Chloromethyltriphenylphosphonium Chloride1

[5293-84-5]  · C19H17Cl2P  · Chloromethyltriphenylphosphonium Chloride  · (MW 347.22)

(precursor to the chloro-substituted ylide for Wittig reactions with aldehydes and ketones to form 1-chloroalkenes and, after elimination of HCl, terminal alkynes)

Physical Data: mp 260 °C.

Solubility: suspensions in most organic solvents can be treated with base to form the soluble phosphorus ylide.

Form Supplied in: white powder, available commercially (chloride or iodide salt) or synthetically from Triphenylphosphine and Chloroiodomethane.2

Handling, Storage, and Precautions: for best results the anhydrous salt should be used. The ylide, formed from the salt and strong base, will react with air, water, or other acidic protons.

Preparation of the Ylide and Stereoselectivity.

The Wittig reaction of chloromethylenetriphenylphosphorane forms chloroalkenes from carbonyl compounds with complete regioselectivity. The ylide is prepared by treating a suspension of dry phosphonium salt under N2 with a strong base. n-Butyllithium has often been used, but the chloroalkene products are usually obtained as (E)/(Z) mixtures,3,4 and side reactions have occasionally been reported.2,3 Better results are obtained with bases such as Potassium Hexamethyldisilazide,5 Potassium t-Butoxide,2 or Sodium Amide.6 Although stereoselectivity for this ylide is often low (even in the absence of Li cation),2 several (E)- or (Z)-selective reactions have been reported. Reaction of the chloro-substituted ylide, prepared from KHMDS in toluene, with an a-keto amino acid derivative (eq 1) gave an 85:15 (Z)/(E) ratio of chloroalkenes in 85% yield.5

High (E) selectivity was obtained in the reaction of this ylide (generated from the salt and t-BuOK in t-butanol) with benzaldehyde. A 1:1 mixture of chlorostyrenes was formed at rt, but 100% (E)-alkene was produced after refluxing the reaction for 4 h (eq 2).2

Synthesis of Alkynes.

Synthetically, the most common use for the chloroalkene products is the preparation of alkynes. Dehydrohalogenation of the vinyl chlorides with an excess of strong base (n-Butyllithium or Lithium Diisopropylamide) gives terminal alkynes in good yield. This methodology has been used in the synthesis of alkynyl steroids (eq 3)7 and carbohydrate derivatives (eq 4).8 The transformation of RCHO to RC&tbond;CH has also been performed in the synthesis of lycopene isomers,9 and derivatives of vitamin D10 and retinal.11

A useful alternative to the Wittig reaction for vinyl halide synthesis is the Chromium(II) Chloride mediated reaction of an aldehyde and chloroform.12 The organochromium intermediate forms 1-chloroalkenes from aliphatic and aromatic aldehydes with high (E) selectivity in yields of 55-75%. The procedure, however, requires 6 equiv of the expensive chromium reagent. Other alkene-forming reactions, such as the Peterson alkenation13 and the Tebbe reaction,14 are not useful for the preparation of vinyl chlorides.

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. (a) Miyano, S.; Izumi, Y.; Fujii, K.; Ohno, Y.; Hashimoto, H. BCJ 1979, 52, 1197. (b) Miyano, S.; Izumi, Y.; Hashimoto, H. CC 1978, 446.
3. (a) Wittig, G.; Schlosser, M. CB 1961, 94, 1373. (b) Köbrich, G.; Trapp, H.; Flory, K.; Drischel, W. CB 1966, 99, 689.
4. Dolbier, W. R., Jr.; Chen, Y. JOC 1992, 57, 1947.
5. O'Donnell, M. J.; Arasappan, A.; Hornback, W. J.; Huffman, J. C. TL 1990, 31, 157.
6. Schlosser, M.; Schaub, B. C 1982, 36, 396.
7. (a) Frye, L. L.; Robinson, C. H. JOC 1990, 55, 1579. (b) Ekhato, I. V.; Robinson, C. H. JOC 1989, 54, 1327. (c) See also Holbert, G. W.; Johnston, J. O.; Metcalf, B. W. TL 1985, 26, 1137.
8. (a) Rochigneux, I.; Fontanel, M. L.; Malanda, J. C.; Doutheau, A. TL 1991, 32, 2017. (b) Mella, M.; Panza, L.; Ronchetti, F.; Toma, L. T 1988, 44, 1673.
9. Hengartner, U.; Bernhard, K.; Meyer, K.; Englert, G.; Glinz, E. HCA 1992, 75, 1848.
10. Hatakeyama, S.; Numata, H.; Osanai, K.; Takano, S. CC 1989, 1893.
11. (a) Baumeler, A.; Brade, W.; Haag, A.; Eugster, C. H. HCA 1990, 73, 700. (b) Hanzawa, Y.; Yamada, A.; Kobayashi, Y. TL 1985, 26, 2881.
12. Takai, K.; Nitta, K.; Utimoto, K. JACS 1986, 108, 7408.
13. Burford, C.; Cooke, F.; Roy, G.; Magnus, P. T 1983, 39, 867.
14. Pine, S. H. OR 1993, 43, 1.

Charles F. Marth

Nalco Chemical Company, Naperville, IL, USA

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