hexacoordinated phosphates: how to teach old chiral anions new asymmetric tricks

275© 2007 The Japan Chemical Journal Forum and Wiley Periodicals, Inc.

Hexacoordinated Phosphates: How toTeach Old Chiral Anions NewAsymmetric Tricks

JEROME LACOUR, DAVID LINDERDepartment of Organic Chemistry, University of Geneva, Quai Ernest Ansermet 30, CH-1211Geneva 4, Switzerland

Received 8 March 2007; Revised 8 May 2007; Accepted 2 April 2007

ABSTRACT: Chemical reactions and processes often involve chiral, yet racemic, cationic reagents,intermediates, or products. To afford instead nonracemic or enantiopure compounds, an asymmet-ric ion pairing of the cations with enantiopure anions can be considered—the counter ions behav-ing as asymmetric auxiliaries, ligands, or reagents. Detailed herein is a short review of our approachtoward gaining reliable and predictable control over stereoselective ion pairing phenomena throughthe synthesis and use of novel configurationally stable hexacoordinated phosphate anions. © 2007The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 7: 275–285; 2007: Published online in Wiley InterScience (www.interscience.wiley.com) DOI 10.1002/tcr.20124

Key words: asymmetric ion pairing; chiral anion; hexacoordinated phosphorus; resolution;supramolecular stereocontrol

The Chemical Record, Vol. 7, 275–285 (2007)

T H EC H E M I C A L

R E C O R D

� Correspondence to: Jérôme Lacour; e-mail:[email protected]

Introduction

Cationic species, omnipresent in coordination, organic,organometallic, and supramolecular chemistry, are ofteninvolved in chemical reactions and processes as reagents, inter-mediates, or products. These cationic species can be prochiralor chiral, and many of the resulting products are, unfortu-nately, racemic molecular structures or supramolecular assem-blies. To afford instead nonracemic or enantiopure adducts,and to benefit from new possible applications, a stereoselectiveion pairing of these cations with enantiopure anions can beconsidered—the counter ions behaving as asymmetric auxil-iaries, ligands, or reagents.1

A wealth of evidence suggests that an ion electrostaticallyremoved from its counterion is never formed in low-polaritysolvents but, instead, an ion pair is produced. The association

of racemic cations with enantiopure counterions thereforeleads to the formation of diastereomeric ion pairs.2 As a result,large chemical and physical differences can happen among thesalts of the tightly associated ions.

In early approaches, chiral anions issued or derived fromthe chiral pool have been essentially considered. Numerousapplications have been developed, especially in the field ofenantiomeric resolutions.3 Today, these anions are still usedwith much success.1 Recent developments in this field have,however, also made use of new synthetic anions that are (i)

© 2007 The Japan Chemical Journal Forum and Wiley Periodicals, Inc.

T H E C H E M I C A L R E C O R D

276

BINOL-based phosphoric acid derivatives,4 (ii) borate anionsmade from amino-acids,5 and (iii) chiral hexacoordinatedphosphate anions; the latter category of anions being particu-larly studied in our group.6 This review will thus survey ourefforts toward the preparation and the use of chiral hexacoor-dinated phosphates as anionic auxiliaries and reagents in par-ticular—other anions and their use being detailed recently inanother review.1 Applications of these moieties as NMR chiralsolvating reagents, as resolving agents for organic and inorganiccations, and as chiral auxiliaries for stereoselective processeswill be presented (Scheme 1).

Chiral Hexacoordinated Phosphate Anions

The octahedral geometry of pentavalent hexacoordinatedphosphorus allows indeed the formation of chiral anions by

complexation of a central phosphorus atom with three identi-cal dianionic bidentate ligands. As early as 1965, Hellwinkelreported the synthesis of hexacoordinated phosphate anion 1,which was shown to be chiral through a resolution procedure.7

The enantiomers exist as Λ or ∆ antipodes with a left- andright-handed propeller shape (M or P helicity), respectively.8 Adecade later, Wolf and Koenig studied the chiral tris(benzene-diolato)phosphate anion 2, of particular interest for its easyone-step preparation from catechol, PCl5, and an amine. It wasthen shown that anion 2 unfortunately racemizes rapidly insolution as an ammonium salt.9 This (negative) observation ofa poor configurational stability for 2 in solution resulted in anoverall lack of interest for this type of compounds from thestereochemical community, and this for more than twodecades.

