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Synthesis 2011(23): 3859-3865  
DOI: 10.1055/s-0031-1289583
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

(R)-[(2-Oxo-4-thiazolidinyl)methyl]triphenylphosphonium Iodide: A Wittig Reagent for the Synthesis of Cysteine-Derived Alkenes

Christina J. Shaffer, RuLin Fan, Michael D. Lewis, James J. Kowalczyk*
Eisai Inc., 4 Corporate Drive, Andover, MA 01810-2441, USA
e-Mail: jkowalczyk@alum.mit.edu;
Further Information

Publication History

Received 27 April 2011
Publication Date:
07 November 2011 (online)

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Abstract

(R)-[(2-Oxo-4-thiazolidinyl)methyl]triphenylphosphonium iodide (1), readily prepared in five steps from l-cysteine ethyl ester (39% overall on a 500 g scale), is a useful Wittig reagent for the synthesis of cysteine-derived alkenes such as those found in dipeptide isosteres and peptidomimetics. Preparation of 1 and its use in Wittig olefination reactions with aldehydes is described. The resulting thiazolidinone compounds are readily unmasked to provide the corresponding thiol, symmetrical disulfide, or S-trityl derivatives.

Key words

Wittig reaction - aldehydes - alkenes - peptidomimetics - thiazolidinones

    References

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1

Current address: School of Pharmacy, JiangSu University, Zhenjiang City, Jiang Su Province, ZP 212003, P. R. of China.

6

Ethyl (R)-(-)-2-oxo-4-thiazolidinecarboxylate (4) has recently become available commercially from Aldrich Chemical Co.

8

Similarly, the enantiomer of 1 was prepared from d-cysteine ethyl ester according to Scheme  [¹] .

10

Compound 27 was prepared in 4 steps from 4-isopropyl-benzaldehyde (bromination; halogen-metal exchange using t-BuLi and quench with ethyl chloroformate; Wittig reaction with (methoxymethyl)triphenylphosphonium chloride + t-BuOK; enol ether hydrolysis with aq HI in MeCN). See ref. 2a. Compound 27 may also be prepared in 6 steps from 5-formylsalicylic acid via Stille coupling using tribut-yl(prop-1-en-2-yl)stannane and a hydrogenation.