Pentacoordinated and HexacoordinatedCompounds

G.-V. Roschenthalera and Romana Pajkerta

DOI: 10.1039/9781849730839-00290

1. Introduction

In recent years, hypervalent phosphorus compounds have been widelystudied as intermediates or transition states in biological phosphoryltransfer reactions. As previously described, in this process a phosphorylcentre interacts with a nucleophile to produce a hypervalent intermediate,possessing a nucleophile at the apical position. Then one of the two apicalligands is released as a nucleofuge. During the reaction, the stability of theintermediate species plays a crucial role in the product distribution and if itis long-lived enough stereomutation can occur, giving an equilibrium mix-ture containing certain stereoisomers. However, to elucidate the mechanismof these transformations, appropriate structural and kinetic studies ofhypervalent phosphoranes need to be investigated. For these reasons,many efforts have been directed towards the synthesis of novel penta- andhexacoordinated phosphorus compounds, especially those with extortedgeometry. As presented by Yamamoto et al. the preparation of novelanti-apicophilic pentacoordinated phosphoranes with frozen stereomuta-tion can be successfully achieved using bulky bidentate ligands with twopentafluoroethyl groups.1 These phosphoranes do not stereomutate at roomtemperature and can be converted into the corresponding more stablestereoisomers (O-apical) at elevated temperatures in solution. Moreover,kinetic studies have shown that the activation enthalpy of the stereomuta-tion of the O-equatorial phosphorane to its O-apical isomer is higher thanfor the analogues with CF3 substituents (Martin ligand) which stems fromthe steric effect of the C2F5 group, freezing the stereomutation of penta-coordinated phosphorus compounds.1

O-Apical stereoisomers of pentacoordinated phosphoranes can be ob-tained by different routes, including the Kawashima’s synthesis of thepentacoordinated phosphorus compound bearing a pentacoordinate siliconatom, both possessing Martin ligands in the structure2 or by the reaction of8-chloro-2-cyclohexyl-4-phenylbenzo[e]-1,2-oxaphosphinine-2-oxide withtetramethylenebis(magnesium bromide) as reported by Konovalov et al.3

The coordination tendencies of phosphorus to form hypervalent stateshave been especially studied due to the fact that penta- and hexacoordinatedphosphoranes are involved in various phosphate transfer reactions in na-ture. These structures are usually very sensitive to many internal and ex-ternal factors such as electrostatic effects, donor coordination and packingeffects in active sites. Thus, to clarify the mechanisms of these transfor-mations, theoretical calculations have been investigated as well as in vitro

aSchool of Engineering and Science, Jacobs University Bremen gGmbH, P.O. Box 750 561,D-28725, Bremen, Germany

290 | Organophosphorus Chem., 2010, 39, 290–307

�c The Royal Society of Chemistry 2010

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studies.4,5 The application of hexacoordinated phosphorus species ascatalysts, such as zwitterionic adducts with CpRu moieties, has been alsodescribed.6

2. Synthesis and stereomutation of pentafluoroethyl containing

spirophosphoranes

Pentacoordinated phosphoranes generally possess a trigonal-bipyramidal(TBP) structure with two different bonds (apical and equatorial) and sites.The apical bond is defined as a three-center-four-electron (hypervalent)bond, whereas the equatorial bond is described as a sp2 bond. Consequentlytwo phenomena play an important role in hypervalent phosphoranechemistry: apicophilicity (a thermodynamic property) and pseudorotation(a kinetic property). The relative preference of ligands to occupy the apicalsite is specifically known as apicophilicity. However, in solution, mostpentacoordinate molecules undergoes rapid stereomutation, giving rise toan exchange between the apical and equatorial ligands. Therefore, suchcompounds exist as an equilibrium mixture of several stereoisomers whichinterconvert via Berry pseudorotation (BPR). The barrier to BPR is usuallyvery low, without any steric restrictions. According to many experimentalstudies and theoretical calculations, electronegative and sterically smallgroups prefer to occupy the apical sites, whereas electron-donating andbulky ligands prefer the equatorial positions.

Yamamoto et al.1 has shown that using the bulky and bidentateligand called the Martin ligand, the stereomutation of pentacoordinatedmolecules can be controlled, and the more stable stereoisomer (O-apical)isolated. On the other hand, the synthesis of the less stable O-equatorialsteeoisomer have not been possible because such compounds isomerize toofast to be isolated. However, recent investigations of Yamamoto have re-vealed,1 that anti-apicophilic phosphoranes can be isolated using a novelrigid bidentate ligand with two pentafluoroethyl groups and monodentateligands including alkyl and aryl substituents (viz. stereoisomers 1–4 inFigure 1).

