Issue 6, 2017

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

Abstract

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).

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

Supplementary files

Article information

Article type
Edge Article
Submitted
13 Feb 2017
Accepted
11 Apr 2017
First published
28 Apr 2017
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2017,8, 4437-4442

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

T. Markovic, B. N. Rocke, D. C. Blakemore, V. Mascitti and M. C. Willis, Chem. Sci., 2017, 8, 4437 DOI: 10.1039/C7SC00675F

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