Ketone from 1,2-diols

Tetramethylammonium triacetoxyborohydride gives anft -l,3-diols from (3-hydroxy ketones.136 These reactions are thought to occur by a rapid exchange that introduces the hydroxy group as a boron ligand. 

The reagent of choice for the reduction of ketals to ethers is alone prepared in situ from lithium aluminum hydride and aluminum chloride in ether. At room temperature ethers are obtained in 61-92% yields [792, 934]. Cyclic ketals prepared from ketones and 1,2- or 1,3-diols afford on hydrogenolysis by alanes alkyl P- or y-hydroxyalkyl ethers in 83-92% yields [792]. 

Cyclic acetals like this are more resistant to hydrolysis than acyclic ones and easier to make—they form quite readily even from ketones. Again, we have entropic factors to thank for their stability. For the formation of a cyclic acetal, two molecules go in (ketone plus diol) and two molecules come out (acetal plus water), so the usually unfavourable AS0 factor is no longer against us. And, as for hemi-acetals (see the explanation above), equilibrium tends to lie to the acetal side because the intramolecular ring-closing reaction is fast. 

Although hydrosilanes reduce ketones, in trifluoroacetic acid, to the corresponding methylene compounds or dimeric ethers via ionic hydrogenation, the reduction of a-amino and a-oxy ketones and p-keto acid derivatives with hydrosilanes, particularly PhMe2SiH, under these conditions proceeded with high anti selectivity to the alcohols. No racemization was observed at the carbon a to the carbonyl group. Intramolecular hydrosilylation catalyzed by Lewis acids provided a highly stereoselective route to anti-1,3-diols from p-hydroxy ketones (Section 1.1.3. ). ... 

N03)j, a newcomer to the arena of oxidants, is useful for the acetoxylation of aromatic side chains in benzylic positions [415, 416] and for the oxidation of methylene or methyl groups that are adjacent to aromatic rings to carbonyl groups [238, 415, 417]. The reagent also oxidizes alcohols to aldehydes [418, 419, 420, 421] and phenols to quinones [422, 423], cleaves vicinal diols to ketones and a-hydroxy ketones to acids [424, 425], and converts diaryl sulfides into sulfoxides [426]. A specialty of ammonium cerium nitrate is the oxidative recovery of carbonyl compounds from their oximes and semicarbazones [422, 427] and of carboxylic acids from their hydrazides [428] under mild conditions. 

The reaction may proceed as homo- or cross-dehydrodimerization [105] and takes place with a wide range of substituted substrates such as higher alcohols, ethers, silanes, and partially fluorinated alcohols and ethers, but also with ketones, carboxylic acids, esters, amides, and amines [106]. Besides the formation of 1,2-diols from saturated alcohols, unsaturated substrates are also dimerized under hydrogen to form l,n-diols other than the 1,2-isomers [107]. The regio-selectivity of the diols is controlled by the formation of the most stable radical, which then dimerizes. 

The symmetrical diols derived from cyclopentanone and cyclohexanone can similarly be converted to ring-expanded ketones in good yield. The diols from reductive coupling of cycloheptanone and cy-clooctanone give mainly the corresponding dienes in aqueous acid, especially when heated, but Chris-tol found that pinacol rearrangement is strongly favored even for these materials when cold concentrated sulfuric acid is used as the solvent. 

Methylthiotrimethylsilane converts aldehydes and ketones into bis(methyl-thio)acetals under very mild conditions, without the need for an acidic catalyst. 5a-Androstane-3,17-dione reacted selectively at C-3.The reaction appears to depend upon the high affinity of silicon for oxygen.2-Methylenepropane-l,3-diol protects ketones as acetals from which the ketones can be regenerated without resort to acidic treatment, if required.Hypophosphorous acid adds on to 3-oxo-steroids to give 3-yl phosphonous acids. 5a-Cholestan-3-one gives the 3-hydroxy-derivative (177), but a 4-en-3-one gives the 3,5-dien-3-yl phosphonous acid (178). ... 

The acid-catalyzed hydrolyses of both cz.s-a net hole oxide (121) and trans-anethole oxide (124) yield identical product mixtures of 20% erythro and 80% threo 1 -(p-methoxyphenyl)-1,2-propanediols, suggesting that there is a common benzylic car-bocation intermediate (127) and common product-forming steps.108 These results indicate that rotation about the (%-C bond of the carbocation intermediate 127 is faster than attack of water on the carbocation. However, the ratio of diol and ketone products from the pH-independent reaction of cw-anethole oxide is very different than that from trans-anethole oxide, so rotation about the Ca-Cp bond in the transformation of 121 to 124 is not rapid compared to the rates of ketone and diol product formation. 

