Bond cleavage ethers

The hydrogenolyaia of cyclopropane rings (C—C bond cleavage) has been described on p, 105. In syntheses of complex molecules reductive cleavage of alcohols, epoxides, and enol ethers of 5-keto esters are the most important examples, and some selectivity rules will be given. Primary alcohols are converted into tosylates much faster than secondary alcohols. The tosylate group is substituted by hydrogen upon treatment with LiAlH (W. Zorbach, 1961). Epoxides are also easily opened by LiAlH. The hydride ion attacks the less hindered carbon atom of the epoxide (H.B. Henhest, 1956). The reduction of sterically hindered enol ethers of 9-keto esters with lithium in ammonia leads to the a,/S-unsaturated ester and subsequently to the saturated ester in reasonable yields (R.M. Coates, 1970). Tributyltin hydride reduces halides to hydrocarbons stereoselectively in a free-radical chain reaction (L.W. Menapace, 1964) and reacts only slowly with C 0 and C—C double bonds (W.T. Brady, 1970 H.G. Kuivila, 1968). 

Direct proof of an oxaziridine intermediate was achieved in photolysis experiments in an organic glass at 77 K (80JA5643). Oxaziridine (75), formed by photolysis of A/-oxide (74) and evidenced by UV spectroscopy under the above conditions, decomposed at higher temperature to form the imino ether (76) by N—O bond cleavage and C -> O migration of an aryl group. 

Remarkable solvent effects on the selective bond cleavage are observed in the reductive elimination of cis-stilbene episulfone by complex metal hydrides. When diethyl ether or [bis(2-methoxyethyl)]ether is used as the solvent, dibenzyl sulfone is formed along with cis-stilbene. However, no dibenzyl sulfone is produced when cis-stilbene episulfone is treated with lithium aluminum hydride in tetrahydrofuran at room temperature (equation 42). Elimination of phenylsulfonyl group by tri-n-butyltin hydride proceeds by a radical chain mechanism (equations 43 and 44). 

Cleavage of Carbon-Oxygen Bonds in Ethers and Esters... 

The cleavage of carbon-oxygen bonds in ethers or esters by nucleophilic substitution is frequently a useful synthetic transformation. 

Another photocyclization to a benzo[c]phenanthridine was reported (127). Oppenauer oxidation of ( )-ophiocarpine (92) with potassium fm-butoxide and benzophenone in dioxane effected C-6—N bond cleavage to afford the hydroxyisoquinoline 219 via berberinephenolbetaine (121) (Scheme 39). Although photolysis of 219 gave only the oxepine 221, that of its methyl ether 220 furnished directly norchelerythrine (222) through electrocyclization followed by spontaneous elimination of methanol. 

An unusual example of an anchimerically assisted (O—C) bond cleavage is found in the electron impact induced dissociation of alkyl silylmethyl ether 137 (33) 6). 

The bonds between an oxygen and an sp3 carbon atom in alcohols, ethers, or esters are quite resistant to hydrogenolysis. Elevated temperatures and pressures are required to induce C-O bond cleavage and the high temperature can cause the cleavage of the C—C bonds, too. 

Schafer reported that the electrochemical oxidation of silyl enol ethers results in the homo-coupling products. 1,4-diketones (Scheme 25) [59], A mechanism involving the dimerization of initially formed cation radical species seems to be reasonable. Another possible mechanism involves the decomposition of the cation radical by Si-O bond cleavage to give the radical species which dimerizes to form the 1,4-diketone. In the case of the anodic oxidation of allylsilanes and benzylsilanes, the radical intermediate is immediately oxidized to give the cationic species, because oxidation potentials of allyl radicals and benzyl radicals are relatively low. But in the case of a-oxoalkyl radicals, the oxidation to the cationic species seems to be retarded. Presumably, the oxidation potential of such radicals becomes more positive because of the electron-withdrawing effect of the carbonyl group. Therefore, the dimerization seems to take place preferentially. 

