Halogen Bonding Initiated Difunctionalization of [1.1.1]Propellane via Photoinduced Polarity Match Additions

Abstract

Bicyclo[1.1.1]pentane (BCP), recognized as a bioisostere for para‐disubstituted benzene, has gained widespread interest in drug development due to its ability to enhance the physicochemical properties of pharmaceuticals. In this work, we introduce a photoinduced, halogen bonding‐initiated, metal‐free strategy for synthesizing various BCP derivatives. This method involves the generation of nucleophilic α‐aminoalkyl radicals via halogen‐bonding adducts. These undergo selective radical addition to [1.1.1]propellane, yielding electrophilic BCP radicals that subsequently participate in polarity‐matched additions, culminating in the difunctionalization of bicyclopentane. The versatility and practicality of this metal‐free approach are underscored by its broad substrate scope, which includes late‐stage functionalization and a series of valuable transformations, all conducted under mild reaction conditions.