Formation of enol ethers

See Section 362 (Ester-Alkene) for the formation of enol esters and Section 367 (Ether-Alkenes) for the formation of enol ethers. Many of the methods in Section 60A (Protection of Aldehydes) are also applicable to ketones. 

C in CH2CI2, in the formation of enol ethers 404 in high yields [26] (Scheme 5.4). Likewise, silylated alcohols 13 and free 1,2- and 1,3-glycols react with ketones in the presence of TMSOTf 20 to cyclic ketals [27]. 

With ethoxypropadiene, the vinylic copper intermediate formed via the allylzinc-cation reacts with another molecule of ethoxyallene leading to the formation of enol ether 112 as an E-Z mixture [55],... 

We start the scheme after the oxidative addition of diphenylsilane and coordination of acetophenone has taken place, after the classic mechanism by Ojima [28], The formation of enol ethers proves, that at least for this part of the products formed (up to 22%, Brunner [27], 40% [29]), the reaction proceeds... 

Formation of enol ethers from aldehydes or ketones... 

Treatment of aldehydes or ketones with acceptor-substituted carbene complexes leads to formation of enol ethers [1271-1274], oxiranes [1048], or 1,3-dioxolanes [989,1275] by O-alkylation of the carbonyl compound. Carboxylic acid derivatives... 

Therefore mercury(II) acetate interacts as an electrophilic transition metal with the nucleophilic alkene to form the three-membered ring 52. This mercurinium ion is opened by relatively feeble nucleophiles like alcohols - or in this reaction water. Similar to a hydroboration the attack happened at the more substituted end of the mercurinium ion according to Markovnikov s rule. To get rid of the metal, solid potassium iodide is added. This means insoluble mercury(Il) iodide is formed, followed by loss of the methoxy group and formation of enol ether 54, which subsequently tautomerizes to the desired aldehyde 55. 

Generally useful reagent with a high silyl donor ability will not react with amino groups will not cause formation of enol-ether on unprotected ketone groups especially useful for ecdysones, norepinephrine, dopamine, steroids, sugars, sugar phosphates, and ketose isomers... 

The review starts with a discussion of the mechanism of keto-enol tautomerisation and with kinetic data. Included in this section are results on stereochemical aspects of enolisation (or enolate formation) and on regioselec-tivity when two enolisation sites are in competition. The next section is devoted to thermodynamic data (keto-enol equilibrium constants and acidity constants of the two tautomeric forms) which have greatly improved in quality over the last decade. The last two sections concern two processes closely related to enolisation, namely the formation of enol ethers in alcohols and that of enamines in the presence of primary and secondary amines. Indeed, over the last fifteen years, data have shown that enol-ether formation and enamine formation are two competitive and often more favourable routes for reactions which usually occur via enol or enolate. 

In the last two sections, it was emphasised that the intermediate formation of enol ethers and enamines in alcohols and in the presence of amines, respectively, provides favourable routes for halogenation and isotope exchange in carbonyl compounds. Since this conclusion is probably also valid for other reactions which usually involve the enol or enolate, studies under these experimental conditions are probably of great interest, especially for the purposes of synthesis. 

Gellerstedt G, Lindfors EL (1987) On the formation of enol ether structures in lignin during kraft cooking Nord Pulp Pap Res J 2 71-75... 

Dipolar cycloaddition reactions are most commonly applied for the synthesis of five-membered heterocyclic compounds.86 87 [3+2] cycloaddition reactions of transition-metal propargyl complexes have been reviewed.88 Addition of diazomethane to carbene complexes (CO)5Cr= C(OEt)R results in cleavage of the M = C bond with formation of enol ethers H2C = C(OEt)R,3 89 but (l-alkynyl)carbene complexes undergo 1,3-dipolar cycloaddition reactions at the M = C as well as at the C=C bond. Compound lb (M = W, R = Ph) affords a mixture of pyrazole derivatives 61 and 62 with 1 eq diazomethane,90 but compound 62 is obtained as sole... 

The group of Barluenga reported the formation of enol ethers, which are protonated in situ to form oxonium... 

It is also worthwhile to add that the versatility of the Wittig reaction suggested entirely new opportunities for the synthetic utilization of carbonyl compounds. Thus, the employment of methoxymethylenephosphorane 83 (easily prepared from chloromethyl ether) as the ylide component represents a standard protocol for the transformation of aldehydes or ketones into homologous aldehydes 84, via the intermediate formation of enol ether 84a. 

The formation of enol ethers and thioethers via coupling between a vinyl bromide and a tin alkoxide or thioalkoxide has been reported by Rossi et al. [205J. Two detailed papers [206,207] have appeared concerning the formation of tertiary aromatic amines via coupling of Bu3SnNMe2 and aromatic systems mechanistic studies are reported. 

F Berthold, E-L Lindfors, G Gellerstedt. Degradation of Guaiacylglycerol- 3-guaiacyl Ether in the Presence of HS or Polysulfide at Various Alkalinities. Part I. Degradation Rate and the Formation of Enol Ether. Holzforschung 52 398 04, 1998. 

G Gellerstedt, EL Lindfors. On the Formation of Enol Ether Structures in Lignin during Kraft Cooking. Nordic Pulp Pap Res J 2 71-75, 1987. 

Temporary tethering of radical precursors has found other applications in natural product synthesis. Crimmins and O Mahony utilized a silyl ether temporary eonnection to direct a hydro-hydroxymethylation of enol ether 139 in their synthesis of talaromycin A, 140 [54]. Since talaromycin A is susceptible to acid-catalyzed isomerization to the thermodynamically more stable talaromycin B in which the hydroxymethyl substituent is equatorial, the use of the essentially neutral conditions of a radical cyclization to install the requisite axial hydroxymethyl group would avoid any potential isomerization problems. Formation of enol ether 139 was achieved in five steps from (4R)-4-ethylvalerolac-tone 141. Exposure of 139 to Bu3SnH in benzene at reflux in the presence of AIBN as initiator effected radical cyclization with delivery of the radical to the same face to whieh the ether tether was attached. Tamao oxidation proceeded uneventfully, furnishing the desired natural product (Scheme 10-47). 

Indeed, even attempts at the formation of enol ethers by O-alkylation of enols (or enolate anions) is generally frustrated by the intrusion of C-alkylation (Scheme 8.93 see Chapter 9), although some adjustment of the ratio of C- to O-alkylation can be effected by choice of metal-base (e.g., t-butyllithium [(CHsjsC LC] rather... 

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