Dimethyl Fumarate

[624-49-7]  · C6H8O4  · Dimethyl Fumarate  · (MW 144.14)

(reactive dienophile; dipolarophile; radical acceptor)

Physical Data: mp 103-104 °C; bp 192-193 °C; d 1.37 g cm-3.

Solubility: sol acetone, chloroform, methanol.

Form Supplied in: white solid.

Purification: recrystallized from benzene.

Handling, Storage, and Precautions: mutagen.

Cycloadditions.

Dimethyl fumarate has frequently been employed as a dienophile in Diels-Alder reactions. Dialkyl fumarates undergo Diels-Alder cycloadditions with aromatic dienes such as anthracene and dihydroquinone (eq 1).1 Dienophiles which are more reactive than dialkyl fumarates include Tetracyanoethylene, N-methylmaleimide, fumaronitrile, and maleonitrile. The [4 + 2] cycloaddition reaction of dimethyl fumarate with a diene is a stereospecific reaction and has been used to determine the geometry and stereoselectivity of Diels-Alder reactions of substituted o-quinodimethanes (eqs 2 and 3).2 High diastereoselectivity has been observed in the organoaluminum catalyzed Diels-Alder reaction of (-)-dimenthyl fumarate with a variety of dienes (eq 4).3 A diastereoselective Diels-Alder addition of the bis-lacate fumarate to an a-hydroxyorthoquinodimethane has also been reported.4

A range of 1,3-dipoles have been trapped by dimethyl and related dialkyl fumarates. Dimethyl fumarate and maleate have been used in experiments which examine the concertedness of cycloadditions through examination of the stereoselectivity of the cycloaddition process. Dipoles which have been trapped with dimethyl fumarate include nitrile (eq 5), azomethine,5 carbonyl, and thiocarbonyl ylides.6,7 Also nitrile oxides, nitrones,8 and nitronates have been trapped by dimethyl fumarate.

Electron rich alkenes such as ketene dithioacetals and enamines react thermally with dimethyl fumarate to yield substituted cyclobutanes.9 Asymmetric [2 + 2] cycloadditions have been developed which employ oxazolidone derivatives in combination with chiral titanium catalyst generated in situ from dichlorodiisopropoxytitanium and a tartrate-derived chiral diol (eq 6).10 Dimethyl fumarate traps carbenoids generated photochemically and thermally (eq 7).11,12

Miscellaneous.

Dimethyl fumarate serves as an excellent radical trap (eq 8).13 Asymmetric dihydroxylation of dimethyl fumarate provides dimethyl tartrate of good optical purity.14

Related Reagents.

Dimethyl Maleate; Maleic Anhydride; N-Phenylmaleimide; Tetracyanoethylene.


1. (a) Nakazali, M.; Naemura, K.; Yoshihara, H. BCJ 1975, 48, 3278. (b) Ohno, M.; Shimizu, S.; Eguchi, S. TL 1990, 31, 4613.
2. (a) Durst, T.; Kozma, E. C.; Charlton, J. L. JOC 1985, 50, 4829. (b) Ito, Y.; Nakatsuka, M.; Saegusa, T. JACS 1982, 104, 7609.
3. (a) Furuta, K.; Iwanaga, K.; Yamamoto, H. TL 1986, 37, 4507. (b) Corey, E. J.; Su, W.-G. TL 1988, 29, 3423.
4. Charlton, J. L.; Plourde, G. L.; Koh, K.; Secco, A. S. CJC 1989, 67, 574.
5. (a) Tian, W. S.; Livinghouse, T. CC 1989, 819. (b) Ohno, M.; Komatsu, M.; Miyata, H.; Ohshiro, Y. TL 1991, 56, 5813.
6. Clawson, P.; Whiting, D. A. TL 1987, 28, 3155.
7. Huisgen, R.; Mloston, G. TL 1989, 30, 7041.
8. Pandey, G.; Kumaraswamy, G.; Krishna, A. TL 1987, 28, 2649.
9. Cook, A.; Gilbert, T.; Enamines: Synthesis, Structure and Reactions; Dekker: New York, 1969.
10. Narasaka, K.; Hayashi, Y.; Shimadzu, H.; Niihata, S. JACS 1992, 114, 8869.
11. (a) Turro, N. J.; Farneth, W. E.; Deuaquet, A. JACS 1976, 98, 7425. (b) Jones, W. M.; Hamon, B. N.; Joines, R. C.; Ennis, C. L.; TL 1969, 3909.
12. Herndon, J. W.; Tumer, S. U. JOC 1991, 56, 286.
13. Barton, D. H. R.; Chern, C.-Y.; Jaszberenyi, J. C. TL 1992, 33, 7299.
14. (a) Tomioka, K.; Nakajima, M.; Koga, K. JACS 1987, 109, 6213. (b) Hanessian, S.; Meffre, P.; Girard, M.; Beaudoin, S.; Sancéau, J-Y.; Bennani, Y. JOC 1993, 58, 1991.

Gary A. Sulikowski & Michelle M. Sulikowski

Texas A&M University, College Station, TX, USA



Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.