Enol ethers formation

Silyl enol ether formation with RsSiCl-p EtsN gives thermodyanamic silyl enol ether... 

Addition of a hydroxy group to alkynes to form enol ethers is possible with Pd(II). Enol ether formation and its hydrolysis mean the hydration of alkynes to ketones. The 5-hydroxyalkyne 249 was converted into the cyclic enol ether 250[124], Stereoselective enol ether formation was applied to the synthesis of prostacyclin[131]. Treatment of the 4-alkynol 251 with a stoichiometric amount of PdCl2, followed by hydrogenolysis with formic acid, gives the cyclic enol ether 253. Alkoxypalladation to give 252 is trans addition, because the Z E ratio of the alkene 253 was 33 1. 

Steroidal 17-cyanohydrins are relatively stable towards chromium trioxide in acetic acid (thus permitting oxidation of a 3-hydroxyl group ) and towards ethyl orthoformate in ethanolic hydrogen chloride (thus permitting enol ether formation of a 3-keto-A system ). Sodium and K-propanol reduction produces the 17j -hydroxy steroid, presumably by formation of the 17-ketone prior to reduction. ... 

O- versus C-a kyIation product ratios in the methylation of desoxybenzoin by dimethyl sulphate can be varied between 0.75 and 63 by the choice of catalyst. The reaction can be steered towards enol-ether formation by large, sterically shielded ammonium ions, while C-alkylation is favoured by small ammonium ions (e.g. RMejN" ) and by crown ethers (Dehmlow and Schrader, 1990). 

TMSIH Does not react with Mino groups. Can be used to form TMS derivatives of carbohydrates in aqueous solution. Does not promote enol-ether formation with unprotected ketone groups. Most generally useful reagent, preferred for most applications. Exceptions are the formation of N-TMS derivatives and the separation of low molecular weight TMS derivatives... 

TMCS A poor silylating reagent unless used in the presence of base (e.g., pyridine, diethylamine). Causes extensive enol-ether formation with unprotected ketone groups. Mainly used to catalyze the reaction of other silylating reagents. 

Difficulties that arise using simple primary alcohols (ketal and enol-ether formation) may be avoided by using phenol or f-butyl alcohol.360... 

As the precursor for the B unit, the selectively benzylated -fucal derivative 75- could be obtained crystalline from L-fucal by applying a phase-transfer-catalyzed process T64). By a Ferrier reaction of di-O-acetyl-L-rhamnal and a subsequent retro enol ether formation trough hydride attack at C-3 (71.) the -amicetal 72 was obtained (64) this reaction was concurrently also es-cribed by others (72). 

A very useful class of chiral auxiliaries has been developed for alkenes substituted with a heteroatom. These auxiliaries, attached to the heteroatom, allow for the preparation of enantiomerically enriched cyclopropanols, cyclopropylamines and cyclopropylboronic acids. Tai and coworkers have developed a method to efficiently generate substituted cyclopropanol derivatives using the cyclopropanation of a chiral enol ether (equation 78) . The reaction proceeds with very high diastereocontrol with five- to eight-membered ring sizes as well as with acyclic enol ethers. The potential problem with the latter is the control of the double bond geometry upon enol ether formation. A detailed mechanistic study involving two zinc centers in the transition structure has been reported. ... 

Corriu and coworkers have reported an alternative procedure for the conjugate addition of ketones to a.P-unsaturated acceptors which employs CsF-(RO)4Si (Scheme 56) 126 this procedure affords adducts with a,3-enones, oc.fj-unsaturated esters and a,3-unsaturated amides. Mechanistically, silyl enol ether formation occurs initially, followed by fluoride ion catalyzed enolate formation. 

Review articles of synthetic importance have featured eliminations involving carbon-halogen bonds and leading to highly strained lings,81 elimination and addition-elimination reactions,82 enol ether formation from unsaturated acetals,83 and the Wittig reaction and related methods.84... 

A Dieckmann reaction of 7 and enol etherification provided trans-octalone 6 in 90% yield. An additional 10% of the transposed /3-ethoxy -enone 24 was also isolated. Compound 24 could easily be removed chromatographically (the first chromatography of the synthesis) and could be isomerized back to the 9 1 mixture in favor of 6 by resubjection to the etherification conditions. Compound 7 had three different CC Et groups, yet only the one adjacent to the CN group was attacked by the nascent ketone enolate. This selectivity, attributed to the effect of the powerfully electron-withdrawing CN group, was expected, as it was observed previously in the preparation of 3c.3 The selectivity of the enol ether formation was also expected from previous work. 

Krapcho decarbomethoxylation of diester 216 provided monoester 217 (06SL1691). Chemoselective Swern oxidation of 3-(3-hydroxypropyl)-1,2,3,4,11, 1 lrt-hexahydro-6/T-pyrazino[l,2-fr]isoquinolin-4-ones 203 followed by silyl enol ether formation with TIPSOTf and Et3N in Et20 for 12 h at room temperature gave compounds 218 as a single isomer in excellent yields (08JA7148,09JOC2046). 

Similar properties and applications as for HMDS useful for amino acid analyses provides good response for electron capture detection has relatively low silyl donating ability and is usually used in the presence of a base such as pyridine may cause enol-ether formation with unprotected ketone groups often used as a catalyst with other silylating reagents... 

The treatment of alkynyliodonium salts not amenable to cyclopentene formation with sodium azide in methanol affords vinyliodonium salts and/or enol ethers (equation 107)". Enol ether formation also occurs when glyme is employed as the solvent (equation 108)". Finally, regeneration of the vinylidene-iodonium ylide, PhC (N3)=C—IPh, from (Z)-(/ -azido-/ -phenylvinyl)phenyliodonium tosylate with potassium J-butoxide in glyme likewise affords an enol ether (equation 109). 

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. 

Equilibrium constants for acetal and enol-ether formation (25 °C)... 

Carbonyl formation0/ enol ether / Enol ether formation 1 ... 

Silyl enol ether formation again results from silylation of carbonyl oxygen but this time no alcohol is added and a weak base, usually a tertiary amine, helps to remove the proton after silylation. 

Different competitive processes are dependent on the diazo compound, on the unsaturated system, and on the solvent. With 1,1,1-trifluorobutan-2-one and diazomethane, the corresponding oxirane is formed almost exclusively. While methyl trifluoropyruvatc reacts with diazomethane to provide a mixture of the oxiranes, reaction of the pyruvate with ethyl diazoacetate provides a stable [3-1-2] cycloadduct.Chiral fluoroalkyl-substituted /i-oxo sulfoxide (e.g., 1) readily react with diazomethane to provide the corresponding chiral epoxides. Use of methanol as solvent favors oxirane formation over the competitive enol ether formation. 

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