Heterogeneous Photocatalysis Divergent Bifunctionalization of Unactivated β-Bromoethylarenes via Base‑Controlled Selectivity

Abstract

The difunctionalization of alkenes and alkynes offers an efficient route to access two functional groups, making it a cornerstone of modern synthetic methodology. Translating this concept to unactivated β-bromoethylarenes, however, confronts a fundamental difficulty, the activation of an inert benzylic C(sp³)-H bond must be orchestrated in the same molecule that contains a labile C-Br bond. In this study, we report a heterogeneous photocatalytic strategy to overcome this challenge based on a distributed activation-synchronous functionalization radical mechanism. This approach employs graphitic carbon nitride (g-C₃N₄) as a recyclable heterogeneous photocatalyst under visible light, enabling the selective conversion of the same precursor into either α-chloroketones or α-trifluoromethylketones, with the product outcome controlled by the base. The reaction accommodates a broad range of substrates and functionalized drug-like molecules, is amenable to gram-scale synthesis, and features good catalyst recyclability. The method's utility is underscored by a 3 step synthesis of Thyroliberin agonists, significantly outperforming the prior 10-step route. Mechanism studies reveal that base governs the quenching of photoexcited g-C₃N₄ by CF₃SO₂Cl, thereby diverting the reaction through distinct radical-mediated pathways.