Switchable and Selective Synthesis of Unsymmetrical N -Aryl Pyrazoles from 1,2,3-Thiadiazine S -Oxides
Year: 2026
Type: article
Abstract: Herein we report a new, highly selective copper-catalyzed synthesis of unsymmetrical N-aryl pyrazoles from 1,2,3-thiadiazine-S-oxides (TDSOs) and diaryl iodonium electrophiles. The regiochemical outcome is determined by the choice of copper catalyst and base, in contrast to typical substrate-controlled approaches. This “switchable” approach enables access to either pyrazole isomer from a given starting material with high selectivity observed in each case. The scope of both protocols is broad and is amenable to automation, thus facilitating rapid generation of a medicinally relevant, diverse pyrazole library. Experimental and computational mechanistic studies reveal the origin of selectivity for each protocol, and rationalize the role of base identity, base concentration and copper ligation state in determining the regiochemical outcome. Overall, this approach addresses long-standing synthetic challenges in the preparation of unsymmetrical N-aryl pyrazoles and provides important mechanistic foundations for the development of further switchable pyrazole syntheses.
DOI: 10.1021/jacs.5c22914
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W7133241222