Synthesis of spirocyclopropylpyrazole derivatives via the cascade reaction of alkylidenecyclopropanes with pyrazolidinones and trifluoroethanol

Abstract

A novel synthesis of spirocyclopropylpyrazole derivatives tethered with a trifluoromethyl unit through an unprecedented cascade reaction of alkylidenecyclopropanes with pyrazolidinones and trifluoroethanol (TFE) has been developed. Mechanistically, the reaction involves the generation of cyclic azomethine imine and its simultaneous [3 + 2] dipolar cycloaddition with alkylidenecyclopropane followed by nucleophilic addition with TFE and C–N bond cleavage of the pyrazolidinone ring. To our knowledge, this is the first example in which pyrazolidinone underwent an oxidative cycloaddition with alkene followed by cleavage of the amide bond to give the synthetically and biologically interesting spirocyclopropylpyrazole products. In this cascade process, air serves as an economical and sustainable oxidant. Compared with the literature methods, this new protocol has advantages such as multi-step transformations accomplished in one pot, valuable products from simple starting materials, broad substrate scope, mild reaction conditions, good efficiency and excellent atom-economy.