Enantioselective synthesis of (S)-1,6,7,8,9,9a-hexahydroquinolizin-4-one. Formal synthesis of the lycopodium alkaloids senepodine G and cermizine C

The synthesis of the title compound, a key intermediate in the synthesis of some lycopodium and lupin alkaloids, is reported. From a stereochemical standpoint the key steps are the stereoselective cyclocondensation of ketodiester 1 with (R)-phenylglycinol and the stereocontrolled reduction, with retention of configuration, of the oxazolidine ring in the resulting oxazolopiperidone lactam 2.

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Methyl (3R,8aR)-5-oxo-3-phenyl-2,3,5,6,7,8-hexahydrooxazolo[3,2-a]piperidine-8a-butyrateC18H23NO4[α]D22=-94.2 (c 1.0, MeOH)Source of chirality: (R)-phenylglycinolAbsolute configuration: (3R,8aR)

Methyl (3R,8aS)-5-oxo-3-phenyl-2,3,5,6,7,8-hexahydrooxazolo[3,2-a]piperidine-8a-butyrateC18H23NO4[α]D22=-50.6 (c 1.2, MeOH)Source of chirality: (R)-phenylglycinolAbsolute configuration: (3R,8aS)

(S)-1-[(R)-1-Phenyl-2-hydroxyethyl]piperidine-2-butanolC17H27NO2[α]D22=-84.7 (c 0.9, MeOH)Source of chirality: (R)-phenylglycinolAbsolute configuration: (2S)

(S)-1-(tert-Butoxycarbonyl)piperidine-2-butanolC14H27NO3[α]D22=-32.6 (c 1.0, MeOH)Source of chirality: (R)-phenylglycinolAbsolute configuration: (2S)

(S)-1-(tert-Butoxycarbonyl)piperidine-2-butanoic acidC14H25NO4[α]D22=-40.8 (c 1.0, MeOH)Source of chirality: (R)-phenylglycinolAbsolute configuration: (2S)

(S)-1,2,3,6,7,8,9,9a-Octahydroquinolizin-4-oneC9H15NO[α]D22=-3.7 (c 1.0, CHCl3)Source of chirality: (R)-phenylglycinolAbsolute configuration: (9aS)

(S)-1,6,7,8,9,9a-Hexahydroquinolizin-4-oneC9H13NO[α]D22=+45.1 (c 1.0, CHCl3)Source of chirality: (R)-phenylglycinolAbsolute configuration: (9aS)