Open AccessEnantioselective Synthesis of N-Alkylamines through β-Amino C–H Functionalization Promoted by Cooperative Actions of B(C6F5)3 and a Chiral Lewis Acid Co-Catalyst
Author(s) -
Yejin Chang,
Min Cao,
Jessica Z. Chan,
Cunyuan Zhao,
Yuan-Kai Wang,
Rose Yang,
Masayuki Wasa
Publication year - 2021
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.0c13200
Subject(s) - enantioselective synthesis , chemistry , electrophile , catalysis , enamine , surface modification , lewis acids and bases , chiral lewis acid , organocatalysis , combinatorial chemistry , organic chemistry
We disclose a catalytic method for β-C(sp 3 )-H functionalization of N -alkylamines for the synthesis of enantiomerically enriched β-substituted amines, entities prevalent in pharmaceutical compounds and used to generate different families of chiral catalysts. We demonstrate that a catalyst system comprising of seemingly competitive Lewis acids, B(C 6 F 5 ) 3 , and a chiral Mg- or Sc-based complex, promotes the highly enantioselective union of N -alkylamines and α,β-unsaturated compounds. An array of δ-amino carbonyl compounds was synthesized under redox-neutral conditions by enantioselective reaction of a N -alkylamine-derived enamine and an electrophile activated by the chiral Lewis acid co-catalyst. The utility of the approach is highlighted by late-stage β-C-H functionalization of bioactive amines. Investigations in regard to the mechanistic nuances of the catalytic processes are described.