Diastereoselective addition of silyl enol ether to chiral imines and 1,3-oxazolidines using a Lewis acid

Article abstract of DOI:10.1055/s-1998-1718

The Lewis acid promoted reaction of silyl enol ether to chiral imines and 1,3-oxazolidines derived from (R)-phenylglycinol afforded with good diastereoselectivity the (R,R)-β-amino ester derivatives from the imines, and the (R,S)-β-amino ester derivatives from the 1,3-oxazolidines.

Full text of DOI:10.1055/s-1998-1718

May 1998
SYNLETT
489
Diastereoselective Addition of Silyl Enol Ether to Chiral Imines and 1,3-Oxazolidines Using a
Lewis Acid
Kimio Higashiyama,* Hideyoshi Kyo, and Hiroshi Takahashi
Institute of Medicinal Chemistry, Hoshi University, Ebara-2-4-41, Shinagawa-ku, Tokyo 142-8501, Japan
FAX 5498-5798; kimio@hoshi.ac.jp
Received 24 February 1998
Abstract: The Lewis acid promoted reaction of silyl enol ether to chiral
imines and 1,3-oxazolidines derived from (R)-phenylglycinol afforded
with good diastereoselectivity the (R,R)-ß-amino ester derivatives from
the imines, and the (R,S)-ß-amino ester derivatives from the 1,3-
oxazolidines.
Chiral ß-amino acids are constituents of many classes of natural
products, and important intermediates in the synthesis of ß-lactam
1
derivatives. Therefore, several approaches have been reported for their
2
synthesis. One of these approaches, the reaction of an imine with metal
enolates or silyl enol ether under Lewis acid catalyzed conditions has
3
Scheme 2
been considered as a useful method for the synthesis of ß-amino acids.
Recently, we developed a synthetic method for the stereoselective
preparation of both amine enantiomers starting from
a single
enantiomeric source using the diastereoselective addition of
organometallic reagents to the chiral imines and 1,3-oxazolidines
4
derived from (R)-phenylglycinol, and we have already reported the
application of such reactions to the asymmetric syntheses of naturally
5
occurring alkaloids and chiral auxiliaries.
With the requisite compound available, we next carried out the reaction
9
of a chiral imine (1a) with silyl enol ether in the presence of various
Lewis acids in CH Cl at -78°C which resulted in pairs of
2
2
diastereomeric adducts (3a). Although the reaction using TiCl , SnCl
4
4
or trimethylsilyl trifluoromethanesulfonate (TMSOTf) exhibited poor
diastereoselectivities and chemical yields, the use of BF -OEt as a
3
2
Lewis acid obtained both good chemical yields and high
diastereoselectivity (entry 4). In particular, for the reaction of chiral
imines (1b-c) having aromatic heterocycles, essentially complete
diastereoselectivity was obtained with good yields (entries 5 and 6),
while in the case of an aliphatic imine (1e), poor results were obtained
with this methodology (entry 8). Furthermore, it was found that
chemical and optical yields in the addition of the silyl enol ether to the
chiral imine (1a) having a hydroxyl group are satisfactory, but that the
addition of the silyl enol ether to the chiral imine (1d) having a methyl
ether group gives a surprisingly lower yield (entries 4 and 7). Therefore,
it is believed that in these reactions, the hydroxyl group is an important
factor in the selectivity process.
Scheme 1
As a part of a program aimed at expanding the generality of this
reaction, we envisaged that this reaction could be extended to the
addition of silyl enol ether in place of organometallic reagents to give
the ß-amino ester derivatives.
The desired starting material was readily prepared as follows. The
condensation of the aldehyde (benzaldehyde, 2-furaldehyde, 2-thiophen
carboxyaldehyde,
acetaldehyde)
6
with
phenylglycinol,
O-
7
methylphenylglycinol or N-benzylphenylglycinol by heating in
10
benzene with the azeotropic removal of water gave the chiral imines
On the other hand, for the reaction of the oxazolidine (2a) that used
1
(1a-e) or 1,3-oxazolidines (2a-d) in quantitative yields. The H-NMR
BF -OEt or SnCl as a Lewis acid, the proposed compound was not
3
2
4
spectrum in CDCl of these products showed that 1a-c were equilibrium
produced, but a complicated decomposition product was provided. In
order to improve the lower yield, we examined several reaction
conditions and finally found that the desired adducts (4a) could be
obtained in high chemical and optical yields when TMSOTf was used.
3
mixtures of the imine form (1a-e) and 1,3-oxazolidine form (1’a-e), and
also 2a-d were inseparable thermodynamic mixtures, depending on the
8
asymmetric center at the 2-position of the 1,3-oxazolidine ring.

