Electrochemical Synthesis of Polysubstituted Sulfonated Pyrazoles via Cascade Intermolecular Condensation, Radical-Radical Cross Coupling Sulfonylation, and Pyrazole Annulation

Jiajun Feng; Yuzhi Wang; Luoyu Gao; Yang Yu; Jonathan B Baell; Fei Huang

doi:10.1021/acs.joc.2c01609

Electrochemical Synthesis of Polysubstituted Sulfonated Pyrazoles via Cascade Intermolecular Condensation, Radical-Radical Cross Coupling Sulfonylation, and Pyrazole Annulation

J Org Chem. 2022 Oct 7;87(19):13138-13153. doi: 10.1021/acs.joc.2c01609. Epub 2022 Sep 27.

Authors

Jiajun Feng¹, Yuzhi Wang¹, Luoyu Gao¹, Yang Yu², Jonathan B Baell^{1

3}, Fei Huang^{1

4}

Affiliations

¹ School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 211816, PR China.
² School of Environmental Science and Engineering, Nanjing Tech University, Nanjing 211816, PR China.
³ Medicinal Chemistry Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.
⁴ School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing 210023, PR China.

PMID: 36166815
DOI: 10.1021/acs.joc.2c01609

Abstract

Electrochemical synthesis of polysubstituted sulfonated pyrazoles from enaminones and sulfonyl hydrazides was established under metal-free, exogenous-oxidant-free, and mild conditions. By judicious choice of different electrochemical reaction conditions, NH₂-functionalized enaminones or N,N-disubstituted enaminones can react with aryl/alkyl sulfonyl hydrazides to afford tetra- or trisubstituted sulfonated pyrazoles in moderate to good yields, respectively. The gram-scale electrochemical transformation demonstrated the efficiency and practicability of this synthetic strategy. In addition, the sulfonated NH-pyrazole can be obtained via the dissociation of the N-tosyl group. Mechanistic studies reveal that the electrochemical cascade reaction synthesis of polysubstituted sulfonated pyrazoles proceeded via the sequence of intermolecular condensation, radical-radical cross coupling sulfonylation, and pyrazole annulation.