A General Approach towards NH-Pyrazoles That Bear Diverse Fluoroalkyl Groups by Means of Fluorinated Iminium Salts

A new and general approach to important fluoroalkyl-substituted pyrazoles has been developed. The approach is based on the use of fluoroalkyl amino reagents and their Lewis acid activation to form a fluoroalkyl iminium salt that acts as a formal fluoroacyl transfer reagent. Their interaction with readily available fluoroalkyl azines followed by spontaneous cyclization of the formed intermediates under acidic conditions leads to the formation of 3,5-disubstituted pyrazoles. The reaction is extremely versatile, high yielding, and allows quick access to pyrazoles that bear two fluoroalkyl functionalities ( identical or different). These compounds are otherwise difficult to prepare. The reaction is scalable and suitable for industrial production.