Enol ethers halogenation

Early transition states in enol ether halogenation 263... 

EARLY TRANSITION STATES IN ENOL ETHER HALOGENATION... 

Imbalance between polar and resonance effects in enol ether halogenation... 

Generally, isolated olefinic bonds will not escape attack by these reagents. However, in certain cases where the rate of hydroxyl oxidation is relatively fast, as with allylic alcohols, an isolated double bond will survive. Thepresence of other nucleophilic centers in the molecule, such as primary and secondary amines, sulfides, enol ethers and activated aromatic systems, will generate undesirable side reactions, but aldehydes, esters, ethers, ketals and acetals are generally stable under neutral or basic conditions. Halogenation of the product ketone can become but is not always a problem when base is not included in the reaction mixture. The generated acid can promote formation of an enol which in turn may compete favorably with the alcohol for the oxidant. 

Enol ethers are readily attacked in buffered medium by electrophilic reagents such as halogens, A -haloamides, perchloryl fluoride and organic peracids to give a-substituted ketones. Similarly, electrophilic attack on... 

A -dien-3-ol ethers gives rise to 6-substituted A" -3-ketones. 6-Hydroxy-A" -3-ketones can be obtained also by autooxidation.Structural changes in the steroid molecule may strongly affect the stability of 3-alkyl-A -ethers. Thus 11 j5-hydroxyl and 9a-fluorine substituents greatly increase the lability of the enol ether/ while halogens at C-6 stabilize this system to autooxidation and acid hydrolysis. 

Instead of direct halogenation of ketones, reactions with more reactive derivatives such as silyl enol ethers and enamines have advantages in certain cases. 

Halogen shifts have been found for tungsten, with assumed formation of iodovinylidenes in reactions of 1-iodo-l-alkynes with W(CO)5(thf) en route to cyclization of 2-(iodoethynyl)styrenes to naphthalenes and of iodo-alkynyl silyl enol ethers [147], while more substantial confirmation is found in Mn =C=C(I)CH (OR)2 (CO)2Cp [R = Me, Et (OR)2 = 0(CH2)30], of which the XRD structure of Mn =C=C(I)CH(OMe)2 (CO)2Cp was determined [148]. 

Azlactone oxidation Azlactones derived from dipeptides are more readily dehydrogenated than the dipeptides. This route to dehydropeptides has been examined with several reagents. Halogenation dehydrohalogenation is possible, but yields at best are 50%. Various oxidation procedures are about as effective. The most satisfactory method is oxidation of the corresponding trimethylsilyl enol ether with DDQ. However, this oxidation is limited to aryl azlactones. 

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... 

Rate coefficients (eqn 36) for the halogenation of enols, enol ethers and enolate ions in aqueous media at 25°C... 

ENOL ETHERS AS INTERMEDIATES IN ISOTOPE EXCHANGE AND HALOGENATION IN ALCOHOL SOLUTION... 

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. 

Silyl enol ethers hydrolyse by a slightly different mechanism, though the first step is the same— protonation at carbon using the lone pair on oxygen. We have already seen how easy it is to attack silicon with nucleophiles, especially those with oxygen or a halogen as the nucleophilic atom. This tips the balance towards attack by water at silicon for the next step. 

Reactions of enol ethers with halogen and sulfur electrophiles... 

The synthetic interest of the reaction is even broader since several functional groups in the substrate, such as C=C double bond, ether, halogen, ester, and amide groups (entries 6-10) can be present in the carbon skeleton. Chemose-lective cyclopropanation reactions involved the enone functionality in the presence of a saturated ketone group (Scheme 9). Recently, the reaction was applied to the conversion of 1,3-dicarbonyl compounds into 2-alkoxyalkenyl cyclopropanes (Scheme 10) [15]. These molecules having both vinylcyclopropane and enol ether moieties are supposed to be versatile synthetic intermediates. 

R = H, R = CHS) with two more equivalents of base.215 When R in compounds of type (60) contains a halogen in the ou-position (60d),217 a tricyclic system including an enol ether (e.g., 2,3-dihydro-6//-oxepino-[c][l,2]-benzothiazine-5(4//)-one-7,7-dioxide)218 is formed. 

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