Fischer Indole Synthesis Inspired De Novo and Modular Assembly of Indolines

Abstract Herein, we report a modular and redox-neutral strategy for the de novo synthesis of structurally diverse indolines. While conventional approaches often rely on prefunctionalized arenes or require oxidative/reductive steps, our method enables direct annulation from ortho-unsubstituted anilines and vinyldiazos. The sequence comprises a rhodium-catalyzed α-selective N–H insertion of vinyldiazoacetates, followed by TFA-promoted aza-Claisen rearrangement and intramolecular aza-Michael addition. This one-pot sequential protocol exhibits broad substrate generality and has been extended to an asymmetric version and intramolecular variant, allowing the synthesis of challenging seven-membered ring-fused indolines. DFT studies support a concerted mechanism via a chairlike transition state. With its operational simplicity and structural versatility, this methodology provides an efficient route to access privileged indoline scaffolds for pharmaceutical and synthetic applications.