[3061-65-2]  · C5H5NO2  · 2-Acetoxyacrylonitrile  · (MW 111.10)

(ketene equivalent for use in the Diels-Alder reaction;1 undergoes other cycloaddition reactions; reacts with nucleophiles and radicals)

Physical Data: bp 80-82 °C/30 mmHg; d 1.040 g cm-3.

Solubility: sol most organic solvents other than pure hydrocarbons.

Form Supplied in: neat light-yellow liquid.

Analysis of Reagent Purity: 1H NMR, 13C NMR.

Preparative Methods: due to the expense of the commercial material it has been suggested2 that for large scale use, preparation3 is more reasonable.

Handling, Storage, and Precautions: highly toxic; use only in a fume hood. Reagent can be absorbed through the skin. Always wear gloves when handling this reagent.

[4 + 2] Cycloaddition Reactions.

Historically, 2-acetoxyacrylonitrile was the first ketene equivalent developed for the Diels-Alder reaction.1 Thus the title compound reacts thermally with cyclopentadiene to yield the cycloadduct (1) which upon treatment with base produces norbornenone (2) (eq 1).4 Since this first report, 2-acetoxyacrylonitrile and 2-Chloroacrylonitrile have been the two most popular ketene equivalents used in the Diels-Alder reaction. Dienes which have been shown to react with 2-acetoxyacrylonitrile include substituted cyclopentadienes5 and cyclohexadienes,6 fulvenes,7 cycloalkadienones,8 polycyclic aromatics,9 furans,2,10b isobenzofurans,11 dihydropyridines,12 vinylcycloalkenes,13 and acyclic dienes.14 In the case of furans the reaction is usually catalyzed by high pressure2,10a,c or Lewis acids.10b The reaction shown in eq 1 has been catalyzed with Lithium Perchlorate.15

An early comparison between 2-chloro- and 2-acetoxyacrylonitrile indicated that the chloro derivative was slightly more reactive and more regioselective in its reaction with cyclohexadienes.6a However, 2-acetoxyacrylonitrile does offer some advantage in that the resulting cycloadduct can, at times, be more easily manipulated. For example, the furan adduct (3) was converted to the desired ketone (5) by treatment with base followed by exposure to formalin (eq 2).2,10 The formalin is used to convert residual cyanohydrin (4) to the ketone.10b The corresponding adduct from 2-chloroacrylonitrile did not yield ketone (5) when treated with base. In an another example, adduct (6) was converted to ketone (7) as shown (eq 3).13a This two-step procedure14b diminished an unwanted isomerization of the double bond to the more stable a,b-unsaturated enone.13b,c Finally, in at least one instance the intermediate a-acetoxynitrile was reduced to a vicinal amino alcohol with Lithium Aluminum Hydride.6b

The preparation of ketone (5) in optically pure form10b,16 has been achieved by use of chiral a-carboxyacrylonitriles derived from camphanic acid16a as well as from tartaric acid.16c In general the facial selectivity exhibited in the cycloaddition is moderate and the obtention of one stereoisomer is dependent on selective recrystallization. Ketone (5) has been used extensively in chiral synthesis.16c

Other Reactions.

2-Acetoxyacrylonitrile undergoes both [2 + 3]17 and [2 + 2]18 cycloaddition reactions. Cyclopropanation of 2-acetoxyacrylonitrile with a variety of diazoalkanes represents a facile route to cyclopropanone cyanohydrins (eq 4).17b As is expected for an electron deficient alkene, 2-acetoxyacrylonitrile reacts with both nucleophiles19 and radicals20 in a conjugate-type addition.

