Silver-Mediated Palladium-Catalyzed Direct C−H Arylation of 3-Bromoisothiazole-4-carbonitrile

Abstract

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.

Expanding a fluorescent RNA alphabet: synthesis, photophysics and utility of isothiazole-derived purine nucleoside surrogates

“…In particular, the alkylation of C5 on functionalized isothiazoles, while previously observed, has only been reported for a limited substrate scope. 19 …”

Palladium‐Catalyzed Direct CH Arylation of Isoxazoles at the 5‐Position

“…Additive salts were found to have al arge impact on the reaction efficiency( entries [12][13][14][15]. Use of either Pd(OAc) 2 or [Pd(dba) 2 ]( dba = dibenzylideneacetone) instead of [PdCl 2 (MeCN) 2 ]l ed to as lightly diminished yield (entries 5a nd 6).…”

Recent Advances in the Synthesis and Reactivity of Isothiazoles

“…Building upon their studies on cross‐coupling reactions of isothiazoles, in 2011, Koutentis and co‐workers described the first direct C−H arylation method of isothiazoles (Scheme ) . They found that the use of PdCl 2 (PPh 3 ) 2 (5 mol%) as a catalyst, AgF (3 equiv.)…”