Hydroxy-ketones, and the

Lil reagent system. It is widely believed that the high. -selectivity originates from a chelate formed between the p-hydroxy ketone and the lithium cation. This locks the ketone into a rigid conformation that is preferentially reduced from the least-hindered direction. For compound... 

Enol ethers, and in particular silylated ends (see Volume 2, Chapter 2.3), react with peroxy acid reagents to give initially a silyloxy qpoxide, which rearranges with silyl migration to yield an a-silyloxy ketone, " as in Scheme 3. The net result is that a ketone is converted to a protected a-hydroxy ketone, and the stereochemistry b determined by the least hindered approach of the peroxy acid to the enol. 

Not only 1,2-di-functionalized substrates with heteroatoms but also tertiary alcohols and hemiketals undergo oxidative C-C bond cleavage at the a position on treatment with lead tetraacetate. For example, a y-hydroxy ketone and the corresponding hemiketal have been fragmented by lead tetraacetate into a 9-membered olefinic lactone (Scheme 13.57) [76]. 

In general, 1.2-diones are good substrates for baker s yeast reduction, however, selectivity is low. In most cases a racemic mixture of the hydroxy ketones and the 1,2-diols is obtained. One exception Lo this rule is the reduction of 1-phenyl-1,2-propanedione to LS )-2-hydroxy-l -phenyl-propanone by baker s yeast in phosphate buffer at pH 5217. If the reaction is carried out with a large excess of yeast in distilled water, the (1 / ,2S)-1-phenyl-1,2-propanediol is obtained in high chemical and optical yield222. 

The first sequence of reactions is simple. Protonation of the enol ether occurs on the convex face so the OH group is pushed into the endo side. Hydrolysis gives the hydroxy-ketone and the tosylate. 

This will always be the case whenever an enolate attacks a carbonyl group, regardless of the structure of the starting ketone and the structure of the enolate. The alpha carbon of the enolate is directly attacking the carbonyl group of the ketone. That wiU always place the OH group in the beta position. Always. This product is called a jS-hydroxy ketone, and the reaction is called an aldol addition. 

The telomer 145 of nitroethane was used for the synthesis of recifeiolide (148)[121], The nitro group was converted into a hydroxy group via the ketone and the terminal double bond was converted into iodide to give 146. The ester 147 of phenythioacetic acid was prepared and its intramolecular alkylation afforded the 12-membered lactone, which was converted into recifeiolide (148),... 

Formaldehyde condenses with itself in an aldol-type reaction to yield lower hydroxy aldehydes, hydroxy ketones, and other hydroxy compounds the reaction is autocatalytic and is favored by alkaline conditions. Condensation with various compounds gives methylol (—CH2OH) and methylene (=CH2) derivatives. The former are usually produced under alkaline or neutral conditions, the latter under acidic conditions or in the vapor phase. In the presence of alkahes, aldehydes and ketones containing a-hydrogen atoms undergo aldol reactions with formaldehyde to form mono- and polymethylol derivatives. Acetaldehyde and 4 moles of formaldehyde give pentaerythritol (PE) ... 

Biacetyl is produced by the dehydrogenation of 2,3-butanediol with a copper catalyst (290,291). Prior to the availabiUty of 2,3-butanediol, biacetyl was prepared by the nitrosation of methyl ethyl ketone and the hydrolysis of the resultant oxime. Other commercial routes include passing vinylacetylene into a solution of mercuric sulfate in sulfuric acid and decomposing the insoluble product with dilute hydrochloric acid (292), by the reaction of acetal with formaldehyde (293), by the acid-cataly2ed condensation of 1-hydroxyacetone with formaldehyde (294), and by fermentation of lactic acid bacterium (295—297). Acetoin [513-86-0] (3-hydroxy-2-butanone) is also coproduced in lactic acid fermentation. 

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. 

Of particular interest are reactions between a-hydroxy ketones and allyl(trifluoro)silanes which proceed with participation of the hydroxy group via a pentacoordinated allylsilane, with intramolecular delivery of the allyl group to the ketone. Excellent stereoselectivity is obtained at up to three contiguous stereogenic centers66. 

A closely related reaction has been performed with other aldehydes and even with ketones without a catalyst, but with heat. The aldehydes and ketones here are active ones, such as chloral and acetoacetic ester. The product in these cases is a 3-hydroxy alkene, and the mechanism is pericyclic ... 

The reaction has also been carried out on a-hydroxy ketones and on a,p-epoxy... 

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. 

In aqueous acid cross-conjugated cyclohexadienones are principally photoconverted to one or more hydroxy ketones. In the case of a-santonin (1), isophotosantonic lactone (5) is formed in about 50% yield. A series of papers by Kropp and co-workers has aided in understanding this reaction/32-39-411 They have shown that the presence of a 4-methyl group (steroid numbering) results in the preferential formation of the 5-7 fused ring system (isophoto-... 

