Chemistry of highly oxidized aporhoeadanes

The aporhoeadane alkaloids

“…1 Basic cleavage of the azepine ring was followed by treatment with trifluoroacetic acid, which initially formed iminium ion 317 (Scheme 105). Intramolecular Friedel-Crafts alkylation (318) preceded extrusion of carbon dioxide to provide nuevamine.…”

“…1 When chilenine (5) is heated at reflux in 35% sulfuric acid, the reaction is understood to proceed through initial formation of the homoannular α-ketocarbinolamide 7. As an aside, this is significant because treatment of the homoannular α-ketocarbinolamide with ammonium hydroxide incites the reverse reaction.…”

“…Given the mild reaction conditions and the tertiary nature of the hydroxyl group, it is presumed that the same iminium ion (17) is an intermediate and that it adds acetate to yield 323. 1 Scheme 108. Nucleophilic exchange with acetic anhydride.…”

“…Conditions that preclude intramolecular participation lead to the cis products, while those that allow intramolecular participation result in trans products. 1 For instance, when chilenine is treated with sodium borohydride in methanol the trans-diol (324) is the predominant product (Scheme 109). It is probable that the C13 hydroxyl group of chilenine complexes with borohydride and that intramolecular addition of hydride to the carbonyl then necessarily occurs from the same side as the hydroxyl group affording the trans product.…”

“…1 Dissolving metal reduction of chilenine (5) in strong acid results in the loss of the C13 and C14 oxygenation yielding lennoxamine (11) as the major product along with a small amount of enaminol 327 (Scheme 112). 1,61 Scheme 112. Dissolving metal reduction of chilenine.…”