Vinyl acetate irreversible transesterification

Prochiral Compounds. The enantiodifferentiation of prochi-ral compounds by lipase-catalyzed hydrolysis and transesterification reactions is fairly common, with prochiral 1,3-diols most frequently employed as substrates. Recent reports of asymmetric hydrolysis include diesters of 2-substituted 1,3-propanediols and 2-0-protected glycerol derivatives. The asymmetric transesterification of prochiral diols such as 2-0-benzylglycerol and various other 2-substituted 1,3-propanediol derivatives is also fairly common, most frequently with Vinyl Acetate as an irreversible acyl transfer agent. 

The asymmetric transesterification of cyclic me o-diols, usually with vinyl acetate as an irreversible acyl transfer agent, includes monocyclic cycloalkene diol derivatives, bicyclic diols, such as the ej o-acetonide in eq 12, bicyclic diols of the norbomyl type, andorganometallic l,2-bis(hydroxymethyl)ferrocenepossessing planar chirality. 

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. 

In transesterification it is difficult to achieve high conversion because of the reversibility of the reaction. This drawback is overcome by employing enol esters such as vinyl and isopropenyl acetates. On transesterification these enol esters are converted to acetaldehyde and acetone, respectively, and removed from the equilibrium enabling irreversible acylation (Scheme 12.185) [307a, 338]. This procedure enables preferential acylation of primary alcohols to secondary alcohols and phenols. 

Biotransformations are now firmly established in the synthetic chemist s armoury, especially reactions employing inexpensive hydrolytic enzymes for the resolution of racemates and for the desymmetrization of prochiral substrates. From a practical viewpoint, biocatalytic resolution is arguably the simplest method available to obtain synthetically useful quantities of chiral synthons. As an illustration of this point, many racemic secondary alcohols ROH can be resolved without prior derivatization by combining with a lipase and a volatile acyl donor (usually vinyl acetate) in an organic solvent, to effect irreversible transesterification once the desired degree of conversion has been reached, routine filtration to remove the enzyme and concentration of the filtrate affords the optically enriched products ROAcyl and ROH directly. 

The most satisfactory method to carry out an irreversible transesterification is the reaction of acylation of an alcohol with vinyl acylates [130,131]. In this reaction the back reaction is prevented by the irreversible tautomerization of vinyl alcohol to acet dehyde. This latest product could cause the inhibition of the enzyme that has been hnmobilized to overcome this complication [132]. In some studies, however, a few cycles of reactions could be performed without affecting the enantioselectivity of the reaction [133]. Also oxime esters have been proposed as acyl transfer agents [134] for irreversible enzymatic transesterifications (Scheme 23). 

Table 3 Asymmetrization of 2-Substituted 1,3-Propenediols by Irreversible Transesterification with Vinyl Acetate...

In contrast to the hydrolysis of prochiral esters performed in aqueous solutions, the enzymatic acylation of prochiral diols is usually carried out in an inert organic solvent such as hexane, ether, toluene, or ethyl acetate. In order to increase the reaction rate and the degree of conversion, activated esters such as vinyl carboxylates are often used as acylating agents. The vinyl alcohol formed as a result of transesterification tautomerizes to acetaldehyde, making the reaction practically irreversible. The presence of a bulky substituent in the 2-position helps the enzyme to discriminate between enantiotopic faces as a result the enzymatic acylation of prochiral 2-benzoxy-l,3-propanediol (34) proceeds with excellent selectivity (ee > 96%) (49). In the case of the 2-methyl substituted diol (33) the selectivity is only moderate (50). 

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