Metal- and photocatalyst-free three-component strategy to prepare benzylalcohol-, aldehyde-substituted BCP building blocks

Abstract

Bicyclo[1.1.1]pentanes (BCPs), which can serve as bioisosteres of para-disubstituted benzene rings, have emerged as useful bioactive scaffolds in drug discovery research. Herein, we report a one-step, light-promoted, three-component radical-coupling method for rapidly generating difunctionalized benzylalcohol-, aldehyde-substituted BCPs from aryl aldehydes, ethers, and [1.1.1]propellane. The method, which does not require metals or photocatalysts, features a broad substrate scope (58 examples) and excellent functional group tolerance. Furthermore, this protocol can be scaled up to the gram-level. Remarkably, these transformations are external-oxidant-free, thus exemplifying an environmentally friendly and practical synthetic strategy.