From DNA to Catalysis: Thymine-acetate ligated non-heme iron(III) catalyst for oxidative activation of aliphatic C-H

bonds

Supporting information

Table of Contents: 1. Materials and methods 2. General reactivity and reaction procedures 3. Isolated product characterization 4. Kinetic analysis 5. H2O18 Measurement 6. High resolution ESI-MS measurement 7. UV-Vis data 8. NMR spectra

1. Material and MethodsAll chemicals were obtained from Aldrich and used without further purification. 1H NMR spectra were recorded with a Varian Gemini 300 MHz spectrometer. HRMS (ESI-TOF) mass spectra were recorded with a Bruker micrOTOF mass spectrometer using sodium formate as a calibrant. GC-MS measurements were performed on an Agilent 6850 GC-MS with FID detector using an Agilent DB-WAX (30.0 m x 0.25 mm) column at 1.8 mL/min He carrier gas flow. UV-vis spectra were collected with a Hewlett Packard 8453spectrophotometer. CAUTION: Mixing a metal salt and peroxide can cause explosion. [1]

[1] Jones, A. K.; Wilson, T. E.; Nikam, S. S. In Encyclopedia of Reagents for Organic Synthesis, Paquette, L. A. Ed.; John Wiley & Sons, Inc. 1995, 2, 880. In our reported procedure for synthesis of ketones, there are no any problems even the 8 mmol scale reactions were carried out under the standard conditions.

Synthesis of iron chloride /thymine-1-acetic acid Complex:A solution of Fe(Cl)3·6H2O (83.8 mg,0.31 mmol) in methanol (5 mL) was added to a solution of thymine-1- acetic acid [L] (117 mg, 0.63 mmol)/NaOH(0.63mmol) in methanol (10 mL); a yellow precipitate formed gradually. The reaction mixture was stirred for 1 h at 50oC after which diethyl ether was added to precipitate the product. The crude product was separated by centrifugation and washed twice with diethyl ether (2x40 mL). The product was obtained as a light yellow powder (85 % yields). IR (solid): ῡ=3160.2, 2906.3, 2851.95, 1711.28, 1612.36, 1449.67,1408.71, 1351.82, 1326.23, 1230.35, 781.25, 740.19,595.62 cm-1; ESI-MS: m/z=457.9908 {[M+H]+,calc. 457.992}; solution magnetic moment (Evans’ method): µeff=1.65 B.M;

Electronic Supplementary Material (ESI) for ChemComm.This journal is © The Royal Society of Chemistry 2015

elemental analysis calcd (%) for C14H14FeN4O8Cl+H2O (475.0): C 35.36,H 3.39,N 11.78; found C 35.07,H 3.419,N 11.87.IR: The IR absorption spectrum obtained for the iron(III) complex shows the asymmetric stretching vibration of the carboxylato group is at the frequency (ῡ =1580 cm-1). The symmetric stretch of the carboxylato group is assigned to the absorption at 1416 cm-1, which results in ∆(ῡas-ῡs) of 200cm-1. It has been shown recently that this ∆ value is determined by the coordination mode symmetry and thus provides a useful structural probe.[2] the ∆(ῡas-ῡs) is identical to the ∆(ῡas-ῡs)ionic obtained from the free carboxylate [3] and thus is indicative of the monodentae binding mode of the carboxylate. In addition the ligand exhibit a band at 1355 due to the v cyclic(C-N) of the pyrimidine. The band is shifted to 1326 in the complex indicating the involvement of the pyridine(N) in the complexation. based on these data the two L ligands facially cap the iron(III) metal center through both pyrimidine N and the carboxylato O donor atoms, very similarly to the coordination observed for the 2- His-1-carboxylate facial triad.[4]

[2] V. Robert, G. Lemercier, J. Am. Chem. Soc. 2006, 128, 1183.[3] P. C. A. Bruijnincx, I.L.C: Buurmans, S. Gosiewska, M.A.H. Moelands, M. Lutzs, A.L. Spek, G. van

Koten, R. J. M. Klein Gebbink. Chem. Eur. J. 2008, 14, 1228 ;P. C. A. Bruijnincx,M. Lutz,A. L. Spek, E. L. van Faassen,B . M.Weckhuysen,G . van Koten, R. J. M. Klein Gebbink, Eur. J. Inorg.Chem. 2005, 779.

[4] M. Costas, M. P. Mehn, M. P. Jensen, L. Que, Jr., Chem. Rev. 2004, 104,939; K. D. Koehntop, J . P. Emerson, L. Que, Jr., J. Biol. Inorg. Chem. 2005, 10, 87.

Evans’ NMR method3 for Fe (III)/thymine-1-acetateTo run experiments, an exact amount of Fe(III)Cl3 (2.62 mg) was solved in 0.40 mL of (CD3)2CO which contained 8 µL D2O. The resulting mixture was placed in the outer sphere of a coaxial NMR tube. The inner tube was filled with a reference solution which contained 4 mL of D2O and 0.20 mL of (CD3)2CO. 1H-NMR spectra of samples showed two different signals for (CD3)2CO corresponding to inner and outer tubes. The difference in the chemical shift between the two peaks was used to determine the μeff and the unpaired electrons of the metal center.

