Enol ethyl vinyl ether

The chiral BOX-copper(ll) complexes, (S)-21a and (l )-21b (X=OTf, SbFg), were found by Evans et al. to catalyze the enantioselective cycloaddition reactions of the a,/ -unsaturated acyl phosphonates 49 with ethyl vinyl ether 46a and the cyclic enol ethers 50 giving the cycloaddition products 51 and 52, respectively, in very high yields and ee as outlined in Scheme 4.33 [38b]. It is notable that the acyclic and cyclic enol ethers react highly stereoselectively and that the same enantiomer is formed using (S)-21a and (J )-21b as the catalyst. It is, furthermore, of practical importance that the cycloaddition reaction can proceed in the presence of only 0.2 mol% (J )-21a (X=SbF6) with minimal reduction in the yield of the cycloaddition product and no loss of enantioselectivity (93% ee). 

More recently, further developments have shown that the reaction outlined in Scheme 4.33 can also proceed for other alkenes, such as silyl-enol ethers of acetophenone [48 b], which gives the endo diastereomer in up to 99% ee. It was also shown that / -ethyl-/ -methyl-substituted acyl phosphonate also can undergo a dia-stereo- and enantioselective cycloaddition reaction with ethyl vinyl ether catalyzed by the chiral Ph-BOX-copper(ll) catalyst. The preparative use of the cycloaddition reaction was demonstrated by performing reactions on the gram scale and showing that no special measures are required for the reaction and that the dihydro-pyrans can be obtained in high yield and with very high diastereo- and enantioselective excess. 

In a similar way, Carreaux and coworkers [53] used 1-oxa-l,3-butadienes 4-155 carrying a boronic acid ester moiety as heterodienes [54], enol ethers and saturated as well as aromatic aldehydes. Thus, reaction of 4-155 and ethyl vinyl ether was carried out for 24 h in the presence of catalytic amounts of the Lewis acid Yb(fod)3 (Scheme 4.33). Without work-up, the mixture was treated with an excess of an aldehyde 4-156 to give the desired a-hydroxyalkyl dihydropyran 4-157. Although this is not a domino reaction, it is nonetheless a simple and useful one-pot procedure. 

Giomi s group developed a domino process for the synthesis of spiro tricyclic nitroso acetals using a, 3-unsaturated nitro compounds 4-163 and ethyl vinyl ether to give the nitrone 4-164, which underwent a second 1,3-dipolar cycloaddition with the enol ether (Scheme 4.35) [56]. The diastereomeric cycloadducts formed, 4-165 and 4-166 can be isolated in high yield. However, if R is hydrogen, an elimination process follows to give the acetals 4-167 in 56% yield. 

Considering the above-mentioned facts, according to which simple diazoketones yield dihydrofurans with ketene acetals but cyclopropanes with enol ethers, one exports an interlink between these clear-cut alternatives to exist, i.e. substrates from which both cyclopropanes and dihydrofurans result. In fact, providing an enol ether with a cation-stabilizing substituent in the a-position creates such a situation The Rh2(OAc)4-catalyzed decomposition of -diazoacetophenone in the presence of ethyl vinyl ether produces mainly cyclopropane 82 (R=H), but a small amount of dihydro-... 

Acylation of enol ethers. Reaction of 1 with ethyl vinyl ether in ether provides an intermediate that undergoes dehydrochlorination when heated to provide the trichloromethyl ketone 2, which is converted by base (haloform reaction) to the ester 3 in high yield. 

The metalation of vinyl ethers, the reaction of a-lithiated vinyl ethers obtained thereby with electrophiles and the subsequent hydrolysis represent a simple and efficient method for carbonyl umpolung. Thus, lithiated methyl vinyl ether 56 and ethyl vinyl ether 54, available by deprotonation with t- or n-butyllithium, readily react with aldehydes, ketones and alkyl halides. When the enol ether moiety of the adducts formed in this way is submitted to an acid hydrolysis, methyl ketones are obtained as shown in equations 72 and 73 . Thus, the lithiated ethers 56 and 54 function as an acetaldehyde d synthon 177. The reactivity of a-metalated vinyl ethers has been reviewed recently . 

