Catalyst-Free Synthesis of 2,3-Dihydrobenzofurans via a Formal [4+1] Annulation of Propargylamines with Sulfur Ylides

Abstract

A simple, general route to the 2,3-dihydrobenzofurans substituted at C3 by an aryethynyl or aryl group, starting from propargylamine and its derivatives with benzoyl sulfonium salts, has been developed. This reaction involved an in situ generated o-quinone methide (o-QM) intermediate followed by [4+1] annulation with sulfur ylides. Notably, this protocol's features include moderate to excellent yields and remarkable diastereoselectivity (>20:1 dr in general), easy performance, as well as applicability to versatile 2,3dihydrobenzofurans with aryethynyl or an aryl group via C−C and C−O bond formation in one pot without any catalyst in an aqueous mixed solvent.

Recent advances in the application of ylide-like species in [4 + 1]-annulation reactions: an updated review

“…49 Another approach to generate quinoid intermediates is the thermolysis of Mannich bases. Thus, He et al 50 showed that phenols 54 produce dihydrobenzofurans 55 upon heating with sulfonium salts 10 in aqueous acetonitrile (Scheme 22). In this case, the piperidine molecule served as a leaving group and also as a base, which generated sulfonium ylides from the corresponding salts 10.…”

Synthesis of 2,3‐dihydrofurans via Lewis acid‐Catalyzed [4+1] Cycloaddition of Enynones with Sulfoxonium Ylides in Ionic Liquids: A Mild and Green Platform

“…[9] More recently, the Shang group described an efficient and simple synthesis of dihydrobenzofurans by employing propargylamines and benzoyl sulfur salts under catalyst-free conditions (Scheme 1a, Eq 4). [10] Those protocols enriched the synthetic routes of 2,3-dihydrofuran derivatives. Nevertheless, their applications were limited by poor enantioselectivity, toxic solvents and high reaction temperature.…”

Rh(III)-Catalyzed Relay Double Carbenoid Insertion and Diannulation of Sulfoximine Benzamides with α-Diazo Carbonyl Compounds: Access to Furo[2,3-c]isochromenes

“…Directing group-assisted catalytic C–H bond functionalization and annulation has attracted much attention due to the feasibility and step economy for access to diverse cyclic heteroarenes, which are ubiquitous in many pharmaceuticals, natural products, and functional materials . Due to our long-standing research interest in the construction of privileged heterocycles, we envisioned that the transformable methylphenyl sulfoximine (MPS) could promote transition metal-catalyzed carbenoid insertion and annulation reactions and open a novel avenue to challenging heterocycles. We herein developed the first Rh-catalyzed continuous double carbenoid insertion and diannulation reaction (Scheme f).…”