490
LETTERS
SYNLETT
25
The effect of the Lewis acid is shown in Table 2. It is of interest to note
from Table 2 that the degree of diastereoselectivity of the addition is
influenced by the kind of substituent at the 2-position on the 1,3-
oxazolidine ring. Namely, the reactions of 1a-c, which have an aromatic
substituent, afford pairs of diastereomeric adducts (4a-c) with high
diastereoselectivities (entries 12-14), but there is poor selectivity in the
case of 2d which has an aliphatic substituent (entry 15).
CHCl )) corresponded well with the literature value ([α]
-27.1
3
D
11
(c=1.0, CHCl )). Furthermore, this compound was treated with MeI
3
in the presence of KH to give the O-methyl product (3d) in quantitative
yields, which was identified as the major product obtained from the
reaction of the chiral imine (1d). Thus, the R,R configuration of major
diastereoisomers (3a and 3d) have been determined, and we think the
other major diastereomers (3b-c) have the same configuration because
these compounds are expected to be produced through a similar reaction
mechanism. On the other hand, since the ß-amino esters (4a-c) derived
from the 1,3-oxazolidines were unknown, the major diastereoisomers,
also isolated by column chromatography, were submitted for reductive
cleavage of the benzyl group with 5% Pd-C to afford the ß-amino esters
(3a-c) in good yield, which were identical to the minor products
obtained from the reaction of the imines (1a-c) with silyl enol ether
1
based on H-NMR spectral comparison.
Thus, the proposed method seems to be of wide interest in the synthesis
of ß-amino acid derivatives since it can be applied to the selective
preparation of both asymmetric carbon atoms from
a single
enantiomeric source. Further studies on the mechanistic and synthetic
aspects of this stereoselective addition reaction are in progress.
References and Notes
1
a) Hart, D. J.; Ha, D. C. Chem. Rev. 1989, 89, 1447. b) Brown, M.
J. Heterocycles, 1989, 29, 2225. c) Van der Steen, F. K.; Van
Koten, G. Tetrahedron 1991, 47, 7503.
2
a) Enantioselective Synthesis of β-Amino Acids; Juraristi, E., Ed.;
Wiley-VCH Publishers: New York, 1996. b) Gennari, C. In
Comprehensive Organic Synthesis, Heathcock, Ed.; Pergamon:
Oxford, U.K., 1991; Vol. 2, p 629.
Scheme 3
3
a) Enders, D.; Reinhold, U. Tetrahedron: Asymmetry, 1997, 8,
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Tetrahedron Lett., 1998, 39, 323.
4
5
Higashiyama, K.; Inoue, H.; Takahashi, H. Tetrahedron Lett.,
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a) Higashiyama, K.; Nakahata, K.; Takahashi, H. Heterocycles,
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Chem. Soc., Perkin Trans. 1, 1995, 111. e) Higashiyama, K.;
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6
Meyers, A. I.; Poindexter, G. S.; Brich, Z. J. Org. Chem., 1978,
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7
8
Hunt, J. H.; McHale, D. J. Chem. Soc., 1957, 2073.
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9
Colvin, E. W. In Best Synthetic Methods, Silion in Organic
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Academic Press: London, 1988; p 122.
10 Diastereoselective addition of silyl enol ether to oxazolidines has
been reported. Berrien, J. F.; Billion, M. A.; Husson, H. P.; Royer,
J. J. Org. Chem., 1995, 60, 2922.
The absolute configurations of the newly formed chiral center in the
adducts was determined as follows.
1
13
The H and C-NMR data for the major diastereoisomer (3a) isolated
11 a) Mokhallalati, M. K.; Wu, M-J.; Pridgen, L. N. Tetrahedron
Lett., 1993, 34, 47. b) Mokhallalati, M. K.; Pridgen, L. N. Synth.
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by column chromatography on silica gel were identical to those
reported, and optical rotation of our product ([α]
11
21
-24.5 (c=2.0,
D