However, this chemistry of hexacoordinated phosphateanions was recently rejuvenated as chiral tris(tetrachloroben-

� David Linder was educated at the Ecole Nationale Supérieure de Chimie de Clermont-Ferrandand obtained his Masters from University Paris VI (Jussieu). He is currently studying towardshis Ph.D. in the group of Professor Lacour. His current research interests concern the useof organoruthenium complexes for the development of enantioselective C¶C bond-formingreactions. �

� Jérôme Lacour was educated at the Ecole Normale Supérieure (Ulm, Paris) and in 1993obtained his Ph.D. in Chemistry at the University of Texas at Austin under the supervision of Pro-fessor Philip D. Magnus. After postdoctoral studies in the laboratory of Professor David A. Evansat Harvard University, he joined the Organic Chemistry Department of the University of Genevain 1995. Since 2004, he holds a full Professor position in the department. In 2001, he receivedthe Werner Prize and Medal of the Swiss Chemical Society and in 2005, the Grammaticakis-Neuman Prize of the French Academy of Sciences. �

C h i r a l H e x a c o o r d i n a t e d P h o s p h a t e s

277

zenediolato)phosphate(v) anion 3 was shown to be configura-tionally stable at room temperature in all common organic solvents.10 This D3-symmetric anion, known as TRISPHAT(Scheme 2), can be resolved by association with N-H-cinchonidinium as cationic counterion. Both ∆ and Λ enan-tiomers can be isolated on large scale as [cinchonidinium][∆-3] and [Bu3NH][Λ-3] salts, respectively.

The synthesis of functionalized /mixed hexacoordinatedphosphate anions containing two tetrachlorocatechols and athird different 1,2-diolato ligand can also be achieved.However, the preparation of such P(VI) anions is not a trivialmatter.11 A practical and general synthetic procedure had to be developed for the making of such novel hexacoordinatedphosphates; anion Bis(tetrachlorobenzenediolato)mono([1,1′]binaphthalenyl-2,2′-diolato) phosphate(V) anion (BINPHAT)4 (Scheme 3), which includes a BINOL moiety, is the arche-type of such derivatives.12 The procedure for the making ofthese advanced anions involves the in situ formation of a

spirophosphorane intermediate (5, Scheme 3), which reactswith essentially any diol to generate, in one pot, mixed hexa-coordinated phosphate anions. For instance, BINPHAT anion4 can be prepared in good yields (70–85% yield) from tetra-chlorocatechol, P(NMe2), o-chloranil, and BINOL. This pro-tocol was recently streamlined—all reagents being added asessentially one equivalent. It can be scaled up to multigramquantities.13 Starting from enantiopure R- or S-BINOL, thediastereoselectivity of the reaction is high (>96%) and yieldsare reproducible in favor of Λ-4 or ∆-4, respectively; the stere-oselectivity being most probably of kinetic rather than ther-modynamic origin.14

It is feasible, although with some risks, to change theoxidant (o-chloranil) in this process for another ortho-quinone,but original phosphate anions such as phenanthroline deriva-tive 6 can result from the operation (see Scheme 4).11 The one-pot procedure can be extended to the making of other mixedphosphates by varying the nature of the diol added last in theprotocol (e.g., mannose, tartrate, dihydrobenzoin derivatives7–9) (Scheme 4).13,15

Two novel anions containing fluorine substituents atselected positions were reported recently (10a and 10b). Forthe resolution of these two anions, a novel and general proto-col was developed using N-benzyl-cinchonidium chloride as aresolving agent; the ∆ and Λ enantiomers of the anions beingafforded in very high chemical and enantiomeric purity.Anions 10a and 10b display unique NMR properties that canbe used for the determination of exact (absolute) ion pairingstructures in solution (Scheme 5).16

Finally, the synthesis of a novel nitrogen-containing hexa-coordinated phosphate anion 11, named TRISPHAT–N, wasvery recently reported. This unique anion, through its Lewis


∆-2

O

O

O

O

O

O

PP

Λ-1

Scheme 1. Historical examples of chiral hexacoordinated phosphates.

