Ethyl (Dimethylsulfuranylidene)acetate

[7380-81-6]  · C6H12O2S  · Ethyl (Dimethylsulfuranylidene)acetate  · (MW 148.25)

(stabilized sulfonium ylide reagent capable of reacting with a variety of electrophiles to produce substituted cyclopropanes, epoxides, enamines, and stabilized ylides, as well as other products1)

Alternate Name: EDSA.

Physical Data: d 1.52 g cm-3.

Solubility: toluene, benzene, CH2Cl2, acetone, THF, EtOH

Form Supplied in: not available commercially.

Preparative Method: synthesized in two simple steps (85% overall yield). An equimolar combination of ethyl bromoacetate and Dimethyl Sulfide is stirred in acetone at rt for three days, after which the precipitated sulfonium salt is isolated by filtration. The salt is then converted to the ylide by treatment with K2CO3/NaOH in CHCl3/water.1b

Analysis of Reagent Purity: 1H NMR (CDCl3) d 1.2 (t, 3H), 3.9 (q, 2H), 2.7-2.8 (br s, 7H).

Handling, Storage, and Precautions: although the reagent is subject to moisture-induced and thermal decomposition, no report of hazard has been found. The presence of water gives rise to ester hydrolysis and quenching of the ylide to form the zwitterionic sulfonium carboxylate Me2+SCH2CO2-. Significant instability has also been noted at slightly elevated temperatures (35% decomposition at 80 °C in 3 h). Successful storage (several weeks) can be accomplished at -10 °C under anhydrous conditions.1b

Cyclopropanations.

A variety of electron-deficient alkenes react with this reagent in aprotic solvents to produce good yields of ethoxycarbonyl-substituted cyclopropanes (eq 1). EtOH and presumably other protic solvents allow alternative reaction pathways which seem to be dependent on proton transfer.1c The mechanism can be thought of as 1,4-addition followed by intramolecular ring closure with loss of dimethyl sulfide. In general, the reaction succeeds for double bonds activated by one or two strong electron-withdrawing groups (EWG) which may include CHO, COR, CO2R, CN, and CF3 (Table 1).1b,2-8 The reaction is stereoselective in favor of the trans product but in certain cases the selectivity is only marginal.

Stabilized Sulfur Ylides.

Acid chlorides, anhydrides, and isocyanates acylate EDSA to generate good yields of stabilized sulfur ylides. In addition, alkynes conjugated with either ketones or esters react in a similar fashion (eq 2).1e

Epoxidations.

In contrast to Dimethylsulfonium Methylide,9 EDSA usually does not react with aldehydes or ketones in a 1,2-sense to generate epoxides. However, under certain conditions,1e electron-deficient carbonyls do undergo this reaction. Thus EDSA can be considered an alternative (albeit of limited scope) to a-haloacetic acid esters in the Darzens condensation (eq 3).10

Interestingly, the carboxylate salt of EDSA has been reported to epoxidize unactivated ketones.11

Alternative Reagents.

While Ethyl Diazoacetate12 also reacts with alkenes to provide good yields of ethoxycarbonyl substituted cyclopropanes, it can be differentiated from EDSA in two ways. In the first place, EDSA, requiring an electron deficient double bond, can be considered more selective. Secondly, in large scale reactions, ethyl diazoacetate carries a risk of explosion which EDSA does not have. Ethyl chloroacetate (or Methyl Chloroacetate) under basic conditions accomplishes the same transformation as EDSA.13

Related Reagents.

Two similar carbonyl-stabilized dimethylsulfonium methylides (1 and 2) have been reported to function as cyclopropanating reagents in a fashion analogous to EDSA.14


1. (a) Speziale, A. J.; Tung, C. C.; Ratts, K. W.; Yao, A. JACS 1965, 87, 3460. (b) Payne, G. B. JOC 1967, 32, 3351. (c) Payne, G. B. JOC 1968, 33, 1284. (d) Payne, G. B. JOC 1968, 33, 1285. (e) Payne, G. B. JOC 1968, 33, 3517.
2. Arbale, A. A.; Naik, R. H.; Kulkarni, G. H. IJC(B) 1990, 29B, 568.
3. Mack, H.; Hanack, M. LA 1989, 833.
4. Wender, P. A.; Hillemann, C. L.; Szymonifka, M. J. TL 1980, 21, 2205.
5. Wanner, M. J.; Hageman, J. J. M.; Koomen, G. J.; Pandit, U. K. RTC 1978, 97, 211.
6. Mitra, R. B.; Muljiani, Z.; Reddy, G. B. SC 1986, 16, 1099.
7. Rao, A. V. R.; Rao, M. N.; Garyali, K. SC 1984, 14, 557.
8. Iwata, C.; Suzuki, K.; Aoki, S.-I.; Okamura, K.; Yamashita, M.; Takahashi, I.; Tanaka, T. CPB 1986, 34, 4939.
9. House, H. O. Modern Synthetic Reactions, 2nd ed.; Benjamin: Menlo Park, CA, 1972.
10. Newman, M. S.; Magerlein, B. J. OR 1949, 5, 413.
11. Adams, J.; Hoffman, L., Jr.; Trost, B. M. JOC 1970, 35, 1600.
12. Dave, V.; Warnhoff, E. W. OR 1970, 18, 217.
13. (a) Uchytil, B.; Procházka CCC 1974, 39, 2085. (b) Ashton, W. T.; Meurer, L. C.; Cantone, C. L.; Field, A. K.; Hannah, J.; Karkas, J. D.; Liou, R.; Patel, G. F.; Perry, H. C.; Wagner, A. F.; Walton, E.; Tolman, R. L. JMC 1988, 31, 2304.
14. (a) Neff, J. R.; Gruetzmacher, R. R.; Nordlander, J. E. JOC 1974, 39, 3814. (b) Chiericato, M.; Croce, P. D.; Licandro, E. JCS(P1) 1979, 211.

Charles W. Murtiashaw

Pfizer, Groton, CT, USA



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