Reversal of regioselectivity of nitrone cycloadditions by Lewis acids

The regio- and stereoselectivity of cycloadditions of the nitrone la and the chiral, sugar-derived nitrones 13a and 13b with 3-(prop-2-enoyl)-1,3-oxazolidin-2-one (2) depends on the nature of the Lewis acid catalyst used. Addition of Lewis acid reverses the regioselectivity of the cycloaddition, and improves the anti-diastereoselectivity in the case of chiral nitrones. The sterically favored isoxazolidin-5-yl-substituted adducts 3. 4, and 14-17 are produced as the major products in the absence of Lewis acid, while the electronically favored regioisomers with isoxazolidin-4-yl substituents (5, 6, and 18-21, respectively) are obtained as major products in the [Ti((OPr)-Pr-i)(2)Cl-2] catalyzed reactions. The reactions of nitrone 13b with 2 in the presence of other Lewis acids such as ZnCl2, ZnBr2 ZnI2 and MgI2/I-2 gave both regioisomeric pairs of the diastereoisomers, favoring the 4-substituted congeners. The diastereoisomeric isoxazolidines 3a-6a were reduced with NaBH4 in THF/H2O with subsequent desilylation to yield the separable diols 9-12. Reduction of the diastereoisomeric isoxazolidines 19a and 18a afforded the chiral alcohols 23 and 22, the latter of which was analyzed by X-ray crystallography.