Asymmetric methoxyselenenylation of alkyl vinyl ethers: A new route to chiral acetals

Article abstract of DOI:10.1016/S0040-4039(00)02285-1

The asymmetric methoxyselenenylation of alkyl vinyl ethers afforded chiral acetals with moderate to good diastereoselectivities. This reaction and subsequent deselenenylation provided a new method for the preparation of enantiomerically enriched acetals in which the acetal carbon was the only stereogenic center.

Full text of DOI:10.1016/S0040-4039(00)02285-1

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TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 1559–1562
Asymmetric methoxyselenenylation of alkyl vinyl ethers: a new
route to chiral acetals
Masahiko Uchiyama,* Shinya Satoh and Akihiro Ohta
School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan
Received 13 November 2000; revised 30 November 2000; accepted 8 December 2000
Abstract—The asymmetric methoxyselenenylation of alkyl vinyl ethers afforded the corresponding chiral acetals with moderate to
good diastereoselectivity. This reaction and subsequent deselenenylation provided a new method of preparing enantiomerically
enriched acetals in which the acetal carbon was the only stereogenic center. © 2001 Elsevier Science Ltd. All rights reserved.
Oxyselenenylation, the addition reaction of electrophilic
organoselenium compounds to alkenes in the presence
of oxygen nucleophiles, is a very useful reaction in
organic synthesis because it is highly stereoselective and
the incorporated organoselenium moiety plays an
important role in subsequent functional group
manipulations.1
nucleophilic substitution of acetals. The mechanism of
this type of reaction (SN1 or SN2), despite the detailed
studies by several groups,5 has not been completely
established because in most of these studies the cyclic
and acyclic acetals with the stereogenic centers placed
away from the acetal carbon were used. In spite of this
situation, only a few methods of preparing such acetals
as 2 are known,6,7 and besides, the reported methods
are not likely to be applicable to the preparation of
varied acetals. For example, Davies and co-workers
synthesized some acetals (2, R=Ar, R1=H, R2=Pri)
The first asymmetric variant to this reaction was
reported by Tomoda and co-workers in 1988.2 After
this report, several groups have devised chiral selenium
electrophiles for use in asymmetric methoxyselenenyla-
tions.3 Many examples of the reaction using a wide
variety of alkenes have also been reported. However, to
our knowledge, only one example of the reaction using
alkyl vinyl ethers is known,3f,4 moreover no notice has
been taken of its utility value to date.
using
enantiopure
(o-substituted
benzaldehyde)
chromium tricarbonyl complexes, and investigated the
stereospecificity of their nucleophilic substitution reac-
tions with Me2CuLi–BF3·OEt2.5l However, the acetals
used in their study were limited to the benzaldehyde
derivatives. Therefore, we undertook to synthesize vari-
ous types of enantiomerically enriched acetals 2 using
the method as shown in Scheme 1. In this paper, we
report the asymmetric methoxyselenenylation of alkyl
vinyl ethers and its first application to the preparation
of an enantiomerically enriched acetal whose acetal
carbon only is chiral.
Asymmetric methoxyselenenylation with alkyl vinyl
ethers and subsequent deselenenylation could gave
enantiomerically enriched acetals 2 in which the acetal
carbon was the only stereogenic center (Scheme 1).
Acetals 2 are suitable substrates for a more conclusive
mechanistic investigation of the Lewis acid-promoted
Scheme 1.
Keywords: chiral selenium compounds; asymmetric methoxyselenenylation; vinyl ethers; chiral acetals.
* Corresponding author. Tel.: +81-426-76-3037; fax: +81-426-76-3040; e-mail: uchiyama@ps.toyaku.ac.jp
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)02285-1

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M. Uchiyama et al. / Tetrahedron Letters 42 (2001) 1559–1562
We attempted the asymmetric methoxyselenenylation of
alkyl vinyl ethers using the known enantiopure dise-
lenide 3,8 which could be easily prepared in a few steps
from the commercially available (R)-(+)-N,N-dimethyl-
1-phenethylamine. Diselenide 3 was converted to the
corresponding electorophilic selenenyl tetrafluoroborate
by successive treatment with sulfuryl chloride and silver
tetrafluoroborate.9 The resulting tetrafluoroborate in-
termediate was then treated with alkyl vinyl ethers 4 to
give a mixture of 5 and 6 (Scheme 2). The results of the
reactions with alkyl vinyl ethers 4a–k10 are summarized
in Table 1.
All the reactions proceeded regioselectively to afford
anti addition products11 5 and 6 as an inseparable
1
mixture, which were fully characterized by H and 13C
NMR, and low and high resolution mass spectroscopy.
1
The diastereomeric ratios (drs) were determined by H
Scheme 2.
Table 1. Asymmetric methoxyselenenylation of various alkyl vinyl ethers

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M. Uchiyama et al. / Tetrahedron Letters 42 (2001) 1559–1562
1561
Scheme 3.
NMR integration of the protons of the methoxy group
and/or that at the acetal carbon. However, up to now it
has not been established which of the diastereomers
was major. The reactions with non-substituted alkyl
vinyl ethers 4a–e (entries 1–5) proceeded smoothly at
−78°C to provide the corresponding acetals in high
yields with moderate diastereoselectivities. The alkyl
groups in the alkyl vinyl ethers had only a small
influence on the diastereoselectivity. Although the reac-
tion with the 1-substituted alkyl vinyl ether 4f also
afforded the acetal products in high yields, the dr was
very low (entry 6). With 2-substituted alkyl vinyl ethers
4g and 4h, the reactions did not proceed at −78°C.
Therefore, the reaction temperature was raised to −
50°C to give the corresponding acetals, but whose
yields were still low (entries 7 and 9). Raising the
reaction temperature further to −20°C improved the
chemical yields without the deterioration of drs and the
epimerization of the products (entries 8 and 10). The
reaction with trans-b-ethoxystyrene (4g) gave a much
better dr than that with cis-b-ethoxystyrene (4h). This
relationship between the regiochemistry of the substrate
and the magnitude of the diastereoselectivity is in
accord with that reported for the reactions with trans-
and cis-b-methylstyrene.3a,b With cyclic vinyl ethers 4i–
k, the corresponding acetals were obtained in high
yields (entries 11–13). Although the diastereoselectivi-
ties in the reactions of 4i and 4j were moderate, that of
4k was rather low.
processes provide a new method of preparing enan-
tiomerically enriched acetals in which the acetal carbon
is the only stereogenic center.
References
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We next attempted the conversion of the methoxysele-
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Bu3SnH in refluxing toluene afforded the acetal (−)-7 in
90% yield (Scheme 3). The enantiomeric excess of (−)-7
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configuration of (−)-7 has not been yet established.
Although Kirmse and co-workers refer to acetal 7 in
non-racemic form in their report, the compound was
not specifically purified nor was its optical purity deter-
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the first to disclose the practical preparation of opti-
cally active 7.
In summary, we have demonstrated that the asymmet-
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the corresponding acetals in good chemical yields with
moderate to good diastereoselectivity, and also that a
diastereomeric mixture of 5g and 6g (dr=90:10 or
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Chem. Commun. 1996, 1803–1804.

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1562 M. Uchiyama et al. / Tetrahedron Letters 42 (2001) 1559–1562
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.