Ethyl Vinyl Ether condensation reactions

A 50-ml., round-bottomed flask equipped with a magnetic stirring bar and a 20-ml. calibration mark (Note 1) is charged with 970 mg. (2.5 mmoles) of 4-cholesten-3/9-ol (Note 2). Ethyl vinyl ether is distilled into the flask to the 20-ml. mark (Note 3). The mixture is stirred to effect solution then 820 mg. (2.55 mmoles) of mercuric acetate (Note 4) is added to the reaction mixture. The flask is fitted with a reflux condenser connected to a gas inlet tube and flushed with argon. The reaction mixture is then stirred and heated (Note 5) at reflux under a positive argon pressure for 17 hours. After the solution has cooled to room temperature, 0.062 ml. (1.09 mmoles) of glacial acetic acid (Note... 

In the condensation of the ketd (95) with ethyl vinyl ether, montmorillonite clay 10 was found to be an effective catalyst and superior to the previously reported Lewis acid. ° In this reaction, the work-up is simplified to filtration of the catalyst. 

Superelectrophilic properties of nitroarenes are retained when mie of the furoxan rings in NBDF is replaced with electron-deficient isoxazole [124] or pyridine fragments [125]. As in case of NBDF, the reactions of these fused nitroarenes with ethyl vinyl ether were found to lead to the correspruiding benzoxazine N-oxides 143 and 144 condensed with heterocyclic rings (Scheme 72). 

A major disadvantage of the tetrahydropyranyl ether as a protecting group is that an asymmetric center is produced at C-2 of the tetrahydropyran ring on reaction with the alcohol. This asymmetry presents no difficulties if the alcohol is achiral, since a racemic mixture results. If the alcohol has an asymmetric center anywhere in the molecule, however, condensation with dihydropyran can afford a mixture of diastereomeric tetrahydropyranyl ethers, which may complicate purification and characterization. One way of surmounting this problem is to use methyl 2-propenyl ether, rather than dihydropyran. No asymmetric center is introduced, and the acetal offers the further advantage of being hydrolyzed under milder conditions than those required for tetrahydropyranyl ethers. Ethyl vinyl ether is also useful as a hydroxyl-... 

The preparation of resin-bound nitroalkenes via microwave-assisted Knoeve-nagel condensation of resin-bound nitroacetic acid with alkyl and aryl substituted aldehydes was described by Kustner and Scheeren [134]. The condensation reactions under microwave irradiation were achieved in 20 min at 350 W, whereas under conventional conditions they needed 17 h at room temperature. The potential of the resin-bound nitroalkenes for application in combinatorial chemistry was demonstrated by Diels-Alder reaction with 2,3-dimethylbutadiene and tandem reaction with ethyl vinyl ether and styrene (Fig. 38). 

Tietze reported a domino-Knoevenagel-hetero-Diels-Alder reaction involving a three-component reaction between an a-nitroketone, formaldehyde, and an alkyl vinyl ether. In one example, a Knoevenagel condensation between ketone 105 and formaldehyde (106) yields electron-poor hetero-diene 108 that undergoes an inverse electron demand Diels-Alder reaction with ethyl vinyl ether to furnish dihydropyran 109. Tietze subsequently converted 109 into the deoxysugar (+)-forosamin. ... 

To a 250-ml 3-necked flask equipped with a magnetic stirring bar, condenser, thermometer, and gas inlet-outlet is added a benzene solution (toluene can be used in place and is less toxic) of 10.77 gm (0.1098 mole) of maleic anhydride and 0.04514 gm (1.863 x lO"" mole) of benzoyl peroxide. Dry nitrogen (oxygen-free) is flushed for 45 min through the flask, and then 9.11 gm (0.1214 mole) of ethyl vinyl ether is injected into the flask via a septrum seal on one of the necks. The reaction mixture is stirred and heated for 8 hours at 59°-61°C. The white precipitate is filtered and dissolved in 125 ml of acetone. The product is isolated from the acetone by gradually... 

The reaction of acetylene 4.978 with ethyl vinyl ether proceeds readily at 0°C, but the cyclobutene is unstable and undergoes spontaneous ring cleavage to form l-ethoxy-2-(trifluoroacetyl)-3-chloro-1,3-butadiene 4.984, and no other isomers or alkynylation products. l-Chloro-2-ethoxyoxalylacetylene is less reactive with vinyl ethers. Condensed cyclobutenes 4.985 and 4.986 were isolated by chromatography in moderate yield (Figue 4.2). 

The reaction mechanism and the application of the enol ether condensation in the synthesis of carotenoids have recently been reviewed [38]. The main advantage of the enol ether condensation, compared with the aldol condensation, is that the enol ether reacts exclusively as the nucleophilic reaction partner and the acetal exclusively as the electrophilic one and this leads unequivocally to the desired, uniform, reaction product. As the alkoxy group of the starting acetal takes part in the formation of the new acetal grouping that results from the enol ether moiety, it is preferable for all the alkoxy groups of both reactant to be identical. Most of the examples published have been carried out with vinyl methyl ether (16) and vinyl ethyl ether (17), used to extend the carbon skeleton by two carbon atoms, or propenyl ethyl ether (18) and 1-methoxy-1-methylethene (19) for the extension by three carbon atoms (Figure 5). 

The commercial apo-p-carotenoids ethyl 8 -apo-p-caroten-8 -oate (286) and 8 -apo-p-caroten-8 -al (287) may be prepared from the Cig-aldehyde 53, used in the synthesis of p,p-carotene (2). By reaction of 53 with the Cg-acetal 288 the C25-aldehyde 15,15 -didehydro-12 -apo-p-caroten-12 -al (289) is obtained [115], This compound can be transformed into the Cso-aldehyde 287 by consecutive enol ether condensations first with vinyl ethyl ether (17), to give the C2/-aldehyde 290, and then with prop-1-enyl ether (18), followed by partial hydrogenation and isomerization [116] Scheme 59... 

Scheme 5 shows the enol ether condensation as exemplified by the reaction of 23 to give the C 16-aldehyde 29. Acetylation of 23 gives 30, which reacts with vinyl ethyl ether 31 to 32, and after hydrolysis and elimination 29 is obtained. Similarly, 29 and prop-l-enyl ethyl ether (28) give the C 19-aldehyde 27 (see Chapter 2 Part I). 

The three-step enol ether condensation is again used in the chain lengthening of 36 (Scheme 9) [22]. Coupling to vinyl ethyl ether (31) leads to the C27-aldehyde 44. Repetition of the reaction sequence with prop-l-enyl ethyl ether (28) yields the corresponding C30-aldehyde. After partial hydrogenation and thermal isomerization in petroleum ether, 8 -apo-P-caroten-8 -al (482) is obtained in a yield of approximately 50% based on 27. The conversion of 44 into ethyl 8 -apo-p-caroten-8 -oate (7) is described in Section C. 

The synthesis of 1 from the C 14-aldehyde 23 requires twenty reaction steps, including the preparation of the C6-acetal 37, and the formation of seven C-C bonds. Nevertheless, the process is economic because of the chemical and technological integration of the manufacturing process. Construction of the polyene chain, for example, only requires the simple chemicals acetylene, triethyl orthoformate, propenyl ethyl ether and vinyl ethyl ether. Five C-C bonds are formed with the aid of the enol ether condensation. This repetition of simple operations simplifies the process and allows even multistep syntheses to be carried out cost-effectively. 

Condensed heteroaromatic cations are reactive in [2 + 4] cycloaddition reactions with inverse electron demand. For instance, 2-benzopyrylium salts (389) react with vinyl ethyl ether to afford... 

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