Acylation of ketones

The acylation of ketones with acid anhydrides may be effected by means of the acid reagent boron trifluoride, for example ... 

The acylation of ketones with esters an example of the Clalsen condensation is generally effected with a basic reagent, such as sodium ethoxide, sodium, sodamide or sodium hy dride. Thus acetone and ethyl acetate condense in the presence of sodium ethoxide to yield acetylacetone ... 

The mechanism, of the base-catalysed acylation of ketones by esters probably involves several steps (compare acetoacetlc ester condensation see discussion prloi to Section 111,151) —... 

Intramolecular acylation of ketones yields cyclic p diketones when the ring that is formed is five or six membered... 

Even though ketones have the potential to react with themselves by aldol addition recall that the position of equilibrium for such reactions lies to the side of the starting materials (Section 18 9) On the other hand acylation of ketone enolates gives products (p keto esters or p diketones) that are converted to stabilized anions under the reaction conditions Consequently ketone acylation is observed to the exclusion of aldol addition when ketones are treated with base m the presence of esters... 

Acylation of ketones (Sec tion 21 4) Diethyl carbo nate and diethyl oxalate can be used to acylate ketone enolates to give p keto esters... 

It s reasonable to ask why one would prepare a ketone by way of a keto ester (ethyl acetoacetate, for example) rather than by direct alkylation of the enolate of a ketone. One reason is that the monoalkylation of ketones via their enolates is a difficult reaction to cany out in good yield. (Remember, however, that acylation of ketone enolates as described in Section 21.4 is achieved readily.) A second reason is that the delocalized enolates of (3-keto esters, being far- less basic than ketone enolates, give a higher substitution-elimination ratio when they react with alkyl halides. This can be quite important in those syntheses in which the alkyl halide is expensive or difficult to obtain. 

Aldehydes and ketones can be converted to ethers by treatment with an alcohol and triethylsilane in the presence of a strong acid or by hydrogenation in alcoholic acid in the presence of platinum oxide. The process can formally be regarded as addition of ROH to give a hemiacetal RR C(OH)OR", followed by reduction of the OH. In this respect, it is similar to 16-14. In a similar reaction, ketones can be converted to carboxylic esters (reductive acylation of ketones) by treatment with an acyl chloride and triphenyltin hydride. " ... 

After succeeding in the asymmetric reductive acylation of ketones, we ventured to see if enol acetates can be used as acyl donors and precursors of ketones at the same time through deacylation and keto-enol tautomerization (Scheme 8). The overall reaction thus corresponds to the asymmetric reduction of enol acetate. For example, 1-phenylvinyl acetate was transformed to (f )-l-phenylethyl acetate by CALB and diruthenium complex 1 in the presence of 2,6-dimethyl-4-heptanol with 89% yield and 98% ee. Molecular hydrogen (1 atm) was almost equally effective for the transformation. A broad range of enol acetates were prepared from ketones and were successfully transformed into their corresponding (7 )-acetates under 1 atm H2 (Table 19). From unsymmetrical aliphatic ketones, enol acetates were obtained as the mixtures of regio- and geometrical isomers. Notably, however, the efficiency of the process was little affected by the isomeric composition of the enol acetates. 

The strategy for the asymmetric reductive acylation of ketones was extended to ketoximes (Scheme 9). The asymmetric reactions of ketoximes were performed with CALB and Pd/C in the presence of hydrogen, diisopropylethylamine, and ethyl acetate in toluene at 60° C for 5 days (Table 20) In comparison to the direct DKR of amines, the yields of chiral amides increased significantly. Diisopropylethylamine was responsible for the increase in yields. However, the major factor would be the slow generation of amines, which maintains the amine concentration low enough to suppress side reactions including the reductive aminafion. Disappointingly, this process is limited to benzylic amines. Additionally, low turnover frequencies also need to be overcome. 

Although most acylations of active methylene compounds are base catalysed, the acylations of ketones carried out with acetic anhydride take place best in presence of BF3. Acetone is converted to acetylacetone. 

The Acylation of Ketones and Aliphatic Anhydrides by Means of Boron... 

J. A. Conroy, J. T. Adams and Ch. R. Hauser The Acylation of Ketones with Esters to Form -Diketones by the Sodium Amide Methode. J. Amer. chem. Soc. 67, 1510 (1945). 

Hegedus Williams McGuire Hayashi J. Am. Chem. Soc. 1980, 102, 4973 Hegedus, Ref. 1447. pp. 9-20., 4 2For a review of the alkylation and acylation of ketones and aldehydes, see Caine, in Augustine Carbon-Carbon Bond Formation, vol. I Marcel Dekker New York, 1979, pp. 85-352. 

Acylation of Ketones and Nitriles by Carboxylic Esters a-Acylalkyl-de-alkoxy-substitution... 

Acylation of carboxylic esters by carboxylic esters (Claisen Dieckmann) 0-109 Acylation of ketones by carboxylic esters... 

Alkylation or acylation of ketones, sulfides, and amines. This reagent generally reacts with alcohols or carboxylic acids to form 2,2,2-trifluoroethyl ethers or esters in satisfactory yields, except in the case of alcohols prone to dehydration. The reaction of these ethers provides a simple synthesis of unsymmctrical sulfides (equation I). A similar reaction can be used for preparation of secondary amines or amides (equation II). Enolatc anions (generated from silyl cnol ethers with KF) can be alkylated or acylated with a or b (equation III). Use of Grignard reagents in this type of coupling results in mediocre yields. 

Acrolein, 446 Acrylonitrile, 916, 1022 reactions with, 914-917 Acrylic acid derivatives, 1016, 1023 Acylation of ketones, with acid anhydrides, 861 with esters, 861, 862 ... 

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