Dicarbofunctionalization of [1.1.1]Propellane Enabled by Nickel/Photoredox Dual Catalysis: One-Step Multicomponent Strategy for the Synthesis of BCP-Aryl Derivatives

Abstract

Bicyclo[1.1.1]pentane (BCP) motifs as para-disubstituted aryl bioisosteres are playing an emerging role in pharmaceutical, agrochemical, and materials chemistry. The vast majority of these structures is obtained from a BCP electrophile or nucleophile, which are themselves derived from [1.1.1]propellane via cleavage of the internal C-C bond through the addition of either radicals or metal-based nucleophiles. Compared with the current stepwise approaches, a multicomponent reaction that provides direct access to complex and diverse disubstituted BCP products would be more attractive. Herein, we report a single-step, multicomponent approach to synthetically versatile arylated BCP products via nickel/photoredox catalysis. Importantly, this three-component process allows two C-C bonds to be formed in a single step and sets three quaternary centers, unprecedented in any previously reported methods. The method has been demonstrated to allow access to complex BCP architectures from aryl halide and radical precursor substrates.