Methyl 3-Oxo-4-pentenoate1

(1; R = Me)

[37734-05-7]  · C6H8O3  · Methyl 3-Oxo-4-pentenoate  · (MW 128.14) (2; R = Et)

[22418-80-0]  · C7H10O3  · Ethyl 3-Oxo-4-pentenoate  · (MW 142.17)

(Michael acceptor in the Robinson annulation2)

Alternate Names: Nazarov's reagent; methyl acryloylacetate; vinyl b-methoxycarbonylmethyl ketone.

Physical Data: (1) bp 65 °C/19 mmHg. (2) bp 76-78 °C/18 mmHg.

Solubility: sol common organic solvents.

Form Supplied in: colorless liquid; not commercially available.

Analysis of Reagent Purity: exists as a mixture of keto and enol forms; IR (film) cm-1 2984, 1741, 1659, 1588, 1423, 1242, 1150, 1038, and 812; 1H NMR (CDCl3) d 1.2-1.3 (overlapping t, 3 H), 3.6 (s, ketonic H at C-2), 4.1-4.3 (m, 2 H), 5.05 (s, enolic H at C-2), 5.50 (appt, 1 H), 5.91-6.43 (m, 2 H), 11.8 (s, enol OH); 13C NMR (CDCl3) d 14.0, 14.2, 46.4, 60.2, 61.4, 91.8, 122.5, 130.2, 131.2, 135.7, 167.1, 168.6, 172.7, and 192.6.

Preparative Methods: first prepared by Nazarov3 in 1953 by the reaction shown in eq 1. (2) is known as Nazarov's reagent, although (1) is often referred to as Nazarov's reagent also.

The original preparation of (2) suffers several problems. It has been termed tedious4 and has a low overall yield. Several new syntheses of esters of 3-oxo-4-pentenoic acid have been reported since 1953.2,4-10

The most facile preparation of Nazarov's reagent and ester analogs was reported by Zibuck and Streiber in 1989. A variety of ester enolates react with Acrolein to provide good yields of b-hydroxy esters that can be oxidized to b-keto esters such as Nazarov's reagent and analogs (eqs 2 and 3).1 The reaction sequence can be safely and successfully carried out on a 1 mol scale. Also, the b-hydroxy ester may be oxidized without purification. Interestingly, (-)-bornyl acetate leads to an annulating agent that contains a chiral auxiliary. Methacrolein and Crotonaldehyde give 4- and 5-methyl substituted reagents. C-4 and C-5 substituted analogs of Nazarov's reagent have been prepared by many other research groups, using reactions similar to those presented above.11-16

Purification: by Kugelrohr distillation at 0.6 mmHg (oven temperature 45 °C) with a receiving bulb cooled at -78 °C.

Handling, Storage, and Precautions: polymerizes rapidly at rt; stable to storage at -20 °C under nitrogen for up to 6 months; toxic; handle in a fume hood.

Robinson Annulations and Other Ring-Forming Processes.

Methyl and ethyl 3-oxo-4-pentenoate (1) and (2) are often used as Michael acceptors in strategies such as the Robinson annulation. Typical examples are shown in eqs 4 and 5.17

Other cyclizations involving this reagent include Mannich and Mannich-like reactions (eqs 6-8).18-20 Thioimidates react as nucleophiles with methyl 3-oxo-4-pentenoate as shown in eq 9.21

Methyl 3-oxo-4-pentenoate has also been used in the well-known carbon zip reaction. Cycloheptyl, -octyl, and -dodecyl nitro ketones yield ring-enlarged adducts in 90-93% yield (eq 10).22 Finally, esters of 3-oxo-4-pentenoate have often been used as Michael acceptors in many other synthetic sequences.23-27


1. (a) Zibuck, R.; Streiber, J. M. JOC 1989, 54, 4717. (b) Zibuck, R.; Streiber, J. M. OS 1992, 71, 236.
2. Wenkert, E.; Afonso, A.; Bredenberg, J. B.; Kaneko, C.; Tahara, A. JACS 1964, 86, 2038.
3. Nazarov, I. N.; Zavyalov, S. I. ZOB 1953, 23, 1703.
4. Stork, G.; Guthikonda, R. N. TL 1972, 13, 2755.
5. Pichat, L. Beaucourt, J.-P. S 1973, 537.
6. Trost, B. M.; Kunz, R. A. JOC 1974, 39, 2648.
7. Orisini, F.; Pelizzoni, F.; Destro, R. G 1978, 108, 693.
8. Pellicciari, R.; Fringuelli, R.; Ceccherelli, P.; Sisani, E. CC 1979, 959.
9. Padwa, A.; Kulkarni, Y. S.; Zhang, Z. JOC 1990, 55, 4144.
10. van den Goorbergh, J. A. M.; van der Gen, A. TL 1980, 21, 3621.
11. Bodalski, R.; Peitrusiewicz, K. M.; Monkiewicz, J.; Koszuk, J. TL 1980, 21, 2287.
12. Pollet, P.; Gelin, S. S 1978, 142.
13. Couffignal, R.; Moreau, J.-L. JOM 1977, 127, C65.
14. Bestmann, H.-J.; Saalfrank, R. W. CB 1976, 109, 403.
15. Pochat, F.; Levas, E. BSF(2) 1972, 3151.
16. Wolfe, J. F.; Harris, T. M.; Hauser, C. R. JOC 1964, 29, 3249.
17. Pelletier, S. W.; Chappell, R. L.; Prabhakar, S. JACS 1968, 90, 2889.
18. Hohenlohe-Oehringen, K. M 1962, 93, 576.
19. Ortuno, J.-C.; Langlois, Y. TL 1991, 32, 4491.
20. Dodd, D. S.; Oehlschlager, A. C.; Georgopapadakou, N. H.; Polak, A.-M.; Hartman, P. G. JOC 1992, 57, 7226.
21. (a) Takahata, H.; Yamabe, K.; Suzuki, T.; Yamazaki, T.; H 1986, 24, 37; (b) Takahata, H.; Yamabe, K.; Suzuki, T.; Yamazaki, T. CPB 1986, 34, 4523.
22. (a) Nakashita, Y.; Hesse, M. AG(E) 1981, 20, 1021. (b) Lorenzi-Riatsch, A.; Nakashita, Y.; Hesse, M. HCA 1981, 64, 1854. (c) Nakashita, Y.; Hesse, M. HCA 1983, 66, 845.
23. Caselli, A. S.; Collins, D. J.; Stone, G. M. AJC 1982, 35, 799.
24. Kametani, T.; Hirai, Y.; Kajiwara, M.; Takahashi, T.; Fukumoto, K. CPB 1975, 23, 2634.
25. Hiroi, K.; Yamada, S.-I. CPB 1975, 23, 1103.
26. Chantegrel, B.; Nadi, A.-I.; Gelin, S. S 1983, 948.
27. van den Goorbergh, J. A. M.; van der Steeg, M.; van der Gen, A. S 1987, 314.

Regina Zibuck

Wayne State University, Detroit, MI, USA



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