Acylation of enolates

Sekine, M., Kume, A., Nakajima, M., and Hata, T., A new method for acylation of enolates by means of dialkyl acylphosphonates as acylating agents, Chem. Lett., 1087, 1981. 

Acylation of enol ethers. Reaction of 1 with ethyl vinyl ether in ether provides an intermediate that undergoes dehydrochlorination when heated to provide the trichloromethyl ketone 2, which is converted by base (haloform reaction) to the ester 3 in high yield. 

Now this is exactly the same situation we encountered when we compared the reactivity of aldehydes and ketones with that of carboxylic acid derivatives (see Section 7.8). The net result here is acylation of the nucleophile, and in the case of acylation of enolate anions, the reaction is termed a Claisen reaction. It is important not to consider aldol and Claisen reactions separately, but to appreciate that the initial addition is the same, and differences in products merely result from the absence or presence... 

Anions derived from malonates are ambident nucleophiles, which can react at the carbon or oxygen atom. Therefore, carbon-carbon bond-forming reactions by alkylation or acylation of enolates have been encountered with difficulties. Side reactions which may cause problems are the above-mentioned competiting O-reaction and dialkylation . 

So what is new here We can save time, materials and effort if we combine two reactions in one operation. These tandem processes, as they are called, avoid the isolation of potentially difficult intermediates and may avoid the need for control over reactions in chapter 19 we discussed the need for control in the acylation of enolates. Workers at Merck1 combined the difficult acylation of enolates 7 by acid chlorides with the capture of the intermediates 9 by hydrazine to give stable pyrroles 10. This is a summary of their method ... 

T. H. Black, Recent Progress in the Control of Carbon Versus Oxygen Acylation of Enolate Anions , Org. Prep. Pmced. Int. 1988, 21, 179-217. 

The combination of fluoride ions and enol silyl ethers provides a useful method for the generation of enolate anions [9]. Watts, Haswell and coworkers applied a borosilicate glass microreactor, having channel dimensions of 100 pm x 50 pm and equipped with an electrosmotic flow (EOF) pumping system, to the C-acylation of enolate anions, which leads to 1,3-diketones [10,11]. A THF solution of tetrabutyl-ammonium fluoride (TBAF) was placed in reservoir A, a THF solution of benzoyl... 

We have spent some considerable time and effort in understanding the aldol reaction simply because it is one of the most important reactions in organic chemistry. In the next chapter you will see how these ideas can be extended with almost no addition of principles to the acylation of enolates—the reaction of enols, enolates, and specific enol equivalents with acid chlorides and esters. We hope that you will see that the ideas introduced in this chapter find immediate application in the next. 

The main problem with the acylation of enolates is that reaction tends to occur at oxygen rather than at carbon. 

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