Enantioselective synthesis of (+)-l-733,060

An efficient enantioselective synthesis of (+)-l-733,060 from cinnamyl alcohol is described. The key steps include a Sharpless asymmetric epoxidation, a regioselective allyl opening of an epoxide and piperidine ring formation via a one pot Staudinger/aza-Wittig reaction.

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(2R,3R)-(3-Phenyl-oxiranyl)-methanolC9H10O2Ee >99%[α]D27=+48.7 (c 2.4, CHCl3)Source of chirality: Sharpless asymmetric epoxidationAbsolute configuration: (2R,3R)

(2S,3S)-3-Azido-3-phenyl-propane-1,2-diolC9H11N3O2[α]D27=+166.3 (c 1.2, CHCl3)Source of chirality: Sharpless asymmetric epoxidationAbsolute configuration: (2S,3S)

(2R,3S)-2-(Azido-phenyl-methyl)-oxiraneC9H9N3O[α]D27=+139.0 (c 1.1, CHCl3)Source of chirality: Sharpless asymmetric epoxidationAbsolute configuration: (2R,3S)

(1S,2S)-1-Azido-1-phenyl-hex-5-en-2-olC12H15N3O[α]D27=+178.4 (c 1.0, CHCl3)Source of chirality: Sharpless asymmetric epoxidationAbsolute configuration: (1S,2S)

(1S,2S)-[1-(Azido-phenyl-methyl)-pent-4-enyloxy]-tert-butyl-dimethyl-silaneC18H29N3OSi[α]D27=+75.3 (c 1.1, CHCl3)Source of chirality: Sharpless asymmetric epoxidationAbsolute configuration: (1S,2S)

(2S,3S)-3-(tert-Butyl-dimethyl-silanyloxy)-2-phenyl-piperidineC17H29NOSi[α]D27=+51.5 (c 1.1, MeOH)Source of chirality: Sharpless asymmetric epoxidationAbsolute configuration: (2S,3S)

(2S,3S)-1-[3-(tert-Butyl-dimethyl-silanyloxy)-2-phenyl-piperidin-1-yl]-2,2-dimethyl-propan-1-oneC22H37NO3Si[α]D27=+18.4 (c 1.1, CHCl3)Source of chirality: Sharpless asymmetric epoxidationAbsolute configuration: (2S,3S)

(2S,3S)-1-(3-Hydroxy-2-phenyl-piperidin-1-yl)-2,2-dimethyl-propan-1-oneC16H23NO3[α]D27=+37.5 (c 1.0, CHCl3)Source of chirality: Sharpless asymmetric epoxidationAbsolute configuration: (2S,3S)

(2S,3S)-1-(tert-Butyoxycarbonyl)-2-phenyl-3-[(3,5)-bis(trifluoromethyl)benzyloxy]piperidineC25F6H27NO3[α]D25=+31.4 (c 1.0, CHCl3)Source of chirality: Sharpless asymmetric epoxidationAbsolute configuration: (2S,3S)

(2S,3S)-2-Phenyl-3-[(3,5)-bis(trifluoromethyl)benzyloxy]piperidine [(+)-l-733,060]C20F6H19NO[α]D25=+36.2 (c 0.66, CHCl3)Source of chirality: Sharpless asymmetric epoxidationAbsolute configuration: (2S,3S)