Pentacoordinated and hexacoordinatedcompounds

Romana Pajkerta and Gerd-Volker Roschenthalera

DOI: 10.1039/9781849732819–00297

1 Introduction

The coordination tendencies of phosphorus to form hypervalentcompounds have been especially studied due to the fact that penta- andhexacoordinated phosphoranes are involved in numerous biologicalprocesses such as hydrolyses of RNA, or phosphoryl transfer reactions.Therefore considerable attention has been given to the synthesis, chemicaltransformations, structures and configurational stability of hypervalent or-ganophosphorus compounds.

During last year the majority of researches in this area has been focusedon the synthesis and structural determination of novel hypervalent phos-phorus compounds as well as on the stereochemistry of pentacoordinatedchiral spirophosphoranes. In these studies, Mironov et al. obtainedtricyclic pentacoordinated spirophosphoranes containing a phosphorus-carbon bond with high regio- and stereo-selectivity1 whereas Kawashimapresented the synthetic route to perfectly ‘‘anti-apicophilic’’ carba-phosphatranes.2

While the chemistry of pentacoordinated spirophosphoranes has been sofar widely explored, cyclic hexacoordinate phosphorus compounds are muchless studied because very often they are transient species anddifficult to detect.However, an interesting example of a stable hexacoordinate phosphoranatebearing Martin ligands was recently described by Yamamoto.3 Anotherapproach involved the participation of donor-acceptor nitrogen-phosphorus4

and sulphur-phosphorus5,6 bonds in the formation of stable hexacoordinatedcompounds.

One particularly fascinating class of pentacoordinate phosphorus com-pounds is the class of chiral spirophosphoranes with amino acid residues aschiral chelate ligands since they can serve as important structural featuresrelevant to chiral phosphoryl transfer pathways. Therefore, their synthesisand stereochemistry were recently widely explored.7,8

To have more insight into the role of hypervalent phosphorus compoundsin driving several phosphorus-mediated reactions, the following investi-gations were carried out. First, the umpolung of hydrogen from water andreductive deuteriation with D2O using hexacoordinated dihydrophosphate.9

Then, diastereoselective phosphination reaction between ‘‘butterfly re-agent’’ and selected Grignard reagents10 and regio-/stereoselective hydro-phosphonylation of activated alkenes and alkynes via fluoride ionactivation.11 As a final point of this chapter, the application of hex-acoordinated phosphorus anion as an effective chiral solvating agent inNMR studies is described.12

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

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�c The Royal Society of Chemistry 2011

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2 Synthesis and structure determination of novel hypervalent

spirophosphoranes

Among the methods used for the synthesis of hypervalent phosphoruscompounds, the most common include: the ligand exchange reaction at PV

atom, reactions of a nucleophile with pentacoordinate molecules, variousaddition reactions of PIII derivatives to unsaturated systems, the reactionswith halogens and the reactions of PIII derivatives bearing functionalsubstitutents at the phosphorus atom with carbonyl compounds. The latterapproach has been recently applied to the one-step synthesis of novelpentacoordinated tricyclic spirophosphoranes containing a phosphorus-carbon bond with high regio- and stereo-selectivity.1 As substrate, 2-(2-acetylphenoxy)benzo-1,3,2-dioxaphosphole was selected, as it possesses thereactive carbonyl group in the d position of one of the aromatic substitu-ents. Dioxaphosphole (1) was then reacted with highly active carbonylcompounds such as chloral and hexafluoroacetone to give polycyclicphosphoranes (2) and (3), as presented in Scheme 1.

The mechanism proposed for the reaction of dioxaphosphole (1) withchloral involved the formation of an intermediate bipolar ion (A) containingPþ -CO� bond which subsequently undergoes a nucleophilic attack on thecarbon atom of the acetyl substituent giving rise to bipolar intermediate (B).The latter ion, after the nucleophilic attack on the phosphorus centre, leadsstereoselectively to the final product (2). In a similar manner, the synthesisof compound (3) has been accomplished (Scheme 1).

The geometry of the phosphorus atom in tricyclic spirophosphoranes (2)and (3) could be best described as nearly regular trigonal-bypiramidal (TBP)for compound (2) and for compound (3) as a trigonal bipyramid moredistorted toward a square pyramid and is formed by the P(1), O(2), O(3)and C(7) atoms. The oxygen atoms O(1) and O(8) are located in the apicalpositions while the equatorial P(1)-O(2) and P(1)-O(3) bonds are slightlyshorter than the corresponding apical bonds.