The synthesis of a new bidentate ligand bearing two C2F5 groups (8) wasachieved by the reaction of pentafluoropropionate (5) with phenyllithium,followed by the Cannizzaro-type disproportionation of pentafluoro-propiophenone (6) involving intermolecular migration of pentafluoroethylgroup. After dilithiation of alcohol (7) using 3 equivalents of n-BuLi/TMEDA (N,N0N0N0-tetramethylethylenedimine), compound (7) was con-verted into o-bromo derivative (8) in 84% yield (Scheme 1).

The new bidentate ligand (8) was then treated with the combined systemof NaH and nBuLi, followed by the addition to the solution of PCl3 in THF,to give a mixture of hydrophosphorane (4) in 50% and O-apical n-butyl-phosphorane (4b; 6%) (Scheme 2).

The stereochemistry of compound (4) was confirmed by X-Ray analysisand was found to be a TPB (trigonal-bypiramidal) structure with the C1–P1–C1 angle in the equatorial plane (136.31) larger by 8.71 than that of P–Hspirophosphorane (4) bearing Martin ligands (127.61). This is presumablythe result of steric repulsion between the bulky endo-C2F5 groups.

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Moreover, the formation of the by-product (4b) could be established by thereaction of the intermediate phosphoranide anion with nBuBr, which wasproduced during the dimetallation process. To avoid this problem, tBuLiwas employed instead of nBuLi, giving compound (4) in 35% yield.

CF3CF2CO2Et CF2CF3

O

OH

F3CF2C

F3CF2C

CF2CF3

OH

CF2CF3

Br

1. PhLi (1.1 equiv.), THF, -78°C, 2h

2. 2M HCl

1. tBuOK (0.5 equiv.), THF, r.t., 15h

2. CF3COOH, CH2Cl2

1. nBuLi/TMEDA (1:1), hexane, r.t., 36h

2. BrCF2CF2Br, r.t.

5 6 (84%) 7 (33%)

8 (84%)

Scheme 1

O

P

O

F3CF2C

F3CF2C

CF2CF3 F3CF2C CF2CF3

F3CF2C CF2CF3CF2CF3

H +OH

CF2CF3F3CF2C

Br

8

O

P

O

nBu

1. NaH (2 equiv.), THF, 0°C, 0.5h2. nBuLi (1 equiv.), THF, -78°C to r.t.

3. PCl3 (0.5 equiv.), -78°C, 1.5h4. 6M HCl

4 (50%) 4b (6%)

Scheme 2

O

P

F3C CF3

O

F3C CF3

R

O

F3C CF3

O

F3CF2C CF2CF3

OP

O

F3C CF3

R

F3C

F3C

A

Martin ligand

B

New bidentate ligand

O -apical

2

O -equatorial

1

O

P

F3CF2C CF2CF3

O

F3CF2C CF2CF3

RO

P

O

F3CF2C CF2CF3

R

F3CF2C

F3CF2C

O-apical

4

O -equatorial

3R = alkyl, aryl

a = Me; b = nBu

Fig. 1

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O-Equatorial phosphoranes (3a–h) were prepared by the reaction of P-Hspirophosphorane (4) with 3 equivalents of RLi followed by the treatmentwith I2. All the O-equatorial phosphoranes (3a–h) were almost quantitativelyconverted into the correspondingO-apical phosphoranes (4a–h) by heating insolution. Notably, the O-equatorial steroisomer was isolated in pure form inthe case of the methyl derivative (3a) indicating that stereomutation of (3a) to(4a) is sufficiently suppressed to permit isolation (Scheme 3).

The stereochemistry of the O-equatorial (3a–h) and O-apical phosphor-anes (4a–b and 4g–h) was confirmed by X-Ray analysis which showed thatall compounds possess a distorted trigonal-bipyramidal (TBP) structureswith a monodentate ligand occupying one of the equatorial sites. The anglesand distances involving the phosphorus atom of arylphosphoranes weregenerally similar to those of the corresponding alkylphosphoranes. More-over, two independent molecules were found in the unit cell for each of the(3d), (3f) and (3h). For the O-equatorial isomers, the angle O2-P-C1 wasfound to be 120.51, 124.01 (3d), 122.51 (3e), 121.71, 124.11 (3f), 123.61 (3g)and 112.781, 115.18 (3h), whereas for alkylphosphoranes (3a–c) this valuewas 119.51, 119.71 and 118.01, respectively. Interestingly, the crystal struc-tures of (3b) and (4b) were slightly affected by the steric bulk of the pen-tafluoroethyl groups increasing the length of the apical P1–O1 bond,compared to the corresponding CF3 derivatives. This was attributed tosteric repulsion between the endo-C2F5 group and the equatorial bidentialaromatic ring (Figure 2).

