Oxidative dimerization 2-methoxyphenols

Although permanganate ions are not generally used to effect oxidative coupling of phenols, it has been shown that, in the presence of a catalyst in an organic solvent, 2-methoxyphenols are coupled oxidatively under very mild conditions to produce the dimeric products (>50%) [48], Unsaturated substituents are not oxidized under the mild conditions. 

Potent antileukemic agent, asatone (11), which was isolated from Asarum taitonense Hayata, was synthesized via dimerization of cyclohexa-2,4-dienone (138) generated by PIDA oxidation of o-methoxyphenol (137) [94] (Scheme 11). 

On controlled electrolysis (+880 mV vi. SCE 2 Fmol ) in MeOH, 2,6-dibromo-4-methoxyphenol (50) underwent 2e oxidation, followed by nucleophilic capture with MeOH to afford 2,6-dibromo-4,4-dimethoxy-2,5-cyclohexadien-l-one (51) in quantitative yield. 50 was also electrolyzed at a less positive potential (+440 mV ca 1 Fmor ) in MeOH containing AcOH-AcONHt to give two dienones (52 and 53) in 32 and 55% yields, respectively, as shown in Scheme 10. Herein, these products must be formed by C—O and C—C couphngs with bromine substitution, respectively. Therefore, the selective formation of 2e oxidation products or radical coupling dimers depends on the choice of the solvent. 

Methoxycarbonyl-2-methoxyphenol (421) underwent PhI(OAc)2-promoted oxidation in MeOH resulting in the formation of 4-carbomethoxy-6,6-dimethoxycyclohexa-2,4-dienone (422), which was spontaneously dimerized to 423 in 85% yield . However, in... 

Generally, on PhI(OAc)2-promoted oxidation of o-methoxyphenols in MeOH containing a large excess of electron-rich dienophiles, the resulting o-quinone monoketals may undergo an intermolecular Diels-Alder reaction with the dienophiles to afford the corresponding dimers. 4-Methoxycarbonyl-2-methoxyphenol (421) was submitted to PhI(OAc)2-promoted oxidation in MeOH containing benzyl vinyl ether (BVE) or dihydrofuran (DHF)... 

However, 2-t-butyl-4-methoxyphenol was oxidized in the same system to give dibenzofuran derivatives concomitantly with dimer. It was useful to use copper(II)compounds in order to get these phenols by one step synthesis. 

The second P-0-4 dimer submitted to reaction with dioxygen (10 bar) at room temperature in the presence of Co(II) salen as the catalyst was l-(3,4-dimethoxyphenyl)-(2-methoxyphenoxy)ethane-l-ol 23, also prepared according to Landucci (22). In the same reaction conditions, again, veratric add methyl ester 4 was recognized after methylation, derived from vanillic acid methyl ester 6 present in the oxidation reaction mixture. The other component of the methylated mixture was 1,2-dimethoxy-benzene 22, derived from ortho-methoxyphenol 20. 

The Lewis acid-catalysed orientation reversal in the reaction between substituted cyclohexa-1,3-dienes and 2,6-dimethyl-l,4-benzoquinone ° has been employed in an interesting synthesis of quassin (218). ° Thus, reaction at room temperature of the diene (215) with the above quinone in the presence of an equivalent quantity of Bp3,OEt2 gave the adduct (216) which was converted by several subsequent steps into (218). In the absence of the catalyst the alternative adduct (217) was obtained. Periodic acid oxidation of substituted o-cresols ° and of 2-methoxyphenols in methanol solution affords intermediate o-quinol methyl ethers or o-quinone dimethyl ketals which dimerize to give dienediones with structures related to those of (216) and (217). Another report concerns the formation of a Diels-Alder dimer upon hypochlorite oxidation of 2,2 -methylenebis(4-methyl-6-t-butyl)phenol. ... 

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