TRISPHAT-N: A chiral hexacoordinated phosphate anion with unique asymmetric coordinating properties

Article abstract of DOI:10.1021/om070074k

A simple and efficient chiral anionic N-ligand: the introduction of a Lewis basic nitrogen onto the TRISPHAT skeleton allows the direct and efficient stereocontrol of tropos chiral ligands bound to metal complexes or of stereogenic metal centers (dr up to 96:4).

Full text of DOI:10.1021/om070074k

Organometallics 2007, 26, 2141-2143
2141
TRISPHAT-N: A Chiral Hexacoordinated Phosphate Anion with
Unique Asymmetric Coordinating Properties
Samuel Constant,† Richard Frantz,† Jessica Mu¨ller,† Ge´rald Bernardinelli,‡ and
Je´roˆme Lacour*,†
De´partement de Chimie Organique, UniVersite´ de Gene`Ve, quai Ernest-Ansermet 30, 1211 Gene`Ve 4,
Switzerland, and Laboratory of Crystallography, UniVersite´ de Gene`Ve, quai Ernest-Ansermet 24,
1211 Gene`Ve 4, Switzerland
ReceiVed January 24, 2007
Summary: A simple and efficient chiral anionic N-ligand: the
introduction of a Lewis basic nitrogen onto the TRISPHAT
skeleton allows the direct and efficient stereocontrol of tropos
chiral ligands bound to metal complexes or of stereogenic metal
centers (dr up to 96:4).
of the phosphate anion was deemed necessary. Lewis acid-
Lewis base interactions would essentially ensure the formation
of zwitterionic complexes and possibly induce stronger chiral
recognition and asymmetric induction processes. In this context,
we report herein the synthesis and resolution of the novel
nitrogen-containing hexacoordinated phosphate anion 2, denoted
TRISPHAT-N, which can interact directly with metal centers
and allow the stereocontrol of molecular events that previous
non-coordinating chiral anions could not achieve.
Recently, the chemistry of chiral hexacoordinated phosphate
anions has been revitalized, as anions such as tris(tetrachlo-
robenzenediolato)phosphate(V) (1; TRISPHAT, Λ or ∆ enan-
tiomer)1 have been shown to be valuable chiral NMR solvating,
resolving, and asymmetry-inducing reagents for chiral cationic
species.2 However, effective chiral recognition was essentially
achieved in solution only in associations with complementary
D3-symmetric metal complexes of the type [M(diimine)3]2+
(diastereomeric ratio (dr) > 90:10).3,4 Efficient stereocontrol
over the configuration of conformationally labile chiral ligands
bound to metal centers was also never described using chiral
anions as supramolecular chiral auxiliaries.5
We interpreted this lack of effective chiral recognition be-
tween 1 and most cationic metallic complexes as the result of the
exclusive presence of ion pairs,6 the chiral anion being posi-
tioned at a distance too far from the metal center or its ligands to
interact efficiently.7 Any modification of the anion structure that
would ensure a tighter anion-cation association would then be
beneficial. As cationic metal complexes are usually Lewis acidic,
the introduction of a Lewis basic nitrogen atom on the skeleton
To modify as little as possible the structural features of
TRISPHAT, only one of the three tetrachlorocatecholate ligands
was exchanged by a nitrogen-containing diol. 5-Chloropyridine-
2,3-diol (3) was selected for its commercial availability and
proven efficiency in metal binding events.4d,8 The derived
phosphate anion 2, namely TRISPHAT-N, was prepared by
following reported guidelines.9 Anhydrous tetrachlorocatechol
and P(NMe2)3 were reacted in toluene at reflux. After concen-
tration in vacuo, successive additions in CH2Cl2 of o-chloranil
(3,4,5,6-tetrachloro-3,5-cyclohexadiene-1,2-dione), 3, and then
[Bu3NH][Cl] yielded the desired tri-n-butylammonium salt of
racemic phosphate 2 (Scheme 1). The analytically pure com-
pound [Bu3NH][rac-2] was obtained after chromatography (yield
79%, 22 g scale, four consecutive steps).
