Taming the 1,5-sigmatropic shift across protonated spirocyclic 4H-pyrazoles

The condensation of 1,3-diketones with hydrazine to access 4H-pyrazoles is a well-established synthetic route that travels through a 4H-pyrazol-1-ium intermediate. In the route to a 3,5-diphenyl-4H-pyrazole containing a cyclobutane spirocycle, density functional theory calculations predict, and experiments show that the protonated intermediate undergoes a rapid 1,5-sigmatropic shift to form a tetrahydrocyclopenta[c]pyrazole. Replacing the 3,5-diphenyl groups with 2-furanyl groups decreases the calculated rate of the 1,5-sigmatropic shift by 6.2 x 10(5)-fold and enables the isolation of new spirocyclic 4H-pyrazoles for click chemistry.