Phenol opening, oxidative

Figure 9-26. The various types of oxidation reaction catalysed by metalloenzymes. The conversion of a phenol to a 1,2-dihydroxybenzene and the ring opening oxidation both involve oxygen atom transfer to the substrate, whilst the oxidation of a 1,2-diol to a 1,2-quinone is of the type discussed earlier in this chapter.

With a similar rationale, Cai and coworkers tried to expand the product library by aiming for structural analogs of the widely applied 1,4-benzoxazepines [42]. These seven-membered rings are usually synthesized in a multistep process, but are now available from three simple starting materials in a palladium-catalyzed multicomponent approach. The reaction cascade is initiated by deprotonation and successive ring opening of the electron-poor aziridine 167 by the phenolate 168. Oxidative addition of palladium to the aryl iodide allows isocyanide insertion to furnish 172. Base-induced... 

Significant quantities of the diphenoquinone are also produced if the ortho substituents are methoxy groups (36). Phenols with less than two ortho substituents produce branched and colored products from the reactions that occur at the open ortho sites. It is possible to minimize such side reactions in the case of o-cresol oxidation by using a bulky ligand on the copper catalyst to block the open ortho position (38). 

The key step in this sequence, achieved by exposure of 46 lo a mixture of sulfuric acid and acetic anhydride, involves opening of the cyclopropane ring by migration of a sigma bond from the quaternary center to one terminus of the former cyclo-l>ropane. This complex rearrangement, rather reminiscent of the i enone-phenol reaction, serves to both build the proper carbon. keleton and to provide ring C in the proper oxidation state. 

A one-pot procedure [9] based on the cycloaddition of 4-aryl-2-silyloxybuta-dienes 7 and bisdiene 8 with alkynes, followed by oxidative aromatization of the cycloadducts, opened a route to polycyclic phenols without isolating the cyclo-hexadiene derivative intermediates (Scheme 2.5). 

A large variety of metabolic cyclization reactions, counterparts to the reactions of hydrolytic ring opening discussed above, occur without any change in the degree of oxidation, and often nonenzymatically. Such reactions proceed by various mechanisms of intramolecular nucleophilic substitution, with elimination of amine, phenol, halide, or H20. 

ARO reaction with phenols and alcohols as nucleophiles is a logical extension of HKR of epoxides to synthesize libraries of stereochemically defined ring-opened products in high optical purity. To this effect Annis and Jacobsen [69] used their polymer-supported Co(salen) complex 36 as catalyst for kinetic resolution of epoxides with phenols to give l-aiyloxy-2-alcohols in high yield, purity and ee (Scheme 17). Conducting the same reaction in the presence of tris(trifluoromethyl)methanol, a volatile, nonnucleophilic protic acid additive accelerates KR reaction with no compromise with enantioselectivity and yield. Presumably the additive helped in maintaining the Co(III) oxidation state of the catalyst. 

A parallel was drawn between stable ion and AMI studies of methylphenanthrenes and solvolytic studies of K-region and non-K-region phenanthrene oxides. The carbocation formed by opening of the 1,2-epoxide closely resembled the 2-methylphenanthrene cation (and 7H ), and the regiochemistry of phenol formation (1-phenanthrol) could be understood. Similarly, phenanthrenium cations derived from the 3-methyl and dimethylated compounds served as models for carbo-cations formed by solvolysis of phenanthrene-3,4-epoxide (formation of 4-phenanthrol following hydride shift). 

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