Enantioselective hydrogenation catalysis aided by a σ-bonded calix[4]arene to a p-chirogenic aminophosphane phosphinite rhodium complex

Article abstract of DOI:10.1021/om100520u

The first P-chirogenic aminophosphane-phosphinite (AMP*P) ligand (4a) supported on the upper rim of a calix[4]arene moiety was synthesized in two steps using the ephedrine methodology. Ligand 4a was used for the preparation of the corresponding rhodium co

Full text of DOI:10.1021/om100520u

3622 Organometallics 2010, 29, 3622–3631
DOI: 10.1021/om100520u
Enantioselective Hydrogenation Catalysis Aided by a σ-Bonded
Calix[4]arene to a P-Chirogenic Aminophosphane Phosphinite
Rhodium Complex†
‡
‡
Naıma Khiri,‡ Etienne Bertrand,‡,§ Marie-Joelle Ondel-Eymin, Yoann Rousselin,
€
Jerome Bayardon, Pierre D. Harvey,* and Sylvain Juge*
‡
,§
,‡
ꢀ ^
ꢀ
‡
ꢀ
Institut de Chimie Moleculaire de l’Universite de Bourgogne, UMR CNRS 5260, 9 Avenue Alain Savary BP
47870, 21078 Dijon Cedex, France, and Departement de Chimie, Universite de Sherbrooke, Sherbrooke,
ꢀ
ꢀ
§
ꢀ
Queꢀbec, Canada J1K 2R1
Received May 27, 2010
The first P-chirogenic aminophosphane-phosphinite (AMP*P) ligand (4a) supported on the
upper rim of a calix[4]arene moiety was synthesized in two steps using the ephedrine methodology.
Ligand 4a was used for the preparation of the corresponding rhodium complex [Rh(COD)-
(AMP*P)]BF4 (5a) (COD=1,8-cyclooctadienyl), which was tested for asymmetric catalyzed hydro-
genation of various substrates. The structures of the AMP*P ligand as diborane and rhodium
complexes 3a and 5a were established by X-ray analysis. The asymmetric hydrogenation catalyzed
with the Rh complex 5a exhibits excellent enantioselectivities up to 98%. Investigation of modified
P-chirogenic aminophosphane-phosphinite ligands 4b,c, bearing an isoelectronic or a sterically
similar substituent on the P-chirogenic aminophosphane unit, demonstrates that the calix[4]arene
substituent of the aminophosphane moiety plays a major role in the better asymmetric induction. The
enantioselectivity of the catalyzed hydrogenation was weakly influenced by the hydrogen pressure,
which is in good agreement with a stereodetermining step involving the substrate-rhodium
complexes. Computer modeling indicated the presence of two conformers for the active AMP*P
rhodium species, according to whether the rhodium metal is outside or inside the calix[4]arene cavity
(called outer and inner). It is obvious that the complexation of the substrate with the active rhodium
species forces this complex to adopt fully the outer conformation and hence explains why the
calixarene fragment plays a key role in the stereodetermining step.
Introduction
restricted by the availability of a library of chiral ligands7
or by the structure modification of an efficient lead series
such as BINAP,8 DUPHOS,9 PHOX,10 monophos,11
bisP*,12 and SDP.13
Aminophosphane phosphinites (AMPP) are also conveni-
ent chiral ligands capable of improving highly steroselective
Asymmetric catalysis using chiral transition metal com-
plexes is a powerful method for the synthesis of chiral
substances, in laboratory scale as well as industrially.1-4
So far, mostly chiral catalysts were prepared by complexa-
tion of a chiral organophosphorus ligand and a transition
metal.5,6 However, improving an asymmetric catalytic reac-
tion for a new substrate is never trivial and is mainly
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2000, 122, 11539–11540. (b) van den Berg, M.; Minnaard, A. J.; Haak, R. M.;
Leeman, M.; Schudde, E. P.; Meetsma, A.; Feringa, B. L.; de Vries, A. H. M.;
Maljaars, C. E. P.; Hyett, D.; Willans, C. E.; Boogers, J. A. F.; Henderickx,
H. J. W.; de Vries, J. G. Adv. Synth. Catal. 2003, 345, 308–323.
† This paper is dedicated to Prof. H. Kagan for his 80th birthday.
*To whom correspondence should be addressed. E-mail: Sylvain.Juge@
u-bourgogne.fr. Tel: þ33 (0)3 80 39 61 13. E-mail: Pierre.Harvey@
USherbrooke. Tel: 1-819-821-7092.
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r
pubs.acs.org/Organometallics
Published on Web 07/23/2010
2010 American Chemical Society

Article
Organometallics, Vol. 29, No. 16, 2010 3623
catalysis, because libraries of such compounds can easily be
synthesized from available chiral amino alcohols in a few
steps.14-16 Numerous works have demonstrated the efficiency
of the synthesis of chiral AMPP ligands that can be applied to
asymmetric catalyses from their corresponding Rh, Ru, Pd, or
Ni complexes.14b,16,17 Recently, we and other groups have
independently described a series of P-chirogenic AMP*P
ligands derived from ephedrine, for catalytic asymmetric hydro-
genation and hydroformylation reactions involving rhodium
complexes18,19
Over the past decades, phosphorus ligands containing
calix[n]arenes have also received extensive attention for their
coordination chemistry and in transition metal catalysis.20
The use of calix[4]arene-based phosphorus ligands in cata-
lysis has been more recently recognized for their potential
applications and has already been evaluated in olefin
hydroformylation,21 oligomerization and polymerization
reactions,22 hydrogenation,21a,23 olefin oxidation,24 carbon-
carbon bond forming reactions,25 and allylic alkylation.26
So far, many chiral organophosphorus ligands derived
from calix[n]arene are known,20-26 but only a few asym-
metric catalyses were described.23 We now report herein the
first stereoselective synthesis of a P-chirogenic AMP*P
ligand with a calix[4]arene as substituent of the amino-
phosphane moiety along with an investigation of a
Rh(I)-catalyzed asymmetric hydrogenation. It is clearly
demonstrated that the calix[4]arene plays a key role in the
enantioselectivity.
Results and Discussion
P-Chirogenic aminophosphane-phosphinite ligand 4a is
prepared in two steps from the (þ)-oxazaphospholidine
borane 1, derived from (-)-ephedrine, according to the
general procedure described for the AMP*P.19 The reaction
of the starting complex 1 with the 25,26,27,28-tetrapro-
poxycalix[4]aren-5-yl lithium reagent leads, after P-O bond
cleavage, to the ring-opening alcoholate intermediate 2a,
which is trapped with chlorodiphenylphosphane. Subse-
quently, it is further trapped with borane to afford the
AMP*P in 62% yield as diborane complex 3a (Scheme 1).
The structure of the calix[4]arene-containing AMP*P
diborane 3a has been determined by X-ray diffraction meth-
ods, and the ORTEP view is shown in Figure 1. The calix-
[4]arene substituent adopts a flattened cone conformation in
the solid state due to the presence of the propoxy groups in
the lower rim. The compound exhibits an unfolded confor-
mation of the AMP*P chain with a flattened nitrogen
pyramidal structure and the P-B bonds disposed anti from
one another. The unit cell contains four independent mole-
cules with similar conformations. The S absolute configura-
tion of the aminophosphane borane fragment is consistent
with the retention of configuration previously reported for
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3624 Organometallics, Vol. 29, No. 16, 2010
Scheme 1. Synthesis of the P-Chirogenic Aminophosphane-Phosphinite Ligands 4a-c
Khiri et al.
the ring-opening cleavage of the starting complex 1 on
treatment with an organolithium reagent (Scheme 1).19
The decomplexation of borane complex 3a was achieved
with retention of configuration on the phosphorus atom,
upon heating with 1,4-diazabicyclo[2,2,2]octane (DABCO)
in toluene at 50 °C. The free uncoordinated P-chirogenic
aminophosphane-phosphinites 4a was then obtained by
short filtration on neutral alumina (Scheme 1).
P2-Rh bond. This conformation features the C7 and C23
phenyl phosphorus substituents in axial positions, but the dis-
tortion of the chelated ring induces a clear facial dissymmetry for
the complex. In addition, the presence of the C22 methyl group
and cyclooctadiene ligand forces the calix[4]arene group to be
situated in the syn position in relation to the P2-C23 axial bond.