For the O-equatorial and O-apical aryl phosphoranes the equatorialC1–P–C2 angles depends mostly on the steric hindrance of the aromatic ringof the monodentate ligand. Thus a smaller angle was observed for theO-equatorial stereoisomer (10h) (112.81, 115.21) than those of (3d–h). In thecase of the O-apical stereoisomer (11h) (125.51), compared to (11g) (139.51).The increase was attributed mainly to the steric repulsion between the bulkymesityl group and the aromatic ring of the bidentate ligand.

For alkyl pentacoordinated phosphoranes, the successful isolation ofstereoisomer (3a) and its high stability at room temperature permitted the

O

P

O

RO

P

O

R

F3CF2C

F3CF2C

F3CF2C CF2CF3 F3CF2C CF2CF3

F3CF2C CF2CF3

3a: R = Me (90%)3b: R = nBu (92%)3c: R = tBu (43%)3d: R = Ph (85%)3e: R =C6H4(p-CF3) (58%)3f: R = C6H4(p-F) (76%)

3g: R = C6H4(p-OMe) (48%)3h: R = Mes (83%)

41. RLi (3 equiv.), Et2O, r.t.

2. I2 (3 equiv.), -78°C to r.t.

O -equatorial

Mes = 2,4,6-trimethylphenyl

4a: R = Me (98%)4b: R = nBu (100%)4c: R = t Bu (92%)4d: R = Ph (98%)4e: R = C6H4(p-CF3) (96%)4f: R = C6H4(p-F) (96%)

4g: R = C6H4(p-OMe) (97%)4h: R = Mes (95%)

O -apical

4a: C6D6, 75°C, 8h4b: C6D6, 80°C, 12h4c: diglyme,195°C, 3 weeks4d-h: C6D6, 80°C, 8h

Scheme 3

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kinetics of the stereomutation to be studied. The structure (Int-3a) pos-sessing one of the two bidentate ligands at the equatorial sites, would bethe structure of highest energy, and thus represent the actual transitionstate (TS) for stereomutation. The difference in the activation enthalpy(DH#¼ 19.3 kcal/mol for for the interconversion of (1) and (2) and 24.4kcal/mol for (3a) and (4a)) contributes to the difference in the activation freeenergy (DG#) for the stereomutation. It was actually higher for (3a) to (4a)than that for (1a) to (2a) by 3.6 kcal/mol (DG#

1� 2¼ 22.5 kcal/mol andDG#

3a–4a¼ 26.1 kcal/mol). This could mean that the steric repulsion be-tween a C2F5 group and the aromatic ring of the diequatorial bidentateligand is larger than for Martin ligand, causing the pentafluoroethyl groupto be more effective in freezing the pseudorotation (Figure 3).

C2

O2

C3

P1

O1

F3C

F3C

C1

CF3F3C

endo

exoendo

exo

P1-O1: 1.770(3) Å

C2

O2

C3

P1

O1

F3CF2C

F3CF2C

C1

CF2CF3F3CF2C

endo

exoendo

exo

P1-O1: 1.800(2) Å

3b1b

Fig. 2

O

P

O

Me

O

P

O

Rf Rf

Me

Rf

Rf

P

O

Me

Rf Rf

ORf

Rf

RfRf

RfRf

steric repulsion

Int-1a: Rf = CF3Int-3a: Rf = C2F5

1a: Rf = CF33a: Rf = C2F5

2a: Rf = CF34a: Rf = C2F5

ΔH# = 19.3 kcal/mol (1a to 2a)24.4 kcal/mol (3a to 4a)

ΔH#

Fig. 3

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With respect to the activation enthalpy (DH#) for the stereomutation ofthe phenyl derivative (3d to 3d) and the mesityl derivative (3h) to (4h), it wasshown that the former is greater than the latter by 2.3 kcal/mol in clearcontrast to the free energy of activation (DG#), which are 24.1 kcal/mol and24.8 kcal/mol, respectively. When considering the high-energy intermediatein the three-step BPR from the O-equatorial to the O-apical (3 to 4), themesityl stereoisomer (Int-3h) should be less stable than phenyl derivative(Int-3d) due to the presence of the bulky mesityl group at the stericallycongested apical site. However, the activation enthalpy (DH#) was higherfor the stereomutation of the phenyl stereoisomer (3d to 4d) than for themesityl stereoisomer (3h to 4h). This has been attributed to p-d*P�O

