Acetals from enol ethers + alcohols

Other functional polyfluorinated compounds are available by addition of perhaloalkyl halides to enol derivatives, e.g. formation of 1 and 2 (see also Table 4). The adducts formed from enol acetates or enol ethers are not very stable and their hydrolysis to give a-perhaloalkyl aldehydes or ketones is often rapid. However, the enol derivatives can be transformed either to give ketals using alcohols or to give various products by oxidation and reduction reactions. The peculiar perfluoroalkyl iodide addition to enamines is spontaneous at room temperature, e.g. formation of 3. ... 

Enol ethers (15) and mixed acetals (16) are readily obtained from secondary but not from tertiary alcohols, whereas tetrahydropyranyl ethers can be formed even from tertiary alcohols. This is a result of the greater steric requirements of the reagents (17) and (18) as compared to (19). 

For those substrates more susceptible to nucleophilic attack (e.g., polyhalo alkenes and alkenes of the type C=C—Z), it is better to carry out the reaction in basic solution, where the attacking species is RO . The reactions with C=C—Z are of the Michael type, and OR goes to the side away from the Z. Since triple bonds are more susceptible to nucleophilic attack than double bonds, it might be expected that bases would catalyze addition to triple bonds particularly well. This is the case, and enol ethers and acetals can be produced by this reaction. Because enol ethers are more susceptible than triple bonds to electrophilic attack, the addition of alcohols to enol ethers can also be catalyzed by acids. " One utilization of this reaction involves the compound dihydropyran... 

Most cyclizations of 3-allenic alcohols have produced six-membered ring products via a 6-endo process (equation 85).168 205 The exception is found with terminally unsubstituted allenes as shown in equation (86).205d The bicyclic acetal results from a 5-exo cyclization to an enol ether, which undergoes a second cyclization to form the acetal. 

Hoffmann and Pete [106] have irradiated D-alk- 3 -e n y I salicylates and obtained products which result from rearrangement reactions of primary ortho adducts (Scheme 31). The authors realized that the linear tricyclic dienes, formed by ring closure of the cyclooctatriene derivatives, are enol ethers which can be converted into acetals by acid-catalyzed addition of an alcohol. This shifts the... 

Enol ether 13 is prepared from butanal 12 by acetalization with alcohol PMBOH 35. The resulting acetal 40 is subjected to elimination with phosphinic acid 36. Acetalization proceeds via nucleophilic attack of the alcohol on the protonated aldehyde 37, dehydratization of the hemiacetal 38 and further nucleophilic attack on the carbenium ion 39. Since all steps are reversible, the created water has to be removed to achieve quantitative turnover. This is carried out by the use of water binding agents or solvents (dry Na2S04, CaCl2, orthoesters) or azeotropic distillation. 

In the second step the TMS enol ether collapses in a 3 1 1 mixture of acetic acid,water and THF to the corresponding ketone. Also the TBS protecting group is removed leading in 72 % yield (from 11) to the primary alcohol.15... 

The alternative to this 0,0-acetal formation is the sequence of addition and El reaction. As a matter of fact, this is familiar from the transformation of alcohols with carbonyl compounds, but only occurs in some (very rare) cases. This is illustrated by Figure 9.31 using acid-catalyzed transformations of ethanol with two /3-diketones as an example. Here, enol ethers, namely 3-ethoxy-2-cyclopentene-l-one and 3-ethoxy-2-cyclohexene-l-one, respectively, are... 

Experiments on the bromination of equilibrated ketone-acetal systems in methanol were also recently performed for substituted acetophenones (El-Alaoui, 1979 Toullec and El-Alaoui, 1979). Lyonium catalytic constants fit (57), but for most of the substituents the (fcA)m term is negligible and cannot be obtained with accuracy. However, the relative partial rates for the bromination of equilibrated ketone-acetal systems can be estimated. For a given water concentration, it was observed that the enol path is more important for 3-nitroacetophenone than for 4-methoxyacetophenone. In fact, the smaller the proportion of free ketone at equilibrium, the more the enol path is followed. From these results, it can be seen that the enol-ether path is predominant even if the acetal form is of minor importance. The proportions of the two competing routes must only depend on (i) the relative stabilities of the hydroxy-and alkyoxycarbenium ions, (ii) the relative reactivities of these two ions yielding enol and enol ether, respectively, and (iii) the ratio of alcohol and water concentrations which determines the relative concentrations of the ions at equilibrium. Since acetal formation is a dead-end in the mechanism, the amount of acetal has no bearing on the relative rates. Bromination, isotope exchange or another reaction can occur via the enol ether even in secondary and tertiary alcohols, i.e. when the acetal is not stable at all because of steric hindrance. 

A similar reaction occurs when enol ethers react with alcohols in acid solution and in the absence of water, but now we are starting in the middle of the acetal hydrolysis mechanism and going the other way, in the direction of the acetal A useful example is the formation of THP (= TetraHydroPyranyl) derivatives of alcohols from the enol ether dihydropyran. You will see THP derivatives of alcohols being used as protecting groups in Chapter 24. 

Other known methods for preparing O-alkyl enol ethers include, most notably, alcohol elimination from acetals, double bond isomeri2ation in allylic ethers, reduction of alkoxy enol phosphates, and phosphorane-based condensation approaches.5 These methods, however, suffer from poor stereoselectivity, low yields, or lack of generality, if not a combination of these drawbacks. 

Alcohols react with a large excess of dimethoxymethane, (bp 41-42 °C) via an acetal exchange process at room temperature in the presence of acidic catalysts such as phosphorus pentoxide.459 474-475 The reaction was adapted to the construction of a 1,3-dioxane ring system in a synthesis of Mycalamide B [Scheme 4<257].47A After installing a MOM ether at a hindered secondary alcohol 257,1, the ketone was converted to its TBS enol ether 257J. Oxidation with wi-chloroperoxybenzoic acid returned a stable oxirane 257.4 that reacted with dimethoxymethane and phosphorus pentoxide to afford the desired L3-dioxane ring in 257 6 in 77% overall yield from 257J. Presumably, O-alkyla-... 

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