Enantioselective 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

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.