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Synthesis 2009(17): 2915-2926  
DOI: 10.1055/s-0029-1216922
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Enantioselective Aldol Reaction of Tetrasubstituted Ketene Silyl Acetals with Achiral Aldehydes for the Construction of Asymmetric Tertiary Alcohols: An Application for the Divergent Total Syntheses of Buergerinins F and G

Isamu Shiina*, Takashi Iizumi, Yu-suke Yamai, Yo-ichi Kawakita, Kazutoshi Yokoyama, Yo-ko Yamada
Contribution from the Department of Applied Chemistry, Faculty of Science, Tokyo University of Science, Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan
Fax: +81(3)32605609; e-Mail: shiina@rs.kagu.tus.ac.jp;
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Publication History

Received 30 May 2009
Publication Date:
30 July 2009 (online)

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Abstract

The asymmetric aldol reaction of heteroatom-substituted ketene silyl acetals with achiral aldehydes has been developed by the promotion of tin(II) triflate coordinated with a chiral diamine to afford the corresponding aldols having chiral tertiary alcohols at the α-positions. This reaction has been successfully applied to the construction of the basic skeletons of buergerinins F and G starting from achiral materials. (+)-Buergerinin G, a potentially antiphlogistic and febrifuge agent having a unique trioxatricyclo[5.3.1.0¹,5]undecane skeleton, is stereoselectively prepared by means of the enantioselective aldol reactions via ten linear steps from crotonaldehyde in 18% overall yield including an effective intramolecular Wacker-type ketalization of the dihydroxy-γ-lactone as a key step. In addition to the former establishment for the synthesis of (+)-buergerinin F, effective divergent methods for the preparation of buergerinins F and G were developed through a unified optically active aldol-type intermediate, which was generated from the tetrasubstituted ketene silyl acetal with crotonaldehyde by the asymmetric Mukaiyama aldol reaction.

Key words

Aldol reaction - tin-chiral amine catalyst - enantioselective - tertiary alcohol - ketene silyl acetal

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