Enantiopure 2-piperidylacetaldehyde as a useful building block in the diversity-oriented synthesis of polycyclic piperidine derivatives

Novel, simple, and convenient strategies for diversely functionalized piperidine derivatives have been developed by using different metal catalyzed reactions starting from enantiopure (R)- and (S)-2-piperidylacetaldehyde.

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(S)-2-Allyl-1-(2-iodobenzyl)-piperidineC15H20IN[α]D23=-32.0 (c 1.12, CHCl3)Source of chirality: enzymatic resolution of starting materialAbsolute configuration: (S)

(S)-11-Methylene-1,2,3,4,6,11,12,12a-octahydropyrido[1,2-b][2]benzazepineC15H19N[α]D23=+44.5 (c 0.31, CHCl3)Source of chirality: enzymatic resolution of starting materialAbsolute configuration: (S)

(11R,12aS)-3′-(3,5-Dichloro-2,4,6-trimethylphenyl)-spiro{pyrido[1,2-b][2]benzazepine-11,5′-isoxazole}C25H28Cl2N2O[α]D23=-34.9 (c 0.28, CHCl3)Source of chirality: enzymatic resolution of starting material and stereoselective synthesisAbsolute configuration: (11R,12aS)

(11S,12aS)-3′-(3,5-Dichloro-2,4,6-trimethylphenyl)-spiro{pyrido[1,2-b][2]benzazepine-11,5′-isoxazole}C25H28Cl2N2O[α]D23=+38.8 (c 0.13, CHCl3)Source of chirality: enzymatic resolution of starting material and stereoselective synthesisAbsolute configuration: (11S,12aS)

(S)-2-Allyl-N-(4-nitrophenyl)piperidine-1-carboxamideC15H19N3O3[α]D23=-62.0 (c 0.49, CHCl3)Source of chirality: enzymatic resolution of starting materialAbsolute configuration: (S)

(3R,4aS)-3-(Chloromethyl)-2-(4-nitrophenyl)octahydro-1H-pyrido[1,2-c]pyrimidin-1-oneC15H18ClN3O3[α]D25=+8.0 (c 0.39, CHCl3)Source of chirality: enzymatic resolution of starting materialAbsolute configuration: (3R,4aS)

(S)-2-Allyl-1-propenoylpiperidineC11H17NO[α]D23=-70.3 (c 0.59, CHCl3)Source of chirality: enzymatic resolution of starting materialAbsolute configuration: (S)

(R)-1,6,7,8,9,9a-Hexahydroquinolizin-4-oneC9H13NO[α]D23=-52.1 (c 0.50, CHCl3)Source of chirality: enzymatic resolution of starting material and stereoselective synthesisAbsolute configuration: (R)

(3aS,9aS,10aS)-3-(3,5-Dichloro-2,4,6-trimethylphenyl)-3a,6,7,8,9,9a,10,10a-octahydroisoxazolo[5,4-b]quinolizin-4-oneC19H22Cl2N2O2[α]D23=+87.2 (c 0.89, CHCl3)Source of chirality: enzymatic resolution of starting material and stereoselective synthesisAbsolute configuration: (3aS,9aS,10aS)