An efficient enantioselective synthesis of florfenicol via a vanadium-catalyzed asymmetric epoxidation

An efficient and highly enantioselective synthesis of florfenicol 1 was achieved with 37% overall yield starting from commercially available 4-methylthiobenzaldehyde. A key feature of the synthesis is the vanadium-catalyzed asymmetric epoxidation of allylic alcohol 5 with aq tert-butyl hydroperoxide to form (2S,3S)-epoxide 6.

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(S,S)-3-[4-(Methylsulfonyl)phenyl]-2,3-epoxypropyl alcoholC10H12O4SEe = 91%[α]D20=-33.1 (c 1.0, CHCl3)Source of chirality: asymmetric epoxidationAbsolute configuration: (2S,3S)

(R)-3-Benzyl-4-[(S)-hydroxy(4-methylsulfonylphenyl)methyl]oxazolidin-2-oneC18H19NO5SDr >20:1[α]D20=-1.1 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3R,4S)

(R)-((R)-3-Benzyl-2-oxooxazolidin-4-yl)[4-(methylsulfonyl)phenyl]methyl acetateC20H21NO6SDr >20:1[α]D20=-3.5 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3R,4R)

(2R,3R)-2-Benzylamino-3-(4-methylsulfonylphenyl)-propane-1,3-diolC17H21NO4S[α]D20=-46.6 (c 1.0, ethanol)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,3R)

(1R,2R)-2-Amino-1-[4-(methylsulfonyl)phenyl]-1,3-propanediolC10H15NO4S[α]D25=-20.1 (c 1.0, ethanol)Source of chirality: asymmetric synthesisAbsolute configuration: (1R,2R)

(4R,5R)-2-(Dichloromethyl)-5-[4-(methylsulfonyl)phenyl]oxazole-4-methanolC12H13Cl2NO4S[α]D20=+10.9 (c 1.0, ethanol)Source of chirality: asymmetric synthesisAbsolute configuration: (4R,5R)

FlorfenicolC12H13Cl2NO4S[α]D20=-18.1 (c 1.0, DMF)Source of chirality: asymmetric synthesisAbsolute configuration: (1R,2R)