Organic chemistry

Combinatorial chemistry

Chiral Lewis acid

Electrophile

Stereochemistry

Surface modification

Enantioselective synthesis

Catalysis

Lewis acids and bases

Physical chemistry

Chemistry

Enamine

Organocatalysis

Journal of the American Chemical Society

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.

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