O

O

O

O

O

O

P

Cl

Cl

Cl

Cl

Cl

Cl

Cl

Cl

Cl

Cl

Cl

Cl

a,b

Bu3NH

Cl

Cl

Cl

Cl

OH

OHrac-3

O

O

O

O

O

O

P

Cl

Cl

Cl

Cl

Cl

Cl

Cl

Cl

Cl

Cl

Cl

Cl

Cl

O

O

O

O

O

O

P

Cl ClBu3NH

61%

cinchonidinium

Cl Cl

Cl

Cl

Cl

Cl

Cl

Cl

Cl∆-3 Λ-3

c

Scheme 2. Synthesis and resolution of TRISPHAT anion 3. (A) PCl5 (0.33equiv), Ph-Me, 70°C. (B) nBu3N, CH2Cl2/n-Hexane, 20°C. (C) cinchonidine(0.50 equiv), CH2Cl2, 20°C.

HO

HO

Cl

Cl

Cl

Cl

PO

O

Cl

Cl

Cl

Cl

P

O

O

O

O

Cl

Cl

Cl

Cl

Cl

Cl

Cl

Cl

O

OP

O

O

O

O

Cl

Cl

Cl

Cl

Cl

Cl

Cl

Cl

> 90%

∆-4

Me2N

Me2N

85%

(S)-BINOL

de > 96%

a

b

Me2NH2

5

Scheme 3. One-pot synthesis of BINPHAT anion 4. (A) P(NMe2), toluene,reflux. (B) o-chloranil (1.0 equiv), BINOL (1.0 equiv), CH2Cl2, 20°C.



278

basic nitrogen atom, can interact directly with metal centersand allow the stereocontrol of molecular events that previousnoncoordinating anions of the TRISPHAT family could notachieve. It can, for instance, control the absolute P or M con-figuration of axially chiral tropos ligands bound to metal centersor the configuration of metal centers themselves (diastere-omeric ratio up to 96 :4) (Scheme 6).17

Successful NMR Chiral Solvating Agents

As mentioned, chiral cations are involved in many areas ofchemistry and, unfortunately, only few methods are availableto determine with precision their optical purity. In the lastdecades, NMR has evolved as one of the methods of choicefor the measurement of the enantiomeric purity of chiral

species.18 Over the past decade, we could demonstrate thatanions 3 and 4 are very effective NMR chiral solvating agents.6

They form tightly associated diastereomeric ion pairs withchiral cations, and the short-range interactions that occur leadto efficient NMR enantiodifferentiations. An arbitrary selec-tion of six cationic systems (12–17) that have been analyzedwith success—out of a collection of more than 30 species—isrepresented in Figure 1.

The cationic moieties can be of organic, organometallic,or metalloorganic nature. The stereogenic elements can be ofcentral, axial, planar, or helical chirality. 1H, 13C, 15N, 19F, and31P NMR spectroscopy can be used in these studies (e.g., Figs. 2 and 3). TRISPHAT 3 is overall more efficient withcationic metallo-organic and organometallic substrates,19 whileBINPHAT 4 has often-superior chiral solvating propertieswhen associated with organic cations.12,20 Anions 3 and 4 canalso be used to determine the enantiomeric purity of planarchiral chromium and palladium complexes such as 18 and 19.This result broadens the fields of application of the anionicreagents to neutral species.21

Very recently, two classes of original chiral objects were studied in conjunction of anions 3 or 4. One class is

O

OMe

O O

Ph

O

O

O

O

P

Cl

Cl

Cl

Cl

Cl

Cl

Cl

O

O

O

O

O

O

O

O

P

Cl

Cl

Cl

Cl

Cl

Cl

Cl

Cl

RO2C

RO2C

O

O

O

O

O

O

P

Cl

Cl

Cl

Cl

Cl

Cl

Cl

Cl

O

O

O

O

O

O

P

Cl

Cl

Cl

Cl

Cl

Cl

Cl

Cl

N

N

6 Λ-7

8 9

Cl

Scheme 4. Functional mixed phosphate anions.

