Catalytic asymmetricaza-Morita-Baylis-Hillman reaction of methyl acrylate: Role of a bifunctional La(O- i Pr)3/linked-BINOL complex

Article abstract of DOI:10.1021/ja103294a

The catalytic asymmetric aza-Morita-Baylis-Hillman reaction using unactivated methyl acrylate is described. A simple Lewis acidic metal catalyst, such as La(OTf)₃, was not suitable for the reaction, but rare earth metal alkoxide/linked-BINOL complexes possessing bifunctional Lewis acid and Bronsted base properties efficiently promoted the reaction in combination with an achiral nucleophilic organocatalyst. The combined use of a La(O-iPr)₃/(S,S)-TMS-linked-BINOL complex with a catalytic amount of DABCO promoted the aza-Morita-Baylis-Hillman reaction of a broad range of N-diphenylphosphinoyl imines. Products from aryl, heteroaryl, and alkenyl imines were obtained in 67-99% yield and 81-95% ee. It is noteworthy that isomerizable alkyl imines could be employed as well, giving products in 78-89% yield and 94-98% ee. Initial rate kinetic studies as well as kinetic isotope effect experiments using α-deuterio-methyl acrylate support the importance of both the nucleophilicity of La-enolate and the Bronsted basicity of a La-catalyst for promoting the reaction.

Full text of DOI:10.1021/ja103294a

Published on Web 08/06/2010
Catalytic Asymmetric Aza-Morita-Baylis-Hillman Reaction of
Methyl Acrylate: Role of a Bifunctional La(O-iPr)3/
Linked-BINOL Complex
Takafumi Yukawa,† Bianca Seelig,†,‡ Yingjie Xu,† Hiroyuki Morimoto,†
Shigeki Matsunaga,*,† Albrecht Berkessel,*,‡ and Masakatsu Shibasaki*,§
Graduate School of Pharmaceutical Sciences, The UniVersity of Tokyo, Hongo 7-3-1,
Bunkyo-ku, Tokyo 113-0033, Japan, Department of Chemistry, UniVersity of Cologne,
Greinstr. 4, 50939 Cologne, Germany, and Institute of Microbial Chemistry,
Tokyo, Kamiosaki 3-14-23, Shinagawa-ku, Tokyo 141-0021, Japan
Received April 19, 2010; E-mail: smatsuna@mol.f.u-tokyo.ac.jp; berkessel@uni-koeln.de;
mshibasa@mol.f.u-tokyo.ac.jp
Abstract: The catalytic asymmetric aza-Morita-Baylis-Hillman reaction using unactivated methyl acrylate
is described. A simple Lewis acidic metal catalyst, such as La(OTf)3, was not suitable for the reaction, but
rare earth metal alkoxide/linked-BINOL complexes possessing bifunctional Lewis acid and Brønsted base
properties efficiently promoted the reaction in combination with an achiral nucleophilic organocatalyst. The
combined use of a La(O-iPr)3/(S,S)-TMS-linked-BINOL complex with a catalytic amount of DABCO promoted
the aza-Morita-Baylis-Hillman reaction of a broad range of N-diphenylphosphinoyl imines. Products from
aryl, heteroaryl, and alkenyl imines were obtained in 67-99% yield and 81-95% ee. It is noteworthy that
isomerizable alkyl imines could be employed as well, giving products in 78-89% yield and 94-98% ee.
Initial rate kinetic studies as well as kinetic isotope effect experiments using R-deuterio-methyl acrylate
support the importance of both the nucleophilicity of La-enolate and the Brønsted basicity of a La-catalyst
for promoting the reaction.
lates as nucleophiles, however, are limited.6-8 Jacobsen6
reported a chiral thiourea combined with a stoichiometric
amount of DABCO for nonisomerizable aryl and heteroaryl
imines in combination with unactivated methyl acrylate. Excel-
lent enantioselectivity was achieved for the first time with
acrylates, but the product yields were not satisfactory. Recently,
Zhu and Masson7a achieved notable advances using bifunctional
ꢀ-isocupreidine derivatives as catalysts. High enantioselectivity
and high yield were realized for aryl and heteroaryl imines with
an activated naphthyl acrylate. In 2010, Zhu and Masson also
successfully realized good yield and excellent enantioselectivity
with isomerizable alkyl imines for the first time,7b but the use
of an activated acrylate was still essential. Compared with
activated acrylates, methyl acrylate is by far the cheapest and
readily available reagent. Consequently, the development of a
new strategy to overcome the poor reactivity of methyl acrylate
in the aza-MBH reaction is highly desirable. Herein, we describe
the successful application of a chiral Lewis acid/Brønsted base
bifunctional rare earth metal catalyst in combination with a
nucleophilic organocatalyst. The combination of bifunctional
La(O-iPr)3/(S,S)-linked-BINOL 1 (Figure 1) complexes9,10 with
DABCO provides good yields and enantioselectivities for aryl,
1. Introduction
The catalytic asymmetric aza-Morita-Baylis-Hillman (aza-
MBH) reaction, i.e. the nucleophile-catalyzed reaction of
electron-deficient alkenes with imines, provides direct access
to functionalized chiral ꢀ-amino carbonyl compounds.1,2 Shi,3
Sasai,4 and others5 have reported various bifunctional hydrogen
bond/nucleophile organocatalysts that realize highly enantiose-
lective aza-MBH reactions using enones as nucleophiles. Highly
enantioselective examples (>90% ee) using less reactive acry-
† Graduate School of Pharmaceutical Sciences, The University of Tokyo.
‡ Department of Chemistry, University of Cologne.
§ Institute of Microbial Chemistry, Tokyo.
(1) General review on aza-MBH reactions and their applications: Declerck,
V.; Martinez, J.; Lamaty, F. Chem. ReV. 2009, 109, 1.
(2) Reviews on catalytic enantioselective aza-MBH reactions: (a) Masson,
G.; Housseman, C.; Zhu, J. Angew. Chem., Int. Ed. 2007, 46, 4614.
(b) Shi, Y.-L.; Shi, M. Eur. J. Org. Chem. 2007, 2905.
(3) (a) Shi, M.; Xu, Y.-M. Angew. Chem., Int. Ed. 2002, 41, 4507. (b)
Shi, M.; Xu, Y.-M.; Shi, Y.-L. Chem.sEur. J. 2005, 11, 1794. (c)
Shi, M.; Chen, L.-H.; Li, C.-Q. J. Am. Chem. Soc. 2005, 127, 3790.
(d) Liu, Y.-H.; Chen, L.-H.; Shi, M. AdV. Synth. Catal. 2006, 348,
973. (e) Shi, Y.-L.; Shi, M. AdV. Synth. Catal. 2007, 349, 2129. (f)
Guan, X.-Y.; Jiang, Y.-Q.; Shi, M. Eur. J. Org. Chem. 2008, 2150.
(g) Qi, M.-J.; Ai, T.; Shi, M.; Li, G. Tetrahedron 2008, 64, 1181. See
also ref 2b.
(4) (a) Matsui, K.; Takizawa, S.; Sasai, H. J. Am. Chem. Soc. 2005, 127,
3680. (b) Matsui, K.; Takizawa, S.; Sasai, H. Synlett 2006, 761.
(5) For selected recent examples, see: (a) Abermil, N.; Masson, G.; Zhu,
J. Org. Lett. 2009, 11, 4648. (b) Garnier, J.-M.; Liu, F. Org. Biomol.
Chem. 2009, 7, 1272. (c) Gausepohl, R.; Buskens, P.; Kleinen, J.;
Bruckmann, A.; Lehmann, C. W.; Klankermayer, J.; Leitner, W.
Angew. Chem., Int. Ed. 2006, 45, 3689. For other examples, see refs
1 and 2.
(6) Raheem, I. T.; Jacobsen, E. N. AdV. Synth. Catal. 2005, 347, 1701.
(7) (a) Abermil, N.; Masson, G.; Zhu, J. J. Am. Chem. Soc. 2008, 130,
12596. (b) Abermil, N.; Masson, G.; Zhu, J. AdV. Synth. Catal. 2010,
352, 656.
(8) For partially successful early trials using acrylates, see ref 3a,c. See
also: (a) Balan, D.; Adolfsson, H. Tetrahedron Lett. 2003, 44, 2521.
