Lewis Acid-Catalyzed Vinyl Transfer Using Vinylene Carbonate for Direct Synthesis of C2,C3-Unsubstituted Indoles

Abstract

C2,C3-unsubstituted indoles are privileged scaffolds in medicinal chemistry, yet their direct assembly from simple C2 feedstocks remains a longstanding synthetic challenge. Herein, we report an example of Y(OTf)3-catalyzed C–H [3 + 2] annulation of anilines with vinylene carbonate, enabling direct access to structurally diverse parent indoles through a Lewis acid-catalyzed vinyl-transfer process. Readily available vinylene carbonate serves dually as a C2 building block and an internal oxidant, allowing the reaction to proceed without directing groups, external oxidants, or preinstalled unsaturation while exhibiting broad functional-group compatibility. Mechanistic studies reveal a bifunctional catalytic role of Y(OTf)3 in sequential N-formylmethylation and electrophilic cyclization. This work establishes a distinct strategy for bulk chemical-based indole synthesis and provides opportunities for Lewis acid-catalyzed vinyl transfer chemistry.