Enantioselective Incorporation of Amine Fragments onto Quaternary Carbons via Metallaphotoredox Catalysis

The enantioselective construction of quaternary carbon stereocenters bearing amine functionalities represents a significant challenge in organic synthesis despite their prevalence in pharmaceutically active compounds. Herein, we report a versatile metallaphotoredox platform for the asymmetric incorporation of amine fragments onto quaternary carbons via coupling of alkene-tethered aryl bromides with readily available α-silylamines. This transformation proceeds under mild conditions without requiring organometallic reagents or stoichiometric reductants. Mechanistically, photocatalytic generation of α-amino alkyl radicals enables their enantioselective coupling with chiral quaternary carbon-containing alkyl nickel species. The method delivers exceptional enantioselectivity and exhibits broad functional group tolerance, providing access to a diverse array of complex drug-like molecules bearing amine-functionalized quaternary stereocenters. Mechanistic investigations revealed the intermediacy of cage-escaped, stereodefined quaternary carbon-containing radicals, which guided the development of complementary asymmetric hydrocyclization and difluoroalkenylation protocols. Our unified platform expands the chemical space of three-dimensional quaternary carbon scaffolds, demonstrating the potential of metallaphotoredox catalysis in addressing longstanding synthetic challenges.