(b) Kawahara, S.; Nakano, A.; Esumi, T.; Iwabuchi, Y.; Hatakeyama,
S. Org. Lett. 2003, 5, 3103.
9
11988 J. AM. CHEM. SOC. 2010, 132, 11988–11992
10.1021/ja103294a  2010 American Chemical Society

Aza-Morita-Baylis-Hillman Reaction of Methyl Acrylate
A R T I C L E S
La(O-iPr)3/(S,S)-linked-BINOL 1a ) 1:1 complex with
DABCO promoted the reaction of N-diphenylphosphinoyl
imine 2a with acrylate 3 to give the aza-MBH adduct 4a in
88% ee, albeit in modest yield (46%, entry 1).13 To improve
the reactivity, an achiral nucleophilic catalyst (entry 2, Ph3P)
and various rare earth metal sources (entries 3-6) were
screened but resulted in an even less satisfactory yield and/
or enantioselectivity. By increasing the amount of ligand 1a
to 15 mol %, the yield was improved to 90% (entry 7).
Because the enantioselectivities in entries 1 and 7 were almost
the same, we speculated that the same chiral La-complex
would be working in both entries and that excess ligand 1a
was not acting as a ligand to change the structure of the La-
species, but rather as a proton source to accelerate the
reaction.14 Thus, sterically hindered achiral phenolic additives
were investigated using 10 mol % of ligand 1a. The use of
30 mol % of 2,6-di-t-Bu-4-Me-phenol (Ar1OH) effectively
improved the yield (91%), while maintaining good enanti-
oselectivity (entry 1 vs entry 8). Among the additives
screened,15 10-30 mol % of 4,4′-thiobis(6-t-Bu-m-cresol)
(Ar2OH)16 gave a slightly better enantioselectivity (entries
9-10). When performing the reaction using a 1:1 ratio of
imine and methyl acrylate, comparably good enantioselec-
tivity was achieved, but the reaction did not complete even
after 48 h (entry 11, 83% yield and 89% ee). To improve
the reactivity, quinuclidine,17 which is known as a superior
catalyst to DABCO in the racemic reaction of aldehydes with
methyl acrylate, was investigated in entry 12. High reactivity
was observed as expected (99% yield after 22 h), but the
enantioselectivity decreased to 81% ee, possibly due to
the competitive racemic pathway without participation of the
chiral La-catalyst. Control experiments (entries 13-14)
suggested that neither the La(O-iPr)3/1a complex alone nor
DABCO with chiral Brønsted acid 1a was suitable to promote
the reaction in good yield and enantioselectivity. Finally, the
Figure 1. Structures of (S,S)-linked-BINOL 1a and (S,S)-TMS-linked-
BINOL 1b.
heteroaryl, alkenyl, and even isomerizable alkyl imines using
unactivated methyl acrylate (up to 99% yield and up to 98%
ee). Mechanistic studies indicated that the simple Lewis acidic
metal catalysis is not sufficient for the effective promotion of
the aza-MBH reaction and shed light on the properties of metal
catalysts crucial for fast and selective reaction.
2. Results and Discussion
2.1. Development of the Catalytic Asymmetric Aza-MBH
Reaction of Methyl Acrylate. The previously reported orga-
nocatalytic asymmetric aza-MBH reactions required the use
of either activated acrylates or excess DABCO for activating
methyl acrylate. To realize good reactivity with unactivated
methyl acrylate, we investigated the combined use of a chiral
metal catalyst with an achiral nucleophilic organocatalyst.
Initial trials to use Lewis acidic rare earth triflates for
activating methyl acrylate, however, failed.11 In the previous
reports on organocatalytic aza-MBH reactions, the rate-
limiting step was postulated to be the intramolecular proton
transfer step following C-C bond formation.6 Thus, we
hypothesized that the use of metal catalysts with Brønsted
basic properties would be effective to accelerate the aza-
MBH reaction. Among the catalysts screened, Lewis acid/
Brønsted base bifunctional12 rare earth metal alkoxide/linked-
BINOL 1a complexes gave promising results. The optimization
studies are summarized in Table 1. The combined use of a
Table 1. Optimization of Reaction Conditions
metal source
(x mol %)
ligand
(y mol %)
additive
(z mol %)
3
(w equiv)
time
(h)
%
yielda
%
ee
entry
Nu-cat.
