a,b-Butenolide1

[497-23-4]  · C4H4O2  · a,b-Butenolide  · (MW 84.07)

(can be transformed into derivatives of 2-furanol including esters2 and silyl ethers;3 provides 3-(1-hydroxyalkyl)-2(5H)-furanones by regioselective aldolization;4 undergoes highly regio- and stereoselective reactions with sulfinylallyl anions;5 serves as keystone for the convergent assembly of lignans6 and prostaglandin analogs7 through tandem vicinal difunctionalization8)

Alternate Names: g-crotonolactone; 2(5H)-furanone; but-2-en-4-olide.

Physical Data: bp 86-87 °C/12 mmHg; mp 5 °C; d 1.185 g cm-3. A pKa value of 18.8 has been determined for its equilibrium acidity in DMSO (pKHA), but this may not be correct.9

Solubility: sol most organic solvents, e.g. CCl4, CH2Cl2, Et2O, toluene, THF, MeOH, and MeCN.

Form Supplied in: colorless or pale yellow liquid, commercially available; expensive.

Preparative Methods: obtainable by oxidation of furfural10 or by dehydrobromination of a-bromo-g-butyrolactone10a,11 at very low cost.

Handling, Storage, and Precautions: avoid contact with skin or eyes; do not inhale or ingest; vapor is irritating to the eyes and upper respiratory track. It should be stored at 4 °C or below. Use in a fume hood.

Tautomerism.

In the free state, isomerization of a,b-butenolide (1) to b,g-butenolide (2) or 2-furanol (3) does not occur to any detectable amount (eq 1). According to MO calculations the order of decreasing stability is (1) > (2) > (3).12 In practice, (3) may not even exist. On the other hand, (2) is easily prepared in multigram quantities although it isomerizes to (1) at a rate of 3% per month on standing at rt.10a

Derivatives of 2-Furanol.

Acid chlorides lacking a-hydrogens and alkyl chloroformates are converted into esters and carbonates by using Triethylamine as a base (eq 2).2 Similarly, noncarbon electrophiles such as Phosphorus Oxychloride10b and silylating agents3 readily afford the corresponding furanol derivatives. 2-Trialkylsilyloxyfurans thus obtained (eq 3)13 can be subsequently transformed into a variety of 5-substituted 2(5H)-furanones (see 2-Trimethylsilyloxyfuran).

Reactions of 2-Furanolates with Carbon Electrophiles.

The alkylation of a,b-butenolide by conversion to lithium 2-furanolate (Lithium Diisopropylamide/THF, -78 °C) and subsequent in situ reaction with prenyl bromide in the presence of HMPA, leads to a mixture of mono- and bis-a-alkylated lactones in low yield.14 Under similar conditions, aldol condensation with aldehydes is only modestly regioselective, giving a- and g-adducts in a 3:1 ratio.15 In contrast, high regioselectivity and yields of 3-(1-hydroxyalkyl)-2(5H)-furanones are obtained with dialkylboron 2-furanolates (eq 4).4 The a regioselectivity is explained by the intervention of a boron-containing six-membered chelate. This method has served as key step in the synthesis of the marine antimicrobial bromobeckerelide.16

In certain cases g regioselectivity is also attainable. Thus base-induced condensation of a,b-butenolide with 5-aryl-2-furaldehydes affords 4-ylidenebutenolides (eq 5).17 Likewise, alkali metal 2-furanolates undergo g-selective conjugate addition to enones (eq 6).18

Bromination.

5-Bromo-2(5H)-furanones can be conveniently prepared from the corresponding a,b-butenolides by radical bromination (eq 7).19 They are useful for the synthesis of alfatoxins20 and other bioactive substances.21 For an alternative viable method for preparing 5-bromo-2(5H)-furanones, see 2-Trimethylsilyloxyfuran.

Michael Acceptor.

