Lithium Methylsulfinylmethylide1

LiCH2SOMe

[57741-62-5]  · C2H5LiOS  · Lithium Methylsulfinylmethylide  · (MW 84.08)

(a strong base and nucleophile, very useful for the introduction of the methylsulfinylmethyl group1)

Alternate Names: lithium dimsylate; dimsyllithium; LiDMSO.

Solubility: sol DMSO; sparingly sol THF.

Form Supplied in: not commercially available.

Analysis of Reagent Purity: titration with formanilide using triphenylmethane as indicator.2

Preparative Methods: by the reaction of alkyllithiums or Lithium Amide with Dimethyl Sulfoxide in DMSO or ethereal solvents.2,3 May also be prepared by the reaction of freshly prepared (but not commercial) LiH.4

Handling, Storage, and Precautions: best prepared as needed, although synthesis and storage procedures similar to those used in some preparations of Sodium Methylsulfinylmethylide (NaDMSO) would probably result in long shelf life.5 Complexes of LiDMSO with ethereal solvents have been isolated and characterized. Solvent-free LiDMSO is shock sensitive.6 Hydrogen gas or hydrocarbon may be emitted during the preparation of this reagent and due caution should be exercised in its preparation, particularly on a large scale. Problems encountered in the preparation of NaDMSO may be relevant to LiDMSO.7

Dimethyl sulfoxide is a weakly acidic compound (pKa = 35) whose conjugate base is both a strong nucleophile and base. The sodium and potassium salts of DMSO have found considerable use in synthesis (see Potassium Methylsulfinylmethylide and Sodium Methylsulfinylmethylide) and much of the chemistry of those reagents is shared with lithium methylsulfinylmethylide. This reagent was introduced nearly contemporaneously with NaDMSO, though the latter has seen more application.2

Lithium Methylsulfinylmethylide as Base.

Carbanion Accelerated Claisen Rearrangement.

LiDMSO, particularly in the presence of excess Lithium Chloride, serves as the best base for inducing the anionic Claisen rearrangement of (1) (eq 1).8 With NaDMSO and KDMSO, 1-(p-tolylsulfonyl)-2-butanone is formed as a side product in 24% and 65% yield, respectively. The side reaction leading to this elimination product is completely suppressed with LiDMSO in the presence of LiCl and leads to the conclusion that undesired reactions mediated by powerfully basic reagents might be minimized through the use of added lithium and other metal salts (see, for example, Cerium(III) Chloride).

Ether Synthesis.

The modification of polysaccharides via alkylation of free hydroxy groups (Hokomori reaction) has been performed using LiDMSO as base.9 Glycoprotein glycans have been similarly modified to facilitate their handling and analysis.10 The superiority of LiDMSO as a reagent for this reaction vis-à-vis NaDMSO has been reported.

Lithium Methylsulfinylmethylide as Nucleophile.

Reactions with Acid Derivatives.

The condensation of dimsyl anions with acid derivatives, almost exclusively esters, leads to the formation of b-keto sulfoxides, whose rich chemistry makes them versatile and useful intermediates (eqs 2 and 3).11,12 For example, the conversion of (4) to (5), an intermediate in a synthesis of vindoline, occurs via a Pummerer reaction followed by cyclization and carbocation rearrangement. Many other transformations of b-keto sulfoxides are known.13 A one-pot conversion of carboxylic acids to b-keto sulfoxides has been developed.13

Reaction of a carboxylic acid with N,N-Carbonyldiimidazole leads to acyl imidazolides which give b-keto sulfoxides upon reaction with LiDMSO (eq 4). b-Enamino sulfoxides can be prepared by condensation of amines with the adduct from the reaction of LiDMSO and DMF (eq 5).14 Finally, methylsulfinylketene dithioacetals are formed stereoselectively when LiDMSO is reacted with dialkyl thiocarbonates and the resulting lithium salts are quenched with alkyl halides (eq 6).15 With NaDMSO, mixtures of (E) and (Z) isomers are produced.

Reactions with Aldehydes and Ketones.

Non-enolizable ketones and aldehydes react successfully with dimsyl anions.1 An interesting route to naphthols was reported involving the nucleophilic addition of LiDMSO to an indenone followed by a ring expansion (eq 7).16 Reaction with a cyclohexadienone has also been reported (eq 8).17

A one-pot synthesis of alkenes from non-enolizable ketones begins with a carbonyl addition reaction, the product of which is treated with a chlorophosphite. Decomposition of the adduct gives the alkene in high yield (eq 9).18

The reaction of LiDMSO with cyclohexanone is reported to give a 45% yield of the addition product along with 51% of recovered starting material, arising from competitive enolization of the ketone. This compares favorably with NaDMSO, with which the same products are formed in 17 and 80% yields, respectively. This is another example of the potential of LiDMSO in circumventing untoward reactions precipitated by the potent basicity of dimsyl anions.

