[39598-55-5]  · C19H16BrP  · Bromomethylenetriphenylphosphorane  · (MW 355.21)

(Wittig reagent for the formation of 1-bromoalkenes from aldehydes and ketones; terminal alkynes are formed by elimination of HBr)

Solubility: sol THF and ether; reacts with water and other acidic protons.

Preparative Method: by using strong base to deprotonate the salt bromomethyltriphenylphosphonium bromide, which is available commercially or synthetically.2

Handling, Storage, and Precautions: the ylide is generally prepared in situ and used immediately, but can be stored under nitrogen for short periods. The ylide will decompose upon exposure to air or water.

Preparation of the Ylide and Stereoselectivity.

The Wittig reaction of bromomethylenetriphenylphosphorane forms 1-bromoalkenes from carbonyl compounds with complete regioselectivity. Unlike most phosphorus ylides, treatment of the starting phosphonium salt with butyllithium does not give the desired bromo-substituted ylide, but forms Ph3P=CH2 via halogen-metal exchange.2,3 The use of PhLi and lithium piperidide are also not recommended.2,4 Bromomethylenetriphenylphosphorane has been cleanly prepared from the dry bromomethyl phosphonium salt using either Potassium t-Butoxide in THF5 or Potassium Hexamethyldisilazide in toluene.6 With these bases the Wittig reaction with aldehydes and ketones proceeds in good yield and often, in the case of aldehydes, with high (Z) selectivity. Table 1 gives results for the ylide prepared using t-BuOK at low temperature (eq 1),5 and shows that (Z)-bromoalkenes were prepared with good selectivity. When 2 equiv of base were used in these reactions, terminal alkynes were formed as the final product.5

High selectivity was also reported in the reaction of the bromo-substituted ylide (prepared from KHMDS in toluene) with an a-keto amino acid derivative (eq 2), which gave a 95:5 (Z:E) ratio of bromoalkenes in 80% yield.6

Synthetic Uses.

The bromoalkene products of the Wittig reaction have most often been used for the preparation of alkynes or in palladium-catalyzed coupling reactions. HBr elimination with an excess of strong base (Lithium Diisopropylamide or t-BuOK) gives terminal alkynes in good yield. The overall transformation (RCHO to RC&tbond;CH) has been used in the synthesis of leukotriene B4 (eq 3),7 derivatives of vitamin D3,8 and methynolide intermediates.9 Palladium(0) coupling of 1-bromoalkenes with alkynes has also been reported, such as in the synthesis of antitumor agent CI-92010 and carotenoids.11

A useful alternative to the Wittig reaction for vinyl halide synthesis is the reaction of Bromoform with CrBr3/LiAlH4 in the presence of an aldehyde.12 The organochromium intermediate formed in situ reacts with aliphatic and aromatic aldehydes to give bromoalkenes with good (E) selectivity in 55-70% yield. This transformation, however, requires 6 equiv of the expensive chromium reagent. For preparation of vinyl bromides from ketones, addition of lithiated methylene bromide to the carbonyl group followed by reduction with Zinc-Acetic Acid gives 1-bromoalkenes in good yield.13

1. (a) Vedejs, E.; Peterson, M. J. Top. Stereochem. 1994, 21, 1. (b) Maryanoff, B. E.; Reitz, A. B. CRV 1989, 89, 863. (c) McEwen, W. E.; Beaver, B. D.; Cooney, J. V. PS 1985, 25, 255. (d) Bestmann, H. J. PAC 1980, 52, 771. (e) Gosney, I.; Rowley, A. G. In Organophosphorus Reagents in Organic Synthesis; Cadogan, J. I. G., Ed.; Academic: New York, 1979; pp 17-153. (f) Schlosser, M. Top. Stereochem. 1970, 5, 1. (g) Johnson, A. W. Ylide Chemistry; Academic: New York, 1966. (h) Maercker, A. OR 1965, 14, 270.
2. Wolinsky, J.; Erickson, K. L. JOC 1965, 30, 2208.
3. Köbrich, G.; Trapp, H.; Flory, K.; Drischel, W. CB 1966, 99, 689.
4. Seyferth, D.; Heeren, J. K.; Grim, S. O. JOC 1961, 26, 4783.
5. Matsumoto, M.; Kuroda, K. TL 1980, 21, 4021.
6. O'Donnell, M. J.; Arasappan, A.; Hornback, W. J.; Huffman, J. C. TL 1990, 31, 157.
7. Avignon-Tropis, M.; Berjeaud, J. M.; Pougny, J. R.; Frechard-Ortuno, I.; Guillerm, D.; Linstrumelle, G. JOC 1992, 57, 651.
8. Wilson, S. R.; Venkatesan, A. M.; Augelli-Szafran, C. E.; Yasmin, A. TL 1991, 32, 2339.
9. Nakano, A.; Takimoto, S.; Inanaga, J.; Katsuki, T.; Ouchida, S.; Inoue, K.; Aiga, M.; Okukado, N.; Yamaguchi, M. CL 1979, 1019.
10. Just, G.; O'Connor, B. TL 1988, 29, 753.
11. Pattenden, G.; Robson, D. C. TL 1987, 28, 5751.
12. Takai, K.; Nitta, K.; Utimoto, K. JACS 1986, 108, 7408.
13. Williams, D. R.; Nishitani, K.; Bennett, W.; Sit, S. Y. TL 1981, 22, 3745.

Charles F. Marth

Nalco Chemical Company, Naperville, IL, USA

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