1
2
3
4
5
6
7
8
La(O-iPr)3 (10)
La(O-iPr)3 (10)
La(OTf)3 (10)
La(HMDS)3 (10)
Sm(O-iPr)3 (10)
Gd(O-iPr)3 (10)
La(O-iPr)3 (10)
La(O-iPr)3 (10)
La(O-iPr)3 (10)
La(O-iPr)3 (10)
La(O-iPr)3 (10)
La(O-iPr)3 (10)
La(O-iPr)3 (10)
none
1a (10)
1a (10)
1a (10)
1a (10)
1a (10)
1a (10)
1a (15)
1a (10)
1a (10)
1a (10)
1a (10)
1a (10)
1a (10)
1a (10)
1b (10)
DABCO
Ph3P
none
none
none
none
none
none
none
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
1.0
2.0
2.0
2.0
2.0
26
26
26
26
26
26
26
26
26
26
48
22
26
26
24
46
0
0
88
s
s
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
quinuclidine
none
23
42
34
90
91
92
96
83
99
0
55
78
81
89
88
91
90
89
81
-
Ar1OH (30)b
Ar2OH (30)b
Ar2OH (10)b
Ar2OH (10)b
Ar2OH (10)b
Ar2OH (10)b
Ar2OH (10)b
Ar2OH (10)b
9
10
11
12
13
14
15
DABCO
DABCO
13
0
93
La(O-iPr)3 (10)
92c
a
b
Determined by H NMR analysis of crude mixture. Ar1OH ) 2,6-di-t-Bu-4-Me-phenol; Ar2OH ) 4,4′-thiobis(6-t-Bu-m-cresol). c Isolated yield of
1
4a after purification by silica gel column chromatography.
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J. AM. CHEM. SOC. VOL. 132, NO. 34, 2010 11989

A R T I C L E S
Yukawa et al.
Table 2. Catalytic Asymmetric Aza-MBH Reaction of Various
best enantioselectivity (93% ee) was achieved by changing
the chiral ligand to (S,S)-TMS-linked-BINOL 1b (entry 15).
The substrate scope of the reaction is summarized in Table 2.18
The optimized reaction conditions were applicable to various
nonisomerizable aryl and heteroaryl imines. Good enantioselectivity
was achieved for aryl imines with either an electron-withdrawing
or an electron-donating substituent at the para-, meta-, or ortho-
positions (entries 2-9, 90-93% ee). Functionalized imines 4j and
4k, with a methyl ketone moiety and a nitrile group at the para-
position, were also applicable, but the enantioselectivity was
somewhat lower (entry 10: 84% ee; entry 11: 81% ee). With
heteroaryl imines, products 4l-4o were obtained with an even
higher enantioselectivity (entries 12-15, 92-95% ee). Catalyst
loading was successfully reduced to 5 mol %, while maintaining
good yield and enantioselectivity (entry 16). The present system
was also applicable to alkenyl and alkyl imines (entries 17-23).
Notably, the desired reaction proceeded nicely even with isomer-
izable alkyl imines, including linear alkyl imine 2s and sterically
hindered R-branched alkyl imine 2v, to afford products in 78-89%
yield and 94-98% ee (entries 19-23). The results in entries 19-23
indicated the high chemoselectivity of the present system, promot-
ing the desired aza-MBH reaction while avoiding competitive
isomerization of imines to enamides.
N-Dpp Imines with Methyl Acrylatea
2.2. Mechanistic Studies. In the present reaction, Lewis acidic
La(OTf)3 did not afford product 4a, even in the presence of
DABCO (Table 1, entry 3 in THF). Thus, a simple chiral Lewis
acid metal complex together with DABCO was not suitable to
efficiently promote the aza-MBH reaction in THF. Kinetic isotope
effect experiments using R-deuterio-methyl acrylate resulted in kH/
kD ) 1.0 (Figure 2).19 The result is different from that observed in
(9) La(O-iPr)3/linked-BINOL 1a complex as a Lewis acid/Brønsted base
bifunctional catalyst for asymmetric Michael reaction of malonates: (a)
Kim, Y. S.; Matsunaga, S.; Das, J.; Sekine, A.; Ohshima, T.; Shibasaki,
M. J. Am. Chem. Soc. 2000, 122, 6506. (b) Takita, R.; Ohshima, T.;
Shibasaki, M. Tetrahedron Lett. 2002, 43, 4661.
(10) For synthesis of linked-BINOLs, see 1a: (a) Matsunaga, S.; Das, J.;
Roels, J.; Vogl, E. M.; Yamamoto, N.; Iida, T.; Yamaguchi, K.;
Shibasaki, M. J. Am. Chem. Soc. 2000, 122, 2252. 1b: (b) Harada, S.;
Handa, S.; Matsunaga, S.; Shibasaki, M. Angew. Chem., Int. Ed. 2005,
44, 4365. (c) Sugita, M.; Yamaguchi, A.; Yamagiwa, N.; Handa, S.;
Matsunaga, S.; Shibasaki, M. Org. Lett. 2005, 7, 5339.
a Reaction was run using 1 equiv of 2, 2 equiv of 3, in THF (1.0 M)
at room temperature. Ar2OH ) 4,4′-thiobis(6-t-Bu-m-cresol). b Isolated
yield after purification by column chromatography. c 5 mol
% of
La(O-iPr)3/(S,S)-1b, 20 mol % of DABCO, and 10 mol % of Ar2OH
were used.
