Synthesis of trans-2,3-Dihydropyridine
N-Oxides and Piperidines

Significance

Reported here is the regioselective and stereoselective synthesis of trans-2,3-dihydropyridine N-oxides by addition of Grignard ­reagents to pyridine N-oxides followed by quenching with electrophiles. Although the scope of pyridine N-oxides was well studied, the scope of electrophiles was limited to benzaldehyde and butyraldehyde. One example with cyclohexanone was included. PhMgCl was used in most of the examples leading to the trans-2,3-dihydropyridine N-oxide products in modest to very good yields. Other Grignard reagents gave the products in low to modest yields. The diastereomeric ratio varied depending on the reaction temperature (-78 ˚C or -40 ˚C). X-ray crystal structures of two compounds were determined to establish the relative configuration.