Ethyl (Phenylsulfinyl)acetate

[54882-04-1]  · C10H12O3S  · Ethyl (Phenylsulfinyl)acetate  · (MW 221.27)

(addition to aldehydes followed by thermal elimination gives 3-keto esters;1 addition to carbonyl compounds followed by desulfurization gives 3-hydroxy esters;2 aldehyde Knoevenagel condensation products undergo thermal rearrangement to give (2E,4E)-dienoate esters or 4-hydroxy-(2E)-enoate esters3,4)

Physical Data: colorless liquid.

Analysis of Reagent Purity: microanalysis; 1H NMR2,3 and 13C NMR5 spectroscopy.

Preparative Methods: sodium thiophenoxide in ethanol is treated with ethyl bromoacetate and refluxed for 1 h, giving ethyl (phenylthio)acetate after distillation (bp 101-104 °C/0.4 mmHg), which is oxidized with sodium periodate or preferably sodium perborate6 in water/methanol to afford the title compound as a colorless liquid.3 Another method is by treatment of the anion of methyl phenyl sulfoxide with diethyl carbonate.2

Addition to Aldehydes to give 3-Keto Esters1 and 3-Hydroxy Esters.2

When deprotonated with bases containing the lithium or sodium counterion ethyl (phenylsulfinyl)acetate exhibits poor reactivity and fails to undergo alkylation or nucleophilic addition. However, deprotonation of ethyl (phenylsulfinyl)acetate with 1 equiv of Ethylmagnesium Bromide in diethyl ether at 0 °C gives the magnesium salt as a milky precipitate, and addition of aldehydes results in the formation of alkyl-2-phenylsulfinyl-3-hydroxy esters. Thermal syn elimination of benzenesulfinic acid affords an enol which tautomerizes to the 3-keto ester (eq 1). Desulfurization of the addition product with Raney Nickel gives 3-hydroxy esters, the result of a formal addition of ethyl acetate anion to an aldehyde.

Preparation of (2E,4E)-2,4-Dienoate Esters or 4-Hydroxy-(2E)-enoate Esters.3,4

Ethyl (2E)-2-phenylsulfinyl-2-alkenoates can be prepared by treatment of the aldehydes with ethyl (phenylsulfinyl)acetate and a catalytic amount of Piperidine in acetonitrile. The resultant vinyl sulfoxide is treated with anhydrous Potassium Carbonate in refluxing xylenes; after 4 h the trans,trans dienoate is isolated in 59% yield as a 91:9 mixture of the trans,trans isomer to other isomers, as determined by GLC. A 12% yield of the 4-hydroxy-(2E)-enoate ester, presumably resulting from hydrolysis of the intermediate sulfenate ester, is also obtained. The vinyl sulfoxide product of the Knovenagel condensation is proposed to undergo a base-catalyzed deconjugation followed by a thermally induced [2,3]-sigmatropic shift to give the sulfenate ester which can either hydrolyze to give the hydroxyenoate or undergo another [2,3]-sigmatropic shift, eliminating the sulfoxide to give the dienoate. Use of anhydrous conditions favors the formation of the diene (eq 2).

Treatment of an aldehyde with ethyl (phenylsulfinyl)acetate under prolonged Knoevenagel conditions using a catalytic amount of piperidine results in the formation, without isolation of intermediates of the hydroxy enoates.7 This reaction has been used in the synthesis of (R)-patulolide (eq 3).8

1. Nokami, J.; Kunieda, N.; Kinoshita, M. TL 1975, 33, 2841.
2. Nokami, J.; Kunieda, N.; Kinoshita, M. TL 1974, 46, 3997.
3. Tanikaga, R.; Nozaki, Y.; Nishida, M.; Kaji, A. BCJ 1984, 57, 729.
4. Solladié, G.; Gerber, C. SL 1992, 449.
5. Barchiesi, E.; Bradamante, S.; Ferraccioli, R.; Pagani, G. A. JCS(P2) 1990, 3, 375.
6. McKillop, A.; Tarbin, J. A. T 1987, 43, 1753.
7. Tanikaga, R.; Nozaki, Y.; Tamura, T.; Kaji, A. S 1983, 134.
8. Solladié, G.; Gerber, C. SL 1992, 449.

Dinos Santafianos

Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ, USA

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