Chiral palladium(II)-catalyzed asymmetric glyoxylate-ene reaction: Alternative approach to the enantioselective synthesis of α-hydroxy esters

Article abstract of DOI:10.1021/ol0066983

(Matrix presented) An effective chiral palladium catalyst [Pd(CH₃CN)₂(S)-Tol-BINAP](SbF₆)₂ (2b) is developed for asymmetric glyoxylate-ene reactions. This palladium dicationic catalyst provides a simple but effi

Full text of DOI:10.1021/ol0066983

ORGANIC
LETTERS
2000
Vol. 2, No. 25
4059-4062
Chiral Palladium(II)-Catalyzed
Asymmetric Glyoxylate−Ene Reaction:
Alternative Approach to the
Enantioselective Synthesis of r-Hydroxy
Esters
Jian Hao, Manabu Hatano, and Koichi Mikami*
Department of Applied Chemistry, Tokyo Institute of Technology,
Tokyo 152-8552, Japan
kmikami@o.cc.titech.ac.jp
Received October 5, 2000
ABSTRACT
An effective chiral palladium catalyst [Pd(CH CN)2(S)-Tol-BINAP](SbF ) (2b) is developed for asymmetric glyoxylate−ene reactions. This palladium
3
6 2
dicationic catalyst provides a simple but efficient approach to the asymmetric synthesis of r-hydroxy esters in excellent yields with high
enantioselectivities at relatively higher reaction temperature (60 °C).
As one of the most important methodologies for carbon-
carbon bond construction, asymmetric ene reactions catalyzed
by chiral Lewis acids have received great attention in recent
years.1 Among those, a number of examples of glyoxylate-
ene reactions, which afford R-hydroxy esters, versatile
synthons in organic synthesis, have been described.2
(BINOL) ligands at low reaction temperature (ca. -30 °C)
to produce the R-hydroxy esters in excellent enantioselec-
tivities and chemical yields.3 However, the BINOL-Ti
catalysts are only successful with 1,1-disubstituted olefins.
The reaction with monosubstituted olefins is still a limitation.
To further explore the possibility of asymmetric glyoxylate-
ene reaction with monosubstituted olefins and at room
temperature or higher reaction temperature, we focused our
attention on the new type of chiral metal complexes, such
as chiral palladium(II) complexes.4 Herein, we report the
enantioselective glyoxylate-ene reaction catalyzed by chiral
BINAPs coordinated palladium diantimonate catalysts (2).
These catalysts provide a simple but efficient way to the
enantioselective synthesis of the R-hydroxy esters in excellent
chemical yields with high enantioselectivities at relatively
We have reported asymmetric glyoxylate-ene reactions
catalyzed by titanum(IV) complexes with chiral binaphthol
(1) (a) Santelli, M.; Pons, J.-M. Lewis Acids and SelectiVity in Organic
Synthesis; CRC Press: New York, 1996. (b) Whitesell, J. K. StereoselectiVe
Synthesis; Houben-Weyl: 1996; Vol. 5; pp 3271-3297. (c) Mikami, K.;
Shimizu, M. Chem. ReV. 1992, 92, 1021-1050. (d) Snider, B. B.
ComprehensiVe Organic Synthesis; Pergamon: London, 1991; Vol. 5, pp
1-27.
(2) (a) Mikami, K.; Nakai, T. Catalytic Asymmetric Synthesis; Wiley-
VCH: New York, 2000; pp 543-568. (b) Dias, L. C. Curr. Org. Chem.
2000, 4, 305-342. (c) Mikami, K.; Terada, M. ComprehensiVe Asymmetric
Catalysis; Springer-Verlag: Berlin, Heidelberg, 1999; Vol. III, pp 1143-
1176. (d) Mikami, K. AdVances in Asymmetric Synthesis; JAI Press:
Greenwich, CT, 1995; Vol. 1, pp 1-44.
(3) (a) Mikami, K. Pure Appl. Chem. 1996, 68, 639-644. (b) Mikami,
K.; Terada, M.; Nakai, T. J. Am. Chem. Soc. 1990, 112, 3949-3954; 1989,
111, 1940-1941. (c) Mikami, K.; Terada, M.; Nakai, T. Annual Meeting
of the Chemical Society of Japan, Tokyo, 1988, April 1-4, Abstract
1XIB43.
(4) For our highly enantioselective ene-type cyclizations catalyzed by
chiral palladium complexes bearing BINAP derivatives, see: Hatano, M.;
Terada, M.; Mikami, K. Angew. Chem., Int. Ed. In press.
10.1021/ol0066983 CCC: $19.00 © 2000 American Chemical Society
Published on Web 12/07/2000