Scheme 1

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Pentacoordinated spirophosphoranes generally possess a trigonal-bypiramidal (TBP) structure with two distinctive sites: the apical and theequatorial positions. The relative preference of substituents to occupy thesepositions is determined by their electronegativity and p-donating ability, aswell as steric hindrance in the pentacoordinted species. According to manyexperimental studies and theoretical calculations, electronegative andsterically small groups prefer to occupy the apical sites, whereas electron-donating and bulky ligands favour the equatorial positions. The apicalbond is defined as a three-center-four-electron (hypervalent) bond involvinga p orbital of the central element and it exhibits unique characteristics, beinga weaker and more polar bond.

Recent developments of Kwashima et al.2 have shown, that the synthesisof pentacoordinated phosphoranes with reversed apicophilicity, in which allequatorial positions are occupied with electronegative oxygen atoms andapical positions with electropositive carbon atoms is also possible, by thereaction of 1-hydro-5-carbaphosphatrane with various nucleophiles andsubsequent oxidation.

Moreover, 1-hydro-5-carbaphosphatrane is also regarded as an exampleof an anti-apicophilic phosphorane, in which all equatorial positions are occu-pied by three oxygen atoms. However the reactivity towards nucleophiles isincreased in theO-equatorial spirophosphoranes compared to theO-apical ones.

The synthesis of novel perfectly anti-apicophilic phosphoranes (6a–d) wasachieved by reacting 1-hydro-5-carbaphosphatrane (4) with an appropriatealkyl- or aryllithium reagent in THF, followed by the hydrolysis and furtheroxidation of the bicyclic intermediate (5a–d) with iodine (4a and 4b) or bypyrolysis (4c and 4d) (Scheme 2).

The formation of bicyclic intermediate (5) during the reaction suggestedthat the carbaphosphatrane framework is not maintened and one five-membered ring is cleaved by nucleophilic substitution. This different re-activity, in comparision to other H-equatorial spirophosphoranes, could bebest explained by the structural difference of compound (4). Because thehydrogen atom in (4) is fixed in an apical position, its acidity is lowerthan that of H-equatorial spirophosphoranes. Therefore, nucleophilicsubstitution is thus preferred over deprotonation.

The unusual anti-apicophilic structures of targeted products wereadditionally confirmed by X-Ray analysis. For compound (6b) the apicalP-C bond is 1.877(2) A, whereas for (6d) it is much longer (1.959(2) A) dueto the steric bulkiness and rigidity of the mesityl group. The equatorial

Scheme 2

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P-O bond lengths fall within the normal bond lengths in pentacoordinatephosphoranes. The axial C-P-C bond angle 179.27(7)1, and equatorialO-P-O bond angles are 118.95(60-121.16)(6) and gave the sum of equatorialbond angles equal 3601. The structural parameters indicated a nearlytrigonal-bypiramidal structure of phosphorane (6b) despite its thermo-dynamically disfavored arrangement around the central phosphorus atom.Generally tert-butyl and mesityl groups are most equatophilic substituents inspite of their steric hindrance and electropositive character and thus form per-fectly anti-apicophilic phosphoranes (6b, 6d) more easily due to the rigidframework that stabilizes the TBP structure. On the other hand, when the api-cophilicity of introduced substituents is large as for a phenyl group or hydrogenatom, the formation of 1-phenyl-5-carbaphosphatrane (6c) or recovery ofthe starting 1-hydro-5-carbaphosphatrane (4) occurs due to the possible equili-brium betweenH-apical andH-equatorial isomers of bicyclic intermediate (5).

Phosphoranes (6a–d) were characterised by 1H, 31P and 13C NMRspectroscopy giving unique characteristics particularly in 31P NMR. Signalsof anti-apicophilic spirophosphoranes (6a–d) were detected at dP 22, 22, 8and 29 ppm, respectively and were shifted downfield compared to thechemical shifts usually observed for pentacoordinated phosphoranes(dP -100 to 0 ppm). This indicates that the central phosphorus atom isdeshielded by the electronegative oxygen atoms occupying all equatorialpositions. Moreover, the extraordinarily large apical coupling constant1JPC is probably a result of a larger contribution of positive charge to the Fermiterm in apical couplingwhile the central phosphorus atomof (6a–d) that has anincreased positive charge is supported by the downfield 31P NMR shifts.

In recent years, the application of H-spirophophoranes bearing Martinligands in reactions with nucleophiles has been extensively investigated forvarious pentacoordinated phosphoranes with frozen stereomutation. As acontinuation of this work, Yamamoto has shown that pentacoordinated O-equatorial spirophosphoranes can serve as substrates in the synthesis ofhexacoordinated phosphatranes. These can be regarded as intermediatemodels for the reaction of O-equatorial spirphosphorane with alkyl lithium.Such intermediates are generally difficult to isolate in a stable form.3 Thehexacoordinate phosphoranates were thus obtained by reacting spirocyclicO-equatorial phosphorane (7) with methyllithium and n-butyllithium, fol-lowed by the hydrolysis to afford the corresponding monocyclic phos-phoranes (8) in the first step. The monocyclic phosphorane (8a) was thentreated with KH in dichloromethane to give hexacoordinated phosphatraneas a mixture of isomers (9A.K and 9B.K) (Scheme 3).

