Oxidation of Acyloins

A solution of bismuth trioxide in hot glacial acetic acid provides a specific method for the oxidation of acyloins. " The reaction rate is dependent on the steric accessibility of the ketol system. A 2,3-ketol requires less than one hour for completion but an 11,12-ketol is not yet fully oxidized in thirty hours." The reaction is highly selective as a-keto acids, hydrazines and phenols are not oxidized. In a direct comparison with cupric acetate, this procedure is somewhat superior for the preparation of a 2,3-diketone from a 2-keto-3-hydroxy steroid. ... 

Cupric acetate is also used for oxidations of acyloins. Diphenylacetoin is converted almost quantitatively into dibenzylglyoxal when refluxed with cupric acetate in 70% acetic acid for 7 min [353]. Sebacoin (2-hydroxy-cyclodecanone) gives sebacil in 88-89% (equation 449) yield [359]. 

The oxide is a specific reagent for oxidation of acyloins to a-diketones, the oxide being reduced to the metal. A solution of the acyloin in acetic acid is treated with 1.2 times the theoretical amount of BijOj and the mixture is heated on the steam bath with stirring for about 15 min. Benzoin—> benzil (95% yield). 12-Hydroxy-11-ketosteroids —> 11,12-diketosteroids (70% yield)." Oxidation of cevine and isomers." Other examples are the oxidation of 2-hydroxypulegone (I) to diosphenolone (2) in 94%i yield (crude), of Ihe 2 -hydroxy-A -3-ketosteroid (3) to (4)," and of (5) to (6)."... 

Oxidation of acyloins to a-diketones with bismuth oxide [51JCS793]... 

Oxidation of acyloins to diketones with bismuth oxide typical procedure... 

Out first example is 2-hydroxy-2-methyl-3-octanone. 3-Octanone can be purchased, but it would be difficult to differentiate the two activated methylene groups in alkylation and oxidation reactions. Usual syntheses of acyloins are based upon addition of terminal alkynes to ketones (disconnection 1 see p. 52). For syntheses of unsymmetrical 1,2-difunctional compounds it is often advisable to look also for reactive starting materials, which do already contain the right substitution pattern. In the present case it turns out that 3-hydroxy-3-methyl-2-butanone is an inexpensive commercial product. This molecule dictates disconnection 3. Another practical synthesis starts with acetone cyanohydrin and pentylmagnesium bromide (disconnection 2). Many 1,2-difunctional compounds are accessible via oxidation of C—C multiple bonds. In this case the target molecule may be obtained by simple permanganate oxidation of 2-methyl-2-octene, which may be synthesized by Wittig reaction (disconnection 1). 

Butyroin has been prepared by reductive condensation of ethyl butyrate with sodium in xylene, or with sodium in the presence of chloro-trimethylsilane. and by reduction of 4,5-octanedlone with sodium l-benzyl-3-carbamoyl-l,4-dihydropyridine-4-sulfinate in the presence of magnesium chloride or with thiophenol in the presence of iron polyphthalocyanine as electron transfer agent.This acyloin has also been obtained by oxidation of (E)-4-octene with potassium permanganate and by reaction of... 

Spiro compound (18), also containing two fIve-membered rings, can be made by oxidation of the acyloin (19) (Chapter T24). 

Scheme 12.2 shows various types of alcohols that are most susceptible to Mn02 oxidation. Entries 1 and 2 illustrate the application of MnOz to simple benzylic and allylic alcohols. In Entry 2, the Mn02 was activated by azeotropic drying. Entry 3 demonstrates the application of the reagent to cyclopropylcarbinols. Entry 4 is an application to an acyloin. Entry 5 involves oxidation of a sensitive conjugated system. 

The method was used for oxidation of an unsaturated nitrile (1) to an aromatic acyloin (2) in a projected synthesis of a model for olivin (4), an aglycone of olivomycin antibiotics.2... 

