Highly Diastereoselective Conjugate Addition of Lithium Dialkylamides to α,β-Unsaturated Esters Having a Chiral Center at the γ-Position

Naoki Asao, Takashi Shimada, Tomoko Sudo, Naofumi Tsukada, Kazuhiko Yazawa, Young Soo Gyoung, Tadao Uyehara, Yoshinori Yamamoto

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    66 Citations (Scopus)

    Abstract

    The conjugate addition of lithium amides 2 to tert-butyl 4-(OR)-substituted-2-pentenoates 1 produced a mixture of the syn- and anrt-amino esters (3 and 4) in high yields. Sterically bulky OR groups, such as trityloxy and tert-butyldiphenylsilyloxy, gave the syn diastereomer 3 either exclusively or predominantly. The syn-selectivity may be explained by a modified Felkin - Anh model. The use of tert-butyldimethylsilyloxy as an OR group afforded a nearly 1:1 mixture of diastereoisomers, and the use of the smallest MeO group produced a 63:37 mixture of the syn 3 and anti isomer 4. The presence of Me group at the α-position (C-2 position) of the enoate enhanced the syn diastereoselectivity up to 100%; the conjugate addition to tert-butyl 4-methoxy-2-methyl-2-pentenoate (17) gave the syn-isomer 18 exclusively. This enhancement may be explained by the combination of chelation and allylic strain model 19 in which the smallest H orients inside to avoid an allylic strain. A phenyl group at the γ-position enhanced the anti selectivity in the case of γ-alkoxy-α,β-enoates such as isopropyl 4-[(tert-butyldimethylsilyl)oxy]-4-phenyl-2-butenoate (20), and in the case of γ-alkyl-α,β-enoates such as tert-butyl 4-phenyl-2-pentenoate (27).

    Original languageEnglish
    Pages (from-to)6274-6282
    Number of pages9
    JournalJournal of Organic Chemistry
    Volume62
    Issue number18
    DOIs
    Publication statusPublished - 1997 Jan 1

    ASJC Scopus subject areas

    • Organic Chemistry

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