Metal enolates acyl halides

It is this equilibrium which renders difficult the explanation of the course of the reactions which take place when metallic sodium or sodium ethoxide and then alkyl or acyl halide are added to these compounds. At first it was thought that the sodio compound formed with acetoacetic ester was CH3.CO.CHNa.COOC2H5, because the reaction with alkyl and acyl halides always yielded a C-derivative, CH3.CO.CHR.COOC2H5. The first example of a different course of reaction was found in the formation of an O-derivative—/3-carhethoxyhydroxycrotonic ester from sodio-acetoacetic ester and chloroformic ester (J. pr., [2], 37, 473 B., 25,1760 A., 277, 64). This could only be explained by assigning an enol formula to the sodium salt—... 

The insight that zinc ester enolates can be prepared prior to the addition of the electrophile has largely expanded the scope of the Reformatsky reaction.1-3 Substrates such as azomethines that quaternize in the presence of a-halo-esters do react without incident under these two-step conditions.23 The same holds true for acyl halides which readily decompose on exposure to zinc dust, but react properly with preformed zinc ester enolates in the presence of catalytic amounts of Pd(0) complexes.24 Alkylations of Reformatsky reagents are usually difficult to achieve and proceed only with the most reactive agents such as methyl iodide or benzyl halides.25 However, zinc ester enolates can be cross-coupled with aryl- and alkenyl halides or -triflates, respectively, in the presence of transition metal catalysts in a Negishi-type reaction.26 Table 14.2 compiles a few selected examples of Reformatsky reactions with electrophiles other than aldehydes or ketones.27... 

The use of 0-metallation of alcohols or enols to enhance their reactivity towards electrophiles, such as aldehydes or alkyl or acyl halides has been reported by Davies.The reaction of triorganotin alkoxides with other polar multiply-bonded acceptors was also reported (Scheme 6.3.8). 

Cyclic cobalt-acyl complexes can be deprotonated, and subsequent reaction of these enolates with aldehydes gives predominantly the anti/threo product (Scheme 63). Rhenium-acyl complexes can be deprotonated in the same manner. These lithium enolates can be alkylated or can react with [M(CO)5(OTf)] (M = Re, Mn) to give the corresponding enolates (Scheme Many transition metal enolates of type (21) or (22) are known, - but only a few have shown normal enolate behavior , e.g. aldol reaction, reaction with alkyl halides, etc. Particularly useful examples have been developed by Molander. In a process analogous to the Reformatsky reaction, an a-bromo ester may be reduced with Smia to provide excellent yields of condensation products (Scheme 65) which are generated through intermediacy of a samarium(III) enolate. ... 

The Use of Acyl Halides or Anhydrides is more satisfactory than that of metallic sodium since the enolic forms of most aldehydes and ketones are not detected by these reagents. 

Treatment of lithium enolate species, such as 7, with a variety of metal halide species produces enolates with different reactivities in particular, diethylaluminum(IH) and copper(I) species have been found to profoundly alter stereodifferentiation in reactions of iron acyl enolates (see Section D.1.3.4.2.5.1.). It has not been established whether complex formation or discrete ti ansmetalation occurs usually, a temperature increase from — 78 °C to — 42 °C is required for maximum effect, suggesting that cation exchange is responsible. In some cases, such additives exert an influence at —78 °C13, and this has been attributed to simple Lewis acid-type interactions with the substrate instead of transmetalation of the enolate species. For simplicity, when such additives are allowed to react with enolate species at temperatures of — 42 =C and above prior to the addition of other reagents, the process shall be referred to as transmetalation. 

While most of the chemistry discussed in this chapter has been developed in the past decade, several important methods have withstood the test of time and have made important contributions in areas such as natural product synthesis. Methods such as cuprate acylation and the addition of organolithiums to carboxylic acids have continued to enjoy widespread use in organic synthesis, whereas older methods including the reaction of organocadmium reagents with acid halides, once virtually the only method available for acylation, has not seen extensive utilization recently. In the following discussion, we shall be interested in cases where selective monoacylation of nonstabilized carbanion equivalents has been achieved. Especially of concern here are carbanion equivalents or more properly organometallics which possess no source of resonance stabilization other than the covalent carbon-metal bond. Other sources of carbanions that are intrinsically stabilized, such as enolates, will be covered in Chapter 3.6, Volume 2. 

Carbonyl compounds can also act as electrophiles to trap the intermediate enolates, and some complementary three-component coupling processes have been developed including halides [62] or metal hydrides [63] as nucleophiles for the Michael initiation step. An interesting example concerns the addition of a borosilane derivative 50 to a,p-unsaturated A-acyl oxazolidin-2-ones 58 in the presence of an aromatic... 

---