Diastereoselective Synthesis of Dimethyl (4R*,4a′R*,7a′R*)-1-Aryl-6′-benzoyl-4a′-methyl-5-oxo-1,4′,4a′,5,5′,6′-hexahydrospiro[pyrazole-4,7′-pyrrolo[3,4-c]pyridazine]-3′,7a′(1′H)-dicarboxylates

Methyl (Z)-2-(benzoylamino)-3-(dimethylamino)propenoate (1) reacted with trimethylenemethane (2) to produce methyl (Z)-2-[benzoyl(2-methylallyl)amino]-3-(dimethylamino)propenoate (3), which was then converted into pyrazole derivatives 11a-h by a consecutive exchange of the dimethylamino group with hydrazine derivates 9a-h and cyclization to the ester group. Reactions of pyrazoles 11a-g with dimethyl 1,2,4,5-tetrazine-3,6-dicarboxylate (6) resulted in the diastereoselective formation of 1-aryl-6'-benzoyl-4a'-methyl-5-oxo-1,4',4a',5,5',6'-hexahydrospiro[pyrazole-4,7'-pyrrolo[3,4-c]pyridazine]-3',7a'(1'H)-dicarboxylates 12a-g. This represents a simple new pathway to novel heterocyclic systems. On the other hand, when (dimethylamino)propenoate 3 reacted with aniline hydrochloride (4), followed by the cycloaddition of 1,2,4,5-tetrazine 6, dimethyl (E)- and (Z)-4-({benzoyl[1-(methoxycarbonyl)-2-(phenylamino)vinyl]amino}methyl)-4-methyl-1,4-dihydropyridazine-3,6-dicarboxylates (7) and (8) were formed, respectively.