HFIP-Mediated (3+2) Annulation of Bicyclobutanes with Indolyl Alcohols for Diastereoselective Access to Tetracyclic Spiroindolenines

Although bicyclo[2.1.1]hexanes (BCHs) have emerged as powerful bioisosteres of substituted benzenes, efficient methods for the synthesis of their spirocyclic variants remain limited. Herein, we disclose HFIP-mediated (3+2) annulation of bicyclo[1.1.0]butanes (BCBs) with in situ-generated exocyclic olefins from N-H indolyl alcohols, furnishing spiro-BCHs in a highly diastereoselective manner over the expected tetracyclic indoles. The reaction proceeds under mild, metal-free, and photocatalyst-free conditions, with HFIP serving as a dual activator via hydrogen bonding. Mechanistic studies reveal the unique ability of HFIP to selectively deliver (3+2) spiro-annulated products over the competing (3+3) annulation.