http://www.loc.gov/mods/v3 http://www.loc.gov/standards/mods/v3/mods-3-2.xsd
Stereoselective synthesis of hydroxypiperidine alkaloids via intramolecular amidomercuration
The stereoselective mercuric-ion-initiated cyclofunctionalization of an acylaminomethyl ether derivative of an allylic alcohol was used as a key step in the synthesis of hydroxypiperidine alkaloid derivatives. trans-N-(Cyclohexyloxycarbonyl)-5-(3-benzyloxypropyl)-4-methyloxazolidine was isolated in 65% yield from the cyclization reaction. The benzyl ether was cleaved, and the resulting alcohol was oxidized to the aldehyde, which was treated with dodecyl lithium and oxidized to the ketone. This intermediate served as the common precursor to two isomeric 2,6-dialkyl-3-hydroxypiperidines. Treatment of trans-N-(cyclohexyloxycarbonyl)-4-methyl-5-(3-oxopentadecyl)oxazolidine with hydrogen bromide in nitromethane for 10 minutes at room temperature resulted in an unexpected rearrangement to a cis-N-(hydroxymethyl)oxazolidinone derivative. This material was oxidized to the N-formyl derivative, then treated with base to yield a cyclic imine. Hydrogenation of the imine over palladium on carbon gave racemic 3-isodeoxocassine (6α-dodecy-3β-hydroxy-2α-methylpiperidine). To remove the cyclohexyloxycarbonyl group from the nitrogen and leave the trans oxazolidine intact required heating the oxazolidine at 120°C, with the ketone protected as a cyclic acetal, in 2 M sodium methoxide in methanol in a sealed ampoule for 12 hours. The oxazolidine was opened to the threo aminoalcohol by treatment with pyridine and malonic acid in refluxing ethanol. The acetal was removed and the aminoalcohol was cyclized to the imine by treatment with dilute sulfuric acid in aqueous tetrahydrofuran. Hydrogenation of the imine over palladium on carbon in ethanol gave racemic deoxocassine (6α-dodecy-3β-hydroxy-2α-methylpiperidine). This methodology allowed the stereoselective synthesis of the two isomeric hydroxypiperidines, deoxocassine and 3-isodeoxocassine, from a single precursor. Different carbamate cleavage conditions were used to generate the two different products. In addition to these syntheses, investigations involving different allylic alcohol synthons and various carbamates are discussed.