Electrochemical atom-transfer radical addition to [1.1.1]propellane for the synthesis of bench-stable BCP–Br linchpins

Abstract

Selective termination of carbon-centered radicals under electrochemical conditions remains challenging, particularly in strained systems where over-reduction and unselective quenching can compete with productive atom transfer. Herein, we report an electrochemically enabled atom-transfer radical bromoalkylation of [1.1.1]propellane that converts activated alkyl bromides into isolable, bench-stable 1-alkyl-3-bromobicyclo[1.1.1]pentanes. Constant-current electrolysis with a zinc anode, nickel-foam cathode, and tetrabutylammonium bromide electrolyte initiates alkyl radical formation while favoring bromine atom transfer to the bicyclopentyl radical intermediate. The reaction accommodates primary, secondary, and tertiary activated alkyl bromides, including complex drug-like substrates, and the resulting BCP–Br products undergo C-, B-, P-, Se-, O-, and N-functionalization. Mechanistic experiments, including radical-clock and radical-trapping studies, cyclic voltammetry, and charge analysis, are consistent with an electrochemically initiated ATRA chain. This method provides a modular entry to brominated BCP linchpins and illustrates how electrochemical initiation can guide radical reactivity in strained molecular scaffolds.