Reaction with Imines and Related Compounds.

As with NaDMSO, the addition of LiDMSO to aromatic nitrogenous heterocycles has been examined. A recent report describes a tandem addition to quinoxaline to give an annulated product in fair yield (eq 10).19

Reaction with Halides.

LiDMSO reacts with chloromethyl alkyl ethers to give substitution products in poor to fair yields.20

Reaction with Michael Acceptors.

a,b-Unsaturated thioamides react in a 1,4-fashion with LiDMSO (eq 11).21 No information on the diastereoselectivity of this reaction was reported.

Reaction with Sulfur Electrophiles.

Optically active b-disulfoxides are available from the reaction of optically pure menthyl sulfoxides and LiDMSO.22

Other Applications.

The use of DMSO as a dummy ligand in cuprate chemistry has been reported.23 The reaction of LiDMSO with Copper(I) Iodide followed by reaction with an alkyllithium (RLi) gives a cuprate (MeSOCH2)RCuLi. Subsequent reactions including conjugate additions, ketone formation from acid chlorides, SN2 reactions, and coupling with primary iodides and tosylates result in selective transfer of the alkyl group. This inexpensive and readily available dummy ligand should find considerable application in cuprate chemistry.


1. (a) Durst, T. Adv. Org. Chem. 1969, 6, 285. (b) Martin, D.; Hauthal, H. G. Dimethyl Sulphoxide; Wiley: New York, 1971; pp 349-374.
2. Corey, E. J.; Chaykovsky, M. JACS 1965, 87, 1345.
3. Ratajczak, A.; Anet, F. A. L.; Cram, D. J. JACS 1967, 89, 2072.
4. Pi, R.; Friedl, T.; von Ragué Schleyer, P.; Klusener, P.; Brandsma, L. JOC 1987, 52, 4299.
5. Sjöberg, K. TL 1966, 6383.
6. Martin, K. R. JOM 1970, 24, 7.
7. (a) Price, C. C.; Yukuta, T. JOC 1969, 34, 2503. (b) Leleu, J. Cah. Notes. Doc. 1976, 85, 583 (CA 1978, 88, 26 914t). (c) Itoh, M.; Morisaki, S.; Muranaga, K.; Matsunaga, T.; Tohyama, K.; Tamura, M.; Yoshida, T. Anzen Kogaku 1984, 23, 269 (CA 1985, 102, 100 117).
8. (a) Denmark, S. E.; Harmata, M. A.; White, K. S. JACS 1989, 111, 8878. (b) Denmark, S. E.; Harmata, M. A. JOC 1983, 48, 3369.
9. Kvernheim, A. L. ACS 1987, B41, 150.
10. Parente, J. P.; Cardon, P.; Leroy, Y.; Montreuil, J.; Fournet, B.; Ricart, G.; Carbohydr. Res. 1985, 141, 41.
11. Andriamialisoa, R. Z.; Langlois, N.; Langlois, Y. JOC 1985, 50, 961.
12. Bravo, P.; Piovosi, E.; Resnati, G. S 1986, 579.
13. For leading references, see: Ibarra, C. A.; Rodríguez, R. C.; Monreal, M. C. F.; Navarro, F. J. G.; Tesorero, J. M. JOC 1989, 54, 5620.
14. Kawçecki, R.; Kozerski, L. T 1986, 42, 1469.
15. Yokoyama, M.; Tsuji, K.; Hayashi, M.; Imamoto, T. JCS(P1) 1984, 85.
16. Buggle, K.; Ghógáin, U. N.; O'Sullivan, D. JCS(P1) 1983, 2075.
17. Fischer, A.; Sankararaman, S. JOC 1987, 52, 4464.
18. Kuwajima, I.; Uchida, M. TL 1972, 649.
19. Vierfond, J.-M.; Legendre, L.; Mahuteau, J.; Miocque, M. H 1989, 29, 141.
20. Böhme, H.; Clement, B. AP 1979, 312, 1052.
21. Tamaru, Y.; Harada, T.; Iwamoto, H.; Yoshida, Z. JACS 1978, 100, 5221.
22. Kunieda, N.; Nokami, J.; Kinoshita, M. BCJ 1976, 49, 256.
23. Johnson, C. R.; Dhanoa, D. S. JOC 1987, 52, 1885.

Michael Harmata

University of Missouri-Columbia, MO, USA



Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.