Vinyl Acetate1

[108-05-4]  · C4H6O2  · Vinyl Acetate  · (MW 86.10)

(enzyme-mediated transacetylation of alcohols; N- and O-transvinylation; acetaldehyde equivalent; cycloaddition reactions with chlorosulfonyl isocyanate to give azetidinones, nitrile oxides to give isoxazoles, nitrones to give isoxazolines, enones to give acetoxycyclobutanes, and arenes to give bi- and tricyclic adducts; source of formaldehyde oxide)

Physical Data: 2 bp 73 °C; mp -92.8 °C; d 0.9335 g cm-3.

Solubility: soluble all common organic solvents; somewhat sol water.

Form Supplied in: colorless liquid stabilized with 4 ppm hydroquinone and 300 ppm diphenylamine.

Handling, Storage, and Precautions: extremely flammable with unusual fire and explosion hazards. Readily polymerizes, especially on exposure to light, to give a solid. Removal or loss of the inhibitors results in rapid polymerization, often quite violently. Vinyl acetate is a cancer suspect agent and may cause genetic damage. It is quite irritating to the eyes, skin, and respiratory system.2a Use in a fume hood.

Transacetylation.

Vinyl acetate is used extensively in irreversible enzyme-mediated transacetylation of racemic and meso-alcohols, usually in organic solvents, to give optically active products with excellent enantiomeric excesses.3-9 In a typical example, enantioselective transacetylation of the glycal (1) with vinyl acetate is performed in dimethoxyethane at room temperature in the presence of the lipase derived from Pseudomonas cepacia to give the monoacetate (2) and diacetate (3), each with an enantiomeric excess of 97% (eq 1).3 Other examples include the following preparations: the chiral auxiliaries (5) and (6) derived from racemic trans-phenylcyclohexanol (4) using an immobilized enzyme (eq 2);4 the diltiazem intermediate (8) (eq 3);5 the acetate (11) derived from the meso-diol (10) (eq 4);6 and (13) and (14), the corresponding racemic alcohol (12) of which could not be resolved efficiently by enantioselective epoxidation (eq 5).7 In addition, regioselective acetylation of primary and secondary alcohols with vinyl acetate in the presence of a lipase proceeds in excellent yields. In general, primary alcohols are acetylated in preference to secondary alcohols,8a,b and, with the latter, excellent regioselectivity is obtained depending on the stereochemistry of the alcohol (eq 6).8c,d See also Acetic Anhydride and Acetyl Chloride.

Transvinylation.

N-Vinylation with vinyl acetate is usually carried out in the presence of Palladium(II) Chloride10 or Mercury(II) Acetate (eq 7),11 although a catalyst is apparently not required in the preparation of the alkaloid (20) (eq 8).12 Vinyl esters may be prepared in moderate to good yields by heating the acid with vinyl acetate in the presence of Hg(OAc)2 (eq 9)13 or PdCl2 (eq 10).14 Vinyl esters of amino acids, prepared by transesterification with vinyl acetate in ethyl cyanoacetate, have been used as activated esters in peptide synthesis.15 In an indole synthesis, O-vinylation of (25) with vinyl acetate in the presence of PdCl2 leads directly, via a hetero-Cope rearrangement, to a regioisomeric mixture of indoles in 83% yield (eq 11).16 Although not as widely used as Ethyl Vinyl Ether, vinyl acetate has been used to prepare allyl vinyl ethers from allyl alcohols with Hg(OAc)2 as the catalyst.17

Acetaldehyde Equivalent.

The reaction of vinyl acetate with a ketone in the presence of Cerium(IV) Ammonium Nitrate gives an a-(2-acetoxy-2-nitrosylethyl) ketone, which may be solvolyzed to the corresponding acetal (eq 12).18 A related reaction of vinyl acetate with 2,4-pentanedione leads to 2-methyl-3-acetylfuran in 56% yield (eq 13).19 Introduction of the Acetaldehyde unit onto an aromatic ring is possible by a Meerwein reaction between a diazonium salt and vinyl acetate in the presence of Copper(II) Chloride (eq 14).20

Cycloaddition Reactions.

Thermal.

Vinyl acetate reacts rapidly with Chlorosulfonyl Isocyanate at low temperatures to give, after reduction with NaHSO3, 2-acetoxyazetidinone in 80% yield (eq 15).21 However, Diels-Alder reactions with vinyl acetate are quite sluggish. With the 2H-pyrrole (35), the cycloadduct is obtained in 83% yield after 7 days (eq 16),22 whereas the pyridine (38) is produced in 78% yield from the 1,2,4-triazene (37) (eq 17).23 1,3-Dipolar addition of vinyl acetate with nitrile oxides gives isoxazolines,24 which may be converted directly to isoxazoles (eq 18);25 isoxazoles are also obtained by heating potassium nitronates with vinyl acetate.26 The cycloaddition of vinyl acetate to nitrones yields isoxazolines in a highly regioselective manner,27 and can be highly stereoselective, as is found with the Cr0-complexed nitrone (41) (eq 19).28

Photochemical.

