Enolate oxidative coupling

Polymerization Mechanism. The mechanism that accounts for the experimental observations of oxidative coupling of 2,6-disubstituted phenols involves an initial formation of aryloxy radicals from oxidation of the phenol with the oxidized form of the copper—amine complex or other catalytic agent. The aryloxy radicals couple to form cyclohexadienones, which undergo enolization and redistribution steps (32). The initial steps of the polymerization scheme for 2,6-dimethylphenol are as in equation 6. 

A)-Ketorolac 132, a nonsteroidal anti-inflammatory dmg (NSAID), was synthesized in a two-step procedure based on an intramolecular oxidative coupling of pyrrole at the C-2 position with a chiral sultam enolate 130 leading to dihydropyrrolizine 131 as a 4.5 1 mixture of epimers (Scheme 23). Subsequent benzoylation, performed on the crude... 

Reaction of compound 134, either with sodium carbonate or potassium /tz -butoxide, leads in moderate yields to the enolized bicyclic compound 135 along with a dimer resulting from the oxidative coupling of the initial enolate of substrate 134 (Scheme 24) <2005T1693>. 

Examples of the synthesis of dissonant 1,4-dicarbonyl systems by oxidative coupling of the corresponding enolates have been described by Saegusa [35] (Scheme 5.26) ... 

Since enol silyl ethers are readily accessible by a number of methods in a regioselective manner and since the trialkylsilyl moiety as a potential cationic leaving group facilitates the termination of a cyclization sequence, unsaturated 1-trialkylsilyloxy-1-alkenes represent very promising substrates for radical-cation cyclization reactions. Several methods have been reported on the synthesis of 1,4-diketones by intermolecular oxidative coupling of enol silyl ethers with Cu(II) [76, 77], Ce(IV) [78], Pb(IV) [79], Ag(I) [80] V(V) [81] or iodosoben-zene/BFa-etherate [82] as oxidants without further oxidation of the products. 

Diketones (8, 126 127). Complete details of the synthesis of 1,4-diketones by oxidative coupling of ketone enolales and trimethylsilyl enol ethers with Cu(OTf)2 are available.1 Use of isobutyronitrile is essential for the coupling it is not only a suitable solvent, but the nitrile group apparently facilitates reduction of the intermediate copper enolate to CuOTf.2 When acetonitrile is used by-products containing a nitrile group are formed. 1,4-Diketones are formed only in traces when DMF, DMSO, or HMPT is used. 

The industrial synthesis of vinyl acetate [14] via palladium-catalyzed oxidative coupling of acetic acid and ethene using direct 02 reoxidation has already been mentioned (Scheme 3, d). Some NaOAc is required in the reaction medium, and catalysis by Pd clusters, as alternative to Pd(II) salts, was proposed to proceed with altered reaction characteristics [14]. Similarly, the alkenyl ester 37 (Table 5) containing an isolated vinyl group yields the expected enol acetate 38 [55] whereas allylphenol 39 cyclizes to benzofuran 40 with double bond isomerization [56]. 

This reaction of cyclohexene with (PhI + )20 2BF4 and lithium perchlorate gave exclusively the cz s-bis-perchlorate adduct (92%). Also, silyl enol ethers underwent efficient oxidative coupling to 1,4-diketones [24] ... 

Racemic yatein 43 was obtained by Michael addition of the anion of piperonaldehyde dithiomethyl acetal to 5/7-furan-2-one (butenolide), followed by trapping of the resulting enolate with 3,4,5-trimethoxybenzyl bromide (see section 3.2.2). This process gave 43 with the desired trans stereochemistry at the butyrolactone. Oxidative coupling of the two... 

Functional 1,5-dienes were also synthesized in good yields by ruthenium-catalyzed regioselective codimerization of enol esters with 2-substituted-l,3-bu-tadienes [20] (Eq. 16). A ruthenacycle intermediate formed by oxidative coupling was proposed followed by intracyclic /1-hydride elimination. The (Z)-selectivity is thought to result from the configurational inhibition for the /1-hydride elimination in the intermediate ruthenacyclopentane. 

The stemona alkaloid stemonamide (49) was synthesized starting from a-stannyl acetate 47 and 2-stannyl pyrrolidine 48. The oxidative coupling of stannyl acetate 47 with acetylenic silyl enol ether affords the functionalized C-7 unit which corresponds to the side arm of the pyrrolidine ring. Then, introduction of the C-7 unit to the pyrrolidine ring is performed by the oxidative generation of acyliminium ion. The carbon skeleton of stemonamide was thus constructed efficiently as shown in Scheme 19 by employing organotin compounds. ... 

Oxidative coupling of silyl enol ethers as a useful synthetic method for carbon-carbon bond formation has been known for a long time. Several oxidants have been successfully applied to synthesize 1,4-diketones from silyl enol ethers, e.g. AgjO [201], Cu(OTf)2 [202], Pb(OAc)4 [203] and iodosobenzene/BFj EtjO [204]. Although some of these reagents above are known to react as one-electron oxidants, the potential involvement of silyl enol ether radical cations in the above reactions has not been studied. Some recent papers, however, have now established the presence of silyl enol ether radical cations in similar C-C bond formation reactions under well-defined one-electron oxidative conditions. For example, C-C bond formation was reported in the photoinduced electron transfer reaction of 2,3-dichIoro-1,4-naphthoquinone (98) with various silyl enol ethers 99 [205], From similar reactions with methoxy alkenes [206,207] it was assumed that, after photoexcitation, an ion radical pair is formed. 

The oxidative coupling of enolates, reported for the first time in 1935, represents an interesting application of enolates in organic synthesis. Examples of these reactions. 

In a series of papers on the total syntheses of alkaloids, Baran and coworkers have recently reported that enolates of carbonyl compounds undergo oxidative coupling with indoles and pyrroles in the presence of oxidants such as copper(II) and iron(III) salts . A detailed study of the oxidative cyclization reported in equation 15 has shown that 26 is converted into 27 with the highest yields when Fe(acac)3 is the oxidant, presumably due to its high redox potential (+1.1 V vs. the ferrocenium/ferrocene couple in THF solution ), which is the most positive among all the oxidizing agents tested for the transformation. 

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. 

Silver enolates are proposed as reactive intermediates in the reaction of sUyl enolates with AgaO in dmso. An important feature of the reaction is the regiospecific formation of l,4-diketones °j. Sessler and coworkers reported that the key step in the preparation of / -substituted tetra- and hexaalkylterpyrrols is the copper(II) triflate-mediated oxidative coupling of the Ida-derived enolates of a-keto pyrrols. The coupling reaction shown in equation 24 produces a mixture of distereoisomers which does not require separation and can be directly converted to the corresponding terpyrroles. 

Oxidative coupling of silyl bis-enolates to 1,4-diketones (equation 25) occurs with a variety of oxidizing agents such as [Fe(phen)3](PFe)3, (NH4)2[Ce(N03)6] and Cu(OTf)2 . The high rf,Z-diastereoselectivity of the coupling is attributed to the energy difference in the transition states of the two diastereomorphic approaches. The steric interactions between... 

Anodic oxidation couples the pendant arm and the silyl enolate fragments of 54 to give the annulated product 55 (equation 40) , a key intermediate in the synthesis of hamigerans, an unusual halogenated marine natural product . 

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