Enantioselective Synthesis of <i>N</i>-Alkylamines through β-Amino C–H Functionalization Promoted by Cooperative Actions of B(C<sub>6</sub>F<sub>5</sub>)<sub>3</sub> and a Chiral Lewis Acid Co-Catalyst
Yejin Chang, Min Cao, Jessica Z. Chan, Cunyuan Zhao, Yuan-Kai Wang, Rose Yang, Masayuki Wasa
Abstract
We disclose a catalytic method for β-C(sp3)–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(C6F5)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.