The resolution of the anion was achieved by the addition of
N-benzylcinchonidinium chloride salt ([4][Cl]; 1.0 equiv) to a
CHCl3 solution of [Bu3NH][rac-2]. Selective precipitation of
the diastereomerically pure (-)-[4][∆-2] salt was afforded in
good yield (46%).10 The Λ enantiomer was isolated from the
mother liquor as (+)-[Bu4N][Λ-2] after ion exchange metathesis
with [Bu4N][Cl] and chromatography (SiO2, CH2Cl2). The non-
racemic anion 2 displayed in our hands good chemical and con-
* To whom correspondence should be addressed. E-mail:
jerome.lacour@chiorg.unige.ch.
† De´partement de Chimie Organique, Universite´ de Gene`ve.
‡ Laboratory of Crystallography, Universite´ de Gene`ve.
(1) Favarger, F.; Goujon-Ginglinger, C.; Monchaud, D.; Lacour, J. J.
Org. Chem. 2004, 69, 8521-8524. Lacour, J.; Ginglinger, C.; Grivet, C.;
Bernardinelli, G. Angew. Chem., Int. Ed. 1997, 36, 608-609.
(2) Lacour, J.; Frantz, R. Org. Biomol. Chem. 2005, 3, 15-19. Lacour,
J.; Hebbe-Viton, V. Chem. Soc. ReV. 2003, 32, 373-382. Constant, S.;
Lacour, J. Top. Curr. Chem. 2005, 250, 1-41.
(3) (a) Bergman, S. D.; Frantz, R.; Gut, D.; Kol, M.; Lacour, J. Chem.
Commun. 2006, 850-852. (b) Jodry, J. J.; Frantz, R.; Lacour, J. Inorg.
Chem. 2004, 43, 3329-3331. (c) Monchaud, D.; Jodry, J. J.; Pomeranc,
D.; Heitz, V.; Chambron, J.-C.; Sauvage, J.-P.; Lacour, J. Angew. Chem.,
Int. Ed. 2002, 41, 2317-2319 and references therein.
(6) Macchioni, A. Chem. ReV. 2005, 105, 2039-2073. Pregosin, P. S.
Prog. Nucl. Magn. Reson. Spectrosc. 2006, 49, 261-288. Marcus, Y.;
Hefter, G. Chem. ReV. 2006, 106, 4585-4621. Pregosin, P. S.; Martinez-
Viviente, E.; Kumar, P. G. A. Dalton Trans. 2003, 4007-4014. Macchioni,
A. Eur. J. Inorg. Chem. 2003, 195-205. Reed, C. A. Acc. Chem. Res. 1998,
31, 133-139. Strauss, S. H. Chem. ReV. 1993, 93, 927-942. Loupy, A.;
Tchoubar, B. Salt Effects in Organic and Organometallic Chemistry;
VCH: Weinheim, Germany, 1992.
(7) In fact, anions such as TRISPHAT can be essentially considered as
noncoordinating counterions. For a review on the topic, see: Krossing, I.;
Raabe, I. Angew. Chem., Int. Ed. 2004, 43, 2066-2090.
(8) Brasey, T.; Scopelliti, R.; Severin, K. Inorg. Chem. 2005, 44, 160-
162. Lehaire, M.-L.; Schulz, A.; Scopelliti, R.; Severin, K. Inorg. Chem.
2003, 42, 3576-3581.
(9) Frantz, R.; Pinto, A.; Constant, S.; Bernardinelli, G.; Lacour, J. Angew.
Chem., Int. Ed. 2005, 44, 5060-5064. Pe´rollier, C.; Constant, S.; Jodry, J.
J.; Bernardinelli, G.; Lacour, J. Chem. Commun. 2003, 2014-2015.
(10) Circular dichroism analysis of salts (-)-[4][∆-2] (MeOH, ∼10-6
M) reveals strong exciton coupling in the π-π* region with positive and
negative Cotton effects at the lowest and highest wavelengths, confirming
the ∆ configuration: Bas, D.; Bu¨rgi, T.; Lacour, J.; Vachon, J.; Weber, J.
Chirality 2005, 17, S143-S148. Of course, the CD spectra of (+)-[Bu4N]-
[Λ-2] present the opposite situation.
