An Efficient Enantioselective
Synthesis of Florfenicol Based on Sharpless Asymmetric Dihydroxylation

Zhong-Hua Wang; Chen Zheng; Feng Li; Lei Zhao; Fen-Er Chen; Qiu-Qin He

doi:10.1055/s-0031-1289706

PAPER

An Efficient Enantioselective Synthesis of Florfenicol Based on Sharpless Asymmetric Dihydroxylation

Zhong-Hua Wang^a, Chen Zheng^a, Feng Li^a, Lei Zhao^b, 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;

Abstract

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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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References

1a Nagabhushan TL. inventors; US 4235892. ; Chem. Abstr. 1982, 96, 180950

1b Schumacher DP. Clark JE. Murphy BL. Fischer PA. J. Org. Chem. 1990, 55: 5291

1c Giordano C. Cavicchioli S. Levi S. Villa M. J. Org. Chem. 1991, 56: 6114

1d Clark JE. Fischer PA. Schumacher DP. Synthesis 1991, 891

2 Li F. Wang ZH. Zhao L. Xiong FJ. He QQ. Chen FE. Tetrahedron: Asymmetry 2011, 22: 1337

3 Wang ZH. Li F. Zhao L. He QQ. Chen FE. Zheng C. Tetrahedron 2011, 67: 9199

For reviews of the Sharpless AD reaction, see:

4a Kolb HC. VanNieuwenhze MS. Sharpless KB. Chem. Rev. 1994, 94: 2483

4b Sharpless KB. Angew. Chem. Int. Ed. 2002, 41: 2024

4c Noe MC. Letavic MA. Snow SL. Org. React. (N. Y.) 2005, 66: 109

5a Denis JN. Correa A. Greene AE. J. Org. Chem. 1990, 55: 1957

5b Fleming PR. Sharpless KB. J. Org. Chem. 1991, 56: 2869

5c Boger DL. Patane MA. Zhou J. J. Am. Chem. Soc. 1994, 116: 8544

6 Wu G.-Z. Schumacher DP. Tormos WE. Clark JB. Murphy L. J. Org. Chem. 1997, 62: 2996

7

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

8

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.

9 Meyers AI. Roth GP. Hoyer D. Barner BA. Laucher D. J. Am. Chem. Soc. 1988, 110: 4611

10 Lu WY. Chen PR. Lin GQ. Tetrahedron 2008, 64: 7822