Aldehydes Switch Regioselectivity: a Prins Cyclization Strategy for the Synthesis of Indoline‐fused THFs and Indole‐fused Oxepanes

Abstract

We have identified a switchable Prins cyclization process to form indoline‐fused tetrahydrofurans and indole‐fused oxepanes by applying different types of aldehydes under two sets of optimized conditions. Significantly, a novel Prins reaction mechanism involving an oxonium‐mediated rearrangement in the formation of five‐membered cyclic ethers is realized for the first time.magnified image

Formal (3 + 4)-Annulation of Propargylic p-Quinone Methides with 2-Indolylmethanols: Synthesis of Polysubstituted Indole-Fused Oxepines

“… In this regard, the synthesis of such tricyclic skeletons has received considerable attention from academic chemists. Traditional methods for the synthesis of indole-fused oxepines include metal-catalyzed cyclization of indoles with alkynes or allenes and intermolecular (5 + 2)-annulations . Alternatively, (4 + 3)-annulation is one of the most powerful methods to synthesize seven-membered rings .…”

Indole-Fused Benzoxepine Synthesis via Visible-Light-Driven Aerobic Dehydrogenative [5 + 2] Annulation

“…In recent decades, extensive efforts have been made to access indole-fused oxepine frameworks, including cascade annulation, Prins cyclization, Brønsted-acid- or Lewis-acid-promoted [4 + 3] annulation, , and rhodium- or palladium-catalyzed [5 + 2] annulation (Scheme , top), etc. Among them, the [5 + 2] annulation represents a versatile synthetic protocol for constructing a valuable seven-membered heterocycle.…”