Hydroxyketone, oxidative cleavage

Over the past several years, Mascarenas and co-workers (150-153) utilized the oxidopyrylium ion with variously hetero-substituted olefin tethers. Mascarenas has used this methodology in tandem with a Diels-Alder reaction to prepare tricyclic cycloheptanoid substrates. Further, Mascarenas and co-workers (154—156) achieved the synthesis of optically active oxabicyclic[3.2.1]octane derivatives through the addition of a homochiral p-tolylsulfinyl group substituted at the olefin tether. The Mascarenas group has also used this methodology to prepare the THF portion of ( )-nemorensic acid via oxidative cleavage of the substituted a-hydroxyketone moiety (157) (Scheme 4.78). 

Oxidative cleavage of the 1,2-dihydroxy- and a-hydroxyketone moieties to carbonyl and carboxylic acid groups, respectively, was accomplished with lead tetracetate and periodic acid (Scheme 74) <1997JOC7430, 2005AGE6187>. 

An oxidative cleavage of cycloalkanones to unsaturated aldehyde-esters has been developed. Thus, for example, cyclononanone was converted into 2,2-dithio-trimethylenecyclononanone, which was cleaved using lead(iv) acetate (66 %), and the product so obtained treated with methanol and sodium periodate to give (208 in = 5). Cyclododecanone was similarly converted into (208 n = 8). 1,2-Bis(trimethyl-silyloxy)cycloalkenes, prepared by acyloin condensations, have been converted into 2-alkyl-2-hydroxycycloalkanones by treatment with methyl-lithium and an alkyl halide, and the oximes of these a-hydroxyketones cleaved to give open-chain co-cyanoketones using mesyl chloride-pyridine. ... 

Periodic acid also cleaves carbon-carbon bonds of a-hydroxyketones and a-hydroxyaldehydes by a similar mechanism. Following are abbreviated structural formulas for these functional groups and the products of their oxidative cleavage by periodic acid. As a way to help you understand how each set of products is formed, each carbonyl in a starting material is shown as a hydrated intermediate that is then oxidized. In this way, each oxidation can be viewed as being analogous to the oxidation of a glycol. 

Oxidation with mepba — -hydroxyketones, using the reaction of isophorone dienol ether (detailed preparation given), and Et3N.HF cleavage of the intermediate silyl ether. 

This explains, for example, the tendency of some 1,2-diols to suffer oxidative carbon-carbon bond breakage under the action of PDC. Thus, although many 1,2-diols can be uneventfully oxidized to a-hydroxyketones with PDC,176 very often a cleavage of a carbon-carbon bond occurs, resulting in two carbonyl functionalities.177 Vicinal tertiary diols, sometimes, are smoothly oxidized to diketones by PDC.178... 

Schmid and co-workers (124) have described a new degradation of (-)-kopsine (325) to (-)-aspidofractinine (326). Sodium periodate cleavage of the hydroxyketone under acidic conditions gave a keto acid which was esterified. Oxidation with chromium trioxide in pyridine at room temperature for 48 hr then gave the 5,6-dehydro compound 327. Hydrolysis of 327 under acidic conditions gave the unstable enamine 328... 

The nonstoichiometric sugar oxidation process in the presence of alkali is used for both qualitative and quantitative determination of reducing sugars (Fehling s reaction with alkaline cupric tartrate Nylander s reaction with alkaline trivalent bismuth tartrate or using Benedict s solution, in which cupric ion complexes with citrate ion). Hydroxyaldehydes and hydroxyketones are formed by chain cleavage due to retroaldol reaction under nonoxidative conditions using dilute alkali at elevated temperatures or concentrated alkali even in the cold. 

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