Evans’ NMR method for Fe (III)/thymine-1-acetic acid under H2O25

A solution containing (CD3)2CO (0.5 mL), iron (III) chloride (2.4 mg) and thymine-1-acetic acid (3.3mg), H2O2 (50 µL) and cyclohexane (20µL) was inserted into the outer part of a coaxial NMR tube at 0 °C for 0.5 h. The inner tube was filled with a reference solution which contained 4 µL of D2O in 0.2 mL of (CD3)2CO. 1H-NMR spectra showed two different signals for (CD3)2CO corresponding to inner and outer tubes. The difference in the chemical shift between the two peaks was used to determine the μeff and the unpaired electrons of the metal center during the reaction. Diamagnetic corrections were calculated using Pascal’s constants.6

[5] G.A. Brain; J.F. Berry. Journal of Chemical Education. 2008, 85,533.[6] G. J. P. Britovsek, V . C. Gibson, S. K. Spitzmesser, K. P. Tellmann, A. J. P. White, D . J. Williams,

J. Chem. Soc., Dalton Trans. 2002, 1159.[27] D. F. J. Evans, J. Chem. Soc. 1959, 2003.

2. Reactivity of the in-situ prepared Fe(III)/thymine-1-acetate towards C-H bonds and general procedure

Table S1. Oxidation of aliphatic hydrocarbons Substrate Protocol [H2O2]

(mM)TONb Product yield Yieldc

n-hexane A 100 17 3-hexanol (6.0%), 3-hexanone (2.1%),2-hexanol (5.8%), 2-hexanone (2.1%)

15.9

t-butylcyclohexane B 0.1020.115 10.2 3-t-butylcyclohexanone (22%), 4-t-butylcyclohexanone (6%)

28

1,1-dimethylcyclohexane

B 0.1020.115 15.6 2,2- dimethylcyclohexanol (8%), 3,3-dimethylcyclohexanone(10%)4,4-dimethylcyclohexanone (18%)

36

trans1,2-dimethylcyclohexane

B 0.1020.115 18.6 3,4- dimethylcyclohexanone(29%)trans1,2- dimethylcyclohexanol(3%)2,3- dimethylcyclohexanone(11%)

43

Adamantane C 10 12 1-adamantanol (53%), 2-admantanol (2%), adamantanone(4%)

59

Octane A 10 14.1 3-Octanone(39%)2-Octanone (24%)4-octanone (5%)

68

Reactions were run at 298 K in MeCN and given numbers for TONs and yields are the average of three independent reactions.

a) Three different procedures were applied: Protocol A) The starting concentrations of the FeCl3/(THA) and the substrate were 1.0 mM and 1.0 M, respectively. A solution of H2O2 diluted in MeCN was added drop wise over the course of 1 min. The final volume of each reaction solution was 2.50 mL. After 90 min reaction, the solution was filtered through silica gel and analyzed. Protocol B) The general procedure was adapted from Reference 7 for comparison. The substrate (0.50 mmol, 1 equiv) and FeCl3/(THA) were dissolved in 1.0 mL of MeCN solution The oxidant, H2O2, was added to the solution in three portions. For each addition, the H2O2 was added dropwise over the course of 90 s. After the first addition, the concentrations were as follows: [Fe] = 4.80 μM, [substrate] = 32.0 μM, [H2O2] = 0.115 mM. 10 min later further equivalents of catalyst and oxidant were added, yielding the following concentrations: [Fe] = 4.26 μM, [substrate] = 85.2 μM, [H2O2] = 0.102 mM. 20 min after the start of the reaction, the third portions of catalyst and oxidant were added, yielding the following concentrations: [Fe] = 4.65 μM, [substrate] = 46.5 μM, [H2O2] = 0.112 mM. After 90 min reaction time, the reaction solution was filtered through a short plug of silica gel prior to analysis.

Protocol C) Identical to Protocol A except that the starting concentration of adamantane was 10 mM, due to its low solubility to MeCN.b) Defined as moles of oxidized organic products generated per one mole of Fe(III).c) GC analysis: substrate conversions and product yields relative to the internal standard integration. Calibration curves using dichlorobenzene as internal standard and when available or from pure isolated products obtained from a retention times with authentic samples of possible oxidized products. ll experiments were repeated at least catalytic reaction. The products were identified by GC/MS by comparing their three times, the data in the table is an average of all experimentsTurnover number (TON) (mol of product/mol of catalyst).Adamantane: 3o/2o ratio in adamantine oxidation=3x(1-adamantanol)/(2-adamantanol+2-adaman tanone).(RC): Percentage of retention of configuration in the oxidation of the tertiary-H bonds of cis-1,2-dimethylcyclohexane (DMCH)=(cis-trans)/(cis+trans)x100.

[7] N. A. Vermeulen, M. S. Chen, M. C. White. Tetrahedron 2009, 65, 3078.

Oxidation of diphenylmethane with H2O2: diphenylmethane (84.1 mg, 83.3 mL, 0.5 mmol) was added to a MeCN (1 mL) solution of FeCl3·6H2O (3.1 mg, 0.011 mmol) and thymine-1-acetate (3.8mg, 0.022mmol). After the addition of H2O2 using a syringe pump in rate of 100µl/hr (30% in H2O; 166 mL, 4.1mmol), the reaction mixture was heated at 40 ⁰C for 6h. The mixture was then allowed to cool to room temperature. The organic phase was extracted with Et2O (20 mL), washed with brine and dried (MgSO4). After filtration, the solvents of the filtrate were evaporated (rotary evaporator). The remaining mixture was separated by column chromatography (silica gel; diethyl ether: pentane=1:20 as eluent) affording benzophenone; yield: 51.1 mg, 56%.

Table S2. Effect of iron precursors on oxidation of ethylbenzene using H2O2 as oxidant a.

