene

solution.

A suitable crystal was selected and analysed on a Xta-

LAB Synergy, Dualflex, Pilatus 300K diffractometer.

The crystal was kept at 100.0(1) K during data col-

lection. Using Olex240, the structure was solved with

the ShelXT37 structure solution program using Intrin-

sic Phasing and refined with the ShelXL39 refinement

package using Least Squares minimization.

Note: There is cocrystallized toluene.

Identification code CCDC 2035750Empirical formula C77H68ClN2O2Rh



Crystal system orthorhombic

Space group P212121 (19)

a/Å 14.77243(5)

b/Å 20.88811(7)

c/Å 21.22572(8)

α/◦ 90

β /◦ 90

γ/◦ 90

Volume/Å3 6549.58(4)

Z 4


µ/mm−1 2.876

F(000) 2688

Crystal size/mm3 0.101×0.084×0.051

Crystal color clear orange

Crystal shape block

Radiation Cu Kα (λ=1.54184)

2θ range/° 5.94 to 159.24


-26 ≤ k ≤ 26

-23 ≤ l ≤ 26



Rint = 0.0524

Rsigma = 0.0193




[I ≥ 2σ(I)] wR2 = 0.0573


[all data] wR2 = 0.0575


Flack x parameter -0.0130(14)

S58


6.3.1 Structure discussion

Supplementary Figure S10: Displacement ellipsoid plot of [Rh(IPr*OMe)(cod)Cl] (10). The H atoms and latticemolecules (toluene) are omitted for clarity. Selected bond distances (Å), angles andtorsion angles (°): Rh1–C9 2.075, Rh1–Cl1 2.384, Rh1–C1/C2 2.194, Rh1–C5/C6 2.194,C9-Rh1–Cl1 87.7, N2-C9-Rh1–Cl 121.2

S59


6.3.2 Space-Filling Model

(a) Space-filling model of 10 showing binding pocketformed by Ph groups of the ligand.

(b) Space-filling model of 10 viewed down the NHC-Rhaxis.

Supplementary Figure S11: Space-Filling Model of [Rh(IPr*OMe)(cod)Cl] (10).

6.3.3 Calculations of Percent Buried Volume (%Vbur)

Calculations of percent buried volume were performed with the SambVca 2.1 web tool.41

The following parameters (set with respect to the parameters suggested by Nolan)42 were employed for the

calculations:

• Center of sphere: metal

• Atoms for Z-axis definition: coordinating carbon atom in NHC (Z-negative)

• Atoms for XZ plane definition: nitrogen atoms in NHC

• All non-NHC atoms were deleted

• Bondii radii scaled by 1.17

• Sphere radius: either 3.5 Å (suggested parameter) or 5.5 Å (expanded radius parameter)

• Distance of coordination point from center of sphere: 0.0 Å

• Mesh spacing for numerical integration: 0.1

• No H atoms included in calculation

S60

7 Computational studies Supporting Information

A summary of the %Vbur calculated for L24 and L30 is shown below (Table S12). In each case, the reference

compound for the calculation was [Rh(NHC)(cod)Cl] and the procedure described above was followed. For

L30, the calculation was performed on the X-ray crystal structure of 10. For L24, a X-ray crystal structure

from the CCDC (PEFNUK ) was used.

�4 �3 �2 �1 0 1 2 3 4�4

�3

�2

�1

0

1

2

3

4

�3.00

�2.25

�1.50

�0.75

0.00

0.75

1.50

2.25

3.00

(a) L24, r = 3.5 Å (b) L24, r = 5.5 Å

�4 �3 �2 �1 0 1 2 3 4�4

�3

�2

�1

0

1

2

3

4

�3.00

�2.25

�1.50

�0.75

0.00

0.75

1.50

2.25

3.00

(c) L30, r = 3.5 Å

�6 �4 �2 0 2 4 6�6

�4

�2

0

2

4

6

�5.00

�3.75

�2.50

�1.25

0.00

1.25

2.50

3.75

5.00

(d) L30, r = 5.5 Å

Supplementary Figure S12: Steric Maps of L24 and L30 generated by SambVca 2.141.

Entry Ligand Radius (Å) %Vbur Radius (Å) %Vbur

1 IPr (L24) 3.5 33.6 5.5 38.62 IPr*OMe (L30) 3.5 37.2 5.5 46.4

7 Computational studies

All calculations were carried out using Density Functional Theory with Orca software version 4.2.0.43,44

Geometry optimizations were carried out at the PBE0 level of theory45 with D3BJ dispersion correction;46,47

S61


the def2-SVP basis set48 was used with def2/J auxiliary basis. Solvent effects were incorporated using

the CPCM solvation model49 and toluene as solvent. All stationary points were fully characterized by

numerical frequency calculations as either a minimum (no imaginary frequencies) or a transition state (only

one imaginary frequency) at the same level of theory. Final single-point energies were calculated with the

PBE0 functional with D3BJ dispersion correction and def2-TZVP basis set. Solvent effects were incorporated

using the CPCM solvation model and toluene as solvent. Free energies reported here thus include single-

point energies at the PBE0-D3(BJ)/def2-TZVP level and zero-point energies, thermal corrections at 398 K

(reaction temperature), and entropy effects at the PBE0-D3(BJ)/def2-SVP level of theory.

OH

PhPh

Ph+

Ph Ph

O

ArF

O OH

ArFArF

Ph+

ArF

1a 2 43a

∆G(398 K) = +0.7 kcal/molF

ArF =Ph =

Supplementary Figure S13: Gibbs free energy change for the transfer arylation between 1a and 2.

Ph ArF

OHArF+

5

∆G(398 K) = -14.9 kcal/mol

OH

ArFArF

Ph

4

Supplementary Figure S14: Gibbs free energy change for the cleavage of 4 to 5 and fluorobenzene.

Ph ArF

OHArF+

5

∆G(398 K) = -14.2 kcal/mol

OH

PhPh

Ph+

ArF

O

ArF

1a 2

Ph Ph

O+

3a

Supplementary Figure S15: Gibbs free energy change for the overall reaction of 1a and 2 to 5 and fluorobenzene.

OH

PhPh

+Ph Ph

OO

OH+

1a 6a 7a 3a

∆G(398 K) = -4.0 kcal/mol

Supplementary Figure S16: Gibbs free energy change for the transfer arylation between 1a and 6a.

OH

MeMe

+Me Me

O+

∆G(398 K) = -1.4 kcal/mol

O

OH

6a 7a

Supplementary Figure S17: Gibbs free energy change for the transfer arylation between PhMe2COH and 6a.