Regioselective oxidation of 1,2-diols.1 The oxidation of di-secondary glycols to acyloins (5, 188) can be extended to oxidation of other glycols. Thus the stan-nylene of 1 is oxidized by bromine to 2 in high yield. The reaction is regioselective with unsymmetrical diols (3 — 4). 

Internal alkynes are oxidized to acyloins by thaUium(IU) in acidic solution (A. McKil-lop, 1973 G.W. Rotermund, 1975) or to 1,2-diketones by permanganate or by in situ generated ruthenium tetroxide (D.G. Lee, 1969, 1973 H. Gopal, 1971). Terminal alkynes undergo oxidative degradation to carboxylic acids with loss of the terminal carbon atom with these oxidants. 

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... 

Acyloins have also been employed extensively as starting materials for the synthesis of imidazoles, usually in the presence of added aldehyde (or acid) and using ammoniacal cupric acetate to oxidize the acyloin to the corresponding a-dicarbonyl compound.24 Alicyclic and aromatic ketols and ketol acetates in an alcoholic solution of cupric acetate and ammonia undergo ring closure to the corresponding 2-imidazoyl ketones. Hence, benzoyl carbinol refluxed for 1 hour in... 

Despite this, some useful oxidations have been achieved using the method, such as that of yohimbine to yohimbinone in 85% yield, which compares well with that achieved by using dimethyl sulfoxide activated with dicylohexylcarbodiimide. The method has also been successfully applied to the oxidation of carbohydrates, as shown by the formation of (11 equation 6), and aromatic a-diketones can be efficiently prepared using this method by oxidation of the corresponding acyloin products. Unfortunately this methodology cannot be extended to the more useful aliphatic diketones. ... 

Krebs and coworkers have synthesized 3,3,6,6-tetramcthyl-l-thiacycloheptyne (55) . The thiacycloheptanedione (53) derived from the corresponding acyloin was converted into the bishydrazone (54). Oxidation of 54 with mercury(ii) oxide gave 55 in 5-5% yield together with the ew-olefin (56, 6-9%). In the absence of oxygen... 

Copper sulfate, CuS04 5H20, is used for the oxidative coupling of terminal acetylenes [5S] for the conversion of a-hydroxy ketones (acyloins) into a-diketones [351, 352] and, in cooperation with potassium peroxy-disulfate, for the selective oxidation of methyl groups on benzene rings to aldehyde groups [355],... 

Copper acetate, Cu(OCOCHj)2 or Cu(0C0CH3)2 H20, resembles copper sulfate in its oxidizing properties and is used for the oxidative coupling of terminal acetylenes [53, 357] and for the conversion of acyloins into a-diketones [353, 359]. Its presence favorably affects the acetoxylation of toluenes to benzyl acetates by sodium persulfate [360]. 

Sodium bromate, NaBrOs, a white crystalline compound, converts acyloins into a-diketones under forcing conditions [740]. More often, this reagent is used as a reoxidant of ammonium cerium nitrate [421], cerium sulfate [741], or ruthenium trichloride [741] in oxidations of alcohols to aldehydes [421] or carboxylic acids [741]. 

The oxidative cleavage of carbon-carbon bonds in vicinal diols [756, 759] is a reaction widely used in saccharide chemistry. Besides its application in this reaction, periodic acid achieves the oxidative coupling [757] or oxidation to quinones [758] of polynuclear aromatic hydrocarbons, the oxidation of methyl groups in aromatic compounds to carbonyl groups [760], the conversion of epoxides into dicarbonyl compounds [761], and the oxidative cleavage of trimethylsilyl ethers of acyloins to carboxylic acids [755]. 

A very suitable oxidant for the conversion of acyloins into a-diketones is ammonium nitrate in the presence of catalytic amounts of cupric acetate. This reagent converts benzoin into benzil in 90% yield [476], The same result is obtained with bismuth sesquioxide 481] and sodium bromate 740 (equation 450). On the other hand, ceric ammonium nitrate does not give benzil but cleaves the bond between the alcoholic and the keto groups and cleaves benzoin into benzaldehyde and benzoic acid [425]. 

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