A variety of carbon and noncarbon nucleophiles undergo conjugate addition to a,b-butenolides.22 These include organocopper reagents,23 stabilized carbanions,24 amines,25 and thiols22,26 among others.27 Ambident allylic anions derived from g-substituted allyl sulfoxides add to butenolide in a highly regio- and diastereoselective manner (eq 8).5a The relative configuration at the allylic carbon in the product is determined by the geometry of the starting sulfoxide. A trans-decalyl-like transition state accounts for both the regio- and stereochemical features of this process.5a This chemistry has been applied to the synthesis of enantiomerically enriched b-alkyl-g-butyrolactones (eq 9).5b

Tandem Vicinal Difunctionalization.

An initial conjugate addition of a nucleophile, and subsequent capture of the resulting enolate with a suitable electrophile, enables rapid introduction of two vicinal substituents.6,8 The intermolecular process leads invariably to trans-a,b-disubstituted lactones (eqs 10 and 11).6a,28 Moreover, when aldehydes are used as electrophiles, aldolization can be effected in a highly syn stereoselective fashion by using Zinc Bromide as additive (eq 11).28 The intramolecular version of this process, known as type II Michael-initiated ring closure (MIRC), provides cis-fused lactones (eq 12).29

Not surprisingly, this methodology has been widely exploited for convergent access to various types of lignans6,28-30 and prostaglandin analogs.7 Applications to the synthesis of enantiomerically pure lignans have also been reported.22,31

Cycloaddition Reactions.

Although a,b-butenolide and its substituted analogs undergo various concerted reactions, such as Diels-Alder32 and [2 + 2] cycloadditions,33 relatively few synthetic applications are known.34 A noteworthy example is the 1,3-dipolar addition to diazomethane.23a,b This process leads to pyrazolinolactones which on thermolysis afford the corresponding 4-methyl-2(5H)-furanones in good yields (eq 13).23b,35 Thus replacement of the b hydrogen by a methyl group can be achieved in just two steps. Other substituents can be installed in this manner by selecting the appropriate diazoalkane, diazo ester or diazo ketone.13,35

Related Reagents.

g-Butyrolactone; Dihydro-5-(hydroxymethyl)-2(3H)-furanone; (R)-Pantolactone; b-Propiolactone; 2-Trimethylsilyloxyfuran; b-Vinyl-a,b-butenolide.


