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

ABSTRACT: Classic nucleophilic substitution reactions (SN1 and SN2) 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 ?-bromoketones generate achiral alkyl radicals that can participate in asymmetric Csp3-Csp3 bonds forming cross-coupling reactions with ?-amino radicals derived from N-aryl amino acids. A wide range of valuable enantiomerically pure ?2- and ?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.

SUBMITTER: Li J 

PROVIDER: S-EPMC6015005 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature