Dimethylsulfonium Methylide

[6814-64-8]  · C3H8S  · Dimethylsulfonium Methylide  · (MW 76.18)

(exceedingly selective methylene transfer reagent capable of converting carbonyl compounds into oxiranes,1 and imines into aziridines2)

Form Supplied in: reactive intermediate generated in situ.

Preparative Methods: Method A.1a,b A solution of dimethylsulfonium methylide is readily prepared by addition of a solution of Trimethylsulfonium Iodide in Dimethyl Sulfoxide (800 mL per mol of sulfonium salt) with stirring (below 5 °C, because of the marked thermal instability of the methylide) to an equivalent molar amount of a 1.5-2 M solution of methylsulfinyl carbanion,3 which is prepared by treatment of dry DMSO with Sodium Hydride under nitrogen followed by dilution with an equal amount of dry THF (to prevent solidification).

Method B.1b Alternatively, a solution of n-Butyllithium (11 mmol) in 8 mL of pentane may be added dropwise to a stirred suspension of 2.45 g (12 mmol) of powdered trimethylsulfonium iodide in 30 mL of dry THF under nitrogen at 0 °C.

Method C.4 To a solution of Dimethyl Sulfate (189.2 g, 1.50 mol) in acetonitrile (700 mL) is added a solution of Dimethyl Sulfide (102.5 g, 1.65 mol) in acetonitrile (300 mL) with stirring at rt. After standing overnight, Sodium Methoxide (89.1 g, 1.65 mol) is added to the mixture at rt to give a solution of dimethylsulfonium methylide, which is successfully applied to the preparation of oxiranes from various kinds of carbonyl compound. In comparison with the former methods, this process is more favorable for preparing oxiranes on a large scale under mild conditions without using expensive alkylating agents and intractable solvents.

Method D.1d To a mixture of 0.1 mol of aldehyde (or ketone) and 22 g (0.14 mol) of trimethylsulfonium bromide dissolved in 60 mL of DMSO is added a solution of 14 g of Potassium t-Butoxide in 60 mL of DMSO with stirring and cooling under nitrogen over 30-45 min. After workup, the expected oxiranes can be separated and purified by distillation or recrystallization. In this method, Sodium Amide or sodium hydride can be used as a base instead of potassium t-butoxide, and DMF may be used as solvent. Benzalaniline may be converted by this method into the corresponding aziridine.

Method E.5 Dimethylsulfonium methylide can also be obtained by phase-transfer catalysis. Thus trimethylsulfonium iodide does not react with benzaldehyde in the system CH2Cl2-NaOH, but on addition of 1-5 mol % of Tetra-n-butylammonium Iodide, 2-phenyloxirane is obtained in >90% yield via the intermediate sulfonium methylide. Yields of oxiranes are rather low (20-35%) when ketones are used in this procedure.

Formation of Oxiranes.

Dimethylsulfonium methylide reacts with a variety of aldehydes and ketones by net methylene transfer to form oxiranes. Thus several compounds, including benzophenone, benzaldehyde, and cycloheptanone were converted into the corresponding oxiranes by selective addition of methylene to the carbonyl group (eqs 1-3).1b

It should be noted that dimethylsulfonium methylide prefers addition to the carbonyl group of a,b-unsaturated carbonyl compounds while Dimethylsulfoxonium Methylide, which is a closely related reagent for methylene transfer to unsaturated compounds, tends to attack the a,b-double bond. For example, carvone was converted to the corresponding oxirane by treatment with the sulfonium ylide, whereas the sulfoxonium ylide reacts with carvone to give the cyclopropyl ketone (eq 4).1b

Similarly, selective oxirane formation was achieved in the cases of other a,b-unsaturated ketones such as eucarvone (93%), benzalacetone (87%), and pulegone (90%).1b

Epoxidation of b-ionone can also be achieved by the treatment of a mixture of trimethylsulfonium chloride (24 g), b-ionone (38.4 g), CH2Cl2 (100 mL), and Benzyltriethylammonium Chloride (1 g) with aqueous NaOH (18 M, 125 mL) at rt (eq 5).6

No epoxide is obtained, however, by reaction of b-ionone with dimethylsulfonium methylide generated by the conventional methods using other trimethylsulfonium halides5,7 or trimethylsulfonium methylsulfate4 as a precursor.

Dimethylsulfonium methylide undergoes stereoselective addition of two methylene units to 9,10-anthraquinone to afford the corresponding trans-bisepoxide (eq 6).8

Asymmetric Oxirane Synthesis.