S62


7.1 Cartesian Coordinates and Energies of Structures optimized at the PBE0/def2-SVP level

of theory

1a

E = -808.2543525 Eh

G = -808.0207540 Eh

O 1.010191 -0.125793 -0.155653

C 2.420438 -0.067735 -0.032374

C 2.758136 -0.752454 1.291289

C 2.003988 -1.861186 1.690002

C 2.316161 -2.541699 2.864335

C 3.390572 -2.127192 3.653393

C 4.144739 -1.022789 3.262067

C 3.827014 -0.336104 2.089313

C 3.090006 -0.846981 -1.172129

C 2.359568 -1.193626 -2.310617

C 2.961727 -1.884188 -3.363472

C 4.306504 -2.239855 -3.291102

C 5.043312 -1.905852 -2.153782

C 4.438749 -1.219673 -1.103094

C 2.836984 1.405327 -0.015476

C 2.170422 2.251722 0.883053

C 2.475823 3.607169 0.943439

C 3.454233 4.142844 0.102163

C 4.115445 3.311723 -0.797849

C 3.807344 1.950130 -0.858297

H 1.164832 -2.182396 1.070984

H 1.716585 -3.404188 3.165997

H 3.635624 -2.662134 4.574074

H 4.983978 -0.685790 3.875465

H 4.413550 0.538581 1.799180

H 1.300364 -0.938775 -2.367379

H 2.369821 -2.151015 -4.242649

H 4.778130 -2.783588 -4.113244

H 6.096314 -2.188546 -2.080831

H 5.023902 -0.976633 -0.213414

H 1.404788 1.831196 1.539257

H 1.949293 4.251835 1.651693

H 3.696157 5.207506 0.149157

H 4.877525 3.720951 -1.465751

H 4.329616 1.311732 -1.572597

H 0.748500 0.508553 -0.833716

2

E = -774.5761085 Eh

G = -774.4560139 Eh

O 11.858953 6.290855 -2.665744

C 10.781416 6.711802 -3.047697

C 10.636718 7.244104 -4.433344

C 9.443702 7.152510 -5.163746

C 9.379516 7.612013 -6.475703

C 10.516217 8.176225 -7.042673

C 11.719736 8.267978 -6.349078

C 11.774778 7.785828 -5.048247

C 9.608638 6.707026 -2.125229

C 9.596383 5.762597 -1.088304

C 8.572056 5.746425 -0.151728

C 7.568214 6.706672 -0.244814

C 7.560085 7.669025 -1.247990

C 8.582811 7.660495 -2.192096

H 8.559690 6.694134 -4.716326

S63


H 8.464093 7.537840 -7.065501

F 10.453090 8.638747 -8.288512

H 12.590467 8.709866 -6.836827

H 12.707182 7.825100 -4.481210

H 10.412889 5.039816 -1.029035

H 8.539882 5.010963 0.654487

F 6.592769 6.706960 0.659657

H 6.761787 8.413213 -1.275145

H 8.594662 8.426195 -2.970536

3a

E = -576.1880312 Eh

G = -576.0482865 Eh

O 11.866092 6.338558 -2.653517

C 10.785374 6.748079 -3.037274

C 10.634799 7.269569 -4.428837

C 9.437415 7.165561 -5.149681

C 9.376173 7.601430 -6.472098

C 10.502874 8.156488 -7.078397

C 11.700663 8.258988 -6.366843

C 11.769353 7.804637 -5.054530

C 9.609623 6.730513 -2.115390

C 9.581454 5.757263 -1.106960

C 8.541365 5.729900 -0.184412

C 7.532479 6.694457 -0.242564

C 7.565767 7.681325 -1.227636

C 8.595166 7.696166 -2.167267

H 8.556564 6.718355 -4.684481

H 8.443523 7.504504 -7.032850

H 10.450497 8.506268 -8.112194

H 12.584990 8.689791 -6.842157

H 12.702115 7.855851 -4.488660

H 10.391667 5.025835 -1.063747

H 8.517605 4.957958 0.588853

H 6.718954 6.679176 0.487389

H 6.786422 8.446547 -1.263766

H 8.624825 8.479139 -2.928311

4

E = -1006.641675 Eh

G = -1006.427320 Eh

O 1.051265 -0.183251 -0.253679

C 2.443902 -0.099542 -0.003527

C 2.767939 -0.764539 1.336393

C 1.988479 -1.849078 1.752069

C 2.287714 -2.541513 2.921738

C 3.385022 -2.140951 3.675083

C 4.173559 -1.062778 3.295940

C 3.856056 -0.376522 2.124438

C 3.127311 -0.866300 -1.136012

C 2.464432 -1.038646 -2.354820

C 3.091552 -1.690332 -3.416520

C 4.391494 -2.173879 -3.276627

C 5.059285 -2.003861 -2.064040

C 4.429362 -1.359962 -1.000641

C 2.848796 1.378072 -0.009269

C 2.337335 2.215731 0.992882

C 2.596652 3.582056 0.995623

C 3.390176 4.112176 -0.016105

C 3.923910 3.311497 -1.014994

C 3.645925 1.944789 -1.006231

H 1.134699 -2.147723 1.141611

H 1.686310 -3.389711 3.254546

S64


F 3.685902 -2.807097 4.792647

H 5.022052 -0.770605 3.917359

H 4.471062 0.474714 1.824305

H 1.448941 -0.657209 -2.461425

H 2.557478 -1.820482 -4.361225

H 4.882019 -2.685196 -4.108425

H 6.076693 -2.382359 -1.940216

H 4.960452 -1.244994 -0.053783

H 1.731312 1.794630 1.800947

H 2.200177 4.239505 1.771523

F 3.646192 5.421095 -0.022290

H 4.546977 3.760433 -1.790858

H 4.060535 1.313908 -1.793766

H 0.609564 0.459831 0.313280

5

E = -675.382090 Eh

G = -675.252214 Eh

O 11.852228 6.29334 -2.682443

C 10.776515 6.723656 -3.058504

C 10.632055 7.261739 -4.444113

C 9.440016 7.163484 -5.174445

C 9.387955 7.612539 -6.492962

C 10.518272 8.174897 -7.085573

C 11.710614 8.272074 -6.364136

C 11.770414 7.804718 -5.056108

C 9.606423 6.715910 -2.132513

C 9.594170 5.761877 -1.104309

C 8.572619 5.739902 -0.164962

C 7.571909 6.704496 -0.245844

C 7.563898 7.675957 -1.240142

C 8.583184 7.672531 -2.188255

H 8.556549 6.708347 -4.721857

H 8.459947 7.519421 -7.061999

H 10.473351 8.534239 -8.116359

H 12.597628 8.708582 -6.829129

H 12.699013 7.850928 -4.483037

H 10.408420 5.035792 -1.055041

H 8.539774 4.996512 0.633975

F 6.598947 6.699198 0.661709

H 6.767818 8.422822 -1.257695

H 8.594012 8.443427 -2.961609

Fluorobenzene

E = -331.250853 Eh

G = -331.198912 Eh

C 9.605828 6.715542 -2.114046

C 9.594297 5.760558 -1.096342

C 8.572062 5.751507 -0.147855

C 7.569717 6.710315 -0.237871

C 7.556910 7.669834 -1.243553

C 8.586397 7.666127 -2.184684

H 10.389887 5.013827 -1.034803

H 8.539890 5.016654 0.659282

F 6.590888 6.708949 0.670882

H 6.747026 8.401576 -1.278993

H 8.589009 8.415603 -2.980178

6a

E = -388.223608 Eh

G = -388.065051 Eh

S65


O 9.918794 5.625846 -2.404713

C 9.784790 6.616781 -3.088972

C 8.442059 7.063061 -3.615348

C 8.494637 7.428650 -5.099624

C 10.945700 7.505136 -3.465801

C 9.605475 8.431500 -5.453709

C 10.944516 7.865408 -4.951868

C 9.322239 9.801400 -4.831085

C 9.671095 8.585713 -6.972404

H 8.660362 6.506913 -5.683915

H 7.516851 7.825989 -5.418679

H 7.708309 6.269991 -3.412760

H 8.142397 7.944082 -3.019810

H 11.877347 7.004641 -3.165581

H 10.856742 8.421096 -2.854606

H 11.755429 8.582500 -5.160784

H 11.176593 6.956988 -5.534569

H 8.365251 10.202618 -5.201018

H 10.113359 10.519529 -5.098810

H 9.264194 9.769199 -3.732757

H 8.718925 8.969260 -7.372303

H 9.877724 7.619844 -7.460401

H 10.466950 9.289385 -7.263563

Acetone

E = -193.0130578 Eh

G = -192.9689145 Eh

O 10.027518 5.383986 -2.655425

C 9.860094 6.458992 -3.187442

C 8.486093 7.050124 -3.368102

C 11.016686 7.279425 -3.697250

H 11.150852 8.155891 -3.041990

H 11.936180 6.680488 -3.689252

H 8.243344 7.089817 -4.442652

H 8.455136 8.086199 -2.996859

H 10.817886 7.664388 -4.708975

H 7.740089 6.437140 -2.847083

S66

8 References Supporting Information

8 References

1. Zhou, H., Campbell, E. J. & Nguyen, S. B. T. Imidazolinium salts as catalysts for the ring-opening

alkylation of meso epoxides by alkylaluminum complexes. Org. Lett. 3, 2229–2231 (2001).

2. Wang, H. et al. NHC Ligands Tailored for Simultaneous Regio- and Enantiocontrol in Nickel-Catalyzed

Reductive Couplings. J. Am. Chem. Soc. 139, 9317–9324 (2017).

3. Jazzar, R. et al. Intramolecular "hydroiminiumation" of alkenes: Application to the synthesis of conju-

gate acids of Cyclic Alkyl Amino Carbenes (CAACs). Angew. Chem. Int. Ed. 46, 2899–2902 (2007).

4. Berthon-Gelloz, G. et al. IPr* an easily accessible highly hindered N-heterocyclic carbene. Dalt. Trans.

39, 1444–1446 (2010).

5. Meiries, S., Speck, K., Cordes, D. B., Slawin, A. M. Z. & Nolan, S. P. [Pd(IPr*OMe)(acac)Cl]: Tuning

the N-Heterocyclic Carbene in Catalytic C–N Bond Formation. Organometallics 32, 330–339 (2013).

6. Pangborn, A. B., Giardello, M. A., Grubbs, R. H., Rosen, R. K. & Timmers, F. J. Safe and convenient

procedure for solvent purification. Organometallics 15, 1518–1520 (1996).

7. Fulmer, G. R. et al. NMR chemical shifts of trace impurities: Common laboratory solvents, organics,

and gases in deuterated solvents relevant to the organometallic chemist. Organometallics 29, 2176–

2179 (2010).

8. Nocera, G. et al. Electron Transfer Reactions: KOtBu (but not NaOtBu) Photoreduces Benzophenone

under Activation by Visible Light. J. Am. Chem. Soc. 140, 9751–9757 (2018).

9. Xu, Y. et al. Deacylative transformations of ketones via aromatization-promoted C–C bond activation.

Nature 567, 373–378 (2019).

10. You, A. et al. Rational design, synthesis and structure–activity relationships of 4-alkoxy- and 4-acyloxy-

phenylethylenethiosemicarbazone analogues as novel tyrosinase inhibitors. Bioorg. Med. Chem. 23,924–931 (2015).

11. Peñafiel, I., Pastor, I. M., Yus, M., Esteruelas, M. A. & Oliván, M. Preparation, hydrogen bonds, and

catalytic activity in metal-promoted addition of arylboronic acids to enones of a rhodium complex

containing an NHC ligand with an alcohol function. Organometallics 31, 6154–6161 (2012).

12. Sargent, B. T. & Alexanian, E. J. Palladium-Catalyzed Alkoxycarbonylation of Unactivated Secondary

Alkyl Bromides at Low Pressure. J. Am. Chem. Soc. 138, 7520–7523 (2016).

13. Cao, J. J., Zhou, F. & Zhou, J. Improving the atom efficiency of the wittig reaction by a "waste as

catalyst/Co-catalyst" strategy. Angew. Chem. Int. Ed. 49, 4976–4980 (2010).

14. Wang, E. S., Choy, Y. M. & Wong, H. N. Synthetic studies on prehispanolone and 14,15-dihydroprehispanolone.

Tetrahedron 52, 12137–12158 (1996).

15. Sakata, T., Maruyama, S., Ueda, A., Otsuka, H. & Miyahara, Y. Stable immobilization of an oligonu-

cleotide probe on a gold substrate using tripodal thiol derivatives. Langmuir 23, 2269–2272 (2007).

S67


16. Ashton, P. R. et al. Self-assembly, spectroscopic, and electrochemical properties of [n]rotaxanes. J. Am.

Chem. Soc. 118, 4931–4951 (1996).

17. Rösel, S. et al. London Dispersion Enables the Shortest Intermolecular Hydrocarbon H···H Contact. J.

Am. Chem. Soc. 139, 7428–7431 (2017).

18. Olah, G. A. et al. Tris(1-naphthyl)- and tris(2-naphthyl)methyl cations: Highly crowded triarylmethyl

cations. J. Chem. Soc. Perkin Trans. 2, 2239–2242 (1998).

19. Nösel, P. et al. Oxidative Gold Catalysis Meets Photochemistry - Synthesis of Benzo[a]fluorenones

from Diynes. Adv. Synth. Catal. 356, 3755–3760 (2014).

20. Tóth, K., Höfner, G. & Wanner, K. T. Synthesis and biological evaluation of novel N-substituted

nipecotic acid derivatives with a trans-alkene spacer as potent GABA uptake inhibitors. Bioorganic

Med. Chem. 26, 5944–5961 (2018).

21. Claveau, R., Twamley, B. & Connon, S. J. Dynamic kinetic resolution of bis-aryl succinic anhydrides:

Enantioselective synthesis of densely functionalised γ-butyrolactones. Chem. Commun. 54, 3231–3234

(2018).

22. Pabel, J. et al. Development of an (S)-1-{2-[Tris(4-methoxyphenyl)methoxy]ethyl}piperidine-3-

carboxylic acid [(S)-SNAP-5114] Carba Analogue Inhibitor for Murine γ-Aminobutyric Acid Trans-

porter Type 4. ChemMedChem 7, 1245–1255 (2012).

23. Kögel, J. F. et al. Three Fluorinated Trityl Alcohols and their Lithium Salts - Synthesis, Molecular

Structures, and Acidity. Eur. J. Inorg. Chem. 2019, 3612–3618 (2019).

24. Taylor, N. J. et al. Derisking the Cu-Mediated 18F-Fluorination of Heterocyclic Positron Emission

Tomography Radioligands. J. Am. Chem. Soc. 139, 8267–8276 (2017).

25. Blessley, G., Holden, P., Walker, M., Brown, J. M. & Gouverneur, V. Palladium-catalyzed substitution

and cross-coupling of benzylic fluorides. Org. Lett. 14, 2754–2757 (2012).

26. Rono, L. J., Yayla, H. G., Wang, D. Y., Armstrong, M. F. & Knowles, R. R. Enantioselective photoredox

catalysis enabled by proton-coupled electron transfer: Development of an asymmetric aza-pinacol

cyclization. J. Am. Chem. Soc. 135, 17735–17738 (2013).

27. Paquette, L. A. & Ra Choon, S. Cleavage of Carbon-Carbon Bonds with High Stereochemical Control.

5. Course of the Haller-Bauer Reaction of Cyclic α-Phenyl Ketones. J. Org. Chem. 53, 4978–4985

(1988).

28. Bouffard, J. & Itami, K. A nickel catalyst for the addition of organoboronate esters to ketones and

aldehydes. Org. Lett. 11, 4410–4413 (2009).

29. Gao, F. et al. A simple and efficient copper oxide-catalyzed Barbier-Grignard reaction of unactivated

aryl or alkyl bromides with ester. Tetrahedron Lett. 55, 880–883 (2014).

30. Evans, D. A., Borg, G. & Scheidt, K. A. Remarkably Stable Tetrahedral Intermediates: Carbinols from

Nucleophilic Additions to N-Acylpyrroles. Angew. Chem. Int. Ed. 41, 3188–3191 (2002).

S68


31. Cory, R. M., Walker, J. R. & Zabel, P. D. Extended chains of six-membered rings 1. model studies and

key intermediates. Synth. Commun. 24, 799–807 (1994).

32. Conway, R. J. et al. Synthesis and SAR study of 4-arylpiperidines and 4-aryl-1,2,3,6- tetrahydropy-

ridines as 5-HT 2C agonists. Bioorganic Med. Chem. Lett. 22, 2560–2564 (2012).

33. Rieke, R. D., Lee, J. S., Kye, Y. S. & Harbison, G. S. Preparation of lithium stannide mixtures in

organic solvents. A alternate source of lithium in organolithium chemistry. J. Organomet. Chem. 689,3421–3425 (2004).

34. Madduri, A. V. R., Harutyunyan, S. R. & Minnaard, A. J. Asymmetric Copper-Catalyzed Addition of

Grignard Reagents to Aryl Alkyl Ketones. Angew. Chem. Int. Ed. 51, 3164–3167 (2012).

35. Lerebours, R., Camacho-Soto, A. & Wolf, C. Palladium-catalyzed chemoselective cross-coupling of

acyl chlorides and organostannanes. J. Org. Chem. 70, 8601–8604 (2005).

36. Sheldrick, G. M. SADABS, Program for Empirical Absorption Correction of Area Detector Data 1996.

37. Sheldrick, G. M. SHELXT - Integrated space-group and crystal-structure determination. Acta Crystal-

logr. Sect. A Found. Crystallogr. 71, 3–8 (2015).

38. Sheldrick, G. M. A short history of SHELX. Acta Crystallogr. Sect. A Found. Crystallogr. 64, 112–122

(2008).

39. Sheldrick, G. M. Crystal structure refinement with SHELXL. Acta Crystallogr. Sect. C Struct. Chem.

71, 3–8 (2015).

40. Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. & Puschmann, H. OLEX2: A complete

structure solution, refinement and analysis program. J. Appl. Crystallogr. 42, 339–341 (2009).

41. Falivene, L. et al. Towards the online computer-aided design of catalytic pockets. Nat. Chem. 11, 872–

879 (2019).

42. Clavier, H. & Nolan, S. P. Percent buried volume for phosphine and N-heterocyclic carbene ligands:

Steric properties in organometallic chemistry. Chem. Commun. 46, 841–861 (2010).

43. Neese, F. The ORCA program system. Wiley Interdiscip. Rev. Comput. Mol. Sci. 2, 73–78 (2012).

44. Neese, F. Software update: the ORCA program system, version 4.0. Wiley Interdiscip. Rev. Comput.

Mol. Sci. 8 (2018).

45. Adamo, C. & Barone, V. Toward reliable density functional methods without adjustable parameters:

The PBE0 model. J. Chem. Phys. 110, 6158–6170 (1999).

46. Grimme, S., Antony, J., Ehrlich, S. & Krieg, H. A consistent and accurate ab initio parametrization

of density functional dispersion correction (DFT-D) for the 94 elements H-Pu. J. Chem. Phys. 132,154104 (2010).

47. Grimme, S., Ehrlich, S. & Goerigk, L. Effect of the damping function in dispersion corrected density

functional theory. J. Comput. Chem. 32, 1456–1465 (2011).

S69


48. Weigend, F. Accurate Coulomb-fitting basis sets for H to Rn. Phys. Chem. Chem. Phys. 8, 1057–1065

(2006).

49. Barone, V. & Cossi, M. Quantum Calculation of Molecular Energies and Energy Gradients in Solution

by a Conductor Solvent Model. J. Phys. Chem. A 102, 1995–2001 (1998).

S70

A NMR spectra Supporting Information

Appendix

A NMR spectra

S71

AN

MR

spectraSupporting

Information

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

17.9

1

3.98

4.00

1.35

1.36

1.36

1.37

1.38

1.39

1.39

1.39

7.26

CD

Cl3

7.48

7.50

7.50

7.76

7.78

1H-NMR (400 MHz, CDCl3)

O

3c

S72

AN

MR

spectraSupporting

Information

-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)

31.3

0

35.2

2

76.8

477

.16

CDCl

377

.48

125.

3013

0.18

135.

26

156.

01

196.

32

13C-NMR (101 MHz, CDCl3)

O

3c

S73

AN

MR

spectraSupporting

Information

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

2.92

2.00

2.02

2.07

0.99

1.94

1.96

1.95

2.17

2.79

2.79

2.81

2.81

2.83

2.93

2.95

2.95

2.97

7.25

7.26

7.26

CD

Cl3

7.26

7.26

7.27

7.28

7.28

7.32

7.32

7.32

7.33

7.34

7.34

7.35

7.36

7.36

7.42

7.43

7.44

7.46

7.52

7.54

7.57

7.57

7.59

7.59


O

6e

S74

AN

MR

spectraSupporting

Information

-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)

29.4

430

.25

45.2

4

76.8

4 CD

Cl3

77.1

6 CD

Cl3

77.1

6 CD

Cl3

77.4

8 CD

Cl3

127.

1212

7.24

127.

3612

8.86

128.

87

139.

2214

0.23

141.

05

208.

04


O

6e

S75

AN

MR

spectraSupporting

Information

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

3.00

2.06

2.06

3.07

2.00

2.00

2.11

2.11

2.12

2.12

2.13

2.14

2.14

2.14

2.71

2.71

2.71

2.71

2.72

2.72

2.72

2.72

2.72

2.72

2.73

2.73

2.73

2.74

2.74

2.74

2.82

2.82

2.83

2.84

2.84

2.84

2.84

2.84

2.85

2.85

3.76

3.76

3.77

3.77

3.77

3.77

3.78

3.79

3.79

3.79

3.79

3.80

6.79

6.80

6.81

6.81

6.82

6.83

6.83

6.84

6.84

6.85

7.07

7.07

7.08

7.08

7.08

7.08

7.08

7.09

7.09

7.09

7.09

7.09

7.10

7.10

7.10

7.11

7.11

7.11

7.11

7.11

7.11

7.12

7.12

7.13

7.26

CD

Cl3


O

MeO

6h

S76

AN

MR

spectraSupporting

Information

-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)

29.0

230

.23

45.5

8

55.3

7

76.9

1 CD

Cl3

77.1

6 CD

Cl3

77.1

6 CD

Cl3

77.4

1 CD

Cl3

114.

02

129.

34

133.

14

158.

09

208.

26


O

MeO

6h

S77

AN

MR

spectraSupporting

Information

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

3.00

2.16

2.31

3.14

2.05

1.99

1.57

2.16

2.79

2.80

2.82

2.97

2.98

3.00

3.03

7.26

CD

Cl3

7.38

7.40

7.40

7.40

7.84

7.86


O

S

O O

6i

S78

AN

MR

spectraSupporting

Information

-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)

29.5

330

.21

44.4

344

.70

76.9

1 CD

Cl3

77.1

6 CD

Cl3

77.1

6 CD

Cl3

77.4

1 CD

Cl3

127.

7712

9.53

138.

57

147.

87

206.

92


O

S

O O

6i

S79

AN

MR

spectraSupporting

Information

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.5f1 (ppm)

9.32

3.00

2.08

2.09

2.02

2.00

0.25

2.15

2.75

2.75

2.75

2.75

2.77

2.77

2.77

2.77

2.77

2.78

2.78

2.78

2.88

2.88

2.89

2.89

2.91

2.91

7.18

7.18

7.19

7.19

7.26

CD

Cl3

7.44

7.45


O

Me3Si

6j

S80

AN

MR

spectraSupporting

Information

-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)

-0.9

5

29.8

030

.19

45.2

0

76.9

1 CD

Cl3

77.1

6 CD

Cl3

77.1

6 CD

Cl3

77.4

1 CD

Cl3

127.

90

133.

7213

8.02

141.

74

208.

04


O

Me3Si

6j

S81

AN

MR

spectraSupporting

Information

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.0f1 (ppm)

2.90

2.00

2.03

2.94

1.97

1.90

2.14

2.76

2.77

2.78

2.79

2.80

2.92

2.94

2.94

2.96

3.91

7.26

CD

Cl3

7.32

7.34

7.35

7.36

7.37

7.37

7.38

7.38

7.39

7.40

7.40

7.85

7.86

7.86

7.86

7.87

7.87

7.87


O

O

O

6k

S82

AN

MR

spectraSupporting

Information

-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)

29.5

230

.21

44.9

7

52.2

4

76.8

4 CD

Cl3

77.1

6 CD

Cl3

77.4

8 CD

Cl3

127.

5712

8.68

129.

4413

0.49

133.

23

141.

48

167.

25

207.

56


O

O

O

6k

S83

AN

MR

spectraSupporting

Information

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

9.28

2.96

2.00

2.03

1.98

1.91

1.59

2.15

2.76

2.77

2.77

2.78

2.78

2.78

2.78

2.78

2.80

2.80

2.80

2.92

2.92

2.92

2.93

2.93

2.93

2.93

2.95

2.95

7.26

CD

Cl3

7.30

7.30

7.32

7.32

7.33

7.33

7.34

7.34

7.34

7.34

7.34

7.34

7.35

7.35

7.36

7.36

7.36

7.80

7.80

7.80

7.80

7.80

7.80

7.80

7.80

7.81

7.81

7.82

7.82

7.82

7.82

7.83


O

O

O

6l

S84

AN

MR

spectraSupporting

Information

-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)

28.3

429

.58

30.2

1

45.0

6

76.9

1 CD

Cl3

77.1

6 CD

Cl3

77.1

6 CD

Cl3

77.4

1 CD

Cl3

81.1

5

127.

4212

8.50

129.

2513

2.37

132.

69

141.

24

165.

94

207.

68


O

O

O

6l

S85

AN

MR

spectraSupporting

Information

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

6.17

2.99

2.00

2.01

1.99

1.96

1.96

1.94

1.11

1.22

1.25

1.67

2.14

2.14

2.14

2.73

2.73

2.74

2.74

2.75

2.75

2.75

2.76

2.76

2.77

2.77

2.77

2.88

2.89

2.90

2.90

2.90

2.92

2.92

3.25

3.53

7.18

7.20

7.20

7.26

CD

Cl3

7.27

7.27

7.27

7.28

7.29

7.29

7.29

7.30


O

N

O

6m

S86

AN

MR

spectraSupporting

Information

-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)

13.0

614

.38

29.5

730

.25

39.3

643

.41

45.0

2

76.9

1 CD

Cl3

77.1

6 CD

Cl3

77.4

1 CD

Cl3

126.

7212

8.46

135.

29

142.

31

171.

39

207.

73


O

N

O

6m

S87

AN

MR

spectraSupporting

Information

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

3.00

2.07

2.07

1.97

1.94

2.12

2.13

2.14

2.14

2.15

2.72

2.72

2.74

2.74

2.75

2.75

2.84

2.85

2.86

2.88

7.10

7.12

7.12

7.23

7.25

7.26

CD

Cl3


O

Cl

6n

S88

AN

MR

spectraSupporting

Information

-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)

29.1

230

.25

45.0

5

77.1

6 CD

Cl3

128.

7212

9.84

132.

01

139.

61

207.

62


O

Cl

6n

S89

AN

MR

spectraSupporting

Information

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

3.09

4.20

1.00

0.95

1.03

2.15

2.69

6.25

6.25

6.25

6.25

7.21

7.21

7.21

7.22

7.26

CD

Cl3

7.33

7.33

7.34


O

O

6o

S90

AN

MR

spectraSupporting

Information

-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)

19.0

9

30.1

6

44.0

4

76.8

4 CD

Cl3

77.1

6 CD

Cl3

77.4

8 CD

Cl3

110.

98

123.

94

139.

12

143.

02

207.

96


O

O

6o

S91

AN

MR

spectraSupporting

Information

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

9.00

0.94

6.03

6.17

2.35

2.70

7.11

7.13

7.16

7.18

7.26

CD

Cl3


OH

1b

S92

AN

MR

spectraSupporting

Information

-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)

21.1

6

76.8

4 CD

Cl3

77.1

6 CD

Cl3

77.4

8 CD

Cl3

81.7

4

127.

9112

8.68

136.

86

144.

44


OH

1b

S93

AN

MR

spectraSupporting

Information

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.5f1 (ppm)

27.0

0

0.97

5.98

6.00

1.32

1.32

2.74

7.19

7.21

7.21

7.26

CD

Cl3

7.31

7.33


OH

1c

S94

AN

MR

spectraSupporting

Information

-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)

31.5

034

.59

76.8

477

.16

CDCl

377

.16

77.4

881

.66

124.

8412

7.68

144.

31

149.

95


OH

1c

S95

AN

MR

spectraSupporting

Information

-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.0f1 (ppm)

18.0

2

1.00

5.79

2.96

2.28

2.68

6.89

6.89

6.89

6.90

6.90

6.91

6.91

6.91

6.91

6.92

6.92

6.92

7.26

CD

Cl3


OH

1d

S96

AN

MR

spectraSupporting

Information

-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)

21.6

6

76.9

1 CD

Cl3

77.1

6 CD

Cl3

77.4

1 CD

Cl3

82.0

2

125.

8612

8.91

137.

31

147.

23


OH

1d

S97

AN

MR

spectraSupporting

Information

-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.0f1 (ppm)

1.05

6.12

3.00

3.01

3.01

3.11

3.06

3.13

7.26

CD

Cl3

7.46

7.46

7.47

7.47

7.48

7.49

7.49

7.49

7.49

7.50

7.51

7.51

7.52

7.52

7.56

7.57

7.58

7.58

7.74

7.74

7.74

7.75

7.76

7.76

7.76

7.76

7.76

7.80

7.80

7.80

7.82

7.82

7.84

7.84

7.85

7.85

7.85

7.85

7.85

7.86

7.87

7.87

7.87


OH

1e

S98

AN

MR

spectraSupporting

Information

-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)

77.1

6 CD

Cl3

82.6

8

126.

3412

6.44

126.

5312

6.93

127.

6612

7.99

128.

6113

2.75

132.