(4) For examples of weaker stereocontrol with other geometries, see:
(a) Hebbe-Viton, V.; Desvergnes, V.; Jodry, J. J.; Dietrich-Buchecker, C.;
Sauvage, J.-P.; Lacour, J. Dalton Trans. 2006, 2058-2065. (b) Desvergnes-
Breuil, V.; Hebbe, V.; Dietrich-Buchecker, C.; Sauvage, J.-P.; Lacour, J.
Inorg. Chem. 2003, 42, 255-257. (c) Hiraoka, S.; Harano, K.; Tanaka, T.;
Shiro, M.; Shionoya, M. Angew. Chem., Int. Ed. 2003, 42, 5182-5185.
Full stereocontrol can be obtained, however, in selective precipitation or
crystallization processes: (d) Mimassi, L.; Cordier, C.; Guyard-Duhayon,
C.; Mann, B. E.; Amouri, H. Organometallics 2007, 26, 860-864. (e)
Habermehl, N. C.; Angus, P. M.; Kilah, N. L.; Noren, L.; Rae, A. D.; Willis,
A. C.; Wild, S. B. Inorg. Chem. 2006, 45, 1445-1462. (f) Mimassi, L.;
Guyard-Duhayon, C.; Rager, M. N.; Amouri, H. Inorg. Chem. 2004, 43,
6644-6649.
(5) Mikami, K.; Yamanaka, M. Chem. ReV. 2003, 103, 3369-3400.
Mikami, K.; Aikawa, K.; Yusa, Y.; Jodry, J. J.; Yamanaka, M. Synlett 2002,
1561-1578.
10.1021/om070074k CCC: $37.00 © 2007 American Chemical Society
Publication on Web 03/24/2007

2142 Organometallics, Vol. 26, No. 9, 2007
Communications
Scheme 1. Synthesis of Phosphate Anion 2 and Its
Resolution using the N-Benzylcinchonidinium Salt [4][Cl]
Figure 1. Ligands 5 (tropos, represented with P (Sa) conformation),
6 (pyridine oxazoline), and 7 (pyridine benzoimidazole).
lipophilicity (SiO2, CH2Cl2, 72%).16,17 NMR spectroscopic
analysis (1H, 13C, and 31P, CDCl3, 293 K) revealed two sets of
signals in a 66:34 ratio and a lack of coordinating CH3CN
ligand(s) upon ion exchange. These results indicated a coordina-
tion of the anion to the Cu center, resulting in two diastereomers,
[Cu(P-5a)(∆-2)] and [Cu(M-5a)(∆-2)],18 the exchange of anion
∆-2 within the complexes being furthermore slow on the NMR
time scale (as evidenced by 31P NMR). The existence of a zwit-
terionic complex was furthermore confirmed by X-ray diffrac-
tion analysis of [Cu(5a)(∆-2)], which crystallized as a single
diastereomer in CH2Cl2/hexane; the biphenyldiimino ligand
adopts a P (Sa) configuration in the solid state (Figure 2).19
Assuming that the relative lack of stereocontrol (dr 66:34)
around the trigonal-planar Cu(I) atom was the result of overly
distant interactions of ligands ∆-2 and diimine 5a, care was
taken to study further systems based on more hindered pseudo-
tetrahedral metal centers that would position the stereogenic
elements closer together. For that purpose, the salt [CpRu(5b)-
(CH3CN)][PF6] was synthesized and treated with (-)-[4][∆-2]
and (+)-[Bu4N][Λ-2]. The resulting complexes [CpRu(5b)(∆-2)]
and [CpRu(5b)(Λ-2)] were isolated using the already described
chromatographic protocol (SiO2, CH2Cl2, Rf ) 0.82, 70-68%).16
Only one set of signals was observed in NMR spectroscopy
(1H, 13C, and 31P), irrespective of the solvent used for the
analyses (CD2Cl2, CDCl3, C6D6, toluene-d8).20 CD spectra
displayed intense Cotton effects in the visible MLCT region
figurational stability. No evidence of racemization could be found
during, for instance, the ion exchange metathesis of cation 4
by Bu4N+. Monocrystals of the cinchonidinium derivative were
obtained, and the absolute ∆ configuration was determined by
a crystal structure analysis.11 P-O bond lengths and O-P-O
bond angles are not so different from those measured for
TRISPHAT (1),12 although one P-O bond linked to the oxypyrid-
onate unitsthe one that involves the oxygen closest to the
nitrogen atomsis much shorter (1.690 Å) than usual; the longest
bond (1.723 Å) is the other P-O bond linked to the heterocycle.
