Regioselective difunctionalization of pyridines via 3,4-pyridynes

Heinz, Benjamin; Djukanovic, Dimitrije; Filipponi, Paolo; Martin, Benjamin; Karaghiosoff, Konstantin und Knochel, Paul (2021): Regioselective difunctionalization of pyridines via 3,4-pyridynes. In: Chemical Science, Bd. 12, Nr. 17: S. 6143-6147

Abstract

A new regioselective 3,4-difunctionalization of 3-chloropyridines via 3,4-pyridyne intermediates is reported. Regioselective lithiation of 3-chloro-2-ethoxypyridine and a related 2-thio-derivative followed by treatment with aryl- and alkylmagnesium halides as well as magnesium thiolates at -78 degrees C produced 3,4-pyridynes during heating to 75 degrees C. Regioselective addition of the Grignard moiety in position 4 followed by an electrophilic quench in position 3 led to various 2,3,4-trisubstituted pyridines. This method was adapted into a continuous flow set-up. As an application, we have prepared a key intermediate for (+/-)-paroxetine.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Chemie und Pharmazie > Department Chemie
• Themengebiete: 500 Naturwissenschaften und Mathematik > 540 Chemie
• ISSN: 2041-6520
• Sprache: Englisch