Bicyclo1.1.1pentane (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 1.1.1propellane. 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.
Li et al. (Mon,) studied this question.