Copper(i)-catalyzed asymmetric [3 + 2] cycloaddition of N-ester acylhydrazones and β-trifluoromethyl-α,β-unsaturated ketones

Abstract

Herein, the first copper(I)-catalyzed asymmetric 1,3-dipolar [3 + 2] cycloaddition of N-ester acylhydrazones and β-trifluoromethyl-α,β-unsaturated ketones has been developed, affording an array of chiral pyrazolidine derivatives containing a trifluoromethyl moiety bearing three vicinal stereocenters in excellent yields with excellent enantioselectivities and diastereoselectivities (up to 96% yield, up to 97% ee and up to >20 : 1 dr). The chiral pyrazolidines could be transformed into 2-pyrazoline derivatives bearing a trifluoromethyl unit with excellent enantio- and diastereoselectivities. Moreover, the selected chiral pyrazolidines exhibited useful biological activities against human cancer cell lines.