A striking asymmetric synthesis of 2-phenyloxirane can be achieved by the reaction of benzaldehyde and dimethylsulfonium methylide generated from trimethylsulfonium iodide in 50% NaOH with the chiral phase-transfer catalyst (-)-N,N-dimethylephedrinium bromide (0.2 equiv) (eq 7).9

The optical yield of oxirane in eq 7 is 67%. If the asymmetric salt derived from y-ephedrine is used, the enantiomeric oxirane is formed preferentially. In this system the choice of the solvent is important. Little asymmetric induction is observed with THF or acetonitrile as solvent, while the use of benzene results in a high degree of induction.

Synthesis of Butenolides.

The reaction of a cyclic a-keto ketene dithioacetal with dimethylsulfonium methylide followed by acid hydrolysis produced the corresponding butenolide in high yield (eq 8).10

The reaction of dimethylsulfonium methylide with acyclic a-keto ketene dithioacetals also provides a simple synthesis of dihydrofurans, which can be converted into various furans and butenolides (eqs 9 and 10).11

Cyclopropanation via Methylene Transfer to Carbon-Carbon Double Bonds.

In contrast to a,b-unsaturated ketones, ethyl cinnamate, an a,b-unsaturated carboxylic acid ester, was transformed into 2-phenyl-1-cyclopropane carboxylate (eq 11).1d

Since dimethylsulfonium methylide is a far more powerful methylene transfer reagent than dimethylsulfoxonium methylide, it can convert 1,1-diphenylethylene into 1,1-diphenylcyclopropane in 60% yield though it is necessary to use an excess amount of methylide (5 equiv) (eq 12).1b However, dimethylsulfonium methylide is inactive toward tolan or trans-stilbene, and unreactive toward nonconjugated carbon-carbon double bond compounds.

Methylation of Aromatic Rings.

Dimethylsulfonium methylide reacts with acenaphthylene in DMSO-THF to give 3-methylacenaphthylene together with some 5-methylacenaphthylene (eq 13).12 Similarly, fluoranthrene gives a mixture of 1- and 3-methylfluoranthrenes upon treatment with dimethylsulfonium methylide (eq 14).12

N-Methylation of Indoles.

Indoles can be selectively N-methylated by dimethylsulfonium methylide in THF at rt (eq 15).13

Aziridine Formation.

Dimethylsulfonium methylide reacts smoothly with imines. For example, benzalaniline can be converted to the corresponding aziridine in 91% yield (eq 16).1b,d

Using this methodology, the first known heterocyclic analog of bicyclobutane, 3-phenyl-1-azabicyclo[1.1.0]butane, has been obtained by the reaction of 3-phenyl-2H-azirine with dimethylsulfonium methylide in dry THF at -10 °C (eq 17).2

Alkene Formation.

Dimethylsulfonium methylide reacts with benzyl chloride in the presence of excess amount of base to give styrene (eq 18).1d

Related Reagents.

Dimethylsulfoxonium Methylide.


1. (a) Corey, E. J.; Chaykovsky, M. JACS 1962, 84, 3782. (b) Corey, E. J.; Chaykovsky, M. JACS 1965, 87, 1353. (c) Franzen, V.; Driesen, H. E. TL 1962, 661. (d) Franzen, V.; Driesen, H. E. CB 1963, 96, 1881.
2. Hortmann, A. G.; Robertson, D. A. JACS 1967, 89, 5974. See also refs. 1b and 1d.
3. Corey, E. J.; Chaykovsky, M. JACS 1962, 84, 866.
4. Kutsuma, T.; Nagayama, I.; Okazaki, T.; Sakamoto, T.; Akaboshi, S. H 1977, 8, 397.
5. Merz, A.; Märkl, G. AG(E) 1973, 12, 845.
6. Rosenberger, M.; Jackson, W.; Saucy, G. HCA 1980, 63, 1665.
7. (a) Yoshimine, M.; Hatch, M. J. JACS 1967, 89, 5831. (b) Hatch, M. J. JOC 1969, 34, 2133. See also ref. 5.
8. McCarthy, T. J.; Connor, W. F.; Rosenfeld, S. M. SC 1978, 8, 379.
9. Hiyama, T.; Mishima, T.; Sawada, H.; Nozaki, H. JACS 1975, 97, 1626.
10. Garver, L. C.; van Tamelen, E. E. JACS 1982, 104, 867.
11. (a) Okazaki, R.; Negishi, Y.; Inamoto, N. CC 1982, 1055. (b) Okazaki, R.; Negishi, Y.; Inamoto, N. JOC 1984, 49, 3819.
12. Trost, B. M. TL 1966, 5761.
13. Bravo, P.; Gaudiano, G.; Umani-Ronchi, A. G 1970, 100, 652.

Renji Okazaki & Norihiro Tokitoh

The University of Tokyo, Japan



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