PIFA-Mediated Intramolecular Dearomatization of Phenol-Tethered 1,2-Diazoles: Synthesis of Spirocyclohexadienone Pyrazolo[3,4-b]piperidinones

Abstract

In recent years, the significance of spirocyclic motifs in drug discovery has increased, owing to their unique ability to engage biological targets. We present the first example of PIFA-mediated dearomative spirocyclization of phenol-tethered pyrazoles, highlighting intramolecular trapping by the pyrazole moiety. This method efficiently affords a variety of spirocyclohexadienone pyrazolo[3,4-b]piperidinones with yields of up to 82%. Mechanistic studies reveal that the dearomatization process involves a cationic intermediate.