Facile Access to Bicyclo2.1.1hexanes by Formal Cycloaddition be-tween Silyl Enol Ethers and Bicyclo1.1.0butanes with Lewis acids

Saturated three-dimensional carbocycles have gained increasing prominence in synthetic and medicinal chemistry. In par-ticular, bicyclo2.1.1hexanes (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-clo1.1.0butanes (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-clo4.1.1octanes (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-clo2.1.1hexane frameworks, and derivatization of silyl enol ethers on bicyclo4.1.1octanes, delivering novel functional-ized bicycles that are traditionally inaccessible.