DIPOLAR CYCLOADDITION REACTIONS OF DIHYDROPYRIMIDINE-FUSED MESOMERIC BETAINES - AN APPROACH TOWARD CONFORMATIONALLY RESTRICTED DIHYDROPYRIMIDINE DERIVATIVES

The bimolecular and intramolecular cycloaddition potential of various 4-aryldihydropyrimidine-fused mesomeric betaines was investigated. Dih ydropyrimidine-fused isothiomunchnones and isomunchnones were found to undergo 1,3-dipolar cycloaddition reactions with electron-deficient d ipolarophiles such as DMAD, methyl propiolate, methyl vinyl ketone, or N-methylmaleimide. In contrast, cross-conjugated mesomeric thiazinium betaines underwent 1,4-dipolar cycloaddition reaction with electron-r ich dipolarophiles such as ynamines or ketene acetals. In general, the se cycloadditions show a high degree of regioselectivity, facial selec tivity, and exo/endo diastereoselectivity. Intramolecular variations o f the above processes involving o-alkenylaryl-tethered dihydropyrimidi ne-fused isomunchnones lead to polycyclic dihydropyrimidine analogs th at closely mimic the proposed receptor-bound conformation of dihydropy ridine calcium channel modulators. These cycloadducts are the result o f an endo-addition of the pi-bond to the carbonyl ylide dipole embedde d in the isomunchnone system. The relative stereochemistry of these cy cloadducts was established by single-crystal X-ray analysis.