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Synlett 2011(19): 2883-2885  
DOI: 10.1055/s-0031-1289858
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

A Facile and Efficient Asymmetric Synthesis of Florfenicol

Feng Lia, Zhong-Hua Wanga, Lei Zhaob, Fen-Er Chen*a,b
a Department of Chemistry, Fudan University, 220 Handan Road, Shanghai 200433, P. R. of China
b Institute of Biomedical Science, Fudan University, 305 Fenglin Road, Shanghai 200032, P. R. of China
Fax: +86(21)65643811; e-Mail: rfchen@fudan.edu.cn;
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Publication History

Received 8 September 2011
Publication Date:
09 November 2011 (online)

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Abstract

A facile and efficient enantioselective synthesis of flor­fenicol starting from commercially available 4-methylthiobenzaldehyde is described. Key features of the synthesis include a one-step oxidation of allyl and thioether groups in allylic alcohol to form (2S,3S)-epoxide under Sharpless epoxidation conditions and a highly efficient conversion of (1R,2R)-azide into amino alcohol via debenzylation and reduction of an azido moiety in one-pot operation.

Key words

florfenicol - Sharpless asymmetric epoxidation - one-pot reaction - SN2 nucleophilic substitution - fluorination

    Primary data for this article are available online and can be cited using the following DOI: 10.4125/pd0021th:
  • Primary Data

    References and Notes

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3

Experimental Procedure - Preparation of 4 To a stirred suspension of 4 Å MS powder (1 g) in dry CH2Cl2 (10 mL), (-)-diisopropyl tartrate (0.174 g, 0.74 mmol) and Ti(Oi-Pr)4 (0.216 g, 0.74 mmol) were added successively at -40 ˚C under nitrogen atmosphere. After stirring 1 h at the same temperature, 3 (0.67 g, 3.7 mmol)
and t-BuOOH (3.3 M, 7.5 mL) in toluene was added. The reaction mixture was stirred for 48 h at -40 ˚C. Sat. aq NaHSO3 (10 mL) was added, and stirring was continued for 1 h. The reaction mixture was then allowed to warm to r.t., extracted with CH2Cl2 (3 × 10 mL), dried over Na2SO4,
and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (EtOAc-PE = 1:2) to afford 4 (0.59 g, 70% yield, 75% ee)
as a white solid.