(Ethoxycarbonylmethyl)triphenylphosphonium Bromide1

Ph3+PCH2CO2Et Br-

[1530-45-6]  · C22H22BrO2P  · (Ethoxycarbonylmethyl)triphenylphosphonium Bromide  · (MW 429.30)

(precursor to Ph3P=CHCO2Et, a widely-used stabilized phosphorane;2,3 Wittig reagent for the formation of a,b-unsaturated ethyl esters2-4)

Physical Data: mp 158 °C (dec).

Solubility: sol water (10 g 100 mL-1), EtOH (35 g 100 mL-1), and CHCl3 (55 g 100 mL-1); insol THF (<1 g 100 mL-1).

Form Supplied in: white, crystalline solid which can adopt a light pink tinge from dissociation of small amounts of HBr.

Handling, Storage, and Precautions: the compound is a mild irritant, due to the partial dissociation of HBr. Drying is not required for most synthetic applications. Storage at room temperature is adequate. Stable in water, but decomposes to triphenylphosphine oxide in 1.0 N NaOH (t1/2 ca. 15 min).

Weakly Acidic Phosphonium Salt.

This compound is easily prepared by reaction of Triphenylphosphine and ethyl bromoacetate,2,3 and has been mainly used as a precursor for Ph3P=CHCO2Et, formed by treatment with base (eq 1); see (Ethoxycarbonylmethylene)triphenylphosphorane and (Methoxycarbonylmethylene)triphenylphosphorane).2 The phosphorane is stabilized by both the ethoxycarbonyl group and dp-pp bonding to the adjacent phosphorus atom, and is a commonly employed Wittig alkenation reagent. The phosphonium bromide is somewhat acidic and can be deprotonated under weakly basic conditions (pKa = 8.95-9.2).5,6 Common bases employed are sodium alkoxides in alcohols,3,4 aqueous sodium hydroxide,7 and tertiary amines.8

(Ethoxycarbonylmethylene)triphenylphosphorane has been generated in situ from the phosphonium bromide and utilized as required, particularly during the first decade or so of general use of the Wittig reaction with aldehydes and ketones.1-4 As an example, the phosphonium bromide was prepared from triphenylphosphine and ethyl bromoacetate and then treated with Sodium Ethoxide to form the phosphorane, which was reacted with a-fluoro ketones to afford a,b-unsaturated esters (eq 2).4 The stereochemistry about the newly formed double bond in unsymmetrical alkenes is generally trans (E), as expected for reactions of stabilized phosphorus ylides, although there are many special conditions which enhance formation of the (Z) isomer.1 (Ethoxycarbonylmethylene)triphenylphosphorane is now commercially available and can be stored without incident for prolonged periods, so that most chemists start with this reagent directly. The main advantage associated with the phosphonium bromide is that it is ca. 50% less expensive than the phosphorane on a molar basis. There is no special requirement for either the phosphonium bromide or the phosphorane to be absolutely dry when using them in Wittig alkenations, as trace amounts of water catalyze the reaction.9 Large amounts of excess aqueous base hydrolyze the reagent, releasing triphenylphosphine oxide.

The phosphonium bromide can be prepared in situ and reacted directly with aldehydes in the presence of Ethylene Oxide (eq 3). The bromide counterion of the phosphonium salt opens ethylene oxide forming an alkoxide anion, which then deprotonates the a-carbon to form the phosphorane.10

In addition to Wittig alkenations, the phosphonium bromide can be expected to substitute for (ethoxycarbonylmethylene)triphenylphosphorane in any of the other applications of the phosphorane, by in situ treatment of the phosphonium bromide with base.

1. (a) Maryanoff, B. E.; Reitz, A. B. CRV 1989, 89, 863. (b) Gosney, I.; Rowley, A. G. In Organophosphorus Reagents in Organic Synthesis; Cadogan, J. I. G., Ed.; Academic: New York, 1979; p 17. (c) Schlosser, M. Top. Stereochem. 1970, 5, 1. (d) Johnson, A. W. Ylid Chemistry, Academic: New York, 1966. (e) Hudson, R. F. Structure and Mechanism in Organo-Phosphorus Chemistry; Academic: New York, 1965. (f) Maercker, A. OR 1965, 14, 270. (g) Trippett, S. QR 1963, 17, 406.
2. Isler, O.; Gutmann, H.; Montavon, M.; Rüegg, R.; Ryser, G.; Zeller, P. HCA 1957, 40, 1242.
3. Wittig, G.; Haag, W. CB 1955, 88, 1654.
4. Machleidt, H.; Hartmann, V.; Bünger, H. LA 1963, 667, 35.
5. Fliszár, S.; Hudson, R. F.; Salvadori, G. HCA 1963, 46, 1580.
6. Speziale, A. J.; Ratts, K. W. JACS 1963, 85, 2790.
7. Denney, D. B.; Ross, S. T. JOC 1962, 27, 998.
8. Kondo, S.; Kondo, Y.; Tsuda, K. J. Polym. Sci., Polym. Lett. Ed. 1983, 21, 217.
9. Kayser, M. M.; Hatt, K. L.; Hooper, D. L. CJC 1991, 69, 1929.
10. (a) Buddrus, J. CB 1974, 107, 2050. (b) Buddrus, J. AG(E) 1972, 11, 1041. (c) Buddrus, J. AG(E) 1968, 7, 536.

Allen B. Reitz & Mark E. McDonnell

The R. W. Johnson Pharmaceutical Research Institute, Spring House, PA, USA

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