9714

3.94


OH

1e

S99

AN

MR

spectraSupporting

Information

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

1.01

6.03

6.00

1.55

2.70

6.98

6.99

6.99

7.00

7.00

7.00

7.01

7.01

7.01

7.02

7.02

7.03

7.04

7.19

7.19

7.20

7.20

7.21

7.22

7.22

7.22

7.23

7.23

7.24

7.25

7.26

CD

Cl3


OH

F

F

F

1f

S100

AN

MR

spectraSupporting

Information

-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)

77.1

6 CD

Cl3

81.0

8

114.

9711

5.18

129.

6212

9.71

142.

4914

2.53

160.

9616

3.41


OH

F

F

F

1f

S101

AN

MR

spectraSupporting

Information

-250-240-230-220-210-200-190-180-170-160-150-140-130-120-110-100-90-80-70-60-50-40-30-20-1001020304050f1 (ppm)

-114

.92

19F-NMR (376 MHz, CDCl3)

OH

F

F

F

1f

S102

AN

MR

spectraSupporting

Information

-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.011.512.012.513.0f1 (ppm)

0.98

6.00

5.95

2.68

2.69

2.69

2.70

2.71

7.18

7.19

7.19

7.26

CD

Cl3

7.29

7.31


OH

Cl

Cl

Cl

1g

S103

AN

MR

spectraSupporting

Information

-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)

76.9

1 CD

Cl3

77.1

6 CD

Cl3

77.1

6 CD

Cl3

77.4

1 CD

Cl3

81.1

0

128.

5012

9.28

133.

87

144.

64


OH

Cl

Cl

Cl

1g

S104

AN

MR

spectraSupporting

Information

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.0f1 (ppm)

0.96

9.00

5.92

5.87

2.75

3.80

6.82

6.84

7.16

7.19

7.26

CD

Cl3


OH

O

O

O

1h

S105

AN

MR

spectraSupporting

Information

-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)

55.4

0

76.8

4 CD

Cl3

77.1

6 CD

Cl3

77.4

8 CD

Cl3

81.2

9

113.

26

129.

18

139.

82

158.

71


OH

O

O

O

1h

S106

AN

MR

spectraSupporting

Information

-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

0.99

6.00

5.99

7.26

CD

Cl3


OH

CF3

CF3

CF3

1i

S107

AN

MR

spectraSupporting

Information

-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)

77.1

6 CD

Cl3

81.4

6

120.

7812

2.95

125.

1112

5.52

125.

5512

5.58

125.

6112

7.28

128.

2613

0.05

130.

3113

0.57

130.

83

149.

2314

9.24

118119120121122123124125126127128129130131132f1 (ppm)

120.

78

122.

95

125.

1112

5.52

125.

5512

5.58

125.

61

127.

28

128.

26

130.

0513

0.31

130.

5713

0.83


OH

CF3

CF3

CF3

1i

S108

AN

MR

spectraSupporting

Information

-240-230-220-210-200-190-180-170-160-150-140-130-120-110-100-90-80-70-60-50-40-30-20-10010203040f1 (ppm)

-62.

68


OH

CF3

CF3

CF3

1i

S109

AN

MR

spectraSupporting

Information

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.0f1 (ppm)

1.00

6.15

6.29

1.52

2.73

7.14

7.14

7.14

7.15

7.15

7.15

7.15

7.16

7.16

7.16

7.16

7.17

7.17

7.17

7.18

7.18

7.18

7.18

7.25

7.26

CD

Cl3

7.26

7.27

7.27

7.27

7.28

7.28

7.28

7.29

7.30


OH

O

O

OCF3

CF3

CF31j

S110

AN

MR

spectraSupporting

Information

-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)

77.1

6 CD

Cl3

81.0

1

117.

5011

9.55

120.

6712

0.68

121.

6012

3.65

129.

41

144.

6314

8.80

148.

82


OH

O

O

OCF3

CF3

CF31j

S111

AN

MR

spectraSupporting

Information

-240-230-220-210-200-190-180-170-160-150-140-130-120-110-100-90-80-70-60-50-40-30-20-10010203040f1 (ppm)

-57.

82


OH

O

O

OCF3

CF3

CF31j

S112

AN

MR

spectraSupporting

Information

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

0.97

5.93

3.00

1.61

3.22

7.26

CD

Cl3

7.77

7.77

7.77

7.94

7.94


OH

CF3

CF3

CF3 CF3

CF3

CF3

1k

S113

AN

MR

spectraSupporting

Information

-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)

77.1

6 CD

Cl3

80.7

7

119.

6912

1.86

123.

1212

3.15

123.

1812

3.21

123.

2412

4.03

126.

2012

7.63

127.

6412

7.66

132.

4013

2.67

132.

9413

3.20

146.

46


OH

CF3

CF3

CF3 CF3

CF3

CF3

1k

S114

AN

MR

spectraSupporting

Information

-240-230-220-210-200-190-180-170-160-150-140-130-120-110-100-90-80-70-60-50-40-30-20-10010203040f1 (ppm)

-63.

10


OH

CF3

CF3

CF3 CF3

CF3

CF3

1k

S115

AN

MR

spectraSupporting

Information

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

1.00

6.00

2.93

3.07

2.93

2.66

5.95

6.69

6.69

6.70

6.70

6.71

6.72

6.73

6.78

6.79

7.26

CD

Cl3


OH

O

O

O

O

O

O

1l

S116

AN

MR

spectraSupporting

Information

-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)

77.1

6 CD

Cl3

81.8

1

101.

27

107.

5410

8.87

121.

47

141.

2714

6.85

147.

52


OH

O

O

O

O

O

O

1l

S117

AN

MR

spectraSupporting

Information

-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

1.00

3.00

3.56

3.35

3.20

3.21

1.27

1.56

3.70

6.83

6.83

7.25

7.25

7.26

7.26

CD

Cl3

7.26

7.26

7.28

7.28

7.31

7.31

7.32

7.33

7.33

7.34

7.34

7.50

7.50

7.51

7.52

7.57

7.57

7.58

7.58

7.59

7.59

7.59

7.59


OH

O

O

O

1m

S118

AN

MR

spectraSupporting

Information

-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)

71.7

576

.91

CDCl

377

.16

CDCl

377

.41

CDCl

3

106.

19

111.

79

121.

7312

3.33

125.

1012

7.87

155.

1115

5.28


OH

O

O

O

1m

S119

AN

MR

spectraSupporting

Information

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

1.00

3.00

3.11

2.97

3.02

3.02

3.01

6.69

6.69

6.70

6.70

7.26

CD

Cl3

7.31

7.31

7.32

7.33

7.44

7.44

7.45

7.46

7.46

7.46

7.50

7.50

7.62

7.63


OH

O

O

O

1n

S120

AN

MR

spectraSupporting

Information

-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)

76.9

1 CD

Cl3

77.1

6 CD

Cl3

77.1

6 CD

Cl3

77.4

1 CD

Cl3

82.7

2

107.

09

110.

88

120.

9612

4.96

127.

01

142.

6214

5.61

154.

20


OH

O

O

O

1n

S121

AN

MR

spectraSupporting

Information

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

4.10

2.00

4.11

2.12

2.12

1.24

2.41

2.42

2.43

2.43

2.44

3.44

3.47

3.54

3.69

3.70

3.71

4.45

7.20

7.22

7.26

CD

Cl3

7.43

7.45


O

N

Br

11

S122

AN

MR

spectraSupporting

Information

-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)

53.6

8

62.8

0

67.0

9

76.8

4 CD

Cl3

77.1

6 CD

Cl3

77.1

6 CD

Cl3

77.4

8 CD

Cl3

121.

11

130.

9413

1.52

131.

5913

6.95

129.0129.5130.0130.5131.0131.5132.0132.5f1 (ppm)

130.

94

131.

5213

1.59


O

N

Br

11

S123

AN

MR

spectraSupporting

Information

-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

12.0

0

0.92

6.10

12.0

5

5.96

6.83

1.21

2.44

2.85

3.49

3.69

3.70

3.71

7.20

7.21

7.25

7.26

CD

Cl3

7.26


OHN

N

N

O

O

O

1o

S124

AN

MR

spectraSupporting

Information

-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)

53.7

8

63.1

9

67.1

5

76.9

1 CD

Cl3

77.1

6 CD

Cl3

77.1

6 CD

Cl3

77.4

1 CD

Cl3

81.8

0

127.

9412

8.87

136.

91

145.

99


OHN

N

N

O

O

O

1o

S125

AN

MR

spectraSupporting

Information

-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

2.88

2.94

2.12

0.91

4.05

1.99

0.63

0.28

1.87

1.88

0.99

1.01

1.30

1.30

1.31

1.32

1.32

1.32

1.33

1.33

1.33

1.34

1.51

1.64

1.65

1.65

1.65

1.66

1.67

1.67

1.68

1.68

1.68

1.68

1.70

1.71

1.73

1.74

1.99

1.99

2.00

2.01

2.02

2.02

2.02

2.04

2.04

2.05

7.23

7.24

7.24

7.25

7.25

7.25

7.25

7.25

7.26

CD

Cl3

7.26

7.26

7.27

7.27

7.34

7.34

7.34

7.35

7.35

7.36

7.37

7.37

7.37

7.51

7.52

7.52

7.52

7.53

7.53

7.53

7.53


OH

7a

S126

AN

MR

spectraSupporting

Information

1520253035404550556065707580859095100105110115120125130135140145150155f1 (ppm)

24.1

5

29.5

432

.48

35.0

135

.19

72.9

976

.91

CDCl

377

.16

CDCl

377

.16

CDCl

377

.41

CDCl

3

124.

7212

6.88

128.

37

149.

42


OH

7a

S127

AN

MR

spectraSupporting

Information

-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

8.81

1.00

3.16

1.99

3.97

0.64

0.10

0.08

0.17

1.92

1.92

0.94

1.10

1.12

1.13

1.13

1.15

1.54

1.54

1.55

1.55

1.55

1.56

1.57

1.57

1.58

1.58

1.59

1.60

1.73

1.73

1.73

1.73

1.73

1.74

1.74

1.74

1.75

1.75

1.75

1.76

1.76

1.76

1.76

1.76

1.76

1.77

1.81

1.82

1.84

1.84

1.85

1.85

1.85

1.85

1.87

1.87

1.87

1.87

1.88

1.88

1.88

1.89

1.89

1.89

1.91

1.91

1.91

7.25

7.26

7.26

7.27

7.27

7.27

7.27

7.27

7.28

7.29

7.29

7.36

7.36

7.36

7.37

7.37

7.38

7.38

7.39

7.39

7.39

7.39

7.52

7.53

7.53

7.53

7.53

7.54

7.55

7.55


OH

cis-7b

S128

AN

MR

spectraSupporting

Information

102030405060708090100110120130140150160f1 (ppm)

23.0

4

27.7

5

32.6

3

39.5

5

47.6

6

72.9

176

.91

CDCl

377

.16

CDCl

377

.16

CDCl

377

.41

CDCl

3

124.

6312

6.80

128.

33

149.

69


OH

cis-7b

S129

AN

MR

spectraSupporting

Information

-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

8.85

2.11

1.14

4.99

2.01

1.09

1.95

1.95

0.76

0.77

0.77

0.77

0.78

0.78

0.78

0.97

0.99

1.00

1.00

1.02

1.02

1.03

1.03

1.05

1.05

1.05

1.06

1.14

1.14

1.15

1.15

1.16

1.17

1.17

1.18

1.19

1.70

1.72

1.72

1.73

1.73

1.73

1.74

1.74

1.74

1.74

1.75

1.75

1.75

1.75

1.76

1.76

1.76

1.77

1.77

1.78

2.53

2.53

2.53

2.55

2.56

2.56

7.26

CD

Cl3

7.27

7.27

7.27

7.28

7.28

7.28

7.28

7.29

7.29

7.30

7.30

7.36

7.36

7.36

7.36

7.36

7.37

7.37

7.37

7.38

7.38

7.38

7.38

7.39

7.39

7.39

7.39

7.39

7.55

7.55

7.57

7.57


OH

trans-7b

S130

AN

MR

spectraSupporting

Information

101520253035404550556065707580859095100105110115120125130135140145150155f1 (ppm)

25.1

327

.73

29.8

632

.38

38.9

9

47.9

3

73.5

876

.91

CDCl

377

.16

CDCl

377

.16

CDCl

377

.41

CDCl

3

126.

