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Synthesis 2017; 49(17): 4055-4064
DOI: 10.1055/s-0036-1589025
DOI: 10.1055/s-0036-1589025
paper
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
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.
Key words
3,4-disubstituted pyridines - N-activation - heterocycles - diorganomagnesium - nucleophilic addition - microwaveSupporting Information
- Supporting information for this article is available online at https://doi.org /10.1055/s-0036-15890025.
- Supporting Information
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For more information about addition of organometallic nucleophiles on N-acylpyridinium ions, see: