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Synthesis 2012(5): 699-704  
DOI: 10.1055/s-0031-1289706
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

An Efficient Enantioselective Synthesis of Florfenicol Based on Sharpless Asymmetric Dihydroxylation

Zhong-Hua Wanga, Chen Zhenga, Feng Lia, Lei Zhaob, Fen-Er Chen*a,b, Qiu-Qin He*a
a Department of Chemistry, Fudan University, 220 Handan Road, 200433 Shanghai, P. R. of China
b Institute of Biomedical Science, Fudan University, 305 Fenglin Road, 200031 Shanghai, P. R. of China
Fax: +86(21)65643811; e-Mail: rfchen@fudan.edu.cn;
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Publication History

Received 23 November 2011
Publication Date:
14 February 2012 (online)

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Abstract

An efficient and highly enantioselective synthesis of florfenicol­ via a new intermediate threo-dihydroxy ester, with a Sharpless asymmetric dihydroxylation as the key step, is reported. A ring-opening/reduction strategy avoids the formation of a chlorinated byproduct that occurs in Schumacher’s phenyloxazoline procedure. The overall yield of florfenicol by this new process is 23% based on 4-(methylsulfonyl)benzaldehyde.

Key words

halogenation - heterocycles - asymmetric synthesis - sulfones - drugs

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Calculated by using ACD ChemSketch software. This software can be downloaded from http://www.acdlabs.com.

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Crystallographic data for compound 11 have been deposited with the accession number CCDC 830167, and can be obtained free of charge from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; Fax: +44(1223)336033; E-mail: deposit@ccdc.cam.ac.uk; Web site: www.ccdc.cam.ac.uk/conts/retrieving.html.