Pericyclic Approach to Synthesis of Substituted Pyrazoles

Significance

Reported is a synthesis of substituted pyrazoles from enol triflates and diazoacetates. The reaction proceeds by Pd-catalyzed cross-coupling, after which an electrocyclization affords the pyrazoles. Studies regarding Pd source, base and solvent led to the optimized conditions shown in the scheme. The reaction tolerates functional groups such as TMS and boronate esters, and the yields range from mediocre to good. Scalability was shown by running the reaction on 50 mmol scale in one instance. E-Enol triflates were shown to afford lower yields compared to their Z-counterparts due to formation of olefinic side products. Furthermore, when tetrasubstituted enol triflates were used, some interesting [1,3]-alkyl shifts and [3,3]-Cope rearrangement products were isolated (D).