Divinyl Ketone

[1890-28-4]  · C5H6O  · Divinyl Ketone  · (MW 82.11)

(highly reactive, easily polymerized, polyfunctional annulation reagent; generally reacts by adding nucleophiles, dienes or radicals)

Alternate Name: 1,4-pentadien-3-one.

Physical Data: bp 38-40 °C/65 mmHg, 30 °C/16 mmHg.

Solubility: sol most common solvents.

Form Supplied in: unstable; prepare immediately before use as described below.

Preparative Methods: the title reagent has been prepared from the precursors listed in Table 1. For example, dehydrohalogenation of 1,5-dihalo-3-pentanones may be effected by distillation from anhydrous Sodium Carbonate (35-80%)1 or from Quinoline (95%).2 Under milder conditions (1.1 equiv Na2CO3 and lower temperature) the dichloro ketone gave 5-chloro-1-penten-3-one (37-80%).1c,3 The dihalo ketone precursors are usually prepared by Friedel-Crafts acylation of Ethylene,1c,4 or from the methyl b-halopropionate via a novel titanium-catalyzed ethyl Grignard addition, followed by N-Bromosuccinimide oxidation of the resulting cyclopropanol.1b The Mannich base precursors in Table 1 have been prepared from 1-methyl-4-piperidone (1) by conversion to its N-methyl iodide salt,5 by reaction of this salt with dimethylamine,6 or by reaction of (1) with p-Toluenesulfonyl Chloride and amines.7 These reagents are normally used for in situ generation of divinyl ketone.

Purification: distillation at reduced pressure.

Handling, Storage, and Precautions: brief storage in solution (ether or hydrocarbon) at low temperature due to ease of polymerization. A toxic, flammable, lachrymatory liquid which must be used with care. As a dialkylating agent, it may be mutagenic. Wastes may be disposed of by treatment with ammonium hydroxide. Use in a fume hood.

Substituted Divinyl Ketones.

Since the late 1970s, a large number of substituted divinyl ketones (2) have been prepared, many as substrates for the Nazarov reaction.8 Tables 2 and 3 list a few simple methyl-, phenyl-, silyl-, and halogen-substituted examples. Other examples have been cataloged.9-20

General Synthetic Methods.

A variety of synthetic methods have been applied to the preparation of substituted divinyl ketones. Among the most general and effective of these are: (a) acylation of alkenyl silanes,9 stannanes,10 and cuprates11 with a,b-unsaturated acyl chlorides; (b) transition metal-catalyzed carbonylation of alkenyl stannanes12 and mercurials;13 (c) formation of dialkenyl secondary carbinols by organometallic addition to aldehydes, followed by oxidation with Chromic Acid,14 Dimethyl Sulfoxide,15 Manganese Dioxide,16 Nickel(II) Peroxide,17 or Barium Manganate;17b,18 (d) palladium-catalyzed coupling of metallated methoxyallenes with alkenyl halides (eq 1);19 and (e) orthoester alkylation of trimethylsilyloxydienes,20a followed by b-elimination.

Many less general, but potentially useful, procedures have been reported. These include: (f) a,a-dibromination of ketone acetals, followed by dehydrohalogenation and acetal hydrolysis;21 (g) retro-ene reaction of substituted vinylcyclopropane derivatives (eq 2);22 (h) pyrolysis of norbornenyl precursors;23 and (i) isomerization of alkynones to dienones.24

Reactions of Divinyl Ketones.

As noted above, many divinyl ketones have been used as substrates for the Nazarov cyclization.8 In addition, the polyfunctional nature of these compounds makes them versatile participants in a variety of other reactions.

Conjugate Addition of Heteronucleophiles.

Tetrahydro-4H-pyran-4-one,4b,25 and its sulfur and selenium analogs,1b,5,26 may be prepared by nucleophilic addition (or substitution) to divinyl ketone (or 1,5-dichloro-3-pentanone). Similar reactions have been used in synthetic approaches to alkaloids related to catharanthine15b and emetine6b (eq 3). In the latter example, subsequent Mannich alkylations culminate in bonding to four of the five carbon atoms in divinyl ketone.

Michael Addition of Carbon Nucleophiles.

The umpolung aldehyde intermediates generated by thiazolium salt catalysis have been used by Stetter et al. to prepare polyketones (eq 4).1c,27 Carboannulations may be effected by sequential Michael reactions28 or a combination of Michael and aldol reactions.3 However, attempts to generate the tricyclo[5.3.1.03,8]undecane ring system by three sequential Michael reactions between divinyl ketone and cyclohexenone enolate failed.29 The desired assembly was eventually achieved by an initial Diels-Alder cycloaddition, followed by a Michael reaction (eq 5),2 and provided the foundation of a synthesis of seychellene.2 A similar case, employing acid catalysis in the cycloaddition step, was interpreted as a threefold sequence of Michael reactions.30

Cycloadditions.

Unsaturated ketones are excellent dienophiles. An interesting study of sequential Diels-Alder reactions of conjugated tetraenes with dialkenyl ketones to give tricyclic products has been reported.23a Dimethylhydrazone derivatives of divinyl ketone react with strong dienophiles to give heterocyclic products.31

Other Reactions.

