Broadening the Scope of van Leusen Reaction: Investigation of Benzofuro[2,3‐d]imidazole Formation

Abstract

The van Leusen reaction utilizes p‐toluenesulfonylmethyl isocyanide as a versatile synthon for constructing nitrogen‐containing heterocycles, such as oxazoles, imidazoles, thiazoles, and pyrroles. In this study, the van Leusen imidazole reaction, employed for synthesizing potential Hsp90 inhibitors, yielded unexpected side products containing novel condensed tricycles, specifically 3a,8b‐dihydro‐1H‐benzofuro[2,3‐d]imidazoles. The mechanism behind the formation of this unprecedented fragment was further analyzed through quantum mechanical calculations and experimental investigations of the reaction outcome under different reaction conditions and with various substituents. Additionally, the stabilities of the products were evaluated.