Phenolic ethers, phenol-dienone

Intramolecular oxidative phenol coupling. The 1,3-bis(hydroxyphenyl)pro-pane (1) is converted into the phenolic dienone (2) in 76% yield by reaction with 2.5 molar equivalents of vanadium oxychloride in refluxing ether (10 hours).1 Use... 

Cross-conjugated dienones are quite inert to nucleophilic reactions at C-3, and the susceptibility of these systems to dienone-phenol rearrangement precludes the use of strong acid conditions. In spite of previous statements, A " -3-ketones do not form ketals, thioketals or enamines, and therefore no convenient protecting groups are available for this chromophore. Enol ethers are not formed by the orthoformate procedure, but preparation of A -trienol ethers from A -3-ketones has been claimed. Another route to A -trien-3-ol ethers involves conjugate addition of alcohol, enol etherification and then alcohol removal from la-alkoxy compounds. 

The reaction is undoubtedly intramolecular. Evidence for this comes from the absence of crossed-over products when two different ethers were rearranged together121. Further, optically active ortho- 1,3-dimethylallyl phenol is formed from optically active 1,3-dimethylallyl phenyl ether122 and the presence of dienone intermediates has been demonstrated. Claisen and Tietze123 first proposed intermediate dienones such as LXXIX and LXXX. This was established124 when... 

Photoaddhion of electron donor olefins such as vinyl ethers and stilbene to variously methyl and halogeno-substituted 1,4-benzoquinones resulted in the formation of dihydrobenzofurans via a dienone-phenol rearrangement of the primary product spirooxetanes <96H(43)619>. High-temperature water seems to be an alternative to use of acid catalysts or organic solvents by the cyclization of allyl phenyl ethers to dihydrobenzofurans <96JOC7355>. 

Accordingly, carbon-carbon bonds involving positions ortho or para to the original phenols, or ether linkages may be formed. The reactive dienone systems formed as intermediates may, in some cases, be attacked by other nucleophilic groupings (see Section 10.10), extending the range of structures ultimately derived from this basic reaction sequence. 

The alkenylation of phenols also proceeds smoothly in the presence of TMG (Scheme 6). The major products are not aryl alkenyl ethers but a-alkenylated cyclohexa-2,4-dienones. That is, C-alkenylation occurs exclusively at the ortho position of phenols. When 2-naphthol reacts with two equivalents of the alkenylbismuthonium salt, a,a-dialkenyl ketone is obtained in good yield as the sole alkenylated product. 

Great differences in product structures and product distributions are obtained by lead(IV) oxide or acetate oxidation of perfluorophenol in different solvents and media. The reaction with the former agent gives a quinoid ether in 22% yield (Table 10).173 The oxidation with lead(IV) acetate has been optimized to such a level as to give perfluoro cyclohexa-2,5-dienone (4) in 65 % yield.174 Treating the phenol with vanadium(V) fluoride or vanadium(III) fluoride as well as xenon difluoride gives a mixture of products,175 therefore, the reactions are only of minor preparative importance. 

Diazo ketone cyclizathn. Some years ago Mander and his group1 demonstrated that the protonated diazomethylcarbonyl group can initiate cyclizations in unsaturatcd systems. In the case of phenolic diazo ketones, formation of spirodienones can predominate over competing side reactions (dienone-phenol rearrangement). Tetra-fluoroboric acid or boron trifluoride etherate can be used, but trifluoroacetic acid is usually the acid of choice. 

Oxidative phenolic coupling.1 A new hiomimetic approach to morphine alkaloids involves oxidative intramolecular coupling of the reticuline derivative 1 to a salutaridine derivative 2 with VOCl3 in ether.1 If the reaction is conducted in CH2C12 2 is obtained in markedly lower yield and the undesired aporphine 3 is formed as a major product. The dienone 2 has been converted into 2-hydroxycodeine (4). 

