Lewis Acid Catalyzed Formal (3+2)‐Cycloaddition of Bicyclo[1.1.0]butanes with Ketenes

Abstract

AbstractDesign, synthesis and application of benzene bioisosteres have attracted a lot of attention in the past 20 years. Recently, bicyclo[2.1.1]hexanes have emerged as highly attractive bioisosteres for ortho‐ and meta‐substituted benzenes. Herein we report a mild, scalable and transition‐metal‐free protocol for the construction of highly substituted bicyclo[2.1.1]hexan‐2‐ones through Lewis acid catalyzed (3+2)‐cycloaddition of bicyclo[1.1.0]‐butane ketones with disubstituted ketenes. The reaction shows high functional group tolerance as documented by the successful preparation of various 3‐alkyl‐3‐aryl as well as 3,3‐bisalkyl bicyclo[2.1.1]hexan‐2‐ones (26 examples, up to 89 % yield). Postfunctionalization of the exocyclic ketone moiety is also demonstrated.