1-Acetoxy-1,3-butadiene

[1515-76-0]  · C6H8O2  · 1-Acetoxy-1,3-butadiene  · (MW 112.13)

(2p or 4p partner in cycloaddition reactions;1 mono-oxygenation allows high levels of regiocontrol2)

Alternate Name: 1,3-butadienyl acetate.

Physical Data: bp 60-61 °C/40 mmHg; d 0.945 g cm-3.

Form Supplied in: colorless liquid, available as an unspecified mixture of (E) and (Z) isomers.3

Handling, Storage, and Precautions: classified as a flammable liquid and is reputed to be toxic. Compound polymerizes upon extended storage and can be regenerated by distillation. Avoid polymerization initiators. Diene performs best when stored in the cold.

Preparation.

1-Acetoxy-1,3-butadiene (1)4 is commercially available as a mixture of (E) and (Z) isomers, and can be prepared by reaction of Crotonaldehyde with acetic anhydride-sodium acetate to provide the diene as an isomeric mixture in ~60% yield.5a Pure (E)-1-acetoxy-1,3-butadiene can be prepared in high yield by the slow addition of crotonaldehyde to refluxing Isopropenyl Acetate containing catalytic amounts of p-toluenesulfonic acid and copper acetate. After distillation to remove acetone and excess isopropenyl acetate, (E)-1-acetoxy-1,3-butadiene can be isolated by vacuum distillation in >80% yield.5

Reactivity.

1-Acetoxy-1,3-butadiene (1) is primarily used as a 4p partner in [p4s + p2s] cycloaddition reactions of the normal electron demand type, and reacts well with electron-deficient dienophiles.1 The presence of the weakly electron-donating 1-acetoxy substituent on this open-chain diene imparts a useful degree of regio- and stereoselectivity in cycloaddition reactions;2 ortho-endo adducts predominate and often single isomers are obtained exclusively (eq 1).6 This high ortho selectivity can be rationalized using frontier molecular orbital (FMO) theory.7 Ab initio STO-3G calculations of energies and coefficients of the frontier molecular orbitals for the s-cis conformation of diene (1) have been reported.8 The moderately electron-rich diene (1) has been found to be slightly more reactive toward polarized dienophiles than simple dienes;5a,9 however, the reported incompatibility of the diene with Lewis acids precludes most low-temperature Lewis acid-catalyzed reaction conditions and limits the general utility of diene (1).8 Reactions employing an excess of a mixture of (E,Z)-1-acetoxy-1,3-butadiene can potentially yield single cycloadducts due to the increased reactivity of the (E) isomer compared to the (Z) isomer, thereby obviating the need for purification of individual diastereomers of (1).

Cycloaddition Reactions.

Reactions utilizing diene (1) and Acrolein or crotonaldehyde were reported to afford single cycloadducts in moderate to fair yield with good regioselectivity.10 However, since that early report, the most frequent use of 1-acetoxy-1,3-butadiene in cycloaddition reactions involves coupling with naphthoquinone derivatives (eq 2). The importance of this reaction is twofold: (1) the cyclohexenyl acetate cycloadduct provides a useful framework upon which further modifications can be made; and (2) either regioisomeric cycloadduct can lead to aromatic products (either spontaneously or promoted) via 1,4-elimination of acetic acid followed by tautomerization to a dihydroquinone system. Employing these tactics, many naphthoquinone,11 anthracycline,6e,12 azaanthraquinone,13 and tetracycline14 derivatives have been efficiently constructed, and this general use as a butadienyl synthon constitutes a significant portion of the literature on diene (1).6a,e,14,15

4-Demethoxydaunomycinone (2)12c and (±)-terramycin (3)14 are representative examples of natural products constructed employing a Diels-Alder strategy with diene (1).

Highly regioselective cycloaddition reactions have been realized between diene (1) and a wide variety of dienophiles, including substituted acrylonitrile derivatives,16 haloquinones (eq 3),17 substituted enones (eq 4),8,18 naphthoquinone derivatives,6e,14,19 nitroalkenes,9 alkenyl sulfones,19,20 alkenyl metal carbene complexes (eq 5),21 substituted maleimides,22 and several others.23 Useful levels of diastereoselection have been achieved in several of these systems.6c,18a,21,22,23c

While these Diels-Alder reactions afford predominately the ortho-endo adducts, ortho-exo product formation predominates in cycloaddition reactions between diene (1) and bridgehead enones (eq 6)24 or unsymmetrical tropones,25 presumably due to repulsive secondary FMO interactions.26

Examples of successful Lewis acid-catalyzed cycloaddition reactions of diene (1) are limited. Boron Trifluoride Etherate-mediated cycloaddition between juglone and diene (1) afforded a single cycloadduct in 97% isolated yield,11 whereas uncatalyzed versions of the same reaction afford <50% of the same adduct.17a Boron trifluoride etherate27a and Tin(IV) Chloride28 have also been used to enhance27 or reverse29 regioselectivity in cycloaddition reactions employing diene (1).

