Syntheses through Phenolic Oxidative Coupling

The first synthesis of an aporphine using phenolic oxidative coupling was reported in 1962 when oxidation of W-methyllaudanosoline meth- 

Similarly the quaternary salt XLIV could be cyclized to the aporphine XLV interestingly enough the pentahydroxylated isoquinoline XLVI also aiforded the aporphine XLI rather than a cularine derivative (47). 

Barton and Cohen (48) were the first to suggest the seminal idea that dienones could be intermediates in the biosynthesis of aporphine alkaloids from benzylisoquinolines, since such dienones could rearrange to the aporphine nucleus either through a dienone-phenol or a dienol-benzene rearrangement as shown in the scheme on the following page. 

The dienol-benzene rearrangement has been used to advantage to explain the structures of several abnormal aporphine alkaloids (49) from a biogenetic point of view, and has also allowed the first s3uithesis of the aporphine alkaloid isothebaine (L) (50). (+ )-Orientaline (XLVII) was oxidized by alkaline ferricyanide to give a mixture of two dienones (XLVIII) in 4% yield. One of the dienones was reduced with sodium borohydride to a mixture of two dienols XLIX which, without 

The above sequence of reactions represents an acciu-ate emulation of at least part of the natural process since it has recently been shown that 

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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. 

The alkaloid isoboldine was first isolated from Nandina domestica Thunb. and correctly assigned structnre XXVIII (19). This structural designation has been further confirmed by a synthesis of the alkaloid through phenolic oxidative coupling (20). 

A group of alkaloids with a unique skeleton known as the Erythrina alkaloids have been isolated from the seeds of Erythrina plants examples include erythraline and erysodienone obtained from the seeds of E. indica [1,2]. The relative and absolute stereochemistry of these alkaloids was determined by X-ray crystallography and chemical degradation studies [3].The chemical synthesis of the Erythrina alkaloid nucleus was achieved biomi-metically through phenol oxidative coupling [4]. 

Scheme 3. Synthesis of advanced intermediate 15 through a phenolic oxidative coupling.

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 . 

Oxidative phenol-benzyl coupling. The key step in a new total synthesis of ( )-picropodophyllone (3) involves oxidation of the phenol 1 with thallium(III) trifluoroacetate in the presence of BF3 etherate in CH2CI2 at 20°. After work-up, which included bisulfite reduction and methylation, the diester (2) was obtained in 55% yield. Some evidence suggests that the cyclization proceeds through a p-quinone methide (a). 

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