For acrolein, styrene and methyl acrylate, see pp. 254, 264 and 268, respetively. 1-Hexene can be modeled by propene (p. 264). Ethyl vinyl ether can be modeled by methyl vinyl ether, enol or even propene. 

The preparation involves an oxymercuration (Section 3.5.3) of the C=C double bond of the ethyl vinyl ether. The Hg(OAc) ion is the electrophile as expected, but it forms an open-chain cation A as an intermediate rather than a cyclic mercurinium ion. The open-chain cation A is more stable than the mercurinium ion because it can be stabilized by way of oxocarbe-nium ion resonance. Next, cation A reacts with the allyl alcohol, and a protonated mixed acetal B is formed. Compound B eliminates EtOH and Hg(OAc) in an El process, and the desired enol ether D results. The enol ether D is in equilibrium with the substrate alcohol and ethyl vinyl ether. The equilibrium constant is about 1. However, the use of a large excess of the ethyl vinyl ether shifts the equilibrium to the side of the enol ether D so that the latter can be isolated in high yield. 

Fig. 11.42. Preparation of an allyl enol ether, D, from allyl alcohol and a large excess of ethyl vinyl ether. Subsequent Claisen rearrangement D —> C proceeding with chirality transfer.

A reversion of the addition direction has been observed in the case of electron rich alkenes such as enol ethers and enamines. For example, ethyl vinyl ether reacts with the mesoionic compound (9) to produce the cycloadduct (108) in 58% yield. Other examples are the reactions of mesoionic 1,3-dithiolones with cyclohexyl vinyl ether, cyclopenten-l-yl ethyl ether, ethyl isobuten-l-yl ether and /V-(isobuten-l-yl)morpholine. The observed regioselectivities have been also qualitatively discussed on the basis of MO perturbation theory (79LA360). 

The use of enol ethers as dienophiles improves the reaction, however, still high temperature is needed and endo/exo-selectivity is low. Thus, cycloaddition of ethyl vinyl ether 2-83 to cyclopentenecarbaldehyde 2-82 gave the cycloadduct 2-84 as a 1 1 mixture which was used for the synthesis of iridoids (Fig. 2-23) [121]. 

Directly related to aldehyde-enol tautomerisation in protogenic solvents are recent results reported by Capon et al. (1979) concerning the decomposition of [61] in D20-[2H3]acetonitrile which generates vinyl alcohol (37), the tautomerisation of which was monitored by H and 13C nmr spectroscopy and compared with ethyl vinyl ether hydrolysis. 

An enol ether type of vinyl group is present in ethyl vinyl ether, a reagent used for the protection of alcohols. This time all the coupling constants are smaller because of the electronegativity of the oxygen atom, which is now joined directly to the double bond. 

In many instances the reaction of an alcohol with dihydropyran (or ethyl vinyl ether or 2-methoxypropene) does not go to completion despite the addition of a large excess of the enol ether as much as 20% of the starting material will be present at equilibrium. The equilibrium, once reached, can be shifted toward product by adding excess finely powdered anhydrous potassium carbonate and stirring the reaction mixture at room temperature. As the acid concentration gradually diminishes, the reaction goes to completion. 

This procedure consists of the synthesis of a precursor, methoxymethyl vinyl ether, an a-hydroxy enol ether, and the intramolecular hydrosilylatlon of the latter followed by oxidative cleavage of the silicon-carbon bonds. The first step, methoxymethylation of 2-bromoethanol, is based on Fujita s method.7 The second and third steps are modifications of results reported by McDougal and his co-workers. Dehydrobromination of 2-bromoethyl methoxymethyl ether to methoxymethyl vinyl ether was achieved most efficiently with potassium hydroxide pellets -9 rather than with potassium tert-butoxide as originally reported for dehydrobromination of the tetrahydropyranyl analog.10 Potassium tert-butoxide was effective for the dehydrobromination, but formed an adduct of tert-butyl alcohol with the vinyl ether as a by-product in substantial amounts. Methoxymethyl vinyl ether is lithiated efficiently with sec-butyllithium in THF and, somewhat less efficiently, with n-butyllithium in tetrahydrofuran. Since lithiation of simple vinyl ethers such as ethyl vinyl ether requires tert-butyllithium,11 metalation may be assisted by the methoxymethoxy group in the present case. 

