Key points are not available for this paper at this time.
Abstract Saturated three-dimensional carbocycles have gained increasing prominence in synthetic and medicinal chemistry. In particular, bicyclo2.1.1hexanes (BCHs) have been identified as the molecular replacement for benzenes. Here, we present facile access to a variety of BCHs via a stepwise two-electron formal (3 + 2) cycloaddition between silyl enol ethers and bicyclo1.1.0butanes (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 can provide access to bicyclo4.1.1octanes (BCOs) equipped with silyl enol ethers that facilitate further transformation. The utilities of this methodology are demonstrated by the late-stage modification of natural products, transformations of tertiary alcohol units on bicyclo2.1.1hexane frameworks, and derivatization of silyl enol ethers on bicyclo4.1.1octanes, delivering functionalized bicycles that are traditionally inaccessible.
Hu et al. (Sat,) studied this question.