Ferrocene-Catalyzed Aromatization and Competitive Oxidative Ring Transformations of 1,2-Dihydro-1-Arylpyridazino[4,5-d]Pyridazines

This paper presents the expected and unexpected, but typically substituent-dependent, ferrocene-catalyzed DDQ-mediated oxidative transformations of a series of 5,8-bis(methylthio)-1-aryl-1,2-dihydropyridazino[4,5-d]pyridazines and 8-(3,5-dimethyl-1H-pyrazol-1-yl)-5-(methylthio)-1-aryl-1,2-dihydropyridazino[4,5-d]pyridazines. Under noncatalytic conditions the reactions were sluggish, mainly producing a substantial amount of undefined tarry materials; nevertheless, the ferrocene-catalyzed reactions of the 5,8-bis(methylthio)-substituted precursors gave the aromatic products the expected aromatic products in low yields. Their formation was accompanied by ring transformations proceeding via aryne-generating fragmentation/Diels–Alder (DA)/N2-releasing retro Diels–Alder (rDA) sequence to construct arene-fused phthalazines. On the other hand, neither the noncatalytic nor the catalytic reactions of the 8-pyrazolyl-5-methylthio-substituted dihydroaromatics yielded the expected aromatic products. Instead, depending on their substitution pattern, the catalytic reactions of these pyrazolyl-substituted precursors also led to the formation of dearylated arene-fused phthalazines competing with an unprecedented multistep fragmentation sequence terminated by the hydrolysis of cationic intermediates to give 4-(methylthio)pyridazino[4,5-d]pyridazin-1(2H)-one and the corresponding 3,5-dimethyl-1-aryl-1H-pyrazole. When 0.6 equivalents of DDQ were applied in freshly absolutized THF, a representative pyrazolyl-substituted model underwent an oxidative coupling to give a dimer formed by the interaction of the cationic intermediate, and a part of the N-nucleophilic precursor remained intact. A systematic computational study was conducted on these intriguing reactions to support their complex mechanisms proposed on the basis of the structures of the isolated products.