Controlled Pyrazole-Hydrazone Annulation: Regiodivergent Synthesis of 1H- and 2H-Pyrazolo[3,4-d]pyridazinones

Anefficient and controlled site-selective annulation of 3,5-diethoxycarbonyl4-hydrazonyl pyrazoles is described. The relative proportion of theproducts is affected by hydrazone intermediate configuration, reactiontemperature, and Lewis acid employed. At a temperature of 110-120 & DEG;C, the reaction preferentially afforded 1H-pyrazolo[3,4-d]pyridazin-7(6H)-ones, whereas using Yb(OTf)(3) in MeCN reflux, 2H-pyrazolo[3,4-d]pyridazin-7(6H)-ones were favored. Computationalinvestigations were performed to clarify the mechanism and the originof the regiodivergence.