1. Ranganathan, S.; Ranganathan, D.; Mehrotra, A. K. S 1977, 289.
2. Brown, D. S.; Paquette, L. A. JOC 1992, 57, 4512.
3. Nowak, R. M. JOC 1963, 28, 1182.
4. Bartlett, P. D.; Tate, B. E. JACS 1956, 78, 2473.
5. (a) Jaeggi, F. J.; Ganter, C. HCA 1980, 63, 214. (b) Moorhoff, C. M.; Paquette, L. A. JOC 1991, 56, 703.
6. (a) Evans, D. A.; Scott, W. L.; Truesdale, L. K. TL 1972, 121. (b) Alfaro, I.; Ashton, W.; Rabone, K. L.; Rogers, N. A. J. T 1974, 30, 559. (c) Gompper, R.; Etzbach, K. H. AG 1978, 90, 630. (d) Hori, K.; Hikage, N.; Inagaki, A.; Mori, S.; Nomura, K.; Yoshii, E. JOC 1992, 57, 2888. (e) Werstiuk, N. H.; Yeroushalmi, S.; Hong, G. L. CJC 1992, 70, 974.
7. (a) DePuy, C. H.; Story, P. R. JACS 1960, 82, 627. (b) Yates, P.; Lokensgard, J. P. SC 1975, 5, 37. (c) Oku, A.; Nozaki, Y.; Hasegawa, H.; Nishimura, J.; Harada, T. JOC 1983, 48, 4374.
8. (a) Sasaki, T.; Kanematsu, K.; Iizuka, K. JOC 1976, 41, 1105. (b) Oku, A.; Hasegawa, H.; Shimazu, H.; Nishimura, J.; Harada, T. JOC 1981, 46, 4152. (c) Deslongchamps, P.; Belanger, A.; et al. CJC 1990, 68, 127.
9. (a) Hudrlik, P. F.; Hudrlik, A. M.; Wan, C.-N. JOC 1975, 40, 1116. (b) Hagishita, S.; Kuriyama, K. JCS(P2) 1978, 59. (c) Quast, H.; Schoen, N. LA 1984, 877.
10. (a) Kotsuki, H.; Nishizawa, H. H 1981, 16, 1287. (b) Black, K. A.; Vogel, P. HCA 1984, 67, 1612. (c) Kotsuki, H.; Mori, Y.; Ohtsuka, T.; Nishizawa, H.; Ochi, M.; Matsuoka, K. H 1987, 26, 2347. (d) Koreeda, M.; Jung, K. Y.; Ichita, J. JCS(P1) 1989, 2129.
11. Cornejo, J. J.; Ghodsi, S.; Johnson, R. P.; Woodling, R.; Rickborn, B. JOC 1983, 48, 2237.
12. Baxter, E. W.; Labaree, D.; Ammon, H. L.; Mariano, P. S. JACS 1990, 112, 7682.
13. (a) Wharton, P. S.; Aw, B. T. JOC 1966, 31, 3787. (b) Bell, M. R.; Herrmann, J. L.; Akullian, V. S 1981, 357. (c) Willmore, N. D.; Goodman, R.; Lee, H. H.; Kennedy, R. M. JOC 1992, 57, 1216.
14. (a) Cobb, R. L.; Vives, V. C.; Mahan, J. E. JOC 1978, 43, 931. (b) Gordon, J.; Tabacchi, R. JOC 1992, 57, 4728.
15. Grieco, P. A.; Nunes, J. J.; Gaul, M. D. JACS 1990, 112, 4595.
16. (a) Vieira, E.; Vogel, P. HCA 1983, 66, 1865. (b) Saf, R.; Faber, K.; Penn, G.; Griengl, H. T 1988, 44, 389. (c) Reymond, J.-L.; Vogel, P. T(A) 1990, 1, 729.
17. (a) Stegmann, W.; Gilgen, P.; Heimgartner, H.; Schmid, H. HCA 1976, 59, 1018. (b) Oku, A.; Yokoyama, T.; Harada, T. JOC 1983, 48, 5333. (c) Padwa, A.; Kline, D. N.; Koehler, K. F.; Matzinger, M.; Venkatramanan, M. K. JOC 1987, 52, 3909.
18. Dilling, W. L.; Kroening, R. D.; Little, J. C. JACS 1970, 92, 928.
19. Oku, A.; Horiie, N.; Harada, T. BCJ 1987, 60, 609.
20. Barton, D. H. R.; Chern, C. Y.; Jaszberenyi, J. C. TL 1992, 33, 5013.

Patrick G. McDougal

Reed College, Portland, OR, USA

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