Acetyl Methanesulfonate1

[5539-53-7]  · C3H6O4S  · Acetyl Methanesulfonate  · (MW 138.14)

(reagent for ether cleavage,2 for the cleavage of activated cyclopropanes as partial structures of cyclopropyl ketones,3-6 and for acetylation of aromatic rings7)

Physical Data: bp 50 °C/10-2 mmHg; mp 33-36 °C.

Solubility: sol MeCN, CH2Cl2.

Form Supplied in: not available commercially.

Preparative Methods: can be prepared on a large scale (1 mol) from Acetyl Chloride and Methanesulfonic Acid by heating at reflux followed by fractional distillation (85% yield).1

Purification: white/colorless solid upon distillation.

Handling, Storage, and Precautions: slightly hygroscopic. However, no particular precautions are required upon exposure to air for a short period of time. Stable if stored at 4 °C for several months. Use in a fume hood.

Ether Cleavage.

Acetyl methanesulfonate (AcOMs) can be used to cleave both acyclic and cyclic ethers.2 The reaction parallels the Lewis acid promoted cleavage (i.e. SN1-type process). The reactivity order is tertiary >> secondary > primary ethers. Cyclic ethers can also be cleaved with the expected rate trends. Unsymmetrical ethers give mixtures.

Cyclopropane Cleavage.

Acetyl methanesulfonate is a very efficient reagent for selective opening of the ring in cyclopropyl ketones. In the latter context, AcOMs is the trigger for the cleavage of a cyclopropane followed by spiroannulation yielding a tricyclic intermediate en route to (epi-)cedrone (eq 1).3

If no intramolecular trapping of cationic-type intermediates is possible, AcOMs adds to cyclopropyl ketones regiospecifically, affording enol acetates (eqs 2-5, X = OMs) with good (eq 2) to excellent (eq 3) regio- and stereocontrol of the cyclopropane cleavage.4 Subtle steric factors seemingly dominate such addition processes as they are consistent with an overall SN2-type mechanism.4 Furthermore, if these substrates are combined with AcOMs in the presence of Tetramethylammonium Bromide or iodide, the parent bromo or iodo enol acetates are the products (eqs 2-5, X = Br or I).4,5 Activation of the ketone moiety of these substrates by AcOMs is likely to increase the electrophilicity of the cyclopropane, allowing introduction of nucleophiles (Br- or I-) which are insufficiently reactive alone. Tetramethylammonium salts are used for these transformations because of their solubility and their potential to effect configurational equilibration in organic solvents.

A reaction cascade of three high-yield consecutive steps is triggered by AcOMs in the case of a tricyclooctanone derivative (eq 6).6,7 If this reaction, which proceeds at room temperature, is run with one equiv of AcOMs (1 h), an enol acetate (eq 6) is obtained with complete stereochemical control. Prolonged reaction time (10 h) and the use of 2.2 equiv of AcOMs leads to cyclization of ring B (eq 7, R = H; after work-up with water). Beneficially, smooth and exclusive C-2 acetylation of the aromatic ring is found to be completed within 24 h when an excess (4-6 equiv) of the reagent is employed (eq 7, R = Ac). As a result, a 2-acetyl-C,18-bisnor-13a,17a-estradiol derivative is assembled. Analogously, ring A acetylation allows a short and clean access to 2-hydroxyestrone 3-methyl ether.7 The same reference also cites successful acetylations of anisole to p-methoxyacetophenone as well as of cyclopentene and cyclohexene to the respective 1-acetylcycloalkenes.

1. Karger, M. H.; Mazur, Y. JOC 1971, 36, 528.
2. Karger, M. H.; Mazur, Y. JOC 1971, 36, 532.
3. Corey, E. J.; Balanson, R. D. TL 1973, 3153.
4. Demuth, M.; Raghavan, P. R. HCA 1979, 62, 2338.
5. Demuth, M.; Mikhail, G. T 1983, 39, 991.
6. Mikhail, G.; Demuth, M. HCA 1983, 66, 2362.
7. Mikhail, G.; Demuth, M. SL 1989, 54.

Martin Demuth

Max-Planck-Institut für Strahlenchemie, Mülheim an der Ruhr, Germany

Gamal Mikhail

Bayer, Leverkusen, Germany

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