Formal enantioconvergent substitution of alkyl halides via catalytic asymmetric photoredox radical coupling

Abstract

Abstract Classic nucleophilic substitution reactions (S N 1 and S N 2) are not generally amenable to the enantioselective variants that use simple and racemic alkyl halide electrophiles. The merging of transition metal catalysis and radical chemistry with organometallic nucleophiles is a versatile method for addressing this limitation. Here, we report that visible light-driven catalytic asymmetric photoredox radical coupling can act as a complementary and generic strategy for the enantioconvergent formal substitution of alkyl haldies with readily available and bench-stable organic molecules. Single-electron reductive debrominations of racemic α-bromoketones generate achiral alkyl radicals that can participate in asymmetric C sp3 –C sp3 bonds forming cross-coupling reactions with α-amino radicals derived from N -aryl amino acids. A wide range of valuable enantiomerically pure β 2 - and β 2,2 -amino ketones were obtained in satisfactory yields with good-to-excellent enantioselectivities by using chiral phosphoric acid catalysts to control the stereochemistry and chemoselectivity. Fluoro-hetero-quaternary and full-carbon quaternary stereocenters that are challenging to prepare were successfully constructed.