Switchable and Selective Synthesis of Unsymmetrical <i>N</i> -Aryl Pyrazoles from 1,2,3-Thiadiazine <i>S</i> -Oxides

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 the copper catalyst and base, in contrast with 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 amenable to automation, thus facilitating the 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.