Heterogeneous photocatalytic 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 common 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. Mechanistic studies reveal that the base governs the quenching of photoexcited g-C₃N₄ by CF₃SO₂Cl, thereby diverting the reaction through distinct radical-mediated pathways.