Entry Metal salt Conversion[%] Time[hr]

1 FeBr2 76 10

2 FeCl2 82 8

3 FeCl3 92 7

4 Fe(OAC)3 35 10

5 Fe(CF3)SO3 10 8

6 CuBr2 26 12

7 CoCl3 48 10

8b Fe(THA)complex 90 7

9c FeCl3 67 7

10d FeCl3 81 7a)Reaction conditions for 2mmol scale: Fe-precursor (1.8mol%), THA (3mol%), H2O2 (3 equiv. , 33% in H2O), and 60 ⁰C. (All experiments were repeated at least 3 times). b) pr-made Iron complex(1.8mol%), H2O2 (3 equiv., 33% in H2O) 60oC. c) reaction was made same general reaction condition under argon. d) same reaction condition, TEMPO 20mol% was added as radical inhibitor.

C-H oxidation of Carboxylic Acids (0.5 mmol substrate): Into a 10 mL microwave vial was added hydrocarbon substrate (0.5 mmol, 1.0 equiv.), followed by 3 mol% Fe/THA catalyst (0.015 mmol, 0.05 equiv.), 0.75 mL CH3CN, acetic acid (0.2ml), a magnetic stir bar. While the resulting deep orange solution stirred, a solution of H2O2 (33 wt% in H2O, 46.36 μL, 0.60 mmol, 1.2 equiv.) in 0.5 mL CH3CN was added over a period of 1 minute (dropwise addition), generating a clear, amber brown solution. Stirring followed for 3hr at 45oC and was monitored by GC-MS. The crude reaction mixture was concentrated in vacuo and purified by flash chromatography using EtOAc/pentane mixtures. Notably, reactions analyzed 60 min after addition of H2O2 showed significantly low yield of lactone product so the reaction was left for 16h.

Representative procedure for preparation of lactone standard curve: Stock solutions of 1,2-dichlorobenzene (100 mg, 10.00 mL EtOAc) and authentic 5,5-dimethyldihydrofuran-2-one (57.1 mg, 5.00 mL EtOAc) were prepared. To each of seven GC vials was added 500 μL 1,2-dichlorobenzene stock solution (4.9 mg, 0.040 mmol per vial), followed by an aliquot of the lactone stock solution, in increasing amounts (300 μL, 400 μL, 900 μL; 0.01 mmol, 0.02 mmol, …, 0.09 mmol). As such, the first GC vial represented a 10% yield of lactone for a 0.10 mmol reaction, while the seventh vial represented a 90% yield of lactone. These solutions were mixed thoroughly and analyzed by GC; a plot of % yield vs. measured lactone/nitrobenzene generated data points that could be readily fit to a linear equation of the form y = mx + b.

Representative procedure for measurement of GC yield from Carboxylic Acids (0.10 mmol): The oxidation reaction of 4-methylvaleric acid (11.6 mg, 0.10 mmol) was performed according to general procedureof carboxylic acids substrates, immediately subsequent to measurement of the standard curve. After the reaction was complete, dichlorbenzene (4.9 mg, 0.040 mmol) was transferred to the reaction mixture from a separate vial using EtOAc. The resulting solution was mixed thoroughly and analyzed by GC, providing the measured lactone/dichlorobenzene ratio.

3. Isolated products characterization

Benzophenone: A white solid, purified by silica gel column using n-pentane/ethyl acetate 7:3 v/v as eluent (342.5mg, 94 %). 1H NMR (300 MHz, CDCl3) δ ppm: 7.80 (d, 4H), 7.56-7.60 (m, 2H), 7.44-7.48 (4H, m); 13C-NMR (75 MHz, CDCl3) δ ppm: 197.6, 138.2, 133.13, 130.4, 129.1; IR (νmax/cm-1): 1659; (GC-MS: M/ɀ = 182). The 1H and 13CNMR spectral data match those found in the literature.8

Cyclohexanone : The product was obtained as a colorless oil without further purification after workup (153 mg, 80%). 1H NMR (300 MHz, CDCl3) δ ppm: 1.67(m, 2H), 1.76(m, 4H), 2.23(m, 4H); 13C-NMR (75 MHz, CDCl3) δ ppm: 24.3, 26.01, 40.89, 210.7; Selected IR data: νmax/cm-1 1804 (C=O); (C6H11O. GC-MS: M/ɀ = 98)

3,4-Dihydronaphthalen-1(2H)-one: The product was obtained after filtration over SiO2 (EtOAc/pentane = 80/20) to provide a dark brown viscous oil (263 mg, 90%). 1H NMR (300 MHz, CDCl3) δ ppm: 2.09 (q, J= 4.5, 2H), 2.65 (t, J= 5.7, 2H), 2.97 (t, J= 5.9, 2H), 7.33 (m, 2H), 7.49-7.4 (m, lH), 8.04 (d, J= 4.5, 1H); 13C-NMR (75 MHz, CDCl3) δ ppm: 8.2, 31.7, 126.5, 127.9, 128.5, 132.5, 136.8, 200.7; selected IR data: νmax/cm-1 1840(C=O). (C10H10O GC-MS: m//ɀ= 146).