Intramolecular oxidative cyclizations in the appropriately substituted phenols and phenol ethers provide a powerful tool for the construction of various practically important polycyclic systems. Especially interesting and synthetically useful is the oxidation of the p-substituted phenols 12 with [bis(acyloxy)iodo]-arenes in the presence of an appropriate external or internal nucleophile (Nu) leading to the respective spiro dienones 15 according to Scheme 6. It is assumed that this reaction proceeds via concerted addition-elimination in the intermediate product 13, or via phenoxenium ions 14 [18 - 21]. The recently reported lack of chirality induction in the phenolic oxidation in the presence of dibenzoyltar-taric acid supports the hypothesis that of mechanism proceeding via phenoxenium ions 14 [18]. The o-substituted phenols can be oxidized similarly with the formation of the respective 2,4-cyclohexadienone derivatives. 

The acid 350 was demethylated with pyridine hydrochloride, then realkylated with benzyl bromide in aqueous potassium hydroxide to give 351. The latter was converted to the diazoketone 352 by the sequential treatment of 351 with oxalyl chloride and etheral diazomethane. Reaction of 352 with concentrated hydrobromic acid gave the bromoketone 353. The latter was reduced with sodium borohydride at pH 8 -9 to yield a mixture of diastere-omeric bromohydrins 354. Protection of the free hydroxyl as a tetrahydro-pyranyl ether and hydrogenolysis of the benzyl residue afforded 355. The phenol 355 was heated under reflux with potassium m/V-butoxide in tert-butyl alcohol for 5 hr to give a 3 1 epimeric mixture of dienone ethers 356 and 357 in about 50% yield. Treatment of this mixture with dilute acid gave the epimeric alcohols 358 and 359. This mixture was oxidized with Jones reagent to afford the diketone 349. 

Rearrangement of phenols to dienones occurs readily in superacids. Some simple bicyclic phenols and their ethers have been investigated as model compounds by use of HF-SbFs [73]. This method is also applicable to natural products [74]. For example, treatment of estrone derivatives in HF-SbFs, then aqueous bicarbonate work-up led to estra-4,9-diene-3,17-dione (Eq. 30). The opposite rearrangement, i.e. that of dienones to phenols, can also be achieved in an HF-SbFs medium (Eq. 31) [75]. 

Electron-rich olefins such as vinyl ethers and stilbenes will photocycloadd to various 1,4-benzoquinones to give a spirooxetane, which following dienone-phenol rearrangement, gives a dihydrobenzofuran. Irradiation of o-benzoqui-... 

Phenols are oxidized by NaBiO3 to polyphenylene oxides, quinones, or cyclohexa-2,4-dienone derivatives, depending on the substituents and the reaction conditions [263]. For example, 2,6-xylenol is oxidized in AcOH to afford a mixture of cyclohexa-dienone and diphenoquinone derivatives (Scheme 14.123) [264] and is oxidatively polymerized in benzene under reflux to give poly(2,6-dimethyl-l,4-phenylene) ether (Scheme 14.124) [265]. Substituted anilines and a poly(phenylene oxide) are oxidatively depolymerized by NaBiO, to afford the corresponding anils [266]. Nal iO, oxidizes olefins to vicinal hydroxy acetates or diacetates in low to moderate yield [267]. Polycyclic aromatic hydrocarbons bearing a benzylic methylene group are converted to aromatic ketones in AcOH under reflux (Scheme 14.125) [268]. 

A totally different synthesis of the diterpene alkaloids has been reported by Masamune (102-104). The carboxylic acid CCXCII was converted via the bromo ketone CCXCIII to the tetrahydropyranyl ethers CCXCIV. Hydrogenolysis of the latter gave the corresponding phenols CCXCV. Base treatment of CCXCV effected cyclization of only one isomer to furnish a dienone ether (CCXCVI). Catalytic hydrogenation of the benzoate (CCXCVII) gave the tetrahydro cis-fused derivative... 

Discovery of the dienone-phenol rearrangement of quinol acetates has made possible the synthesis of dihydric phenols that were difficult of access by other routes. The starting materials are obtained from phenols and lead tetraacetate, and with acetic anhydride and sulfuric acid (Thiele acetylation) or with boron trifluoride in ether they give, respectively, di- and mono-acetyl derivatives of resorcinol or hydroquinone.309 When treated with lN-sodium hydroxide, 0-quinol acetates of type (1) undergo nucleophilic addition of an OH" ion, giving resorcinol derivatives (2).310 Occurrence of the reaction is considered... 

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