Cu-catalyzed interrupted [3+2] cycloaddition of trifluoroacetonitrile imines with terminal alkynes: facile access to diverse tetrasubstituted 3-trifluoromethyl pyrazoles

Abstract

Trifluoromethylated pyrazoles represent high-value heterocyclic scaffolds widely utilized in pharmaceutical and agrochemical sectors, while conventional synthetic strategies suffer from severe limitations in efficient access to their fully substituted variants. Herein, we report a copper-catalyzed cascade [3+2] cycloaddition/interception reaction of trifluoroacetonitrile imines with terminal alkynes, which delivers tetrasubstituted 3-trifluoromethyl pyrazoles in good to excellent yields via trapping the transient 5-copper-pyrazole intermediate. This protocol features broad substrate scope, excellent functional group tolerance, gram-scale scalability, and applicability for late-stage functionalization of complex bioactive molecules, providing a robust tool for relevant drug discovery research.