Reversal of regioselectivity of nitrone 1,3-dipolar cycloadditions by Lewis acids

The regio- and stereoselectivity of cycloaddition of N-benzyl-2-benzyloxyethylideneamine N-oxide (1) with 3-acroyl- 1,3-oxazolidin-2-one (2) in dichloromethane at room temperature depends upon the nature of the Lewis acid. Addition of Lewis acid reverses the regioselectivity of the cycloaddition. The sterically controlled isoxazolidine-5-oxazolidinones 3a,b are produced as the major products in the absence of Lewis acid, while the electronically controlled isoxazolidine-4-oxazolidinones 4a,b are given as dominant products in the Ti(Oi-Pr)(2)Cl-2 complex-catalyzed reactions. The reactions with other Lewis acids such as BF3, ZnBr2 and Mg(ClO4)(2) gave both regioisomeric pairs of the diastereoisomers favouring 4-substituted regioisomers.