Hexafluoroisopropanol Mediated Ring-Opening Reactions of Epoxides with Indoles Under Catalyst-Free Conditions

An efficient, catalyst-free, and room-temperature protocol has been developed for the ring-opening reactions of ring cyclic ethers with indoles in Hexafluoroisopropanol (HFIP). Under these mild conditions, a diverse range of indoles smoothly reacted with oxirane within 6 h, affording the corresponding C3-alkylated indoles in good-to-excellent yields. Notably, this method also shows promising reactivity toward four-membered oxetanes. Furthermore, stereospecific investigations employing enantiopure (R)-styrene oxide afforded the corresponding products with high enantiomeric excess, suggesting an S_N2 pathway with inversion of configuration. The unique hydrogen-bonding ability and acidity of HFIP are crucial for driving this facile transformation. This protocol offers a green, atom-economical, and sustainable approach for constructing structurally diverse indole derivatives, showcasing high practical utility for organic synthesis.