O

O

O

O

O

O

P

Cl

Cl

Cl

Cl

F

Cl

Cl

Cl

Cl

Cl∆-10a

O

O

O

O

O

O

P

Cl Cl

Cl

FCl

Cl

Cl Cl∆-10b

Scheme 5. Fluoro-phosphate anions for detailed structural NMR studies.

O

O

O

O

O

O

P

N

Cl

Cl

Cl

Cl

Cl

Cl

Cl Cl11

Cl

Scheme 6. Lewis basic phosphate anion.

2

NN

NN

N

NRu

P

CD3

CH3

OMe

NMe

MeMe

OMe

Me

Mn(CO)3

S

Ph

MeMe

12 14

15 16

O

N N

O

Pr Pr

13

17

Fig. 1. Some chiral cations analyzed efficiently with anions 3 or 4.


279

Efficient Resolving Agents

The lipophilicity of TRISPHAT anion 3 confers to its salts anaffinity for organic solvents and, once dissolved, the ion pairsdo not partition in aqueous layers. This rather uncommonproperty was used to develop a practical resolution procedureof racemic cationic substrates by preferential extraction of oneenantiomer from water into immiscible organic solvents.[Ru(Me2bpy)3]2+ 28 and [Ru(Me2phen)3]2+ 29 were selected asracemic substrates for their ease of synthesis and high watersolubility as chloride salts (Me2bpy = 4,4′-dimethyl-2,2′-bipyridine; Me2phen = 4,7-dimethyl-1,10-phenanthroline).


5.05.25.45.65.8 5.05.25.45.65.8

H(3)H(6)

(a)

(b)

(c)

(d)

18 19

CH3

SiMe3

Cr(CO)3

Pd

Cr(CO)3

N

Me2NMeO

MeO

Fig. 2. 1H NMR spectra (parts, 400MHz, C6D6/2% DMSO-d6) of (A) rac-18; (B) rac-18 + 2.3 equiv of [n-Bu4N][∆-3]; (C) (+)-(1S)-18 (87% e.e.) + 3.7equiv of [n-Bu4N][∆-3]; (D) (+)-(1S)-18 (>99% e.e.) + 2.3 equiv of [n-Bu4N][∆-3].

NN

N

N NN

L

1H

[Co4(L)6(BF4)] [BF4]7

(a)

19F

–246–245–244–243455055

(b)

21

Fig. 3. 1H and 19F NMR spectra (5% CD3NO2 in CDCl3) of[Co4(L)6(BF4)][BF4]7 21 with (A) 0 and (B) 8.0 equiv of [Bu4N][∆-3].

NN

N

N

N

N

Ru

Ru

N

N

N

N

N

Ru

Ru

Ru

Ru

6+

N

O O

O O

O O

O O

O O

O O

R

R

R

R

R

R

20

Scheme 7. Chiral triangular metalloprisms.

constituted of cationic triangular metalloprisms of type[Ru6(arene)6(tpt)2(C2O4)3]6+ 20 (arene = C6Me6 and p-iPrC6H4Me; tpt = 2,4,6-tripyridyl-1,3,5-triazine). Thanks tothe presence of anion 4, it was shown that the oxalato deriva-tives 20 possess a double helical chirality induced by (i) a twistof the tpt units and (ii) a concerted tilt of pyridyl moieties;something not so obvious at first sight (Scheme 7).22

The second class of interesting derivatives is that of chiralpseudo-tetrahedral cationic cages of type [Co4(L)6(BF4)]7+ (21)made of four metal ions at each corner of an approximate tetra-hedron, and of six bis-bidentate bridging ligand L spanningeach edge. The central cavity is occupied by one tetrahedralcounterion (BF4

