An asymmetric aminohydroxylation route to (+)-l-733,060

An enantioselective synthesis of (+)-l-733,060 starting from cinnamic acid using Sharpless asymmetric aminohydroxylation and Wittig reactions as the key steps is described.

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Isopropyl (2R,3S)-3-(acetylamino)-2-hydroxy-3-phenylpropionateC14H19NO4[α]D25=+28.5 (c 1.0, CHCl3)Source of chirality: asymmetric aminohydroxylationAbsolute configuration: (2R,3S)

Methyl (2R,3S)-3-(tert-butoxycarbonylamino)-2-hydroxy-3-phenylpropionateC15H21NO5[α]D25=-7.1 (c 0.89, CHCl3)Source of chirality: asymmetric aminohydroxylationAbsolute configuration: (2R,3S)

Methyl (2R,3S)-3-(tert-butoxycarbonylamino)-2-(tert-butyldimethylsilanyloxy)-3-phenylpropionateC21H35NO5Si[α]D25=+11.1 (c 0.92, CHCl3)Source of chirality: asymmetric aminohydroxylationAbsolute configuration: (2R,3S)

(2R,3S)-2-[(tert-Butyldimethylsilanyloxy)-3-hydroxy-1-phenylpropyl]-carbamic acid tert-butyl esterC20H35NO4Si[α]D25=+34.3 (c 1, CHCl3)Source of chirality: asymmetric aminohydroxylationAbsolute configuration: (2R,3S)

(4S,5S)-5-tert-Butoxycarbonylamino-4-[(tert-butyldimethylsilanyloxy)-5-phenyl-pent-2-enoic acid ethyl esterC24H39NO5Si[α]D25=+10.6 (c 0.74, CHCl3)Source of chirality: asymmetric aminohydroxylationAbsolute configuration: (4S,5S)

(4S,5S)-5-(tert-Butoxycarbonylamino)-4-hydroxy-5-phenylpentanoic acid ethyl esterC18H27NO5[α]D25=+10.8 (c 0.68, CHCl3)Source of chirality: asymmetric aminohydroxylationAbsolute configuration: (4S,5S)

(4S,5S)-(2,5-Dihydroxy-1-phenylpentyl)-carbamic acid tert-butyl esterC16H25NO4[α]D25=+15.1 (c 0.32, CHCl3)Source of chirality: asymmetric aminohydroxylationAbsolute configuration: (4S,5S)

(2S,3S)-3-Hydroxy-2-phenylpiperidine-1-carboxylic acid tert-butyl esterC16H23NO3[α]D25=+36.2 (c 0.66, CHCl3)Source of chirality: asymmetric aminohydroxylationAbsolute configuration: (2S,3S)

(2S,3S)-1-(tert-Butyoxycarbonyl)-2-phenyl-3-[(3,5)-bis(trifluoromethyl)benzyloxy]piperidineC25H27F6NO3[α]D25=+31.5 (c 1.0, CHCl3)Source of chirality: asymmetric aminohydroxylationAbsolute configuration: (2S,3S)

3-(3,5-Bis-trifluoromethylbenzyloxy)-2-phenylpiperidineC20H19F6NO[α]D25=+36.2 (c 0.66, CHCl3)Source of chirality: asymmetric aminohydroxylationAbsolute configuration: (2S,3S)