Among the five possible stereoisomers, the major isomer was assigned to(I) whereas the minor was represented by structures (II) and (III) (Figure 1).Moreover, the ratio of stereoisomers was calculated to be 79:21, based onthe integral values in the 19F NMR. The phosphatrane (9K) was isolated inthe presence of 18-crown-6 ether as colourless crystals (Scheme 3) and thestructure of the product was additionally confirmed using X-Ray analysis,showing that the molecular structure of the anionic moitey corresponded tothe major isomer (9A). The two P-C(methyl) distances (P-C3 and P-C4) arealmost the same (1.876(8)A and 1.873(7)A) while the length of O-equatorialP-O2 is 1.917(5)A.

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The hexacoordination of phosphorus atom may also occur if there is atleast one donor atom in a substrate that could inter- or intramolecularlycoordinate phosphorus after oxidative addition step to PIII derivatives. Forinstance, the reaction of diimine (10) containing phenol groups withethylenechlorophosphite (11) has been found to undergo a stereoselectivecascade cyclization affording tetracyclic derivative of the hexacoordinatedphosphorus atom with intramolecular transannular N-P bond (Scheme 4).4

The possible mechanism for the formation of (12) includes the phos-phorylation of one of the hydroxy group of diimine (10) to form phosphateand release of hydrogen chloride. The latter protonates one of the iminenitrogen atoms simultaneously increasing electrophilicity of the C=N

Scheme 3

PO

O

F3C CF3

F3CF3C

Me

MeP

O

O

F3CF3C

F3CF3C

Me

MeP

O

O

F3C CF3

Me

Me

PMe

O

F3C CF3

O

Me

CF3

CF3

PMe

O

F3C CF3

Me

O

F3C CF3

I II III

IV V

9A 9B

CF3F3C

Fig. 1

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bond. After P-C bond formation, that resulted from the nucleophilic attackof PIII on the activated C=N linkage, the cyclization arises from theattack of the second hydroxy group on the phosphorus atom, giving rise tothe appearance of two chiral centres in a molecule as well as N-Pcoordination. An X-Ray structure of this compound as well as spectraldata revealed that the product crystallized as one diastereoisomercomplexed with methylene chloride. Configurations of stereogenic centerswere opposite and the transannular N-P distance was 2.006(6)A. More-over, dehydrochlorination of salt (12) with triethylamine provided theneutral phosphorate (13).

Similarly, the reactions of various cyclic PIII derivatives with diisopro-pylazodicarboxylate (DIAD) to achieve hypercoordination of phosphorusstemmed from the possibility of sulfur-phosphorus coordination.5,6 In one

Scheme 4

Scheme 5

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such example, sulfur-containing chlorophosphite (14) was treated withDIAD to give hexacoordinated phosphorus compound (15) possessing oneS-P bond. Further reaction of product (15) with pyrazole gave two dif-ferent hexacoordinated phosphoranes: the first one (16) possessed one S-Pbond while the second exhibited two unusual S-P linkages (17).6 It hasbeen postulated that the formation of compound (17) came from ligandreorganization for which literature precedence is available (Scheme 5).

31P NMR analysis of compound (17), showed the presence of a singlesignal at d -58.4 ppm, suggesting the coordination with sulfur atom.However, the structure elucidation of product (16) was not so evident dueto the existence of geometrical isomerism in solution and thus multiple 31PNMR signals. Although, the most probable structure of one of isomers hasbeen presented at Scheme 5.

Interestingly, oxidative addition of DIAD to other sulfur containing PIII

compounds (18, 19), gave pentacoordinated spirophosphoranes (20) and(21) instead of hexacoordinated species. Plausibly,the –OCH2CH2SH moi-ety may not be able to render the phosphorus sufficiently acidic to givehexacoordination, thus the pentacoordination of phosphorus was assignedto structures (20) and (21), by comparison with compound (22) and otherrelated compounds (Scheme 6).