−) which is tightly bound and does notexchange with external anions on the NMR timescale. Thetetranuclear complexes are chiral, having T symmetry in solu-tion with all four metal centers in each complex having thesame tris-chelate configuration. Addition of enantiopureanions ∆-3 to complexes 21 led to the enantiodifferentiationof the ligands of the racemic salts and, more interestingly, ofthe achiral tetrafluoroborate anion trapped inside in the cage.The discrimination of the inside BF4

− anion was even easierthan that of the surrounding chiral cages (∆δ ∼2.0 and 0.4ppmin 19F and 1H NMR, respectively).23

Several reports independent from our group have con-firmed the efficiency of these NMR chiral solvating agents andthose of Amouri, Andraud, Cordier, Gruselle, LeBozec,Lemercier, Maury, Mikami, Nitschke, Rose-Munch, and Stoddart in particular; some of the studied analytes (22–27)are represented in Scheme 8.24



280

Solutions of salts [Bu3NH][Λ-3] in CHCl3 or [cinchoni-dinium][∆-3] in 7.5–10% DMSO/CHCl3 were prepared (1equiv) and added to orange-coloured solutions of racemic[28]Cl2 or [29]Cl2 in water (1 equiv). Upon vigorous stirringof the biphasic mixtures, a partial transfer of colorationoccurred from the aqueous layer to the organic one (Fig. 4).Selectivity ratios as high as 49 :1 were measured for the enan-tiomers of the cations in the organic and aqueous layers,demonstrating without ambiguity the efficiency of the resolu-tion procedure.25 An extension of this protocol was furtherdeveloped for diiron(II) triple helicate 30 and afforded in separated phases the P or M enantiomers of the [Fe2L3]4+ helix(see Scheme 9).26

Previously, it was also found that the lipophilicity ofTRISPHAT anion 3 modifies profoundly the chromatographicproperties of the cations associated with it and the resultingion pairs are usually poorly retained on polar chromatographicphases (SiO2, Al2O3).27 Using enantiopure TRISPHAT anion,accessible from [cinchonidinium][∆-3] in particular, the chromatographic resolution of chiral cations is feasible as thediastereomeric ion pairs often possess rather different retarda-tion factors. For instance, complex [Ru(Me2bpy)3]2+ 28 (Fig.4) was separated into diastereomeric homochiral [∆-RuL3][∆-3]2 and heterochiral [Λ-RuL3][∆-3]2 salts by column chro-matography over silica gel (eluent CH2Cl2).28 Rather largedifferences in retardation factors were observed (∆Rf

0.10–0.23). The resolution is often best performed on prepar-ative thin-layer chromatographic plates.16 The protocol wasextended to monocationic cyclometallated ruthenium com-plexes of type 31 and to a configurationally stable mononu-clear iron(II) complex 32 (Fig. 5).29

Finally, resolution of chiral cations by selective precipita-tion of one diastereomeric salt is, of course, still a possibility.TRISPHAT 3 was recently used in such a manner with successby the groups of Amouri, Gruselle, Hamelin, and Fontecavefor the resolution of metal-containing moieties, among whichare triangular metallo-macrocycle 33 and ruthenium complex34 (Scheme 10).30 BINPHAT 4 was more efficient thanTRISPHAT for the isolation of enantiopure helicenium cation16 (Fig. 1).31

Effective Asymmetry-Inducing Agents

Chiral compounds are sometimes configurationally stable assolids and configurationally labile in solution. When opticallyactive samples of these derivatives are solubilized, a racemizationoccurs due to the free interconversion of the enantiomers insolution. To obtain these compounds in one predominant con-figuration over time, one strategy is to add stereogenic elementsto their backbone; intramolecular diastereoselective interactionshappen and favor one of the equilibrating diastereomers. If the

O

R

RhCp*

2322

Co Co P

PC

C

P

P

OCOC

COCO

RR

R R

RR

R R

2

N

NRu

NMe2

NMe2 3

(CO)3Cr24

(depe)2Ru SMe

N N CO2Et

Me

NCu

N N

N

N

N

N

NCu

N

N

N

NCu

3

26 27

25

Scheme 8. Selected examples of chiral cations analyzed successfully withanion 3.

