Pyridine sulfinates as general nucleophilic coupling partners in palladium-catalyzed cross-coupling reactions with aryl halides

Journal article

Pyridine rings are ubiquitous in drug molecules; however, the pre-eminent reaction used to form carbon–carbon bonds in the pharmaceutical industry, the Suzuki–Miyaura cross-coupling reaction, often fails when applied to these structures. This phenomenon is most pronounced in 2-substituted pyridines, and results from the difficulty in preparing, the poor stability of, and low efficiency in reactions of pyridine-2-boronates. We demonstrate that by replacing these boronates with pyridine-2-sulfinates, a cross-coupling process of unrivalled scope and utility is realized. The corresponding 3- and 4-substituted pyridine variants are also efficient coupling partners. In addition, we apply these sulfinates in a library format to the preparation of medicinally relevant derivatives of the drugs varenicline (Chantix) and mepyramine (Anthisan).

Authors: Markovic, T; Rocke, B; Blakemore, D; Mascitti, V; Willis, M

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Royal Society of Chemistry
• Journal: Chemical Science
• Volume: 8
• Issue: 6
• Pages: 4437-4442
• Publication date: 2017-04-28
• Acceptance date: 2017-04-11
• DOI: 10.1039/C7SC00675F
• EISSN: 2041-6539
• ISSN: 2041-6520