Facile Access to Bicyclo[2.1.1]hexanes by Formal Cycloaddition be-tween Silyl Enol Ethers and Bicyclo[1.1.0]butanes with Lewis acids

Saturated three-dimensional carbocycles have gained increasing prominence in synthetic and medicinal chemistry. In par-ticular, bicyclo[2.1.1]hexanes (BCHs) was identified as the molecular replacement for benzenes. Here, we present a facile access to a variety of BCHs via a stepwise two-electron formal [2+3] cycloaddition between silyl enol ethers and bicy-clo[1.1.0]butanes (BCBs) under Lewis acid catalysis. The reaction features wide functional group tolerance for silyl enol ethers, allowing the efficient construction of two vicinal quaternary carbon centers and a silyl-protected tertiary alcohol unit in a streamlined fashion. Interestingly, the reaction with conjugated silyl dienol ethers could provide access to bicy-clo[4.1.1]octanes (BCOs) equipped with silyl enol ethers that facilitate further transformation. The utilities of this methodol-ogy were demonstrated by the late-stage modification of natural products, transformations of tertiary alcohol units on bicy-clo[2.1.1]hexane frameworks, and derivatization of silyl enol ethers on bicyclo[4.1.1]octanes, delivering novel functional-ized bicycles that are traditionally inaccessible.