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

The condensation of 1,3-diketones with hydrazine to access 4-pyrazoles is a well-established synthetic route that travels through a 4-pyrazol-1-ium intermediate. In the route to a 3,5-diphenyl-4-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[]pyrazole. Replacing the 3,5-diphenyl groups with 2-furanyl groups decreases the calculated rate of the 1,5-sigmatropic shift by 6.2 × 10-fold and enables the isolation of new spirocyclic 4-pyrazoles for click chemistry.