Synthesis of 2-Substituted Pyridines via a Regiospecific Alkylation, Alkynylation, and Arylation of Pyridine N-Oxides

Abstract

[structure: see text]. Sequential addition of Grignard reagents to pyridine N-oxides in THF at room temperature followed by treatment with acetic anhydride at 120 degrees C afforded 2-substituted pyridines in good to high yields. Furthermore, by exchanging acetic anhydride for DMF in the second step, 2-substituted pyridine N-oxides were obtained, as intermediates suitable for addition of a second Grignard reagent for the synthesis of 2,6-disubstituted pyridines.

Synthesis of functionalized 2-arylpyridines from 2-halopyridines and various aryl halides via a nickel catalysis

“…4 More recently, a transition-metal free regiospecific sequential addition of Grignard reagents to pyridine N-oxides was reported. 5 To avoid the preparation of a stoichiometric organometallic reagent, different one-pot selective crosscoupling procedures have been reported. These include coupling of a 2-halopyridine with an aryl halide under phase-transfer conditions 6 or using a stoichiometric amount of hexamethylditin, 7 both in the presence of Pd-catalysis.…”

Green strategy from waste to value-added-chemical production: efficient biosynthesis of 6-hydroxy-3-succinoyl-pyridine by an engineered biocatalyst

“…Biocatalysis is a useful supplementary technology for the chemical industry in the reactions that are not easily conducted in the organic chemistry methods17. For example, the reactions involved in the formation of 2-substituted pyridines and their derivatives from pyridine N -oxides are useful synthetic methods; however, these methods require strict conditions for high product yields910. In microorganisms, the pyridine 2-hydroxylation step is specifically catalyzed by a molybdenum-containing protein, such as nicotinic acid dehydrogenase (EC1.17.1.5) in nicotinic degradation pathway, and nicotine hydroxylase (EC1.5.99.4) and Spm (Figure 2a) in nicotine degradation pathways1112.…”

Regioselective alkynylation followed by Suzuki coupling of 2,4-dichloroquinoline: Synthesis of 2-alkynyl-4-arylquinolines

“…Methodologies based on strategy ‘a’ have been reported earlier. For example, Sonogashira coupling of a terminal alkyne with 2-chloro-4-aryl substituted quinoline [3] in the presence of (PPh 3 ) 2 PdCl 2 -CuI or treatment of 4-aryl pyridine- N -oxide with alkynyl Grignard [5] provided the required quinoline or pyridine derivatives, respectively. Notably, synthesis of A following the strategy ‘b’ has not been explored.…”