Acyloin oxidation

When the hydroxyJic group is in an a position with respect to the keto group, as in acyloins, oxidation to a-diketones is easily accomplished by many oxidants. 

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... 

Acyloins are useful starting materials for the preparation of a wide variety of heterocycles (e.g., oxazoles and imidazoles ) and carbocyclic compounds (e.g., phenols ). Acyloins lead to 1,2-diols by reduction, and to 1,2-diketones by mild oxidation. 

Tropolone has been made from 1,2-cycloheptanedione by bromination and reduction, and by reaction with A -bromosuccinimide from cyolo-heptanone by bromination, hydrolysis, and reduction from diethyl pimelate by acyloin condensation and bromination from cyclo-heptatriene by permanganate oxidation from 3,5-dihydroxybenzoic acid by a multistep synthesis from 2,3-dimethoxybenzoic acid by a multistep synthesis from tropone by chlorination and hydrolysis, by amination with hydrazine and hydrolysis, or by photooxidation followed by reduction with thiourea from cyclopentadiene and tetra-fluoroethylene and from cyclopentadiene and dichloroketene. - ... 

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. ... 

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 addition of any one of several dialkyl chlorophosphates to an arylalkyne-derived vinyl zirconocene in the presence of catalytic amounts of CuBr in THF leads to the corresponding vinyl phosphonate in high yields (78—92% see, for example, Scheme 4.38) [25]. Here, alkyl-substituted acetylenic starting materials do not react beyond the initial hydrozirconation stage. Vinyl phosphonates may be readily converted to acyloins by oxidation to the diol followed by base-induced cleavage. 

Asymmetric microbial acyloin condensation, 16 402 Asymmetric oxidation, 23 735 Asymmetric ring-closing metathesis (ARCM), 26 922... 

Preparation and phytochemical reduction of 2,2 -thenoin and 2,2 -thenil have been studied in the authors laboratory (20a). It has been shown that 2,2 -thenoin gives a color reaction similar to that shown by benzoin and other acyloin condensation products in- the presence of alcoholic alkali. The hydroxy ketone may be oxidized by iodine in the presence of sodium methoxide to give the diketone, 2,2 -thenil, in excellent yields. Phytochemical reduction was shown also to be applicable to both compounds. It is significant that thenoin differs from benzoin, since reduction products were not obtained enzymatically from the latter. 

In the course of biogenesis-type syntheses of lupin alkaloids, reduction of protected macrocyclic acyloin 50 (Scheme 15) has been found to be a second route to bicyclic aminoalcohol 14a (69JA7372). Another 11-membered ring compound, namely caprinolactam (51), on anodic oxidation in the presence of halide ions produces 6/7 bicyclic lactam 52 together with two isomeric 5/8 bicyclic lactams (87CJC2770). 

When heated with trimethyloxonium fluoroborate in 1,1-dichloroethane, dilactone 842 experiences cleavage of both lactone rings to give a mixture of diene diesters, catalytic reduction of which produced 853 Reductive methylation of 853 proceeded with installation of the methyl groups on the exterior face for obvious steric reasons. Acyloin condensation followed by ferric cloride oxidation furnished a-diketone 854 which proved to be highly responsive to photoexcitation. However, irradiation of 854 did not provide 855 as expected. Rather, a most unusual reaction pathway was followed to deliver diol 856. 

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... 

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