Regioselectivity and endo/exo selectivity in the cycloadditions of the phthalazinium dicyanomethanide 1,3-dipole with unsymmetrical alkene and alkyne dipolarophiles. Unexpected reversals of regiochemistry: a combined experimental and DFT theoretical study

Abstract

In the reactions of phthalazinium dicyanomethanide 1,3-dipole with electron-poor monosubstituted alkene and alkyne dipolarophiles the dicyanomethanide terminus bonds to the unsubstituted carbon giving 1-substituted pyrrolo[2,1-a]phthalazines. With electron-rich dipolarophiles the regiochemistry is reversed and the products are 2-substituted pyrrolo[2,1-a]phthalazines. An unexpected reversal of regiochemistry occurred with methyl methacrylate, due to a steric effect of the C–Me group, and the main product was 2-exo-methyl-2-endo-methoxycarbonyl-3,3-dicyano-1,2,3,10b-tetrahydropyrrolo[2,1-a]phthalazine, 17. endo Cycloadditions were strongly favoured with alkene dipolarophiles containing π bonds in substituents on the alkene unit. With N-substituted maleimides endo products were formed exclusively even when the N-substituent was ^tBu or adamantyl. Only with alkoxyvinyl ethers were exo-cycloadducts encountered. The mechanisms are discussed in conjunction with DFT calculations. An X-ray crystal structure is reported on endo-N-tert-butyl-3,3-dicyano-1,2,3,10b-tetrahydropyrrolo[2,1-a]phthalazine-1,2-dicarboximide, 25.