First, the rhodium-catalyzed asymmetric hydrogenation
of methyl 2-acetamidocinnamate 6a was used to determine
the catalytic behavior of the new P-chirogenic AMP*P
ligand 4a. Initial hydrogenation experiments were performed
at 1 bar of hydrogen pressure in methanol, using 3 mol % of
[Rh(COD)(AMP*P)]BF4 5a. In these conditions, the hydro-
genation of the substrate 6a was total, and the (R)-N-acetyl-
phenylalanine methyl ester 7a was obtained with 76% ee
(Table 1, entry 1). This relative high ee compelled us toward
further optimization. The influence of the solvent on the
enantioselectivity was then investigated, as previously reported
by many authors,27 and the results are also summarized in
Table 1. In THF and CH2Cl2, the (R)-phenylalanine derivative
7a is obtained in 95% and 85% ee, respectively (Table 1, entries
2, 3). In the case where toluene or benzene is used, the
enantioselectivities reach 97% or 98% ee, respectively (entries
4, 5). At last, when the reaction is performed under higher
pressure (15 or 40 bar), the hydrogenated product is always
obtained with full conversion, but with slightly lower ee, i.e.,
95% and 87%, respectively (Table 1, entries 6, 7).
The precatalyst 5a was also investigated in the asymmetric
hydrogenation of various substrates 6b-d in benzene, and
the experimental results are reported in Table 2. The hydro-
genation of dimethyl itaconate 6b under 1 bar of H2 pressure
in benzene affords the (S)-dimethyl 3-methylsuccinate 7b
in low conversion (10%, Table 2, entry 1). However, under
15 bar of hydrogen pressure, the conversion was total, and
the product (S)-7b was obtained with ee up to 43% (entry 2).
The hydrogenation of methyl 2-acetamidoacrylate 6c under
the same reaction conditions leads to the (R)-alanine deri-
vative 7c with lower enantioselectivity (ee 34%, entry 3). The
calix[4]arenyl-AMP*P ligand 4a was also used for the asym-
metric hydrogenation of the industrial substrate 6d, which
is the precursor of levetiracetam, useful for the treatment
of epilepsy and other neurological disorders.28 When the
In order to investigate the role of the calix[4]arene back-
bone in asymmetric induction, two AMP*P ligand models,
4b and 4c, bearing isoelectronic or sterically similar substit-
uents, were prepared using the same methodology starting
from (-)-ephedrine described above (Scheme 1). Thus, the
AMP*P 4b and 4c were obtained with overall yields of 42%
and 25%, respectively, by reaction of the corresponding m-
xylyl- or m-dimethyl-p-propoxyphenyllithium reagent R1Li
with the (þ)-oxazaphospholidine borane complex 1(Scheme 1).
The three P-chirogenic aminophosphane-phosphinites
4a-c were then tested as ligands in the rhodium-catalyzed
asymmetric hydrogenation of various prochiral substrates 6
(Tables 1, 2). The [Rh(COD)2]BF4 precursor was used to
prepare the corresponding chiral Rh complexes with the
AMP*P ligands 4a-c. The reaction of 0.9 equiv of [Rh-
(COD)2]BF4 with the ligands 4a-c in dichloromethane
provides the cationic rhodium complexes [Rh(COD)(AMP*P)]-
BF4 5a-c as air-stable orange powders, in good to excellent
yields (52-92%; Scheme 2). The structure of the cationic
complex 5a was established by X-ray crystallography, and the
ORTEP view is shown in Figure 2. The P-chirogenic aminopho-
sphane moiety shows the Rabsolute configuration, which proves
the retention of configuration of the decomplexation for
AMP*P-diborane 4a. On the other hand, the coordination
sphere about the rhodium atom exhibits a distorted square-
planar geometry with a P1-Rh-P2 angle of 91.18(5)°, and
two other vertices are coordinated by the 1,5-cyclooctadiene
η2-bonded double bonds. The dihedral angles between the planes
defined by P1-Rh-P2 and either C72-Rh-C76 or C71-
Rh-C75 are 8.15(21)° and 42.10(15)°, respectively. Interest-
ingly, the seven-membered Rh-AMP*P chelate ring adopts a
boat-like conformation, with a slight distortion of -12.71(38)°
for the O1-C13-N1-P2 dihedral angle and where the substit-
uents of the ephedrine backbone (i.e., Ph, Me) are located at the
equatorial positions. As a consequence, the H-C20 bond points
(27) (a) Ohkuma, T.; Kitamura, M.; Noyori, R. In Catalytic Asym-
metric Synthesis, 2nd ed.; Ojima, I., Ed.; VCH Publishers Inc.: New York,
2000; pp 1-110. (b) Brown, J. M. In Comprehensive Asymmetric Catalysis;
Jacobsen, E. N.; Pfaltz, A.; Yamamoto, H., Eds.; Springer: Berlin, 1999;
in the direction of the rhodium atom with a H Rh distance of
3 3 3
˚
2.913 A. Noteworthy, the sum of the angles around the N atom
ꢀ
ꢀ
Vol. 1, pp 121-182. (c) Nogradi, M. Stereoselective Synthesis; VCH:
(i.e., 356.57°) indicates an almost flattened geometry, which
places the C22 methyl group on a side face of the tetrahedral
phosphorus center and in the anti position with respect to the
Weinheim, 1987; p 53.
(28) Ates C.; Surtees, J.; Burteau, A. C.; Marmon, V.; Cavoy, E. WO
03/014080 A2, 2003.

Article
Organometallics, Vol. 29, No. 16, 2010 3625
Table 1. Asymmetric Catalyzed Hydrogenation of Methyl
2-Acetamidocinnamate (6a) in the Presence of
[Rh(COD)(calix[4]arenyl-AMP*P 4a)]BF4 (5a)a,b
entry
pH2 (bar)
solvent
ee (%)c,d
1
2
3
4
5
6
7
1
1
1
1
1
MeOH
THF
76
95
85
97
98
95
87
CH2Cl2
toluene
benzene
benzene
benzene
15
40
a All reactions were carried out at room temperature with 3 mol % of
Rh complex 5a and 0.5 mmol of substrate. b In all cases, complete
conversion was achieved. c Determined by HPLC with a Chiralcel OD-H
column. d R absolute configuration.
hydrogenation in the presence of 5a leads to (S)-dimethyl
3-methylsuccinate in 43% ee, whereas lower enantioselectivities
are obtained with the complexes 5b and 5c (4% and 0% ee,
respectively; entries 5, 6). Morover, the benefic effect of the calix-
[4]arene AMP*P 4a on the asymmetric catalysis is also observed
for the industrial susbstrate 6d, which affords the hydrogenated
product 7d with 57% ee, when the ligands 4b and 4c exhibit only
16 and 19% ee, respectively (entries 10-12). On the other hand,
the asymmetric catalyzed hydrogenation of the methyl 2-acet-
amidoacrylate 6c showed little significant effect of the R1-substit-
uents on the ligand, since the alanine derivative 7c was obtained
with enantiomeric excesses close to 37% for the AMP*P ligands
4a-c (entries7-9). Noteworthy, the comparison of the observed
enantioselectivity for substrates 6a and 6c (R2 = Ph and H, res-
pectively) illustrates the importance of the phenyl group in the
stereodetermining step. Indeed for substrate 6c, no significant
changes were observed in the enantioselectivity regardless of
the nature of the AMP*P-containing ligand used (entries 1, 2, 3
vs 7, 8, 9).
Figure 1. ORTEP view of the AMP*P-diborane complex 3a.
Thermal ellipsoids are set at the 50% probability level. Hydro-
gen atoms have been omitted for clarity. Selected bond lengths
˚
[A], angles [deg], and dihedral angles [deg]: P1-B1 1.897(4),
P2-B2 1.907(4), P2-N1 1.668(2), P1-O1 1.612(2); C20-
N1-P2 121.5(2), C22-N1-P2 121.2(2); C22-N1-C20
116.5(2), B2-P2-N1-C22 170.9(2), B2-P2-C23-C24 7.7(3),
O1-C13-C20-N1 178.9(2), B2-P2-C29-C30 97.8(3), B2-
P2-C29-C34 85.3(3).
asymmetric hydrogenation of 6d was performed in methanol
or benzene under 15 bar of H2 pressure, the reaction was
total, and the product (R)-7d was obtained with 56% and
57% ee, respectively (entries 4, 5). Finally, the best asym-
metric induction was obtained using THF as solvent, affording
thus the hydrogenated product (R)-7d with 71% ee (entry 6).
