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

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.