Scheme 1. [Pd(CH3CN)2(S)-Tol-BINAP](SbF6)2 (2b)-Catalyzed
Glyoxylate-Ene Reaction between Methylenecyclohexane and
Ethyl Glyoxylate
Table 1. Effect of Ligand and Counterion in Glyoxylate-Ene
Reaction
5a
entry
Pd(II)
yield (%)a
ee (%)b
higher reaction temperature (60 °C) with 1,1-disubstituted
and trisubstituted olefins.
1
2
3
4
5
1a
1b
2a
2b
2c
72
76
82
88
87
48
72
61
78
42
After careful examination of various palladium(II) com-
plexes and counterions, we found that the combination of
palladium(II) dication species with its strongly anionic ligand,
-
such as BF4- and SbF6 , could be employed as an efficient
a Isolated yield. b Determined by chiral GC using CP-Cyclodextrin-B-
2,3,6-M-19 column.
catalyst in glyoxylate-ene reactions. Among those, the (S)-
Tol-BINAP-coordinated palladium(II) diantimonate complex
(2b), which can be stored under argon atmosphere at room
temperature, provides not only high enantioselectivities but
also excellent control of regioselectivity leading to homoal-
lylic rather than allylic alcohols in glyoxylate-ene reactions
(Scheme 1).
were obtained in the reaction using methylene-cyclohexane
(3a) and ethyl glyoxylate (4) as starting materials (Table 1).
Both palladium complexes 1 and 2 provided good chemical
yields and enantioselectivities in glyoxylate-ene reaction.
The reaction of 3a with 4 by using the (S)-Tol-BINAP-
coordinated palladium diantimonate (2b) in CH2ClCH2Cl
proceeded smoothly at room temperature to give (R)-5a in
88% yield with 78% ee (entry 4). This result was better than
that obtained using the complexes 1 as catalyst because of
the higher electron negativity of the SbF6- group compared
-
to that of the BF4 group. Steric effect of BINAP ligands
was observed in this reaction. The sterically less demanding
BINAP gives lower ee (entries 1 and 3), while the middle
size of the Tol-BINAP ligand offers better enantioselectivity
(entries 2 and 4). More sterically bulky DM (i.e., Xylyl)-
BINAP7 gives lower ee (entry 5), which is much worse than
that using BINAP as chiral ligand.
The effect of solvent and temperature in this reaction was
also investigated (Table 2). Both dichloromethane and 1,2-
dichloroethane provide high solubility of complexes 1 and
2. The reactions carried out in these solvents are relatively
faster so as to slightly decrease the enantioselectivity.
Toluene itself is not a proper solvent for this palladium-
catalyzed glyoxylate-ene reaction at room temperature as
a result of the extremely low solubility of the palladium
complexes therein (entry 8). Raising the temperature, for
instance, to 60 °C, could greatly improve the solubility of
the complex 2 and afford the ene product in 95% yield with
84% ee (entry 9). Therefore, toluene as a cosolvent could
retard the reaction but improve the enantioselectivity at room
The palladium complexes 1, a yellowish green powder,
and 2, a chocolate powder, employed in this reaction were
prepared from Pd(BINAP)Cl2 with AgBF4 and AgSbF6
in CH3CN at room temperature, respectively (Scheme 2).
5
6
Scheme 2. Preparation of 1 and 2 from Pd(BINAPs)Cl2
(6) [Pd(CH3CN)2(R)-BINAP](BF4)2: (a) Hori, K.; Kodama, H.; Ohta,
T.; Furukawa, I. J. Org. Chem. 1999, 64, 5017-5023. (b) Oi, S.; Terada,
E.; Ohuchi, K.; Kato, T.; Tachibana, Y.; Inoue, Y. J. Org. Chem. 1999, 64,
8660-8667.
(7) Mashima, K.; Matsumura, Y.; Kusano, K.; Kumobayashi, H.; Sayo,
N.; Hori, Y.; Ishizaki, T.; Akutagawa, S.; Takaya, H. Chem. Commun. 1991,
609-610.
The initial results of the effect of ligands and counterions
of palladium complexes 1 and 2 on glyoxylate-ene reactions
(5) Ozawa, F.; Kubo, A.; Matsumoto, Y.; Hayashi, T. Organometallics
1993, 12, 4188-4196.
4060
Org. Lett., Vol. 2, No. 25, 2000

