Control of Diastereo- and Enantioselectivity in Metal-Catalyzed 1,3-Dipolar Cycloaddition Reactions of Nitrones with Alkenes. Experimental and Theoretical Investigations

The scopes and limitations of the catalytic effects of achiral and chiral Mg(II) and Cu(II) complexes on the stereochemistry of the 1,3-dipolar cycloaddition reaction of nitrones with alkenes have been investigated. A remarkably high degree of <i>endo-</i>selectivity (<i>endo</i>/<i>exo</i> > 20) is induced in the 1,3-dipolar cycloaddition reaction by the presence of a catalytic amount of, especially, a Mg(II)−phenanthroline complex. The diastereochemical assignment of the product is confirmed by an X-ray crystallographic determination of the structure of the <i>exo</i>-isoxazolidine. By the reaction of an alkene bearing a chiral auxiliary, with different nitrones and a catalytic amount of the Mg(II)−phenanthroline complex, one of four possible diastereomers of the isoxazolidines is exclusively formed. The absolute stereochemistry of this product is also assigned by an X-ray crystallographic investigation. The presence of a catalytic amount of a chiral Mg(II)−bisoxazoline complex in the 1,3-dipolar cycloaddition reaction leads to high <i>endo-</i>selectivity and occasionally with an ee > 80%. The reaction mechanism of the Mg(II)-catalyzed reaction is discussed on the basis of the experimental results and semiempirical quantum chemical calculations. The calculations are used to account for the catalytic effect of the Mg(II)−ligand complexes and to determine transition state energies for both the uncatalyzed and Mg(II)−ligand-catalyzed reactions.