Copper-catalyzed enantioselective cycloaddition/amination cascade of azomethine imines, alkynes and O-benzoylhydroxylamines

Abstract

Azomethine imines as a class of important dipoles have been widely employed in enantioselective 1,3-dipolar cycloaddition reactions. Copper-catalyzed enantioselective cycloaddition of azomethine imines with alkynes is one of the most efficient tools for furnishing chiral pyrazolines. However, it is difficult to construct fully substituted pyrazolines through such copper-catalyzed reactions because the dipolarophiles are limited to terminal alkynes. Herein, we report a copper-catalyzed enantioselective cycloaddition/amination cascade reaction of azomethine imines, terminal alkynes and O-benzoylhydroxylamines to form chiral amino-substituted bicyclic pyrazolines with high enantioselectivities. This is the first description of direct synthesis of chiral fully substituted pyrazolines from readily available terminal alkynes.