Brønsted Acid-Promoted Oxa-Pictet-Spengler Reaction for the Synthesis of Indole-Fused Pyran Derivatives.

A novel Brønsted acid-catalyzed oxa-Pictet-Spengler reaction was developed for the efficient synthesis of indole-fused pyran derivatives under metal-free conditions. The proposed mechanism involves acid-mediated protonation of cyclohexanone to generate an electrophilic intermediate that undergoes attack by an oxidized indole species. Subsequent steps─including intramolecular proton transfer, dehydration, cyclization, and dehydroaromatization─facilitate the assembly of the fused heterocyclic scaffold. Notably, this methodology exhibits a broad substrate scope, accommodating diverse aliphatic ketones (both cyclic and linear), thereby significantly expanding the structural diversity of accessible indole-fused pyran architectures.