[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.

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.

In this perspective we discuss the recent developments of stereoselective synthesis of substituted pyridines, piperidines, and piperazines from cheap and commercially readily available starting materials. Pyridine N-oxides and pyrazine N-oxides are reacted with alkyl, aryl, alkynyl and vinyl Grignard reagents to give a diverse set of heterocycles in high yields. Optically active substituted piperazines are obtained by an asymmetric reaction from pyrazine N-oxides using sparteine as chiral ligand. In addition, a stereoselective synthesis of dienal-oximes from the reaction between pyridine N-oxides and Grignard reagents is presented, which results in a useful intermediate for the synthesis of a diverse set of compounds.

Reactivity N-Own: Pyridine N-oxides can be used for the complete regio- and stereoselective synthesis of trans-substituted piperidines. The sequential addition of Grignard reagents and aldehydes or ketones to pyridine N-oxides yields a complete regio- and stereoselective trans 2,3-addition reaction in high yields, and the substituted 2,3-dihydropyridine N-oxide can be reduced to form 2,3-trans-substituted piperidines (see scheme).