Enantioselective acylation, hydrolases alcohols

The dynamic kinetic resolution (DKR) of secondary alcohols and amines (Scheme 11.11) is a prominent, industrially relevant, example of chemo-enzymatic chemistry in which a racemic mixture is converted into one enantiomer in essentially 100% yield and in high ee. This is in sharp contrast to enzyme-catalyzed kinetic resolutions that afford the desired end-product in a yield of at most 50%, while 50% of the starting material remains unreacted. In DKR processes, hydrolases are typically employed as the enantioselective acylation catalyst (which can be either R or S selective) while a concurrent racemization process racemizes the remaining substrate via an optically inactive intermediate. This ensures that all starting material is converted into the desired end-product. The importance of optically pure secondary alcohols and amines for the pharmaceutical industry triggered the development of a number of approaches that enable the racemization of sec-alcohols and amines via their corresponding ketones and imines, respectively [42],... 

Such a process, which runs in water and is based on a palladium-catalyzed racemization of O-acylated allyUc alcohols in combination with a hydrolase-catalyzed enantioselective hydrolysis of the ester, was developed in an early pioneering work by Allen and Williams [11]. In this type of DKR process, the resulting allylic alcohols of type, for example, (S)-6, were obtained with satisfactory to high enan-tioselectivities (Scheme 19.3). For example, under these conditions, the hydrolysis of racemic ester rac-5 in the presence of a lipase from Pseudomonas Jluorescms gave... 

A general procedure for enantioselective acylation of an alcohol with enol acetate or sucdnic anhydride is as follows. Dissolve 1 g of substrate alcohol in solvent (35 mL of hexane, toluene, or tetrahydrofuran) containing vinyl or iso-propenyl acetate (3 mL) and triethylamine (0.5 mL) (see following note). Add 0.5 g of hydrolase powder or immobilized hydrolase the enzyme powder will not dissolve Stir the suspension with a magnetic stirrer and monitor the progress of... 

This chapter deals with the use of hydrolases for enantioselective transformations of alcohols and amines, describing acylation reactions as synthetic challenges. Initially, general comments regarding the action and use of hydrolases in different media will be discussed. Special attention will be paid to the selection of reactants... 

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