Acetophenone: colorless oil in 89% yield, purified by a silica gel column using n-pentane/ethyl acetate 7:3 v/v as eluent. (213mg); 1H NMR (300 MHz, CDCl3) δ ppm: 2.79 (s, 3H), 7.14-7.24(m, 5H); 13C-NMR (75 MHz, CDCl3) δ ppm: 24.1, 70.0, 125.3, 127.2, 128.2, 145.7, 200.1; νmax/cm-1 1685 (C=O); (GC-MS, C8H9O m/ɀ=120). Both 1H and 13C NMR data are in accordance with those reported in the literature.8

Octane analysis: Purification by flash chromatography over silica (hexane 100%).Ketone C2. (2-Octane):2-octanone: (97.1 mg, 37.8%). 1H NMR (300 MHz, CDCl3) δ ppm: 2.38 (t, J= 7.5, 2H), 2.14 (s, 3H), 1.62 – 1.49 (m, 2H), 1.24 (d, 6H), 0.87 (t, 3H). 13C-NMR (75 MHz, CDCl3) δ ppm: 14.0, 22.5, 23.8, 28.8, 29.8, 31.6, 43.8, 209.4; MS (C8H16O GC-MS m/ɀ = 128). The spectroscopic data are in accordance with those reported in the literature.2 KetoneC3 (3-octane): 1H-NMR (300 MHz, CDCl3) δ, ppm: 0.82 (m, 3H), 0.92 (m, 2H) 1.11-1.19 (m,3H), 1.47 (d, J = 5.8 Hz, 3H), 1.93 (d, J = 6.1 Hz, 3H). 13C-NMR: δ ppm 7.8, 14, 22.7, 23.7, 31.7, 35.4, 42.1 and 209.0 ppm GC-MS (m/z):126.1.The spectroscopic data are in accordance with those reported in the literature.

trans-dimethylcyclohexane analysis (trans-DMCH):Purification by flash chromatography over silica (hexane 100%).3ºOH. 1H-NMR (300 MHz, CDCl3) δ, ppm: 1.69-1.63 (m, 2H), 1.54-1.48 (m, 2H) 1.46-1.20 (m,5H), 1.18 (s, 3H), 0.90 (d, J = 6.5 Hz, 3H). GC-MS (m/z): 128.1. Ketone C2. 1H-NMR (300 MHz, CDCl3) δ, ppm: 2.42-2.36 (m, 1H), 2.29 (ddt, J1 = 1.2, J2 = 5.9, J3 = 13.2Hz; 1H) 2.08-1.99 (m, 2H), 1.86-1.81 (m, 1H), 1.71-1.59 (m, 1H), 1.53-1.40 (m, 2H), 1.06 (d, J = 6.1 Hz,3H), 1.03 (d, J = 6.6 Hz, 3H). GC-MS (m/z): 126.1. KetoneC3. 1H-NMR (300 MHz, CDCl3) δ, ppm: 2.36-2.31 (m, 3H), 2.09-1.96 (m, 2H) 1.54-1.35 (m,3H), 1.01 (d, J = 5.8 Hz, 3H), 1.00 (d, J = 6.1 Hz, 3H). GC-MS (m/z):126.1.

[8] Fukuyama, T., Arai, M., Matsubara, H. and Ryu, I., J. Org. Chem., 2004, 69, 8105; Alagiri, K., Prabhu, K. R., Tetrahedron. 2011,67,8544; Suzuki, Y., Iinuma, M., Moriyama, K., Togo, H., Synlett. 2012, 23, 1250-1256; Shejwalkar, P., Rath, N. P, Bauer, E. B. Dalton Trans. 2011, 40, 7617-7631; A. K. Tucker-Schwartz, R. L. Garrell, Chem. Eur. J. 2010, 16, 12718-12726; Tanaka, K., Matsui, S., Kaji, A., Bull. Chem. Soc. Jpn. 1980, 53, 3619-3622.

4. Kinetic analysis

Kinetic isotope effects for stoichiometric and catalytic oxidation of cyclohexane were investigated by using an equimolar mixture of cyclohexane and cyclohexane-d12 as substrates. The organic products were quantified and identified by GC and GC-MS analysis. The product values were obtained by taking the ratio of the corresponding areas from the GC analysis. Kinetic isotope effect for stoichiometric oxidation was also determined by comparing the reaction rates of single-substrate experiments.

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 170

10

20

30

40

50

60

70

80

90

100

Time [hr]

Con

vers

ion

[%]

Cyclohexane

[product]

Figure S1. Influence of time on the conversion of hexane to cyclohexanone (psuedo first order kinetics) Conditions:[FeCl3(THA)] = 1 mM and [substrate] = 5 – 30 mM, H2O2: 2 equivlent, MeCN as solvent,40oC.

0 5 10 15 20 25 30 350

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1

Conc mM

Kobs

/S-1 CO

EtBz

DHA

CH

Figure S2. Plots of the pseudo-first-order rate constants, kobs (s-1) against substrate concentrations to determine second-order rate constants, k2, for 9,10-dihydroantrance (▲, DHA), ethylbenzene (■, EtBz), cyclooctane (x, CO), and cyclohexane (♦, CH) oxidation in CH3CN at 40 °C. Reaction conditions: [FeCl3(THA)2]= 1 mM and [substrate] = 5 – 30 mM. See Table S3 for the determined k2 values.

0 0.2 0.4 0.6 0.8 1 1.2 1.40

0.05

0.1

0.15

0.2

0.25

0.3

0.35

0.4

0.45

0.5cyclohexane

[Cyclohexane]/M

Kob

s/10

-2S-

1

C6D12

C6H12

Figure S3. Plot of psudo-first order-rate constant,kobs(S-1), against substrate concentrations to determine second-order- rate constant, k2 and C-H isotopic effect ( KIE).

