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Importance of a Fluorine Substituent for the Preparation of meta ‐ and para ‐Pentafluoro‐λ 6 ‐sulfanyl‐Substituted Pyridines
Author(s) -
Kosobokov Mikhail,
Cui Benqiang,
Balia Andrii,
Matsuzaki Kohei,
Tokunaga Etsuko,
Saito Norimichi,
Shibata Norio
Publication year - 2016
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201605008
Subject(s) - chemistry , sulfanyl , pyridine , substituent , fluorine , nucleophile , medicinal chemistry , ring (chemistry) , fluoride , chloride , combinatorial chemistry , organic chemistry , catalysis , inorganic chemistry
Although there are ways to synthesize ortho ‐pentafluoro‐λ 6 ‐sulfanyl (SF 5 ) pyridines, meta ‐ and para ‐SF 5 ‐substituted pyridines are rare. We disclose herein a general route for their synthesis. The fundamental synthetic approach is the same as reported methods for ortho ‐SF 5 ‐substituted pyridines and SF 5 ‐substituted arenes, that is, oxidative chlorotetrafluorination of the corresponding disulfides to give pyridylsulfur chlorotetrafluorides (SF 4 Cl‐pyridines), followed by chloride/fluoride exchange with fluorides. However, the trick in this case is the presence on the pyridine ring of at least one fluorine atom, which is essential for the successful transformation of the disulfides into m ‐and p ‐SF 5 ‐pyridines. After enabling the synthesis of an SF 5 ‐substituted pyridine, ortho ‐F groups can be efficiently substituted by C, N, S, and O nucleophiles through an S N Ar pathway. This methodology provides access to a variety of previously unavailable SF 5 ‐substituted pyridine building blocks.