5312

7.52

128.

69

144.

52


OH

trans-7b

S131

AN

MR

spectraSupporting

Information

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.0f1 (ppm)

3.00

0.88

2.07

4.21

3.73

1.95

1.95

1.95

1.96

1.96

1.96

1.96

1.96

1.97

1.97

1.98

1.98

2.15

5.48

7.24

7.24

7.24

7.25

7.25

7.25

7.25

7.26

7.26

7.26

CD

Cl3

7.27

7.27

7.27

7.31

7.31

7.32

7.32

7.33

7.33

7.33

7.33

7.33

7.33

7.34

7.34

7.35

7.35

7.42

7.42

7.42

7.44

7.44

7.44


HO

7c

S132

AN

MR

spectraSupporting

Information

-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)

30.9

8

76.3

576

.91

CDCl

377

.16

CDCl

377

.16

CDCl

377

.41

CDCl

3

125.

9712

7.09

128.

30

148.

12


HO

7c

S133

AN

MR

spectraSupporting

Information

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

3.00

0.96

2.14

1.08

1.09

2.13

0.88

1.80

1.12

1.98

1.96

1.62

1.74

2.11

2.12

2.13

2.14

2.14

2.15

2.15

2.17

2.41

2.42

2.44

2.44

2.45

2.46

2.47

2.49

2.59

2.61

2.62

2.62

2.63

2.64

2.65

2.67

7.11

7.11

7.11

7.11

7.11

7.12

7.12

7.13

7.13

7.13

7.13

7.13

7.15

7.16

7.16

7.17

7.18

7.18

7.23

7.25

7.25

7.25

7.26

CD

Cl3

7.26

7.27

7.27

7.27

7.28

7.29

7.29

7.35

7.36

7.36

7.36

7.36

7.37

7.37

7.38

7.38

7.38

7.38

7.38

7.39

7.39

7.40

7.40

7.40

7.47

7.47

7.48

7.49

7.50


HO

7d

S134

AN

MR

spectraSupporting

Information

20253035404550556065707580859095100105110115120125130135140145150155f1 (ppm)

30.6

030

.71

46.1

0

74.8

776

.84

CDCl

377

.16

CDCl

377

.48

CDCl

3

124.

9012

5.90

126.

8212

8.42

128.

4512

8.52

142.

40

147.

68


HO

7d

S135

AN

MR

spectraSupporting

Information

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.0f1 (ppm)

3.08

1.01

2.13

1.00

1.00

1.98

1.04

1.02

4.02

3.99

2.04

1.68

1.88

2.19

2.19

2.20

2.20

2.21

2.22

2.23

2.23

2.24

7.23

7.23

7.23

7.23

7.23

7.24

7.24

7.24

7.25

7.26

CD

Cl3

7.30

7.31

7.32

7.32

7.32

7.32

7.33

7.33

7.34

7.35

7.36

7.36

7.36

7.36

7.37

7.38

7.38

7.41

7.41

7.41

7.42

7.42

7.43

7.43

7.43

7.43

7.44

7.44

7.44

7.44

7.44

7.45

7.45

7.46

7.46

7.46

7.46

7.46

7.46

7.46

7.46

7.47

7.47

7.48

7.52

7.52

7.53

7.53

7.53

7.54

7.54

7.54

7.55

7.55

7.55

7.55

7.56

7.60

7.60

7.60

7.60

7.60

7.61

7.61

7.62

7.62


HO

7e

S136

AN

MR

spectraSupporting

Information

0102030405060708090100110120130140150160170f1 (ppm)

30.2

130

.68

46.0

5

74.8

277

.16

CDCl

3

124.

9012

6.80

127.

0812

7.12

127.

2212

8.40

128.

8212

8.84

138.

8314

1.15

141.

53

147.

64


HO

7e

S137

AN

MR

spectraSupporting

Information

-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.0f1 (ppm)

0.98

2.06

2.07

4.16

4.00

1.37

1.98

2.01

1.25

1.53

1.69

1.69

1.71

1.71

1.72

1.80

1.81

1.81

1.83

1.83

1.84

2.08

2.08

2.10

2.10

2.11

2.11

2.13

2.13

2.16

2.17

2.19

2.19

2.21

2.22

3.96

3.97

3.98

3.99

3.99

3.99

3.99

4.00

4.01

4.02

7.24

7.24

7.24

7.25

7.26

7.26

CD

Cl3

7.26

7.27

7.27

7.27

7.34

7.35

7.35

7.37

7.37

7.52

7.52

7.54

7.54


HO

O O

7f

S138

AN

MR

spectraSupporting

Information

-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)

30.9

2

36.7

7

64.3

964

.51

72.6

076

.91

CDCl

377

.16

CDCl

377

.41

CDCl

3

108.

58

124.

6612

7.07

128.

43

148.

64


HO

O O

7f

S139

AN

MR

spectraSupporting

Information

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

2.11

2.07

2.02

2.00

2.01

2.26

5.93

1.96

1.73

1.73

1.73

1.76

1.76

1.77

2.14

2.15

2.17

2.18

2.18

2.19

2.21

2.22

2.46

2.47

2.49

2.49

2.52

2.53

2.78

2.79

2.80

2.81

2.82

3.60

7.24

7.25

7.25

7.26

7.26

7.26

CD

Cl3

7.26

7.27

7.27

7.28

7.28

7.28

7.28

7.29

7.29

7.32

7.32

7.32

7.33

7.34

7.34

7.34

7.35

7.35

7.35

7.36

7.36

7.36

7.36

7.37

7.37

7.37

7.38

7.38

7.38

7.51

7.52

7.52

7.52

7.53

7.53

7.53

7.54

7.54


HO

NBn

7g

S140

AN

MR

spectraSupporting

Information

-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)

38.6

2

49.5

8

63.3

7

71.4

576

.84

CDCl

377

.16

CDCl

377

.48

CDCl

3

124.

7012

7.11

127.

1612

8.37

128.

4612

9.38

138.

53

148.

56


HO

NBn

7g

S141

AN

MR

spectraSupporting

Information

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.0f1 (ppm)

3.04

0.99

2.20

1.06

1.05

3.00

1.97

1.98

0.19

0.73

1.96

1.97

1.61

1.73

2.07

2.08

2.09

2.09

2.10

2.10

2.11

2.12

2.12

2.13

2.13

2.15

2.37

2.38

2.39

2.39

2.40

2.41

2.42

2.43

2.53

2.54

2.55

2.56

2.57

2.57

2.58

2.59

3.77

6.79

6.79

6.80

6.80

6.81

7.02

7.02

7.02

7.03

7.03

7.03

7.04

7.04

7.04

7.04

7.04

7.25

7.25

7.25

7.26

CD

Cl3

7.26

7.26

7.26

7.26

7.27

7.28

7.28

7.28

7.35

7.36

7.36

7.36

7.37

7.37

7.37

7.37

7.37

7.37

7.37

7.38

7.38

7.38

7.39

7.39

7.39

7.46

7.47

7.47

7.47

7.47

7.47

7.48

7.48

7.48

7.49

7.49


HO

MeO

7h

S142

AN

MR

spectraSupporting

Information

-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)

29.6

630

.71

46.2

9

55.4

0

74.8

976

.91

CDCl

377

.16

CDCl

377

.16

CDCl

377

.41

CDCl

3

113.

97

124.

9212

6.78

128.

4012

9.32

134.

40

147.

76

157.

87


HO

MeO

7h

S143

AN

MR

spectraSupporting

Information

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

2.96

0.99

2.11

1.07

1.08

3.00

2.86

1.90

1.88

1.86

1.67

1.76

2.12

2.13

2.13

2.14

2.14

2.15

2.16

2.16

2.51

2.52

2.53

2.53

2.54

2.55

2.55

2.57

2.74

2.75

2.76

2.77

2.78

2.78

2.79

2.80

3.04

7.30

7.31

7.31

7.31

7.32

7.33

7.33

7.33

7.39

7.39

7.40

7.40

7.40

7.42

7.49

7.49

7.50

7.50

7.82

7.83


HO

S

OO

7i

S144

AN

MR

spectraSupporting

Information

0102030405060708090100110120130140150f1 (ppm)

1.17

30.6

830

.82

44.7

345

.75

74.6

376

.91

CDCl

377

.16

CDCl

377

.16

CDCl

377

.41

CDCl

3

124.

8312

7.04

127.

6212

8.54

129.

43

138.

11

147.

2414

9.31


HO

S

OO

7i

S145

AN

MR

spectraSupporting

Information

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

8.89

3.00

0.96

2.09

1.05

1.03

2.00

0.20

0.86

4.02

1.96

0.23

0.24

0.25

1.56

1.61

1.62

1.62

1.74

2.11

2.13

2.13

2.14

2.14

2.15

2.16

2.17

2.40

2.42

2.43

2.44

2.45

2.46

2.48

2.59

2.60

2.61

2.62

2.63

2.63

2.65

7.11

7.11

7.11

7.12

7.12

7.12

7.13

7.13

7.13

7.14

7.14

7.25

7.25

7.25

7.26

CD

Cl3

7.26

7.26

7.27

7.27

7.27

7.27

7.28

7.29

7.29

7.35

7.36

7.36

7.36

7.37

7.37

7.37

7.38

7.38

7.38

7.38

7.39

7.39

7.39

7.40

7.40

7.40

7.40

7.41

7.41

7.42

7.42

7.42

7.43

7.47

7.47

7.47

7.47

7.48

7.48

7.49

7.49

7.49


HO

Me3Si

7j

S146

AN

MR

spectraSupporting

Information

-100102030405060708090100110120130140150160170180f1 (ppm)

-0.9

4

30.5

430

.75

45.9

5

74.8

876

.84

CDCl

377

.16

CDCl

377

.16

CDCl

377

.48

CDCl

3

124.

9012

6.82

127.

9312

8.41

133.

62

137.

54

143.

05

147.

66


HO

Me3Si

7j

S147

AN

MR

spectraSupporting

Information

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.0f1 (ppm)

3.06

0.97

2.12

1.04

1.04

3.00

0.20

0.80

1.92

1.96

1.98

1.01

0.94

1.63

1.63

1.64

1.75

1.76

2.09

2.11

2.11

2.12

2.12

2.13

2.13

2.14

2.15

2.16

2.17

2.17

2.45

2.46

2.48

2.48

2.49

2.49

2.50

2.50

2.51

2.52

2.66

2.66

2.67

2.67

2.68

2.68

2.69

2.69

2.70

2.70

2.70

2.70

2.71

3.90

7.25

7.25

7.26

7.26

7.26

CD

Cl3

7.27

7.27

7.27

7.27

7.27

7.28

7.28

7.29

7.30

7.30

7.30

7.31

7.31

7.36

7.36

7.38

7.38

7.38

7.39

7.47

7.47

7.47

7.48

7.48

7.48

7.49

7.49

7.49

7.49

7.49

7.49

7.80

7.80

7.81

7.82

7.82

7.83

7.83

7.83

7.84

7.84


HO

O

O

7k

S148

AN

MR

spectraSupporting

Information

-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)

30.4

130

.69

46.0

3

52.2

0

74.7

276

.91

CDCl

377

.16

CDCl

377

.16

CDCl

377

.41

CDCl

3

124.

8812

6.90

127.

2112

8.46

128.

5312

9.51

130.

3313

3.18

142.

80

147.

51

167.

38


HO

O

O

7k

S149

AN

MR

spectraSupporting

Information

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.0f1 (ppm)

8.73

3.27

1.13

2.12

1.01

1.02

0.24

2.58

2.00

1.98

0.92

1.00

1.59

1.63

1.74

2.10

2.12

2.13

2.13

2.15

2.16

2.44

2.45

2.47

2.47

2.48

2.49

2.50

2.51

2.64

2.66

2.67

2.67

2.68

2.69

2.70

2.72

7.25

7.25

7.26

7.26

CD

Cl3

7.26

7.27

7.27

7.27

7.27

7.28

7.28

7.28

7.29

7.35

7.37

7.37

7.39

7.47

7.47

7.47

7.48

7.48

7.49

7.49

7.49

7.50

7.74

7.75

7.75

7.76

7.77

7.77

7.77

7.78

7.78

7.78

7.79


HO

O

O

7l

S150

AN

MR

spectraSupporting

Information

0102030405060708090100110120130140150160170180190f1 (ppm)

28.3

530

.44

30.7

3

46.0

6

74.7

776

.84

CDCl

377

.16

CDCl

377

.48

CDCl

381

.06

124.

