METAL-CATALYZED ASYMMETRIC 1,3-DIPOLAR CYCLOADDITION REACTIONS

The 1,3-dipolar cycloaddition reaction is an important reaction in org anic chemistry since synthetically versatile isoxazolidines with up to three contiguous chiral centers can be formed. The most recent highli ghts in metal-catalyzed asymmetric 1,3-dipolar cycloaddition reactions of alkanes with nitrones are described. A new catalytic approach for the 1,3-dipolar cycloaddition reaction between N-acryloyloxazolidinone s and nitrones has been developed. By the application of a chiral TiCl 2-TADDOLate catalyst this 1,3-dipolar cycloaddition reaction proceeds with both exo- and enantio-selectivity. When the coordination mode of the ligands at the catalyst is changed to, e.g., a Mg-II-phenanthrolin e catalyst, the 1,3-dipolar cycloaddition reaction proceeds with a hig h degree of endo-selectivity. Employing a chiral alkene in the Mg-II-p henanthroline-catalyzed reaction leads to high, or complete, double di astereoselectivity. By the use of a chiral Mg-II-bisoxazoline catalyst high endo-selectivity, and up to 82% enantioselectivity in the 1,3-di polar cycloaddition reaction of alkenes with nitrones can be achieved. On the basis of a series of semiempirical quantum chemical calculatio ns of the transition states for the magnesium(II) complex catalyzed re actions the catalytic and the diastereo- and enantio-selective course of the reactions can be accounted for. The endo- and enantio-selectivi ty in the 1,3-dipolar cycloaddition reaction of alkenes with nitrones can be further improved by replacement of the chloride ligands in the exo-selective TiCl2-TADDOLate catalyst with tosylato ligands to give d iastereo- and enantio-selectivities of >90%. The development of these aspects of the 1,3-dipolar cycloaddition reaction of alkenes with nitr ones is based on the isolation and characterisation of a TiCl2-TADDOLa te-alkene intermediate which has led to an understanding of the mechan ism of the approach of the nitrone to the alkene.