The ability of anion 2 to form zwitterionic species and thus
behave as ligand and chiral auxiliary together was first assessed
in association experiments with Lewis acidic metal complexes
bearing the chiral conformationally labile (tropos) ligands 5a
and 5b (Figure 1),13 our purpose being the stereocontrol of the
absolute P or M geometry of the ligands. Salts [Cu(5a)(CH3-
CN)2][PF6] and [CpRu(5b)(CH3CN)][PF6] were selected as
precedents and indicated clearly that the biaryldiimine ligands
5a and 5b would adopt indeed atropoisomeric P and M confor-
mations (Sa and Ra, respectively) at the vicinity of metal ions.14,15
The complex [Cu(5a)(∆-2)] was prepared by ion exchange
metathesis of [Cu(5a)(CH3CN)2][PF6] and (-)-[4][∆-2] and
readily isolated by chromatography due to remarkable air and
moisture stability for a 16-electron species and noticeable
(11) Crystal data for (-)-[4][∆-2] ((C17H2Cl9NO6P)(C26H29N2O)-
(C3H6O)): Mr ) 1109.9, orthorhombic, P212121, a ) 11.5179(5) Å, b )
19.1156(11) Å, c ) 23.1645(11) Å, V ) 5100.2(4) Å3; Z ) 4, µ ) 0.580
mm-1, dexptl ) 1.445 g cm-3, Mo KR radiation (λ ) 0.710 73 Å), 64 539
reflections measured at 200 K, 9948 unique reflections, of which 4195 were
observed (|Fo| > 4σ(Fo)). Data were corrected for Lorentz and polarization
effects and for absorption (Tmin, Tmax ) 0.8971, 0.9427). The structure was
solved by direct methods (SIR97). All calculations were performed with the
(16) In a typical association experiment, a solution of [4][∆-2] (0.138
mmol) in acetone (4 mL) was added at 20 °C to a solution of [Cu(5a)-
(NCMe)2][PF6] (0.126 mmol) in dry N2-saturated CH2Cl2 (5 mL). The
resulting mixture was stirred for 5 min and then concentrated in vacuo.
Chromatography of the residue (SiO2, 1 × 7 cm, CH2Cl2) afforded [Cu-
(5a)(∆-2)] as a yellow solid (Rf ) 0.91, 72%).
(17) The corresponding PF6 and TRISPHAT salts are unstable. They are
air- and moisture-sensitive and cannot be purified by chromatography (SiO2).
(18) The atropisomerism of ligands 5 was studied at low and high
temperature by VT-NMR. Whereas no changes were observed at low
temperature, the occurrence of stereodynamics (coalescence around 343 K
of most signals) was monitored at elevated temperature for [Cu(5a)(∆-2)].
See the Supporting Information.
XTAL system. Full-matrix least-squares refinement based on F using
2
weights of 1/(σ2(Fo) + 0.0002(Fo )) gave the final values R ) 0.037, Rw
)
0.034, and S ) 1.65(2) for 636 variables; Flack parameter x ) -0.02(9).
CCDC-629076 contains the supplementary crystallographic data. These data
can be obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html
(or from the Cambridge Crystallographic Data Centre, 12 Union Road, Cam-
bridge CB2 1EZ, U.K.; fax (+ 44) 1223-336-033; email deposit@
ccdc.cam.ac.uk).
(19) Crystal data for [Cu(P-5a)(∆-2)] ((C43H18Cl13CuN3O6P)(CHCl3)2):
(12) TRISPHAT (1) adopts an octahedral geometry and a D3 sym-
metry: i.e., all P-O bond lengths (1.714 Å) and O-P-O bond angles
(90°) are identical.
(13) For a previous use of ligand 5b, see: Costa, A. M.; Jimeno, C.;
Gavenonis, J.; Carroll, P. J.; Walsh, P. J. J. Am. Chem. Soc. 2002, 124,
6929-6941. For a general review on the use of achiral ligands to convey
asymmetry in enantioselective catalysis, see: Walsh, P. J.; Lurain, A. E.;
Balsells, J. Chem. ReV. 2003, 103, 3297-3344.