In order to shine light on the role of the calix[4]arene
substituent in this asymmetric induction, the hydrogenation
of the substrates 6a-c was performed in benzene and under
15 bar of H2 pressure, using the Rh complexes 5a-c prepared
from the corresponding isoelectronic or sterically similar
substituted AMP*P ligands 4a-c (Table 3). In the presence
of the complex 5a, the methyl 2-acetamidocinnamate 6a is
hydrogenated to (R)-phenylalanine derivative 7a with 95%
ee (entry 1). Conversely, 5b and 5c give lower enantioselec-
tivities of 66% and 47% ee, respectively (entries 2, 3). First, it
should be noted that the asymmetric induction decreases in
the presence of the propoxy group at the para position of the
AMP*P substituent. Indeed, ligand 4c leads to a lower ee
than the 3,5-xylyl-substituted ligand 4b (66% ee vs 47% ee,
entries 2, 3). Surprisingly, this decreasing effect is likely
overcome by the influence of the calix[4]arene substi-
tuent, bearing a propoxy at the para position, since the
ligand AMP*P 4a leads to 95% ee under the same conditions
(entry 1). In the case of dimethyl itaconate 6b, the asymmetric
In order to provide an explanation for the difference in
asymmetric induction between the Rh complexes 5a, 5b, and
5c, computer models were examined. Although the X-ray
structure reveals the presence of the Rh fragment located
outside the calix[4]arene cavity (Figure 2), the other possibi-
lity with the Rh moiety inside the cavity may exist based
on the other complexes containing the calix[4]arene unit
(Scheme 3a,b).20c
This is well exemplified in Figure 3 where two models
of calix[4]arenyl-AMP*P/RhCl2 were computed (outer and
inner). The outer model exhibits the lowest calculated total
energy (only by a slim value, 5.1 kJ mol-1), consistent with
the X-ray structure presented in Figure 2.
For the [Rh(COD)(calix[4]arenyl-AMP*P)]BF4 complex
5a, the elimination of the COD must also lead to a similar
outer/inner equilibrium. For the inner conformation, the un-
saturated rhodium complex 8 can be protected from solvent
coordination by the shielding effect of the calix[4]arene
cavity (Figure 3). It should be noted that the chirality of
complex 8 in the inner conformation is obvious, as shown in
the space-filling model (Figure 3, right). Finally, both con-
formations may exist and their relative population (inner vs
outer) must depend on the coordinating solvent.
From a mechanistic point of view, this series of AMP*P
ligands are interesting for the understanding of the interactions

3626 Organometallics, Vol. 29, No. 16, 2010
Khiri et al.
Table 2. Asymmetric Catalyzed Hydrogenation of the Substrates 6b-d in the Presence of Complex [Rh(COD)(calix[4]-
arenyl-AMP*P)]BF4 (5a)a
a All reactions were carried out at room temperature with 3 mol % of Rh complex 5a and 0.5 mmol of substrate. b Determined by 1H NMR.
c Determined by HPLC on a chiral column. d The reaction was carried out at 1 bar.
leading to product 7 (Scheme 4).30 Finally, the difference bet-
Scheme 2. Preparation of [Rh(COD)(AMP*P)]BF4 5a, 5b,
and 5c.
ween the unsatured and the dihydride pathway results mainly
from the influence of the hydrogen pressure on the enantio-
selectivity. Thus, when the enantioselectivy was weakly influ-
enced or decreased with an increase in hydrogen pressure, the
former mechanism was invoked. Conversely, when the enantio-
selectivity increases with the hydrogen pressure, the stereode-
termining step is the dihydro-rhodium-substrate complex 10
step (dihydro route).
Interestingly, when the hydrogenation of the substrate 6a
was performed at 1, 15, and 40 bar of H2 pressure, using 3
mol % of [Rh(COD)(AMP*P)]BF4 5a complex, the (R)-N-
acetylphenylalanine methyl ester 7a was obtained with 98%,
95%, and 87% ee, respectively (Table 1, entries 5, 6, 7).
Moreover for substrate 6b, the Rh-catalyzed hydrogenation
under 1 and 15 bar of hydrogen pressure leads to the product
(R)-7b with the same enantioselectivity (Table 2, entries 1, 2).
Consequently, these results are consistent with the mechan-
ism using the unsaturated route presented in Scheme 4. In
this case, the enantioselectivity is directed by the formation
of the Rh-substrate complex 9, where the presence of the
calix[4]arenyl substituent plays an obvious role. It is reason-
able to think that the complexation of substrate 6 with the
unsaturated rhodium complex 8, on the re- or the si-face,
respectively, forces the corresponding complexes 9 to adopt
the outer conformation for obvious steric reasons (Scheme 4).
occurring between the prochiral substrate and the Rh-(calix-
[4]arenyl-AMP*P) complexes 5, 8, and 9, owing to the mod-
ification on the aminophosphine moiety. The modified AMP*P
ligands 4b and 4c, bearing either the m-xylyl or m-dimethyl-p-
propoxyphenyl substituent, respectively, afford lower asym-
metric induction than 4a. This observation rules in favor of the
key role of the calix[4]arenyl moiety on the stereoselectivity.
Multiple works focused on the origin of the enantioselectivity
of the Rh-catalyzed hydrogenation, and for a long time, it was
considered that the enantioselectivity does not stem from the
relative stability of the substrate rhodium complexes, but from
their rate constants of the oxidative addition of H2 to the
dihydro derivative (unsatured route), such as 9 or 10, respec-
tively (Scheme 4).29 However, other experimental and compu-
tational data supported a second reaction pathway via a fast
equilibrium of the dihydride substrate complexes such as 10,
followed by the stereodetermining migration insertion step
(30) (a) Landis, C. R.; Feldgus, S. Angew. Chem., Int. Ed. 2000, 39,
2863–2866. (b) Gridnev, I. D.; Higashi, N.; Asakura, K.; Imamoto, T. J. Am.
Chem. Soc. 2000, 123, 7183–7194. (c) Giernoth, R.; Heinrich, H.; Adams,
N. J.; Deeth, R. J.; Bargon, J.; Brown, J. M. J. Am. Chem. Soc. 2000, 122,
12381–12382. (d) Gridnev, I. D.; Imamoto, T. Organometallics 2001, 20,
545–549. (e) Heinrich, H.; Giernoth, R.; Bargon, J.; Brown, J. M. J. Chem.
Soc., Chem. Commun. 2001, 1296–1297. (f) Gridnev, I. D.; Higashi, N.;
Imamoto, T. Organometallics 2001, 20, 4542–4553. (g) Gridnev, I. D.;
Yasutake, M.; Higashi, N.; Imamoto, T. J. Am. Chem. Soc. 2001, 123, 5268–
(29) (a) Brown, J. M.; Chaloner, P. A. J. Am. Chem. Soc. 1980, 102,
3040–3048. (b) Chan, A. S. C.; Halpern, J. J. Am. Chem. Soc. 1980, 102,
838–840. (c) Chan, A. S. C.; Pluth, J. J.; Halpern, J. J. Am. Chem. Soc. 1980,
102, 5952–5954. (d) Chua, P. S.; Roberts, N. K.; Bosnich, B.; Okrasinski,
S. J.; Halpern, J. J. Chem. Soc., Chem. Commun. 1981, 102, 1278–1280. (e)
Landis, C. R.; Halpern, J. J. Am. Chem. Soc. 1987, 109, 1746–1754. (f)
Nagel, U.; Rieger, B. Organometallics 1989, 8, 1534–1538. (g) Giovannetti,
J. S.; Kelly, C. M.; Landis, C. R. J. Am. Chem. Soc. 1993, 115, 4040–4057.
(h) Landis, C. R.; Hilfenhaus, P.; Feldgus, S. J. Am. Chem. Soc. 1999, 121,
8741–8754.
