Zwitterion-Induced Synthesis of Pyrazines and Pyrazolopyridazines

Significance

A synthesis of pyrazoline and pyrazolopyridazine derivatives from the reaction of chalcones with azo diesters is reported. The reaction proceeds via the Huisgen zwitter­ions, formed from the combination of triphenyl­phosphine with dialkyl azodicarboxylate, which is suggested to undergo reaction with chalcones or dienones via an oxadiazoline intermediate, which upon fragmentation, followed by ring closure, leads to the product pyrazolines. Vinyl pyrazolines, derived from dienones undergo further reaction with a second dialkyl azodicarboxylate in a Diels-Alder fashion to afford pyrazolopyridazines in good yields. In cases of nonidentical R¹ and R² substituents, the regioselectivity depends on their relative electronegativities. Broad scope for both pyrazoline and pyrazolopyridazine products with respect to aryl substitution was established.