High yields of acetoxycyclobutanes, in which the head-to-tail regioisomer predominates, are obtained from the photoaddition of vinyl acetate to cyclic enones.29 As illustrated in an approach to the synthesis of taxol, photoaddition of vinyl acetate to the enolic form of the 1,3-dione (43) produces the cycloadduct (44) in 90% yield as a mixture of diastereomers (eq 20).30 Similar excellent regioselectivity is realized in the photoaddition of vinyl acetate to the naphthoquinone (45), yielding the acetoxycyclobutane (46) in an almost quantitative yield (eq 21).31

Vinyl acetate also undergoes photoaddition to arenes, producing 1,2- and 1,3-photoadducts.29,32 Irradiation of benzene at 254 nm in the presence of a large excess of vinyl acetate gives, in low yield, a single 1,2-cycloadduct (48) and a regioisomeric mixture of 1,3-cycloadducts (49) (eq 22).33 The latter predominates, except when there is a large difference in electron-donor/acceptor capacity between the aromatic compound and vinyl acetate, as is found with benzonitrile.34 The photoaddition of ethenes to arenes has been used in the synthesis of several structurally complex natural products,35 typified by the construction of the propellane system of rac-modhephene from the photoaddition of vinyl acetate to indan (eq 23).36

Formaldehyde Oxide.

Ozonolysis of vinyl acetate yields formaldehyde oxide, which reacts rapidly with ketones to give lactones (eq 24),37 and is therefore an alternative to the Baeyer-Villiger oxidation.


