Isopropenyl Acetate enol acetylation

Ketones with labile hydrogen atoms undergo enol acetylation on reaction with ketene. Strong acid catalysis is required. If acetone is used, isoptopenyl acetate [108-22-5] (10) is formed (82—85). Isopropenyl acetate is the starting material for the production of 2,4-pentanedione (acetylacetone) [123-54-6] (11). 

Enol esterification with acetyl chloride-acetic anhydride gives the A -trien-3-acetate, but reaction with isopropenyl acetate or with hot acetic anhydride-pyridine gives A " -trien-3-acetates. " Since A"" -3-ketones react with Girard reagents, these linear dienones can be separated from A ""-3-ketones. ... 

The diacylation of isopropenyl acetate with anhydrides of dicarboxylic acids is applicable for the synthesis of several other cyclic jS-triketones in moderate yield. - It has been used for the synthesis of 2-acetylcyclohexane-l,3-dione (40% yield), 2-acetyl-4-methylcyclopentane-l,3-dione (10% yield), 2-acetyl-4,4-dimethylcyclopentane-l,3-dione (10% yield), 2-acetyl-5,5-dimethylcyclohexane-l,3-dione (10% yield), 2-acetylcyclo-heptane-l,3-dione (12% yield) and 2-acetylindane-l,3-dione (26% yield). Maleic anhydrides under more drastic conditions give acetylcyclopent-4-ene-l,3-diones in yields from 5% to 12%. The corresponding acylation of the enol acetate of 2-butanone with succinic anhydride has been used to prepare 2-methylcyclopentane-l,3-dione, an important intermediate in steroid synthesis. - ... 

The direction of enohsation of steroid 3-ketones was a subject of much debate from the early 1950 s, for 5a-3-ketones give A2-enols (17), and 5ji -3-ketones give mainly A -enols (18) [12, 128]. The preference for A -enolisation in the 5j8-series was fairly easily explained [128] in terms of relief of non-bonded interactions between the qa-hydrogen and the 7a- and qa-hydrogens when a trigonal centre is formed at C 4) . Recent calculations [ 126] suggest that the A -isomer is favoured by an enthalpy difference of 1.9 kcal/mole. This would result in a A8/A2 ratio of 96 4, compared with the experimentally determined 93.5 6.5. It is interesting that kineticaUy controlled enol acetylation of a 5j5 3-ketone with isopropenyl acetate The preferential Ca-formylation of 5 j -3-ketones is discussed on p. 182. Heferences p. 214... 

House and Trost state that enol acetylation with isopropenyl acetate yields chiefly the less highly substituted isomer whereas the reverse is true of enol acetylation with acetic anhydride, but we fail to find in the paper experimental evidence in support of these generalizations. 

Enol acetylation. An a-halo-a-arylacetophenone such as (1) cannot be converted into the enol acetate by reaction with isopropenyl acetate, and conversion into the sodium enolate by sodium methoxide followed by treatment with acetyl chloride gives low yields. However, Cooper and Owen28 found that, if the ketone is treated with dry methanol and sodium hydride and the mixture let stand until evolution of hydrogen has ceased and then treated with acetyl chloride, the enol acetate is obtained in yield of50-70%. 

Watanabe and Yoshikoshi have converted dihydro-a-santonin (213) into dihydronovanin (216 R = a-Me), the reduction product of novanin (216 R = =CH,), by a route which is not dissimilar to that used by Corey and Hortmann in the synthesis of dihydrocostunolide. Enol acetylation of (213) with isopropenyl acetate gave the diene (214) which, on photolysis and treatment with potassium hydroxide, yielded the dienone (215). Reduction of (215) with sodium borohydride and subsequent acetylation afforded (216 R = a-Me). 

The acetylation of amines with isopropenyl acetate appears to be a transition between the highly exothermic reactions of acyl halides and anhydrides with amines on the one hand and the reaction of amines with more conventional esters on the other. While this reagent is of particular value in the preparation of enol acetate, it has been used for the preparation of amides. One interesting aspect of its use is that acetone forms as a coproduct which may distill off as the reaction proceeds. Isopropenyl acetate and other isopropenyl esters may also be used to Y-acylate amides and imides. By the judicious selection of starting amides and isopropenyl esters, tertiary amides with three different acyl groups may be synthesized. This may very well be one of very few reaction systems which permits the synthesis of this rare group of tertiary amides. 

Enol Acetylation. In the presence of catalytic acid, isopropenyl acetate reacts with enolizable ketones to give the enol acetate plus acetone. This reactivity has been exploited to accomplish selective enolization of ketones, and to provide dienol acetates for Diels-Alder reactions. Each of these reactions is described in more detail in the following sections. 

Acetylation of Other O, N, and C Centers. In addition to the preparation of enol acetates from ketones, isopropenyl acetate has also seen use in the acetylation of other O, N, and C centers. Hydroxy acetylation was first noted" as a simultaneous reaction... 

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