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

Abstract

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 × 105‐fold and enables the isolation of new spirocyclic 4H‐pyrazoles for click chemistry.