Catalytic enantioselective 1,3-dipolar cycloaddition reactions of cyclic nitrones: A simple approach for the formation of optically active isoquinoline derivatives

The first highly diastereo- and enantioselective catalytic 1,3-dipolar cycl oaddition reaction of cyclic nitrones activated by chiral Lewis acids with electron-rich alkenes has been developed. The nitrones, mainly 3,4-dihydroi soquinoline N-oxides, are activated by chiral 3,3'-aryl BINOL-AlMe complexe s and undergo a regio-, diastereo-, and enantioselective 1,3-dipolar cycloa ddition reaction with especially alkyl vinyl ethers, giving the exo diaster eomer of the cycloaddition products in high yield, >90% de and up to 85% ee . The reaction has been investigated under various conditions, and it is de monstrated that the reaction is an attractive synthetic procedure for the i ntroduction of a chiral center in the 1-position of the isoquinoline skelet on. The mechanism of the reaction is discussed on the basis of the assignme nt of the absolute configuration of the cycloaddition product and theoretic al calculations.