ꢀ
5376. (h) Crepy, K. V. L.; Imamoto, T. Adv. Synth. Catal. 2003, 345, 79–
101. (i) Gridnev, I. D.; Imamoto, T. Acc. Chem. Res. 2004, 37, 633–644.

Article
Organometallics, Vol. 29, No. 16, 2010 3627
Figure 2. ORTEP view of the cationic [(COD)Rh(AMP*P)]BF4 complex 5a. The thermal ellipsoids are at the 50% probability level.
Hydrogen atoms, except for those located on C20 and C13 carbon atoms, BF4 counterion, and solvent molecules, have been omitted for
˚
clarity. Selected bond lengths [A], angles [deg], and dihedral angles [deg]: P1-O1 1.628(4), P2-N1 1.676(5), P1-Rh 2.2732 (10),
P2-Rh 2.3146(13), Rh-HC20 2.913; P1-Rh-P2 91.18(5); O1-C13-N1-P2 -12.71(38), P1-O1-C13-C14 -179.23(32), P1-
O1-C20-C21 118.57(62), phenyl planes C7-C12 and C23-C28 13.05(37).
oxidatively added dihydro derivatives 10, which ultimately
leads to the major product 7 (Scheme 4). Noteworthy, the
interaction model proposed for substrates 6a-d in the co-
ordination sphere of the rhodium complex 9 explains the
enantioselectivity of the corresponding product 7, i.e., (R)-7a,
(S)-7b, (R)-7c, and (R)-7d (Scheme 4). Finally, the rhodium
complex 8, reformed from the elimination of the hydro-
genated product 7, most likely adopts again the inner con-
formation prior to a subsequent complexation with another
substrate, 6 (Scheme 4).
Table 3. Asymmetric Rh-Catalyzed Hydrogenation Using the
AMP*P 4a-ca,b
Conclusion
The first synthesis of a P-chirogenic aminophosphane-
phosphinite (AMP*P) ligand supported on the upper
rim of a calix[4]arene moiety was achieved in two steps, using
the ephedrine methodology. Two other AMP*P models,
bearing an isoelectronic or sterically similar substituent to
the calix[4]arene fragment, were prepared using the same
ephedrine methodology. These ligands were used in a Rh-
catalyzed asymmetric hydrogenation of prochiral unsatu-
rated substrates, reaching excellent activities and enantio-
selectivities up to 98% for the AMP*P bearing the calix[4]-
arene substituent on the P-center. The enantioselectivity of
the catalyzed hydrogenation, which was weakly influenced
or slightly decreased with the hydrogen pressure, is consis-
tent with the unsaturated route and a stereodetermining
step involving the substrate-rhodium complexes. Computer
models indicate the presence of two conformers for the active
AMP*P rhodium species, where the rhodium metal is either
outside or inside the calix[4]arene cavity (outer or inner, re-
spectively). It is obvious that the complexation of the substrate
with the active rhodium species forces this one to completely
a All reactions were carried out in benzene at room temperature with
3 mol % of catalyst 5a, 5b, or 5c and 0.5 mmol of substrate, under 15 bar
of H2. b In all cases, complete conversion was achieved. c Determined by
HPLC (Chiralcel OD-H, OD).
Indeed, diasteromeric substrate-rhodium complexes 9 and 90
are structurally completely different, and finally the presence of
the bulky calix[4]arenyl substituent amplifies this difference
with respect to the simple phenyl substituent on the phosphinite
moiety (Scheme 4). A full analysis to address the relative
amount or stability of substrate-rhodium complexes 9 and 90
cannot be provided at this stage. Subsequently, the faster addi-
tion of hydrogen to complex 9 provides the corresponding

3628 Organometallics, Vol. 29, No. 16, 2010
Khiri et al.
Figure 3. Left and center: Space-filling representation of the calix[4]arenyl-AMP*P/RhCl2 computed models where the RhCl2 unit is
placed either outside (outer) or inside (inner) the cavity. Right: Space-filling model of the inner calix[4]arenyl-AMP*P/Rh computed
model stressing the relative dimension of the opening on both sides of the intermediate structure and, therefore, chirality.
Scheme 3. Two Possible Conformations for Complexe 5a with the Rh Moiety: (a) outer; (b) inner
Scheme 4
adopt the outer conformation. This process explains why the
calixarene fragment plays a key role in the stereodetermining
step.
and dried by azeotropic shift of toluene on a rotary evaporator.
[Rh(COD)2]Cl2 was purchased from Strem and used as received.
The methyl R-acetaminocinnamate 6a and methyl R-acetamino-
acrylate 6c were prepared from their corresponding acids,
using trimethylsilyldiazomethane reagent.31 The substrate 6d was
prepared according to a literature procedure.32 The precatalyst
complex [Rh(COD)2]BF4 was prepared following a modified
procedure of Schrock and Osborn.33 The 5-bromo-25,26,27,28-
tetrapropoxycalix[4]arene34 and 5-bromo-2-propoxy-1,3-dimethyl-
phenyl35 were prepared according to literature procedures.
Experimental Section
General Procedures. All reactions were carried out under an
argon atmosphere in dried glassware with magnetic stirring.
Solvents were dried prior to use. Tetrahydrofuran (THF),
toluene, benzene, and diethyl ether (Et2O) were distilled from
sodium/benzophenone and stored under argon. Methanol (Me-
OH) was distilled from sodium. Dichloromethane (CH2Cl2) was
distilled from CaH2. Hexane and propan-2-ol for HPLC were of
chromatographic grade and used without further purification.
s-Butyllithium (1.4 M in cyclohexane), tert-butyllithium (1.6 M
€
(31) Presser, A.; Hufner, A. Monatsh. Chem. 2004, 135, 1015–1022.
(32) (a) Ates, C., Surtess, J., Marmon, V., Burteau, A. C., Cavoy, E.
PCT WO 03/014080 A2. (b) Surtess, J., Marmon, V., Differding, E.,
Zimmermann, V. PCT WO 0164637 A1. (c) Schreiber, M. J. Ann. Chim.
1947, 84–117.
in pentane), 5-bromo-1,3-dimethylphenol, 1-bromo-m-xylene, BH3
3
(33) Schrock, R. R., Osborn, J. A. J. Am. Chem. Soc. 1971,
2397-2407 and 3083-3091.
SMe2, chlorodiphenylphosphane, R-acetamidocinnamic acid,
R-acetamidoacrylic acid, trimethylsilyldiazomethane, dimethyl
itaconate 6b, and 1,4-diazabicyclo[2.2.2]octane (DABCO) were
purchased from Aldrich, Acros, or Alfa Aesar and used as
received. (þ)- and (-)-Ephedrine were purchased from Aldrich
ꢀ
(34) Vezina, M.; Gagnon, J.; Villeneuve, K.; Drouin, M.; Harvey,
P. D. Organometallics 2001, 20, 273–281.
(35) Larsen, M.; Krebs, F. C.; Harrit, N.; Jorgensen, M. J. Chem
Soc., Perkin Trans. 2 1999, 1749–1757.

Article
Organometallics, Vol. 29, No. 16, 2010 3629
(2R,4S,5R)-(þ)-3,4-Dimethyl-2,5-diphenyl-1,3,2-oxazaphospholi-
dine-2-borane 1 was prepared from (-)-ephedrine, as previously
described.36 Reactions were monitored by thin-layer chromatogra-
phy (TLC) using 0.25 mm E. Merck precoated silica gel plates.
Visualization was accomplished with UV light and/or appropriate
staining reagents. Flash chromatography was performed with the
indicated solvents using silica gel 60 (particle size 0.035-0.070).
NMR spectra (1H, 13C, and 31P) were recorded on Bruker DRX
500 or Avance 300-600 MHz spectrometers. Chemical shifts are
reported in ppm relative to 85% H3PO4 (31P) as an external
standard. Data are reported as s=singlet, d = doublet, t = triplet,
q=quartet, m=multiplet, br s=broad singlet, integration, coupling
constant(s) in Hz. Melting points were measured on a Kofler bench
melting point apparatus and are uncorrected. Optical rotation
values were determined at 20 °C on a Perkin-Elmer 341 polarimeter.
