Broad scope direct decarboxylative alkylation of bicycloalkylcarboxylic acids enabled by redox-mediated visible-light photoorganocatalysis

In this work, we report a mild and scalable decarboxylative Giese strategy that enables the direct formation of C(sp³)–C(sp³) bonds from bicyclo[x.y.z]alkanes, including bicyclo[1.1.1]pentane (BCP) carboxylic acids without the need for preactivation to redox-active derivatives. Motivated by the growing importance of BCP motifs as three-dimensional bioisosteres in medicinal chemistry and the longstanding challenges associated with their direct decarboxylative functionalization, we developed a metal-free protocol that operates under visible light using substoichiometric amounts of biphenyl as a redox mediator and an inorganic base. The acridinium photocatalyst 9-mesityl-3,6-di-tert-butyl-10-phenylacridinium proved optimal, combining a high excited-state oxidation potential with excellent stability. This approach avoids the use of metals, UV irradiation, and poorly atom-economical redox-active handles, offering a practical and versatile entry to high-value sp³-rich building blocks that are well suited for applications in medicinal chemistry and late-stage diversification.