(11) In striking contrast, a chiral La(OTf)3 complex with DABCO was
reported as an efficient system for the reaction of aldehydes with
acrylates. (a) Yang, K.-S.; Lee, W.-D.; Pan, J.-F.; Chen, K. J. Org.
Chem. 2003, 68, 915.
(12) For reviews on acid/base bifunctional asymmetric catalysis, see: (a)
Ma, J.-A.; Cahard, D. Angew. Chem., Int. Ed. 2004, 43, 4566. (b)
Yamamoto, H.; Futatsugi, K. Angew. Chem., Int. Ed. 2005, 44, 1924.
(c) Taylor, M. S.; Jacobsen, E. N. Angew. Chem., Int. Ed. 2006, 45,
1520. (d) Mukherjee, S.; Yang, J. W.; Hoffmann, S.; List, B. Chem.
ReV. 2007, 107, 5471. (e) Shibasaki, M.; Kanai, M.; Matsunaga, S.;
Kumagai, N. Acc. Chem. Res. 2009, 42, 1117.
(13) Initial screening with other BINOL derivatives resulted in poor
enantioselectivity.
(14) For positive effects of achiral Brønsted acids to accelerate catalytic
asymmetric aza-MBH reaction, see refs 3e,5a, and 7. The effects of
the proton source in Morita-Baylis-Hillman reactions of aldehydes
were investigated in detail; see: Robiette, R.; Aggarwal, V. K.; Harvey,
J. N. J. Am. Chem. Soc. 2007, 129, 15513, and references therein.
(15) 2,6-Di-tBu-phenol, 2,6-di-tBu-4-MeO-phenol, 2-tBu-phenol, and 2-tBu-
4-MeO-phenol also had positive effects, and 4a was obtained in greater
than 80% yield and 87-89% ee. 4,4′-Thiobis(6-t-Bu-m-cresol) was
selected for further studies, because it gave the highest enantioselec-
tivity.
(16) For the utility of 4,4′-thiobis(6-t-Bu-m-cresol) as a radical inhibitor
in organic synthesis, see: (a) Kishi, Y.; Aratani, M.; Tanino, H.;
Fukuyama, T.; Goto, T.; Inoue, S.; Sugiura, S.; Kakoi, H. J. Chem.
Soc., Chem. Commun. 1972, 64. For the utility as an antioxidant for
stabilizing polymers, see: (b) Gordon, D. A.; Rothstein, E. C. Polym.
Eng. Sci. 1966, 6, 231.
Figure 2. Kinetic isotope effect study using deuterated methyl acrylate d-3.
Jacobsen’s system (kH/kD ) 3.8),6 indicating that the proton transfer
step following C-C bond formation is not the rate-determining
step in this system. On the other hand, kinetic isotope effect
(17) Aggarwal, V. K.; Emme, I.; Fulford, S. Y. J. Org. Chem. 2003, 68,
692.
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Aza-Morita-Baylis-Hillman Reaction of Methyl Acrylate
A R T I C L E S
Figure 3. (A-D) Reaction profiles of catalytic asymmetric aza-MBH reactions; (a-d) rate dependency on each component.
experiments using d-3 in the absence of an achiral proton source
(Ar2OH) resulted in kH/kD ) 2.5,20 suggesting the importance of
the proton source in the proton transfer step. To obtain further
information on the catalytic cycle, we performed initial rate kinetic
studies. The reaction profile of the catalytic asymmetric aza-MBH
reaction and the rate dependency on each component are sum-
marized in Figure 3. The reaction rate had a first-order dependency
on acrylate (Figure 3a), a zeroth-order dependency on imine (Figure
3b), a zeroth-order dependency on the La(O-iPr)3/linked-BINOL
complex (Figure 3c), and 1.4th-order dependency on DABCO
(Figure 3d).
