Ethyltriphenylphosphonium Bromide

Ph3+PEt X-
(X = Br)

[1530-32-1]  · C20H20BrP  · Ethyltriphenylphosphonium Bromide  · (MW 371.26) (X = Cl)

[896-33-3]  · C20H20ClP  · Ethyltriphenylphosphonium Chloride  · (MW 326.81) (X = I)

[4736-60-1]  · C20H20IP  · Ethyltriphenylphosphonium Iodide  · (MW 418.26)

(generation of the nonstabilized phosphorus ylide ethylidenetriphenylphosphorane for Wittig alkenation reactions1)

Physical Data: Br, mp 209-210.5 °C;2 Cl, mp ca. 235 °C (dec); I, mp 164-165 °C.

Form Supplied in: white to off-white solids; 98-99% (bromide; mp 206-208 °C), 98% (chloride), &egt;98% (iodide).

Preparative Methods: involves alkylation of triphenylphosphine with ethyl bromide, chloride, or iodide. The ethyl bromide reaction, performed in benzene at 135 °C in a pressure vessel for 20 h, gives an 89% yield of phosphonium salt (recrystallized from water and dried).2

Handling, Storage, and Precautions: may absorb moisture. Store in tightly sealed bottles in a dry place.

Ethylidene Transfer.

The most important synthetic reaction of the title phosphonium salts entails transfer of an ethylidene group, via ethylidenetriphenylphosphorane, to the carbonyl group of aldehydes and ketones in good yields.1 This nonstabilized phosphorus ylide is prepared in situ by treatment of the phosphonium salt in a suitable dry solvent (e.g. THF, DMSO, toluene, t-butanol) with a reasonably strong base (e.g. sodium amide, potassium t-butoxide, sodium hydride, butyllithium, sodium hexamethyldisilazide, or dimsylsodium). The choice of base and solvent can significantly impact the yield and stereochemistry of the alkene products.1,3 With standard aldehydes, the Wittig reaction affords (Z)-alkenes preferentially under most conditions. (E)-Alkenes are more likely to predominate in an alcohol solvent3c,h or by use of a lithium base;3a,c-f under lithium salt-free conditions in polar aprotic solvents, (Z) stereoselectivity is usually maximized (eqs 1-3).3a-g

Unsymmetrical ketones with similar substituents on the carbonyl do not furnish good alkene stereoselectivity.1b,c When one of the groups is bulkier, such as with i-PrCOMe, ethylidenetriphenylphosphorane furnishes a (Z)/(E) ratio of ca. 9:1 under lithium-salt conditions.4 The stereochemistry of ketone alkenation with ethylidenetriphenylphosphorane can be strongly influenced by certain substituents in the carbonyl component, especially an a-alkoxy substituent, which enhances (Z) stereoselectivity (eqs 4 and 5).5 An a-amido substituent can also direct (Z) stereoselectivity (eq 6).5e

Schlosser has developed a modification of the Wittig reaction in which the intermediate adducts from condensation of ethylidenetriphenylphosphorane and aldehydes (betaines or oxaphosphetanes) are equilibrated by the addition of excess alkyllithium or phenyllithium.3c,6 This allows the preparation of alkenes highly enriched in the (E)-isomer (eq 7),6 and forms the basis for alkenation reactions with elaborated ylides, sometimes referred to as the SCOOPY reaction.7,8

Elaboration of Ylides for Alkylidenation.

Ethylidenetriphenylphosphorane has been elaborated by electrophilic reagents into more complex phosphorus ylides, which can be effectively employed in subsequent alkenation chemistry. By using aldehydes as electrophiles, Schlosser and Corey independently developed useful stereocontrolled syntheses of various trisubstituted alkenes (eqs 8-10).7,8 Intermediate b-oxido ylides were derivatized with electrophiles such as halogenating agents, reactive alkyl halides, aldehydes, and epoxides (SCOOPY reaction). Acylation of ethylidenetriphenylphosphorane can provide stabilized ylides for the synthesis of complex alkenes (eq 11).9

1. For relevant reviews on the Wittig reaction: (a) Maryanoff, B. E.; Reitz, A. B. CRV 1989, 89, 863. (b) Organophosphorus Reagents in Organic Synthesis; Cadogan, J. I. G., Ed.; Academic: New York, 1979. (c) Bestmann, H. J.; Vostrowsky, O. Top. Curr. Chem. 1983, 109, 85. (d) Schlosser, M. Top. Stereochem. 1970, 5, 1. (e) Maercker, A. OR 1965, 14, 270.
2. House, H. O.; Rasmusson, G. H. JOC 1961, 26, 4278.
3. For example: (a) Reitz, A. B.; Nortey, S. O.; Jordan, A. D., Jr.; Mutter, M. S.; Maryanoff, B. E. JOC 1986, 51, 3302. (b) Schlosser, M.; Müller, G.; Christmann, K. F. AG(E) 1966, 5, 667. (c) Schlosser, M.; Christmann, K. F. LA 1967, 708, 1. (d) Maryanoff, B. E.; Reitz, A. B.; Mutter, M. S.; Inners, R. R.; Almond, H. R., Jr.; Whittle, R. R.; Olofson, R. A. JACS 1986, 108, 7664. (e) Maryanoff, B. E.; Duhl-Emswiler, B. A. TL 1981, 22, 4185. (f) Maryanoff, B. E.; Reitz, A. B.; Duhl-Emswiler, B. A. JACS 1985, 107, 217. (g) Vedejs, E.; Meier, G. P.; Snoble, K. A. J. JACS 1981, 103, 2823. (h) Le Bigot, Y.; Delmas, M.; Gaset, A. SC 1982, 12, 1115. (i) Boden, R. M. S 1975, 784.
4. Dusza, J. P. JOC 1960, 25, 93.
5. (a) Sreekumar, C.; Darst, K. P.; Still, W. C. JOC 1980, 45, 4260. (b) Burke, S. D.; Schoenen, F. J.; Nair, M. S. TL 1987, 28, 4143. (c) Trost, B. M.; Romero, A. G. JOC 1986, 51, 2332. (d) Koreeda, M.; Patel, P. D.; Brown, L. JOC 1985, 50, 5910. (e) Mori, M.; Uozumi, Y.; Kimura, M.; Ban, Y. T 1986, 42, 3793.
6. Schlosser, M.; Christmann, K. F. AG(E) 1966, 5, 126.
7. (a) Schlosser, M.; Christmann, K. F. S 1969, 38. (b) Schlosser, M.; Christmann, K. F.; Piskala, A.; Coffinet, D. S 1971, 29. (c) Schlosser, M.; Coffinet, D. S 1971, 380. (d) Schlosser, M.; Coffinet, D. S 1972, 575.
8. (a) Corey, E. J.; Ulrich, P.; Venkateswarlu, A. TL 1977, 3231. (b) Corey, E. J.; Yamamoto, H. JACS 1970, 92, 226. (c) Corey, E. J.; Shulman, J. I.; Yamamoto, H. TL 1970, 447. (d) Corey, E. J.; Yamamoto, H. JACS 1970, 92, 6636.
9. Ireland, R. E.; Wardle, R. B. JOC 1987, 52, 1780.

David F. McComsey & Bruce E. Maryanoff

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

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