1. FF 1967, 1, 649, 1271; 1982, 10, 175; 1986, 12, 565; 1990, 15, 71.
2. (a) Lewis, R. J. Sax's Dangerous Properties of Industrial Materials, 8th ed.; Van Nostrand Reinhold: New York, 1992; Vol. 3, p 3492. (b) CRC Handbook of Chemistry and Physics, 73rd ed.; CRC Press: Boca Raton, FL, 1992.
3. Berkowitz, D. B.; Danishefsky, S. J.; Schulte, G. K. JACS 1992, 114, 4518.
4. Laumen, K.; Seemayer, R.; Schneider, M. P. CC 1990, 49.
5. Kanerva, L. T.; Sundholm, O. JCS(P1) 1993, 1385.
6. Tsuji, K.; Terao, Y.; Achiwa, K. TL 1989, 30, 6189.
7. Burgess, K.; Jennings, L. D. JACS 1990, 112, 7434.
8. (a) Wang, Y. F.; Lalonde, J. J.; Momongan, J.; Bergbreiter, D. E.; Wong, C.-H. JACS 1988, 110, 7200. (b) Pedrocchi-Fantoni, G.; Servi, S. JCS(P1) 1992, 1029. (c) Chinn, M. J.; Iacazio, G.; Spackman, D. G.; Turner, N. J.; Roberts, S. M.; Iacazio, G. JCS(P1) 1992, 661. (d) Theil, F.; Schick, H. S 1991, 533.
9. In addition to TA 1993, 4 (5-6), 757-1391, see the following for a selection of recent papers on enzyme-mediated enantioselective acetylation of alcohols with vinyl acetate: (a) Prostaglandin intermediates: Babiak, K. A.; Ng, J. S.; Dygos, J. H.; Weyker, C. L.; Wang, Y. F.; Wong, C.-H. JOC 1990, 55, 3377; Weidner, J.; Theil, F.; Kunath, A.; Schick, H. LA 1991, 1301; Sugahara, T.; Satoh, I.; Yamada, O.; Takano, S. CPB 1991, 39, 2758. (b) Various pharmaceutical intermediates: Hsu, S.-H.; Wu, S.-S.; Wang, Y.-F.; Wong, C.-H. TL 1990, 31, 6403. (c) Propranolol: Terao, Y.; Murata, M.; Nishio, T.; Akamtsu, M.; Kamimura, M.; Achiwa, K. TL 1988, 29, 5173; Wang, Y. F.; Chen, S. T.; Liu, K. K. C.; Wong, C.-H. TL 1989, 30, 1917; Bevinakatti, H. S.; Banerji, A. A. JOC 1991, 56, 5372. (d) b-Adrenergic blockers: Ader, U.; Schneider, M. P. TA 1992, 3, 521. (e) Cycloalkanols and cycloalkenols: Takano, S.; Yamane, T.; Takahashi, M.; Ogasawara, K. TA 1992, 3, 837; Roberts, S. M.; Shoberu, K. A. JCS(P1) 1991, 2605; Theil, F.; Lapitskaya, M. A.; Pivnitsky, K. K.; Schick, H. LA 1991, 195; Seemayer, R.; Schneider, M. P. CC 1991, 49; Ader, U.; Breigoff, D.; Klein, P.; Laumen, K. E.; Schneider, M. P. TL 1989, 30, 1793. (f) Calicheamicinone intermediate: Yamashita, D. L.; Rocco, V. P.; Danishefsky, S. J. TL 1991, 32, 6667. (g) Ferrocene derivative: Nicolosi, G.; Morrone, R.; Patti, A.; Piattelli, M. TA 1992, 3, 753. (h) Vitamin D2 metabolite intermediate: Choudhry, S. C.; Belica, P. S.; Coffen, D. L.; Focella, A.; Maehr, H.; Manchand, P. S.; Serico, L.; Yang, R. JOC 1993, 58, 1496.
10. Bayer, E.; Geckeler, K. AG(E) 1979, 18, 533.
11. (a) Pitha, J. JOC 1975, 40, 3296. (b) Chen, Y. L.; Hedberg, K. G.; Guarino, K. J. TL 1989, 30, 1067.
12. Kuehne, M. E.; Frasier, D. A.; Spitzer, T. D. JOC 1991, 56, 2696.
13. Swern, D.; Jordan, E. F. OSC 1963, 4, 977.
14. Bjorkquist, D. W.; Bush, R. D.; Ezra, F. S.; Keough, T. JOC 1986, 51, 3192.
15. Wegland, F.; Steglich, W. AG 1961, 73, 757.
16. Martin, P. HCA 1988, 71, 344.
17. (a) Burgstahler, A. G.; Nordin, I. C. JACS 1961, 83, 198. (b) Büchi, G.; White, J. D. JACS 1964, 86, 2884.
18. Baciocchi, E.; Civitarese, G.; Ruzziconi, R. TL 1987, 28, 5357.
19. Baciocchi, E.; Ruzziconi, R. SC 1988, 18, 1841.
20. Raucher, S.; Koolpe, G. A. JOC 1983, 48, 2066.
21. Hauser, F. M.; Ellenberger, S. R. S 1987, 324.
22. Jung, M. E.; Shapiro, J. J. JACS 1980, 102, 7862.
23. Dittmar, W.; Sauer, J.; Steigel, A. TL 1969, 5171.
24. (a) Mukaiyama, T.; Hoshino, T. JACS 1960, 82, 5339. (b) Paul, R.; Tchelitcheff, S. BSF(2) 1962, 2215.
25. (a) Cherton, J. C.; Lanson, M.; Ladjama, D.; Guichon, Y.; Basselier, J. CJC 1990, 68, 1271. (b) Micetich, R. G. CJC 1970, 48, 467.
26. Rahman, A.; Clapp, L. B. JOC 1976, 41, 122.
27. (a) DeShong, P.; Lauder, F., Jr.; Longinus, J. M.; Dicken, C. M. In Advances in Cycloaddition; Curran, D. P., Ed.; JAI: Greenwich, CT, 1988; Vol. 1, p 87. (b) Confalone, P. N.; Huie, E. M. OR 1988, 36, 1.
28. Mukai, C.; Cho, W. J.; Kim, I. J.; Hanoaka, M. TL 1990, 31, 6893.
29. (a) Synthetic Organic Photochemistry; Horspool, W. M., Ed.; Plenum: New York, 1984; p 61. (b) Crimmins, M. T.; Rheinhold, T. L. OR 1993, 44, 297.
30. Benchikh le-Hocine, M.; Khac, D. D.; Fetizon, M. SC 1992, 22, 245.
31. Liu, H. J.; Chan, W. H. CJC 1980, 58, 2196.
32. Al-Jalal, N.; Gilbert, A.; Heath, P. T 1988, 44, 1449.
33. Gilbert, A.; bin Samsudin, M. W. JCS(P1) 1980, 1118.
34. Gilbert, A.; Yianni, P. T 1981, 37, 3275.
35. Wender, P. A.; Siegel, L.; Nuss, J. M. In Organic Photochemistry; Padwa, A., Ed.; Dekker: New York, 1989; Vol. 10, p 357.
36. Wender, P. A.; Dreyer, G. B. JACS 1982, 104, 5805.
37. Lapalme, R.; Borschberg, H.-J.; Soucy, P.; Deslongchamps, P. CJC 1979, 57, 3272.

Percy S. Manchand

Hoffmann-La Roche, Nutley, NJ, USA



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