Direct Synthesis of Pyrazolones via N–B Bond Functionalization: Sequential Carbonyl Insertion Using In Situ Generated N , N ′-Diborylated Hydrazines

Abstract

We report a metal-free protocol for the synthesis of 1,2-diaryl pyrazol-3-ones through the strategic exploitation of N,N′-diborylated hydrazine reactivity. The transformation employs a 4,4′-bipyridyl-catalyzed system that enables in situ generation of N,N′-diborylated hydrazines from azoarenes and bis(pinacolato)diboron, followed by their unprecedented sequential insertion of carbonyl groups from β-keto esters. Gram-scale synthesis and downstream derivatizations demonstrate the practical utility of this method, while the resulting compounds exhibit promising anti-inflammatory activity. Mechanistic studies, including control experiments and DFT calculations, delineate a sequential pathway in which the diborylated hydrazine intermediate undergoes two distinct carbonyl insertion events via four-membered transition states, ultimately affording the pyrazolone core.