Mass spectral analyses were performed on a Bruker Daltonics
OPr), 76.6 (s, CH2O, OPr), 57.4 (dd, J = 11.4, 8.2 Hz, CH-CH3),
30.9 (s, ArCH2Ar), 30.8 (s, ArCH2Ar), 28.7 (d, J = 4.5 Hz,
CH3N), 23.4 (s, CH2CH3, OPr), 23.1 (s, CH2CH3, OPr), 23.0 (s,
CH2CH3, OPr), 16.3 (s, CH3CH), 10.6 (s, CH3, OPr), 10.6
(s, CH3, OPr), 10.0 (s, CH3, OPr), 9.9 (s, CH3, OPr). 31P
NMR (CDCl3, 121 MHz): δ 106.2 (P-O), 70.4 (P-N). ESI-MS:
m/z (%) = 1098.6 (100) [M þ Na]þ, 1114.5 (18) [M þ K]þ. Anal.
Calcd for C68H81B2NO5P2 (1075.94): C, 75.91; H, 7.59; N, 1.30.
Found: C, 75.69; H, 7.54; N, 1.30.
(SP)-(-)-{[(1S,2R)-2-(Diphenylphosphinitoborane)-1-methyl-
2-phenylethyl](methyl)amino}{[3,5-dimethyl-4-propoxy]phenyl}phos-
phaneborane, 3c. This compound was prepared using the same
procedure as for AMP*P 3a, using 5-bromo-2-propoxy-1,3-di-
methylphenyl (2 g, 8.22 mmol) to generate the corresponding
organolithium reagent. Yield: 43%. White solid. Mp = 124-
126 °C. Rf=0.27 (toluene/petroleum ether, 1:1). [R]25D=þ58.6 (c
1
ꢀ
microTOF-Q apparatus at Universite de Bourgogne. Elemental
analyses were measured at the Microanalysis Laboratory of the
0.5, CHCl3). H NMR (CDCl3, 300 MHz): δ 7.68-7.61 (m, 2H,
CHarom), 7.47-7.35 (m, 3H, CHarom), 7.29-7.16 (m, 7H, CHarom),
7.10-6.96 (m, 8H, CHarom), 6.54 (td, 2H, J = 8.1, 1.2 Hz, CHarom),
5.29 (t, 1H, J = 9.3 Hz, CHO), 4.48 (m, 1H, CHCH3), 3.67 (t, 2H,
J = 6.6 Hz, CH2O, OPr), 2.20 (d, 3H, J = 7.8 Hz, CH3N), 2.16 (s,
6H, CH3Ar), 1.75 (m, 2H, CH2CH3, OPr), 1.25 (d, 3H, J = 6.6 Hz,
CH3CH), 0.99 (t, 3H, J=7.2Hz, CH3, OPr). 13CNMR(CDCl3, 75
MHz): δ 138.1 (s, Carom), 133.2 (d, J = 11.2 Hz, CHarom), 131.7 (d,
J = 4.5 Hz, CHarom), 131.6 (d, J = 5.9 Hz, CHarom), 131.3 (s,
CHarom), 131.2 (s, Carom), 131.1 (d, J = 11.2 Hz, CHarom), 128.7 (s,
CHarom), 128.7 (d, J = 5.9 Hz, CHarom), 128.5 (d, J = 4.4 Hz,
CHarom), 128.2 (s, CHarom), 127.9 (d, J = 7.1 Hz, CHarom), 127.8 (d,
J=7.2 Hz, CHarom), 83.3 (dd, J = 11.9, 2.5 Hz, CHO), 73.8 (s,
CH2O, OPr), 57.3 (d, J = 15.4 Hz, CHCH3), 29.3 (d, J = 4.1 Hz,
CH3N), 23.6 (s, CH2CH3, OPr), 16.5 (s, CH3Ar), 16.2 (s, CH3CH),
10.6 (s, CH3, OPr). 31P NMR (CDCl3, 121 MHz): δ 106.6 (P-O),
69.9 (P-N). ESI-MS: m/z (%) = 670.33 (100) [M þ Na]þ.
ꢀ
Universite de Bourgogne.
(SP)-(-)-{[(1S,2R)-2-(Diphenylphosphinitoborane)-1-methyl-
2-phenylethyl](methyl)amino{25,26,27,28-tetrapropoxycalix[4]-
arene}phosphaneborane, 3a. A solution of sec-butyllithium
(1.27 M in hexane, 2.6 mL, 3.3 mmol) was added under argon
at -78 °C to a solution of 5-bromo-25,26,27,28-tetrapropoxy-
calix[4]arene (2 g, 3 mmol) in THF (6 mL). After 45 min, the
mixture was added slowly to a solution of (þ)-oxazaphospho-
lidineborane 1 (941 mg, 3.3 mmol) in THF (6 mL). The reaction
mixture was warmed to -40 °C and stirred for 2 h. When the
starting complex 1 was totally consumed (TLC), the mixture was
cooled to -78 °C and a solution of chlorodiphenylphosphane
(1.1 mL, 6 mmol) was added. After 2 h at room temperature,
borane dimethylsulfide (BH3-DMS) (2.8 mL, 30 mmol) was
added, and the mixture was stirred overnight. BH3-DMS and
THF were evaporated under reduced pressure, and the residue
was hydrolyzed with water at 0 °C and then extracted with
CH2Cl2. The organic layers were dried with anhydrous MgSO4,
and the solvent was removed. The residue was purified by
column chromatography on silica gel using petroleum ether,
then petroleum ether/ethyl acetate (9:1) as eluant to afford the
AMP*P diborane 3a, which was recrystallized with methanol
(yield 62%). Suitable crystals for X-ray crystal structure deter-
mination were grown from dichloromethane/methanol at room
temperature. White solid; mp=157-160 °C. Rf = 0.43 (AcOEt/
(SP)-(-)-{[(1S,2R)-2-(Diphenylphosphinitoborane)-1-methyl-
2-phenylethyl](methyl)amino}{[3,5-dimethyl]phenyl}phosphane-
borane, 3b. This compound was prepared by the same procedure
as AMP*P 3a using 1-bromo-3,5-dimethylphenyl (2 mL, 14.7
mmol), to generate the corresponding 3,5-dimethylphenyl-
lithium. Yield: 34%. White solid. Mp=193-195 °C. Rf=0.28
1
(Et2O/petroleum ether, 1:9). [R]25D = þ78.8 (c 1, CHCl3). H
NMR (CDCl3, 300 MHz): δ 7.68-7.61 (m, 2H, CH arom),
7.46-7.35 (m, 3H, CH arom), 7.30-7.16 (m, 6H, CHarom),
7.08-6.96 (m, 10H, CHarom), 6.54 (td, 2H, J = 8.1, 1.2 Hz,
CHarom), 5.30 (t, 1H, J = 9.3 Hz, CHO), 4.50 (m, 1H, CH3CH),
2.22 (d, 3H, J = 6 Hz, CH3N), 2.21 (s, 6H, CH3Ar), 1.25 (d, 3H,
J = 6.6 Hz, CH3CH). 13C NMR (CDCl3, 75 MHz): δ 138.1 (s,
Carom), 137.9 (d, J = 10.5 Hz, Carom), 132.9 (d, J = 2.2 Hz,
CHarom), 132.9 (s, Carom), 132.1 (d, J = 21.8 Hz, Carom), 131.7 (s,
CHarom), 131.7 (d, J = 5.5 Hz, CHarom), 131.6 (d, J = 7 Hz,
CHarom), 131.4 (d, J = 2.2 Hz, CHarom), 131.1 (d, J = 11.3 Hz,
