Secondary alcohols substrates irreversible transesterifications

Kinetic Resolution by Transesterification. Asymmetric transformation involving acylation of chiral alcohols is by far the most common example of kinetic resolution by lipase-catalyzed transesterification, most commonly with irreversible vinyl esters. This field is now becoming the most widely applied technique involving lipases. Recent reports of the numerous secondary alcohol substrates include various monocyclic (eq 6) andacyclic compounds, cyanohydrins, sulfones, and glycals, to name a few. 

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. 

For the above reasons, secondary alcohols are frequently used as model substrates for studies devoted to the optimization of the enantioselectivity of the enzymatic process when immobilized lipases are used as biocatalysts [50]. This applies also to the choice of the most suitable solvent [175], or to the activity of new lipases [176], or to variations on the irreversible transesterification methodology [135,177]. The highly enantioselective resolution of racemic secondary alcohols has been reported for aliphatic and aromatic substrates [178-181] and few results are reported in Table 1 and Scheme 39. 

Scheme 39 Secondary alcohols as substrates for irreversible transesterifications.

Special attention should be devoted to less conventional applications of the enzymatic transesterification methodology such as resolution of unstable substrates as racemic secondary hydroperoxides [291]. The development of new reactions in the presence of enzymes should pursued, as, for example, the simultaneous formation of a hemithioac-etal and die irreversible transesterification in the presence of a lipase [292]. Also, for synthetic applications, the combination of enzymatic and chemical asymmetrical methods could lead to interesting results, such as the one-pot lipase-catalyzed acylation and the Mitsonobu inversion of the configuration of the unreacted alcohol, which should lead to only one enantiomeric ester [293]. 

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