PAPER: Control of diastereo- and enantioselectivity in metal-catalyzed 1,3-dipolar cycloaddition reactions of nitrones with alkenes. Experimental and theoretical investigations

Gothelf, K. V.; Hazell, R. G.; Jørgensen, K. A.

J. Org. Chem. 1996, 61, 346–355, doi: 10.1021/jo951204e

Department of Chemistry, Aarhus University, DK-8000 Aarhus C, Denmark


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 endo-selectivity (endo/exo > 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 exo-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 endo-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.

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