CHarom), 130.5 (d, J = 9.8 Hz, Carom), 130.2 (d, J = 2.2 Hz,
CHarom), 130.1 (d, J = 10.4 Hz, CHarom), 129.6 (d, J = 23.4 Hz,
Carom), 128.7 (s, CHarom), 128.7 (d, J = 5.9 Hz, CHarom), 128.5
(d, J = 3.3 Hz, CHarom), 128.2 (s, CHarom), 128.0 (d, J = 7.7 Hz,
CHarom), 127.9 (d, J=7.7 Hz, CHarom), 83.3 (dd, J = 8.9, 2.7 Hz,
CHO), 57.3 (dd, J = 11.0, 8.7 Hz, CHCH3), 29.4 (d, J = 4.3 Hz,
CH3N), 21.4 (s, CH3Ar), 16.2 (s, CH3CH). 31P NMR (CDCl3,
121 MHz): δ 106.7 (P-O), 71.0 (P-N). ESI-MS: m/z (%) =
588.29 (100) [M - H]þ. Anal. Calcd for C36H43B2NOP2
(589.30): C, 73.34; H, 7.30; N, 2.38. Found: C, 73.26; H, 7.46;
N, 2.34
petroleum ether, 1:9). [R]25D = þ3.1 (c 1, CHCl3). H NMR
1
(CDCl3, 300 MHz): δ 7.70-7.50 (m, 2H, CH arom), 7.50-7.40
(m, 3H, CH arom), 7.30-6.80 (m, 17H, CH arom), 6.70-6.50 (m,
4H, CH arom), 6.40-6.20 (m, 5H, CH arom), 5.10 (t, 1H, J = 9.3
Hz, CHO), 4.50 (AX system, 4H, J = 12.9 Hz, ArCH2Ar), 4.40
(m, 1H, CHCH3), 4.00 (m, 4H, CH2O, OPr), 3.70 (m, 4H,
CH2O, OPr), 3.00 (AX system, 4H, J = 12.9 Hz, ArCH2Ar),
2.00 (m, 4H, CH2CH3, OPr), 1.90 (m, 4H, CH2CH3, OPr), 1.40
(d, 3H, J = 7.1 Hz, CH3N), 1.30 (d, 3H, J = 6.5 Hz, CH3CH),
1.00 (td, 6H, J = 7.3, 0.8 Hz, CH3, OPr), 0.90 (q, 6H, J = 7.5 Hz,
CH3, OPr). 13C NMR (CDCl3, 75 MHz): δ 157.2 (d, J = 2.2 Hz,
Carom), 156.9 (d, J = 15.8 Hz, Carom), 155.7 (s, Carom), 138.0 (s,
Carom), 136.3 (d, J = 10.1 Hz, Carom), 135.9 (d, J = 14.7 Hz,
Carom), 134.2 (d, J = 11.0 Hz, Carom), 134.0 (d, J = 12.1 Hz,
Carom), 133.8 (d, J = 10.9 Hz, Carom), 132.9 (s, Carom), 132.6 (d,
J = 12.2 Hz, CH arom), 132.3 (s, Carom), 131.9 (d, J = 10.8 Hz,
CHarom), 131.6 (s, CHarom), 131.5 (s, CHarom), 131.2 (d, J = 2.0
Hz, CHarom), 131.1 (d, J = 11.1 Hz, CHarom), 129.8 (br s,
CHarom), 128.9 (s, CHarom), 128.6 (s, CHarom), 128.5 (d, J = 11.0
Hz, CHarom), 128.3 (s, CHarom), 128.2 s, CHarom), 127 (s,
CHarom), 127.8 (d, J = 10.4 Hz, CHarom), 127.7 (d, J = 4.4
Hz, CHarom), 127.6 (d, J = 2.7 Hz, CHarom), 122.6 (s, CHarom),
122.4 (s, CHarom), 122.2 (s, CHarom), 82.9 (dd, J = 6.4, 2.7 Hz,
CHO), 77.4 (s, CH2O, OPr), 77.3 (s, CH2O, OPr), 76.7 (s, CH2O,
(SP)-(-)-{[(1S,2R)-2-(Diphenylphosphinito)-1-methyl-2-phenyl-
ethyl](methyl)amino}{25,26,27,28-tetrapropoxycalix[4]arene}phos-
phane, 4a. To a solution of AMP*P diborane 3a (0.28 g, 0.26 mmol)
in 3 mL of toluene was added DABCO (0.12 g, 1.06 mmol), and the
mixture was heated at 50 °C for 12 h. The crude product was
rapidly filtered on a neutral alumina column using degassed
1
dichloromethane as eluent. Yield: 98%. White solid. H NMR
(CDCl3, 300 MHz): δ 7.50 (td, 2H, J = 7.8, 1.8 Hz, CHarom), 7.40
(m, 3H, CHarom), 7.30 (m, 2H, CHarom), 7.20-7.10 (m, 8H,
ꢀ
(36) Bauduin, C.; Moulin, D.; Kaloun, E. B.; Darcel, C.; Juge, S.
J. Org. Chem. 2003, 11, 4293–4301.

3630 Organometallics, Vol. 29, No. 16, 2010
Khiri et al.
CHarom), 6.98 (td, 2H, J = 7.9, 1.4 Hz, CHarom), 6.80 (dd, 1H, J =
6.4, 2.1 Hz, CHarom), 6.70 (dd, 1H, J = 6.5, 2.1 Hz, CHarom), 6.55
(m, 6H, CHarom), 6.40 (dd, 2H, J = 17.2, 7.1 Hz, CHarom), 6.35 (m,
4H, CHarom), 4.70 (t, 1H, J = 8.7 Hz, CHO), 4.40 (AX system, 2H,
J = 13.1, 7.9 Hz, ArCH2Ar), 4.30 (A0X0 system, 2H, J = 12.9, 12.6
Hz, ArCH2Ar), 3.89 (t, 4H, J = 7.8 Hz, CH2O, OPr), 3.78 (m, 1H,
CHCH3), 3.56 (td, 4H, J = 5.2, 2.1 Hz, CH2O, OPr), 3.10 (AX
system, 2H, J = 17.7, 13.2 Hz, ArCH2Ar), 2.98 (A0X0 system, 2H,
J = 17.9, 13.0 Hz, ArCH2Ar), 1.97 (m, 4H, CH2CH3, OPr), 1.89
(m, 4H, CH2CH3, OPr), 1.67 (d, 3H, J = 2.8 Hz, CH3N), 1.22 (d,
3H, J = 6.6 Hz, CH3CH), 0.99 (t, 6H, J = 7.4 Hz, CH3, OPr), 0.94
(q, 6H, J = 7.5 Hz, CH3, OPr). 13C NMR (CDCl3, 75 MHz): δ
155.6 (d, J=5.2Hz, Carom), 155.1 (d, J= 28.1 Hz, Carom), 141.3 (d,
J = 9.8 Hz, Carom), 141.1 (d, J = 10.5 Hz, Carom), 140.2 (d, J = 1.8
Hz, Carom), 137.7 (d, J = 13.4 Hz, Carom), 136.7 (s, Carom), 134.5 (br
s, Carom), 133.3 (d, J = 9.3 Hz, Carom), 132.7 (d, J = 6.2 Hz, Carom),
132.6 (d, J = 5.4 Hz, Carom), 131.2 (d, J = 20.1 Hz, CHarom), 131.2
(d, J = 22.5 Hz, CHarom), 130.9 (s, CHarom), 129.9 (d, J = 22.7 Hz,
CHarom), 129.3 (d, J = 21.8 Hz, CHarom), 128.1 (d, J = 17.6 Hz,
CHarom), 127.6 (d, J = 12.0 Hz, CHarom), 127.1 (br s, CHarom),
126.8 (d, J = 2.3Hz, CHarom), 126.7 (d, J = 3.1Hz, CHarom), 126.4
(br s, CHarom), 124.3 (s, CHarom), 121.3 (s, CHarom), 121.1 (d, J =
9.3 Hz, CHarom), 85.4 (dd, J= 18.1 Hz, J= 10.3 Hz, CHO),76.0(s,
CH2O, OPr), 75.6 (s, CH2O, OPr), 75.5 (s, CH2O, OPr), 64.6 (dd,
J = 37.6, 7.3 Hz, CHCH3), 30.4 (d, J = 9.8 Hz, CH3N), 29.8 (br s,
CH2, ArCH2Ar), 29.7 (s, CH2, ArCH2Ar), 22.4 (s, CH2CH3, OPr),
22.3 (s, CH2CH3, OPr), 22.1 (s, CH2CH3, OPr), 22.0 (s, CH2CH3,
OPr), 15.8 (d, J=4.64Hz, CH3CH), 9.5 (s, CH3, OPr), 9.1(s, CH3,
OPr). 31P NMR (CDCl3, 121 MHz): δ 110.3 (P-O), 65.0 (P-N).
