Modular Access to Bridgehead Heterocycle-Substituted Bicyclo[1.1.0]butanes via Late-Stage Functionalization of Alkynylbicyclo[1.1.0]butanes

Abstract

Strain-release transformations of bicyclo[1.1.0]butanes are powerful methods for constructing four-membered rings and bicyclo[n.1.1]alkane scaffolds of medicinal interest. However, the lack of efficient methods for the synthesis of bridgehead-heterocycle-substituted bicyclo[1.1.0]butanes limits their application in the synthesis of corresponding heterocycles. Herein, we disclose alkynylbicyclo[1.1.0]butanes (ABCBs) as versatile synthons: the strained bicyclobutane core remains unscathed while the alkyne handle undergoes mild, late-stage cycloadditions to deliver triazole-, isoxazole-, free-NH-pyrrole, free-NH-pyrazole or silacyclohexene-decorated BCBs that are otherwise difficult to access by conventional routes.