(14) The salts [Cu(5a)(CH3CN)2][PF6] and [CpRu(5b)(CH3CN)][PF6]
were simply prepared by treatment of [Cu(CH3CN)4][PF6] and [CpRu(CH3-
CN)3][PF6] with the corresponding ligands 5a and 5b. For the preparation
of ruthenium precursor, see: Ku¨ndig, E. P.; Monnier, F. R. AdV. Synth.
Catal. 2004, 346, 901-904.
(15) The complex [Cu(5a)(CH3CN)2][PF6] is reminiscent of catalysts used
previously for enantioselective alkene aziridination reactions: Shi, M.;
Wang, C.-J. Chirality 2002, 14, 412-416. Gillespie, K. M.; Sanders, C. J.;
O’Shaughnessy, P.; Westmoreland, I.; Thickitt, C. P.; Scott, P. J. Org. Chem.
2002, 67, 3450-3458 and references therein.
Mr ) 1466.7, orthorhombic, P212121, a ) 14.4833(10) Å, b ) 19.3609-
(18) Å, c ) 20.7455(13) Å, V ) 5817.2(8) Å3; Z ) 4, µ ) 1.323 mm-1
,
dexptl ) 1.675 g cm-3, Mo KR radiation (λ ) 0.710 73 Å), 72 581 reflections
measured at 200 K, 11 264 unique reflections, of which 6024 were observed
(|Fo| > 4σ(Fo)). Data were corrected for Lorentz and polarization effects
and for absorption (Tmin, Tmax ) 0.7810, 0.8366). The structure was solved
by direct methods (SIR97). All calculations were performed with the XTAL
system. Full-matrix least-squares refinement based on F using weights of
2
1/(σ2(Fo) + 0.0002(Fo )) gave final values R ) 0.044, Rw ) 0.040, and S
) 1.46(1) for 677 variables; Flack parameter x ) 0.00(3). CCDC-629067
contains the supplementary crystallographic data for 1. These data can be
obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html (or
from the Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, U.K.; fax (+ 44) 1223-336-033; email deposit@
ccdc.cam.ac.uk).
(20) Stereocontrol within “classical” diastereomeric ion pairs is usually
highly dependent of the polarity of the solvent. See refs 3a,b and references
therein.

Communications
Organometallics, Vol. 26, No. 9, 2007 2143
Table 1. Synthesis and Properties of [CpRu(ligand)(∆-2)]
Zwitterionic Complexes
ligand
yield (%)
dra
drb
∆δmaxb (ppm)
6a
6b
7a
7b
70
71
54
60
72:27
89:11
89:11
95:05
80:20
91:09
92:08
96:04
0.33
0.73
0.71
0.70
a Conditions: 1H NMR, 500 MHz, CD2Cl2. b Conditions: 1H NMR, 500
MHz, toluene-d8 + 5% CD3NO2.
The compounds [CpRu(6)(∆-2)] and [CpRu(7)(∆-2)] were
prepared in a manner analogous to that for [CpRu(5b)(∆-2)].16
Slightly better yields were obtained for the formation of the
oxazoline over the benzoimidazole derivatives (70-71% vs 54-
60% from 6a,b and 7a,b, respectively).24 Significantly, both
1H and 13C NMR spectra revealed the complete displacement
of the acetonitrile ligands from the starting metal fragment. As
expected, an efficient enantiodifferentiation was achieved in the
presence of ∆-2, as dual sets of signals were obtained in both
1H and 31P NMR, the latter observation indicating slow exchange
kinetics of the chiral ions on the NMR time scale. Of all the
split signals, the higher frequency singlets of pyridine protons
H2 (Figures 1 and 3) were particularly easy to monitor and very
large differences in chemical shifts (∆δmax up to 0.73 ppm) were
observed, allowing a ready determination of the asymmetry
induction by integration of the respective signals. Good to
excellent selectivity was achieved for the two classes of ligands
(dr from 80:20 to 96:04) using nonpolar solvent conditions
(toluene-d8 + 5% CD3NO2), the solvent having little influence
over the diastereoselectivity. The ratios remained overall the
same with the more polar CD2Cl2. These observations are
summarized in Table 1, along with some spectroscopic informa-
tion.