(SP)-(-)-{[(1S,2R)-2-(Diphenylphosphinito)-1-methyl-2-phenyl-
ethyl](methyl)amino}{[3,5-dimethyl-4-propoxy]phenyl}phosphane,
4c. This compound was obtained from the decomplexation of 3c
(0.5 g, 0.77 mmol), using a similar procedure to that described for
4a. Yield: 97%. White solid. 1H NMR (CDCl3, 300 MHz): δ 7.45
(m, 2H, CHarom), 7.24 (br s, 5H, CHarom), 7.15-7.00 (m, 11H,
CH arom), 6.75 (d, 2H, J = 7.5 Hz, CH arom), 6.61 (t, 2H, J = 6.9
Hz, CH arom), 4.73 (t, 1H, J = 9 Hz, CHO), 3.85 (m, 1H,
CHCH3), 3.63 (t, 2H, J = 6.6 Hz, CH2O, OPr), 2.10 (br s, 9H,
CH3Ar), 1.72 (m, 2H, CH2CH3, OPr), 1.25 (d, 3H, J = 6.6 Hz,
CH3CH), 0.99 (t, 3H, J=7.5 Hz, CH3, OPr). 13C NMR (CDCl3,
75 MHz): δ 156.6 (s, Carom), 142.3 (d, J = 12.1 Hz, Carom), 142.1
(d, J=13.2 Hz, Carom), 141.1 (d, J = 1.8 Hz, Carom), 139.4 (d, J =
10.5 Hz, Carom), 133.3 (d, J=21.8 Hz, CHarom), 133.3 (s, Carom),
131.6 (d, J = 18.1 Hz, CHarom), 131.1 (d, J = 22.6 Hz, CHarom),
130.4 (s, Carom), 130.3 (d, J = 21.8 Hz, CHarom), 129.4 (s,
CHarom), 128.7 (s, CHarom), 128.3 (br s, CHarom), 127.9 (s,
CHarom), 127.7 (d, J = 9.8 Hz, CHarom), 127.6 (d, J = 9.0 Hz,
CHarom), 86.6 (dd, J=18.1, 11.3 Hz, CHO), 73.7 (s, CH2O, OPr),
65.4 (dd, J=37, 7.5 Hz, CHCH3), 32.0 (d, J = 9 Hz, CH3N), 23.7
(s, CH2CH3, OPr),17.0(d, J = 7.5Hz, CH3CH), 16.4(s, CH3Ar),
10.7 (s, CH3, OPr). 31P NMR (CDCl3, 121 MHz): δ 110.4 (P-O),
63.5 (P-N).
37.7, 7.5 Hz, CHCH3), 32.2 (d, J = 9.8 Hz, CH3N), 21.3 (s,
CH3Ar), 17.1 (d, J = 4.5 Hz, CH3CH). 31P NMR (CDCl3, 121
MHz): δ 110.5 (P-O), 63.6 (P-N).
(Cycloocta-1,5-diene)[(SP)-(-)-{[(1S,2R)-2-(Diphenylphosphi-
nito)-1-methyl-2-phenylethyl] (methyl)amino}{25,26,27,28-tetra-
propoxycalix[4]arene}phosphane]rhodium Tetrafluoroborate, 5a. A
Schlenk tube was charged with AMP*P 4a (0.29 g, 0.28 mmol)
in freshly distilled dichloromethane (3 mL), and this solution was
added at room temperature by cannula to a solution of [Rh-
(COD)2]BF4 (0.07 g, 0.17 mmol) in the dichloromethane (3 mL).
The mixture was stirred at room temperature for 2 h, and the
solvent was removed under reduced pressure to give an orange
powder, which was crystallized from a CH2Cl2/diethyl ether
mixture to afford the corresponding complex as orange crystals.
Yield: 92%. Mp = 228-230 °C. 1H NMR (CDCl3, 300 MHz): δ
7.83 (m, 2H, CHarom), 7.64 (m, 3H, CHarom), 7.55 (m, 3H,
CHarom), 7.43-7.39 (m, 5H, CHarom), 7.28-7.20 (m, 7H,
CHarom), 7.13 (m, 3H, CHarom), 6.91 (d, 1H, J=7 Hz, CHarom),
6.84 (m, 1H, CHarom), 6.62 (m, 5H, CHarom), 6.50 (m, 1H,
CHarom), 5.86 (br s, 2H, CHO and CHCH3), 5.01 (br s, 2H,
COD), 4.8 (br s, 1H, COD), 4.72 (br s, 1H, COD), 4.41 (m, 4H,
ArCH2Ar), 4.01 (m, 4H, CH2O), 3.62 (m, 4H, CH2O), 3.43 (d, 1H,
J = 12.9 Hz, ArCH2Ar), 3.17 (d, 1H, J = 12.9 Hz, ArCH2Ar),
3.03 (d, 1H, J = 12.9 Hz, ArCH2Ar), 2.94 (d, 1H, J = 12.9 Hz,
ArCH2Ar), 2.88 (m, 1H, COD), 2.62 (m, 1H, COD), 2.31 (m, 6H,
COD), 2.03 (m, 4H, CH2CH3, OPr), 1.87 (m, 7H, CH2CH3 and
CH3N), 1.06 (m, 9H, CH3CH and CH3), 0.91 (m, 6H, CH3, OPr).
31P NMR (CDCl3, 121 MHz): δ 119.1 (d, J = 179.3 Hz, P-O),
91.4 (d, J = 154.3 Hz, P-N). ESI-MS: m/z (%) = 1258.48 (100)
[M - BF4]þ.
(Cycloocta-1,5-diene)[(SP)-(-)-{[(1S,2R)-2-(diphenylphosphi-
nito)-1-methyl-2-phenylethyl](methyl)amino}{[3,5-dimethyl-4-pro-
poxy}phosphane]rhodium Tetrafluoroborate, 5c. This complex was
prepared by a similar procedure to that described for 5a. Yield:
52%. Orange crystals. Mp = 128-130 °C. 1H NMR (CDCl3, 300
MHz): δ 7.71 (m, 2H, CHarom), 7.52 (m, 2H, CHarom), 7.38 (m,
4H, CHarom), 7.24 (m, 3H, CHarom), 7.26-7.18 (m, 6H, CHarom),
7.12-7.04 (m, 5H, CHarom), 5.31(m,2H, CHO and CHCH3), 4.57
(br s, 2H, COD), 4.46 (br s, 1H, COD), 4.34 (br s, 1H, COD), 3.66
(t, 2H, J = 6.6 Hz, CH2O, OPr), 2.85 (m, 1H, COD), 2.52 (m, 1H,
COD), 2.2 (m, 12H, CH3Ar and COD), 1.89 (d, 3H, J = 6.9 Hz,
CH3N), 1.72 (m, 2H, CH2CH3, OPr), 1.34 (d, 3H, J = 6.9 Hz,
CH3CH), 0.97 (t, 3H, J = 4.5 Hz, CH3, OPr). 31P NMR (CDCl3,
121 MHz): δ 120.0 (d, J = 170.1 Hz, P-O), 92.7 (d, J = 164.0 Hz,
P-N). ESI-MS: m/z (%) = 830.28 (100) [M - BF4]þ.
(Cycloocta-1,5-diene)[(SP)-(-)-{[(1S,2R)-
2-(diphenylphosphinito)-1-methyl-2-phenylethyl](methyl)amino}-
{[3,5-dimethylphenyl]phenyl}phosphane]rhodium Tetrafluorobo-
rate, 5b. This complex was prepared by a similar procedure to
that described for 5a. Yield: 66%. Orange crystals. Mp = 226-
228 °C. 1H NMR (CDCl3, 300 MHz): δ 7.89 (m, 2H, CHarom),
7.53 (m, 4H, CHarom), 7.40 (m, 3H, CHarom), 7.28-7.20 (m, 6H,
CHarom), 7.08 (m, 4H, CHarom), 6.96 (br s, 1H, CHarom), 6.84 (m,
1H, CHarom), 5.35 (m, 2H, CHO and CHCH3), 4.58 (br s, 2H,
COD), 4.47 (br s, 1H, COD), 4.34 (br s, 1H, COD), 2.85 (m, 1H,
COD), 2.52 (m, 1H, COD), 2.23 (s, 6H, CH3Ar), 2.14 (m, 6H,
COD), 1.90 (d, 3H, J = 6.6 Hz, CH3N), 1.35 (d, 3H, J = 6.9 Hz,
CH3CH). 31P NMR (CDCl3, 121 MHz): δ 120.0 (d, J = 170.0
Hz, P-O), 93.5 (d, J = 162.8 Hz, P-N). ESI-MS: m/z (%) =
772.23 (100) [M - BF4]þ.
