Rh-Catalyzed [4 + 2] Benzannulation Enabling the Construction of Quinazoline-2,4-diones from Uracil and Ynamides

Abstract

As an indispensable nucleobase in RNA, uracil has recently attracted increasing attention as a privileged scaffold for functionalization. Herein, we report a Rh-catalyzed [4+2] benzannulation of uracil-derived aldehydes with ynamides, enabling the efficient synthesis of polysubstituted quinazoline-2,4-dione derivatives in moderate yields. This protocol exhibits a broad substrate scope and high functional-group tolerance, and the resulting products are readily amenable to diverse downstream derivatizations. Notably, this strategy was successfully applied to install a fused uracil motif into nine bioactive molecules, highlighting its utility for late-stage modification and medicinally relevant scaffold diversification.