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

A palladium-catalyzed denitrogenative Suzuki coupling
of N-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.