Chlorides, acyl reaction with ester enolates

Magnesium enolates play an important role in C-acylation reactions. The magnesium enolate of diethyl malonate, for example, can be prepared by reaction with magnesium metal in ethanol. It is soluble in ether and undergoes C-acylation by acid anhydrides and acyl chlorides (entries 1 and 3 in Scheme 2.14). Monoalkyl esters of malonic acid react with Grignard reagents to give a chelated enolate of the malonate monoanion. 

The preparation of diethyl benzoylmalonate (entry 12) represents the use of an acid anhydride, a function in which it is much more reactive than an ester, as the acylating agent. The reaction must be carried out in nonnucleophilic solvents to prevent solvolysis of the anhydride from competing with the desired reaction. Other limitations on the use of highly reactive acylating agents, such as acid anhydrides and acid chlorides, in reactions with enolates derive from the fact that O-acylation may be the dominant reaction. The magnesium salt of diethyl malonate (entries 12 and... 

The acylation of enamino ketones can take place on oxygen or on carbon. While reaction at nitrogen is a possibility, the N-acylated products are themselves acylating agents, and further reaction normally takes place. The first reported acylation of enamino ketones (72) was that of 129, prepared by acylation of the enamine (113), which was shown to have undergone O acylation because on mild hydrolysis the enol ester (130) could be isolated. A similar reaction took place with other aliphatic acid chlorides (80) and with dibasic acid chlorides [e.g., with succinyl chloride to give 118 above]. 

In summary, reactions of nitronates with acid anhydrides or acyl chlorides give the O-acylated products, and reactions with acyl imidazoles, phenyl esters, acyl nitriles, and enol-lactones gives the C-acylated products, (see Eq. 5.13).25 The C/O selectivity of nitronate acylation by RCOX is qualitatively correlated with strength (pKJ of the acid HX conjugated to the leaving group X .25... 

Acylation of ester enolates can also be carried out with more reactive acylating agents such as acid anhydrides and acyl chlorides. These reactions must be done in inert solvents to avoid solvolysis of the acylating agent. The preparation of diethyl benzoylmalonate (entry 1 in Scheme 2.14) is an example employing an acid anhydride. Entries 2-5 illustrate the use of acyl chlorides. Acylations with these more reactive compounds can be complicated by competing O-acylation. /V-Mcthoxy-iV-methylamidcs are also useful for acylation of ester enolates. 

The 3-oxo-2//-furans (260) obtained from the reaction of a-halogenoacyl halides with /3-ketonic esters at -20 °C show no tendency to enolize to the hydroxyfurans (261) but rather behave as unsaturated ketones (Scheme 71) (73RTC731). 2,4-Dialkylfurans (262) are obtained by condensation of acyl halides with allyl halides catalyzed by aluminum chloride (73KGS1434). The acid catalyzed condensation of 2-chlorocyclopentanone with dimethyl /3-oxoglutarate leads to the furan ester (263) (77JHC711). 

One preparative procedure for achieving this reaction involves the acylation of the magnesium enolate of diethyl malonate with an acid chloride in benzene solution (cf. Expt 5.96), and the resulting aclymalonic ester is then heated to 200 °C with an arylsulphonic acid to effect the decarbethoxylation step. An illustrative example is the preparation of ethyl 3-oxopentanoate (ethyl propionyl-acetate, Expt 5.177). 

Silyl enolates react with acyl cation equivalents to give the C- and/or O-acylated products (Equation (90)).333 Fluoride-catalyzed reaction using acyl fluorides is valuable for O-acylation of silyl enolates derived from aldehydes and ketones.334 CuCl also promotes the 0-acylation with acyl chlorides.335 The CuCl-promoted reaction of ester silyl enolates results in exclusive (7-acylation. Combined use of BiCfl and Znl2 (or Nal) effects catalytic (7-acylation of ketone silyl enolates with acyl chlorides. 

Carboranyl acid halides can be very easy prepared. We have studied the acylation of malononitrile and acetoacetic ester by methylcarboranyl carboxylic acid chloride (15). The reaction with malononitrile leads to the compound 17a, which exists also as a enol form, similar to compound 13. Compound 17a can be methylated to give compound 17b, a novel synthon for the preparation of wide range of heterocyclic compounds (Scheme 7). 

A reaction similar to the above involves the acylation of malonic ester through its magnesium enolate. Thus, the reaction of propionyl chloride with the ester enolate leads to diethyl propionylmalonate. Thermal decomposition of this compound with /3-naphthalenesulfonic acid yields ethyl propionylacetate (57%). This modification appears to be general in that it has been extended to the use of aliphatic, aromatic, and car-balkoxy acyl chlorides. ... 

Synthesis of trifluoromethylated compounds 152 has been achieved via ester-enolate [2,3]-Wittig and [3,3]-lreland-Claisen rearrangements. Perfluorocyclo-butane phosphonium ylides, e.g. 153, have been used as a masked fluoride anion source in their reactions with alcohols and carboxylic acids which lead to alkyl-and acyl-fluorides. Ylides 153 are also reported to cleave Si-C and Si-O bonds, cause dimerisation of fluoro-olefins, and also react with acid chlorides or other activated aromatic compounds under halogen exchange. ... 

Silyl alkyl ketene acetals, as ester enolate equivalents, are capable of regioselective acylation by acid chlorides. Rathke and Sullivan showed that a variety of acid chlorides reacted with the acetal (3) to give protected -keto esters (Scheme 11). Acid hydrolysis of the silylated products gave the free -keto ester. The reaction was successful with a variety of acyl chlorides, including acetic, butanoic, (2 )-buten-... 

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