Synthesis of 1-Fluoroalkyl-5-Substituted-1,2,3-Triazoles from Carbonyl-Stabilized Phosphonium Ylides

Abstract

A mild, rapid, and regioselective cyclization of azidofluoroalkanes with carbonyl-stabilized phosphonium ylides, resulting in the formation of 1-fluoroalkyl-5-substituted-1,2,3-triazoles, is presented. The synthetic method tolerates air and water, works at room temperature in a benign solvent, and is metal-free. Both starting materials are commercially available and easily prepared. The cyclization method was expanded to 4-halogen-substituted analogues of target triazoles, which underwent either rhodium-catalyzed transannulation with benzonitrile to yield uniquely substituted N-fluoroalkylated 4-haloimidazoles or cross-coupling reactions to produce fully substituted N-fluoroalkylated triazoles.