Compound (17) bearing two unusual coordinate S-P’S linkagesrepresents the first example of a hexacoordinated phosphorus compound ofthis type. The structure of (17) was established by X-Ray analysis and

P

O

O

OX

N

O Oi-Pr

N

C(O)Oi-Pr

P

O

O

S

HS

18 X = S19 X = CH2

O

O

Cl

Cl

Cl

Cl

O

O

O

SH

ClCl

Cl

Cl

P

O

O

O

O

O

SH

Oi-Pr

C(O)(Oi-Pr)

P

O

O

O

ClCl

Cl

Cl

ON

20 ( P -56.1, -56.4 ppm)

21 ( P -66.1, -66.8 ppm)

22 ( P -40.0 ppm)δ

δ

δ

Scheme 6

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showed the octahedral geometry with facial arrangement of the two fusedrings. In contrast however to previously reported Cavell’s phosphoranepossessing two Pa-P’Pb bonds where the coordinating phosphorusatoms are trans to each other, in the case of S’P-S linkages two sulfuratoms of (17) have a cis configuration (Figure 2).

Moreover, two equivalent S-P bonds are quite strong [2.334(1)A] andare comparable to that in the chloro precursor (15) [2.317(1)A] but shorterthan other hexacoordinate phosphorus compounds with only one S-Pcoordination. The presence of hydrogen bonded chloride (to pyrazole NH)ion also enhances the stability of hexacoordinated phosphate (17).

3 Stereochemistry of pentacoordinated chiral spirophosphoranes

Enzymatic phosphoryl transfer reactions are ubiquitous in nature and playsignificant roles in ATP hydrolysis and protein phosphorylation processess.As previously described, pentacoordinate phosphorus species have beenassumed as transient intermediates or transition states in these pathwaysand their structural and electronic properties are undoubtedly related to theoutcome of the process. Therefore, to aid understanding of the phosphorus-catalyzed biological routes, many model pentacoordinated phosphoraneshave been synthesized. While most studies have focused on aspects ofapicophilicity, anti-apicophilicity or Berry pseudorotation, there have beenlimited investigations on the stereochemistry of pentacoordinated spir-ophosphoranes with a chiral phosphorus atom. In the past year, muchattention has been paid to the synthesis and determination of absoluteconfiguration of several chiral pentacoordinate spirophosphoranes derivedfrom D- and L-aminoacids. Some significant achievements in this area willbe discussed in this section.

The chiral pentacoordinated spirophosphoranes were synthesized usingmethod outlined in Scheme 7.7,8

As detected by 31P NMR, in each case a pair of isomers was formed,derived from D- and L-amino acids. Isomers (25b–30b) are soluble indichloromethane or chloroform, whereas compounds (25a–30a) are prac-tically insoluble in these solvents but are soluble in polar solvents such asdimethyl sulfoxide.

To investigate the stereochemistry of pentacoordinated spiropho-sphoranes with chiral chelate ligands such as amino acids, the diastereoi-somers could be differentiated by reverse-phase high-performance liquidchromatography (HPLC), solution or solid-state circular dichroism (CD),

OO

O

O

S

S

POO

OO

P

P

P

17Cavell's phosphorane

Fig. 2

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nuclear magnetic resonance (NMR) and X-Ray crystallography. Amongthem, HPLC is the most effective method for their separation while X-Rayis necessary for the determination of absolute configuration of chiralphosphorus atom. Solid-state CD spectroscopy provides additionally somesubtle structural information that could be correlated with that of singleX-Ray crystallography. The above diastereoisomers (25a–30a) and (25b–30b)were thus separated by reverse-phaseHPLCwith a TC-C18 column. Generallycompounds (25a–30a) exhibited the same retention time, while (25b–30b)were retained longer (methanol : deionizedwater v/v=3:2as eluent). Thereforeit was evident that isomers (25a)/(26a), (25b)/(26b), (27a)/(28a), (27b)/(28b),(29a)/(30a) and (29b)/(30b) could be a pairs of enantiomers. Moreover, everyisomer could be obtained with 99% of enantiopurity.

The absolute configuration of phosphorus atom of enantiomers 25a/26aand 25b/26b was determined using X-Ray analysis. All aforementionedcompounds exhibit distorted trigonal bypiramidal structure (TBP) with twonitrogen atoms and a hydrogen atom in an equatorial possitions and two

Scheme 7

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apical oxygens. The deviation from the ideal angle of 1201 for the anglesN(4)-P(5)-N(9) was calculated to be 4.571 (25a), 5.151 (26a), 5.791 (25b) and5.901 (26b) whereas other angles were close to 901. In the crystal latticestructures, the presence of N-H �O intramolecular hydrogen bond led to theformation of a chain parallel to the b-axis and then the Van der Waalsinteractions provide the stability of the crystal structure.

The crystal structures of (27a), (28a), (25b) and (26b) display an endo-configuration like a ‘‘resting butterfly’’ where the benzene rings of phenyl-alanine in (25b), (26b) semi-stack together. By contrast, the non-crystalineenantiomers (25a), (26a) exhibit an exo-configuration that looks like a‘‘resting moth’’ with near coplanar rings.

