Other Ether Oxidations

Oxidative cleavage of P-hydroxyethers to keto-lactones was accomplished by RuClj/aq. Na(10 )/CCl -CH3CN thus hexahydro-benzofuran-3a-diol gave the corresponding nine-membered ketolactones (R =Me, Bu, R =H, Me Fig. 5.14) [87]. 

4 Ether Oxidations Not Covered Here but Included in Chapter 1 

Oxidations of sulfides catalysed by Ru porphyrin complexes have been reviewed [4, 97, 98]. In their pioneering work of 1953 Djerassi and Engle showed that stoich. RuOyCCl oxidised several sulfides to sulfones (Table 5.2) [99]. 

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A refined grade of MTBE is used ia the solvents and pharmaceutical iadustries. The main advantage over other ethers is its uniquely stable stmctural framework that contains no secondary or tertiary hydrogen atoms, which makes it very resistive to oxidation and peroxide formation. In addition, its higher autoignition temperature and narrower flammabihty range also make it relatively safer to use compared to other ethers (see Table 3). 

The Dim ester was developed for the protection of the carboxyl function during peptide synthesis. It is prepared by transesterification of amino acid methyl esters with 2-(hydroxymethyl)-l,3-dithiane and Al(/-PrO)3 (reflux, 4 h, 75°, 12 torr, 75% yield). It is removed by oxidation [H2O2, (NH4)2Mo04 pH 8, H2O, 60 min, 83% yield]. Since it must be removed by oxidation it is not compatible with.sulfur-containing amino acids such as cysteine and methionine. Its suitability for other, easily oxidized amino acids (e.g., tyrosine and tryptophan) must also be questioned. It is stable to CF3CO2H and HCl/ether. - ... 

Epoxides, like other ethers, are cleaved by nucleophiles under acidic conditions. For example, cyclopentene oxide produces a mixture of 1,2-cyclopentanediol stereoisomers when treated with water and sulfuric acid. 

The one general exception to the rule that ethers don t typically undergo Sn2 reactions occurs with epoxides, the three-membered cyclic ethers that we saw in Section 7.8. Epoxides, because of the angle strain in the three-membered ring, are much more reactive than other ethers. They react with aqueous acid to give 1,2-diols, as we saw in Section 7.8, and they react readily with many other nucleophiles as well. Propene oxide, for instance, reacts with HC1 to give l-chloro-2-propanol by Snj2 backside attack on the less hindered primary carbon atom. We ll look at the process in more detail in Section 18.6. 

Silylformylation, defined as the addition of RsSi- and -CHO across various types of bonds using a silane R3SiH, CO, and a transition metal catalyst, was discovered by Murai and co-workers, who developed the Co2(CO)8-catalyzed silylformylation of aldehydes, epoxides, and cyclic ethers [26]. More recently, as described in detail in Section 5.3.1, below, alkynes and alkenes have been successfully developed as silylformylation substrates. These reactions represent a powerful variation on hydroformylation, in that a C-Si bond is produced instead of a C-H bond. Given that C-Si groups are subject to, among other reactions, oxidation to C-OH groups, silylformylation could represent an oxidative carbonylation of the type described in Scheme 5.1. 

The action of the amine over the alkoxysulfonium intermediate— ROS(+)Me2—can produce either the desired oxidation, or the generation of H2C=S(+)-Me. This compound can react with alcohols, resulting in the formation of methylthiomethyl ethers, R-0-CH2-S-Me. It can also react with other nucleophilic sites, resulting in the introduction of a methylthiomethyl group. Unhindered alcohols are particularly prone to the generation of methylthiomethyl ethers, whose formation can be difficult to avoid by adjusting reaction conditions. Nevertheless, like other Molfatt oxidations, it... 

As in other Moffatt oxidations, a Corey-Kim oxidation may produce minor amounts of methylthiomethyl ethers. These can be minimized by using a solvent of low polarity, like toluene.248a Nonetheless, very often dichloromethane is used, because of its better solubilizing power. Almost always triethylamine is used as base. 

Similar to other Moffatt oxidations, the Corey-Kim method results sometimes in the generation of methylthiomethyl ethers by reaction of alcohols with H2C=S(+)-Me, resulting from decomposition of activated DMSO.259... 

The best anaesthetic vapour was found to be a 1 2 3 mixture of alcohol, chloroform, and ether, known as ACE. Despite being widely used, it was always known that ACE presented a risk, and yet it was the anaesthetic of choice for more than 100 years. Ether caused serious fires and explosions in operating theatres and while the risk of this was small - about one serious incident every 100,000 operations - it was alarming when it happened. Chloroform was not a fire risk but it could be deadly to some patients, killing them within minutes in certain tragic cases, and seriously damaging the liver of others. (Nitrous oxide was less risky, and continues to be used even today, but it does not produce deep anaesthesia.)... 

Alkoxides and aryloxides have been intensively studied because of their interest, especially for Ba, as precursors to oxide materials having desirable electronic properties this development was stimulated by the discovery of superconducting materials such as YBajG CVx. The same interest applies to other volatile complexes like /3-diketonates. The alkyl or aryl oxides (also siloxides) are readily obtained by a variety of methods, notably (a) direct interaction of the metals with ROH in THF, toluene saturated with NH3,22 or other ether solvents (b) the interaction of... 

The majority of oxygen compounds contain 2-coordinate oxygen, in which the O atom forms two single bonds to other atoms and has two unshared pairs of electrons in its valence shell. Such compounds include water, alcohols, ethers, and a variety of other covalent oxides. In the simple systems without significant tt bonding the X—O—X group is bent typical angles are 104.5° in H20 and 111° in (CH3)20. 

Other recent oxidative methods have yet to make a major impact. Photochemical bromination can be used for the oxidative cleavage of a benzyl ether on a substantial scale.290-291 An intermediate a-bromo ether hydrolyses to a hemiace-tal intermediate that collapses to give benzaldehyde and the liberated alcohol [Scheme 4 156] ... 

Although a number of different reagents have been discovered for the selective oxidation of ethers, e.g. halogens, iodine tris(trifluoroacetate), trichloroisocyanuric acid, UFs, A(,N-dibromobenzenesul-fonamide and lead tetraacetate, few have assumed any synthetic importance. Of these, the most significant are the metallic oxidants chromic acid and ruthenium tetroxide. DDQ has also been widely used for the oxidative d rotection of benzyl ethers. It is the aim of this chapter to review the latest developments in ether oxidation by these, and other reagents, with particular emphasis on chemo- and regio-selectivity. Several reviews on the subject have appeared previously. " The related oxidation of acetals has been reviewed recently" and will not be dealt with here. 

Others [180,260]). In general, enol radical cations may be obtained from either direct oxidation of stable ends or by selective oxidation of the enol tautomer of the keto/enol equilibrium. In addition it has been outlined that enol radical cations offer an access to a-carbonyl radical chemistry. Other enol systems like silyl enol ethers, enol esters and enolates similarly may open up after oxidation the chemistry of a-carbonyl radical or a-carbonyl cation intermediates, whereas enol ether oxidative a-functionalization reactions work by another route. 

On the other hand, oxidative polymerization involves formation of C —O —C bonds. Polymers with ether and peroxide linkages are formed in the presence of oxygen. They may also contain hydroxy, oxo, or epoxy groups. Such compounds are undesirable in deep-fried oil or fat because they permanently diminish the flavoring characteristics of the oil or fat and also cause a foaming problem. 

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