8912

6.88

127.

0612

8.34

128.

4612

9.35

132.

2113

2.63

142.

57

147.

55

166.

08


HO

O

O

7l

S151

AN

MR

spectraSupporting

Information

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.5f1 (ppm)

6.33

3.29

0.97

2.04

0.99

1.00

4.03

1.95

2.18

0.67

1.92

1.94

1.10

1.22

1.62

1.82

2.06

2.07

2.08

2.08

2.09

2.09

2.10

2.10

2.11

2.11

2.12

2.12

2.13

2.13

2.15

2.16

2.41

2.42

2.44

2.44

2.45

2.45

2.46

2.47

2.61

2.63

2.63

2.64

2.65

2.65

2.66

2.68

3.24

3.52

7.11

7.11

7.13

7.13

7.24

7.24

7.25

7.25

7.25

7.25

7.26

7.26

CD

Cl3

7.26

7.26

7.26

7.27

7.27

7.28

7.28

7.35

7.35

7.36

7.37

7.37

7.37

7.37

7.37

7.38

7.38

7.39

7.47

7.47

7.48

7.49


HO

N

O

7m

S152

AN

MR

spectraSupporting

Information

102030405060708090100110120130140150160170f1 (ppm)

13.0

514

.37

30.4

530

.71

39.3

4

43.3

9

45.9

6

74.7

476

.91

CDCl

377

.16

CDCl

377

.41

CDCl

3

124.

8912

6.58

126.

8512

8.41

128.

43

134.

87

143.

66

147.

60

171.

52


HO

N

O

7m

S153

AN

MR

spectraSupporting

Information

-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

3.16

1.02

2.10

1.00

1.00

1.88

1.87

1.32

1.93

1.93

1.62

1.72

2.07

2.08

2.09

2.09

2.10

2.11

2.37

2.38

2.39

2.40

2.40

2.41

2.42

2.43

2.57

2.58

2.59

2.60

2.61

2.61

2.62

2.63

7.03

7.03

7.04

7.05

7.19

7.21

7.25

7.26

7.26

7.26

7.26

CD

Cl3

7.27

7.27

7.27

7.27

7.27

7.28

7.28

7.29

7.35

7.36

7.36

7.37

7.37

7.37

7.38

7.39

7.39

7.39

7.46

7.46

7.46

7.47

7.48

7.48

7.48


HO

Cl

7n

S154

AN

MR

spectraSupporting

Information

-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)

29.9

930

.71

46.0

5

74.7

577

.16

CDCl

3

124.

8612

6.90

128.

4612

8.56

129.

7913

1.56

140.

89

147.

51


HO

Cl

7n

S155

AN

MR

spectraSupporting

Information

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.5f1 (ppm)

3.00

1.04

2.14

1.01

1.03

0.91

0.84

0.18

0.32

0.88

1.99

1.90

1.61

1.71

2.03

2.04

2.05

2.06

2.07

2.07

2.07

2.08

2.09

2.09

2.10

2.10

2.11

2.12

2.13

2.15

2.23

2.23

2.24

2.24

2.25

2.25

2.26

2.26

2.26

2.27

2.27

2.28

2.28

2.29

2.29

2.40

2.41

2.42

2.42

2.43

2.43

2.43

2.44

2.44

2.44

2.45

2.45

2.46

2.46

2.46

2.47

2.47

6.22

6.22

6.22

6.22

7.15

7.15

7.15

7.15

7.15

7.15

7.24

7.25

7.25

7.26

7.26

7.26

CD

Cl3

7.26

7.26

7.27

7.28

7.28

7.31

7.32

7.32

7.35

7.36

7.36

7.37

7.37

7.38

7.38

7.45

7.45

7.46

7.47

7.47

7.47


HO

O

7o

S156

AN

MR

spectraSupporting

Information

-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)

19.6

9

30.6

1

44.3

1

74.7

976

.91

CDCl

377

.16

CDCl

377

.16

CDCl

377

.41

CDCl

3

111.

04

124.

9012

4.99

126.

8412

8.40

138.

7414

2.92

147.

57


HO

O

7o

S157

AN

MR

spectraSupporting

Information

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

3.05

0.97

2.08

1.04

1.04

2.99

2.00

1.02

0.96

1.97

1.00

1.98

2.00

1.65

1.65

1.77

2.16

2.17

2.19

2.19

2.20

2.20

2.21

2.22

2.22

2.23

2.23

2.24

2.25

2.26

2.55

2.56

2.57

2.58

2.58

2.59

2.60

2.61

2.73

2.74

2.75

2.75

2.76

2.76

2.78

2.79

3.90

7.09

7.09

7.10

7.10

7.11

7.12

7.22

7.22

7.23

7.24

7.26

7.26

7.27

7.27

7.28

7.28

7.28

7.28

7.28

7.29

7.30

7.30

7.37

7.38

7.38

7.38

7.39

7.39

7.39

7.39

7.39

7.39

7.40

7.40

7.41

7.41

7.41

7.47

7.47

7.48

7.48

7.50

7.50

7.50

7.51

7.51

7.52

7.52

7.52

7.52

7.52

7.62

7.64


O

HO

7p

S158

AN

MR

spectraSupporting

Information

-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)

30.5

630

.75

46.0

7

55.4

2

74.9

376

.91

CDCl

377

.16

CDCl

377

.16

CDCl

377

.41

CDCl

3

105.

78

118.

8112

4.95

126.

2012

6.83

126.

9312

7.89

128.

4412

8.98

129.

2513

3.07

137.

5414

7.75

157.

29


O

HO

7p

S159

AN

MR

spectraSupporting

Information

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.0f1 (ppm)

1.23

1.13

3.04

2.19

2.02

0.97

3.03

5.00

0.98

1.98

1.96

1.00

1.15

1.17

1.17

1.17

1.18

1.18

1.18

1.19

1.19

1.19

1.20

1.20

1.21

1.21

1.29

1.30

1.31

1.31

1.32

1.33

1.33

1.34

1.34

1.35

1.35

1.36

1.52

1.56

1.58

1.59

1.61

1.62

1.84

1.85

1.86

1.86

1.87

1.88

1.89

2.42

3.52

3.91

3.92

3.93

3.93

3.93

3.93

3.94

3.94

3.94

3.95

3.95

7.17

7.17

7.17

7.18

7.18

7.18

7.19

7.19

7.20

7.20

7.20

7.26

CD

Cl3

7.27

7.27

7.28

7.29

7.29

7.29

7.29

7.30

7.30

7.30

7.31

7.39

7.40

7.40

7.40

7.40

7.41

7.41

7.41

7.42

7.42

7.46

7.46


N

N

N

N

O

OHO Me

7q

S160

AN

MR

spectraSupporting

Information

-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)

21.0

5

28.0

229

.77

30.2

733

.63

40.8

943

.48

74.3

976

.91

CDCl

377

.16

CDCl

377

.16

CDCl

377

.41

CDCl

3

107.

74

124.

8712

6.44

128.

12

141.

54

148.

2114

8.82

151.

5715

5.45


N

N

N

N

O

OHO Me

7q

S161

AN

MR

spectraSupporting

Information

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.5f1 (ppm)

3.15

0.91

2.13

3.02

1.07

1.05

2.18

2.82

1.62

0.30

2.00

1.60

1.60

1.60

1.61

1.73

2.09

2.10

2.11

2.11

2.12

2.13

2.14

2.15

2.16

2.36

2.36

2.36

2.43

2.44

2.45

2.46

2.46

2.47

2.48

2.49

2.59

2.60

2.61

2.62

2.62

2.63

2.64

2.65

7.12

7.12

7.12

7.12

7.12

7.12

7.12

7.12

7.13

7.13

7.13

7.13

7.14

7.14

7.14

7.14

7.14

7.15

7.15

7.16

7.16

7.16

7.17

7.17

7.18

7.18

7.18

7.18

7.18

7.18

7.18

7.19

7.19

7.19

7.19

7.19

7.20

7.20

7.20

7.20

7.23

7.23

7.24

7.24

7.25

7.25

7.25

7.26

CD

Cl3

7.26

7.26

7.26

7.27

7.36

7.38


HO

8a

S162

AN

MR

spectraSupporting

Information

101520253035404550556065707580859095100105110115120125130135140145150155f1 (ppm)

21.1

1

30.6

530

.73

46.0

7

74.7

676

.91

CDCl

377

.16

CDCl

377

.16

CDCl

377

.41

CDCl

3

124.

8412

5.86

128.

4512

8.50

129.

10

136.

36

142.

49

144.

75


HO

8a

S163

AN

MR

spectraSupporting

Information

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.5f1 (ppm)

9.07

3.01

0.97

2.07

1.00

1.02

2.88

2.11

3.94

1.35

1.62

1.75

2.09

2.10

2.11

2.11

2.12

2.13

2.13

2.14

2.14

2.15

2.15

2.15

2.15

2.16

2.17

2.18

2.19

2.48

2.49

2.50

2.50

2.51

2.52

2.53

2.54

2.61

2.62

2.63

2.64

2.65

2.65

2.66

2.67

7.13

7.14

7.14

7.14

7.14

7.15

7.15

7.15

7.15

7.15

7.16

7.16

7.17

7.18

7.24

7.24

7.24

7.25

7.26

7.26

CD

Cl3

7.26

7.27

7.27

7.38

7.38

7.39

7.40

7.40

7.40

7.41

7.41

7.42

7.42


HO

8b

S164

AN

MR

spectraSupporting

Information

20253035404550556065707580859095100105110115120125130135140145150155160f1 (ppm)

30.4

230

.63

31.5

234

.54

46.0

0

74.6

676

.91

77.1

6 CD

Cl3

77.1

677

.41

124.

6112

5.26

125.

8412

8.45

128.

48

142.

53

144.

73

149.

61


HO

8b

S165

AN

MR

spectraSupporting

Information

-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

3.00

0.99

2.06

5.91

1.06

1.03

0.94

1.91

2.10

0.81

1.49

0.40

1.56

1.60

1.72

2.05

2.07

2.08

2.09

2.09

2.10

2.11

2.11

2.12

2.12

2.13

2.13

2.14

2.14

2.14

2.15

2.16

2.17

2.34

2.35

2.35

2.35

2.45

2.46

2.48

2.48

2.49

2.49

2.50

2.51

2.60

2.62

2.63

2.63

2.64

2.64

2.65

2.67

6.91

6.91

6.91

6.91

6.91

6.91

7.08

7.08

7.09

7.09

7.09

7.13

7.13

7.13

7.13

7.13

7.13

7.13

7.14

7.14

7.14

7.14

7.14

7.15

7.15

7.15

7.16

7.16

7.16

7.17

7.17

7.18

7.24

7.24

7.24

7.24

7.25

7.26

7.26

7.26

CD

Cl3

7.26

7.27

7.27

7.27


HO

8c

S166

AN

MR

spectraSupporting

Information

-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)

21.6

9

30.6

230

.67

45.9

9

74.8

076

.91

CDCl

377

.16

CDCl

377

.16

CDCl

377

.41

CDCl

3

122.

7012

5.85

128.

4212

8.46

128.

49

137.

8714

2.55

147.

77


HO

8c

S167

AN

MR

spectraSupporting

Information

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

3.09

0.94

2.08

1.04

1.04

1.97

0.98

1.75

2.00

1.01

2.99

1.00

1.71

1.71

2.21

2.21

2.22

2.22

2.22

2.23

2.24

2.24

2.24

2.25

2.25

2.25

2.26

2.26

2.27

2.27

2.29

2.43

2.44

2.45

2.45

2.46

2.46

2.48

2.49

2.63

2.64

2.66

2.66

2.67

2.67

7.11

7.11

7.12

7.13

7.14

7.14

7.16

7.17

7.17

7.23

7.23

7.23

7.23

7.24

7.25

7.25

7.26

7.26

CD

Cl3

7.26

7.47

7.47

7.48

7.48

7.48

7.49

7.49

7.49

7.49

7.50

7.50

7.50

7.51

7.52

7.56

7.56

7.57

7.58

7.58

7.58

7.84

7.84

7.85

7.85

7.86

7.86

7.86

7.87

7.87

7.88

7.88

7.97

7.97

7.97

7.98


HO

8d

S168

AN

MR

spectraSupporting

Information

-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)

30.6

630

.82

45.9

1

75.0

876

.91

CDCl

377

.16

CDCl

377

.16

CDCl

377

.41

CDCl

3

123.

