Cross-ketone deacylative coupling via oxidative SH2 homolytic substitution

The α-C-C cleavage coupling of ketones offers a highly challenging yet promising approach for C–C bond formation, particularly given the ubiquity and ready accessibility of ketones as fundamental synthons in organic synthesis. However, the deacylative cross-coupling between two distinct ketones via a single activation mode remains an unmet challenge, although this coupling paradigm could be leveraged to construct C(sp3)–C(sp3) linkages with exceptional structural diversity. Herein, we describe a cross-ketone deacylative coupling via nickel-catalyzed bimolecular homolytic substitution (SH2), in which the synergistic oxidative photocatalysis is combined to produce simultaneously two distinct open-shell carbons from ketone-derived dihydroquinazolinones. This hetero-selective radical-radical coupling protocol enables the construction of quaternary carbon centers through a critical SH2 displacement mechanism, providing an efficient approach to furnish β-quaternary aliphatic amines. Additionally, a wide array of biorelevant small molecules, including β-amino alcohol, β-diamine and β-aminothiol derivatives, can also be obtained via this cross-double deacylative C1-alkylation approach between distinct ketones. The α-C–C cleavage of ketones provides a versatile route for C–C bond formation but remains challenging, particularly for selective cross-coupling between distinct ketones. Here the authors report a nickel- and photocatalysis-enabled deacylative coupling via bimolecular homolytic substitution to forge diverse C(sp³)–C(sp³) bonds.