N-Difluorocyclopropyl-Substituted Pyrazoles: Synthesis and Reactivity

Difluorocyclopropanation of N‐vinylazoles with the CF₃SiMe₃–NaI system was studied. It was found that N‐vinylpyrazoles could be transformed into the corresponding N‐difluorocyclopropyl‐substituted derivatives. The method was efficient on a 100 g scale and could be applied for the preparation of various functionalized regioisomeric pyrazole derivatives bearing a gem‐difluorocyclopropane moiety, such as amines, carboxylic acids, aldehydes, bromides, and boronic esters. It was found that N‐difluorocyclopropylpyrazole moiety tolerated many common reagents including nitrating mixture, bromine, aqueous acids and alkali, KMnO₄, LiBH₄, and Pd⁰ complexes; it was unstable towards AlCl₃, catalytic hydrogenation and lithiation conditions. The products obtained are advanced building blocks which of potential importance to medicinal and agrochemistry.