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 3trifluoromethyl 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.