Ketones ether formation

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. 

Trifluoromethanesulfonic acid is miscible in all proportions with water and is soluble in many polar organic solvents such as dimethylformamide, dimethyl sulfoxide, and acetonitrile. In addition, it is soluble in alcohols, ketones, ethers, and esters, but these generally are not suitably inert solvents. The acid reacts with ethyl ether to give a colorless, Hquid oxonium complex, which on further heating gives the ethyl ester and ethylene. Reaction with ethanol gives the ester, but in addition dehydration and ether formation occurs. 

Bromochloromethane Methyl ether Methyl ethyl ether Methyl ethyl ketone Methyl formate 2-Methyl furan... 

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. ... 

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. 

Nicolaou hydroxy-ketone reductive cyclic ether formation... 

Williams83 has recently considered the possibility of ion molecule reactions in alcohols, ketones, ethers, and esters. He postulates that the primary reactions of the parent ion are the inter- or intra-molecular abstraction of a hydrogen atom and the formation of a x-bond between oxygen and the adjacent carbon atom after homolytic scission of a bond to that adjacent carbon atom. After examining some of the liquid phase data on the radiolysis of these oxygen compounds it was concluded that such ion molecule reactions may be of importance in these systems also. 

V. Ketones / 134 Selectivity / 134 Stereochemistry / 135 Ether formation / 136 Experimental procedures / 136... 

The product distribution depends on the reaction conditions. Selective formation of either 1 or 2 can be accomplished if the appropriate solvent and amount of silane are used. Functional groups such as ester, ketone, ether, and amide are well tolerated. The authors suggest that this system involves a different type of mechanism for CO incorporation than that seen in other reactions. In this case, the key catalytic step is proposed to involve an oxycarbyne complex as intermediate. 

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. 

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. 

Not surprisingly, an attempt at direct Mitsunobu inversion of (3-hydroxyketone 14 led only to elimination, yielding the corresponding a,(3-unsaturated ketone. To circumvent this problem, 14 was converted to homoallylic alcohol 15 by Petasis methylenation via the corresponding TES ether. Attempts to methylenate (3-hydroxyketone 14 directly under Petasis conditions led to substantial decomposition via elimination and retro-aldol pathways. Alcohol 15 underwent smooth Mitsunobu inversion to give, following methanolysis and TES ether formation, the desired 1,4-anti compound 16 (Scheme 3). This was then converted in three straightforward steps to aldehyde 17, ready for the proposed aldol union with ketone 10. 

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... 

Ether Formation. It is reported that the reduction products of certain a,j8-unsaturated ketones, for example, dibenzalacetone (XL), contained sonfe of the isopropyl ethers pf the carbinols.6 Carbinols of this type are especially susceptible to ether formation often recrystallization from an alcohol is sufficient to give the ether. However, ether formation is by no means the usual reaction with unsaturated ketones. Indeed, in most cases no ether was noted in the products. Even in the case of dibenzalacetone, the normal product, i.e., the carbinol, has been obtained in 58% yield.36 9,9-Dimethylanthrone-10 (XLI) gave 64% of a material corresponding in analysis to the isopropyl ether (XLII).17 Similar observations of ether formation with a-halogen ketones will be discussed later. There appears to be no way of predicting with any degree of certainty when ether formation is likely, but it is not a common side reaction. 

Homologation of ketones (1, 369-370 6, 252-253 8, 222). Ethyl diazoacetate is recommended as the most useful diazoalkane for monohomologation of cyclic and acyclic ketones without formation of epoxides as by-products. One advantage is that the usually slow reaction can be catalyzed by BF3 etherate (or triethyloxonium tetrafluoro-borate). 

Regioselective silylenol ether formation allows for introduction of oxygen away from the more highly alkylated side of a ketone. 

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