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

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.

Wittig reaction - aldehydes - alkenes - peptidomimetics - thiazolidinones

References

<A NAME="RM44811SS-1">1</A>

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

<A NAME="RM44811SS-2A">2a</A> Garcia AM, Kowalczyk JJ, and Lewis MD. inventors; US Patent 6486202 B1  20021126.  ; Chem. Abstr. 2003, 138, 4818

<A NAME="RM44811SS-2B">2b</A> Lewis MD, Kowalczyk JJ, Christuk AE, Fan R, Harrington EM, Sheng XC, Yang H, Garcia AM, Hishinuma I, Nagasu T, and Yoshimatsu K. inventors; US Patent  5840918.  ; Chem. Abstr. 1995, 124, 146855

<A NAME="RM44811SS-2C">2c</A> Lewis MD, Garcia AM, Kowalczyk JJ, Yang H, and Schwartz CE. inventors; PCT Int. Appl. WO  9838162.  ; Chem. Abstr. 1998, 129, 231021

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<A NAME="RM44811SS-8">8</A>

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

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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.