DHA

Ethylbenzene

CyclooctaneCyclohexane

70 75 80 85 90 95 100 105-4

-3

-2

-1

0

1

2

C-H BDEs [kcal/mol]

Log(

K2'

)

Figure S4. Plot of K2’ against C-H BDE of alkanes (DHA=Dihydroanthracene) in MeCN at 296 K . K2’ values are calculated based on the number of equivalent target C–H bonds of substrates. BDE’s for C–H bonds are from reference 17.

5. H218O labeling experiments

H218O labeling experiments were carried out for both cyclohexane and octane. The same procedure was

used for both substrates: 0.25 mg of iron/THA (1mM) and the desired substrate (100mM) were solved in 0.4 mL of a CH3CN:H2

18O 1:1 v:v solution. 200µl of H2O2 were solved in 0.2 mL of CH3CN, and 0.1 mL of this solution is added using a syringe pump over 30 minutes. After the addition the reaction was stirred extra 30 min and 1,2-dichlorobenzene is added as an internal standard (0.4 equiv.). After that the reaction was immediately quenched by addition of 1 mL of a saturated NaHCO3 solution. The crude product was extracted with pentane (1ml x 3), the organic phase has been run through short silica plunge and GC sample was taken to the GC and GC-MS for analysis.

6. ESI-MS of the complex solution

Mass spectrometry analyses were performed using a time-of-flight mass spectrometer equipped with an electrospray ion source (Bruker microTOF). All analyses were carried out in a positive ion mode. The sample solutions were introduced by continuous infusion with the aid of a syringe pump at a flow-rate of 180 μL/min. The instrument was operated at end plate offset -500 V and capillary -4500 V. Nebulizer pressure was 0.8 bar (N2) and the drying gas (N2) flow 7 L/min. Capillary exit and skimmer 1 were 90 and 30 V, respectively. Sodium formiate was used for mass calibration for a calibration range of m/z 100-2000. Drying gas temperature was set at 220°C. The software used for the simulations is Bruker Daltonics Data Analysis (version 3.3). Measurement was taken from the in-situ prepared thymine-acetate/FeCl3 complex in acetic acid/MeCN solution which was diluted with MeCN. Only one main species were found in spectrum (FigS5-6). Another measurement was taken from the reaction mixture of a thymine-acetate/FeCl3 complex and H2O2 in methanol solution which was diluted with MeCN (Figure S6-8).

309.

9195

333.

9637 35

0.94

65

369.

1035

383.

1184

391.

0841

445.

1184

457.

9911

472.

0065

493.

9684

507.

9847

519.

1372

593.

1568

606.

0657

642.

0404

656.

0567 73

0.92

73

+MS, 1.7-1.9min #(103-113)

0.0

0.5

1.0

1.5

2.0

4x10Intens.

300 400 500 600 700 800 m/z

Figure S5: Full spectra of the catalyst solution. High resolution analysis of the main peak is given the below figures.

[(THA)2FeCl2]+

[(THA)Fe(CH3CO2)Cl]+ [(THA)2FeCl]+

49

1.9

71

8

49

3.9

66

6

49

4.9

68

9

49

5.9

64

3

49

6.9

66

7

49

7.9

62

4

49

8.9

98

0

50

7.9

82

5

50

9.9

79

1

+MS, 0.5-1.0min #(30-60)

49

1.9

73

6

49

3.9

69

0

49

4.9

71

6

49

5.9

66

4

49

6.9

68

8

49

7.9

64

4

C14H16O8N4FeCl2 ,493.970.0

0.2

0.4

0.6

0.8

1.0

1.2

4x10Intens.

0

500

1000

1500

2000

2500

485 490 495 500 505 510 m/z

Figure S6: Experimental (top line) and simulated ( lower line) HRMS(+) spectra of [C14H16N4O8FeCl2]=: [(THA)2FeCl2]+ calc.: 493.966 m/z, obs.: 493.9690 m/z, error 4.764 ppm.

456.

0092

457.

9913

458.

9987

459.

9912

461.

0024

+MS, 0.0-0.0min #(2-3)

455.

9969

457.

9923

458.

9948

459.

9900

460.

9923

C 14 H 15FeN 4 O8Cl ,457.990

1000

2000

3000

4000

Intens.

0

500

1000

1500

2000

453 454 455 456 457 458 459 460 461 m/z

Figure S7: Experimental (top line) and simulated (lower line) HRMS(+) spectra of [C14H15N4O8FeCl]= [(THA)2FeCl]H+: calc.: m/z 457.992, obs.: 457.9913 m/z, error 3.235 ppm.

[L2FeCl+H]1+

33

1.9

69

6

33

3.9

65

0

33

4.9

67

5

33

5.9

62

5

33

6.9

64

9

C 9H 11FeN 2 O6Cl ,333.97

33

1.9

69

4

33

3.9

64

5

33

4.1

12

5

33

4.9

67

3

33

5.9

61

7

33

6.9

65

1

+MS, 1.0-1.1min #(62-65)0

500

1000

1500

2000

Intens.

0.0

0.2

0.4

0.6

0.8

1.0

4x10

331 332 333 334 335 336 337 m/z

Figure S8: Experimental (lower line) and simulated (top line) HRMS(+) spectra of thymine -1-acetate/ FeCl3. [C9H11N2O6FeCl] = [L Fe(CH3CO2)Cl]H+: calc. =333.9945 m/z, obs. = 333.9650 m/z, error = 1.285 ppm.

[(THA)FeCl(CH3CO2)]

6.1 ESI-MS of the complex solution after addition of H2O2

The reaction mixture after the addition of the oxidant (H2O2) in 10⁰C, was diluted with MeOH/MeCN mixture was added just before injection.

