Of a-hydroxy ketones

Treatment of a-hydroxy-ketones or -aldehydes with ammonium acetate (65BSF3476, 68BSF4970) results in the formation of dihydropyrazines, presumably by direct amination of the hydroxyketone followed by self-condensation (79AJC1281). Low yields of pyrazines have been noted in the electrolysis of ketones in admixture with KI and ammonia, and again it appears probable that the a-aminoketone derived by way of the a-iodoketone is the intermediate (69CI(L)237>. 

Whereas condensation of a-hydroxy ketones such as benzoin and acetoin on heating with formamide [240] or ureas in acetic acid [239, 242] to form imidazoles such as 769 or 770 is a well known reaction, only two publications have yet discussed the amination of silylated enediols, prepared by Riihlmann-acyloin condensation of diesters [241], by sodium, in toluene, in the presence of TCS 14 [241, 242]. Thus the silylated acyloins 771 and higher homologues, derived from Riihl-... 

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... 

DKR of a-hydroxy ketones with Shvo s catalyst (racemization) and lipase TL (esterification) Lipase encapsulated by silicone elastomer spheres... 

The oxidation of enol ethers and their derivatives is a useful method for the synthesis of a-hydroxy-ketones or their derivatives, which are versatile building blocks for organic synthesis. Since enol ethers and esters are types of olefin, some asymmetric epoxidation and dihydroxylation reactions have been applied to their oxidation. 

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. 

M. Masui, A. Ando, T. Shioiri, Asymmetric Synthesis of a-Hydroxy Ketones Using Chiral Phase Transfer Catalysts , Tetrahedron Lett. 1988, 29, 2835-2838. 

Stable acylzirconocene chloride has been utilized by Hanzawa and coworkers [58] for the synthesis of a-hydroxy ketones. Consecutive hydrozir-conation of terminal alkenes or alkynes with Schwartz reagent and in situ carbonylation with gaseous CO at room temperature affords acylzirconocene... 

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 reduction of a-hydroxy ketones 43 to 1,2-diols 44 was achieved in good yield and high diastereoselectivity in favour of the anti product by using ClsSiH and photolytic conditions [56]. In the proposed mechanism of Scheme 5.8, the addition proceeded via the intermediate adduct 45, which participated in the stereo-controlled hydrogen donation, and via the a-silylether 46, affording 1,2-diols in a preferential anti conformation. 

Scheme 5.8 Reduction of a-hydroxy ketones using CbSiH...

Not only a zinc-copper couple, but also a zinc-lead couple forms a gem-dimetal species from diiodomethane, according to the 1975 Nysted patent5. He also insisted that treatment of dibromethane with a zinc-lead couple in THF at 80 °C forms a characteristic gem-dizinc species 1 (equation 3). However, there was no further evidence concerning the structure except H NMR data, which was not enough for the complete structural determination. The obtained compound was definitely a gem-dizinc species, but the written structure 1 was not fully characterized. The white solid 1 is obtained as a dispersion in THF, and does not dissolve in DMF and DMI (l,3-dimethyl-2-imidazolidinone). This THF dispersion is commercially available from Aldrich Co. as Nysted reagent. Nysted also showed that this dizinc compound is effective for the methylenation of a-hydroxy ketone moiety in steroid derivatives5. 

Diazo ketones are relatively easy to prepare (see 0-112). When treated with acid, they add a proton to give a-keto diazonium salts, which are hydrolyzed to the alcohols by the SnI or Sn2 mechanism.456 Relatively good yields of a-hydroxy ketones can be prepared in this... 

The Merck system can be extended to the asymmetric synthesis of a-hydroxy ketones by using oxygen as electrophile (Scheme 18) (47). The hydroperoxide intermediates are reduced by triethyl phosphite. The sense of asymmetric induction is again consistent with the ion-paired, 7r-stacked assembly model given in Scheme 13. 

Various approaches have been used to prepare pyrroles on insoluble supports (Figure 15.1). These include the condensation of a-halo ketones or nitroalkenes with enamines (Hantzsch pyrrole synthesis) and the decarboxylative condensation of N-acyl a-amino acids with alkynes (Table 15.3). The enamines required for the Hanztsch pyrrole synthesis are obtained by treating support-bound acetoacetamides with primary aliphatic amines. Unfortunately, 3-keto amides other than acetoacetamides are not readily accessible this imposes some limitations on the range of substituents that may be incorporated into the products. Pyrroles have also been prepared by the treatment of polystyrene-bound vinylsulfones with isonitriles such as Tosmic [28] and by the reaction of resin-bound sulfonic esters of a-hydroxy ketones with enamines [29]. 

Thiamine pyrophosphate promotes the decarboxylation of a-keto acids and the cleavage of a-hydroxy ketones. 

The employment of trityl trifluoroborate is particularly interesting. This reagent is able to introduce trityl groups on both primary and secondary alcohols54 and to selectively oxidize secondary trityl ethers to ketones in the presence of primary trityl ethers.55 Thus, treatment of diols with trityl trifluoroborate leads to tritylation of both alcohols followed by oxidation of the secondary trityl ether, resulting in the formation of a ketone possessing a trityl-protected primary alcohol. A work-up by mild acidic hydrolysis provides the deprotection of the primary trityl ether and formation of a hydroxy ketone.54... 

Yields of a-hydroxy ketones by enolate hydroxylation with 1 are generally in the range 45-80% the a-diketone is sometimes obtained in addition in 5-26% yield. For unknown reasons, these hydroxylations often do not go to completion, and 5-15% of the carbonyl substrate is recovered. Yields are poor from hydroxylations of methyl ketones. 

The reagent is effective for oxidative cleavage of a-glycols to aldehydes, of a-hydroxy ketones to an aldehyde and a carboxylic acid, and of a-diketones and a-keto iicids to acids.3... 

Aromatic aldehydes form a condensation product when heated with a cyanide ion dissolved in an alcohol-water solution. This condensation leads to the formation of a hydroxy ketones. 

The different steps which are relevant for thiamine-catalyzed decarboxylation and the formation of a-hydroxy ketones are summarized in Scheme 3. 

Scheme 3. Reaction path of enzymatic pyruvate decarboxylation and formation of a-hydroxy ketones...

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