To facilitate the identification of the absolute configuration of thephosphorus center, the nomenclature system for a coordination compound[MX(AB)2] (AB=hetero-bidentate ligand) that can have TBP orsquare-pyramidal (SP) geometry was used. In the TBP geometry, when amonodentate ligand X occupies one equatorial position, the ‘‘chiral-at-metal’’ configuration can be defined as L or D (Figure 3).

X-Ray analysis showed that the phosphorus centres in (25b) and (27a)have an LP configuration and both a-carbons of the amino acids possessan (S)-configuration and the absolute configuration of (25b) and (27a) is(LP, SC, SC) and (26b) and (28a) is (DP, RC, RC). Since other isomers couldnot be obtained as suitable single crystals for structure determination, theirabsolute configuration could not be assigned directly.

In order to show a stereochemical relationship between two pairs ofenantiomers, solid-state circular dichroism spectroscopy was measured. TheCD spectra confirmed that (25a)/(26a), (25b)/(26b), (27a)/(28a), (27b)/(28b),(29a)/(30a) and (29b)/(30b) are indeed pairs of enantiomers. However,spirophosphorane stereoisomers derived from L-amino acids as well asthose synthesized from D-amino acids show opposite Cotton effects andthus do not follow the chirality of the amino acids. This means that thecontrolling factor for the absolute configuration of these isomers is thechirality of the phosphorus center.

All the above mentioned isomers were additionally characterized by 1HNMR solution spectroscopy. As expected, the epimeric (a)/(b) pairs ofenantiomers showed significantly different spectra whereas the spectra ofenantiomers (a)/(a) are identical. Whether the hydrogen bond to nitrogenis deuterated or not, the proton bound to phosphorus gave a doublet in1H NMR with splitting only with phosphorus or doublet of triplets as aresult of splitting with phosphorus and two magnetically-equivalentprotons. This special phenomenon of coupling was further confirmed by

Fig. 3

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1H-1H COSY spectra that identified an interaction between the P-H protonand the a-hydrogen of amino acid establishing an unusual four-bonddistance coupling for these cases. Nevertheless, in the case of epimers this1H-1H COSY effect was not detected. Furthermore, all isomers exhibit highconfigurational stability (potential epimerization was monitored by 1H and31P NMR in DMSO or CDCl3 over a period of a month).Thus, they canserve as simple models for pre-biological activity.

4 Hypervalent phosphorus compounds in chemical processess

It is well known that the coordination ability of phosphorus to formhypervalent compound, mainly penta- and hexacoordinated, is the drivingforce in describing the mechanistic action of phosphoryl transfer enzymes.On the other hand, organophosphorus compounds play also a fundamentalrole in inorganic, organic and applied chemistry as a key species, reactionintermediates or final products. Therefore, the utility of hypervalent phos-phorus compounds in many chemical processess is indisputable and in somecases facilitate the outcome of the reaction to be defined. Recently, someachievements on the role of hypervalent phosphoranes in various chemicalprocessess have been described.

As reported by Kawashima et al.,9 using a hexacoordinate dihydropho-sphate bearing Martin ligands, the umpolung of hydrogen atom of waterand deuterium oxide is possible without any transition metal catalyst. Itshould be noted, that the umpolung of hydrogen from heavy water (D2O)will provide deuterium ion (D� ), valuable donor for isotope-labelling in acheaper and easier way than other isotope-labelled reagents such as hydridereagents (LiAlD4). On the other hand, umpolung of a hydrogen atom isdifficult due to the fact that the reaction of a proton source such as water(Hdþ -OH) with the product of umpolung (Hd� -Z) or reagent producesmolecular hydrogen. To confirm the activity of hexacoordinated dihy-drophosphate, a proton of water was exchanged with hydrogen on thephosphorus and next the hydride reduction and reductive deuteriation ofselected carbonyl compounds was accomplished.9

A key species, hexacoordinate dihydrophosphate (32) was synthesizedfrom hydrophosphorane (31) by the treatment of lithium naphthalenide(3eq.), water (excess) and tetraethylammonium bromide (1.5 eq.) to give thedesired dihydrophosphate (32) as depicted in Scheme 8.

Scheme 8

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A dideutero derivative was obtained via a H-D (hydrogen-deuterium)exchange reaction of dihydrogenphosphate (32) with D2O in the presence ofAcOH to form (32-d2) bearing two P-D bonds. Further investigationsrevealed that dihydrophosphate, as well as dideuterophosphate, act aseffective reductive agents of various aliphatic, aromatic and a,b-unsaturatedaldehydes and ketones, giving appropriate alcohols in good yields(Scheme 9). It should be however noted that the addition of a Lewis acidthat activates carbonyl group (LiCl or AcOH) dramatically accelerate thereduction process in the case of both (32-h2) and (32-d2). Thus reductivedeuteriation is a promising isotope-labelling method because the reactionachieves deuteride reduction under mild conditions, using simple pro-cedures and does need expensive deuteride reagents, transition metalcatalysts and careful handling.

