Synthesis of Dihydropyridones Involving Directed ortho-Metallation

Significance

Starting with N-Boc-2-isobutyl-2,3-dihydro-4-methoxypyridine, readily available by alkylmagnesium bromide addition to N-Boc pyridinium salts, an efficient synthesis of poly-functionalized 2,3-dihydro-4-pyridones is reported. A sequence of N-Boc-directed ortho-metallation (DoM) and C₂Cl₆ quench followed by chloro group directed metallation and reaction with a variety of electrophiles leads to the dihydropyridone products in moderate to high yields. The Cl → X conversion was achieved by several methods including Pd-catalyzed cross-coupling.