An example of an asymmetric Diels-Alder reaction involving diene (1) has been reported.30 Use of a binaphthol-based borane catalyst in the reaction of juglone with diene (1) afforded a single adduct in good yield with >98% enantiomeric excess (eq 7).

1-Acetoxy-1,3-butadiene participates in other cycloaddition reactions as well. Assembly of an azetidinone system, a key substructure in the total synthesis of (±)-thienamycin, was accomplished by [2 + 2] cycloaddition of diene (1) and Chlorosulfonyl Isocyanate (eq 8).31 Diene (1) has also been employed as the 2p partner in a 1,3-dipolar cycloaddition reaction.32

A highly endo-selective cycloaddition for the construction of bicyclo[4.4.1]undecane systems using a photochemical metal-mediated cycloaddition reaction between (h6-cycloheptatriene)chromium tricarbonyl and diene (1) (eq 9) has been reported.33 In an example of a thermal [6 + 4] cycloaddition reaction, diene (1) and unsymmetrical tropone derivatives afforded predominately exo adducts in modest yields.25b This type of Diels-Alder strategy was utilized in the synthesis of [4](2,7)troponophane.25c

Miscellaneous Reactions.

Diene (1), formally a dienol acetate, undergoes anodic oxidation and regioselective g-methoxylation, which provides a key intermediate in a method for 1,4-carbonyl transposition.34 A palladium-assisted heteroannulation of diene (1) with organomercurials also has been reported (eq 10).35