The H-D exchange of deuterium of D2O is interesting and a plausiblemechanism for this transformation has been proposed. After the addition ofan acid to phosphate (32), a negatively charged oxygen atom is protonatedto form dihydrophosphorane (33) that equilibrates with phosphate (32)(Scheme 10). The pentavalent phosphorane also equilibrates with trivalentphosphine (34) by tautomerization, which is common in such phosphoruscompounds. The formation of phosphine (34) was additionally confirmedby 31P NMR (d, dP -19.9 ppm, 1JPH 223 Hz). In the next step, one of thehydrogen atoms on the phosphorus of phosphate (32) migrates to theoxygen in (34) through the tautomerization, and then three reversibleprocesses : protonation, tautomerization and H-D exchange, and acidtreatment of phosphate (32) would finally provide (32-d2), by repetition ofthese processes (Scheme 10).

The possibility for the formation of hypervalents states by organo-phosphorus species could also find an application in veryfing the stereo-chemical outcome of reactions involving phosphorus species. An importantexample confirming this thesis has been recently presented by Baccolini’s

Scheme 9

Scheme 10

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group. In these studies, assymetric alkyl phospholanes were diaster-eoselectively synthesized by addition of an unsymmetrical bis-Grignardreagent and of a mono-reagent to benzothiadiphosphole and isolated assulfides. The authors postulated the formation of pentacoordinated andmetastable hexacoordinated intermediates that influences the reactionsselectivity.10

Synthesis of 2,10-dimethyl[1,2,3]-benzothiadiphospholo[2,3-b][1,2,3]ben-zothiadiphospholo (35), the so-called ‘‘butterfly reagent’’ due to its foldedstructure, was achieved by the addition of PCl3 and AlCl3 to p-methylani-sole (Scheme 11).

Assymetric tertiary phosphines (38a–f) were then obtained in differentdiasteromeric ratios by reacting benzothiadiphosphole (35) with the un-symmetrical bis-Grignard reagent (36, R0=Me), followed by the addition ofa mono-Grignard reagent (37). The phosphines cis-(38a-f, R0=Me) andtrans-(38a–f, R0=Me) were further isolated as sulfides by the addition ofelemental sulfur to the crude reaction mixture (Scheme 12).

The cis/trans ratio of the corresponding tertiary phosphine sulfides (39,R0=Me) slowly decreased down the series, parallel to the increase of thesteric hindrance of the R group of an appropriate mono-organomagnesiumreagent (37a–f). Nevertheless, the use of a very bulky Grignard reagent,such as tert-butylmagnesium chloride (37f), caused a strong enhancement ofthe diastereoselectivity degree but in the opposite sense with respect to thatobserved in cases (37a–d). A borderline situation occurred with isopropylderivative (37e) that gave an equimolar amount of cis and trans isomers.

These phenomena could be best explained by the formation of hyper-valent phosphorus species. Plausible pathways of the diastereoselctive

R'

R

S

P2

P1S

S

P2

P1S

S

MgBrMgBr

P2

P1S

S

MgBrMgBr

MgBr

P

R

P

MgBr

S S

MgBrBrMg

PSR

PCl3AlCl3

(36)

35A

RMgBr (37)

B

PCl3

40

38

S8

39

R' R'

R'

BrMgMgBr

R'

R' = H, Me

Scheme 11

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outcome of the reaction of benzothiadiphosphole with bis- and mono-Grignard reagents were presented (Scheme 13).

In the first step, the addition of bis-Grignard reagent (36) to benzothia-diphosphole (35) occurs. Since the Grignard reagent is non-symmetrical,four possible pentacoordinate intermediates A

I-AIV could be formed.Intermediates AI and AII are enantiomeric forms as are AII and AIV.

Moreover, AI, AIII and AII, AIV can be converted into one another through

Scheme 12

Scheme 13

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Berry pseudorotation. The stability of the abovementioned intermediates isadditionally limited by steric factors and intramolecular overcrowding intrigonal bypiramidal structures. The more favorable isomers are AI and A

II

due to the equatorial position of the methyl substituent of the phospholanering. The presence of pentacoordinated intermediates was confirmed by 31PNMR. Nevertheless, the relative stability of isomeric isomers AI–AIV is nota factor determining the stereochemical outcome of this reactions, since thesubstituent derived from mono-Grignard reagent is not yet present in thesestructures.

