| Abstract
| - Nucleophilic substitution reactions of 2-methoxy- and 2-acyloxypiperidines were investigated. First,new and efficient methods for the preparation of the starting piperidine derivatives were developed.N-Benzyloxycarbonyl-2-methoxypiperidine (3) and 3-substituted-2-acyloxy-N-benzyloxycarbonylpiperidines (4a−d), which are recognized as the simplest imino-sugars, were prepared and wereexamined as substrates for nucleophilic substitution reactions with silyl enolates under the influenceof catalytic amounts of metal triflates (Sc(OTf)3, Sn(OTf)2, Cu(OTf)2, Hf(OTf)4, etc). Among thetriflates tested, Sc(OTf)3 gave the best results. It was found that 2-acetoxy-3-benzyloxy-N-benzyloxycarbonylpiperidine (4a) reacted with silyl enolates to afford the 2-alkylated adducts inhigh cis-selectivity, while 2,3-diacyloxy-N-benzyloxycarbonylpiperidines (4b−d) showed trans-selectivity. The stereochemical assignments were carefully performed using NMR analysis, X-raycrystallography, and synthetic transformations. Febrifugine (1), a potent antimalarial alkaloid,was successfully synthesized from 2,3-diacetoxy-N-benzyloxycarbonylpiperidine (4b) on the basisof these diastereoselective nucleophilic substitution reactions.
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