C–H Functionalization of Amines via Alkene-Derived Nucleophiles through Cooperative Action of Chiral and Achiral Lewis Acid Catalysts: Applications in Enantioselective Synthesis

Catalytic
transformations of α-amino C–H bonds to afford valuable
enantiomerically enriched α-substituted amines, entities that
are prevalent in pharmaceuticals and bioactive natural products, have
been developed. Typically, such processes are carried out under oxidative
conditions and require precious metal-based catalysts. Here, we disclose
a strategy for an enantioselective union of N-alkylamines
and α,β-unsaturated compounds, performed under redox-neutral
conditions, and promoted through concerted action of seemingly competitive
Lewis acids, B­(C6F5)3, and a chiral
Mg–PyBOX complex. Thus, a wide variety of β-amino carbonyl
compounds may be synthesized, with complete atom economy, through
stereoselective reaction of an in situ-generated
enantiomerically enriched Mg-enolate and an appropriate electrophile.