stabilizing interactions in the ground state of (3d) (Figure 4).These p-d*P�O stabilizing interactions were based on investigations of

the structure in solution by 31P, 19F and 1H NMR. All isolated phosphor-anes showed singlets in their 31P NMR (CDCl3) spectra where as in solutionthe chemical shifts for O-equatorial phosphoranes (d¼ � 10.6 (3d) and� 2.6 (3h) ppm) were shifted downfield when compared with O-apicalstereoisomers (d¼ � 26.9 (4d) and � 23.6 (4h) ppm). In the 19F NMRspectra the O-equatorial stereoisomer (3h) showed four CF3 signals atroom temperature (d¼ � 78.1, � 78.4, � 79.1 and � 79.2 ppm), whereasonly two were present for the stereoisomer (3d) as a consequence of its C2

symmetrical structure. These four distinct CF3 signals for the O-equatorialstereoisomer (3h) resulted from the observed equilibrium: if a fast exchangebetween RP* and SP* occurred, the two endo-CF3 groups (a-endo-CF3 and

O

P

O

Ar

OP

O

P

O

CF2CF3F3CF2C F3CF2C

F3CF2C

F3CF2C

CF2CF3

CF2CF3

CF2CF3

CF2CF3

CF2CF3

F3CF2CF3CF2C

F3CF2C

F3CF2C F3CF2C

F3CF2C

CF2CF3CF2CF3

CF2CF3

CF2CF3

O

3d

ΔH1# = 23.9 kcal/mol (3d to 4d)

ΔH2# = 21.6 kcal/mol (3h to 4h)

OP

O

Me

Me

Me

P

O

O

Me Me

Me

3d 3h

3h

4

Int-3d

Int-3h

Int-3d Int-3h

ΔH1#

ΔH2#

Fig. 4

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b-endo-CF3) coalesced into one, as well as exo-CF3 groups (a-exo-CF3 andb-exo-CF3). Therefore, the stereomutation of (3h) was slow on the NMRtimescale (Scheme 4).

In the 1H NMR spectrum, two kinds of ortho-methyl protons (d¼ 2.65and 2.27 ppm) and meta-protons (d¼ 6.81 and 6.73 ppm) were observed for(3h), while only a set of ortho and meta-aromatic protons was detected for(3d). This meant that sites a and b of (3h) are not equivalent and sites c and dof (10d) are equivalent in 1H NMR (Scheme 4). If the conformation of themonodentate ligand is fixed, sites a (or c) and b (or d) are not exchangedwith each other under the one-step pseudorotation between RP* and SP*.This implied, that the P–C(ipso) rotation of the mesityl stereoisomer (3h) isslow, in contrast to the fast rotation of the ortho-unsubstituted (3d), on theNMR timescale. As a consequence, in solution the degree of free rotation inthe P-C(ipso) bond is higher for stereoisomer (3d) than for (3h). Therefore,the monodentate aromatic ring of (3d) should be capable of being nearlyperpendicular to the equatorial plane while the mesityl group of (3h) is morefixed in solution, similarly to the crystal structure. As a consequence, it wasproposed that the p-d*P�O stabilizing interactions can occur with theperpendicular aryl ring of the O-equatorial pentacoordinated spirophos-phorane (3d) in the ground state.

OP

O

F3CF2C CF2CF3

F3CF2C

F3CF2C

Me

Me

Me H

H

a

b

a-exoa-endo

b-endo

b-exo

3h

OP

O

CF2CF3F3CF2C

CF2CF3

CF2CF3

Me

Me

MeH

H

a

b

b-exo b-endo

a-endo

a-exo

3h

OP

O

F3CF2C CF2CF3

F3CF2C

F3CF2C

H

H

H H

H

c

d

a-exoa-endo

b-endo

b-exo

3d

OP

O

CF2CF3F3CF2C

CF2CF3

CF2CF3

H

H

HH

H

c

d

b-exo b-endo

a-endo

a-exo

3d

Exchange between RP* and SP

* = FastExchange between c and d = Fast

Exchange between RP* and SP

* = SlowExchange between a and b = Slow

SP*RP

*

SP*RP

*

Scheme 4

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3. Synthetic strategies of novel pentacoordinated phosphoranes

In recent years, several hypervalent compounds bearing two or moreidentical pentacoordinated atoms have been described. Among them arethose containing both phosphorus and silicon atoms which are of interestbecause they possess two reactive sites. For the first time, the synthesis ofsuch phosphoranes was presented by Kawashima et al.2 and included thethree-component reaction involving phosphoranide (9) and silane (10), bothcontaining two Martin ligands, and tetrahydrofuran at room temperature.Phosphoranylalkoxysilicate (11) was obtained as a mixture of two diaster-eoisomers due to the presence of chiral pentacoordinated phosphorus andsilicon atoms (Scheme 5).

