Alkynyl <i>Halo-</i>Prins Cyclizations for the Synthesis of Bicyclo[4.3.1] and [3.3.1] Oxygen-Bridged Heterocycles

This report presents the alkynyl <i>halo</i>-Prins cyclization of Achmatowicz adducts, enabling the synthesis of up to 24 (24) highly functionalized [4.3.1] and [3.3.1] heterocycles containing a bridging oxygen. The substrate scope demonstrates that this method is compatible with a range of substitution patterns and ring substituents and does not appear to depend upon the electronic nature of the ring system. Furthermore, the reaction can be carried out on a multigram scale without a significant loss in yield. To showcase the versatility of these oxacycles as synthetic tools, we explore their application in various chemical transformations, including cross-coupling reactions, [4 + 2] cycloaddition, cyclopropanation, addition, and reduction reactions, ultimately facilitating the preparation of a modest compound library.