1. (a) Rao, Y. S. CRV 1976, 76, 625. (b) Rao, Y. S. CRV 1964, 64, 353. (c) Avetisyan, A. A.; Dangyan, M. T. RCR 1977, 46, 643.
2. Hormi, O. E. O.; Näsman, J. H. SC 1986, 16, 69.
3. (a) Asaoka, M.; Miyake, K.; Takei, H. CL 1977, 167. (b) Kraus, G. A.; Roth, B. JOC 1978, 43, 4923. (c) Fiorenza, M.; Ricci, A.; Romanelli, M. N.; Taddei, M.; Dembech, P.; Seconi, G. H 1982, 19, 2327.
4. Jefford, C. W.; Jaggi, D.; Boukouvalas, J. CC 1988, 1595.
5. (a) Binns, M. R.; Haynes, R. K.; Katsifis, A. G.; Schober, P. A.; Vonwiller, S. C. JACS 1988, 110, 5411. (b) Hua, D. H.; Venkataraman, S.; Coulter, M. J.; Sinai-Zingde, G. JOC 1987, 52, 719.
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7. Haynes, R. K.; Schober, P. A. AJC 1987, 40, 1249.
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9. Bordwell, F. G.; Fried, H. E. JOC 1991, 56, 4218.
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11. Price, C. C.; Judge, J. M. OSC 1973, 5, 255, For an improvement see Ref. 10a.
12. Bodor, N.; Dewar, M. J. S.; Harget, A. J. JACS 1970, 92, 2929.
13. Boukouvalas, J.; Maltais, F.; Lachance, N. TL 1994, 35, 7897.
14. Gedge, D. R.; Pattenden, G. TL 1977, 4443.
15. Brown, D. W.; Campbell, M. M.; Taylor, A. P.; Zhang, X. TL 1987, 28, 985.
16. Jefford, C. W.; Jaggi, D.; Boukouvalas, J. TL 1989, 30, 1237.
17. Kaklyugina, T. Y.; Badovskaya, L. A.; Sorotskaya, L. N.; Kozhina, N. D.; Jurá˘sek, A.; Kada, R.; Ková˘c, J.; Kulnevich, V. G. CCC 1986, 51, 2181.
18. (a) Asaoka, M.; Yanagida, N.; Sugimura, N.; Takei, H. BCJ 1980, 53, 1061. See also: (b) Kraus, G. A.; Roth, B. TL 1977, 3129.
19. Wolff, S.; Hoffmann, H. M. R. S 1988, 760; see also Ref. 17.
20. (a) Sloan, C. P.; Cuevas, J. C.; Quesnelle, C.; Snieckus, V. TL 1988, 29, 4685. (b) Schmidt, B.; Hoffmann, H. M. R. T 1991, 47, 9357.
21. (a) Doerr, I. L.; Willette, R. E. JOC 1973, 38, 3878. (b) Heather, J. B.; Mittal, R. S. D.; Sih, C. J. JACS 1976, 98, 3661. (c) Shono, T.; Matsumura, Y.; Yamane, S. TL 1981, 22, 3269.
22. Feringa, B. L.; de Lange, B.; Jansen, J. F. G. A.; de Jong, J. C.; Lubben, M.; Faber, W.; Schudde, E. P. PAC 1992, 64, 1865.
23. (a) Hanessian, S.; Murray, P. J. T 1987, 43, 5055. (b) Jefford, C. W.; Sledeski, A. W.; Boukouvalas, J. HCA 1989, 72, 1362. (c) Hollingworth, G. J.; Lee, T. V.; Sweeney, J. B. TL 1992, 33, 5591. (d) Caine, D.; Venkataramu, S. D.; Kois, A. JOC 1992, 57, 2960.
24. (a) Haynes, R. K.; Schober, P. A.; Binns, M. R. AJC 1987, 40, 1223. (b) Binns, M. R.; Haynes, R. K.; Katsifis, A. G.; Schober, P. A.; Vonwiller, S. C. JOC 1989, 54, 1960. (c) Ishibashi, H.; Ito, K.; Tabuchi, M.; Ikeda, M. H 1991, 32, 1279. (d) Hanessian, S.; Gomtsyan, A.; Payne, A.; Hervé, Y.; Beaudoin, S. JOC 1993, 58, 5032.
25. (a) Jacobi, P. A.; Blum, C. A.; DeSimone, R. W.; Udodong, U. E. S. JACS 1991, 113, 5384. (b) Lubben, M.; Feringa, B. L. TA 1991, 2, 775.
26. Watanabe, M.; Shirai, K.; Kumamoto, T. BCJ 1979, 52, 3318.
27. Huryn, D. M.; Okabe, M. CRV 1992, 92, 1745.
28. Ogiku, T.; Yoshida, S.; Takahashi, M.; Kuroda, T.; Ohmizu, H.; Iwasaki, T. TL 1992, 33, 4473.
29. Harrowven, D. C. TL 1991, 32, 3735.
30. (a) Tomioka, K.; Kawasaki, H.; Koga, K. CPB 1990, 38, 1898. (b) Mitra, J.; Mitra, A. K. JCS(P1) 1992, 1285.
31. (a) Ward, R. S. T 1990, 46, 5029. (b) Ward, R. S. S 1992, 719.
32. Keay, B. A.; Plaumann, H. P.; Rajapaska, D.; Rodrigo, R. CJC 1983, 61, 1987.
33. (a) Fillol, L.; Miranda, M. A.; Morera, I. M.; Sheikh, H. H 1990, 31, 751. (b) Hayashi, Y.; Niihata, S.; Narasaka, K. CL 1990, 2091.
34. (a) Choy, W. T 1990, 46, 2281. (b) de Jong, J. C.; van Bolhuis, F.; Feringa, B. L. TA 1991, 2, 1247.
35. Pelletier, S. W.; Djarmati, Z.; Laj˘sić, S. D.; Mićović, I. V.; Yang, D. T. C. T 1975, 31, 1659.

John Boukouvalas

Université Laval, Québec, Canada



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