A practical solution to achieve the elusive etherification of bicyclo[1.1.1]pentyl alcohols

Since the first synthesis of bicyclo[1.1.1]pentane (BCP) analogues in the 1960s, both the academic and industrial communities have continued to deliver novel transformations and synthetic strategies that provide access to diverse polysubstituted BCPs. Despite these efforts, access to ether-substituted BCPs via direct etherification of a BCP-alcohol remains a significant challenge. Here, we detail our approach toward overcoming this limitation by exploiting trichloroacetimidate reactivity under acidic conditions, obviating the intrinsic base-mediated decomposition pathway which previously limited the syntheses of BCP alcohols. This is the first general synthesis of BCP ethers via direct alkylation of BCP alcohols.