Iodo-substituted bicyclo1.1.1pentanes (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 1.1.1propellane (TCP) using recyclable tetragonal tet -BaTiO 3 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.
Gao et al. (Wed,) studied this question.