The telomer of nitroethane, 134, was used for the synthesis of 11-hydroxy-8-frans-dodecenoic acid (135) (125). Apparently, the internal double bond of 134 must have a trans configuration from a mechanistic consideration. The nitro group was converted to alcohol via ketone, and the two-carbon homologation was carried out from the terminal double bond. This acid is converted to recifeiolide (136), a naturally occurring macrolide. 

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-... 

Carbon monoxide rapidly inserts into the carbon—zirconium bond of alkyl- and alkenyl-zirconocene chlorides at low temperature with retention of configuration at carbon to give acylzirconocene chlorides 17 (Scheme 3.5). Acylzirconocene chlorides have found utility in synthesis, as described elsewhere in this volume [17]. Lewis acid catalyzed additions to enones, aldehydes, and imines, yielding a-keto allylic alcohols, a-hydroxy ketones, and a-amino ketones, respectively [18], and palladium-catalyzed addition to alkyl/aryl halides and a,[5-ynones [19] are examples. The acyl complex 18 formed by the insertion of carbon monoxide into dialkyl, alkylaryl, or diaryl zirconocenes may rearrange to a r 2-ketone complex 19 either thermally (particularly when R1 = R2 = Ph) or on addition of a Lewis acid [5,20,21]. The rearrangement proceeds through the less stable... 

With a-hydroxy ketones and their related tosyloxy derivatives. The imidazo [2,T ]thiazole 364 was prepared by acetic acid-catalyzed cyclocondensation of 2-hydroxy-l,2-diphenyl-ethanone with thiophenyl-substituted 2-aminothiazole 363 (Equation 163) <2002MI110>. Under MW irradiation and in the presence of montmorillonite K-10 clay, a mixture of a-tosyloxyketones 365 and 2-imidazolidinethione led to the substituted 5,6-dihydro-imidazo[2,l- ]thiazoles 366 (Equation 164) <1998J(P1)4093>. When using a-tosyloxyacetophenone, prepared by reaction of acetophenone with [hydroxyl(tosyloxy)iodo]benzene (HTIB), 5-aminopyrazole 367 could be converted to imidazo[l,2- ]pyrazole 368 in basic medium (Equation 165) <2005JHC209>. 

In numerous complex aldol adducts it is not always possible to extract the relevant vicinal proton coupling constants. Heathcock and co-workers have recently noted that for the -hydroxy ketones and esters that exist in the preferred hydrogen-bonded conformations A and A, NMR spectroscopy may be conveniently employed to assign stereochemistry (13). 

The hydroxynitrile lyase (HNL)-catalysed cyanohydrin reaction is a useful method to synthesize enantiopure a-hydroxy nitriles and the corresponding a-hydroxy acids. However, small ketones, such as 2-butanone, are converted with low selectivities, due to the poor discrimination between methyl and ethyl. ... 

Chiral cyanohydrins are versatile intermediates in the synthesis of a-hydroxy acids, /3-amino alcohols, amino nitriles, a-hydroxy ketones and aziridines. For the synthesis of enantiopure cyanohydrins, the use of hydroxynitrile lyases is currently the most effective approach.Application of an organic-solvent-free system allows thermodynamically hindered substrates to be converted with moderate to excellent yields. With the use of the highly selective hydroxynitrile lyase from Manihot esculenta, the syntheses of several acetophenone cyanohydrins with excellent enantioselectivities were developed (Figure 8.2). (5)-Acetophenone cyanohydrin was synthesized on a preparative scale. ... 

Kalaitzakis, D., Rozzell, J.D., Kambourakis, S. and Smonou, I., Synthesis of valuable chiral intermediates by isolated ketoreductases application in the s3mthesis of -alkyl—hydroxy ketones and 1,3-diols. Adv. Synth. Catal, 2006, 348, 1958-1969. 

Hydroxy ketones and hydroxy-a,/3-unsaturated ketones in the steroids such as estrone and testosterone, respectively, can be reduced to diols biochemically. Estrone acetate gave 68% yield of a-estradiol on incubation with baker s yeast at room temperature after five days [909]. Testosterone was reduced by bacteria to the saturated hydroxy ketones, etiocholan-17-ol-3-one and androstan-17-ol-3-one, and further to the diols, ep/-etiocholane-3,17-diol and the epimeric isoandrostane-3,17-diol, both in low yields [329]. 

In steroidal a-hydroxy ketones with the keto group in position 20 and the hydroxylic group in position 17, the hydroxy, and better still, acetoxy group is replaced by hydrogen on refluxing for 24 hours with zinc dust and acetic... 

Amides of keto acids were reduced to amides of hydroxy acids biochemically using Saccharomyces cerevisiae to give optically pure products [7059]. Refluxing with lithium aluminum hydride in ether for 6 hours reduced both the ketonic and the amidic carbonyl in A -methyl-5-phenyl-5-oxopentanamide and gave 82% yield of 5-methylamino-l-phenylpentanol [1134]. 

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