Silver-mediated palladium-catalyzed direct C-H arylation of 3-bromoisothiazole-4-carbonitrile.

Silver(I) fluoride-mediated Pd-catalyzed C-H direct arylation/heteroarylation of 3-bromoisothiazole-4-carbonitrile (1a) gives twenty-four 5-aryl/heteroaryl-3-bromoisothiazole-4-carbonitriles. The reaction was partially optimized with respect to catalyst, ligand, and base. During this study 3,3'-dibromo-5,5'-biisothiazole-4,4'-dicarbonitrile (3a) was isolated as a byproduct and subsequently prepared via the silver-mediated Pd-catalyzed oxidative dimerization of 3-bromoisothiazole-4-carbonitrile in 67% yield. The analogous phenylation and oxidative dimerization of 3-chloroisothiazole-4-carbonitrile (1b) gave 3-chloro-5-phenylisothiazole-4-carbonitrile (4) and 3,3'-dichloro-5,5'-biisothiazole-4,4'-dicarbonitrile (3b) in 96% and 69% yields, respectively.