Endo-Selective Asymmetric Inverse Electron-Demand 1,3-Dipolar Cycloaddition Reaction of Nitrones

In the presence of a catalytic amount of the optically active cobalt(III) hexafluoroantimonate, the inverse electron-demand 1,3-dipolar cycloaddition reaction of dihydrofuran with nitrones bearing an electron-withdrawing group effectively proceeded to afford the corresponding adducts with excellent endo-selectivity.The catalytic enantioselective 1,3-dipolar cycloaddition reaction of nitrones is one of the most practical methods for the construction of enantiomerically pure isoxazolidines, which are then employed as key intermediates in transformation into -amino alcohols under mild reducing conditions, and as useful synthons for the preparation of various biologically active compounds, such as alkaloids, -lactams, and -amino acids.1 Several groups have recently reported the catalytic enantioselective 1,3-dipolar cycloaddition reactions of nitrones with alkenoyl oxazolidinones, electron-deficient alkenes 2 favorable for the bidentate coordination of a Lewis acid catalyst.However, monodentate alkenals have also been applied 3 to the enantioselective 1,3-dipolar cycloaddition reaction.It was found that cationic 3-oxobutylideneaminatocobalt(III) complexes could be employed as effective Lewis acid catalysts for the enantioselective 1,3-dipolar cycloaddition reaction of alkenals even in the presence of electron-donating nitrones. 4n these catalytic systems, the HOMO(nitrone)-LUMO(alkene) interaction is assumed to dominate the reactivity and selectivity, but the alternative HOMO(alkene)-LUMO(nitrone) interaction is also expected due to the lowering of the LUMO level through the coordination of the electron-donating nitrone to the Lewis acid catalyst and the raised HOMO level of the electron-rich alkenes