Ethyl Vinyl Ether acetal condensations

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... 

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-... 

Acetal Condensations. The acid-catalyzed condensation of ethyl vinyl ether with acetals derived from a,p-unsaturated aldehydes and ketones is an excellent method to lengthen a carbon chain by two carbon atoms, particularly of polyenals. In an industrial process for the manufacture of the Cie aldehyde (eq 13), the C14 acetal is reacted with ethyl vinyl ether in the presence of Zinc Chloride to give an alkoxy acetal, which, without isolation, is then hydrolyzed with moist acetic acid. Longer conjugated carotenals have been synthesized by this method, and montmo-rillonite K-10 clay (see MontmoriUonite KIO) has been reported to be an excellent replacement for the Lewis acids normally used in the condensation. ... 

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... 

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. 

---