Dimethyl Bis(methylthio)methylphosphonate1

[61779-87-1]  · C5H13O3PS2  · Dimethyl Bis(methylthio)methylphosphonate  · (MW 216.29)

(treatment with base gives a carbanion that reacts with aldehydes and ketones1-5)

Alternate Name: O,O-dimethyl formylphosphonate S,S-dimethyl thioacetal.

Physical Data: bp 72 °C/0.05 mmHg.

Solubility: sol THF, DME.

Form Supplied in: not commercially available.

Preparative Methods: (MeO)2P(O)CH(SMe)26 and related S,S-thioacetals of formylphosphonates6,7 are readily prepared in high yields by the Arbuzov reaction of trialkyl phosphites with chloro dithioacetals (eq 1).1,8 Other syntheses of thiophosphonates are known.9

Reactions with Aldehydes and Ketones.

The carbanion derived from the treatment of (MeO)2P(O)CH(SMe)2 with a base reacts with cyclic and acyclic, aliphatic and aromatic aldehydes and ketones in a Horner-Wadsworth-Emmons reaction to give ketene S,S-thioacetals in high yields1-5 (eq 22,3). The carbanion is generated using either n-Butyllithium in THF at -78 °C2,3 or, less commonly, Sodium Hydride in DME.2 Alternatively, with aromatic aldehydes the reaction may be performed under two-phase conditions using Benzyltriethylammonium Chloride (TEBA) as a phase-transfer catalyst.2

Ketene S,S-thioacetals are key synthetic intermediates, susceptible to nucleophilic and electrophilic attack.1,2b,10 Hydrolysis and alcoholysis of ketene S,S-thioacetals yields carboxylic acids and esters, respectively. Other transformations of ketene S,S-thioacetals allow homologation of the precursor carbonyl compound and polyfunctional ketene S,S-thioacetals provide access to heterocycles (e.g. eq 3).11

Alternative methods for the preparation of ketene S,S-thioacetals from carbonyl compounds include the Wittig reaction with phosphite ylides and the Peterson reaction with lithium derivatives of trimethylsilyl dithioacetals (eq 4).1 The Wittig preparation is limited to aldehydes and is further restricted by the availability of the phosphite ylides. Also, whereas the phosphate ester byproduct of the Horner-Wadsworth-Emmons reaction is water soluble and therefore easily separated from the ketene S,S-thioacetal, the phosphine oxide byproduct of the Wittig reaction is usually of a solubility similar to the product. The Peterson alkenation is a general synthesis, but suffers long reaction times and low yields with sterically hindered ketones.

Related Systems.

The carbanions of related S,S-thioacetals of formylphosphonates also react with aldehydes and ketones, including a,b-unsaturated aldehydes and ketones, to give the corresponding ketene S,S-thioacetals2,4,5,12 (e.g. eq 52,12). Horner-Wadsworth-Emmons reactions of carbonyl compounds with O,S-thioacetals of formylphosphonates2a,5 [e.g. (MeO)2P(O)CH(SMe)OMe] and mono(thio)phosphonates4,13 [e.g. (MeO)2P(O)CH2SMe] are also known.

1. (a) Kolb, M. In The Chemistry of Ketenes, Allenes and Related Compounds; Patai, S., Ed.; Wiley: Chichester, 1980; Part 2, p 669 and refs therein. (b) Kolb, M. S 1990, 171 and refs therein.
2. (a) Mikolajczyk, M.; Grzejszczak, S.; Zatorski, A.; Mlotkowska, B. TL 1976, 2731. (b) Mikolajczyk, M.; Grzejszczak, S.; Zatorski, A.; Mlotkowska, B.; Gross, H.; Costisella, B. T 1978, 34, 3081.
3. Hanessian, S.; Desilets, D.; Rancourt, G.; Fortin, R. CJC 1982, 60, 2292.
4. Martin, S. F. S 1979, 633 and refs therein.
5. Cherkasov, R. A.; Kutyrev, G. A.; Pudovik, A. N. T 1985, 41, 2567 and refs therein.
6. Mlotkowska, B.; Gross, H.; Costisella, B.; Mikolajczyk, M.; Grzejszczak, S.; Zatorski, A. JPR 1977, 319, 17.
7. Gross, H.; Keitel, I.; Costisella, B. JPR 1978, 320, 255.
8. (a) Shahak, I.; Almog, J. S 1969, 170. (b) McGuire, H. M.; Odom, H. C., Jr.; Pinder, A. R. JCS(P1) 1974, 1879.
9. (a) Ishikawa, K.; Akiba, K.; Inamoto, N. TL 1976, 3695. (b) Gross, H.; Costisella, B. S. 1977, 622. (c) Mikolajczyk, M.; Grzejszczak, S.; Chefczynska, A.; Zatorski, A. JOC 1979, 44, 2967.
10. Gröbel, B.-T.; Seebach, D. S 1977, 357.
11. Gupta, A. K.; Ila, H.; Junjappa, H. TL 1988, 29, 6633.
12. Mikolajczyk, M.; Balczewski, P. T 1992, 48, 8697.
13. Mikolajczyk, M.; Grzejszczak, S.; Midura, W.; Zatorski, A. S 1975, 278.

Andrew Abell & Jane Taylor

University of Canterbury, Christchurch, New Zealand

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