Another interesting example of O-apical spirophosphorane, basedon the unexpected product from the reaction of 8-chloro-2-cyclohexyl-4-phenylbenzo[e]1,2-oxaphosphinine-2-oxide (12) with tetramethylenebis(magnesium bromide) that was described by Konovalov et al.3 As presentedin Scheme 6, the formation of diphosphine oxide derivative (13) is not themajor pathway of the process as expected. The main pathway involved thereaction of phosphinine oxide (12) with the organomagnesium compound toyield organodimagnesium derivative (14) or its cyclic form (14a), which thenwas reacted with compound (12) to give magnesium-containing phosphineoxide (15). The subsequent hydrolysis of oxide (15) resulted in a pre-dominant formation of unexpected hypervalent phosphorane (16) in 47%yield. It is worth mentioning, that the product was isolated as a solvate withtwo benzene molecules, with the phosphorus atom in an almost regulartrigonal-bypiramidal configuration and oxygen atoms in apical positions.

4. Hypervalent phosphoranes in biochemical processes

Phosphate transfer reactions are ubiquitous in nature and play fundamentalroles in ATP hydrolysis and protein phosphorylation processes. The interestin understanding these reactions is thus unquestionable, especially the roleof enzymes in accelerating a chemical step, that otherwise would not takeplace. The coordination tendencies of phosphorus to form hypervalentcompound might be the driving force in describing the mechanistic actionof phosphoryl transfer enzymes. However, the deep knowledge of these

O

P

O

F3C

F3C

CF3

CF3

F3C F3C

F3C

CF3 CF3

F3C CF3

F3C CF3

F3C CF3CF3

O

Si

O

K+,18-crown-6 K+,18-crown-6

THFr.t.

O

P

O O

Si

O

O

119 10

Scheme 5

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processes requires the concurrence of both theoretical and experimentalinvestigations.

Most theoretical approaches4 assume that the mechanism of phosphoryltransfer reactions is associative and gives rise to pentacoordinated phos-phorus, which can represent a relatively stable and long-lived intermediate(phosphorane) or transition state. These intermediates represent a trigonalbypiramid structure and their energy or stability strongly depends on theinductive effect of the equatorial substituents at phosphorous. Furthermore,the intramolecular polarization formed by the ability of both apical groups totransfer charge to the phosphoryl moiety is also responsible for the stabilizingeffect of the intermediate (or transition state). Thus, when two apical groupsdiffer, there is competition between them to form a dative bond to phos-phorus. Obviously, the influence of an electric field created by an active site ofenzyme can also modify not only the geometrical features but even the sta-bility and reactivity of nucleophlic substitutions on phosphorus.

To describe the polarization and transformations of a pentacoordinatedtransition state, given by an external field, two model reactions of a com-petitive interaction between the apical substituents were chosen. In the firstone, with equal substituents, the polarization of the phosphorus atom arisesfrom the conformation of the phosphoryl moiety itself and not from the apicalsubstituents which are the same. In the second model, the asymmetry resultsfrom the different electrodonor ability of the axial substituents (Scheme 7).

PO O

Ph

Cl

O MgBr

Ph

MgBr

Cl

MgO

Ph

Cl

MgBr2

OMgBr

Ph

ClP O

Ph

OMgBr

Cl

P

O OCl Cl

Ph Ph

Cl

OH

Ph

P

O

Cl

HO

Ph

P

O1. [BrMg(CH2)2]2

[BrMg(CH2)2]2

2. H+,H2O

-BrMgX(X = Cl, Br)

HCl, H2O

12

15

13

14 14a

15 16

Scheme 6

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The field generated by an enzyme is not constant because enzymes canform flexible structures. Nevertheless, it strongly influences the apical bondsi.e. d1 (the weakest apical bond) and d2 (the strongest one). It has beencalculated, using molecular modelling, that the length of apical bonds d1and d2 of the intermediate structure undergo significant changes underdifferent field magnitudes (0.130 and 0.066 A, respectively). However, thetransition state apical distances in model 1, showed a stronger variation ofthe d1 bond compared to d2 (0.155 vs. 0.025 A). This was attributed to themore covalent character of d2, which is far less polarisable than the dative d1bond in the transition state. Furthermore, for a given field, it was found thatlarger energy changes occurred in model 2 thus the weakest apical bond isstrengthened and the molecule is less unstable with respect to the productcomplex, whose electronic structure is far more insensitive to an externalfield. As a consequence, according to the Hammond postulate, the electricfield shifts the geometry of the transition state to the geometry of thecomplex product, giving larger distances and higher energies, since thisgeometry change enhances the charge separation, against the external field.It is postulated, that this feature is usually used by enzymes to stabilise thetransition states of phosphoryl transfer reactions and also explains the de-pendence of these processes on the electrostatic environment.

