Carboxylic esters acyloin condensation

Upon heating of a carboxylic ester 1 with sodium in an inert solvent, a condensation reaction can take place to yield a a-hydroxy ketone 2 after hydrolytic workup. " This reaction is called Acyloin condensation, named after the products thus obtained. It works well with alkanoic acid esters. For the synthesis of the corresponding products with aryl substituents (R = aryl), the Benzoin condensation of aromatic aldehydes is usually applied. 

In this section primarily reductions of aldehydes, ketones, and esters with sodium, lithium, and potassium in the presence of TCS 14 are discussed closely related reductions with metals such as Zn, Mg, Mn, Sm, Ti, etc., in the presence of TCS 14 are described in Section 13.2. Treatment of ethyl isobutyrate with sodium in the presence of TCS 14 in toluene affords the O-silylated Riihlmann-acyloin-condensation product 1915, which can be readily desilylated to the free acyloin 1916 [119]. Further reactions of methyl or ethyl 1,2- or 1,4-dicarboxylates are discussed elsewhere [120-122]. The same reaction with trimethylsilyl isobutyrate affords the C,0-silylated alcohol 1917, in 72% yield, which is desilylated to 1918 [123] (Scheme 12.34). Likewise, reduction of the diesters 1919 affords the cyclized O-silylated acyloin products 1920 in high yields, which give on saponification the acyloins 1921 [119]. Whereas electroreduction on a Mg-electrode in the presence of MesSiCl 14 converts esters such as ethyl cyclohexane-carboxylate via 1922 and subsequent saponification into acyloins such as 1923 [124], electroreduction of esters such as ethyl cyclohexylcarboxylate using a Mg-electrode without Me3SiCl 14 yields 1,2-ketones such as 1924 [125] (Scheme 12.34). 

Carboxylic esters react with sodium metal to give a-hydroxy ketones (often referred to as acyloins). The reaction, known as the acyloin condensation, is thought to proceed by the mechanism shown in Figure Si3.13. 

Fig. 17.59. Reduction of a carboxylic ester with dissolving sodium. Branching of the reduction paths in the presence (Bouveault-Blanc reduction) and absence (acyloin condensation) of protons.

Fadel, A., Canet, J. L., Salaun, J. Ultrasound-promoted acyloin condensation and cyclization of carboxylic esters. Syn/eff 1990, 89-91. 

Acyloin condensation. The usual preparation of acyloins from aliphatic esters is not applicable to aromatic esters. In this case the reaction with sodium results in formation of the sodium carboxylate and a radical from the R group which undergoes further reactions. However, benzoin can be prepared in moderate yield by treatment of the trimethylsilyl ester of benzoic acid with sodium or by treatment of ethyl benzoate with sodium naphthalenide in THF at room temperature (397 yield). ... 

Carboxy-4-methyl-5-pentyl-2-furanpropanoic acid (273), isolated from blood and urine, is a hitherto unknown class of metabolic compound. The structure of (273) has recently been confirmed by synthesis (80CB699). 2,4,5-Trialkyl substituted furan-3-carboxylic acids have been synthesized from acyloin and /3-ketoesters by treatment with zinc chloride. By analogy with this synthetic route, the reaction of acetoin with 3-oxoadipic acid dimethyl ester was found to yield the 2,3-dimethylfuran (274). The dimethyl ester (275) was prepared by condensation of 3-chloro-2-octanone with 3-oxoadipic acid dimethyl ester and was shown to be identical with the dimethyl ester of the natural product. 

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