Diketones hydroxy ketones

This chapter explores several different carbon-carbon bond-forming reactions that lead to a variety of functionalized molecules diketones, hydroxy-ketones and hydroxy-aldehydes, keto-esters, keto-aldehydes, keto-nitriles, cyano-esters, hydroxy-nitriles, and cyano-aldehydes and cyano-ketones. The reactions that form these products may be categorized by defining the relevant disconnection. 

The above appears to be a general reaction for converting a-hydroxy ketones into diketones in excellent yield thus furoin and anisoin give furil and anisil respectively. The reaction is probably ... 

The rt,/3-unsaturated linear carbonyl compound 39 is obtained by the decomposition of the cyclic hydroperoxide 38 with PdCl2,[35]. The a, 0-epoxy ketone 40 is isomerized to the /3-diketone 41 with Pd(0) catalyst[36]. The 1,4-epiperoxide 42 is converted into the /3-hydroxy ketone 43 and other products[37]. 

DMSO, molybdenum peroxide, benzene, reflux, 7-20 h, 60% yield. This method was used to m onoprotect 1,2-diols. The method is not general because oxidation to a-hydroxy ketones and diketones occurs with some substrates. On the basis of the mechanism and the results it would app>ear that overoxidation has a strong conformational dependence. 

For the mechanistic course of the reaction the diketone 5 is assumed to be an intermediate, since small amounts of 5 can sometimes be isolated as a minor product. It is likely that the sodium initially reacts with the ester 1 to give the radical anion species 3, which can dimerize to the dianion 4. By release of two alkoxides R 0 the diketone 5 is formed. Further reaction with sodium leads to the dianion 6, which yields the a-hydroxy ketone 2 upon aqueous workup ... 

Metals in Water or Alcohol. A single carbonyl group of an a-diketone can be reduced (to give an a-hydroxy ketone) by heating with zinc powder in... 

Certain ketoximes can be converted to nitriles by the action of proton or Lewis acids. Among these are oximes of a-diketones (illustrated above), a-keto acids, a-dialkylamino ketones, a-hydroxy ketones, p-keto ethers, and similar compounds. These are fragmentation reactions, analogous to 17-25 and 17-26. For example, ot-dialkylamino ketoximes also give amines and aldehydes or ketones besides nitriles. 

Cyclic 1,2-diamines are cleaved to diketones with dimethyl dioxirane. a-Diketones and a-hydroxy ketones are also cleaved by alkaline H202. HIO4 has... 

Products detected or isolated from these oxidations include the corresponding a-hydroxy ketone and a-diketone and also adipic acid (from cyclohexanone) in up to 95 % yield. However, IrCI gives a-chloroketone in quantitative yield . Evidently when the rate of oxidation exceeds enolisation attack is on the keto form, probably via a complex, although this is definite only for Ce(IV) perchlorate, to give a radical, e.g. 

A key step in the approach to 3(2//)-furanone ring systems via the acid-catalyzed cyclization-dehydration of appropriately substituted a -hydroxy-l,3-diketones involves the acylation of a-hydroxy-ketone dianions 11141... 

Literature search showed the dihydro-chromandione motif in 53, or other related system, is relatively unknown and/or under-investigated, and the proposed conjugate reduction to this system was unprecedented. Fortuitously, our attempt employed NaBH4 in MeOH at 0 °C, and while a new spot was rapidly produced, the conversion was slow. When the solution was warmed to ambient temperature and additional aliquots of NaBH4 were added, a mixture of diketone 55 and hydroxy ketone 56 was isolated. In subsequent trials, 55 could be reduced cleanly to 56 especially at elevated temperatures. 

Symmetrical and unsymmetrical benzoins have been rapidly oxidized to benzils in high yields using solid reagent systems, copper(II) sulfate-alumina [105] or Oxone-wet alumina [105, 106] under the influence of microwaves (Scheme 6.32). Conventionally, the oxidative transformation of a-hydroxy ketones to 1,2-diketones is accomplished by reagents such as nitric acid, Fehling s solution, thallium(III) nitrate (TTN), ytterbium(III) nitrate, ammonium chlorochromate-alumina and dayfen. In addition to the extended reaction time, most of these processes suffer from drawbacks such as the use of corrosive acids and toxic metals that generate undesirable waste products. 

