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

The condensation of 1,3-diketones with hydrazine to access 4 H -pyrazoles is a well-established synthetic route that travels through a 4 H -pyrazol-1-ium intermediate. In the route to a 3,5-diphenyl-4 H -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 × 10 5 -fold and enables the isolation of new spirocyclic 4 H -pyrazoles for click chemistry.