Dienolates, oxidative coupling

Interestingly, the dienolate generated from di-/er/-butyl adipate underwent oxidative cycliza-tion with copper(II) chloride to afford di-/m-butyl cyclobutane-l,2-dicarboxylate (12) in 21 % yield, together with the competitive Dieckmann product (30%) as well as unreacted starting material (17%).20 The formation of the cyclobutane diester is presumably due to the steric hindrance of the /e/v-butyl groups, which impedes the Dieckmann condensation and thus favors, to some extent, an oxidative coupling reaction.20... 

Paquette has reported an intramolecular oxidative coupling using ferric chloride to prepare the intermediate 30 for the synthesis of cerorubenic acid-III. Addition of the dienolate of 28 to FeCls in dmf at —78°C produced the cyclopropane intermediate 29 in 54% yield (equation 16). Although the mechanism of this oxidative cyclization is not discussed in the paper, it is likely that a one-electron transfer pathway is involved. Copper(n) salts have also been utilized for intramolecular enolate coupling, but they proved to be somewhat less effective in the present context. 

Two studies have appeared dealing with the phenolic oxidative coupling of the dihydric benzylisoquinoline LI. In the first study, oxidation of LI with potassium ferricyanide yielded two dienones (LII), one of which was obtained crystalline. The crystalline material was reduced with sodium borohydride to two noncrystalline dienols (LIII) which underwent dienol-benzene rearrangement in anhydrous methan-olic hydrogen chloride to ( )-corydine (XXVI). Rearrangement of the... 

Aporphine Alkaloids.—Isothebaine (65) derives from orientaline (62) along a pathway which involves thedienone(63)and the dienol(64). The biosynthesis of the aporphine alkaloids of Dicentra eximia is quite different but dienone intermediates are also implicated. By comparison the biosynthesis of bulbocapnine (66) is simple, for the alkaloid arises directly from reticuline (67), in Corydalis cava, by ortho-ortho phenol oxidative coupling. 

Overman s retrosynthetic analysis is depicted in Scheme 1. Pentacyclic ketone 4, derived from allylic alcohol 7 by an aza-Cope-Mannich rearrangement of formaldiminium ion derivative 6 furnished 3 through the C5 hemiketal disconnection. An intramolecular oxidative coupling of a dienolate generated from indole-... 

Citral is prepared starting from isobutene and formaldehyde to yield the important C intermediate 3-methylbut-3-enol (29). Pd-cataly2ed isomeri2ation affords 3-methylbut-2-enol (30). The second C unit of citral is derived from oxidation of (30) to yield 3-methylbut-2-enal (31). Coupling of these two fragments produces the dienol ether (32) and this is followed by an elegant double Cope rearrangement (21) (Fig. 6). 

Unsymmetrical 1,4-diketones have been prepared in good yields by (NH4)2[Ce(N03)6] oxidative cross coupling between 1,2-disubstimted and 1-substituted trimethylsilyl eno-lates . The same cerium(IV) compound has been also applied to the preparation of 6-oxo-Q ,/ -unsaturated carbonyl compounds trimethylsilyl dienolates are easily oxidized... 

The key step in the biosynthesis of morphine involves the oxidative phenolic coupling of reticuline (31) to salutaridine (32). This step can be viewed mechanistically as (1) oxidation of the two aromatic rings to phenoxy radicals followed by an intramolecular radical-radical coupling or (2) oxidation of one ring to a radical cation or cation, followed by an intramolecular electrophilic aromatic reaction. This process is very important in the biosynthesis of a number of natural products, and is a process that nature has used to crosslink peptides containing aromatic residues. The biosynthesis of morphine continues with reduction of salutaridine (32) to salutaridinol (33) followed by an intramolecular Sn2 reaction to give thebaine (34). Dienol ether hydrolysis to codeinone (35), reduction of the ketone to codeine (3) and 0-demethylation completes the biosynthesis of morphine (1). 

In Scheme 3, two general mechanistic pathways that may be operative for the Ni-catalyzed coupling of 1,3-enynes with carboxaldehydes are depicted. The first pathway involves a prior oxidative addition of Ni(0) to the reductant M R leading to a metal hydride or a metal alkyl species A. The reactive catalyst A may proceed by sequential insertion into the alkyne bond and the carbonyl bond of the electrophile to the formation of the polysubstituted 2,4-dienol 5 via vinyl nickel 4. 

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