H2O

CHCl3

[29][Cl]2racemic

[R3NH][Λ-3]

stirring

[Λ-29][Λ-3]2(d.r. up to 49 : 1)

[∆-29][Cl]2(e.r. up to 35 : 1)

N

NRu

Me

Me

N

NRu

Me

Me

2

2928

3

2

3

Fig. 4. Schematic representation of the asymmetric resolution of salt [29]Cl2;e.r. and d.r. indicate enantiomeric and diastereomeric ratios.

MP

N

NFe

N

NFe

3

4

30

Scheme 9. Chiral diiron(II) triple helicate 30.


281

chiral compounds are charged, an alternative strategy is to con-sider their ion pairing with chiral counterions; intermolecular—rather than intramolecular—diastereoselective interactionsthen control the stereoselectivity (Pfeiffer effect).32

The induction of optical activity by chiral anions ontocationic racemic substrates has been previously considered.33

Unfortunately, in many of these examples, the extent of theasymmetry induction was determined by chiroptical measure-ments (optical rotatory dispersion [ORD], circular dichroism[CD]) that gave qualitative and not exact quantitative infor-mation. The NMR chiral solvating efficiency of anions 3 and4 is therefore an excellent analytical tool to provide accuratemeasurement of the induced selectivity.

Monomethine dyes 35, diquats 36 and configurationallylabile ammonium cation 37 were thus studied with success inthe presence of anions 3, 4 and others (Fig. 6).12,13,34 Copper(I)bis(diimine) complexes 38, dicobalt(II) helicate 39 and manylabile tris(diimine) metal complexes (e.g., iron(II) derivatives40 and 41) were also paired with the chiral counterions.35 TheNMR signals of the chiral cations were split by the presenceof the anions and diastereomeric ratios up to 49 :1 were measured for some of the substrates.

In a study performed in collaboration with ProfessorsConstable and Housecroft, it was shown that the configura-tion of the metal core of ribose-decorated iron(II) metallostar40 (Fig. 6) was better controlled though interionic diastere-omeric interactions with TRISPHAT 3 than by the intrinsicproximity of the chiral sugars—the supramolecular stereocon-trol from the anions being much more effective than theintramolecular one.36 Recently, we could show that such high diastereoselectivity can be achieved even in polar mediadespite lower electrostatic attraction and stronger solvent competition (diastereometric excess >95% in 90% acetone/chloroform) via a careful choice of ligands on the iron(II)center, and polycyclic elatin ligand in particular (Fig. 7,complex 41).37

Very recently, the stereocontrol over the propeller iso-merism of trimesitylmethylphosphonium cation 42 was alsoachieved through an ion pairing with chiral anions 3 and 4.Salts [42][∆-3] and [42][∆-4] were prepared, and the chiralrecognition (induction) was studied by 1H and 31P NMR spec-troscopy (toluene-d8). A very decent enantiodifferentiation wasobserved (∆δmax ∼0.60ppm, P+CH3) and an honest diastere-omeric excess was measured (d.e. 39 and 47% for salts ofanions 3 and 4, respectively, Fig. 8). Maybe more importantly,the asymmetric ion pairing allowed also the first experimentalevidence of the solution enantiomerization mechanism (two-ring flip) of the propeller cation using a simple kineticanalysis and two readily determined rate constants.38

The existence of Pfeiffer effects upon addition of anions 3and 4 was also confirmed by reports of Shionoya and Stoddart;the configurationally labile molecules being sandwich-shapedtrinuclear silver complexes and catenanes, respectively.39


Fe

N

N

N

N

p-Anisyl

p-Anisyl

N

N

2

C

N

N

N

N

N

Ru

31

32

[∆-32][∆-3]2

[Λ-32][∆-3]2

Fig. 5. Complexes 31 and 32. Ion-pair chromatographic resolution of [rac-32][PF6]2 with [cinchonidinium][∆-3] (eluent CH2Cl2).

