Piperidine derivatives absolute configuration

Deprotonation of the 9-azabicyclo 3.3.11nonan-3-one derivative 1 with chiral lithium amides in tetrahdyrofuran at low temperatures in the presence of chlorotrimethylsilane (internal quench) gives the trimethylsilyl enol ether (lS,5/ )-2 in high yield with high enantiomeric excess. The absolute configuration and enantiomeric excess of 2 are based on chemical correlation and HPLC on a chiral Daicel OJ column, respectively38. The 2,2-dimethylpropyl- and 4-methyl-l-piperazinyl- substituted lithium amide is, as noted in other cases, superior. The bicyclic trimethylsilyl enol ether 2 serves as intermediate in the synthesis of piperidine alkaloids. 

Other bicyclic piperidine derivatives have been prepared by olefin metathesis reactions (Scheme 61). The perhydroquinoline + )-trans- 95A 213 was synthesized via a RRM reaction of 214. The chirality transfer to the product 215 was essentially complete and permitted assignment of the absolute configuration to the natural product <05OL1227>. 

The geometry about the double bond was shown to be trans by the presence of a band in the IR-spectra of pinidine and its derivatives at 970 cm i and hy the 18 cps coupling between the olefinic protons in the NMR-spectrum. The absolute configuration was determined by hydrogenation of A-methylpinidine methiodide to give (-f- )-2-dimethylamino-nonane which was enantiomeric with synthetic S — )-2-dimethylamino-nonane prepared from [Pg.489]

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