Photoinduced Generation of Alkyl Radicals from Dihydroquinazolinones for Difunctionalization of [1.1.1]Propellane.

Bicyclo[1.1.1]pentane (BCP) motifs have emerged as highly valuable bioisosteres for benzene rings in drug discovery. However, the use of alkyl radicals derived from C-C bond cleavage of ketones for the synthesis of BCP derivatives has remained unexplored. Herein, we report a method for the synthesis of BCP benzylalcohol building blocks. The process proceeds through a hydrogen atom transfer (HAT) mechanism mediated by photoexcited aryl aldehydes to generate alkyl radicals from dihydroquinazolinones, thereby achieving the difunctionalization of [1.1.1]propellane. This protocol exhibits broad substrate scope (43 examples) and excellent functional group tolerance, operating under metal- and photocatalyst-free conditions. Furthermore, the synthetic utility of this approach is underscored by the successful transformation of the resulting BCP products into a variety of valuable derivatives.