Simultaneous Activation of Bicyclobutanes and Indolyl Alcohols Using HFIP: Access to Indole-Fused Bicyclo[3.1.1]heptanes

The concept of strain release has long intrigued chemists, unleashing the unique reactivity that drives a wide range of synthetically valuable transformations. Among various strained systems, bicyclo[1.1.0]butanes (BCBs), highly reactive species, have recently emerged as versatile building blocks for constructing bicyclic scaffolds. Despite the existence of various activation pathways for BCBs, the use of hexafluoro isopropanol (HFIP) for activating BCBs has not been realized so far. Herein, we report the first HFIP-promoted (3+3) annulation of BCBs with indolyl alcohols via 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 via an initial (3+2) annulation followed by a ring expansion/aromatization cascade.