Copper(II)-Bisoxazoline Catalyzed Asymmetric 1,3-Dipolar Cycloaddition Reactions of Nitrones with Electron-Rich Alkenes

Abstract

A transition-metal-catalyzed diastereo- and enantioselective 1,3-dipolar cycloaddition reaction between electrophilic nitrones and electron-rich alkenes has been developed employing chiral copper(II)- and zinc(II)-bisoxazolines as catalysts. In the presence of Cu(OTf)2-bisoxazoline as the catalyst, the nitrones, which coordinate to the chiral catalyst in a bidentate fashion, reacted smoothly with alkenes at room temperature to give isoxazolidines in good yields and diastereoselectivity and with high enantioselectivities of up to 94% ee. The influence of the metal salts, chiral ligands, and solvents on the reaction course has been investigated, and a general reaction protocol is developed. On the basis of the absolute stereochemistry of the 1,3-dipolar cycloaddition product, the coordination of the nitrone to the catalyst is discussed and a mechanistic approach of the reaction is presented. It is proposed that the intermediate is one in which both the nitrone and alkene are coordinated to the chiral copper(II)-bisoxazoline catalyst.