Addition of carbon radicals to divinyl ketone may yield useful polyfunctional products (eq 6).32 1,2-Carbonyl addition reactions are best accomplished with precursors (Table 1). In this manner, cross-conjugated allenes were prepared by Lithium Acetylide addition to 1,5-dichloro-3-pentanone, followed by organocuprate substitution.33


1. (a) Jones, N.; Taylor, H. T. JCS 1961, 1345. (b) Sviridov, S. V.; Vasilevskii, D. A.; Kulinkovich, O. G. ZOR 1991, 27, 1431. (CA 1992, 116, 173 531r). (c) Stetter, H.; Basse, W.; Kuhlmann, H.; Landscheidt, A.; Schlenker, W. CB 1977, 110, 1007.
2. Jung, M. E.; McCombs, C. A.; Takeda, Y.; Pan, Y.-G. JACS 1981, 103, 6677.
3. Danishefsky, S.; Migdalof, B. H. JACS 1969, 91, 2806.
4. (a) Baddely, G.; Taylor, H. T.; Pickels, N. JCS 1953, 124. (b) Owen, G. R.; Reese, C. B. JCS(C) 1970, 2401.
5. (a) Thompson, M. D.; Holt, E. M.; Berlin, K. D. JOC 1985, 50, 2580. (b) Evers, M.; Christiaens, L.; Renson, M. TL 1985, 26, 5441.
6. (a) Cardwell, H. M. E. JCS 1950, 1056. (b) Whittaker, N. JCS(C) 1969, 85.
7. Laronze, J. Y.; Sapi, J.; Levy, J. S 1988, 619.
8. (a) Santelli-Rouvier, C.; Santelli, M. S 1983, 429. (b) Denmark, S. E. COS 1991, 5, 751.
9. (a) Tabul, A.; Santelli, M. T 1988, 44, 3975. (b) Kjeldsen, G.; Knudsen, J. S.; Ravn-Petersen, L. S.; Torssell, K. B. G. T 1983, 39, 2237. (c) Paquette, L. A.; Fristad, W. E.; Dime, D. S.; Bailey, T. R. JOC 1980, 45, 3017.
10. Chenard, B. L.; Van Zyl, C. M.; Sanderson, D. R. TL 1986, 27, 2801.
11. Marino, J. P.; Linderman, R. J. JOC 1981, 46, 3696.
12. Goure, W. F.; Wright, M. E.; Davis, P. D.; Labadie, S. S.; Stille, J. K. JACS 1984, 106, 6417.
13. Larock, R. C.; Hershberger, S. A. JOC 1980, 45, 3840.
14. (a) Vanstone, E. A.; Whitehurst, J. S. JCS(C) 1966, 1972. (b) Bondarev, G. N.; Ryzhov, V. A.; Chelpanova, L. F.; Petrov, A. A. ZOR 1967, 3, 816 (CA 1967, 67, 53 562z).
15. (a) Tidwell, T. T. S 1990, 857. (b) Kuehne, M. E.; Bornmann, W. G.; Earley, W. G.; Marko, I. JOC 1986, 51, 2913.
16. (a) Malacria, M.; Roumestant, M. L. T 1977, 33, 2813. (b) Stork, G.; Tomasz, M. JACS 1964, 86, 471.
17. (a) Jones, T. K.; Denmark, S. E.; HCA 1983, 66, 2377. (b) Denmark, S. E.; Hubermas, K. L.; Hite, G. A. HCA 1988, 71, 168.
18. Firouzabadi, H.; Moostafavipoor, Z. BCJ 1983, 56, 914.
19. Russell, C. E.; Hegedus, L. S. JACS 1983, 105, 943.
20. (a) Makin, S. M.; Nazarova, O. N.; Dymshakova, G. M.; Kundryutskova, L. A. ZOR 1988, 24, 1152 (CA 1989, 110, 57 090y). (b) Fleming, I.; Perry, D. A. T 1981, 37, 4027.
21. (a) Krabbenhoft, H. O. JOC 1979, 44, 4285. (b) Raphalen, A.; Sturtz, G. BSF 1971, 2962.
22. Nakamura, E.; Kubota, K.; Masahiko, I. JOC 1992, 57, 5809.
23. (a) Kraus, G. A.; Taschner, M. J. JACS 1980, 102, 1974. (b) Stetter, H.; Landscheidt, A. CB 1979, 112, 1410.
24. Trost, B. M.; Schmidt, T. JACS 1988, 110, 2301.
25. Kanojia, R.; Adams, R. OPP 1976, 4, 59.
26. Chen, C. H.; Reynolds, G. A.; Van Allan, J. A. JOC 1977, 42, 2777.
27. Stetter, H.; Jansen, B. CB 1985, 118, 4877.
28. Hamanaka, N.; Nakai, H.; Kurono, M. BCJ 1980, 53, 2327.
29. Spitzner, D. AG 1978, 90, 213.
30. Hagiwara, H.; Okano, A.; Uda, H. JCS(P1) 1990, 2109.
31. Koldobskii, A. B.; Lunin, V. V. ZOR 1991, 27, 533 (CA 1991, 115, 183 141g).
32. Giese, B.; Bartmann, D.; Hasskerl, T. LA 1987, 427.
33. Lehrich, F.; Hopf, H. TL 1987, 28, 2697.

William H. Reusch

Michigan State University, East Lansing, MI, USA



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