[43042-58-6]  · C5H8O2  · 1-Methoxy-3-buten-2-one  · (MW 100.13)

(methyl vinyl ketone equivalent used in Robinson annulation,1 and Diels-Alder,2 [2 + 2],3 and Michael addition4 reactions)

Alternate Name: methoxymethyl vinyl ketone.

Physical Data: bp 52 °C/30 mmHg.

Solubility: sol dichloromethane, methanol, ethanol, diethyl ether.

Form Supplied in: generated in situ from 1,4-dimethoxy-2-butanone,5 which is in turn synthesized from 2-butyne-1,4-diol (widely available).

Analysis of Reagent Purity: 1H NMR1a [(CDCl3, d 3.43 (s, 3H, Me); 4.25 (s, 2H, CH2); 5.83 (dd, 1H, J = 1.7, 10 Hz, 4-H); 6.32 (dd, 1H, J = 1.7, 18 Hz, 4-H); 6.49 (dd, 1H, J = 10, 18 Hz, 3-H)] and GC.

Preparative Methods: the precursor, 1,4-dimethoxy-2-butanone, is prepared5 by dimethylation of 2-butyne-1,4-diol, followed by oxidation with red Mercury(II) Oxide. In situ generation is possible either by acid-induced elimination using p-Toluenesulfonic Acid,1a base-induced elimination using ethanolic Potassium Hydroxide,1b or pyrolysis in the presence of sodium benzoate.6

Purification: distillation at reduced pressure.

Handling, Storage, and Precautions: the colorless liquid is best used immediately upon generation. This toxic reagent should be handled in a fume hood.

Robinson Annulation.

This reagent was introduced by Wenkert1b in 1967 as a Robinson annulation component (Methyl Vinyl Ketone equivalent) which produces cyclohexenones bearing an oxygen substituent at the 4-position of the newly constructed six-membered ring. The a-oxygenation provides flexibility in the elaboration of cyclic frameworks, as seen in the synthesis of the decalone derivative (-)-valeranone (eq 1),1b as well as in the synthesis of the spirocyclic (-)-acorenone via an alkylative 1,2-carbonyl transposition (eq 2).1c,d

Diels-Alder Chemistry.

The use of (1) as a dienophile in Diels-Alder reactions provides a route for the construction of useful synthetic building blocks such as isopiperitenone derivatives (eq 3)2a and, after ozonolysis and treatment with N-aminophthalimide, 2-methoxypyrrole derivatives (eq 4).2b

[2 + 2] Cycloadditions.

Another facet of this reagent's utility involves Lewis acid-catalyzed [2 + 2] cycloaddition,3 allowing for the construction of functionalized cyclobutane rings (eq 5).

Michael Additions.

In addition to annulations, this reagent functions as a Michael acceptor for nucleophiles. Somei et al.4 have shown that a tricyclic heterocycle can be generated via Heck coupling of (1) to the iodoindole (2) followed by a Michael addition involving the nitronate anion (eq 6).

1. (a) Wenkert, E.; Golob, N. F.; Sathe, S. S.; Smith, R. A. J. SC 1973, 3, 205. (b) Wenkert, E.; Berges, D. A. JACS 1967, 89, 2507. (c) Lange, G. L.; Neidert, E. E.; Orrom, W. J.; Wallace, D. J. CJC 1978, 56, 1628. (d) Lange, G. L.; Wallace, D. J.; So, S. JOC 1979, 44, 3066.
2. (a) Friedrich, D.; Bohlmann, F. T 1988, 44, 1369. (b) Jacobi, P. A.; Cai, G. TL 1991, 32, 1765.
3. Engler, T. A.; Ali, M. H.; Velde, D. V. TL 1989, 30, 1761.
4. Somei, M.; Yamada, F.; Ohnishi, H, Makita, Y.; Kuriki, M. H 1987, 26, 2823.
5. Hennion, G. F.; Kupiecki, F. P. JOC 1953, 18, 1601.
6. Fieser, M.; Fieser, L. F. FF 1972, 3, 198.

Steven D. Paget

The Ohio State University, Columbus, OH, USA

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