Palladium-catalyzed heteroaryl thioethers synthesis overcoming palladium dithiolate resting states inertness: Practical road to sulfones and N H-sulfoximines

• Published in: Catalysis communications Vol. 111; pp. 52 - 58
• Main Authors: Guilbaud, Johan, Labonde, Marine, Selmi, Awatef, Kammoun, Majed, Cattey, Hélène, Pirio, Nadine, Roger, Julien, Hierso, Jean-Cyrille
• Format: Journal Article
• Language: English
• Published: Elsevier 01.06.2018
• Subjects: Chemical Sciences; Physics; efficient; acid salts; Palladium; NH-sulfoximines; C-S coupling; H functionalization; indoles; Resting state; arenes; s-arylation; Thiolates; thiols; directing group; Sulfones; bond formation; sulfides
• ISSN: 1566-7367
• DOI: 10.1016/j.catcom.2018.03.025

We provide efficient synthetic access to heteroaryl sulfones in two-steps using a simple palladium-1,1'-bis [(diphenyl)phosphanyl]ferrocene catalyst to form in high yields variously functionalized heteroaromatic thioethers. Pyridinyl-containing substrates can be subsequently selectively oxidized into sulfones and NH-sulfoximines by using very mild oxidation conditions with a high functional group tolerance. In the palladium catalyzed C-S coupling of heteroaromatic thiols, reactivity limitation is attached with electron-deficient thiols. We show that this limitation can be resolved by the successful use of 2-bromoheteroarenes in the C-S coupling. We established herein that this choice of heteroaryl electrophilic reagent in palladium-catalyzed C-S bond formation allows overcoming palladium dithiolate out-of-cycle resting state inertness. This was illustrated in the stoichiometric reactivity study of the palladium dithiolate formed from 4-trifluoromethylbenzen-1-thiol-isolated and characterized by multinuclear NMR and XRD-with both 2-chloropyridine and 2-bromopyridine.