Phenol coupling reactions, anodic

Kirste A, Nieger M, Malkowsky IM, Stecker F, Fischer A, Waldvogel SR (2009) ortho-Selective phenol-coupling reaction by anodic treatment on boron-doped diamond electrode using fluorinated alcohols. Chem-Eur J 15 2273-2277... 

Malkowsky IM, Rommel CE, Frohlich R, Griesbach U, Putter H, Waldvogel SR (2006) Novel template-directed anodic phenol-coupling reaction. Chem Eur J 12 7482-7488... 

Numerous investigations have centered on the trapping of anodically generated phenoxonium ions with nucleophilic centers tethered to the reacting phenol ring. Much of the early work in this area centered on anodic phenolic coupling reactions, which are essentially Friedel-Crafts type cyclizations, affording spirodienones such as (LIII), often in excellent yield [Eq. (23)] [53]. Anodic cyclizations are treated in detail elsewhere in this edition. 

Bobbitt and coworkers have reported a number of intermolecular phenol coupling reactions, the most intriguing being a stereospecific phenol coupling reaction.12 Using a carbon anode they were able to produce only... 

Scheme 17 shows the final steps of each synthesis of ( )-discorhabdin C. For the details of our synthesis, see Sect. 4. In Yamamura s synthesis, discorhabdin C was obtained in 24% yield upon anodic oxidation of the bromophenol derivative 60 (R=H) [72, 73]. In Heathcock s synthesis, discorhabdin C was obtained by a phenolic coupling reaction of 60 (R=Ts) with CuCl2 and EtsN under bubbling O2 followed by detosylation [74]. 

Waldvogel SR (2010) Novel anodic concepts for the selective phenol coupling reaction. Pure Appi Chem 82(4) 1055-1063... 

The earlier literature on oxidative coupling of phenols is reviewed in Ref. [168] and that on anodic coupling in Ref. [169, 170] some examples of the coupling reactions are summarized in Table 11, see also Chapter 6. 

Diarylamides with arenes activated by electron-donating substituents can be converted to azacycles by anodic oxidation through phenolic oxidative coupling reactions that can be a key step in the synthesis of alkaloids (Schemes 16 and 17). According to the nature of substituents and the experimental conditions, either spiro compounds [22] or non-spiro compounds [23, 24] were obtained. 

Anodic treatment of 1,2- or 1,4-dihydroxy-substituted benzenes to form the corresponding quinones or masked congeners is well known, since they represent valuable synthetic intermediates [64]. Benzoquinone ketals of electron rich arenes like 18 can be challenging since the oxidative aryl-aryl coupling reaction usually competes. When using BDD anodes the benzoquinone ketal 19 is obtained in an almost quantitative manner, demonstrating the superior properties of this electrode material. Despite the basic conditions, no deblocking of the silyl-protected phenol moiety is observed [65] (Scheme 9). 

Oxidative coupling has been observed for benzene (52), methyl substituted benzenes (53), triphenylethylene (54), triphenyl-amines (55-59), anilines (57), carbazoles (60,61), iminobibenzyls (62), and heterocyclic phenols (71,72). Intramolecular anodic coupling reactions are used for synthesizing specific ring structures (63-68). Both dimer and octamer of dibenzothiophene have been detected (69,70)... 

Fockedey, E. and Van Lierde, A. (2002) Coupling of anodic and cathodic reactions for phenol electro-oxidation using three-dimensional electrodes. Water Res. 36,4169 4175. 

Substituted di- and triphenylamines lead to carbazoles (XXII, 0, Y = NR Table 7, number 8). The yields are poor, however, and the cyclization is restricted to tertiary amines with the para position blocked by substituents not susceptible to substitution or elimination. The 2-methyltetramethoxybibenzyl derivative XXIII cyclizes in an anodic 2,6 -coupling reaction, with a subsequent dienone-phenol rearrangement, to give an 88-98% yield of the dihydrophenanthrene XXIV [Eq. (15)], which contains the essential structural elements of the B, C, and D ring of steroids [143]. 

