The danger we have to face is that acylation is inclined to occur on oxygen rather than on carbon. In the extreme case, naked enolates (those with completely non-coordinating cations) acylate cleanly on oxygen with anhydrides or acid chlorides.

Fortunately, the reagents we have just discussed for aldol reactions (lithium and zinc enolates) are also acylated at carbon rather than on oxygen. Even with acid chlorides magnesium enolates, particularly those of 1,3-dicarbonyl compounds, give reliable C-acylation. The magnesium atom bonds strongly to both oxygens, lessening their effective negative charge.

Hydrolysis and decarboxylation in the usual way lead to keto-esters or keto-acids. Of the more common metals used to form enolates, lithium is the most likely to give good C-acylation as, like magnesium, it forms a strong O–metal bond. It is possible to acylate simple lithium enolates with enolizable acid chlorides.

We shall describe two examples of this reaction being used as part of the synthesis of natural products. The first is pallescensin A, a metabolite of a sponge. It is quite a simple compound and some chemists in Milan conceived that it might be made from the chloro-diketone shown below, which might in turn be made by acylation of the enolate of a symmetrical ketone.

The route chosen was to react the lithium enolate of 4-t-butyl cyclohexanone with the correct acid chloride. This reaction worked well, as did the rest of the synthesis of pallescensin A, which was first made by this route. The key step, the acylation of the lithium enolate, is interesting because alkylation could have occurred instead. The acid chloride is more electrophilic than the alkyl chloride in this reaction, although alkylation does occur in the next step. Notice how the lithium atom holds the molecules together during the reaction.

Even the dilithio derivatives of carboxylic acids, made by treating a carboxylic acid with two molecules of LDA, can give good reactions with acid chlorides. In these reactions it is not necessary to have a proton remaining between the two carbonyl groups of the product as the reaction is between a strong nucleophile and a strong electrophile and is under kinetic control.

It is rather more common to use enamines or silyl enol ethers in acylations with acid chlorides. These are more general methods—enamines work well for aldehydes and ketones while silyl enol ethers work for all classes of carbonyl compounds. It is possible to combine two enolizable molecules quite specifically by these methods, and we shall consider them next.

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المزيد

الآخبار التكنلوجية

هل هاتفك مراقب؟.. 5 علامات خطيرة تكشف التجسس عليك

دبي تطلق أول رحلة تجريبية للتاكسي الجوي

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المزيد

مواضيع ذات صلة

Sulfur-stabilized anions

Sulfur is a very versatile element

Symmetry in intramolecular crossed Claisen condensations

Intramolecular crossed Claisen ester condensations

Crossed Claisen ester condensations between two different esters

Claisen condensations between ketones and esters

Reactive esters that cannot enolize

The Claisen ester condensation and other self-condensations

Problems with acylation at carbon

Cross-condensations

The aldol reaction

Nitroalkanes are superb nucleophiles for conjugate addition