Anodic oxidation benzylic position

Allylsilanes and benzylsilanes are more susceptible to anodic oxidation than tetraalklsilanes and arylsilanes. It should also be noted that the oxidation potentials of allylsilanes and benzyl silanes are much less positive than those of... 

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. 

Anodic oxidation of j9-methylbenzyl-sulfonic ester, -carboxylic ester, and -nitrile in Et3N-3HF/CH3CN affords fluorides and acetamides at tbe metbyl (Me) and substituted (CH2E) benzyl position Me/CH2E = 24/76 (E = C02Et), 9/91(CN), 69/31 (SOsEt). In tbe radical bromination of these compounds, substitution at CH3 is enhanced [20],... 

Chemoselective anodic methoxylation at a distinct carbon atom in the a-position to an amino group in a polypeptide was achieved by prior introduction of a silyl group as an electroauxiliary at this carbon atom [156]. Amide oxidation in A-acetylpyrrolidines substituted with electron-rich phenyl rings led to either methoxylation a to the nitrogen atom or in the benzylic position. Mechanistic studies indicate that both the amide and the phenyl oxidation compete, but intramolecular electron transfer leads to... 

The indirect anodic cleavage of carbon-hydrogen bonds in the benzyl position using triarylamine mediators was also used for mild and selective deblocking of hydroxy, carboxyl, and amino groups. The primarily formed cation radical of the protective group is readily deprotonated in the benzyl position by an added base (Eq. (107)). This benzylic radical is easily further oxidized to the benzyl cation which subsequently is cleaved by attack of a nucleophile, such as water (Eq. (108)). 

Fuchigami and coworkers and Yoshida and coworkers independently found that anodic oxidation of benzylsilanes in the presence of nucleophiles such as alcohols and carboxylic acids resulted in a selective cleavage of the C—Si bond and the oxygen nucleophiles were introduced exclusively into the benzylic position (equation 6)11-13. In the absence of nucleophiles, the benzylsilane itself plays a role of a nucleophile and benzyl(trimethylsilyl-methyl)benzene is formed (equation 7)11,12. 

Anodic oxidation of 4-silylazetidin-2-ones in the presence of fluoride ions provides 4-fluoroazetidin-2-ones in high yields33. This fluorination is completely regioselective. Even in the case of the TV-benzyl derivative, a fluorine atom is selectively introduced into the C-4 position of the /1-lactam ring (equation 28). In contrast, unsilylated azetidin-2-ones give no fluorinated product. 

Table 4-1 compares two different reactions, namely, anode oxidation and oxidation with cerium ammonium nitrate (which are bona fide electron-transfer processes) and bromination by /V-bromosuccinimide in the presence of azobis(iso-butyro)nitrile (which is bona fide hydrogen-atom-transfer process). Both electron-transfer and hydrogen-atom-transfer processes have the benzylic radical as a common intermediate, but positional selectivity is stronger for electron-transfer processes. Another important point is the preference of the 2-positioned methyl group over the 1-positioned group, in terms of selectivity. For 1,2,3-tetramethylbenzene, such a preference reaches values from 16 to 55, and it is over 200 for 5-methoxy-1,2,3-tctramcthylbcnzcnc. 

A wide variety of compounds have been selectively monofluorinated in the benzylic position by anodic oxidation in 70% hydrogen fluoridc/pyridine, tricthylamine trishydrofiuoride in sulfolane, triethylamine trishydrofluoride, and triethylaminc trishydrofluoride in acetonitrile. I n general the reaction supports a wide range of substrates with benzyl fluorides formed selectively and in high yield. 

The reason for the unexpected predominant substitution at the methyl group instead of the benzyl group was the matter of some discussion [22-24], In the case of the 7V-benzyl-A -methylethanolamine, anodic oxidation in MeOH/KOH leads to the intramolecular cyclization by attack of the hydroxy function onto the positively charged benzylic a-C atom. Thus, 3-methyl-2-phenyl-l,3-oxazolidine is formed in 60% yield [20]. 

Anodic oxidation of A -benzyl-A/ -methylethanolamine leads to the formation of a mixture of 3-methyl-2-phenyl- and 3-benzyloxazolidine by intramolecular attack of the hydroxy group at the intermediate iminium ion, mainly in the benzylic position [181]. The typical fragmentation of jS-amino alcohols occurs as a side reaction, in this case giving foiTnaldehyde and A/ -benzyl-A/ -methoxymethyl-A -methyl amine. The direct anodic oxida-... 

The anodic oxidation of A/ -alkyl- and A/ -benzyl-y3-lactams in methanol at Pt anodes in the presence of Et4NBp4 as an electrolyte leads to the methoxylation of both the endo-and exocyclic carbon in a-position to nitrogen. Usually the exocyclic carbon was more easily oxidized than the endocyclic carbon. With a tertiary exocyclic a-carbon, the formation of the endo-oxidation product was increased. A/"-Benzyl-)3-lactams were predominantly oxidized in the exocyclic a-position. In case of 7V-4-methoxybenzyl-)3-lactam exocyclic oxidation occurred with total regioselectivity [227,228]. 

The silyl group and ArS groups are effective for the oxidation of the benzylic position. The anodic oxidation of benzylic sulfides in the presence of allylsilanes takes place smoothly, giving rise to selective C-S bond cleavage and introduction of an allyl group on the benzylic carbon Eq. 11 [15]. 

Kabore L, Chebli S, Faure R, Lament E, Marquet B. Diaster-eoselective fluorination at benzylic position by anodic oxidation. Tetrahedron Lett. 1990 31 3137. 

Moeller and co-workers published the electron transfer cyclization of silyl enol ethers initiated by anodic oxidation. The in situ generated radical cation of 54 intramolecularly attacks the double bond. The resulting benzylic radical position is further oxidized and attacked by a solvent molecule as well as the remaining cationic center to yield 55. Cleavage of the SiO bond leads to the formation of 56 (Scheme 12). 

Benzylic CH bonds Benzylic CH bonds can be preferentially substituted at the anode by oxidation of the aromatic ring to a radical cation, which can undergo side-chain substitution at the benzylic carbon atom and/or nuclear substitution. Benzylic substitution preponderates, when there is an alkyl substituent at the aromatic carbon bearing the highest positive charge density in the radical cation, while a hydrogen at this position leads to a nuclear substitution [16]. Anodic benzylic substitution is used in technical processes for the conversion of alkyl aromatics into substituted benzaldehydes [17, 18]. Anodic benzylic substitution has been used for the regioselective methoxylation of estratrienone at C9 (Fig. 4) [19]. 

The scheme of reactions proposed to explain the products obtained is shown, after small modifications, in Scheme 8. Primary radicals 12 formed at the anodes produce with added 30 or 36 (equation lOe) the substituted benzyl or allyl radicals 38, which can dimerize to 39 or can couple with the added olefin to form radicals 40 or 41. For allyl radical (38) a 1,1 - or l,3 -coupling is possible yielding 41 and 40, respectively. Further couplings of 40 and 41 with the primary radical 12 produce 39 and head-to-tail dimer 42, respectively. It was evident from the products obtained that the coupling of 38 in the 1-position occurs 5 to 11 times faster than in the 3-position. However, for readily polymerizable olefins, rather polymerization occurs, in particular at graphite electrodes. At Pt electrodes both dimers 39 and 42 are formed, but for Cu electrodes exclusively dimers 39 were obtained with moderate yields. Thus, an indirect electrolysis including the oxidation of copper to Cu+ ions and their further reaction with 5 yielding intermediate RCu was considered, but not proved . ... 

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