From these data, it can be estimated that chlorphenoxamine (11.24, R = 4-C1, R = Me) should hydrolyze ca. 17 times faster than diphenhydramine. This decreased stability appears sufficient to drive formation of detectable amounts of the benzhydrol metabolite (11.25, R = 4-C1, R = Me) in the stomach of patients dosed with chlorphenoxamine. Indeed, ether bond cleavage to form this and derived metabolites was a major pathway in humans [49], Whether the reaction was entirely nonenzymatic or resulted in part from oxidative O-dealkylation (Chapt. 7 in [50]) remains unknown. 

For many years, intramolecular reactions such as conformational changes, bond cleavage, bond formation, and valence isomerizations have been observed only when hydrocarbons were reduced with alkali metals in ethereal solvents. In most electrochemical experiments, these reactions were dominated by the electrophilic processes already described. However, progress in experimental techniques [8, 9, 27-29] has made these reactions accessible to electroanalytical investigations, providing new mechanistic insight. 

Furthermore, the mediator has been used for the bond cleavage of benzyl ethers, the oxidation of benzyl alcohol to benzaldehyde, the oxidation of toluene derivatives to benzoic acid esters, and the oxidation of aliphatic ethers [47]. 

Because the reduction potential of ether is usually more negative than that of halides, examples that belong to this category are rather rare. Generally, cathodic reduction of ethers is similar to that of alcohols, and nonactivated ethers are not reducible under the conditions of electroreduction. Activated ethers such as benzylic and allylic ethers are elec-trochemically reduced to a limited extent (Scheme 7) [1, 15, 16]. Reduction of epoxides is usually difficult however, electroreductive cleavage of activated epoxides to the corresponding alcohols is reported [17, 18]. The cleavage of the C—O bond of ethers is more easily accomplished in anodic oxidation than in cathodic reduction, which is stated in Chapter 6. 

As for (i-0-4 ethereal bond cleavage, reaction of the primary cation-radical with solvent water under the same conditions of bio-oxidation was shown to form an arylglycerol and the corresponding phenoxy radical (Kirk et al. 1986, Fabbri et al. 2005) (Scheme 8.22). Since the p-0-4 ethereal bond is the most abundant type of interunit linkage in the lignin polymer, this ethereal bond cleavage represents an important depolymerization reaction. 

Ethers are the least reactive of the functional groups. The cleavage of C-O bond in ethers takes place under drastic conditions with excess of hydrogen halides. The reaction of dialkyl ether gives two alkyl halide molecules. 

Diethyl ether has been shown to enhance decarboxylation [32] as a secondary reaction after C—O bond cleavage when the ortho and para positions are blocked. Scheme 7 shows this effect for compound 17. Some esters with the ortho and para positions free to react but with bulky substiments at the meta position also undergo decarboxylation in ether, tetrahydrofuran, and dioxane [33,34],... 

Cyclopropanes are oxidised at less positive potentials than -alkanes. Carbon-carbon bond cleavage occurs. When methanol is the solvent, the carbonium ion formed by bond cleavage reacts to form a methyl ether. The remaining carbon... 

Levoglucosan 14, which is derived from Z)-glucose, has a strained ether ring system. Oxidation in methanol causes carbon-carbon bond cleavage to yield D-arabinose. High yields are obtained in methanol with addition of sodium methoxide... 

For primary alkyl phenyl ethers 47, their hthiation under catalytic conditions (DTBB, 5%) in THF at room temperature gave the expected alkyUithiums, which by reaction with carbonyl compounds afforded, after hydrolysis, the expected alcohols 48 (Scheme 15) . In this case, only the O—Caiiyi bond cleavage was observed . On the other hand, the reaction shown in Scheme 15 failed for secondary (R = i-Pr) or tertiary (R = f-Bu) starting materials. 

Screttas and Micha-Screttas synthesized various dilithiated alkyls by the method of reductive sulphur-carbon bond cleavage with metallic lithium. The example of compound 147 shows that thioethers 146 are cleaved selectively in the presence of ether functionalities (Scheme 53). ... 

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