Oxidative coupling of enolates

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. 

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. 

Scheme 16. Titanium(IV)-mediated oxidative coupling of enol ethers 46...

In a related study, intramolecular oxidative coupling of enolate derivatives has been investigated by Schmittel and co-workers [167]. The intermolecular version of this reaction provides a useful route to 1,4-dicarbonyl compounds but typically suffers from low levels of stereoselectivity. Furthermore, in mixed systems, the desired heterocoupling products are often accompanied by appreciable amounts of homocoupling products. It was hoped that the use of a single metal for both enolate precursors with concomitant intramolecularization of the bond-forming event might overcome some of these problems. 

Both 3-aIkoxycarbonyl- and 3-acylfurans can be prepared by oxidative coupling of enol ethers with 1 3-dicarbonyl compounds in the presence of Mn(III) and subsequent treatment of the resulting 2,3-dihydrofurans with acids (Scheme 25) <87CL223,88SC1841,93S833). 

Several new methods for oxidative coupling of enolates, enol silanes, and enamines have been reviewed and illustrated with reference to natural product synthesis. Copper(II)-catalysed oxidative cross-coupling of aldehydes and alkylbenzenes, to form benzyl esters on reaction with t-BuOOH, has been demonstrated. ... 

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) ... 

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. 

Oxidative homo-coupling of enolates from acyl oxazolidinones to give the corresponding dimers can be achieved in the presence of oxidants. Titanium and ytterbium enolates of 252 were coupled in the presence of a chiral diol or chiral bisoxazoline in the presence of ferrocenium cation 254 (Scheme 63) [166]. The amount of the meso dimer varied with the chiral ligand with a maximum of 5 1. TADDOL 172 performed best providing a 76% ee for the meso product. Ytterbium enolate gave a low ee of 34% with the same ligand. 

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]. 

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... 

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. 

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... 

This ligand coupling method was quite efficient for acetophenone and rerf-butylketone derivatives. However, coupling of the TMS ether of cyclohexanone (121) failed. The oxidative coupling of the TMS ether of cyclohexanone (121) to give 2,2 -bicyclohexanone was successful only when this silyl enol ether was treated with the iodosobenzene-tetrafluoroborate complex.230,231... 

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