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Dynamic Kinetic Asymmetric Reductive Amination: Synthesis of Chiral Primary β‐Amino Lactams
Author(s) -
Lou Yazhou,
Hu Yutao,
Lu Jiaxiang,
Guan Fanfu,
Gong Gelin,
Yin Qin,
Zhang Xumu
Publication year - 2018
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201809719
Subject(s) - reductive amination , kinetic resolution , chemistry , iminium , ruthenium , amination , primary (astronomy) , yield (engineering) , combinatorial chemistry , enantioselective synthesis , stereochemistry , catalysis , organic chemistry , materials science , astronomy , metallurgy , physics
A highly efficient ruthenium‐catalyzed asymmetric reductive amination (ARA) of racemic β‐keto lactams with molecular hydrogen and ammonium salts is disclosed for the synthesis of enantiomerically pure primary amino lactams through dynamic kinetic resolution (DKR). By this approach, a range of syn primary β‐amino lactams were obtained in high yields with high chemo‐, enantio‐, and diastereoselectivity (up to 98 % yield, 99 % ee , >20:1 d.r., syn products). The utility of the products has been demonstrated by rapid access to a key synthetic intermediate towards biologically active drug molecules. Meanwhile, mechanistic studies and control experiments indicate that the reaction may proceed through the hydrogenation of an iminium intermediate.