Methyl 2-Methylthioacrylate

[43228-10-0]  · C5H8O2S  · Methyl 2-Methylthioacrylate  · (MW 132.20)

(versatile and reactive Michael acceptor2-5)

Physical Data: bp 78 °C/12 mmHg.

Solubility: sol Et2O, THF, EtOH, and most organic solvents.

Analysis of Reagent Purity: IR, NMR, GLC.

Preparative Methods: prepared either by the reaction of methyl 2-chloroacrylate1a or methyl 2-bromoacrylate1b with Methanethiol in the presence of Triethylamine and N,N-Dimethylformamide. It is also obtained1c quantitatively by chlorination of methyl 2-alkylthiopropionates (alkyl = Me/Et) with Sulfuryl Chloride at 0 °C followed by dehydrochlorination using refluxing chloroform. For preparation of alkyl 2-alkylsulfonylacrylates and its uses, see Gipstein.8

Handling, Storage, and Precautions: since the reagent is an acrylate, it should be stored under N2 in the refrigerator and should be inhibited with ionol or 100 ppm of hydroquinone monomethyl ether. Use in a fume hood.

1,4-Dicarbonyl Compounds.

Lithium enolates derived from esters,2a lactones,2a and thioacetal monosulfoxide2b undergo smooth Michael addition in high yield. These adducts on hydrolysis give the corresponding carbonyl analogs (eqs 1-3). Enamines2a give high yields of Michael adducts (eq 4).

Synthesis of (±)-Vincamine.3

The lithium enolate of a lactam undergoes Michael addition to methyl 2-methylthioacrylate at -78 °C, furnishing 98% yield of the adduct (eq 5) which was later converted to (±)-vincamine alkaloid. A similar Michael addition was used in the synthesis of a-kainic acid (eq 6).4

Diels-Alder Substrate.

The reagent undergoes a facile, Aluminum Chloride-catalyzed Diels-Alder5a reaction with Isoprene, Cyclopentadiene, and cyclohexadiene and gives [4 + 2] addition products (eqs 7 and 8). If the reaction is carried out under thermal conditions, mixtures of endo and exo adducts are formed. These adducts are converted to ketones using N-Chlorosuccinimide/t-butanol.

This further demonstrates that methyl 2-methylthioacrylate can be regarded as a ketene5b equivalent. With electron-poor dienes such as 3-aryl-1,2,4,5-tetrazine,6 it gives regioselectively only one of two possible [4 + 2] cycloadducts (eq 9).

Use of this reagent in the acid-catalyzed ene reaction7 does not give any ene product; instead, it rearranges to trans-b-(methylthio)acrylate (eq 10).

Related Reagents.

Methyl 2-Trimethylsilylacrylate; Trimethyl 2-Phosphonoacrylate.

1. (a) Gundermann, K.-D.; Thomas, R. CB 1958, 91, 1330 (CA 1958, 52, 19 930b). (b) Boucher, J.-L.; Stella, L. T 1988, 44, 3595. (c) Iriuchijima, S.; Tanokuchi, K.; Tadokoro, K.; Tsuchihashi, G. ABC 1976, 40, 1031.
2. (a) Cregge, R. J.; Herrmann, J. L.; Schlessinger, R. H. TL 1973, 2603. (b) Herrmann, J. L.; Richman, J. E.; Schlessinger, R. H. TL 1973, 3271.
3. Herrmann, J. L.; Cregge, R. J.; Richman, J. E.; Kieczykowski, G. R.; Normandin, S. N.; Quesada, M. L.; Semmelhack, C. L.; Poss, A. J.; Schlessinger, R. H. JACS 1979, 101, 1540.
4. Oppolzer, W.; Andres, H. HCA 1979, 62, 2282.
5. (a) Stella, L.; Boucher, J.-L. TL 1982, 23, 953. (b) Boucher, J.-L.; Stella, L. T 1988, 44, 3607.
6. Meier, A.; Sauer, J. TL 1990, 31, 6855.
7. Duncia, J. V.; Lansbury, Jr., P. T.; Miller, T.; Snider, B. B. JACS 1982, 104, 1930.
8. Gipstein, E.; Willson, C. G.; Sachdev, H. S. JOC 1980, 45, 1486.

Anubhav P. S. Narula

International Flavors & Fragrances, Union Beach, NJ, USA

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