Synthesis of Pyrimidines via N-Vinyl Tertiary Enamides

Significance

This reported reaction is an improvement of work by the Movassaghi group (M. Movassaghi, M. D. Hill J. Am. Chem. Soc. 2006, 128, 14254; O. K. Ahmad, M. D. Hill, M. Movassaghi J. Org. Chem. 2009, 74, 8460), who successfully demonstrated the formation of pyrimidines from secondary N-vinyl enamides, which can be problematic targets. The current work improves upon this procedure through the use of N-PMB (para-methoxybenzyl) protected tertiary N-vinyl enamides, which are formed in a one-pot reaction between para-methoxybenzyl­amine and the required ketone to form an imine, which is then acylated. The application of the Movassaghi conditions then provides the desired pyrimidines. A potential mechanism of the reaction is discussed which proceeds through nitrilium intermediate A, formed as a result of the loss of 2-chloropyridine and the PMB cation. This mechanism is entirely reasonable as N-alkyl enamides are thought to react through nitrilium intermediates. Although NMR experiments were performed to investigate the mechanism, no stable intermediates were identified, probably as a result of the highly reactive system.