Rh

NO

O

Cl

Rh

N

O

O Cl

Rh

Li

N

O O

Cl

33 34

2

N

NRu

2

H3CCN

H3CCN

Scheme 10. Some chiral cationic entities resolved with anions 3 or 4.

N

NMe

N N

Me

N

N

Co

N

N

Co

3

4

N

N

N

N

N

N

Fe

O

O

O

O

O

O

OR'

OR'

R' = 2,3,5-triacetyl-β-D-ribofuranose

R'O

R'O2

X

35, X = H, Br 36

39 40

N

N

N

R

Cu NN

R

R = Alkyl, Aryl

38

OR'

OR'

37

Fig. 6. Some configurationally labile cations.



282

Superior Ion Pairing Properties

Anion 3 also enhances the binding affinity of cationic guestswithin classical host–guest systems. In the context of quater-nary ammonium recognition by cyclophanes or crown ethers,the presence of 3 as anionic counterion increases the bindingaffinity of the ammonium salts by two- to sevenfold. Currently,it seems that 3 is the best counterion ever reported for ammo-nium host–guest chemistry. It was used to demonstrate thatfull ion pairs, and not just the ammonium cation, must be con-sidered in host–guest studies in CHCl3 leading to interestingphotophysical properties or,40 in conjunction with chiral cyclichexapeptidic hosts of type 43, to effective matched/mis-matched asymmetric ion pairing situations (Scheme 11).41

This knowledge was used further in a study directedtoward the stereoselective synthesis of inherently chiralpseudorotaxanes 44. 1H NMR spectra (parts) of dissymmetricaryl-substituted macrocycle DB24C8F6 are reported on Figure9 for the PF6

− (left) and rac-TRISPHAT (right) salts; U and Tindicating the unthreaded and threaded (diastereomeric)macrocycle, respectively. Clearly, they indicate a much higherconcentration of diastereomeric pseudorotaxanes in the pres-ence of the lipophilic counterion 3; the threading process withTRISPHAT counterions being thus much more effective(×7.3) than with the PF6

− analog.42

In a somewhat related study, it was shown by the Stod-dart group that TRISPHAT anions 3 can have a profoundinfluence upon the ratio of translational isomers in bistabledonor–acceptor rotaxanes where a p-accepting tetracationiccyclophane shuttles between two different p-donating recog-nition sites—the presence of anions 3 as counterions favoringpredominantly the encirclement of bispyrrolotetrathiafulva-lene over dioxynaphthalene recognition sites.43

NN

NN

N

NFe

NN

N

N

NN

2

NN

NN

N

NFe

NN

N

N

NN

2

∆-41 ∆-41[∆-3]2 [∆-3]2

Fig. 7. Supramolecular stereocontrol over the configuration of iron(II) tris-diimine complexes, e.g., complex Fe(eilatin)3 41.

1.501.802.102.202.502.803.10

H2O

Intensity x 4

P

Me

P

Me

P-42 M-42

(a)

(b)

(c)

Fig. 8. 1H NMR spectra (500MHz, Toluene-d8) of salts of cation 29 and sub-sequent diastereoselectivity: (A) [42][I]; (B) [42][∆-3], d.e. 39%; (C) [42][∆-4], d.e. 47%.

N

HN

NNH

N

NHO

O

O

OO

O

R

R

43a : R = H43b : R = OCH3

43c : R = COOCH3

43d : R = COOCH2Ph

R

N

Me

TRISPHATrac-3, Λ-3 or Λ-3

Scheme 11. Chiral cyclic hexapeptidic hosts for asymmetric ammoniumrecognition.

3.203.30

(a)

O O

OO

O

O

O

O

CF3

CF3

O

N N

O

Pr Pr

H2N

Ph

O O

OO

O

O

O

OCF3

CF3

O

N N

O

Pr Pr

H2N

Ph

U

T T UT T

3.203.30

(b)

44

Fig. 9. 1H NMR spectra (500MHz, parts, CDCl3) of dissymmetric aryl-substituted macrocycle DB24C8F6—U and T indicate the unthreaded andthreaded (diastereomeric) macrocycle, respectively: (A) PF6

− salt; (B) rac-3 salt.