1. Fringuelli, F.; Taticchi, A. Dienes in the Diels-Alder Reaction; Wiley: New York, 1990; pp 45-124.
2. (a) Kakushima, M. CJC 1979, 57, 2564. (b) For a review, see: Titov, Y. A. RCR 1962, 31, 267.
3. It has been reported that 1-acetoxy-1,3-butadiene obtained from Aldrich Chemical Company is a 60:40 mixture of (E/Z) isomers as determined by 1H NMR: Edwards, O. E.; Greaves, A. M.; Sy, W. W. CJC 1988, 66, 1163.
4. FF 1967, 1, 7.
5. (a) McDonald, E.; Suksamrarn, A.; Wylie, R. D. JCS(P1) 1979, 1893. (b) Hagemeyer, H. J., Jr.; Hull, D. C. Ind. Eng. Chem. 1949, 41, 2920.
6. For representative examples, see: (a) Ohgaki, E.; Motoyoshiya, J.; Narita, S.; Kakurai, T.; Hayashi, S.; Hirakawa, K. JCS(P1) 1990, 11, 3109. (b) Kraus, G. A.; Yu, F. X. SC 1989, 19, 2401. (c) Cooper, S. C.; Sammes, P. G. JCS(P1) 1984, 10, 2407. (d) Oda, M.; Kanao, Y. CL 1981, 11, 1547. (e) Gupta, D. N.; Hodge, P.; Khan, N. JCS(P1) 1981, 3, 689.
7. For a comprehensive review, see: Fleming, I. Frontier Orbitals and Organic Chemical Reactions; Wiley: New York, 1976; pp 121-142.
8. Reyes, A.; Aguilar, R.; Muñoz, A. H.; Zwick, J.-C.; Rubio, M.; Escobar, J.-L.; Soriano, M.; Toscano, R.; Tamariz, J. JOC 1990, 55, 1024.
9. Ono, N.; Miyake, H.; Kamimura, A.; Kaji, A. JCS(P1) 1987, 9, 1929.
10. Wichterle, O.; Hudlicky, M. CCC 1947, 12, 564.
11. Ichihara, A.; Ubukata, M.; Oikawa, H.; Murakami, K.; Sakamura, S. TL 1980, 21, 4469.
12. (a) Kraus, G. A.; Fulton, B. S. JOC 1985, 50, 1782. (b) Krohn, K.; Ostermeyer, H. H.; Tolkiehn, K. CB 1979, 112, 2640. (c) Krohn, K.; Tolkiehn, K. TL 1978, 4023. (d) Krohn, K.; Roesner, A. TL 1978, 353. (e) Lee, W. W.; Martinez, A. P.; Smith, T. H.; Henry, D. W. JOC 1976, 41, 2296.
13. Potts, K. T.; Bhattacharjee, D.; Walsh, E. B. JOC 1986, 51, 2011.
14. Muxfeldt, H.; Haas, G.; Hardtmann, G.; Kathawala, F.; Mooberry, J. B.; Vedejs, E. JACS 1979, 101, 689.
15. (a) Weeratunga, G.; Prasad, G. K. B.; Dilley, J.; Taylor, N. J.; Dmitrienko, G. I. TL 1990, 31, 5713. (b) Krohn, K.; Tolkiehn, K. CB 1979, 112, 3453.
16. Farina, F.; Victory, P. TL 1969, 3219.
17. Boisvert, L.; Brassard, P. TL 1983, 24, 2453.
18. (a) Taschner, M. J.; Cyr, P. T. TL 1990, 31, 5297. (b) Aguilar, R.; Reyes, A.; Tamariz, J.; Birbaum, J. L. TL 1987, 28, 865.
19. (a) Colonna, S.; Manfredi, A.; Annunziata, R. TL 1988, 29, 3347. (b) Gaveby, B. M. G.; Huffman, J. C.; Magnus, P. JOC 1982, 47, 3779.
20. Houge-Frydrych, C. S. V.; Motherwell, W. B.; O'Shea, D. M. H 1989, 28, 603.
21. Wulff, W. D.; Bauta, W. E.; Kaesler, R. W.; Lankford, P. J.; Miller, R. A.; Murray, C. K.; Yang, D. C. JACS 1990, 112, 3642.
22. McKenzie, T. C.; Fanshawe, W. J.; Epstein, J. W.; Collins, J. B. JOC 1982, 47, 352.
23. (a) Isobe, M.; Fukami, N.; Nishikawa, T.; Goto, T. H 1987, 25, 521. (b) Johnson, M. P.; Moody, C. J. JCS(P1) 1985, 1, 71. (c) Darling, S. D.; Brandes, S. J. JOC 1982, 47, 1413. (d) Dauben, W. G.; Krabbenhoft, H. O. JOC 1977, 42, 282.
24. (a) Kraus, G. A.; Hon, Y. S.; Sy, J.; Raggon, J. JOC 1988, 53, 1397. (a) Kraus, G. A.; Hon, Y. S. JOC 1986, 51, 116.
25. (a) Rigby, J. H.; Moore, T. L.; Rege, S. JOC 1986, 51, 2398. (b) Garst, M. E.; Roberts, V. A.; Houk, K. N.; Rondan, N. G. JACS 1984, 106, 3882. (c) Fujise, Y.; Shiokawa, T.; Mazaki, Y.; Fukazawa, Y.; Fujii, M.; Ito, S. TL 1982, 23, 1601.
26. (a) Hoffmann, R.; Woodward, R. B. JACS 1965, 87, 4388. (b) Houk, K. N. TL 1970, 2621. (c) Houk, K. N.; Woodward, R. B. JACS 1970, 92, 4145.
27. (a) Trost, B. M.; Ippen, J.; Vladuchick, W. C. JACS 1977, 99, 8116. (b) Kelly, T. R.; Montury, M. TL 1978, 45, 4311.
28. (a) Liu, H. J.; Browne, E. N. C.; Pednekar, P. R. CJC 1982, 60, 921. (b) Nicolaou, K. C.; Zipken, R. E. AG(E) 1981, 20, 785.
29. Stojanac, Z.; Dickinson, R. A.; Stojanac, N.; Woznow, R. J.; Valenta, Z. CJC 1975, 53, 616.
30. Kelly, T. R.; Whiting, A.; Chandrakumar, N. S. JACS 1986, 108, 3510.
31. (a) Bouffard, F. A.; Johnston, D. B. R.; Christensen, B. G. JOC 1980, 45, 1130. (b) Johnston, D. B. R.; Schmitt, S. M.; Bouffard, F. A.; Christensen, B. G. JACS 1978, 100, 313.
32. Fliege, W.; Huisgen, R.; Kolbeck, W.; Weberndoerfer, V. CB 1983, 116, 3438.
33. Rigby, J. H.; Ateeq, H. S. JACS 1990, 112, 6442.
34. (a) Shono, T.; Kashimura, S. JOC 1983, 48, 1939. (b) Baltes, H.; Steckhan, E.; Schaefer, H. J. CB 1978, 111, 1294.
35. Larock, R. C.; Song, H. SC 1989, 19, 1463.

Andrew J. Carpenter & Robert S. Coleman

University of South Carolina, Columbia, SC, USA



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