The proposed catalytic cycle, based on the kinetic data
summarized in Figures 2 and 3, is shown in Figure 4. The results
of the kinetic studies suggest that the rate-determining step is
the 1,4-addition of DABCO to methyl acrylate. Apparently, the
chiral La-catalyst s showing a zeroth-order dependency s is not
participating in the rate-limiting 1,4-addition of DABCO to
acrylate (I). Thus, Lewis acid activation of methyl acrylate does
(18) The absolute configuration of 4a was determined by comparing
the sign of the optical rotation with the reported data reported in
ref 8b.
(19) 85% deuterated 3 was used for the experiments depicted in Figure 2.
The degree of deuteration of 3 did not change under the reaction
conditions in Figure 2 as confirmed by NMR.
(20) See Supporting Information for experimental data.
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J. AM. CHEM. SOC. VOL. 132, NO. 34, 2010 11991

A R T I C L E S
Yukawa et al.
Figure 4. Postulated catalytic cycle.
not appear to be involved in our aza-MBH reaction. To induce
enantioselectivity, the chiral La(O-iPr)3/linked-BINOL complex
needs to be involved in the enantio-discriminating step, possibly
the C-C bond formation.21 We propose that the La/linked-
BINOL complex interacts with the zwitterionic enolate species
to generate a La-enolate (II). Simple Lewis acidic La(OTf)3
did not promote the reaction (Table 1, entry 3), possibly because
the La-enolate derived from La(OTf)3 was of lower nucleophi-
licity compared to that derived from the La(O-iPr)3/linked-
BINOL complex. The La(O-iPr)3/linked-BINOL complex would
also work as a Lewis acid to activate the imine component for
C-C bond formation via the cyclic transition state (III), thereby
inducing high enantioselectivity. In contrast to other organo-
catalytic aza-MBH reactions, kinetic isotope effect experiments
indicated that the proton transfer step following C-C bond
formation is fast. We assume that the Brønsted basicity of the
La-species (IV) would play a key role, accelerating the proton
transfer step from (IV) to generate a La-enolate intermediate
(V). The role of the achiral proton source to accelerate the proton
transfer step is not clear. But, we speculate that the protonation
of the La-intermediate (IV) might change the conformation of
the intermediate (IV), thereby accelerating the deprotonation
of the R-proton by a Brønsted basic La-catalyst. The elimination
of DABCO from the zwitterionic intermediate (V) regenerates
the La(O-iPr)3/linked-BINOL catalyst as well as DABCO.
catalyst for the aza-MBH reaction using unactivated methyl
acrylate as a donor. Simple Lewis acidic La(OTf)3 was not
suitable for promoting the asymmetric aza-MBH reaction, and
the use of a bifunctional rare earth metal catalyst was important.
The La(O-iPr)3/(S,S)-TMS-linked-BINOL 1b/DABCO system
was applicable to a broad range of aryl, heteroaryl, alkenyl, and
alkyl imines at ambient temperature, giving products in 67-99%
yield and 81-98% ee. Mechanistic studies pointed to the
importance of the nucleophilicity of an intermediate La-enolate
species as well as the Brønsted basicity of metal catalyst, rather
than its Lewis acidity, for accelerating the enantioselective aza-
MBH reaction. In addition to their preparative importance, the
results reported herein are expected to pave the way for the
design of other and potentially more active chiral metal/
organocatalyst combinations for aza-MBH reactions using
methyl acrylate.
Acknowledgment. This work was supported by Grants-in Aid
for Scientific Research (S) (for M.S.) and Scientific Research on
Priority Areas (No. 20037010, Chemistry of Concerto Catalysis)
(for S.M.). B.S. thanks the Fonds der Chemischen Industrie for a
doctoral stipend and the Deutsche Akademische Austauschdienst
for a fellowship. H.M. and Y.X. are thankful for JSPS fellowships.
We thank Dr. D. Mu¨ller for the generous supply of ligand during
initial screening.
3. Conclusion
Supporting Information Available: Experimental procedures,
spectral data of new compounds, determination of the absolute
configuration, and detailed reaction profiles in kinetic studies
and kinetic isotope effect studies. This material is available free
of charge via the Internet at http://pubs.acs.org.
In summary, we described the utility of a chiral rare earth
metal catalyst in combination with an achiral nucleophilic
(21) Possibility of the enantio-differentiation at the proton transfer step,
which is often postulated in other systems (see ref 6), cannot be
excluded. But, we speculate that the enantioselectivity would be
kinetically determined at the C-C bond-formation step, because the
proton transfer step is fast in the present system.
JA103294A
9
11992 J. AM. CHEM. SOC. VOL. 132, NO. 34, 2010