Organocatalytic Intramolecular [4+2] Cycloaddition between In Situ Generated Vinylidene ortho-Quinone Methides and Benzofurans

Abstract

Described herein is the enantioselective construction of oxygen-containing [5-6-5] tricyclic heterocycles by an organocatalyzed asymmetric [4+2] cycloaddition of vinylidene ortho-quinone methides and benzofurans. According to this methodology, a series of oxygen-containing [5-6-5] tricyclic heterocycles with various functional groups were synthesized in excellent enantio- and diastereoselectivities (>99 % ee, >20:1 d.r.). Furthermore, the deuterium-labeling experiments and high-resolution mass spectroscopy demonstrated that a vinylidene ortho-quinone methide intermediate was involved and possibly resulted from a prototropic rearrangement of 2-ethynylphenol. Remarkably, a catalyst loading as low as 0.1 mol %, and a gram-scale synthesis were achieved for this transformation.

Keywords: cycloaddition; heterocycles; organocatalysis; polycycles; rearrangements.