As has been already mentioned, theoretical investigations suggest mech-anisms of phosphoryl transfer reactions that involve pentacoordinatedphosphorus atom that can be a trigonal bypiramidal intermediate or tran-sition state. However, recent experimental work has outlined the involve-ment of higher coordinate forms of phosphorus, particularly the ease offormation of hexacoordinated phosphoranes. These species can be formedby utilising residues at active sites of phosphoryl transfer enzymes to enterinto donor interactions at the phosphorus atom and as a consequence co-operate in nucleophilic attack. To prove this assumption, biorelevantphosphoranes have been synthesized and studies of their behaviour in activesites of enzymes have been described.5 As representative analogues of atransition state in phosphoryl transfer reaction some phosphorus-atrane

P

O

O HO H

HO OH

P

O

O HO

H3CO O

H

O

H

TS1

TS2

P

O

HO

O

O

HO

HH

P

O

HOd2d2 d1

d2 d2d1

O

OOH

model 1

model 2

H

OH

Scheme 7

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structures have been prepared. As presented at Figure 5, the phosphate-atrane structure (17) expresses a slight degree of P-N coordination whiletetraoxyphosphorane-atrane (18) shows strong P-N coordination and rep-resents an activated enzyme complex produced by an attacking nucleophile.

Thus, this could serve as a good example of how amino acid donor actiontakes place at active sites of phosphoryl transfer enzymes. Due to the donorcoordination produced by an amino acid residue at an enzyme penta-coordinated activated state, a hexacoordinated phosphorus transition stateis envisioned. As a consequence, there will be a weakening of all bonds tophosphorus allowing the leaving group to depart more readily and result inan increase of the accompanying enzymatic rate. What is more, the energiesassociated with the formation of six from five coordinated phosphorus arefound to be small, hence the existence of a hexacoordinated transition statebecomes a real possibility.

On the other hand, the capability to achieve hexacoordinated transitionstates could be only viable if there is a donor atom present. This phenom-enon was also observed in the synthetic pathway of biorelevant compound(23), in which the order of addition of reagents determined the direction ofthe reaction. For example, in the second step of Scheme 8, the addition of anamine first to the substrate (19) gives phosphite (22) via the chloride (21),whereas adding N-chloramine first forms intermediate (20) that is convertedto hexacoordinated phosphorane (23).

This donor coordination of phosphorus seems to be stronger for thehexacoordinated state, according to the P-donor bond distances obtainedfrom X-ray studies performed on 4, 5 and 6 coordinate phosphorus com-pounds using sulphur as a donor. Experimental results have shown that therange of P-S distances extends from 2.8 to 3.2 A for the lower coordinatephosphites and phosphates whereas much stronger coordination occurs forthe hexacoordinated phosphoranes.

5. Application of hypervalent phosphorus compounds in organometallic

catalysis

Very recently, complexes of ruthenium derivatives with hexacoordinatedphosphorus ligands have been recognized as efficient catalysts in the fieldof organic synthesis. This includes, among others, the decarboxylativeCarroll rearrangement of secondary and tertiary allyl b-ketoesters which is

P

O

OOO

N

P

OPh

OOO

NPhO

31P NMR � -37.1 ppmP-N 2.980(1) Å

31P NMR � -134.5 ppmP-N 2.114(6) Å

17 18

Fig. 5

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SO

O

OH

OH

PC

l 3

SO

O

O

PO

Cl

ClC

l

iPr 2

NC

l

SO

OO O

PC

l

OH

HH

O

OH

HO

HO

HO SO

O

O

PO

OO O

OOO

PO

O O

OOO

Isop

ropy

liden

e-D

-gl

ucof

uran

ose

Isop

ropy

liden

e-D

-gl

ucof

uran

ose2E

t 3N

CH

2Cl 2

1.iP

rNC

l2.

Et 3

N

3Et 3

N

Isop

ropy

liden

e-D

-gl

ucof

uran

ose

Et 3

N19

19 20

2122

23X

-Ray

stru

ctur

e

Schem

e8

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particularly interesting since chiral g,d-usaturated ketones are obtained(Scheme 9).

