Cross-ketone deacylative coupling via oxidative S_H2 homolytic substitution.

Abstract

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 (S_H2), 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 S_H2 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.