Phenols dimerization, oxidative

Further utility of the 4-oxazolin-2-one as a protective group (see Vol. 2) is evidenced in the synthesis of the hydroxylated tetrahydrobenzylisoquinolines of the type (59). An attempt to effect phenolic oxidative dimerization of homo-orientaline (60) gave instead, after acetylation, the 1-acetoxy-derivative (61) in low yield. A series of 5-hydroxy-6-hydroxymethyl-, 6-hydroxy-7-hydroxy-methy 1, and 7-hydroxy-6-hydroxymethyl-1 -(3,4,5-trimet hoxybenzy 1)-1,2,3,4-... 

The primary synthetic route proceeds via oxidative dimerization of 2-aminoan-thraquinone in the presence of an alkali hydroxide. 2-aminoanthraquinone, for instance, is fused with potassium hydroxide/sodium hydroxide at 220 to 225°C in the presence of sodium nitrate as an oxidant. New techniques involve air oxidation of 1-aminoanthraquinone at 210 to 220°C in a potassium phenolate/sodium acetate melt or in the presence of small amounts of dimethylsulfoxide. A certain amount of water which is formed during the reaction may be removed by distillation in order to improve both efficiency and yield. 

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]. 

In phenolic oxidative coupling reactions, these phenol-derived radicals do not propagate a radical chain reaction instead, they are quenched by coupling with other radicals. Thus, coupling of two of these resonance structures in various combinations gives a range of dimeric systems, as shown. The... 

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. 

Organometallic compounds asymmetric catalysis, 11, 255 chiral auxiliaries, 266 enantioselectivity, 255 see also specific compounds Organozinc chemistry, 260 amino alcohols, 261, 355 chirality amplification, 273 efficiency origins, 273 ligand acceleration, 260 molecular structures, 276 reaction mechanism, 269 transition state models, 264 turnover-limiting step, 271 Orthohydroxylation, naphthol, 230 Osmium, olefin dihydroxylation, 150 Oxametallacycle intermediates, 150, 152 Oxazaborolidines, 134 Oxazoline, 356 Oxidation amines, 155 olefins, 137, 150 reduction, 5 sulfides, 155 Oxidative addition, 5 amine isomerization, 111 hydrogen molecule, 16 Oxidative dimerization, chiral phenols, 287 Oximes, borane reduction, 135 Oxindole alkylation, 338 Oxiranes, enantioselective synthesis, 137, 289, 326, 333, 349, 361 Oxonium polymerization, 332 Oxo process, 162 Oxovanadium complexes, 220 Oxygenation, C—H bonds, 149... 

Wynberg studied stereochemistry of the McMurry reductive dimerization of camphor in detail (64). In Scheme 37, A and B are homochiral dimerization products derived by the low-valence Ti-promoted reduction, while C and D are achiral heterochiral dimers. The reaction of racemic camphor prefers homochiral dimerization (total 64.9%) over the diastereomeric heterochiral coupling (total 35.1 %). Similarly, as illustrated in Scheme 38, oxidative dimerization of the chiral phenol A can afford the chiral dimers B and C (and the enantiomers) or the meso dimer D. In fact, a significant difference is seen in diastereoselectivity between the enaritiomerically pure and racemic phenol as starting materials. The enantiomerically pure S substrate produces (S,S)-B exclusively, while the dimerization of the racemic substrate is not stereoselective. In the latter case, some indirect enantiomer effect assists the production of C, which is absent in the former reaction. Thus, it appears that, even though the reagents and reaction conditions are identical, the chirality of the substrate profoundly affects the stability of the transition state. 

Biaryls have also been prepared by coupling support-bound aryl halides with aryl-zinc compounds (Figure 5.20) or with aryl(fluoro)silanes [203]. As with Suzuki or Stille couplings, these reactions also require transition metal catalysis. An additional strategy for coupling arenes on solid phase is the oxidative dimerization of phenols (Figure 5.20). 

