Ethers electrooxidation

OS 30] [R 30] [P 22] The feasibility of generating a cation pool, i.e. of performing multiple reactions with various reactants, by means of electrooxidative micro flow processing was demonstrated [66,67]. The micro reaction system was consequently termed cation flow . By this means, various C-C bonded products were made from carbamates, having pyrrolidine, piperidine, diethylamine and trihydroisoquinoline moieties. These carbamates were combined with various silyl enol ethers, yielding nine products. 

Studies on the electrochemical oxidation of silyl-substituted ethers have uncovered a rich variety of synthetic application in recent years. Since acetals, the products of the anodic oxidation in the presence of alcohols, are readily hydrolyzed to carbonyl compounds, silyl-substituted ethers can be utilized as efficient precursors of carbonyl compounds. If we consider the synthetic application of the electrooxidation of silyl-substituted ethers, the first question which must be solved is how we synthesize ethers having a silyl group at the carbon adjacent to the oxygen. We can consider either the formation of the C-C bond (Scheme 15a) or the formation of the C-O bond (Scheme 15b). The formation of the C Si bond is also effective, but this method does not seem to be useful from a view point of organic synthesis because the required starting materials are carbonyl compounds. 

Another useful route to alkaloids involves the electrochemical oxidation of lactams (145) bearing functionality on nitrogen that can be used to intramolec-ularly capture an intermediate acyl im-minium ion (146). The concept is portrayed in Scheme 33 and is highlighted by the synthesis of alkaloids lupinine (150) and epilupinine (151) shown in Scheme 34 [60]. Thus, the electrooxidation of lactam (147) provided a 71% yield of ether (148). Subsequent treatment with titanium tetrachloride affected cyclization and afforded the [4.4.0] bicyclic adduct (149). Krapcho decarbomethoxylation followed by hydride reduction of both the... 

The electrooxidation of alcohols and ethers into aldehydes is successfully carried out by using the [(L2)2Mn02Mn [ 2)2 [(L2)2Mn02Mn(L2)2] system [199] and the results are indicated in Table 10 [200-204]. 

Tab. 10 Indirect electrooxidation of alcohols, ethers and aromatics with manganese mediators... 

Column III shows the effect of ultrasound upon the product ratio with methanol as solvent. As can be seen there is now 53 % bibenzyl, 32 % of methyl ether and 6% of methyl ester (with a total of 5 % of other products) suggesting a slight shift towards the two-electron products, but with an overall diminuition of solvent discharge (approx. 6% ester) and side-reactions (approx. 6%). This result confirms the fact the phenyl acetate electrooxidation favours the one-electron route (to bibenzyl) in a wide range of conditions [61], and is much less sensitive to mechanistic switches by manipulation of parameters (e. g. ultrasound) than is cyclohexane carboxylate electrooxidation [54]. 

Electrochemical oxidation of alkyl aryl ethers results m oxidative dealkylation and coupling of the intermediate radicals Electrooxidation in the presence of hydrogen fluoride salt leads to fluonnated dienones [66] (equation 58)... 

Electrooxidative activation is just one of the tools with which synthetic organic chemists can effect the dearomatization of arenois and their ethers to give cyclohexa-2,4-dienone derivatives. Other methods are based on the utilization of oxidizing reagents that mediate the oxidative nucleophilic substitution of 2-substituted arenois in the presence of appropriate nucleophilic species. These reagents are for the most part all based on metals (Section 15.2.2) or halogens (Section 15.2.3). 