In the presence of appropriate enantiopure diimine ligands, CpRu(Cp¼ cyclopentadienyl) half-sandwich complexes can catalyze these trans-formations and afford complete conversion with significant enantio- andregioselectivity.6 Typical catalysts used in this allylic alkylation are com-plexes of CpRu, possessing often various imine derivatives as ligands andhexafluorophosphate as a counterion (Figure 6). Compounds (25) and (26)could be easily obtained by the reaction of acetonitrile complex (24) with 1equivalent of the corresponding diimine usually in dry CH2Cl2.

As reported by Lacour et al. changing the imine ligands dramaticallyinfluences the selectivity of the Carroll rearrangement. For these reasonsseveral imines have been checked using ruthenium source (24) to optimisethe efficiency of the catalyst (Figure 7). For example, in the reaction ofsecondary allylic ester (27) to produce products (28) and (29), the highestlevel of both regio- and enantioselectivity was obtained when the rutheniumcomplex (24) was used as the metal source and chiral imine (30h) as theligand (Scheme 10).

RuNCMe

MeHCNMeCN

PF6

RuNCMe

PF6

N

N

RuNCMe

PF6

NAr

NAr

24 25 26

Fig. 6

R X

R

X R NuR

Nu[Ru]

NuX = Cl,OCOR′

*

branched (b) linear (l)

Scheme 9

RuNCMeMeCN

MeCN

PF6N

N

Ph

NN

Ph

PhN

N

PhMe2N

NN

Ph

Me

NN

Ph

NN

PhPh

NN

Ph

NN

OMe

30a 30b 30c 30d

30e 30e 30f30g

24

LigandsRuthenium source

Fig. 7

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MeO

OO

O

MeO

O

[Ru]

(10

mol

%)

Liga

nd (

10 m

ol%

) MeO

2728

29

Lig

and

Tim

e (h

)C

onv.

(%

)ee

Con

f.b

(31)

:(32

) ra

tioa,

c

-48

0-

--

30a

2010

056

(+)

>99

:1

bpy

410

0-

->

99:1

30b

3010

0-

->

99:1

30c

1397

50(+

)>

99:1

30d

9247

20(+

)>

99:1

30e

2410

058

(+)

>99

:1

30f

2210

066

(+)

>99

:1

30g

2010

072

(+)-

(S)

>99

:1

30h

2410

080

(+)

>99:

1

a (24

) (1

0 m

ol%

), li

gand

(10

mol

%),

TH

F, 6

0 °C

, c 0

.5 M

b Si

gn o

f th

e op

tical

rot

atio

n w

hen

know

nc

Rat

ios

of b

ranc

hed

(28)

to li

near

(29

) de

term

ined

at c

ompl

ete

conv

ersi

on

Schem

e10

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Similar results were observed for the rearrangement of enantio-enrichedsecondary allyl ester (31) to give ketones (32) and (33). Both enantiomersreacted with retention of configuration in the presence of chiral ligands(30a, c–h), however in the case of R-(31) the product of the Carrol re-arrangement was isolated with the same enantiomeric purity with both thechiral imine (30h) and the achiral imine (30b). The explanation of thisphenomenon is however not clear (Scheme 11).

During these investigations it was also found, that all the catalysts weresensitive to moisture, oxygen, isolation conditions and therefore in-appropriate to use in a microwave-assisted Carroll rearrangement. Forthese reasons, novel zwitterionic adducts of a hexacoordinated phosphateanion denoted TRISPHAT-N (34) with CpRu moieties were synthesised.The application of TRISPHAT-N as a counterion and ligand in zwitterionicmetal complexes stems from the fact, that these complexes possess highlipophilicity, as well as air and moisture stability and, as a consequence,could be readily purified and recycled. The synthesis involved dissolving salt(24) and bipyridine (bpy) in N2-saturated CH2Cl2 to yield [CpRu(bpy)(NCCH3)][PF6], followed by the addition of [Bu3NH][34] to afford complex(35). The resulting compound was readily isolated by column chroma-tography due to the remarkable elution properties bestowed by the TRI-SPHAT-N counterion (34) (Scheme 12).

Further experiments on the Carroll rearrangement have shown that theefficiency of novel catalyst (35) was better than catalyst (26). Not too sur-prisingly a longer reaction time was necessary with complex (35) to com-plete the process. However, under microwave irradiation, the reactionproceeded smoothly at 140 1C, in a relatively short time (30 min.) and withperfect regioselectivity, in favour of the branched isomer – in sharp contrastto the reaction with catalyst (26).

