[43042-58-6] · C5H8O2 · 1-Methoxy-3-buten-2-one · (MW 100.13)
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.
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
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
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).
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).
Steven D. Paget
The Ohio State University, Columbus, OH, USA