283

Finally, most of the above-described examples have usedthe chiral hexacoordinated phosphate anions in enantiomeri-cally enriched or pure forms. Applications of the chiral anionsin their racemic form are also possible. Maury, Le Bozec,Ledoux, and coworkers have used the lipophilicity of racemicTRISPHAT to enhance the solubility of cationic, octupolarnonlinear optically active, metal trisbipyridyl complexes, andtheir polymeric or dendrimeric forms in particular.44 Salts ofvarious racemic cations and anions 3 crystallize readily in cen-trosymmetric unit cells providing interesting new phases orsupramolecular arrangements as a result.45 In term of syntheticapplications, the superior lipophilicity that TRISPHAT anionsconfers to its salts allows the perfect containment in organiclayers of reactive cationic systems when reactions are per-formed in biphasic CH2Cl2/water conditions. This effectivepartitioning of the organic reagents was recently used for thedevelopment of enantioselective olefin epoxidation reactionsmediated by catalytic iminium/oxaziridinium species; com-pounds 45 and 46 being prototypical examples of the iminiumcatalysts used (Scheme 12).46

The strict biphasic CH2Cl2/water conditions that can beenforced due to the presence of anions 3 can enhance the selec-tivity of the epoxidation reaction and help the recovery of thenonracemic epoxides.

Conclusion

In conclusion, hexacoordinated phosphate anions such asTRISPHAT 1 and BINPHAT 2 are able NMR solvating,resolving, and asymmetry-inducing reagents when paired withconfigurationally stable or labile chiral cations. The organic,inorganic, or organometallic nature of the cationic moieties isnot influential, as good anionic matches can usually be found.We believe that there is much to gain from this supramolecu-lar approach to stereoselective synthesis as both configurationsof a chiral cationic complex can be generated in high diastere-omerical purity with no need to prepare two sets of enan-tiomeric ligands. It is a priori sufficient to form the cationic

derivative with achiral ligands and exchange the traditionalachiral anions (PF6

−, BF4−, etc.) for chiral versions.

Addendum

Since the initial submission of this paper, two manuscripts con-cerning hexacoordinated phosphate anions were accepted forpublication. In one of them, it was shown that the configura-tional stability of axially chiral concave bimacrocyclic imida-zolinium ions of type 47 can be readily investigated by NMRusing TRISPHAT 3 and BINPHAT 4 as stereodynamicalprobes (Scheme 13).47

In the second study, TRISPHAT 3 was shown to be aneffective NMR chiral solvating and resolving agent for novelcyclometallated iridium dinuclear complex [(ppy)2Ir(µ-L)Ir(ppy)2]2+ 48 (ppy = 2-phenylpyridine) which was synthe-sized initially as a mixture of three stereoisomers (meso ∆,Λ;Λ,Λ; ∆,∆) (Scheme 14).48

We are grateful for financial support of this work by theSwiss National Science Foundation, the State Secretariat forEducation and Research, the European Science Foundation(COST Office), as well as the Société Académique de Genève,the Schmidheiny Foundation, and the Sandoz FamilyFoundation.


R2

H

R3

R1 [Iminium][rac-3] saltsas catalysts (5 mol%)

NaHCO3, Oxone®

CH2Cl2 / Water 3:20 °C

R2

H

R3

R1O

NMe

45 46

NEt

NEt

Scheme 12. Enanioselective epoxidation of olefins mediated by [Iminium][rac-3] salts.

N N

O

O

O

O

N NO

O

O

O

(Sa,Ra)-47 (Ra,Sa)-47

∆G‡ < 77 kJ/mol

Scheme 13. Axially chiral concave bimacrocyclic imidazolinium ion 47.

IrIr

meso {Λ∆}-48 ΛΛ-48∆∆-48

IrIr IrIr

NN

NN

Ir NN

NN

Ir

2+

48

Scheme 14. Stereoisometric cyclometallated iridium dinuclear complex 48.



284

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hexacoordinated phosphates: how to teach old chiral anions new asymmetric tricks

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