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Enantioselective Hydroamidation of Enals by Trapping of a Transient Acyl Species
Author(s) -
Yuan Pengfei,
Chen Jiean,
Zhao Jing,
Huang Yong
Publication year - 2018
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201803556
Subject(s) - enantioselective synthesis , chemistry , yield (engineering) , protonation , carbene , imidazole , catalysis , organocatalysis , combinatorial chemistry , organic chemistry , ion , materials science , metallurgy
Abstract An enantioselective synthesis of β‐chiral amides through asymmetric and redox‐neutral hydroamidation of enals is reported. In this reaction, a chiral N‐heterocyclic carbene (NHC) catalyst reacts with enals to generate the homoenolate intermediate. Upon highly enantioselective β‐protonation through proton‐shuttle catalysis, the resulting azolium intermediate reacts with imidazole to yield the key β‐chiral acyl species. This transient intermediate provides access to diversified β‐chiral carbonyl derivatives, such as amides, hydrazides, acids, esters, and thioesters. In particular, β‐chiral amides can be prepared in excellent yield and ee (40 chiral amides, up to 95 % yield and 99 % ee ). This modular strategy overcomes the challenge of disruption of the highly selective proton‐shuttling process by basic amines.