Phenols suffer oxidation to quinones and oxidative dimerizations under the action of silver carbonate on Celite .13... 

Autoxidation of 9-hydroxyellypticine (60) is a good example of degradation of phenols, showing the formation of a quinone-imine (XV) and an oxidative dimer (XVI, Fig. 12). Phenols can be quite stable in the protonated... 

Yields of dimer in phenol oxidations are often decreased by competing reactions such as subsequent oxidation of the dehydro dimer or the anodically hydro-... 

Not many catalyzed processes involving free radicals are known with these metals. Some vanadium-catalyzed pinacol coupling reactions were developed (reviews [129, 171], [172, 173] and cited ref, [174]). Niobium and tantalum complexes were applied in pinacol coupling reactions [130]. Vanadium(IV) [175-179] and vanadium(V) ([129], reviews [180-186]) complexes are known to catalyze asymmetric oxidative dimerizations of phenols and naphthols in moderate to excellent ees applying oxygen as the terminal oxidant. Biaryls are accessible by intramolecular coupling of sodium tetraarylborates, catalyzed by EtOVOCl2 in the presence of air [187]. 

Other radical-based transformations are ruthenium-catalyzed oxidative dimerizations of phenols [263] and reductive dimerizations [264], The isomerization of chiral c/s-epoxides to tram-epoxides catalyzed by 2-10 mol% TpRu(py)2Cl proceeds at 100 °C in 95-98% yields with inversion of configuration [265], A radical or SN2 mechanism was discussed for this process. 

Scheme 51. Di-tert-butyl peroxide-mediated oxidative dimerization of a chiral phenol precursor to the magistophorenes.

The tyramide amplification technique is based on the ability of phenolic compounds to become oxidized to highly reactive and unstable intermediates (8). When biotinyl tyramide is oxidized, dimerization with electron-rich aromatic compounds, such as those found in protein molecules, occurs (9). This reaction can be harnessed in immunohistochemistry to generate highly reactive biotinyl-tyramide intermediates that bind rapidly to protein molecules in the immediate vicinity of peroxidase enzymes. This reaction results in the deposition... 

The final products of phenol oxidation are generated by secondary reactions of the radicals produced by the peroxidase. One very common pathway involves dimerization or oligomerization of the radicals, as illustrated in Fig. 5.14 for the oxidation of a para-substituted phenol such as tyrosine [R = CH2CH(NH2)C02H]. The dimerization can occur between two ring carbon atoms or by addition of the oxygen of one phenoxy radical to a ring carbon of the other. 

Notwithstanding the phenol dimers are builder compounds with respect to the starting substrate, thus making their access to the peroxidase active site more difficult, they have a lower redox potential and compete with monomeric phenols in the reaction with compound I and compound II. Furthermore, the phenoxy radical can oxidize a phenol dimer to its radical form. This results in the formation of oligomeric and then polymeric compounds at longer reaction times [17]. Thus, if the products of interest are the diphenolic compounds, the reaction must be carried out in mildest conditions and only the products formed in the initial phase have to be collected. But in some cases [18-20], the o.o -biphenyl is the principal product of phenol oxidation, such as with p-cresol. tyrosine, etc. All peroxidases can be employed for these reactions, but HRP is usually preferred with respect to other peroxidases due to its higher availability and to its broad specificity. Whole cell... 

Oxidation of orr/to-alkoxyphenols in alcohol solvents leads to highly reactive ortho-quinone monoketals, which undergo spontaneous dimerization unless appropriately substituted. In one useful example of such a [4 -f 2]-cycloaddition, monoketal (XXXVIII), derived from constant current electrolysis of phenol (XXXVII), dimerized to give the neolignan natural product asatone (XXXIX) in 34% yield [45] ... 

The ready oxidation of phenols to dimeric products has been well known for more than a century. The invaluable survey of the area by Musso lists over 20 papers published before 1900 on, for example the... 

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