Synthesis of Bioactive Fluorinated 2-Heterocyclic Pyrrolidines via Copper(I)-Catalyzed Asymmetric 1,3-Dipolar Cycloaddition of Azomethine Ylides

Abstract

Abstract A copper-catalyzed asymmetric 1,3-dipolar cycloaddition of α-N-(heteroaryl-methyl)imines with gem-difluoroalkenes is reported. Using a Cu(I)/Segphos complex, this protocol provides diverse chiral fluorinated 2-heterocyclic pyrrolidines in high yields (up to 99%) with excellent stereoselectivity (up to 98% ee, >20:1 dr). This method is compatible with various heteroaryl groups and complex natural products. Notably, these scaffolds exhibit potent antifungal activity against Magnaporthe oryzae, with the lead compound 4a outperforming the commercial fungicide isoprothiolane by 50% in EC50 values.