Oxidative 1,2-Diol Cleavage

Silylation of 276 with TBSOTf furnishes the bis-TBS ether, which undergoes an osmium tetroxide hydroxylation to afford the syn,anti,syn,anti,syn- iQi o 278 in 73% yield and with high diastereoselectivity. Selective diol oxidative cleavage with periodic acid, PCC oxidation of the resulting epimeric lactols to the lactone, followed by deprotection with /7-toluene-... 

Concomitant loss of the a-methyl-p-methoxybenzyl group of 48 led to the resulting pyrrolizidine 49 as a single diastereomer, after crystallization from the crude reaction mixture. Reduction of the hydroiodide salt 49 led to the diol 50 in 87% yield. Diol oxidative cleavage and deprotection in 51 finally afforded the 7a-epimer of hyacinthacine Ai 52 with a final 10% overall yield (nine steps from 2,3,5-tri-O-benzyl-ribofuranose Scheme 8). 

The AT-Boc-lactam 107 was submitted to a three-step sequence (Scheme 31). First, a Grignard addition allowed the installation of the vinyl moiety, then the unsaturated ketone intermediate was reduced and after mesy-lation, the alcohol underwent a diastereoselective cyclization to provide the five-membered ring 108. The latter was then converted into the A -Cbz pyrrolidine 109 which was transformed into aldehyde 110 via a 1,2-diol oxidative cleavage. The aUylation of 110, under Reformatsky type conditions, then gave a mixture of separable diastereoisomers 111a and 111b (d.r. 79 21). 

This chapter will define an oxidation in general terms. Various reagents will be introduced that oxidize an alcohol to an aldehyde or to a ketone. In some cases, alcohols may be oxidized to a carboxylic acid. Oxidation of alkenes will be revisited—specifically, for the oxidation of an alkene to an oxirane or to a 1,2-diol. Oxidative cleavage with ozone will be revisited, and new methods for oxidative cleavage will be introduced. 

A reaction characteristic of vicinal diols is their oxidative cleavage on treatment with periodic acid (HIO4) The carbon-carbon bond of the vicinal diol unit is broken and two carbonyl groups result Periodic acid is reduced to iodic acid (HIO3)... 

The reaction is based, on the one hand, on the oxidative cleavage of vicinal diols by lead(IV) acetate and, on the other hand, on the reaction of dichlorofluorescein with lead(IV) acetate to yield a nonfluorescent oxidation product. The dichlorofluorescein only maintains its fluorescence in the chromatogram zones where the lead(IV) acetate has been consumed by the glycol cleavage reaction [1],... 

The oxidative cleavage of the central carbon-carbon bond in a vicinal diol 1, by reaction with lead tetraacetate or periodic acid, yields two carbonyl compounds 2 and 3 as products. 

Fatty acids, both saturated and unsaturated, have found a variety of applications. Brassilic acid (1,11-un-decanedicarboxylic acid [BA]), an important monomer used in many polymer applications, is prepared from erucic acid (Scheme 2), obtained from rapeseed and crambe abyssinica oils by ozonolysis and oxidative cleavage [127]. For example, an oligomer of BA with 1,3-butane diol-lauric acid system is an effective plasticizer for polyvinylchloride. Polyester-based polyurethane elastomers are prepared from BA by condensing with ethylene glycol-propylene glycol. Polyamides based on BA are known to impart moisture resistance. 

The next key step, the second dihydroxylation, was deferred until the lactone 82 had been formed from compound 80 (Scheme 20). This tactic would alleviate some of the steric hindrance around the C3-C4 double bond, and would create a cyclic molecule which was predicted to have a greater diastereofacial bias. The lactone can be made by first protecting the diol 80 as the acetonide 81 (88 % yield), followed by oxidative cleavage of the two PMB groups with DDQ (86% yield).43 Dihydroxylation of 82 with the standard Upjohn conditions17 furnishes, not unexpectedly, a quantitative yield of the triol 84 as a single diastereoisomer. The triol 84 is presumably fashioned from the initially formed triol 83 by a spontaneous translactonization (see Scheme 20), an event which proved to be a substantial piece of luck, as it simultaneously freed the C-8 hydroxyl from the lactone and protected the C-3 hydroxyl in the alcohol oxidation state. 

In the Mukaiyama variation of the aldol reaction, 3-benzoyloxy-2-trimethylsiloxy-l-butene adds to 2-methylpropanal in a stereoselective manner. Best results are obtained in the presence of titanium(IV) chloride, giving the adducts 9/10 in a diastereomeric ratio of 92 8. Hydrolysis of the benzoyl group and subsequent oxidative cleavage of the 1,2-diol moiety liberates / -hy-droxycarboxylic acids593. 

The oxidative cleavage of v/c-diols to give two carbonyl functions (Eq. 5.3) by periodates was first observed by Malaprade and has since been widely applied to the carbohydrate area.50 Since both the reagent sodium periodate and the carbohydrate substrate are water soluble, the reaction is usually carried out in aqueous media.51 The reaction has been applied to polysaccharides such as starch.52 The periodate oxidations of sodium alginate in water as well as a dispersion in 1 1 ethanol-water mixture have been compared.53 Because sodium alginate forms a highly viscous solution, the oxidation was observed to be more extensive in ethanol-water. 

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