Enols enolethers

E. Stark, K.-H. Spohn, C. Skotsch, H. Pech, E. Lorch, J. Haufel, G. Bouchon and E. Breitmaier, Ringschliisse mit / Enol-, -Enolether und jS-Enamino-Carbonylverbindungen , Chemiker Zeitung, 101, 161-164 (1977). 

Conjugate addition of silyl enolethers leads to the silyl enol ether of the product... 

The enolic form of alkylcarbonyl substrates is usually considered when these substrates undergo attack by the reagent. - The use of enolates and enolethers is thoroughly described in Sec. A.l (see also Refs. 49, 51, and 259). 

The reductive coupling of carbonyl compounds with formation of C-C double bonds was developed in the early seventies and is now known as McMurry reaction [38, 39]. The active metal in these reactions is titanium in a low-valent oxidation state. The reactive Ti species is usually generated from Ti(IV) or Ti(III) substrates by reduction with Zn, a Zn-Cu couple, or lithium aluminum hydride. A broad variety of dicarbonyl compounds can be cyclized by means of this reaction, unfunctionalized cycloalkenes can be synthesized from diketones, enolethers from ketone-ester substrates, enamines from ketone-amide substrates [40-42], Cycloalkanones can be synthesized from external keto esters (X = OR ) by subsequent hydrolysis of the primary formed enol ethers (Scheme 9). 

Paternd-Biichi reactions [152] this competition has been investigated for electron-rich alkene substrates for several combinations of carbonyl compounds and electron-donors, e.g. a-diketones and ketene acetals [153], aromatic aldehydes and silyl ketene acetals, and enol ethers. In polar solvents, the assumption of a 1,4-zwitterion as decisive intermediate is reasonable. This situation then resembles the sequence observed for ET-induced thermal [2 -I- 2]-cycloaddition reactions [154]. Both regio- and diastereoselectivity are influenced by this mechanistic scenario. The regioselectivity is now a consequence of maximum charge stabilization and no longer a consequence of the primary interaction between excited carbonyl compound and alkene. Whereas 3-alkoxyoxetanes are preferentially formed from triplet excited aldehydes and enolethers, 2-alkoxyoxetanes result from the reaction of triplet excited ketones or aldehydes and highly electron-rich ketene silylacetals (Scheme 40) [155]. 

Silyl-Enolethers and -Ethers — New Results of Keto-Enol Tautomerism... 

The silyl group stabilizes the enol form and the fluorosilyl-enolethers are isolable. The formation of the silyl-enoleth depends on the lithiated reagent. 

By changing the molar ratio in further reaction of the fluorosilyl-enolether with the lithiumenolate, it was possible to synthesize the first bis(enol)fluorosilanes. 

Cycloadditions only proceeding after electron transfer activation via the radical cation of one partner are illustrated by the final examples. According to K. Mizono various bis-enolethers tethered by long chains (polyether or alkyl) can be cyclisized to bicyclic cyclobutanes using electron transfer sensitizer like dicyanonaphthalene or dicyano-anthracene. Note that this type of dimerization starting from enol ethers are not possible under triplet sensitization or by direct irradiation. Only the intramolecular cyclization ci the silane-bridged 2>. s-styrene can be carried out under direct photolysis. E. Steckhan made use of this procedure to perform an intermolecular [4+2] cycloaddition of indole to a chiral 1,3-cyclohexadiene. He has used successfully the sensitizer triphenylpyrylium salt in many examples. Here, the reaction follows a general course which has been developed Bauld and which may be called "hole catalyzed Diels-Alder reaction". 

Da die Enolether-Gruppe letztlich einem Aldehyd entstammt, ist die Reaktionsfolge syn-thetisch Equivalent der Allylierung eines Aldehyd-Enolates (vgl. S. 563). 

The success of the strategy is further applied for the synthesis of carbo-and spiro-aimulated aromatic compounds [146,147] by the intramolecular cyclization of silyl enolethers to PET-generated arene radical cations. Two types of carbocyclic compounds (170 and 173), varying in ring sizes, may be synthesized [146] starting from the same ketone (i.e., 169), as two types of silyl enol ethers can be produced using either thermodynamic or kinetic enolisation procedures. The core spiro structure (177) of the anticancer antibiotic ffed-ericamycin is also prepared [147] by the PET cyclization of 176 (Scheme 36). 

The preparation of the quinoline system by pericyclic reactions is less important than the previous syntheses. Some cyclization/elimination reactions of iV-phenylimines 95 and 96 with alkynes, enol ethers or enamines are of preparative interest. Although they correspond to [4+2] cycloadditions, they are likely to proceed by SeAt mechanisms and are usually catalysed by Lewis acids. In the enolether cycloaddition to imines 95 ytterbium(III)triflate proved to be particularly effective [104]. 

The enantioselective a-enolation of aldehydes reported by MacMillan and co-workers [136] proceeded well with various ir-rich silyl enolethers containing aUtyl, vinyl, or aryl moieties without loss of reaction efficiency and enantiocontrol. The incorporation of bulkier silyl group (TBS) not only increased substrate stability versus hydrolysis, but also led to increased enantioselectivity. Furthermore, inter-molecular enolation rather than intramolecular enolation was observed as preferred. 

In the above reaction the initially formed enols and enolethers are unstable and are instantaneously hydrolysed to give the corresponding carbonyl compounds. 

In order to overcome the tricky regioselectivity problem, hydroformylation of the corresponding enol ethers has been suggested (Scheme 6.67) [181]. These substrates are accessible via acetalization of a relevant propiophenone derivative, followed by elimination of 1 equiv ethanol. The hydroformylation reaction with a rhodium cluster was performed in a 100 g scale. The enolether reacts in the P position. A second elimination step afforded the a,p-unsaturated aldehyde, which was reduced with H2 to give selectively the desired 2-formyl compound. 

Activated alkenes, for example, enamines or enol ethers, likewise undergo cycHzing addition to N-arylimines catalyzed by Lewis acids like BF3 or, particularly effective, Yb(OTf)3 [190]. With enolethers, the primary products of cyclization 131 are aromatized to quinolines 132 by Lewis acid-promoted ROH-elimination and dehydrogenation. 

Whatever one decides on, the final enolate 234 can be captured by silyltriflate, to arrive at the stable enolether 233 [88]. 

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