Iodine(I)‐Induced Skeletal Rearrangement of α‐Bicyclobutanyl Alcohols and Amines: A Universal Approach to 2‐Oxabicyclo[2.1.1]hexanes and 2‐Azabicyclo[2.1.1]hexanes

Abstract Bicyclo[1.1.0]butane (BCB) has been widely explored as a scaffold for constructing 3D bioisosteres of benzene, owing to its olefin‐like reactivity and ability to undergo cycloaddition reactions. Herein, we report that BCB derivatives bearing β ‐positioned hydroxyl or tosylamino groups (i.e., α ‐BCB alcohols or amines) undergo an unusual iodine(I)‐mediated 4‐endo cyclization to afford 2‐oxabicyclo[2.1.1]hexanes and 2‐azabicyclo[2.1.1]hexanes (BCHs). This strategy addresses a major limitation of prior BCHs synthesis, which typically require substrates tethered to carbonyl groups or aromatic rings to enable electronic polarization or photo‐excitability. By circumventing this requirement, our method significantly broadens the range of substituents that can be incorporated into the BCH framework. Additionally, the transformation features practical advantages, including straightforward one‐step substrate preparation, mild reaction conditions, and rapid kinetics—often completing within minutes. Mechanistic studies suggest that the 4‐endo cyclization proceeds via an iodonium‐induced carbocation intermediate, which is intramolecularly trapped by the nucleophilic ─OH or ─NHTs group.