Mechanochemical Synthesis of Iodine-Substituted Bicyclo[1.1.1]pentanes Via a Piezoelectric Catalytic System

Iodo-substituted bicyclo[1.1.1]pentanes (iodo-BCPs) are valuable synthetic linchpins for the preparation of diverse BCP-containing bioisosteres. However, existing methods often require photocatalysts, specialized equipment, or large amounts of organic solvents. Herein, we report the first piezocatalytic mechanochemical radical iodination of [1.1.1]propellane (TCP) using recyclable tetragonal tet-BaTiO3 under ball-milling conditions. Mechanical energy promotes single-electron transfer, enabling efficient strain-release functionalization of TCP with pyridyl, benzyl, and α-carbonyl iodides. The protocol proceeds without photocatalysts and exhibits broad substrate scope. Mechanistic studies support a piezocatalytically initiated radical pathway. This sustainable method provides straightforward access to synthetically versatile iodo-BCPs for medicinal chemistry applications.