Ethoxyvinyl acetate

The Diels-Alder addition of enantiomerically pure oxadienes to (Z)-2-ethoxyvinyl acetate are highly diastereoselective and have allowed Tietze and coworkers to prepare derivatives of 4-deoxy-D-/yv(9-hexose [146]. 

Use of the Simmons-Smith reagent for the formation of cyclopropanone precursors has been reported in the case of ethoxy vinyl carboxylates (1) and ketene ketals (2) (Scheme 2). Using 1-ethoxyvinyl acetate and benzoate, it was found that the zinc iodide generated in the reaction tends to favor opening of the cyclopropane ring. However use of glyme as a solvent prevents attack on the ring by this Lewis acid since the zinc salt is insoluble in that medium . 

Regioselective acylations of polyhydroxylated compounds such as carbohydrates, glycerols, steroids, or alkaloids have been carried out with lipases, esterases, and proteases [13, 20]. One example is the Candida antartica lipase (immobilized on acrylic resin) catalyzed monoacylation of the signalling steroid ectysone (1) giving selectively the 2-C)-acetate 2 (eq. (1)). Using vinyl acetate for this transesterification the reaction was irreversibly pushed to the product side, since the liberated enol instantaneously isomerizes to acetaldehyde [21]. The sometimes unfavorable aldehyde is avoided when 1-ethoxyvinyl acetates [22], trichloro- or -fluoroethyl esters [23 a, b], oxime esters [23 c] or thioesters [23 d] are employed for the quasi-irreversible reaction courses. 

Resolutions. The following types of substrates have been resolved via lipase-mediated enantioselective esterification malic and aspartic esters, 3-hydroxyalken-l-yl p-tolyl sulfoxides, P-hydroxy sulfoxides." A practical method involves sequential transacetylation and sulfation, followed by extraction and treatment of the aqueous layer with methanolic HCl to recover the alcohol (the organic layer yields the acetate). The use of 1-ethoxyvinyl acetate as acetyl donor in these reactions has been proposed."... 

Pummerer reaction. Upon reaction with a-ethoxyvinyl acetate chiral sulfoxides in which the a-carbon is substituted with an electron-withdrawing group are transformed into a-acetoxy sulfides. In most cases the enantiomer excess of the products amount to 70-80%. 

The possibly harmful effects of acetaldehyde can be avoided by employing i-propenyl acetate, which yields (more innocuous) acetone as byproduct. Alternatively, ethoxyvinyl acetate can be used as acyl donor (Scheme 3.4) [162-164]. 

Recently, 1-ethoxyvinyl acetate has been proposed as a novel and reliable acyl donor for the enzymatic resolution of alcohols (Scheme 24) in a lipase-catalyzed irreversible transesterification procedure [135]. A similar protocol has been utilized for the irreversible acetoacetylation of alcohols with diketene in the presence of lipases in organic solvents [136,137] and the reaction has been reported to proceed with high enantioselectivity [136], as shown in Scheme 25. 

Scheme 24 1-Ethoxyvinyl acetate, a new acyl donor for irreversible transesterifications.

All the syntheses of this type give piperid-4-ones or pyrid-4-ones. Errera reported that diethyl acetonedicarboxylate condensed with triethyl orthoformate in hot acetic anhydride, and that treatment of the product with ammonia gave a poor yield of the pyrid-4-one (644) (1898CB1682). It is certain that the intermediate is the di(ethoxyvinyl) ketone (643), so that this is perhaps better classified as a [5 + 1] synthesis, but most developments from this beginning do not involve isolation of intermediates. An arylamine has been used to obtain an A-arylpyrid-4-one (645) (46JA1253). 

Some l-(2-furyl)-l-alkanols have also been resolved by hydrolase-catalyzed acylations (Scheme 4.20). Thus l-(2-furyl)-l-ethanol (46) is efficiently resolved by acylation with vinyl acetate catalyzed either by Lipozyme IM or PPL [77]. Resolution with a more complex acyl donor, ethoxyvinyl methyl fumarate, catalyzed by Lipase LIP (from Pseudomonas aeruginosa) has also been achieved [95]. The... 

Synthesis of 4-amino-2-pyrazolin-5-ones is usually achieved by treatment of an a-amido-/3-aldehydo- or /9-ketoester with hydrazines according to the classical method for preparation of 2-pyrazolin-5-ones. Variants on this procedure consist of using an a-amidoester which has /9-substituents whose reaction is equivalent to that of a /9-carbonyl substituent. Such compounds are D-benzylpenicilloic acid a-methyl ester,1027 ethyl phenylpenaldate243 and the acetal of an a-amido-/9-formyl ester.59,243 Cornforth has isomerized 2-phenyl-4-hydrazino-methylidyneoxazolidone to 4-benzamido-2-pyrazolin-5-one. The same compound was obtained by treatment of 1-ethoxyvinyl-2-phenyl-oxazolidone with phenylhydrazine.319... 

The esterases and lipases are members of a still larger group of enzymes that catalyze acyl transfer, either in the direction of solvolysis or by acylation of the substrate. Both types of enzymes are called hydrolases. In water, hydrolysis occurs, but in the presence of alcohols, transesterification can occur. Reactions in the acylation direction are done in the presence of acyl donors. Esters of enols such as vinyl acetate or isopropenyl acetate are often used as sources of the acyl group. These enol esters are more reactive than alkyl esters, and the enol that is displaced on acyl transfer is converted to acetaldehyde or acetone. To avoid side products arising from these carbonyl compounds, one can use 1-ethoxyvinyl esters, which give ethyl acetate as the by-product. ... 

Cyclic amidines are prepared by the condensation of 1,2-diamines and p-ketoester derivatives [18]. Reaction of At-monomethyl-1,2-diamine and formylacetate acetal in the presence of an acid catalyst such as hydrochloric acid (HCl) or p-TsOH initially forms amidines by cyclocondensation. Elimination of ethanol to ethoxyvinyl amidine, followed by incorporation of a different 1,2-diamine, furnishes 1,3-dimethyl- and 1-butylimidazo-lidines (Scheme 3.7). This reaction is applied to the preparation of several kinds of diamines as a key step [19]. 

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