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

An efficient and controlled site-selective annulation of 3,5-diethoxycarbonyl 4-hydrazonyl pyrazoles is described. The relative proportion of the products is affected by hydrazone intermediate configuration, reaction temperature, and Lewis acid employed. At a temperature of 110-120 °C, the reaction preferentially afforded 1 H -pyrazolo[3,4- d ]pyridazin-7(6 H )-ones, whereas using Yb(OTf) 3 in MeCN reflux, 2 H -pyrazolo[3,4- d ]pyridazin-7(6 H )-ones were favored. Computational investigations were performed to clarify the mechanism and the origin of the regiodivergence.