Acid-Catalyzed Rearrangement of α-Aminoalkylidene-β-alkoxy β-Lactams

Article abstract of DOI:10.1021/jo01294a004

Hydrolysis of six nonfused 4-methoxy β-lactams (1-6) on alumina gave the corresponding enamino ketone derivatives (11-16), whereas the fused β-alkoxy β-lactams (7 and 8) afforded the alkyl 2-piperidylideneacetoacetates 17 and 18, respectively.The structures of the products (11, 17, and 18) were confirmed by synthesis.Treatment of the fused β-methoxy β-lactam 7 in ethanol solution containing water (11percent) and a catalytic amount of acetic acid (1percent) leads to a mixture of two products, 17 and enamino ketone derivative 21.Similarly, treatment of the fused β-ethoxy β-la ctam 8 in an acidic methanol solution containing water (11percent) afforded 18 and 21.Under similar conditions the fused β-alkoxy β-lactams 9 and 10 also gave the corresponding alkyl 2-(2-hexahydroazepinylidene)acetoacetate (19 and 20), enamino ketone derivative 22, and 3-acetyl-β-alkoxy β-lactams (23 and 24), respectively.Furthermore, hydrolysis of 24 in a similar acidic solution gave the enol-type product 25.Hydrolysis of fused CD3O β-lactam 7a and fused CH3(18)O β-lactam 7b on alumina gave methyl-d₃ 2-piperidylideneacetoacetate(17a) and methyl 2-piperidylideneacetoacetate-carboxy-(18)O (17b), respectively.These observations suggest that an intramolecular migration of the alkoxy group to the amide carbonyl carbon is responsible for the formation of the products (17-20).