The selective oxidative phenolic orf/io-coupling reaction of simple methyl-substituted phenols turned out to be challenging [12]. When 2,4-dime thy Iphenol (1) is treated by conventional or electro-organic methods, not only the desired biphenol (2) is formed but rather a plethora of polycyclic architectures (Scheme 2) is observed. The major product is Pummerer s ketone (3) and related compounds with a wide structural diversity [13-16]. Application of a boron tether ameliorated the situation tremendously, and biphenol (2) was obtained as the major product [17, 18]. This templated anodic oxidation of 1 represents a multistep process but is suitable for the electro-organic synthesis of (2) on larger scale (see entry Electrosynthesis Using Template-Directed Methods ) [19]. 

Kirste A, Schnakenburg G, Stecker F et al (2010) Anodic phenol-arene cross-coupling reaction on boron-doped diamond electrodes. Angew Oiem IntEd49(5) 971-975... 

The trimethylsilyloxy (TMSO) group is stable under the coupling conditions in acetonitrile (Table 12, number 6). After oxidative dimerization the TMS-ether can be mildly hydrolyzed (H+ and H2O) to the phenol or converted to a dibenzofuran. 1,2-Dialkoxybenzenes have been trimerized to triphenylenes (Table 5, numbers 7, 8). The reaction product is the triphenylene radical cation, which is reduced to the final product either by zinc powder or in a flow cell consisting of a porous anode and cathode [188]. Anodic trimerization of catechol ketals yields triphenylene ketals, which can function as a platform for receptors, for example, in an artificial caffeine receptor [190]. 

Anodic C, C-coupling is a very powerful tool to synthesize cyclic compounds with high regio- and stereoselectivity. It involves inter- and intramolecular coupling of arylolefins, dienes, enolethers, phenol ethers, and aromatic amines and often opens a quick entry into complex natural products in a few steps. Although the mechanism is fully established in only a few cases, it does appear to involve the coupling of two radical cations at the site of their highest radical density and is further controlled by steric constraints. This important type of reaction is reviewed in Chap. 5 and in Refs. [89, 90]. 

One of the most synthetically useful anodic C-C bond forming reactions developed to date involves the intramolecular coupling of phenol derivatives with olefins. Yamamura has demonstrated that these reactions tend to lead to three classes of products (Scheme 22) [36]. The type of product generated depended strongly on both the nature and stereochemistry of the functional groups attached to the olefin moiety. For example, consider the two cyclization reactions illustrated in Scheme 23 [37]. In this experiment, the stereochemistry of the initial olefin substrate completely dictated the ring skeleton of the product. 

In an effort to explore the factors that govern anodic C-C bond formation, Swenton and coworkers have also been exploring the intramolecular coupling of phenols and olefins (Scheme 28) [44]. In these reactions, initial oxidation of the phenol followed by loss of a proton and a second oxidation led to the formation of a cationic intermediate (26). This intermediate was trapped by the olefin to form a second cation that was in turn trapped by methanol to form the final product 28. When R2 was equal to methyl (25b) or phenyl (25c) the reaction led to a good yield of the cyclized product. Reactions where the R2 was equal to a hydrogen (25a and 25d) were not so successful. The cyclizations were compatible with the incorporation of the olefin into a third ring (25e). 

Using a different dimerization method, namely phenolic oxidation, chiral substrates react in a more stereoselective manner than under reductive conditions. The choice of oxidizing reagent may drastically affect the stereochemical outcome of the reaction. Thus, when potassium hexacyanoferrate(III) is used (17 )-l,2,3,4-tetrahydro-6-methoxy-l,2-dimethyl-7-isoquino-linol couples to give a mixture of atropisomers 3 in 38 % yield and with a d.r. (M)I(P) of 45 553,4. Only one single atropisomer, namely (A/)-3, is formed, in a 66% yield by anodic oxidation, which is attributed to electrode surface effects3. 

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