Simultaneous Activation of Bicyclobutanes and Indolyl Alcohols with HFIP: Access to Indole‐Fused Bicyclo[3.1.1]Heptanes

Abstract The concept of strain release to unleash unique reactivity that drives a wide range of synthetically valuable transformations has long intrigued chemists. Among the various strained systems, highly reactive bicyclo[1.1.0]butanes (BCBs) have recently emerged as versatile building blocks for constructing bicyclic scaffolds. Despite the existence of various activation pathways for BCBs, the use of 1,1,1,3,3,3‐hexafluoroisopropan‐2‐ol (HFIP) to activate BCBs has not been realized so far. Herein, we report the first HFIP‐promoted (3 + 3) annulation of BCBs with indolyl alcohols through the simultaneous activation of both partners, facilitating the metal‐ and photocatalyst‐free synthesis of indole‐fused bicyclo[3.1.1]heptanes. Mechanistic studies reveal the role of HFIP in activating both components, and the reaction proceeds by an initial (3 + 2) annulation followed by a ring expansion/aromatization cascade.