Methyl 3-Nitroacrylate

[4749-37-5]  · C4H5NO4  · Methyl 3-Nitroacrylate  · (MW 131.10) (E)

[52745-92-3] (E)-ethyl ester

[5941-50-4]  · C5H7NO4  · Ethyl 3-Nitroacrylate  · (MW 145.13)

(Diels-Alder dienophile;4 Michael acceptor13)

Physical Data: bp 73 °C/10 mmHg; mp 38 °C.1

Preparative Methods: by reaction of Methyl Acrylate with either nitryl chloride1 or N2O4/iodine (see Nitrogen Dioxide and Iodine),2 followed by elimination with sodium acetate (eq 1). An Organic Synthesis preparation of the corresponding ethyl ester using N2O4/iodine has been reported.3

Purification: can be crystallized from methanol-water or vacuum distilled.1 However, significant losses were reported on vacuum distillation of the ethyl ester, which was best crystallized from pentane at -15 to 0 °C.3

Handling, Storage, and Precautions: lachrymatory solid; best stored in a refrigerator.

Diels-Alder Reactions.

Methyl 3-nitroacrylate is a very electron-deficient and highly reactive dienophile with electron-rich or unactivated dienes in Diels-Alder reactions (e.g. eq 2).4-7 The nitro group is readily eliminated from the adducts, making the reagent a useful Methyl Propiolate equivalent for Diels-Alder reactions (eq 3).4

A most useful aspect of these reactions is that the nitro group controls the regioselectivity. Thus the regioselectivity after elimination is reversed from that preferred in reactions of methyl propiolate, affording meta disubstituted final products instead of the usual ortho/para (eq 4).5 This regioselectivity has been used to advantage in the Diels-Alder-based synthesis of isogabaculine.8

The Diels-Alder adducts can also be reduced to the amine, as in an approach to the synthesis of gelsemine (eq 5).9 The adduct with furan (eq 2) has seen particular use in synthesis of various C-nucleosides4,10 and (+)-compactin.11

Very low endo stereoselectivity has generally been observed in the reactions of methyl 3-nitroacrylate. The high regioselectivity of the Diels-Alder reactions does not also necessarily apply to 1,3-dipolar cycloadditions; reactions with nitrones afforded all four possible adducts with very low selectivity.12

Michael Additions.

Methyl nitroacrylate is also a powerful Michael acceptor. The nitro group dictates the regiochemistry of the addition of nucleophiles. This allows the equivalent of Michael additions a in methyl propiolate. McMurry takes advantage of this in his a-methylenelactone synthesis (eq 6).13

1. Shechter, H.; Conrad, F.; Daulton, A. L.; Kaplan, R. B. JACS 1952, 74, 3052.
2. Stevens, T. E.; Emmons, W. D. JACS 1958, 80, 338.
3. McMurry, J. E.; Husser, J. H. OS 1977, 56, 65.
4. Just, G.; Martel, A. TL 1973, 1517.
5. Danishefsky, S.; Prisbylla, M. P.; Hiner, S. JACS 1978, 100, 2918.
6. Michael, J. P.; Blom, N. F.; Glintenkamp, L. A. JCS(P1) 1991, 1855.
7. Jung, M. E.; Browm, R. N. TL 1981, 22, 3355.
8. Danishefsky, S.; Hershenson, F. M. JOC 1979, 44, 1180.
9. Clarke, C.; Fleming, I.; Fortunak, J. M. D.; Gallagher, P. T.; Honan, M. C.; Mann, A.; Nuebling, C. O.; Raithby, P. R.; Wolff, J. J. T 1988, 44, 3931.
10. Sera, A.; Itoh, K.; Yamaguchi, H. TL 1990, 31, 6547.
11. Grieco, P. A.; Zelle, R. E.; Lis, R.; Finn, J. JACS 1983, 105, 1403.
12. Padwa, A.; Fisera, L.; Koehler, K. F.; Rodriguez, A.; Wong, G. S. K. JOC 1984, 49, 276.
13. Patterson, J. W.; McMurry, J. E. CC 1971, 488.

Daniel A. Singleton

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

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