Non-phenolic oxidative coupling

In the non-phenolic oxidative coupling reaction the electron-rich arene 19 undergoes electron transfer yielding the radical cation 20, which is preferably treated in chlorinated solvents or strongly acidic media. Attack of 20 on the electron-rich reaction partner 21 will proceed in the same way as an electrophilic aromatic substitution involving adduct 22 which extrudes a proton. The intermediate radical 23 is subsequently oxidized to the cationic species 24 which forms the biaryl 25 by rearomatization. In contrast with the mechanism outlined in Scheme 5, two different oxidation steps are required. 

Phenolic or non-phenolic oxidative coupling methods have been extensively used since the 1970 s to synthesize polyoxygenated bridged biaryl compounds, as will be illustrated later in the case of steganes. Remarkably enough, the use of transition metal oxidants is particularly suited to perform intramolecular biaryl coupling whereas most other methods are better suited to intermodular coupling. 

Novel phenanthro[9,1 ()-r/ isoxazoles 37 have been prepared by intramolecular Stille-Kelly stannylation/coupling of o,o -diiodo-4,5-diarylisoxazoles and by PIFA-mediated non-phenolic oxidative coupling of the corresponding non-halogenated substrates <02T3021>. 

A short synthesis of ( )-isostegane, a tetracyclic dibenzocycloota-diene lactone, has been achieved by a sequential double a, -substitution of an electron-deficient ethylene derivative, in this case zl P-butenolide, followed by non-phenolic oxidative coupling with VOFg . An equally short synthesis of methyl jasmonate has been achieved through 1,4-addition-alkylation of cyclopentenone . 

A novel non-phenol oxidative coupling of phenylethyltetrahydroisoquinolines using VOF3-TFA has been developed into a useful synthesis of homoaporphines thus (34 R, = H, Me) were prepared from the corresponding phenylethyltetra-... 

Diarylamides with arenes activated by electron-donating substituents can be converted to azacycles by anodic oxidation through phenolic oxidative coupling reactions that can be a key step in the synthesis of alkaloids (Schemes 16 and 17). According to the nature of substituents and the experimental conditions, either spiro compounds [22] or non-spiro compounds [23, 24] were obtained. 

Murrayafoline A (7) required for this total synthesis was obtained starting from 3-formylindole (618) (577) (see Scheme 5.40). Lead tetraacetate-mediated oxidative non-phenolic biaryl coupling of 7 led to murrastifoline F (191) in 60% yield. The... 

Phenolic oxidative coupling of the benzylisoquinoline (85) gave the aporphine (86) which led to the non-phenolic thalicsimidine upon O-methylation. Alternatively, oxidative coupling of (87) gave rise to a mixture of dienones (88) which on acid-catalysed dienone-phenol rearrangement furnished the aporphines (89) and... 

Therefore, the role that the ferrocenium group plays in the in vitro cytotoxicity appears to be that of an intramolecular electron acceptor. The inertness of the non-phenolic compound 7 to pyridine in this model system shows that a phenolic group is necessary for the reaction to take place. Likewise, for the unconjugated 20a-c, chemical reduction of the Fe(III) atoms was not observed suggesting that the electron transfer process occurs through a coupling in the molecular Ti-system. Thus, as soon as an adequate base is available, a substantially fast intramolecular electron transfer may occur, thereby leading to the oxidation of the phenolic moiety made easier because of its displacement by the reaction of the phenoxy cation with the pyridine base [153-155]. 

In the case of allocolchicinoids, a non-phenolic intramolecular oxidative coupling was used by Macdonald for the total synthesis of ( )-iV-acetylcolchinol 31, Fig. (12) [96]. 

The use of vanadium(V) salts in oxidative coupling reactions was prompted by the work of Funk et al. who recognized the ability of vanadium oxytrichloride to form phenoxyvanadium complexes with phenols [llO]. As it was shown by Schwartz et al., such complexes can be isolated and used for oxidative couplings [111]. Vanadium oxytrifluoride, a superior reagent [112] was found to be effective not only with free phenols but also with phenol ethers revealing the non-phenolic mechanism of this oxidation [113]. The method was successfully adapted to the oxidative macrocyclisation of a vancomycin subunit [114]. 

Riordan and Stammer (335, 336) employed o-chloranil to oxidize saturated A -oxazolinones, and obtained dioxinones. Treatment of the latter with nucleophiles such as CH3O", PhNH2 or PhCH2SH afforded a-substituted amino acid derivatives, possibly by addition to the acylimine in equilibrium with the quinone adduct. Use of a non-nucleophilic base coupled with scavenging of the phenolic hydroxy groups by etherification made possible the isolation of acylenamino acid derivatives. 

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