Scheme 3. Glyoxylate-Ene Reaction with Allylbenzene
Table 2. Effect of Solvent and Temperature in Palladium
Complex 2b-Catalyzed Glyoxylate-Ene Reaction
5a
temp time yield
ee
(%)b
coordination to improve the enantioselectivity. However, a
too high reaction temperature, for instance, 80 °C (entry 5),
would accelerate the reaction too much to reduce the
enantioselectivity. The best result of the palladium complex
catalyzed glyoxylate-ene reaction was obtained in the
reaction using [Pd(CH3CN)2(S)-Tol-BINAP](SbF6)2 (2b) as
a catalyst and toluene/1,2-dichloroethane (2/1 in volume) as
a solvent system at 60 °C (entry 7).
entry
solvent
(°C)
(h)
(%)a
1
2
CH2Cl2
rt
rt
18
18
8
83
88
97
97
98
85
95
76
78
82
86
75
84
88
CH2ClCH2Cl
3
CH2ClCH2Cl
40
60
80
rt
4
CH2ClCH2Cl
4
5
CH2ClCH2Cl
2
6
CH2ClCH2Cl/toluene, 1/2
CH2ClCH2Cl/toluene, 1/2
toluene
20
4
7
60
rt
Although the palladium complex (2b) gave a promising
result in the reaction of 1,1-disubstituted olefin with gly-
oxylate at relatively high reaction temperature, we could not
8
20
4
9
toluene
60
60
95
97
84
43
10c
CH2ClCH2Cl/toluene, 1/2
4
a Isolated yield. b Determined by chiral GC using CP-Cyclodextrin-B-
2,3,6-M-19 column. c Using 2c as catalyst.
Table 3. Enantioselective Glyoxylate-Ene Reactions with
1,1-Disubstituted and Trisubstituted Olefins
temperature (entry 6). More sterically demanding chiral
ligand (S)-Xylyl-BINAP gave only 43% ee (entry 10) even
at 60 °C.
It is also interesting that the enantioselectivity of this
reaction catalyzed by Pd(II) complex is somewhat temper-
ature dependent. Increase of reaction temperature from
ambient (ca. 25 °C) to 60 °C could improve the enantiose-
lectivity from 78% to 86% in the case of CH2ClCH2Cl as a
solvent (entries 2 and 4) (Figure 1). The chemical yield of
this reaction was also increased from 88% to 97%. This
unusual result suggests that there is a competitive factor,
which may arise from the coordination of the hydroxy group
of the ene product with the palladium center. Increase of
reaction temperature could break down and reduce such
Figure 1. Temperature dependence in enantioselective glyoxylate-
ene reactions catalyzed by Pd(II) complex (2b) in CH2ClCH2Cl as
solvent.
a Isolated yield. b Determined by chiral GC using CP-Cyclodextrin-B-
2,3,6-M-19 column. c At room temperature.
Org. Lett., Vol. 2, No. 25, 2000
4061

step to form the bidentate intermediate 6. Subsequent addition
of the ene component to the carbonyl-Pd complex leads to
the formation of the ene product 5 and regeneration of Pd
complex 1 or 2 in situ for the next catalytic cycle. This
catalytic system is generally applicable to other 1,1-disub-
stituted olefins, such as R-methylstyrene and 2-ethyl-1-
butene, and furthermore to trisubstituted olefin, such as
ethylidenecyclohexane (Table 3).8
Scheme 4. Proposed Mechanism for Palladium(II)-Catalyzed
Glyoxylate-Ene Reaction
In conclusion, an effective chiral palladium catalyst [Pd-
(CH3CN)2(S)-Tol-BINAP](SbF6)2 (2b) is developed for the
asymmetric glyoxylate-ene reaction with 1,1-disubstituted
olefins at relatively higher temperature (60 °C). This pal-
ladium cationic catalyst provides a simple but efficient
approach to asymmetric synthesis of R-hydroxy esters in
excellent yields with high enantioselectivities. This reaction
is currently still under investigation to further expand the
scope of this process with, in particular, monosubstituted
olefins.9
OL0066983
make a breakthrough in the reaction with monosubstituted
olefin at present. Palladium complex (2b) catalyzed ene
reaction with monosubstituted olefin, such as allylbenzene
(7), unfortunately gave no desired product (8) even at 80 °C
but only recovery of starting materials (Scheme 3). It suggests
that the initial step should not include the C-H activation
of an ene olefin to give π-allyl palladium species in this
glyoxylate-ene reaction.
On the basis of the results described above, the mechanism
of palladium(II) complex catalyzed glyoxylate-ene reaction
is exemplified in Scheme 4. The reaction is considered totake
place through the complexation of the carbonyl groups of
glyoxylate with dicationic palladium catalyst at the initial
(8) General Procedure (Table 3). To a solution of [Pd(CH3CN)2-
(BINAP)]X2 (1 or 2) (0.025 mmol, 10 mol % of ethyl glyoxylate) in 2 mL
of CH2ClCH2Cl was added 0.5 mmol of olefin 3 and 0.25 mmol of ethyl
glyoxylate 4 in 4 mL of toluene at room temperature under an atmosphere
of argon. This yellow solution was then stirred at 60 °C for 4 h (reaction
was monitored by TLC, AcOEt/hexane ) 1/2), solvent was removed in
vacuo, and the residue was purified by column chromatography (AcOEt/
hexane ) 1/3) to afford R-hydroxy ester (5) as colorless oil.
(9) Recently, Evans D. A. et al reported the first example using chiral
box copper(II) complexes for catalytic enantioselective carbonyl-ene
reactions with monosubstituted olefins in up to 98% ee: (a) Johnson, J. S.;
Evans, D. A. Acc. Chem. Res. 2000, 33, 325-335. (b) Evans, D. A.; Tregay,
S. W.; Burgey, C. S.; Paras, N. A.; Vojkovsky, T. J. Am. Chem. Soc. 2000,
122, 7936-7943. (c) Evans, D. A.; Burgey, C. S.; Paras, N. A.; Vojkovsky,
T.; Tregay, S. W. J. Am. Chem. Soc. 1998, 120, 5824-5825.
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Org. Lett., Vol. 2, No. 25, 2000