REVERSING THE REGIOCHEMICAL COURSE OF 1,3-DIPOLAR CYCLOADDITION OF NITRILE OXIDES BY MODIFICATION OF DIPOLAROPHILES

The orientation of the cycloaddition of nitrile oxide to beta-substituted-alpha,beta-unsaturated aldehyde equivalents was directed by choice of the carbonyl protective group; both of the two possible regioisomers of 2-isoxazolines were selectively prepared. Cycloaddition to the acetal derivatives preferentially gave the regioisomer bearing acetal group on C(4) position. While the opposite regioselectivity was observed for the cycloaddition to dithioacetal derivatives, where the sulfur functional group was mainly located at C(5) position. Theoretical studies on these regiochemical courses showed the C(5) orientation of dithioacetal groups to be directed by steric control, whereas frontier orbital interaction controlled the C(4) orientation of the acetal groups.