(SP)-(-)-{[(1S,2R)-2-(diphenylphosphinito)-1-methyl-2-phenyl-
ethyl](methyl)amino}{[3,5-dimethyl]phenyl}phosphane 4c. This
compound was obtained from the decomplexation of 3c (0.28 g,
0.47 mmol), using similar procedure as described for 4a. Yield:
73%. White solid. 1H NMR (CDCl3, 300 MHz): δ 7.45 (m, 2H,
CHarom), 7.25 (br s, 5H, CHarom), 7.20-6.98 (m, 11H, CHarom),
6.82 (br s, 1H, CHarom), 6.71-6.62 (m, 4H, CHarom), 4.75 (t, 1H,
J = 8.7 Hz, CHO), 3.85 (m, 1H, CHCH3), 2.13 (br s, 9H, CH3Ar
and CH3N), 1.27 (d, 3H, J= 6.6Hz, CH3CH). 13C NMR (CDCl3,
75 MHz): δ 142.2 (d, J = 12.07 Hz, Carom), 142.0 (d, J = 12.8 Hz,
Typical Procedure for the Asymmetric Hydrogenation. A
solution of [Rh(COD)(AMP*P)]BF4 5a-c (0.02 mmol, 3 mol
%) and substrate 6 (0.59 mmol) in dry solvent (8 mL) was
introduced in a stainless steel autoclave and stirred for 10 min.
The autoclave was closed, purged with hydrogen, and then
pressurized with hydrogen. After 16 h of stirring at room
temperature, the pressure was released to atmospheric pressure
and the solution was transferred to a round-bottom flask. The
solvent was removed on a rotary evaporator to give a residue,
which was purified by column chromatography on silica gel to
Carom), 141.0 (d, J = 1.5 Hz, Carom), 139.7 (d, J = 11.3Hz, Carom),
138.8 (d, J = 15.8 Hz, Carom), 137.2 (d, J = 6.8 Hz Carom), 131.8
(d, J = 18.8 Hz, CHarom), 131.3 (d, J = 22.6 Hz, CHarom), 130.3
(d, J = 15.8 Hz, Carom), 130.2 (s, CHarom), 130.0 (d, J=12.1 Hz,
CHarom), 129.3 (s, CHarom), 128.7 (s, CHarom), 128.3 (br s,
CHarom), 128.3 (br s, CHarom), 128.2 (s, CHarom), 127.9 (d, J =
1.5 Hz, CHarom), 127.7 (d, J = 8.3 Hz, CHarom), 127.6 (d, J = 1.5
Hz, CHarom), 86.5 (dd, J = 18.1, 10.6 Hz, CHO), 65.3 (dd, J =

Article
Organometallics, Vol. 29, No. 16, 2010 3631
afford the hydrogenated product. The enantiomeric excess was
determined by HPLC on a chiral column.
Crystal Structure Determination. Diffraction data were col-
lected on a Nonius Kappa CCD diffractometer equipped with a
nitrogen jet stream low-temperature system (Oxford
Cryosystems). The X-ray source was graphite-monochromated
Methyl 2-Acetamido-3-phenylpropionate, 7a. The enantio-
meric excess of 7a was determined by HPLC on Chiralcel OD-
H (25 cm): hexane/i-PrOH = 95:5, 1 mL/min, tR(R) = 21.4 min,
tR(S) = 34.7 min. 1H NMR (300 MHz, CDCl3): δ 7.20 (m, 5H,
CHarom), 6.11 (br s, 1H, NHCOCH3), 4.87 (m, 1H, CHCO2-
CH3), 3.64 (s, 3H, CO2CH3), 3.07 (m, 2H, CH2Ph), 1.97 (s, 3H,
COCH3).
Dimethyl 3-Methylsuccinate, 7b. The enantiomeric excess of
7b was determined by HPLC on Chiralcel OD (25 cm): hexane/i-
PrOH = 95:5, 1 mL/min, tR(R) = 6.4 min, tR(S) = 11 min. 1H
NMR (300 MHz, CDCl3): δ 3.62 (s, 3H, CO2CH3), 3.60 (s, 3H,
CO2CH3), 2.85 (m, 1H, CH2CO2CH3), 2.66 (dd, 1H, J = 16.5,
8.1 Hz, CH2CO2CH3), 2.31 (dd, 1H, J = 16.5, 3 Hz,
CH2CO2CH3), 1.14 (d, 3H, J = 7.1 Hz, CHCH3).
Methyl 2-Acetamidopropionate, 7c. The enantiometic excess
of 7c was determined by HPLC on Chiralcel OD-H (25 cm):
hexane/i-PrOH = 95:5, 1 mL/min, tR(R) = 19.9 min, tR(S) =
23.1 min. 1H NMR (300 MHz, CDCl3): δ 6.11 (br s, 1H,
NHCOCH3), 4.57 (m, 1H, CHCO2CH3), 3.72 (s, 3H, CO2CH3),
1.99 (s, 3H, NHCOCH3), 1.36 (d, 3H, J = 6.8 Hz, CHCH3).
Methyl 2-(2-Oxo-pyrrolidin-1-yl)butanoate, 7d. The enantio-
metic excess of the 7d was determined by HPLC on Chiralcel OD
(25 cm): hexane/i-PrOH = 95:5, 1 mL/min, tR(S) = 18.5 min,
tR(R) = 22.4 min. 1H NMR (300 MHz, CDCl3): δ 4.52 (dd, 1H,
J = 10.5, 5.4 Hz, CHCO2Me), 3.55 (s, 3H, CO2CH3), 3.35 (AB
system, 1H, CH2N), 3.20 (AB system, 1H, CH2N), 2.28 (t, 2H,
J = 8.1 Hz, CH2CON), 1.88 (m, 3H, CH2CH3 and CH2CH2N),
1.52 (m, 1H, CH2CH3), 0.76 (t, 3H, J = 7.2 Hz, CH2CH3).
˚
Mo KR radiation (λ = 0.71073 A) from a sealed tube. The lattice
parameters were obtained by least-squares fit to the optimized
setting angles of the entire set of collected reflections. No
significant temperature drift was observed during the data
collections. Data were reduced by using DENZO37 software
without applying absorption corrections; the missing ab-
sorption corrections were partially compensated by the data
scaling procedure in the data reduction. The structure was
solved by direct methods using the SIR9238 program. Re-
finements were carried out by full-matrix least-squares on F2
using the SHELXL9739 program on the complete set of
reflections. Absolute configurations of all compounds were
determined reliably from anomalous scattering, using the
Flack method.40
Computer Modeling. The computations were performed with
PCModel version 7.0 from Serena Software.
Acknowledgment. This research was supported by the
CNRS (Centre National de la Recherche Scientifique),
ꢁ
the “Ministere de l’Education Nationale et de la Recherche”,
the Natural Sciences and Engineering Research Council
of Canada (NSERC), and Synthelor S.A (Nancy). S.J. and
P.D.H. are grateful to the Agence Nationale de la Recherche
for funding (ANR BLAN MetChirPhos) and for an
Excellence Research Chair held in Dijon.
(37) (a) Otwinowski, Z.; Minor, W.; Carter, C. W., Jr. Methods
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1997, 30, 565.
Supporting Information Available: Crystallographic data in
CIF format for compound 3a and complex 5a. This material is
available free of charge via the Internet at http://pubs.acs.org.
(38) Altomare, A.; Cascarano, G.; Giacovazzo, C.; Guagliardi, A.
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(39) (a) Sheldrick, G. Acta Crystallogr., Sect. A 2008, 64, 112–122. (b)
SHELX-97, Program for the Refinement of Crystal Structures; Bruker
AXS: Madison, WI, 1997.
(40) (a) Flack, H. Acta Crystallogr., Sect. A 1983, 39, 876–881. (b)
Flack, H. D. Helv. Chim. Acta 2003, 86, 905–921. (c) Flack, H. D.;
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