Palladium-Catalyzed Denitrogenative Suzuki Coupling of Benzothiatriazine Dioxides for Bi(hetero)aryl-2-sulfonamides

A palladium-catalyzed denitrogenative Suzuki coupling of <i>N</i>-alkyl benzothiatriazine dioxides with (hetero)aryl boronic acids as well as potassium trifluoroborates is reported, affording a variety of 1,1'-bi(hetero)aryl-2-sulfonamides in yields up to 99% using as low as 0.2 mol % PdCl₂(PPh₃)₂/2PPh₃ catalyst in weakly basic aqueous toluene. The protocol shows functional group compatibility as good as the traditional Suzuki coupling. Remarkable steric and electronic effects have been observed from both benzothiatriazine and boron counterparts but could be alleviated by increasing the catalyst loadings alone or in combination with methanol cosolvent. Applications of the protocol have been preliminarily demonstrated in a gram-scale synthesis of κ-opioid receptor antagonist PF-4455242.