With these excellent results in hand, the preparation of other potentialcatalysts bearing TRISPHAT-N as a ligand was investigated especiallythose possessing bimetallic system which could be then used in an enan-tioselective variant of the Carroll rearrangement. This pathway involved thetreatment of [CpRu(NCCH3)3][PF6] (2 equiv.) with tetradentate ligandN,N0-bis(2-pyridyl-methylidene)-1,2-(R,R)-cyclohexanediamine (36) to ob-tain a complex mixture of several CpRu species (37), including three ste-reoisomeric bimetallic complexes, which could not be isolated from thecrude reaction mixture. The subsequent addition of 2 equivalents of[Bu3NH][34] led to the formation of biszwitterion (38) which was isolated bythe column chromatography in a modest yield (43%) as a complex mixtureof stereoisomers (Scheme 13).

The assymetric protocol for the Carroll rearrangement was then testedwith mixture (37) and with (38) (5mol%) under the classical conditions(THF, 60 1C, 0.5M, 48 h). In both cases, excellent regioselectivity and goodconversion was observed however the enantioselectivity differed. In the caseof catalyst (37) there was much lower selectivity and it was suggestedthat this might be due to in situ degradation of the bimetallic catalystor of the activity of other species present initially in the mixture. For theTRISPHAT-N adducts (38), an essentially constant enantioselectivitythroughout the reaction was noticed, indicating, most probably, that the

304 | Organophosphorus Chem., 2010, 39, 290–307

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O

OO

O

[Ru]

(10

mol

%)

Liga

nd (

10 m

ol%

)

3132

33

O

Est

erL

igan

dT

ime

(h)

eeC

onf.

b(3

2):(

32)

ratio

a,c

(S)-

31bp

y2

48(+

)-(S

)94

:6

(S)-

3130

b6

72(+

)-(S

)94

:6

(S)-

3130

a10

84(+

)-(S

)92

:8

(S)-

3130

h10

92(+

)-(S

)93

:7

(R)-

31bp

y2

46(-

)-(R

)93

:7

(R)-

3130

b6

72(-

)-(R

)94

:6

(R)-

3130

a6

68(-

)-(R

)94

:6

(R)-

3130

h6

70(-

)-(R

)99

:1

a (24

) (1

0 m

ol%

), li

gand

(10

mol

%),

TH

F, 6

0 °C

, c 0

.5 M

b Si

gn o

f th

e op

tical

rot

atio

n w

hen

know

nc

Rat

ios

of b

ranc

hed

(32)

to li

near

(33

) de

term

ined

at c

ompl

ete

conv

ersi

on Schem

e11

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results are due to the bimetallic catalysts and not to other species. More-over, the enantiomeric excess (ee 85%) was the highest reported so far in aRu-catalyzed enantioselective Carroll rearrangement.

References

1 X.-D. Jiang, S. Matsukawa and Y. Yamamoto, Dalton. Trans., 2008, 3673.

2 H. Miyake, N. Kano and T. Kawashima, Phosphorus, Sulfur and Silicon Relat.

Elem., 2008, 183, 673.

O

O

Cl

Cl

Cl

Cl

O

O

Cl

Cl

Cl

Cl

P

N

Cl O

O

TRISPHAT-N

RuNCMe

MeCNMeCN

PF6

RuNCMe

PF6

bpy

CH2Cl2N

N

RuN

N

N

O

O

Cl

P(Clcat)2[Bu3NH][34]

34

24

35

Scheme 12

N

N

N

N

N N

N N

RuMeCN

PF6Ru

NCMe

PF6

N N

N N

Ru Ru

Cl Cl

O

O

(Clcat)2P

O

O

P(Clcat)2

[RuCp(NCMe3)][PF6] (2 equiv.)

CH2Cl2

[Bu3NH][34] (2 equiv.)

36 37

38

Scheme 13

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3 D. A. Tatarinov, V. F. Mironov, E. N. Varksina, D. B. Krivalapov, I. A.

Litvinov, R. Z . Musin, B. I. Buzykin and A. I. Konovalov,Mendeleev Commun.,

2008, 18, 147.

4 E. Marcos, J. M. Anglada and R. Crehuet, Phys. Chem. Chem. Phys., 2008,

10, 2442.

5 R. R. Holmes, A. Chandrasekaran and N. V. Timosheva, Phosphorus, Sulfur and

Silicon Relat. Elem., 2008, 183, 209.

6 M. Austeri, F. Buron, S. Constant, J. Lacour, D. Linder, J. Muller and

S. Tortoioli, Pure Appl. Chem., 2008, 80, 967.

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