Syntheses of highly functionalized cyclobutenes via [2 + 1 + 1] cycloaddition of isocyanides and an unprecedented ring expansion

Abstract

A new type of Lewis acid catalyzed [2 + 1 + 1] cycloaddition reaction of isocyanides with alkylidene malonates and 3-alkylideneindolinones is reported herein. The method exhibited advantages such as easily accessible starting materials, a broad substrate scope, easy scale-up and high atom-economy. A series of functionalized cyclobutene skeletons were obtained in up to 90% yield under mild reaction conditions. In addition, the cyclobutenes could be subjected to diverse downstream transformations. Intriguingly, an unprecedented ring expansion of cyclobutene was performed to afford a range of polysubstituted maleimides. Mechanistic experiments revealed that the acid and water play an important role in the ring expansion process. The theoretical calculation studies provided guidance on the in-depth insight into the mechanistic underpinnings of this skeletal ring expansion protocol.