Synthesis 2017; 49(17): 4055-4064
DOI: 10.1055/s-0036-1589025
paper
© Georg Thieme Verlag Stuttgart · New York

Regioselective and Transition-Metal-Free Addition of tert-Butyl Magnesium Reagents to Pyridine Derivatives: A Convenient Method for the Synthesis of 3-Substituted 4-tert-Butylpyridine Derivatives

Sebastian Rappenglück
a  Ludwig-Maximilians-Universität München, Department für Pharmazie – Zentrum für Pharmaforschung, Butenandtstr. 5-13, Haus C, 81377 Munich, Germany   Email: [email protected]
,
Karin V. Niessen
b  Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstraße 11, 80937 Munich, Germany
,
Thomas Seeger
b  Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstraße 11, 80937 Munich, Germany
,
Franz Worek
b  Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstraße 11, 80937 Munich, Germany
,
Horst Thiermann
b  Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstraße 11, 80937 Munich, Germany
,
a  Ludwig-Maximilians-Universität München, Department für Pharmazie – Zentrum für Pharmaforschung, Butenandtstr. 5-13, Haus C, 81377 Munich, Germany   Email: [email protected]
› Author Affiliations
This study was funded by the German Ministry of Defense (E/U2AD/CF514/DF561).
Further Information

Publication History

Received: 27 March 2017

Accepted: 07 April 2017

Publication Date:
18 May 2017 (online)


Abstract

A variety of 3,4-disubstituted pyridine derivatives with a tert-butyl group in the 4-position were synthesized in a transition-metal-free, two-step reaction sequence from 3-substituted pyridine precursors. Highly regioselective addition of t-Bu2Mg to TIPS-activated pyridines and an efficient microwave-assisted aromatization with sulfur as oxidant afforded the desired 3,4-disubstituted pyridine derivatives in moderate to excellent yields. The method is compatible with many functional groups such as ester, amide, halide, nitrile or alkyne groups present in the 3-position.

Supporting Information

 
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