Pyridine sulfinates as general nucleophilic coupling partners in palladium-catalyzed cross-coupling reactions with aryl halides.
Chem Sci
; 8(6): 4437-4442, 2017 Jun 01.
Article
em En
| MEDLINE
| ID: mdl-28936330
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).
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MEDLINE
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En
Ano de publicação:
2017
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Article