The scope of the reaction was considerably enlarged in 1935, when Clutterbuck and Reuter6 observed that the compound tetrahydroterrein, derived from the mold metabolite terrein, consumes more than the calculated amount of periodate per mole. They found that 1,2-diketones and a-hydroxy ketones are also oxidized under the conditions used by Malaprade. Although this type of oxidation had been earlier noted [in a study7 of the action of periodate on 1,3-dihydroxy-2-propanone (dihydroxyace-tone)], Clutterbuck and Reuter made a more thorough exploration of the reaction.6 In a series of model compounds, Ri and R2 were varied from... 

In the hydrogenation of diketones by Ru-binap-type catalysts, the degree of anti-selectivity is different between a-diketones and / -diketones [Eqs (13) and (14)]. A variety of /1-diketones are reduced by Ru-atropisomeric diphosphine catalysts to indicate admirable anti-selectivity, and the enantiopurity of the obtained anti-diol is almost 100% (Table 21.17) [105, 106, 110-112]. In this two-step consecutive hydrogenation of diketones, the overall stereochemical outcome is determined by both the efficiency of the chirality transfer by the catalyst (catalyst-control) and the structure of the initially formed hydroxyketones having a stereogenic center (substrate-control). The hydrogenation of monohydrogenated product ((R)-hydroxy ketone) with the antipode catalyst ((S)-binap catalyst) (mis-... 

Two-step asymmetric hydrogenation of (3-diketones shows that the overall stereochemistry is determined by the catalyst and by the chirality of the intermediate hydroxy ketone. Thus partial hydrogenation of acetylacetone (2) catalyzed by Ru-... 

Stereoselective hydrogenation ofl -diketones. Hydrogenation of 1,3-alkane-diones catalyzed by Ru2Cl4[(R)-l][N(C2H5)3] results in anf/-l,3-diols with high dias-tereoisomeric and enantiomeric excesses (equation I). Under the same conditions l-phenyl-l,3-butanedione (2) is reduced mainly to the (3-hydroxy ketone 3 in 98%... 

Oxidation of p-hydroxy ketones. Reaction of the Corey-Kim reagent with these substrates can result in dimethylsulfonium dicarbonylmethylides in 80-98% yield. These S-ylides are desulfurized to p-diketones by zinc in acetic acid, p-... 

Hydroxy ketones that are mono- or disubstituted at the a-position are oxidized directly to 1,3-diketones by the reagent in moderate to good yield. 

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. 

Utsukihara, T., Nakamura, H., Watanahe, M. and Horiuchi, C.A., Microwave-assisted synthesis of a-hydroxy ketone and a-diketone and pyrazine derivatives from a-halo and a,a -dibromo ketone. Tetrahedron Lett., 2006, 47, 9359. 

The ketone 73 was reduced chemo- and diastereoselectively and protected to provide the silyl ether 74. The ester function was then deprotonated to the corresponding ester enolate (75) that was alkylated with methyl iodide exclusively from the Re face of the enolate to afford the bicycle 76 (Scheme 11). The substrate for the retro-aldol reaction (77) was prepared by a sequence that consists of seven functional and protecting group transformations. The retro-aldol reaction converted the bicyclic yS-hydroxy ketone 77 into the 1,3-diketone 69 via the alkoxide (78) in very good yield. 

The reduction of diketones is very complex. They can be partially reduced to ketols (hydroxy ketones) or ketones, or completely reduced to hydrocarbons. Depending on the mutual distance of the two carbonyl groups and reagents used, carbon-carbon bond cleavage may occur and may be followed by recyclizations or rearrangements. Some reactions may result in the formation of alkenes. Quinones react in their own specific way. 

Reduction of diketones to either hydroxy ketones or diols can be accomplished by different biochemical reductions [327, 834] Procedure 50, p. 218). 

The Clemmensen reduction of j8-diketones (1,3-diketones) is rather complicated. The first step in the reaction of 2,4-pentanedione with zinc amalgam is an intramolecular pinacol reduction leading to a cyclopropanediol. Next the cyclopropane ring is opened in the acidic medium, and a rearrangement followed by a reduction gives the final product, a ketone, with a changed carbon skeleton [924, 925]. The ketone is usually accompanied by small amounts of the corresponding hydrocarbon [924] or an a-hydroxy ketone [925]. 

Table 20 Reduction of hydroxy ketones, diketones and quinones...

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