By adding mono-organomagnesium (37) compound to the mixture of AI-AIV, nucleophilic attack on the pentacoordinated phosphorus center occurs,

giving rise to four diastereomeric hexacoordinated BI–BIV species. Inintermediates BI and BIV the methyl substituent R0 on the phospholane ringand the R group on the hypercoordinate phosphorus are in trans relation-ship (less hindered, more stable) whereas in BII and BIII they are in cisrelative position (less stable). In the next step, hexacoordinated intermedi-ates BI–BIV spontaneously collapse, forming racemic mixtures of trans- andcis-phospholanes in a ratio depending on the mono-Grignard reagent addedto pentacoordinated precursor.

The different diastereoselectivity observed during the reaction could bebest explained considering steric hindrance of R groups in mono-Grignardreagents. In cases (37a–d), in which the steric hindrance is parallel and notvery high, trans and cis hexacoordinated intermediates can be formed in asimilar amount. As previously mentioned, the cis form is less stable and thusimmediately collapses, causing the shift of the equilibria and producing acis-phosphine as the final major product. When R=t-Bu (37f), because ofthe high steric hindrance, the formation of hexacoordinated species isshifted through trans BI and BIV, which cannot equilibrate giving almostexclusively trans-phosphine (38f). In the case of isopropyl group, all thesefactors influence the stereochemical outcome of the reaction, producing anequimolar amounts of trans and cis diastereomeric phosphines.

The hypothesis of penta- and hexacoordinates species was additionallyverified by 31P NMR, by monitoring the reaction progress. After the add-ition of bis-Grignard reagent to (35), the presence of pentacoordinatedintermediates was detected, however the fast interconversion of these iso-mers gives rise to one averaged signal as two doublets at d -10.7 ppm (1JPP196 Hz) and d -44.4 ppm (1JPP 196 Hz). By adding mono-Grignard reagentto this mixture (CH3MgBr), signals in the region of hexacoordinated speciesappear together with the signals of the diastereomeric tertiary cyclic phos-phines (38a) (d -19.3 and d -28.6 ppm). When R=Et (37b) the 31P NMRanalysis showed two pairs of doublets probably belonging to two morestable diastereomeric (B) forms (d 89.4 ppm (d, J 113 Hz) and d -61.2 ppm(d, J 196 Hz, and d 85.3 ppm (d, J 103 Hz) and d -57.0 ppm (d, J 103 Hz).When R=t-Bu (37f), only one pair of doublets was observed, together withthe signals of tetrtiary phosphines (38f), which like all the cases disappearedafter the addition of elemental sulfur to the final reaction mixture.

As mentioned, the ability of phosphorus compounds to form hypervalentstates is a driving force in several processes in which phosphorus substratesare involved. One of the significant example that have been recently

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described includes the hydrophosphonylation/hydrothiophosphonylationof various Baylis-Hillman adducts that leads selectively to g-hydroxypho-sphonates, vinyl or allyl phosphonates, etc. via the pentacoordination ofphosphorus. In this process, cyclic phosphites (41a,b) were reactedwithBaylis-Hillmanadducts suchasactivatedalkenes (42a,b), alkynes (42c) or allenes (42d)in the presence of tetrabuthylammonium fluoride (TBAF) in ionic liquid,1-butyl-3-methylimidazolium hexafluorophosphate, [bmim]þ [PF6]

� to give adiverse range of phosphonates (43–46) with good yields (Scheme 14).11

When cyclic phosphites were treated with allyl bromide (42b), in thepresence of TBAF, a-arylphosphonates were regioselectively obtained.However, the more reactive thiophosphite (41b) gave the double phos-phonylation product under these conditions in a single step.

Mechanistically, hydrophosphonylation and hydrothiophosphonylationtakes place via pentacoordinate state that could be achieved only towardfluoride ion activation F� in ionic liquid medium. Other anions, e.g. Cl� ,Br� , I� or HPO4

2� did not work because they are not strong enough tolead to hypervalency. If other sterically hindered and less reactive cyclicphosphites (47a) and (47b) were treated with equimolar quantity of TBAF,the P-F bonded intermediate (48a) or (48b) was formed as confirmed byNMR analysis. These intermediates were then reacted with allyl bromideH2C=C(CO2Me)CH2Br, to give phosphonate (49) as a sole product(Figure 4).