289.

0030

294.

9427

298.

0766

301.

5739

304.

2648

305.

9455

340.

0572

362.

9341

365.

0447

379.

0439

383.

1355

393.

9951

413.

2743

420.

8949

423.

0763

425.

0748

430.

9238

447.

9145

461.

0776

463.

0787

469.

0741

473.

0704

478.

0821

484.

0233

486.

0200

488.

0172

498.

9122

+MS, 3.4-3.8min #(143-158)

0.0

0.5

1.0

1.5

2.0

2.5

5x10Intens.

275 300 325 350 375 400 425 450 475 m/z

Figure S9: Full spectra of the in-situ catalyst samples. The new peak are analyzed in the below figures S10-S12.

[M+2H]+2[(THA)2Fe (Cl)(CH3OO)]+2 FeL1(CH3COOH)2

484.

0203

485.

0227

486.

0112

487.

0165

488.

0097

489.

0138

490.

0107

491.

0125

+MS, 1.5-1.8min #(65-74)

483.

9999

485.

9952

486.

9978

487.

9994

C 14 H 14 Fe 1 N 4 O 12 ,486.000

2

4

6

8

4x10Intens.

0

2

4

6

8

4x10

482 484 486 488 490 m/z

[M+H]+ [(THA)2Fe (OOH)(OOH)l] +

297.

0808

297.

4997

297.

9908 +MS, 1.2-1.4min #(72-86)

296.

9906

297.

4920

297.

9883

298.

4896

298.

9903

C 18H 20 Fe 2 N 4 O12 ,595.980

100

200

300

400

Intens.

0

500

1000

1500

2000

297.00 297.25 297.50 297.75 298.00 298.25 298.50 298.75 299.00 m/z

484.

0203

485.

0227

486.

0112

487.

0165

488.

0097

489.

0138

490.

0107

491.

0125

+MS, 1.5-1.8min #(65-74)

483.

9999

485.

9952

486.

9978

487.

9994

C 14 H 14 Fe 1 N 4 O 12 ,486.000

2

4

6

8

4x10Intens.

0

2

4

6

8

4x10

482 484 486 488 490 m/z

Figure S10: HRMS(+) spectra of Thymine -1-acetate/ FeCl3. [M+H]+ [(L2)Fe (OO)(OO)]+2 (calculated mass =486.0112/2 m/z) while the observed one is (485.9952 m/z) The error between simulated and observed isotopic patterns is 32.0808 ppm.

485.

0227

486.

0112

487.

0165

488.

0097

489.

0138

490.

0107

491.

0125

498.

9068

+MS, 1.5-1.8min #(65-74)

486.

0155

488.

0109

489.

0135

490.

0151

C14H14O8N4FeOOHOOH ,488.010

2

4

6

4x10Intens.

0

500

1000

1500

2000

486 488 490 492 494 496 498 500 m/z

Figure S11: HRMS(+) spectra of Thymine -1-acetate/ FeCl3. [M+H]+ [(L2)Fe(OOH)(OOH)]+ (calculated mass =488.0097 m/z) while the observed one is (488.019 m/z) The error between simulated and observed isotopic patterns is 2.465 ppm.

297.

0719

297.

5744

298.

0704

298.

5718

299.

0723

+MS, 3.4-3.8min #(143-158)

297.

0663

298.

0640

298.

5654

299.

0664

C 22H 30Fe N 5 O11 ,596.130.0

0.5

1.0

1.5

5x10Intens.

0

500

1000

1500

2000

2500

296.75 297.00 297.25 297.50 297.75 298.00 298.25 298.50 298.75 299.00 m/z

Figure S12: Experimental (top line) and simulated ( lower line) HRMS(+) spectra of [C22H30N5O11Fe]=: [Fe(L)2(C6H11O)(OOH)H]+2 calc.: 596.13/2 m/z, obs.: 298.0704 m/z, error 0.646 ppm.

7. UV-Vis

The sample was prepared at -10 °C from the in-situ complex, [(THA)2[FeIII(Cl)], in CH3CN with distinct absorption maxima at 364 nm (Figure S16a). Addition of 0.5 equiv. of H2O2 (5 × 10−5 M) to mixture (10-4 M) at -10°C in CH3CN afforded a dark-colored solution and a new species with a distinct absorption maxima at 436 nm and 591 nm (Figure 16b).

320 520 720 9200

0.1

0.2

0.3

0.4

0.5

0.6

Wavelength [nm]

Abso

rban

ce (A

U) FeIII

(a)

350 450 550 650 750 850 9500

0.05

0.1

0.15

0.2

0.25

0.3

0.35

0.4

FeIVFeIV

(b)

Figure S13. (a)UV-vis spectra of 5x10-5 M thymine-1- acetate/ FeCl3 CH3CN -solution (b) UV-vis spectral changes upon addition of 0.5 equiv. of H2O2 to (5x10-5 M) thymine-1-acetate/FeCl3 in CH3CN/HOAc (v/v = 3:1). The starting Fe(III) complex (dark colored species which is proposed to be FeIV.

