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 beta-C(sp(3))-H functionalization of N-alkylamines for the synthesis of enantiomerically enriched beta-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 alpha,beta-unsaturated compounds. An array of delta-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 beta-C-H functionalization of bioactive amines. Investigations in regard to the mechanistic nuances of the catalytic processes are described.

Automated summary

This study presents a catalytic method for beta-C(sp(3))-H functionalization of N-alkylamines to synthesize enantiomerically enriched beta-substituted amines. By using a catalyst system comprising seemingly competitive Lewis acids and chiral metal-based complexes, a variety of delta-amino carbonyl compounds were efficiently synthesized, demonstrating the potential application of the method in synthesizing pharmaceutical compounds and chiral catalysts. Investigations into the mechanistic nuances of the catalytic processes were also described.