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

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.