NMR:

1H NMR Spectrum of Benzophenone in CDCl3

13C NMR Spectrum of benzophenoene in CDCl3

-2-10123456789101112f1 (ppm)

-100

0

100

200

300

400

500

600

700

800

900

1000

1100

1200

1300

1400

1500

1600

b.phenon_01STANDARD 1H OBSERVE

1HNMR spectrum of acetophenone in CDCl3

-2-10123456789101112f1 (ppm)

0

100

200

300

400

500

600

700

800

900

1000

1100

1200

1300

1400

1500

1600

1700

1800

190011092013-005hSTANDARD 1H OBSERVE

13C NMR spectrum of acetophenone in CDCl

1H NMR spectrum of 3,4-Dihydronaphthalen-1-one in CDCl3

1H NMR spectrum of 2-octanone in CDCl3

1H NMR spectrum of cyclohexanone in CDCl3

-2-10123456789101112f1 (ppm)

0

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

320

340ctyclohexo_001STANDARD 1H OBSERVE

3.07

1.93

1.62

1.63

1.64

1.64

1.65

1.65

1.66

1.68

1.68

1.69

1.69

1.70

1.71

1.73

1.76

1.76

1.76

1.77

1.78

1.78

1.79

1.80

1.81

1.82

1.82

1.84

1.84

2.02

2.05

2.24

2.24

2.26

2.28

7.39

13C NMR spectrum of cyclohexanone in CDCl3

-30-20-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)

0

100

200

300

400

500

600

700

800

900

1000

1100ctyclohexo_002Helsinki Univ Organic chemistry5mm asw pfg probe#C13 pw 90 probe tuned for C13only using 6.8pF stickNOTE ! new low band RF amp at 125 Wtpwr 57 pw90 10.5 uSec

4.98

9.15

9.00

0.86

24.3

826

.01

40.8

9

76.2

177

.16

Chlo

rofo

rm-d

210.

60

GC-data:

tert-butyl hexanone:

4.00 5.00 6.00 7.00 8.00 9.0010.0011.0012.0013.0014.0015.0016.0017.000

200000

400000

600000

800000

1000000

1200000

1400000

1600000

1800000

2000000

2200000

2400000

2600000

2800000

3000000

3200000

3400000

3600000

3800000

Time-->

Abundance

TIC: afn-0012.D

10 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 1700

5000

10000

15000

20000

25000

30000

35000

40000

45000

50000

55000

60000

65000

70000

75000

m/z-->

Abundance

Scan 2412 (13.624 min): afn-0012.D149

65 121

43164

5076

104932815 85 132

Product analysis by GC-MS for oxidation of tert-butyl hexane:; original chromatogram

(all ions) and a) chromatograms based on selected ions that represent tert-butyl hexanone.

O

Acetophenone:

4.60 4.80 5.00 5.20 5.40 5.60 5.80 6.00 6.20 6.40 6.600

100000

200000

300000

400000

500000

600000

700000

800000

900000

1000000

Time-->

Abundance

TIC: afn-0015.D

Product analysis by GC-MS for oxidation of ethylbenzene; original chromatogram(all ions) and a) chromatograms based on selected ions that represent acetophenone.

Octane oxidation:

2.00 2.50 3.00 3.50 4.00 4.50 5.00 5.50 6.00 6.500

500000

1000000

1500000

2000000

2500000

3000000

3500000

4000000

4500000

5000000

Time-->

Abundance

TIC: afn-0011.D

Product analysis by GC-MS for oxidation of Octane; original chromatogram(all ions) and a) chromatograms based on selected ions that represent 2-octanone. The products 2-octanone, 3-octanone and 4-octanone were compared by authentic samples purchased from Aldrich and analyzed by GC-FID.

10 20 30 40 50 60 70 80 90 100 110 120 1300

10000

20000

30000

40000

50000

60000

70000

80000

90000

100000

110000

120000

m/z-->

Abundance

Scan 968 (5.515 min): afn-0015.D105

77

51

120

43

63 912715 37 85 98

a

O O

O

a

10 20 30 40 50 60 70 80 90 100 110 120 1300

5000

10000

15000

20000

25000

m/z-->

Abundance

Scan 710 (4.067 min): afn-0011.D5743

71

85

27

128

9918 11351

O

Decane oxidation:

1.802.002.202.402.602.803.003.203.403.603.804.004.204.404.604.80

500000

1000000

1500000

2000000

2500000

3000000

3500000

4000000

4500000

Time-->

Abundance

TIC: afn-13072012-03.D

Product analysis by GC-MS for oxidation of decane; original chromatogram(all ions) and a) chromatograms based on selected ions that represent 2-decanone. The products 2-decanone, 3-decanone and 4-decanone were compared by authentic samples purchased from Aldrich and analyzed by GC-FID.

isochromane oxidation:

3.00 3.50 4.00 4.50 5.00 5.50 6.00 6.50 7.00 7.50 8.00

2000000

4000000

6000000

8000000

1e+07

1.2e+07

1.4e+07

1.6e+07

1.8e+07

2e+07

2.2e+07

2.4e+07

2.6e+07

2.8e+07

Time-->

Abundance

TIC: AFN-18052012-2.D

Product analysis by GC-MS for oxidation of isochromane; original chromatogram(all ions) and a) chromatograms based on selected ions that represent 3,4-Dihydronaphthalen-1-one.

a

0 50 100 150 200 250 300 350 400 4500

20000

40000

60000

80000

100000

120000

140000

160000

180000

200000

220000

m/z-->

Abundance

Scan 223 (2.931 min): afn-13072012-03.D43

71

99

15612718 207 355267 446

O

O

O

10 20 30 40 50 60 70 80 90 1001101201301401501601701801902002100

200000

400000

600000

800000

1000000

1200000

1400000

1600000

1800000

2000000

2200000

m/z-->

Abundance

Scan 513 (4.560 min): EKA-0462_290613.D118

148

90

63

5139 77 10329 12918 207165

a

O

O

Cyclohexane oxidation:

0.501.001.502.002.503.003.504.004.505.005.506.006.507.007.508.008.500

200000

400000

600000

800000

1000000

1200000

1400000

1600000

Time-->

Abundance

TIC: MR-20140408_016.D

Product analysis by GC-MS for oxidation of hexane; original chromatogram(all ions) and a) chromatograms based on selected ions that represent hexanone.