Cycloadditions with enol ethers The Diels-Alder reaction of vinyl ethers with a,(3-unsaturated aldehydes proceeds at room temperature when catalyzed by the related lanthanide Yb(fod),. An example is the reaction of crotonaldehyde with ethyl vinyl ether (equation I). 

The quaternary center was constructed stereospecifically by Claisen rearrangement (Scheme 46). The necessary enol ether was obtained by reaction of the secondary alcohol of 399 with ethyl vinyl ether and mercuric acetate. To change the polarity of the endocyclic double bond, the unsaturated ketone was reduced with lithium aluminum hydride to the allylic alcohol, 400, at low temperature. Then, prolonged heating with xylene led to the aldehyde, 401. Protection of the secondary alcohol was achieved by bromoether formation with W-bromosuccinimide in acetonitrile before the aldehyde of 402 was reacted with methyllithium. The epimeric mixture of secondary alcohols was protected as acetates 403. Then, the cyclic ketone... 

A useful preparative application of enolate oxidation was presented by Torii in the context of a facile synthesis of 4-hydroxyindole 59 [145]. Similar to Schafer s work [114], the anion of 1,3-cyclohexadione was added anodically to ethyl vinyl ether providing products 56 and 57 in 65%. The mixture of both can be transformed by reaction with (NH4)2C03 in methanol into 58 that is finally converted to 59. 

There have been a number of unsuccessful attempts to trap 1,4-zwitterionic intermediates, - but there have also been some reported successes. At best, then, such trapping experiments are not uniformly diagnostic for zwitterionic intermediates. truns-Propenyl ethyl ether reacts with TONE in ethanol solvent at 25 C to give product (140). " The normal [2 + 2] adduct (139) gives this same product when allowed to react in ethanol, but at a slower rate. Just how fast this solvolysis might take place under the conditions of the cycloaddition reaction, with enol ether and TCNE present, is not clear. Acetone does not interfere with the addition of ethyl vinyl ether to TCNE, but the adduct (141) is converted over one week at room temperature to the six-membered ring product (142), which may be postulated as being derived from ci ture of a 1,4-zwitterionic intermediate in equilibrium with the cyclobutane structure. Alternatively, since acetone like ethanol is known to react with TCNE, it may be a case of acid-catalyzed solvent-assisted solvolysis. 

Stronger oxidants convert enol ethers into esters or lactones. Ethyl vinyl ether added to a suspension of pyridininm chlorodiromate (PCC) in dichloromethane at room temperature furnishes ethyl acetate in 75% yield after 1 h (equation 331) [608]. Glucals produce lactones (equation 332) [609],... 

Satisfactory to good yields of adducts have been found for styrenes [Eq. (21a), Y = phenyl], conjugated dienes (Y = vinyl), enamines (Y = NR2), and enol ethers (Y = alkoxy), particularly if they are unsubstituted at the 6-carbon atom to Y. Nonactivated alkenes react less satisfactorily. In the oxidation of anionized 1,3-dicarbonyl compounds (Table 11, numbers 1-8) at potentials between 0.6 and 1.4 V (SCE) and in the presence of butadiene, only the additive dimer LXII is obtained in the presence of ethyl vinyl ether only the disubstituted monomers LXVI or LXVII arise, but with styrene both types of products LXII and LXVI are formed. This result indicates that the primary adduct LXIII is oxidized rapidly between 0.6 to 1.4 V to the carbenium ion in the case of an ethoxymethyl radical (Y = OEt), and slowly in the case of an allyl radical (Y = vinyl). 

Enol ethers. Enol ethers are prepared from alcohols by an exchange reaction with ethyl vinyl ether using the complex of Pd(OAc)2 with 1,10-phenanthroline. 

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