Both pyrrolizidine and indolizidine alkaloids can be synthesized by taking advantage of the anodic a-alkoxylation of A -alkoxycarbonylpyrrolidines (e.g., 83 to 84). The method, first developed by Ross, Finkelstein, and Petersen, and later explored by Ban and coworkers [24, 25], has been utilized by Shono s group to synthesize isoretronecanol (87), trachelanthamidine (88), elaeokanine A (89), and elaeokanine C (90) [26] (Scheme 7). Once the or-methoxy group has been installed via electrooxidation and nucleophilic capture of the intermediate by methanol, the product 84 is treated with enol ether 85 and titanium tetrachloride to affect C-C bond formation adjacent to nitrogen and afford 86. The latter served nicely in syntheses of both indolizidine alkaloids elaeokanine A (89) and C (90). 

Swenton and coworkers have devised and achieved an exceptionally elegant synthesis of anthracyclinone aglycons. Key to the successful outcome is the ability to intercept the intermediate radical cation 226 formed in the oxidation of aromatic ethers, either inter- or intramolecularly, with the alkoxy radical, CH30, which is also formed electrooxidatively [55,56]. As illustrated, the methodology leads to the facile assembly of substituted quinone mono- or bisketals, 230 and 231. 

Triphenylhydrazine reacts in a similar way with enol ethers to cinnoline derivatives (Table 12, number 5). The electrooxidation of A -alkylhydrazines leads to an iminium ion, which can react with olefins to five-membered rings [Eq. (28)] [254]. The anodic oxidation of phenylhydrazones of benzaldehyde affords diphenylnitrilimines, which add to dipolarophilic compounds [255]. 

Vicinally tri- or tetramethoxy compounds may also be cleaved anodically. Thus 1,1,2-trimethoxycyclohexane obtained on electrooxidation of cyclohexanone enol ether may be oxidized to the acetal ester, (CH30)2CH(CH2)4 COOCH3 [34]. 

Electrooxidation is also viable for phenol ether-phenol ether coupling and has been thoroughly investigated. For example a range of compounds (65) with R = H or Me, Z = CH2 or O, = 1 or 2, reacted at the anode to give fair yields of the corresponding biaryls (66), together with spirodienone products (see Section 2.9.3.2). 

The Coventry group has also examined the behavior ofp-chlorophenyl acetate electrooxidation under ultrasound [187]. This substrate is known to markedly favor the two-electron mechanism [180], showing that the choice of reaction pathway is more dependent on substrate nature than upon manipulation of electrolysis parameters. A further feature of this system is the appreciable yield of p-chlorobenzalde-hyde-derived products. This is shown in Table 6 where it can be seen that sonication produces little change in relative product ratio, although there is an increase in total yield after ether extraction. Thus 46% by weight of mixed product is obtained (unreacted acid is not recovered by this procedure) with ultrasound, but only 23% by weight from the silent reaction. This represents increased reaction efficiency since the same quantity of charge was passed in each case. 

Instead of nucleophiles such as H2O, MeOH, RNH2 and halide ions, both the aryl group and olefinic double bond will react with an electrogenerated phenoxonium ion to give carbon-carbon coupled products. In particular, electrooxidative coupling reactions of a,ft)-diarylalkanes leading to cyclic diaryl ethers have been known to take place in a radical or cationic manner depending on the oxidation potential, the nature and location of substituents, the solvent systems and other factors, as cited in many books Electrochemical carbon-carbon bond formations will be described here. 

Electrooxidation of aromatic compounds has been intensively investigated, and many useful fine chemicals have been prepared by both side-chain and aromatic nucleus oxidation. Side-chain oxidation of alkylbenzenes may furnish benzyl alcohols, benzyl acetates, benzyl methyl ethers, Af-benzyl acetamides, benzaldehydes, benzoic acids, and so on. For instance, electrooxidation of p-methoxytoluene affords p-methoxybenzyl methyl ether, p-methoxybenzaldehyde, and/or its dimethylacetal depending on the choice of electrolysis media [3]. Many examples of electrooxidation of aromatic nucleus have been also reported. p-Quinones and their methyl acetals and semiquinones are prepared by electrooxidation of phenol derivatives and hydroquinones [3]. Nucleus-nucleus coupling of methoxybenzene derivatives... 

---