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

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.