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C‐Selective and Diastereoselective Alkyl Addition to β,γ‐Alkynyl‐α‐imino Esters with Zinc(II)ate Complexes
Author(s) -
Hatano Manabu,
Yamashita Kenji,
Mizuno Mai,
Ito Orie,
Ishihara Kazuaki
Publication year - 2015
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201408916
Subject(s) - chemistry , moiety , alkyl , umpolung , reagent , regioselectivity , alkylation , zinc , electrophile , lewis acids and bases , nucleophile , chelation , medicinal chemistry , nucleophilic addition , organic chemistry , catalysis
Abstract Since umpolung α‐imino esters contain three electrophilic centers, regioselective alkyl addition with traditional organometallic reagents has been a serious problem in the practical synthesis of versatile chiral α‐amino acid derivatives. An unusual C‐alkyl addition to α‐imino esters using a Grignard reagent (RMgX)‐derived zinc(II)ate was developed. Zinc(II)ate complexes consist of a Lewis acidic [MgX] + moiety, a nucleophilic [R 3 Zn] − moiety, and 2 [MgX 2 ]. Therefore, the ionically separated [R 3 Zn] − selectively attacks the imino carbon atom ,which is most strongly activated by chelation of [MgX] + . In particular, chiral β,γ‐alkynyl‐α‐imino esters can strongly promote highly regio‐ and diastereoselective C‐alkylation because of structural considerations, and the corresponding optically active α‐quaternary amino acid derivatives are obtained within 5 minutes in high to excellent yields.