Figure 2. tropos ligands: solution equilibrium among diastereo-
meric Cu(I) complexes and X-ray crystal structure of the zwitter-
ionic complex [Cu(P-5a)(∆-2)]. Ellipsoids are represented at the
50% probability level.
We have just described the synthesis and resolution of a novel
chiral hexacoordinated phosphate that behaves as an enantiopure
anionic N-ligand. This TRISPHAT-N anion, although binding
at a single point, acts as an effective chiral auxiliary able to
control with high selectivity the conformation of tropos ligands
and the configuration of stereogenic metal ions. Further studies
are being performed to exploit the asymmetric potential of anion
2 and the interesting chromatographic, air, and moisture stability
that it confers to Lewis acidic metal complexes.
Figure 3. Chirality at metal: stereocontrol among (SRu)-[CpRu-
(6a)(∆-2)] and (RRu)-[CpRu(6a)(∆-2)]. The priority sequence of
the ligands is η5-C5H5 > 2 > “imine” > pyridine.
with perfect mirror image symmetry (CH2Cl2, 4 × 10-5 M,
∆ꢀ397 +12 and -13 for [CpRu(5b)(∆-2)] and [CpRu(5b)(Λ-2)],
respectively), all data indicating the occurrence of a single
zwitterionic complex in solution.
Acknowledgment. We are grateful for financial support of
this work by the Swiss National Science Foundation and the
State Secretariat for Education and Science. We thank Prof.
Dr. Claude Piguet (Geneva, Switzerland) for a generous initial
gift of ligands 7.
Having established that anion 2 can control effectively the
conformation of tropos ligands bound to a metal center, we
decided to study the possibility of controlling the configuration
of the metal center itself using, as models, CpRu complexes of
achiral ligands 6 and 7 (Figures 1 and 3). These compounds
belong to the class of chiral organometallic half-sandwich
complexes made of unsymmetrical bidentate ligands and arene
metal fragments that have been strongly studied for their “chiral-
at-metal” properties.21 In the particular case of CpRu complexes
bearing diimino ligands, however, there is to our knowledge
only one report detailing the stereocontrol of the metal center
by an enantiopure pyridine imine ligand; a moderate level of
selectivity was achieved under kinetic control (dr 56:44).22,23
In view of this precedent, it was decided to study the
stereocontrol of this challenging class of (η5-C5H5)Ru moieties.
Supporting Information Available: CIF files giving crystal
data for [4][∆-2] and [Cu(P-5a)(∆-2)], text giving spectroscopic
data for the salts [nBu3NH][rac-2], [4][∆-2], [nBu4N][∆-2], and [n-
1
Bu4N][Λ-2], and figures giving H and 31P NMR spectra of the
aforementioned organometallic complexes. This material is available
free of charge via the Internet at http://pubs.acs.org.
OM070074K
(23) With the more sterically demanding Cp* as the arene, better
selectivity (dr up to 91:9) can be achieved under kinetic or thermodynamic
control; see ref 22 and Koelle, U.; Bucken, K.; Englert, U. Organometallics
1996, 15, 1376-1383.
(24) Torelli, S.; Delahaye, S.; Hauser, A.; Bernardinelli, G.; Piguet, C.
Chem. Eur. J. 2004, 10, 3503-3516. Charbonniere, L. J.; Williams, A. F.;
Piguet, C.; Bernardinelli, G.; Rivara-Minten, E. Chem. Eur. J. 1998, 4, 485-
493. Charbonniere, L. J.; Williams, A. F.; Frey, U.; Merbach, A. E.;
Kamalaprija, P.; Schaad, O. J. Am. Chem. Soc. 1997, 119, 2488-2496.
(21) Ganter, C. Chem. Soc. ReV. 2003, 32, 130-138. Brunner, H. Eur.
J. Inorg. Chem. 2001, 905-912. Brunner, H. Angew. Chem., Int. Ed. 1999,
38, 1194-1208.
(22) Brunner, H.; Klankermayer, J.; Zabel, M. Organometallics 2002,
21, 5746-5756.