Indane oxidation:

4.00 4.10 4.20 4.30 4.40 4.50 4.60 4.70 4.80 4.90 5.00 5.10 5.20 5.30

200000

400000

600000

800000

1000000

1200000

1400000

1600000

1800000

2000000

2200000

Time-->

Abundance

TIC: EKA-05072012-1.D

Product analysis by GC-MS for oxidation of indane; original chromatogram(all ions) and a) chromatograms based on selected ions that represent indanone.

a

10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 95 1001050

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

11000

12000

13000

14000

15000

m/z-->

Abundance

Scan 299 (3.658 min): afn-21112012-016.D57

82

67

41

28

9872

18 51 77

MeCN

O

0 50 100 150 200 250 300 350 400 4500

200000

400000

600000

800000

1000000

1200000

1400000

1600000

1800000

2000000

2200000

m/z-->

Abundance

Scan 378 (4.101 min): afn-06112012-001.D132

104

78

51

27 152 446

O

a

Admantane:

Sclareolide:

6.10 6.20 6.30 6.40 6.50 6.60 6.70 6.80 6.90 7.00 7.10 7.20 7.30 7.40 7.50

2000000

4000000

6000000

8000000

1e+07

1.2e+07

1.4e+07

1.6e+07

1.8e+07

Time-->

Abundance

TIC: AFN-04092013-018.D

Product analysis by GC-MS for oxidation of ambroxide; original chromatogram(all ions) and a) GC-MS analysis of sclareolide, and its chromatogram based on selected ions that presented sclareolide.

4-methylvaleric acid oxidation:

3.603.804.004.204.404.604.805.005.205.405.605.806.006.206.406.606.800

200000

400000

600000

800000

1000000

1200000

1400000

1600000

1800000

2000000

2200000

Time-->

Abundance

TIC: afn-0014.D

Product analysis by GC-MS for oxidation of valeric acid; original chromatogram(all ions) and b)the lactone product was compared to authentic sample.

20 40 60 80 100 120 140 160 180 200 220 2400

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

5500

6000

6500

m/z-->

Abundance

Scan 2948 (16.634 min): afn-0016.D235

43

559528 109

2178167 123137

14718 177161 193 207

O

OO

10 20 30 40 50 60 70 80 90 100 110 1200

2000

4000

6000

8000

10000

12000

14000

16000

18000

20000

22000

24000

26000

28000

m/z-->

Abundance

Scan 674 (3.864 min): afn_002.D43

9955

70

28

60

8315 38 7550 114

a

a

Cyclooctene:

3.00 3.50 4.00 4.50 5.00 5.50 6.00 6.50 7.000

50000

100000

150000

200000

250000

300000

350000

400000

450000

500000

550000

Time-->

Abundance

TIC: mr-07042014-012.D

10 20 30 40 50 60 70 80 90 100 110 120 1300

5000

10000

15000

20000

25000

30000

m/z-->

Abundance

Scan 1136 (6.459 min): mr-07042014-012.D55

98

41

83

27 69

126111

18 776348

OHHO OH

a

10 20 30 40 50 60 70 80 90 1001101201301401501601701801902002100

500

1000

1500

2000

2500

3000

3500

4000

m/z-->

Abundance

Scan 1119 (6.364 min): mr-07042014-012.D55

4128

67

83

9818

111207

Product analysis by GC-MS for oxidation of cyclooctene; original chromatogram(all ions) and a) chromatograms based on selected ions that represent 1-cyclooctanone. The products 1-cyclooctanone, 1,2-dicyclooctanone were compared by authentic samples purchased from Aldrich and analyzed by GC-FID.

Admantane oxidation:

3.10 3.20 3.30 3.40 3.50 3.60 3.70 3.80 3.90 4.00 4.10 4.20 4.30 4.40 4.50

1000000

2000000

3000000

4000000

5000000

6000000

7000000

8000000

9000000

1e+07

Time-->

Abundance

TIC: afn-15112012-07.D

b

OH

OOH

a) admantanol:

20 40 60 80 100 120 140 160 180 200 220 240 260 2800

200000

400000

600000

800000

1000000

1200000

1400000

1600000

1800000

2000000

2200000

m/z-->

Abundance

Scan 372 (4.068 min): afn-15112012-07.D95

152

1097741 5527 13712315 209 286177

b)2-admantone

20 40 60 80 100 120 140 160 180 200 220 240 260 2800

20000

40000

60000

80000

100000

120000

140000

160000

180000

200000

220000

240000

260000

280000

300000

320000

340000

360000

m/z-->

Abundance

Scan 432 (4.405 min): afn-15112012-07.D150

79

117

9110439 6753 1322715 209 286

Product analysis by GC-MS for oxidation of adamnatone; original chromatogram(all ions) and a) chromatograms based on selected ions that represent 1-adamntanol.b) chromatograms based on selected ions that represent 2-adamntanone. The products 1-adamantol, 2-adamantanone were compared by authentic samples purchased from Aldrich and analyzed by GC-FID.