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Synthesis of α‐Methylidene‐γ‐amino Acid Esters from Aldehydes via an Aminative Umpolung Strategy
Author(s) -
Xu Juan,
Chen Jing,
Yang Qin,
Ding Lei,
Liu Xuliang,
Xu Dongfang,
Zhao Baoguo
Publication year - 2014
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.201400210
Subject(s) - chemistry , umpolung , dabco , decarboxylation , electrophile , amino acid , organic chemistry , acetonitrile , methanol , adduct , amination , electrophilic amination , catalysis , octane , organocatalysis , combinatorial chemistry , nucleophile , enantioselective synthesis , biochemistry
This paper describes an efficient method for the synthesis of α‐methylidene‐γ‐amino acid esters from readily available aldehydes by using aminative umpolung strategy. Electrophilic aromatic aldehydes were converted to α‐imino anions via amination with 2,2‐diphenylglycine in methanol and subsequent decarboxylation in acetonitrile. The in situ generated α‐imino anions displayed high activity in the reaction with Morita‐Baylis–Hillman adducts in the presence of 1,4‐diazabicyclo[2.2.2]octane (DABCO) as catalyst, to give a variety of substituted α‐methylidene‐γ‐amino acid esters in 54–96% yields with 3.2–7.1:1 diastereoselectivity. The resulting α‐methylidene‐γ‐amino acid esters can be efficiently converted into biologically important α‐ exo ‐methylidene‐γ‐lactams under mild conditions.