Stereoselective synthesis of (2S,3S)-3-hydroxy-2-phenylpiperidine from d-mannitol

A novel stereoselective synthesis of N-Boc-(2S,3S)-3-hydroxy-2-phenylpiperidine was achieved from d-mannitol involving the highly stereoselective addition of phenyl Grignard to an allyl imine (de >98%) and ring-closing metathesis (RCM) in the key steps.

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1,2:3,4-Di-O-isopropylidene-(2R,3R,4S)-5-chloropentane-1,2,3,4-tetraolC11H19ClO4[αD25]=+13.2 (c 1, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (2R,3R,4S)

(1S)-1-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2-propen-1-olC8H14O3[α]D25=+2.8 (c 1, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (1S,4R)

(4R)-4-[(1S)-1-(benzyloxy)-2-propenyl]-2,2-dimethyl-1,3-dioxolaneC15H20O3[α]D25=+49.2 (c 1 CHCl3)Source of chirality: d-mannitolAbsolute configuration: (1S,4R)

(2R,3S)-3-(benzyloxy)-4-pentene-1,2-diolC12H16O3[α]D25=+55 (c 1 CHCl3)Source of chirality: d-mannitolAbsolute configuration: (2R,3S)

N-allyl-N-[(1S,2S)-2-(benzyloxy)-phenyl-3-butenyl] amineC20H23NO[α]D25=+51 (c 1 CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,2S)

tert-Butyl-N-allyl-N-[(1S,2S)-2-(benzyloxy)-1-phenyl-3-butenyl] carbamateC25H31NO3[α]D25=+46 (c 1 CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,2S)

tert-Butyl (2S,3S)-3-(benzyloxy)-2-phenyl 1,2,3,6-tetrahydro-1-pyridine carboxylateC23H27NO3[α]D25]=+44 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3S)

(2S,3S)-3-Hydroxy-2-phenyl-piperidine-1-carboxylic acid tert-butyl esterC16H23NO3[α]D25=+39 (c 1 CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3S)