Open AccessA Selenourea-Thiourea Brønsted Acid Catalyst Facilitates Asymmetric Conjugate Additions of Amines to α,β-Unsaturated Esters
Author(s) -
Yingfu Lin,
William J Hirschi,
Anuj Kunadia,
Anirudra Paul,
Ion Ghiviriga,
Khalil A. Abboud,
Rachael W. Karugu,
Mathew J. Vetticatt,
Jennifer S. Hirschi,
Daniel Seidel
Publication year - 2020
Publication title -
journal of the american chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.115
H-Index - 612
eISSN - 1520-5126
pISSN - 0002-7863
DOI - 10.1021/jacs.9b12457
Subject(s) - chemistry , thiourea , conjugate , protonation , catalysis , kinetic resolution , brønsted–lowry acid–base theory , organocatalysis , organic chemistry , enantioselective synthesis , ion , mathematical analysis , mathematics
β-Amino esters are obtained with high levels of enantioselectivity via the conjugate addition of cyclic amines to unactivated α,β-unsaturated esters. A related strategy enables the kinetic resolution of racemic cyclic 2-arylamines, using benzyl acrylate as the resolving agent. Reactions are facilitated by an unprecedented selenourea-thiourea organocatalyst. As elucidated by DFT calculations and 13 C kinetic isotope effect studies, the rate-limiting and enantiodetermining step of the reaction is the protonation of a zwitterionic intermediate by the catalyst. This represents a rare case in which a thiourea compound functions as an asymmetric Brønsted acid catalyst.