C3-Selective Trifluoromethylthiolation and Difluoromethylthiolation of Pyridines and Pyridine Drugs via Dihydropyridine Intermediates

Herein, we report a method for C3-selective C–H tri- and difluoromethylthiolation of pyridines. The method relies on borane-catalyzed pyridine hydroboration for generation of nucleophilic dihydropyridines; these intermediates react with trifluoromethylthio and difluoromethylthio electrophiles to for...

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Bibliographic Details
Published inJournal of the American Chemical Society Vol. 144; no. 32; pp. 14463 - 14470
Main Authors Zhou, Xin-Yue, Zhang, Ming, Liu, Zhong, He, Jia-Hao, Wang, Xiao-Chen
Format Journal Article
LanguageEnglish
Published WASHINGTON American Chemical Society 17.08.2022
Amer Chemical Soc
Subjects
aromatization
Chemistry
Chemistry, Multidisciplinary
drugs
Lewis acids
Lewis bases
Physical Sciences
pyridines
Science & Technology
HETEROARENES
HYDROBORATION
ACTIVATION
FUNCTIONALIZATION REACTIONS
REDUCTION
ARENES
ARYL
C-H TRIFLUOROMETHYLATION
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Summary:Herein, we report a method for C3-selective C–H tri- and difluoromethylthiolation of pyridines. The method relies on borane-catalyzed pyridine hydroboration for generation of nucleophilic dihydropyridines; these intermediates react with trifluoromethylthio and difluoromethylthio electrophiles to form functionalized dihydropyridines, which then undergo oxidative aromatization. The method can be used for late-stage functionalization of pyridine drugs for the generation of new drug candidates.
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ISSN:0002-7863
1520-5126
1520-5126
DOI:10.1021/jacs.2c06776