Ethyl thiooctanoate

With the exception of 2-butanol (E = 9), simple 2-alkanols can be efficiently resolved by using CALB-catalyzed (Novozym 435) acylation in hexane using S-ethyl thiooctanoate or vinyl butyrate as acyl donor to produce the esters 51-59... 

To make a reaction irreversible, it can be performed in neat acyl donor, for instance, in ethyl acetate, which otherwise is reversible (Fig. 12, entry 9). Acylation with S-ethyl thiooctanoate has allowed successful kinetic resolution of secondary alcohols, because evaporation of the formed thioethanol easily shifts the equilibrium to the product side (entry 3) (18). However, acid anhydrides and especially activated esters, which liberate a low nucleophilic (entry 8) or unstable (entries 1, 5, and 6) alcohol, are usually more appropriate. When acid... 

Frykman, H., Ohrner, N., Norin, T., and Hult, K. (1993) S-ethyl thiooctanoate as acyl donor in lipase catalysed resolution... 

Removal of products may be an experimental procedure adopted to shift the equilibrium of the transesterification to the forward reaction [123-125]. A similar approach consists of transesterification of hydroxy groups with ethyl thiooctanoate in the presence of C. antarctica lipase (Scheme 21). By this method the enantioselective resolution of alcohols can be achieved [126,127]. 

Scheme 21 irreversible transesterifications with ethyl thiooctanoate. 

Many such activated acyl derivatives have been developed, and the field has been reviewed [7-9]. The most commonly used irreversible acyl donors are various types of vinyl esters. During the acylation of the enzyme, vinyl alcohols are liberated, which rapidly tautomerize to non-nucleophilic carbonyl compounds (Scheme 4.5). The acyl-enzyme then reacts with the racemic nucleophile (e.g., an alcohol or amine). Many vinyl esters and isopropenyl acetate are commercially available, and others can be made from vinyl and isopropenyl acetate by Lewis acid- or palladium-catalyzed reactions with acids [10-12] or from transition metal-catalyzed additions to acetylenes [13-15]. If ethoxyacetylene is used in such reactions, R1 in the resulting acyl donor will be OEt (Scheme 4.5), and hence the end product from the acyl donor leaving group will be the innocuous ethyl acetate [16]. Other frequently used acylation agents that act as more or less irreversible acyl donors are the easily prepared 2,2,2-trifluoro- and 2,2,2-trichloro-ethyl esters [17-23]. Less frequently used are oxime esters and cyanomethyl ester [7]. S-ethyl thioesters such as the thiooctanoate has also been used, and here the ethanethiol formed is allowed to evaporate to displace the equilibrium [24, 25]. Some anhydrides can also serve as irreversible acyl donors. 

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