Lewis acid-catalyzed [4+3] cyclization of para-quinone methides and 1,3-dipolarophiles to construct benzofused seven-membered heterocycles

Abstract

This study presents a Lewis acid-catalyzed [4+3] cyclization approach for synthesizing benzofused seven-membered heterocycles using paraquinone methides (p-QMs) and 1,3-dipolarophiles such as aziridines and donor–acceptor cyclopropanes. Various Lewis acids and conditions were screened, with yielding the desired benzoxazepine in moderate yield and good diastereoselectivity. Mechanistic insights suggest a Lewis acid-promoted aza-Michael addition pathway and highlight conditions leading to by-product formation. This work advances the construction of nitrogen–oxygen-containing heterocycles, offering a promising method for accessing complex scaffolds relevant to medicinal chemistry and synthetic organic applications.