PAPER: Metal-catalyzed asymmetric 1,3-dipolar cycload- dition reactions

Gothelf, K. V.; Jørgensen, K. A.

Acta Chem. Scand. 1996, 50, 652–660.

Aarhus Univ. Dept. Chem. Langelandsgade 140, DK-8000 Aarhus C

Abstract

The 1,3-dipolar cycloaddition reaction is an important reaction in organic chemistry since synthetically versatile isoxazolidines with up to three contiguous chiral centers can be formed. The most recent highlights in metal-catalyzed asymmetric 1,3-dipolar cycloaddition reactions of alkanes with nitrones are described. A new catalytic approach forthe 1,3-dipolar cycloaddition reaction between N-acryloyloxazolidinones and nitrones has been developed. By the application of a chiral TiCl2-TADDOLate catalyst this 1,3-dipolar cycloaddition reaction proceedswith both exo- and enantio-selectivity. When the coordination mode ofthe ligands at the catalyst is changed to, e.g., a Mg-II-phenanthroline catalyst, the 1,3-dipolar cycloaddition reaction proceeds with a high degree of endo-selectivity. Employing a chiral alkene in the Mg-II-phenanthroline-catalyzed reaction leads to high, or complete, double diastereoselectivity. By the use of a chiral Mg-II-bisoxazoline catalyst high endo-selectivity, and up to 82% enantioselectivity in the 1,3-dipolar cycloaddition reaction of alkenes with nitrones can be achieved. On the basis of a series of semiempirical quantum chemical calculations of the transition states for the magnesium(II) complex catalyzed reactions the catalytic and the diastereo- and enantio-selective courseof the reactions can be accounted for. The endo- and enantio-selectivity in the 1,3-dipolar cycloaddition reaction of alkenes with nitronescan be further improved by replacement of the chloride ligands in theexo-selective TiCl2-TADDOLate catalyst with tosylato ligands to give diastereo- and enantio-selectivities of >90%. The development of theseaspects of the 1,3-dipolar cycloaddition reaction of alkenes with nitrones is based on the isolation and characterisation of a TiCl2-TADDOLate-alkene intermediate which has led to an understanding of the mechanism of the approach of the nitrone to the alkene.

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