Based on the above observation, a reaction mechanism has been pro-posed, involving pentacoordinate phosphorus intermediates (48a) and(48b). Due to the strong affinity between fluoride and phosphorus, thenucleophilic attack of a fluoride anion to give cyclic phosphite (41a) orthiophosphite (41b) generates pentacoordinated phosphorus compounds

PYO

O

EWG

OH

Ar

BrEWG

Ar

EWG = CO2MeCO2EtCN

PYO

O

EWG

Ar

R H

PYO

O TBAF30-50% mol[bmim]+[PF6]-

r.t., 6h

R

PYO

HO

R•

R'

R''

PYO

O

PYO

O

R

R' R''

PY O

O

41a Y = O41b Y = S

42b42c

42d

Ar

OH

EWG

42a

TBAF30-50% mol[bmim]+[PF6]-

r.t., 6h

TBAF30-50% mol[bmim]+[PF6]-

r.t., 6h

30-50% molTBAF

[bmim]+[PF6]-

r.t., 6h

43

44

45

46

Scheme 14

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(48a) and (48b). For the subsequent step, it is possible that fluoride ion hassimply increased the acidity of phosphorus centre or the reaction entails afree radical mechanism to form intermediate (50), that liberates F� givingthe expected product (51) as depicted at Scheme 15.

5 Application of hypervalent phosphorus compounds in NMR studies

In the last decades, NMR has evolved as one of the methods used forthe determination of chiral species. Among recent examples, chiralhexacoordinated phosphate anion, [bis(tetrachlorobenzenediolato)mono([1,1’]binaphtalenyl-2,2’-diolato)phosphate], (D,R)-BINPHAT (52), as itstetrabutylammonium salt, has found widespread use as a very efficientNMR chiral solvating agent (CSA) for quaternary ammonium cations(quats) derived from a Troger base (53) (Figure 5).5,12

P

O

O

PO

O

47a X = O47b X = S

H

O

F

P

O

O

F

H

O

O

H

48a 48b

or

P

O

O

49 (quantitative)

OCO2Me

Fig. 4

PYO

HO41a Y = O41b Y = S

(n-Bu)4N+F- P

F

O

YO

HP

F

H

YO

Oor

48a (Y = O) 48b (Y = O)

Cation: (n-Bu)4N+

activation via pentacoordinationor a radical pathway

H

R'

R

EWG P

F

YO

O

H R'EWG

R-F-

fast PYO

O

R

EWGHR'

50 51a Y = O51b Y = S

Scheme 15

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BINPHAT (52) is commercially available but it can be easily synthesizedas outlined in Scheme 16.5

Recent work of Lacour et al.12 has focused attention on the use of C2-symmetrical BINPHAT (52) in enantiodifferentation of N-alkyl-Troger(53a-c) quats, possessing at least one stereogenic nitrogen atom in solventsof different polarity (Figure 5).

The preparation of salts [rac-53a][D-52] and [rac-53b][D-52] wasaccomplished by mixing appropriate rac-(53a) or (53b) bromides and[Me2NH2][D-52] in acetone and dichloromethane. Aliquots were then elutedover alumina to give analytical samples. 1H NMR spectroscopy of CD2Cl2and CDCl3 solutions showed that [rac-53a][D-52] gave the most dis-tinguished signals for the N-methyl groups. However a rather large differ-ence in chemical shifts was observed for protons next to the N-atom(DDdmax 0.25 and 0.28 ppm in CD2Cl2 and CDCl3, respectively). Interest-ingly, the methyl protons attached to the aromatic nuclei, were poorly split

Fig. 5

Scheme 16

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for [rac-53a][D-52] (DDdmax B0.01 and 0.08 ppm in CD2Cl2 and CDCl3,respectively) in contrast to those for [rac-53b][D-52] (DDdmax 0.21 and 0.09ppm in CD2Cl2 and CDCl3, respectively). This large magnitude of changesis possibly linked to the enhancement of steric hindrance around thecharged N-atom and to the necessity for counter ion (52) to interact with(53b) away from the chiral pocket of quat.

Having demonstrated the high efficiency of anion (52) as CSA in halo-genated solvents, further investigations included the measurements of NMRsolvating efficiency of (52) in polar solents such as acetone-d6 and acetonitrile-d3 and in non polar benzene-d6. Distinguishable signals were noticed for thediastereometric salts of [rac-53][D-52] in all solutions and a slow decrease inNMR splitting occurred in spectra from benzene to acetonitrile solutions. Asexpected, for salt [rac-53a][D-52], Nþ -Me signals were well resolved givingtwo signals (Dd 0.03 ppm) whereas the Ar-Me groups were not or poorlyseparated for [rac-53a][D-52] and [rac-53b][D-52]. In contrast, detailedobservation of the aromatic region of the spetra indicated that better protonprobes can be found using polar solvents. For instance, the signals ofaromatic protons in 7 and 4 positions are sharply separated in BINPHATsalts of racemic (53a) and (53b). Hence, it is possible that the chiral anioninteracts with the Troger base derivative on the side of the charged nitrogenatom. In the case of salt [rac-53c][D-52] in CD3CN the most easily monitoredsignal is that of a diastereotopic proton of the phenylacetyl side chain. Thevery large magnitude of changes (DDd 0.12 ppm) indicates a strong inter-action of the ions at the vicinity of the charged atom in this polar solvent.

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