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

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 - microwave

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