A-Ketol ester

The decarboxymethylation of substituted o -hydroxy-o -carbomethoxy hexacyclic substituted ketones (43), one of these used as an advanced intermediate in the synthesis of the alkaloid aspidophytine, can be effected by heating with Mgl2 in CH3CN in good yields (75-84%) (Scheme 12).34 The reaction was shown to proceed through a novel a-hydroxy /3-dicarbonyl to a-ketol ester rearrangement mechanism, which is supported by the isolation of the carbonate (45) intermediate. 

The use of a-ketol esters with formamide has been reported by Novelli and de Santis72 for the synthesis of oxazoles and imidazoles. It appears that in this case the reaction proceeds through reaction of the oxazole with formamide. The a-ketol esters are prepared by treating the corresponding a-bromoketones with the potassium salt of the appropriate carboxylic acid. 

Whereas a-amino ketones readily form imidazoles with formamide, they are often not easy to prepare. Accordingly, they can be replaced by precursors, a-oximino ketones, which can be reduced either by dithionite or using catalytic mehods in formamide at 70-100 °C. Ring closure can then be achieved by raising the temperature (Scheme 80). When a-ketol esters are used it appears that the imidazole formation may in this instance proceed by way of the oxazole. A further special case is the formation of 4,5-disubstituted imidazoles from 1-chloro-l,2-epoxides and formamide. One recent example of an application of Bredereck s method is the synthesis of the imidazolepropanol (144) from 3-bromo-2-methoxytetra-hydropyran (Scheme 81) (80AHC(27)241). 

Oxidative cleavage of a-ketols. Esters of dicarboxylic acids are formed when the ketols are treated with VOCOEtljCl under oxygen in ethanol. 

Several recent patents42 127 128 describe the preparation of 4,5-disubsti-tuted oxazole-2-yl alkanoic acids (58) by the reaction of an a-ketol ester with urea in acetic acid or by acetylation of an a-ketol with a cyclic anhydride followed by refluxing with ammonium acetate in acetic acid. 

A further general route to the 1,2-dicarbonyl system involves the oxidation of a-ketols (acyloins) (cf. the preparation of benzil from benzoin, Expt 6.143). The acyloins may be prepared from carboxylate esters by a radical coupling reaction involving the use of finely divided sodium metal in anhydrous ether, benzene, or toluene.144... 

In the presence of a tertiary amine, particularly DABCO, S,S -diethyl dithiomalon-ate undergoes 1,4-addition to 2,/ -enones and a,/ -unsaturated esters that are not disubstituted in the /(-position. The products are reduced by acid-washed Raney nickel to 1,5-ketols and 5-hydroxy esters.2... 

Generally speaking the classical alkaline hydrolysis reaction followed by back-titration could be used to determine steroid esters. The results for 21-acyloxycortico-steroids (where R = H, OH) are however quite unsatisfactory. The reason behind the unacceptable result is the auto-oxidation of the a-ketol side-chain in an alkaline medium. Because of the formation of acidic products in side reactions, there is an over consumption of base in the titration and a corresponding over determination of the amount of steroid. 

The asymmetric variant of a-oxybenzoylation makes use of lithioenamines. Lithioena-mines formed with / -ketoesters and ( S)-valine f-butyl ester were in fact easily oxidized with benzoyl peroxide53 with high enantioselectivity (78-92% e.e.) to give, after hydrolysis, the corresponding protected tertiary a-ketols having (i ) configuration (Scheme 36). 

An interesting effect of light intensity has been observed in the reaction of bicyclo[2.2.2]octanedione 170) with aromatic aldehydes 140). These reactions produced esters of a-ketols 171) and labile a-aroyl-a-hydroxyketones 172). At first... 

The biogenesis of solerone 1 and related compounds was successfully rationalized by biomimetic model reactions. As key step we established the pyruvate decarboxylase catalyzed acyloin condensation of pyruvic acid with ethyl 4-oxobutanoate 4 or ethyl 2-oxoglutarate 3 with acetaldehyde. The importance of the ethyl ester function in 3 and 4 serving as substrates for the enzymatic formation of a-hydroxy ketones 5 and 6 was demonstrated. The identification of six yet unknown sherry compounds including acyloins 5 and 6, which have been synthesized for the first time, confirmed the relevance of the biosynthetic pathway. Application of MDGC-MS allowed the enantiodifferentiation of a-ketols and related lactones in complex sherry samples and disclosed details of their biogenetic relationship. 

Reductive cleavage of a-ketol acetates can also be effected in moderate yield by Fe(CO)s. Ketones, esters and alkenes are unreactive toward this reagent. 

Oxiranes can be converted to dialdehydes with hydrogen peroxide in the presence of a boric acid ester or phosphoric acid ester.The base-catalyzed oxidation of oxirane and alkyl-substituted oxiranes with fcA-r-butylhydroperoxide has been reported. With increased substitution the molecule undergoes fragmentation. With DMSO in the presence of terf-butylhydroperoxide and strong acids, a-ketols are formed via a sulfonium salt (Eq. 156). ... 

The electrochemical deprotection of carbonyl compounds proved to be a useful method especially in cases where alternative chemical reactions are unsuccessful, a-Keto- and a-hydroxythioacetals, when oxidized in MeCN-HoO (9 1 v/v) on a Pt anode, are transformed into the corresponding a-diones and a-ketols [142]. Diethyl dithioacetals of sugars were anodically oxidized in MeCN-H20 (5% H2O) on Pt electrode, and the substrates were successfully deprotected producing the correspondent carbohydrates in 65-85% yield [143]. It is noteworthy that protected hydroxy groups as esters or cyclic acetals were not affected. Selective deprotection to carbonyl compounds electrooxidizing mixtures of thioacetals, like a ketone and an aldehyde thioacetal, the former being preferentially deprotected, was described [144]. 

The reaction of alkenes with alkaline potassium permanganate proceeds rapidly via formation of a cyclic manganese ester, which is hydrolyzed to the 1,2-diol. To avoid overoxidation to an acyloin (a-ketol), the pH of the reaction medium has to be monitored. Although the yields of cA-diols obtained are usually modest ( 50%), the procedure is less hazardous and much less expensive than using osmium tetroxide and thus is well suited for large-scale preparations. Improved yields of diols are obtained when the oxidation is carried out in water in the presence of a phase transfer agent such as benzyltriethylammonium chloride. 

Keto esters, 230-231 d-Keto esters, 127, 311 7-Keto esters, 229 Ketolactones, 420 a-Ketols, 426,530 d-Ketols, 141 y-Ketols, 141 7-Ketonitriles, 447 Ketonitrones, 281 5-Keto-l-nonene, 572... 

A Favorskii-like intermediate (655), and the rearranged product (657), arise in a novel way from fragmentation of the a-ketol enol-sulphite (654). Loss of sulphur dioxide is thought to afford the zwitterion (655), which gives the methoxy-ketone (656) in methanol, but the A-nor carboxylic ester (657) with sodium methoxide in ether. ... 

V-Bromosuccinimide. 13, 49 14, 57-58 I 0 Deprotection. Free-radical-initiatc< water removes a benzyl ester. A similar metl Regioselective oxidations. An alkaix give the ketol (instead of the hydroxy aldch] nvlene acetal. ... 

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