Phenolic coupling reactions

Reaction that can be carried out by the oxidative coupling of radicals may also be initiated by irradiation with UV light. This procedure is especially useful if the educt contains oleflnic double bonds since they are vulnerable to the oxidants used in the usual phenol coupling reactions. Photochemically excited benzene derivatives may even attack ester carbon atoms which is generally not observed with phenol radicals (I. Ninoraiya, 1973 N.C. Yang, 1966). 

In the first of these, the key step in the synthetic sequence involves an oxidative phenol coupling reaction patterned after the biosynthesis of the natural product. Preparation of the moiety that is to become the aromatic ring starts by methyla-tion of phloroglucinol (5) with methanolic hydrogen chloride to give the dimethyl ether (6). Treatment of that intermediate with sulfuryl chloride introduces the chlorine atom needed in the final product (7). 

Scheme 3. Phenolic coupling reactions caused by one-electron oxidations.

Vanillin (4-hydroxy-3-methoxybenzaldehyde) in ethanolic solution - as supplied as a flavouring agent - was dimerized by sunlight or more rapidly under a mercury lamp to dehydrodivanillin (3). This is a typical ortho-phenol coupling reaction [20],... 

If the five resonance forms of the phenoxy radical (Figure 3.6) can couple to any other phenoxy radical, the theoretical number of dimeric structures possible is 25. The relative frequency of involvement of individual sites in the phenolic coupling reaction depends on their relative electron densities. Quantum mechanical calculations predict that the high electron densities at the phenolic oxygen atom and the carbon atom would give rise to a high proportion of fi-O-4 linkages, which is indeed observed to be the case (Table 3.1). 

The previous section has presented evidence that phenolic units are carefully positioned within the wall polymers. When these units undergo oxidative phenolic coupling reactions in the cell wall, the coupling reactions themselves are also remarkably specific. This can be illustrated by reference to the tyrosine residues of extensin. 

The formation of o-quinones by the above oxidative methods is less reliable since the ortho quinonoid system is more susceptible to attack by electrophilic and nucleophilic species mild conditions are therefore essential. The use of the silver carbonate/Celite reagent noted above for phenol coupling reactions is particularly suitable the conditions are those described in Expt 6.129, and they have been applied to the oxidation of catechol, 4-methylcatechol, 4-t-butylcatechol, and 3,5-di-t-butylcatechol to yield the corresponding o-quinones in almost quantitative yield. 

The peroxidase reaction of heme peroxidases has found technical uses mainly for the polymerization of phenols and anilines (Scheme 2.13) [206-216] and for waste water treatment [217-220], whereas phenol coupling reactions in the biosynthesis of e.g. vancomycin are carried out by P450-type cytochromes [221],... 

Toward the industrial production of 34, Node and co-workers improved the yield of this phenolic coupling reaction using the suitably protected norbella-dine-type derivative (154) [115] (Scheme 25). 

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... 

Barton(29) devised a biomimetic route to thebaine (3), dihydrothebainone (13), and thus morphine following observations of Battersby.(30,3l) The alkaloid salutaridine (19) was derived from (+)-reticuline (18) by a low-yielding (0.03%) regioselective para-ortho phenolic coupling reaction according to Scheme 2.3. By the use of thallium tristrifluoracetate, Schwartz(32) improved yields to up to 23%. 

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... 

Biomimetic syntheses of benzylisoquinoline alkaloids have been performed by intramolecular oxidative phenol-coupling reactions using a variety of oxidants. Of them, K3Fe(CN)e has long been used for alkaloid syntheses The amine 732 bearing... 

SCHEME 145. Intramolecular oxidative phenol-coupling reactions with K3Ee(CN)6... 

SCHEME 154. Oxidative phenol coupling reactions with silver carbonate/Celite... 

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