Metal and photocatalyst-free alkylboration of [1.1.1]propellane enabled by red-light-induced electron transfer

Abstract

Highly strained 1,3-disubstituted bicyclo[1.1.1]pentanes (BCPs) have emerged as bioisosteres of para-disubstituted benzene rings because of the ability of the former to impart valuable pharmacokinetic properties. However, challenges such as the lack of convenient and green access to useful BCP building blocks continue to hinder early-stage discovery research. Herein, we report a metal and photocatalyst-free method for deaminative borylation of [1.1.1]propellane for the synthesis of BCP boronates. This method involves the generation of alkyl or α-ester alkyl radicals via red-light-induced formation of a ternary electron donor–acceptor complex between a Katritzky salt, Cs₂CO₃, and B₂pin₂. Selective addition of the radicals to [1.1.1]propellane produces BCP radicals that undergo polarity-matched addition to B₂pin₂, leading to BCP difunctionalization. The method, which does not require metals or photocatalysts, allows for direct construction of alkyl species from readily available amines and α-amino acids and concurrent introduction of synthetically versatile pinacol boronate (Bpin) groups onto the BCP substructure. We demonstrate the synthetic utility of our method through several important transformations of the Bpin and hydroxyl functional groups of the products, including photoinduced cross-coupling reactions of BCP-BF₃K derived from BCP-Bpin.