Efficient, mild and completely regioselective synthesis of substituted pyridines

Abstract

Addition of Grignard reagents to pyridine N-oxides in THF at low temperature (-78 to -20 degrees C) and treatment with TFAA provides an efficient general procedure for synthesis of substituted pyridines. The method is compatible with a range of functional groups such as esters, halogens and nitriles.

Transition‐Metal‐Free Regioselective Alkylation of Pyridine N‐Oxides Using 1,1‐Diborylalkanes as Alkylating Reagents

“…described C2‐methylation reactions of pyridine N ‐oxides using Tebbe's reagent involving a nucleophilic addition/elimination process . Almqvist, Olsson,, and Duan discovered that Grignard reagents act as facile nucleophiles in the C2 alkylation of pyridine N ‐oxides. Herein, we report the development of the transition‐metal‐free alkylation of pyridine N ‐oxides by employing 1,1‐diborylalkanes as facile alkylating reagents (Scheme c).…”

Copper‐Catalyzed ortho‐Functionalization of Quinoline N‐Oxides with Vinyl Arenes

“…[3] Recently, pyridine or quinoline N-oxides, which serve as N-activated pyridines, have emerged as ideal and versatile synthetic intermediates for the introduction of functional groups at the C2-position of N-heterocycles. [4] A wide variety of chemical transformations including deoxgenative or nondeoxgenative reactions has been developed employing pyridine or quinoline N-oxides as the substrates, such as arylation, [5] alkylation, [6] radical reaction, [7] 1,3-dipolar cycloaddition, [8] transition-metal-catalyzed CÀH bond functionalization [9] etc. [10] Although much progress has been achieved, the regioselective CÀC bond formation reactions of N-oxides with unsaturated p-systems such as alkenes have less been developed.…”

Reductive C2‐Alkylation of Pyridine and Quinoline N‐Oxides Using Wittig Reagents

“…[6] Grignard reagents have also been used to prepare C2-alkylated pyridines through nucleophilic addition to pyridine Noxides,f ollowed by elimination. [7] Very recently,C ho and co-workers demonstrated site-selective alkylation reactions of pyridine N-oxides with 1,1-diboryl alkanes as alkylating reagents to give C2-alkylated pyridines. [8] TheW ittig reaction, which is based on the reaction of an aldehyde or ketone with ap hosphonium ylide,i sr anked among the most important reactions for CÀCb ond formation.…”