3712

3.69

125.

9112

5.92

126.

2712

7.64

128.

1912

8.30

128.

4512

8.53

132.

4313

3.36

142.

3514

5.01

123124125126127128129

123.

3712

3.69

125.

9112

5.92

126.

27

127.

6412

8.19

128.

3012

8.45

128.

53


HO

8d

S169

AN

MR

spectraSupporting

Information

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.5f1 (ppm)

3.00

0.95

2.04

1.03

1.02

1.92

1.99

1.05

2.46

1.97

1.60

1.61

1.61

1.71

2.08

2.09

2.10

2.10

2.11

2.12

2.13

2.13

2.15

2.16

2.41

2.42

2.43

2.43

2.44

2.45

2.45

2.47

2.58

2.60

2.60

2.61

2.62

2.62

2.63

2.65

7.02

7.03

7.03

7.03

7.04

7.04

7.05

7.05

7.05

7.05

7.06

7.06

7.07

7.10

7.10

7.11

7.11

7.12

7.12

7.12

7.12

7.12

7.14

7.15

7.15

7.16

7.16

7.16

7.17

7.17

7.18

7.18

7.23

7.24

7.24

7.24

7.25

7.25

7.25

7.26

7.26

7.26

CD

Cl3

7.26

7.27

7.27

7.27

7.42

7.43

7.43

7.43

7.44

7.44

7.44

7.45

7.45

7.46

7.46


HO

F

8e

S170

AN

MR

spectraSupporting

Information

-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)

30.4

530

.68

46.1

0

74.4

776

.77

CDCl

377

.03

CDCl

377

.28

CDCl

3

114.

8711

5.04

125.

8512

6.50

126.

5712

8.29

128.

43

142.

0714

3.27

143.

30

160.

6916

2.64


HO

F

8e

S171

AN

MR

spectraSupporting

Information

-240-230-220-210-200-190-180-170-160-150-140-130-120-110-100-90-80-70-60-50-40-30-20-10010203040f1 (ppm)

-116

.79


HO

F

8e

S172

AN

MR

spectraSupporting

Information

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.0f1 (ppm)

3.09

0.99

2.12

1.04

1.04

2.00

1.05

1.63

0.38

1.96

1.99

1.58

1.60

1.72

2.06

2.07

2.09

2.09

2.10

2.10

2.11

2.12

2.12

2.13

2.14

2.15

2.16

2.39

2.40

2.41

2.42

2.43

2.43

2.44

2.45

2.59

2.60

2.61

2.61

2.62

2.63

2.64

2.65

7.09

7.10

7.10

7.10

7.10

7.10

7.10

7.10

7.11

7.11

7.11

7.11

7.12

7.12

7.12

7.12

7.15

7.15

7.15

7.16

7.16

7.17

7.18

7.18

7.18

7.23

7.24

7.24

7.24

7.25

7.25

7.25

7.26

7.26

7.26

CD

Cl3

7.26

7.27

7.27

7.27

7.28

7.28

7.32

7.33

7.33

7.33

7.34

7.34

7.35

7.40

7.41

7.41

7.42

7.42

7.42

7.43


HO

Cl

8f

S173

AN

MR

spectraSupporting

Information

-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)

30.5

230

.78

46.0

7

74.6

376

.91

CDCl

377

.16

CDCl

377

.16

CDCl

377

.41

CDCl

3

126.

0012

6.51

128.

4212

8.49

128.

5813

2.61

142.

10

146.

19


HO

Cl

8f

S174

AN

MR

spectraSupporting

Information

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.0f1 (ppm)

3.02

0.89

2.06

1.00

1.02

3.00

1.90

1.92

0.98

2.04

1.95

1.62

1.82

2.10

2.12

2.12

2.13

2.14

2.15

2.15

2.16

2.16

2.17

2.46

2.47

2.48

2.49

2.49

2.50

2.51

2.52

2.60

2.62

2.62

2.63

2.64

2.64

2.65

2.66

3.84

6.92

6.94

7.14

7.14

7.14

7.14

7.14

7.14

7.15

7.16

7.16

7.16

7.16

7.16

7.17

7.17

7.17

7.18

7.18

7.19

7.19

7.20

7.20

7.26

7.26

CD

Cl3

7.26

7.27

7.27

7.28

7.29

7.42

7.43


HO

OMe

8g

S175

AN

MR

spectraSupporting

Information

-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)

30.6

030

.68

46.1

7

55.3

8

74.5

476

.91

CDCl

377

.16

CDCl

377

.16

CDCl

377

.41

CDCl

3

113.

67

125.

8512

6.12

128.

4312

8.48

132.

38

139.

8714

2.47

158.

41


HO

OMe

8g

S176

AN

MR

spectraSupporting

Information

-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

2.92

0.91

2.03

1.00

1.00

1.93

0.95

2.05

3.89

1.63

1.79

1.80

2.10

2.10

2.12

2.12

2.12

2.13

2.13

2.13

2.13

2.14

2.14

2.14

2.14

2.15

2.15

2.15

2.16

2.17

2.17

2.17

2.18

2.18

2.19

2.20

2.21

2.39

2.40

2.41

2.42

2.43

2.43

2.44

2.45

2.62

2.64

2.64

2.65

2.66

2.66

2.67

2.68

7.11

7.11

7.12

7.12

7.13

7.16

7.16

7.18

7.18

7.19

7.19

7.19

7.25

7.26

CD

Cl3

7.26

7.26

7.28

7.59

7.60

7.60

7.60

7.61

7.61

7.63

7.63

7.64

7.65


HO

CF3

8h

S177

AN

MR

spectraSupporting

Information

-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)

30.4

330

.83

45.9

9

74.8

077

.16

CDCl

3

121.

1512

3.31

125.

3212

5.35

125.

3812

5.41

126.

0712

7.64

128.

4112

8.60

128.

7112

8.94

128.

9712

9.23

129.

4814

1.93

151.

68

121122123124125126127128129130f1 (ppm)

121.

15

123.

31

125.

3212

5.35

125.

3812

5.41

126.

07

127.

64

128.

4112

8.60

128.

7112

8.94

128.

9712

9.23

129.

48


HO

CF3

8h

S178

AN

MR

spectraSupporting

Information

-96-94-92-90-88-86-84-82-80-78-76-74-72-70-68-66-64-62-60-58-56-54-52-50-48-46-44-42-40f1 (ppm)

-62.

35


HO

CF3

8h

S179

AN

MR

spectraSupporting

Information

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

3.00

0.97

2.04

1.00

1.01

1.97

1.02

1.98

2.13

1.95

1.62

1.76

2.09

2.11

2.12

2.12

2.12

2.13

2.13

2.14

2.14

2.15

2.15

2.17

2.42

2.43

2.44

2.45

2.46

2.46

2.47

2.48

2.61

2.62

2.63

2.64

2.65

2.65

2.66

2.67

7.11

7.11

7.13

7.13

7.13

7.13

7.15

7.16

7.16

7.17

7.17

7.18

7.18

7.19

7.19

7.20

7.20

7.22

7.22

7.24

7.24

7.24

7.25

7.26

7.26

CD

Cl3

7.26

7.26

7.27

7.27

7.50

7.51

7.52


HO

OCF3

8i

S180

AN

MR

spectraSupporting

Information

-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)

30.5

030

.74

46.0

9

74.6

076

.91

77.1

6 CD

Cl3

77.4

1

117.

5911

9.64

120.

7712

0.78

121.

6812

3.72

126.

0212

6.50

128.

4112

8.58

142.

0514

6.40

148.

0514

8.07

148.

0814

8.09


HO

OCF3

8i

S181

AN

MR

spectraSupporting

Information

-240-230-220-210-200-190-180-170-160-150-140-130-120-110-100-90-80-70-60-50-40-30-20-10010203040f1 (ppm)

-57.

82


HO

OCF3

8i

S182

AN

MR

spectraSupporting

Information

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

3.00

0.97

2.05

1.03

1.05

1.95

0.96

2.30

0.94

1.93

1.55

1.66

1.83

2.12

2.13

2.15

2.15

2.16

2.16

2.17

2.17

2.18

2.18

2.18

2.19

2.21

2.22

2.41

2.43

2.43

2.44

2.45

2.45

2.46

2.47

2.65

2.66

2.67

2.67

2.68

2.69

2.70

2.71

7.08

7.09

7.09

7.09

7.09

7.09

7.09

7.10

7.10

7.10

7.10

7.10

7.11

7.15

7.15

7.16

7.17

7.17

7.17

7.18

7.18

7.19

7.24

7.24

7.25

7.25

7.25

7.26

CD

Cl3

7.26

7.27

7.78

7.78

7.78

7.93

7.93

7.93

7.93

7.93

7.94


HO

CF3

CF3

8j

S183

AN

MR

spectraSupporting

Information

-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)

30.3

630

.76

45.9

0

74.6

376

.91

CDCl

377

.16

CDCl

377

.16

CDCl

377

.41

CDCl

312

0.35

120.

8512

0.88

120.

9112

0.94

120.

9712

2.51

124.

6812

5.42

125.

4312

5.46

126.

2512

6.85

128.

2612

8.40

128.

7113

1.30

131.

5613

1.82

132.

09

141.

37

150.

49

120125130f1 (ppm)

120.

3512

0.85

120.

8812

0.91

120.

9412

0.97

122.

51

124.

6812

5.42

125.

4312

5.46

126.

2512

6.85

128.

2612

8.40

128.

71

131.

3013

1.56

131.

8213

2.09


HO

CF3

CF3

8j

S184

AN

MR

spectraSupporting

Information

-240-230-220-210-200-190-180-170-160-150-140-130-120-110-100-90-80-70-60-50-40-30-20-10010203040f1 (ppm)

-62.

72


HO

CF3

CF3

8j

S185

AN

MR

spectraSupporting

Information

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

3.30

0.99

2.06

1.00

1.00

1.97

0.98

1.00

0.98

2.96

2.10

1.58

1.72

2.04

2.05

2.06

2.06

2.06

2.07

2.08

2.08

2.09

2.10

2.11

2.11

2.13

2.14

2.44

2.45

2.46

2.46

2.47

2.48

2.48

2.50

2.58

2.60

2.60

2.61

2.62

2.62

2.63

2.64

5.96

6.79

6.81

6.93

6.93

6.95

6.95

6.99

7.00

7.12

7.12

7.12

7.12

7.13

7.13

7.14

7.14

7.14

7.14

7.14

7.15

7.16

7.17

7.18

7.24

7.24

7.25

7.26

7.26

7.26

CD

Cl3

7.27


HO

OO

8k

S186

AN

MR

spectraSupporting

Information

-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)

30.6

430

.79

46.2

0

74.7

777

.16

CDCl

3

101.

1210

6.06

107.

98

118.

00

125.

9012

8.44

128.

52

141.

9514

2.35

146.

2914

7.81


HO

OO

8k

S187

AN

MR

spectraSupporting

Information

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

3.14

0.97

2.16

2.16

1.00

3.06

1.71

2.14

1.02

1.02

1.70

2.14

2.21

2.22

2.23

2.24

2.25

2.25

2.26

2.26

2.27

2.27

2.29

2.29

2.30

2.30

2.31

2.32

2.60

2.61

2.62

2.63

2.64

2.65

2.66

2.67

2.67

2.68

2.70

6.65

6.66

7.16

7.16

7.16

7.16

7.16

7.17

7.17

7.17

7.17

7.17

7.18

7.18

7.18

7.18

7.19

7.19

7.19

7.21

7.22

7.23

7.23

7.24

7.25

7.25

7.25

7.26

7.26

CD

Cl3

7.26

7.26

7.27

7.27

7.27

7.27

7.28

7.28

7.28

7.28

7.28

7.29

7.29

7.46

7.46

7.47

7.47

7.48

7.48

7.48

7.48

7.55

7.55

7.55

7.55

7.56

7.56

7.57

7.57


HO O

8l

S188

AN

MR

spectraSupporting

Information

-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)

27.3

330

.65

43.3

7

72.2

376

.91

CDCl

377

.16

CDCl

377

.16

CDCl

377

.41

CDCl

3

101.

73

111.

34

121.

1112

2.93

124.

1012

6.03

128.

4412

8.47

128.

56

141.

94

154.

89

162.

26


HO O

8l

S189

AN

MR

spectraSupporting

Information

-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

3.16

1.02

2.19

1.09

1.10

1.00

2.06

1.09

1.67

1.07

1.02

0.99

1.03

1.68

1.81

2.14

2.15

2.15

2.16

2.17

2.17

2.17

2.18

2.18

2.19

2.19

2.20

2.20

2.21

2.21

2.22

2.22

2.23

2.24

2.24

2.25

2.43

2.44

2.45

2.46

2.46

2.47

2.48

2.49

2.60

2.62

2.63

2.63

2.64

2.64

2.66

2.67

6.78

6.78

6.78

6.78

7.11

7.12

7.13

7.13

7.14

7.16

7.17

7.17

7.17

7.23

7.25

7.26

CD

Cl3

7.40

7.41

7.42

7.43

7.48

7.49

7.49

7.50

7.64

7.64

7.75

7.75

7.75


HO

O

8m

S190

AN

MR

spectraSupporting

Information

-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)

31.0

731

.37

47.0

653

.57

53.7

854

.00

CD2C

l254

.22

54.4

3

75.1

8

107.

32

111.

25

118.

0112

2.18

126.

1912

7.79

128.

8112

8.84

143.

1314

3.14

145.

97

154.

40


HO

O

8m

S191

AN

MR

spectraSupporting

Information

-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

3.25

1.01

2.26

1.14

1.15

0.95

3.07

2.03

1.02

0.97

0.90

1.00

1.53

1.65

1.87

2.12

2.13

2.14

2.15

2.17

2.18

2.38

2.39

2.41

2.41

2.42

2.42

2.43

2.45

2.58

2.59

2.60

2.61

2.62

2.62

2.63

2.64

5.32

CD

2Cl2

6.80

6.80

6.80

6.80

6.81

7.10

7.10

7.10

7.10

7.11

7.12

7.12

7.12

7.12

7.12

7.13

7.15

7.21

7.21

7.22

7.23

7.23

7.24

7.41

7.41

7.41

7.41

7.43

7.43

7.43

7.43

7.47

7.47

7.48

7.49

7.49

7.49

7.65

7.66

7.75

7.75

7.75

7.76

1H-NMR (500 MHz, CD2Cl2)

HO

O

8m

S192

AN

MR

spectraSupporting

Information

-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)

31.0

731

.37

47.0

653

.57

53.7

854

.00

CD2C

l254

.22

54.4

3

75.1

8

107.

32

111.

25

118.

0112

2.18

126.

1912

7.79

128.

8112

8.84

143.

1314

3.14

145.

97

154.

40

13C-NMR (126 MHz, CD2Cl2)

HO

O

8m

S193

AN

MR

spectraSupporting

Information

-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.011.512.012.513.0f1 (ppm)

3.04

1.12

2.12

4.86

1.09

1.95

4.00

1.94

1.02

1.68

1.95

1.98

1.61

1.78

2.08

2.10

2.11

2.11

2.12

2.13

2.13

2.14

2.15

2.17

2.43

2.44

2.45

2.45

2.46

2.47

2.48

2.49

2.59

2.60

2.61

2.62

2.63

2.63

2.64

3.51

3.71

3.72

3.73

7.11

7.11

7.11

7.11

7.12

7.12

7.13

7.13

7.13

7.14

7.14

7.14

7.15

7.15

7.15

7.16

7.17

7.17

7.17

7.23

7.23

7.23

7.23

7.24

7.24

7.24

7.25

7.26

7.26

7.26

CD

Cl3

7.31

7.31

7.33

7.33

7.42

7.44


HO

N O

8n

S194

AN

MR

spectraSupporting

Information

-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)

30.6

130

.63

46.0

9

53.7

8

63.2

3

67.1

5

74.7

576

.91

77.1

6 CD

Cl3

77.4

1

124.

8812

5.90

128.

4312

8.51

129.

2613

6.19

142.

39

146.

70


HO

N O

8n

S195

AN

MR

spectraSupporting

Information

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

3.04

0.98

2.10

1.02

1.03

1.95

1.00

1.70

1.61

1.95

1.95

1.62

1.75

2.09

2.10

2.11

2.12

2.12

2.13

2.13

2.14

2.14

2.15

2.16

2.16

2.17

2.18

2.19

2.42

2.44

2.45

2.45

2.46

2.46

2.47

2.49

2.60

2.61

2.62

2.63

2.64

2.64

2.65

2.66

7.11

7.12

7.12

7.12

7.13

7.13

7.13

7.13

7.14

7.14

7.16

7.16

7.16

7.17

7.17

7.18

7.23

7.24

7.24

7.24

7.25

7.25

7.26

7.26

7.26

CD

Cl3

7.26

7.26

7.27

7.27

7.27

7.27

7.27

7.27

7.28

7.29

7.29

7.36

7.36

7.37

7.38

7.38

7.39

7.39

7.40

7.48

7.48

7.50

7.50


HO

9a

S196

AN

MR

spectraSupporting

Information

-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)

30.6

030

.70

46.1

0

74.8

677

.16

CDCl

3

124.

9112

5.89

126.

8212

8.41

128.

4512

8.52

142.

41

147.

70


HO

9a

S197

AN

MR

spectraSupporting

Information

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

2.95

3.01

2.60

0.92

4.06

2.00

1.17

1.90

1.88

0.99

1.01

1.30

1.30

1.31

1.31

1.32

1.32

1.33

1.33

1.33

1.33

1.34

1.34

1.52

1.65

1.65

1.65

1.68

1.68

1.68

1.70

1.71

1.73

1.99

1.99

2.00

2.02

2.02

2.04

2.05

2.05

7.24

7.24

7.24

7.25

7.25

7.25

7.25

7.26

7.26

CD

Cl3

7.26

7.27

7.27

7.27

7.34

7.36

7.36

7.36

7.37

7.37

7.52

7.52

7.52

7.52

7.53

7.53

7.53

7.53


OH

9b

S198

AN

MR

spectraSupporting

Information

-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)

24.1

429

.53

32.4

835

.00

35.1

8

72.9

876

.91

77.1

6 CD

Cl3

77.1

677

.41

124.

7212

6.87

128.

0712

8.36

149.

42


OH

9b

S199

AN

MR

spectraSupporting

Information

-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.0f1 (ppm)

3.00

0.92

2.15

1.02

1.03

1.87

1.03

1.96

1.15

1.90

1.89

1.62

1.63

1.76

2.12

2.13

2.13

2.14

2.14

2.15

2.16

2.16

2.17

2.43

2.44

2.45

2.46

2.47

2.48

2.49

2.60

2.62

2.63

2.63

2.64

2.64

2.66

7.12

7.12

7.12

7.12

7.12

7.12

7.13

7.13

7.13

7.13

7.14

7.14

7.14

7.15

7.16

7.16

7.17

7.17

7.18

7.18

7.24

7.24

7.25

7.26

CD

Cl3

7.26

7.27

7.27

7.27

7.28

7.28

7.29

7.29

7.29

7.37

7.37

7.37

7.38

7.38

7.38

7.38

7.38

7.38

7.38

7.39

7.39

7.40

7.40

7.40

7.40

7.48

7.48

7.48

7.48

7.49

7.49

7.49

7.50

7.50

7.50

7.50

7.50


HO

7d’

S200

AN

MR

spectraSupporting

Information

-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)

30.6

030

.69

46.1

0

74.8

676

.91

77.1

6 CD

Cl3

77.4

1

124.

9112

5.89

126.

8112

8.41

128.

4512

8.51

142.

41

147.

70


HO

7d’

S201

AN

MR

spectraSupporting

Information

-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.0f1 (ppm)

4.05

2.00

3.96

1.58

7.26

CD

Cl3

7.47

7.49

7.49

7.49

7.50

7.50

7.58

7.59

7.61

7.80

7.80

7.82


O

3a’

S202

AN

MR

spectraSupporting

Information

-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)

76.9

177

.16

CDCl

377

.16

77.4

1

128.

4213

0.21

132.

5513

7.75

196.

90


O

3a’

S203

AN

MR

spectraSupporting

Information

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.0f1 (ppm)

2.43

4.14

2.08

5.66

2.15

2.00

2.10

2.01

2.09

10.3

02.

0312

.48

14.3

61.

16

3.68


Rh

OO

NN

Ph

Ph Ph

Ph

Ph

Ph

Ph

Ph

Cl

10

S204

AN

MR

spectraSupporting

Information

-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)

28.5

8

32.7

1

51.1

351

.87

55.2

9

69.0

369

.14

76.9

1 CD

Cl3

77.1

6 CD

Cl3

77.1

6 CD

Cl3

77.4

1 CD

Cl3

96.7

996

.85

114.

4711

5.44

123.

8612

6.01

126.

1412

6.62

126.

7912

7.88

128.

0612

8.27

129.

2712

9.78

130.

2613

1.01

131.

9714

2.43

143.

1014

4.21

144.

7414

6.23

158.

91

184.

4518

4.87


Rh

OO

NN

Ph

Ph Ph

Ph

Ph

Ph

Ph

Ph

Cl

10

S205

AN

MR

spectraSupporting

Information

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

4.02

1.97

1.92

6.00

1.96

1.94

1.97

1.91

22.5

12.

003.

474.

21

3.99

5.78

3.83

0.00

TM

S

1.56

1.56

1.57

1.57

1.59

1.59

1.60

1.60

1.61

1.62

1.62

1.63

1.63

1.90

1.90

1.91

1.91

1.91

1.92

1.92

1.93

1.93

2.03

2.03

2.04

2.04

2.05

2.05

2.06

2.06

2.08

2.08

2.09

2.09

3.17

3.93

3.93

3.94

3.94

4.82

5.32

5.32

5.33

5.33

5.34

5.44

6.11

6.79

6.80

6.81

6.83

6.84

6.84

6.84

6.85

6.85

6.86

6.86

6.87

6.87

6.88

6.89

6.90

6.91

6.95

6.95

6.98

7.01

7.09

7.09

7.10

7.22

7.23

7.24

7.34

7.36

7.95

7.96

1H-NMR (600 MHz, toluene-d8)

Rh

OO

NN

Ph

Ph Ph

Ph

Ph

Ph

Ph

Ph

Cl

10

S206

AN

MR

spectraSupporting

Information

-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)

20.1

8 To

l20

.30

Tol

20.4

3 To

luen

e-d8

20.5

6 To

l20

.69

Tol

28.8

5

33.1

1

51.6

252

.46

54.5

9

68.8

768

.96

97.0

097

.04

114.

9411

5.51

123.

9512

4.97

Tol

125.

13 T

ol12

5.29

Tol

125.

4212

6.18

126.

5212

6.76

127.

0812

7.81

Tol

127.

96 T

ol12

8.13

Tol

128.

2612

8.38

128.

5412

8.71

Tol

128.

87 T

ol12

9.03

Tol

129.

1812

9.66

130.

2813

0.70

131.

6613

2.29

137.

48 T

ol14

3.04

143.

6014

4.74

144.

7714

5.45

147.

3915

9.70

186.

0618

6.41

124125126127128129130131132f1 (ppm)

123.

95

125.

42

126.

1812

6.52

126.

7612

7.08

128.

2612

8.38

128.

5412

9.18

129.

6613

0.28

130.

70

131.

66

132.

29

13C-NMR (151 MHz, toluene-d8)

Rh

OO

NN

Ph

Ph Ph

Ph

Ph

Ph

Ph

Ph

Cl

10

S207

AN

MR

spectraSupporting

Information

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f2 (ppm)

-7800

-7700

-7600

-7500

-7400

-7300

-7200

-7100

-7000

f1 (

ppm

)

{1.59,-7536.19}{3.94,-7535.43}{5.33,-7535.21}

1H-103Rh HMBC (16 MHz, toluene-d8)

Rh

OO

NN

Ph

Ph Ph

Ph

Ph

Ph

Ph

Ph

Cl

10

S208

download fileview on ChemRxivLutzetal_SI.pdf (6.21 MiB)



shuttle arylation by rh(i) catalyzed reversible carbon

Documents