A change of a polarity from a polar to nonpolar state (reverse polarity change) can be accomplished by the pinacol-pinacolone rearrangement and has been exploited in chemically amplified lithographic imaging [151, 348-350]. The pinacol rearrangement involves conversion of vie-diols to ketones or aldehydes with an acid as a catalyst (Fig. 115). 

Acetals formed from ketones and 1,2-diols are of major significance in carbohydrate chemistry, and can be converted into acylox-onium salts only in special cases. Acetals (7) from acetophenone react with the highly reactive ketonium salts (8) to give benzoxonium... 

Contrary to some reports, electrophilic addition reactions may occur in other multiple-bond systems. In many of the reactions of aldehydes and ketones the first stage involves the addition of some entity across the carbon-oxygen bond, e.g., the formation of oximes, semicarbazones, hydrazones, hydrates (1,1-diols) and their ethers, and the aldol condensation. Most of these reactions entail a subsequent loss (elimination) of a small molecule e.g. water, ammonia, ethanol) and, while one must be careful to determine whether the rate-determining stage involves attack on the carbonyl compound or elimination from the adduct , there are some systems in which it is evident that electrophilic attack is involved in the slow stage of the reaction sequence. Examples of such reactions are the acid-catalysed formation of oximes of aliphatic - and aromatic carbonyl compounds, of furfural semi-carbazone , and of 1,1-diols from aldehydes or ketones . 

Dioxans.—A series of 1,3-dioxans (310) have been synthesized, in one step, from ketones, paraformaldehyde, and a cation-exchanger in its acid form. Good yields were obtained, provided that the medium was anhydrous.Condensation of the (15,25 )-amino-diol (311) with ketones gave the dioxan, e.g. (312), whose... 

The second general route to 1,3-dioxepanes (1) involves acid-catalyzed alcohol exchange of an acyclic acetal (6) with a 1,4-diol (transacetalization) <8iJOC298i>, as demonstrated by the synthesis of (12 X = C1, Br) by reaction of 2-halo-1,1-dialkoxyethane with 1,4-butanediol <79MI 911-01, 95JOC5729) or the preparation of (13) from benzil dimethyl acetal <90UKZlll6>. Transacetalization is preferred for the synthesis of 1,3-dioxepanes derived from ketones <61JOC4762> and the stereo-... 

CS-670 is a racemic NSAID which is readily metabolized to active metabolites trans and unsaturated mono-ols. When cw-OH is administered to rats, approximately 9% of the trans diols were excreted in urine. However, the production of c -diols from trans-OH was only 0.51% of the dose. The chiral inversion from c -OH to trans-OH has been suggested to occur through the saturated ketone intermediate [63,133] (Fig. 9). Nevertheless, as the trans and the unsaturated alcohol (Fig. 9) are active anti-inflammatory analgesics and the ds alcohol has immuonomodulating activity, it is very important to evaluate the disposition of each enantiomer in order to understand pharmacological and toxicological properties of CS-670 [62,133]. 

Support for the concept of an unsaturated intermediate in the formation of allo-acids is provided by recent experiments of Yamasaki et at. (98, 89). After administration of 3-ketochol-4-enoic-24- - C acid to rats and examination of the biliary metabolites, all four isomers of 3-hydroxycholanoic acid were identified other di- and trihydroxy acids were not investigated. Of the four possible 3-hydroxy-isomers about twice as much lithocholate was present as each of the other isomers. Similar results were obtained following administration of 3/3-acetoxychol-5-enoic-24-i- C acid in addition, 3f,6 -dihydroxy-5a-cholanoic acids were obtained. Yamasaki et al. (89) propose that a 3/3-dehydrogenase converts the 3/3-hydroxy-J -cholenoic acid to the a,/3-unsaturated ketone from which both 5 and 5 acids are derived, whereas hydroxylation of the above acid provides the diol from which only 5 acids are produced, somewhat analogous to the scheme of metabolism proposed by Mitropoulos and Myant (132) for the formation of chenodeoxycholic acid and the muricholic acids. 

Oxone in conjunction with OSO4 cleaves alkenes to ketones or carboxylic acids (eq 43). This protocol has the advantage over traditional methods in that there is no need for intermediate 1,2-diols. This method has been exploited in the direct synthesis of lactones from alkenols (eq 44) and tetrahydrofuran-diols from 1,4-dienes as well. ... 

Typical Procedure for the Preparation of 1,2-Diols from the Reaction of Aryl Ketones with Mn ... 

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