DKR of Acyloins

Figure4.18 DKR of acyloins through meso-enediol intermediates.

In 2005, Bornscheuer s group studied the DKR of acyloins, which constitute important building blocks in organic synthesis e.g. for the total synthesis of epothilones). " No combination of base and solvent was found that could selectively racemise the acyloins or the corresponding esters under the conditions needed for a DKR. In contrast to bases, an acidic resin such as Amberlyst 15 was found to racemise the acyloins selectively in n-hexane and in water. Unfortunately, the acidic resin deactivated the lipase Candida antarctica lipase... 

Ogasawara ef al. took advantage of the easy racemization of acyloins in the presence of a weak base for the DKR of ewdo-3-hydroxytricyco[4.2.1.0 ]non-7-en-4-one (Figure 4.18) [43]. Acylation of the hydroxyl group was catalyzed by a lipase, and racemization took place via a transient meso-enediol. 

Another example of enzyme- and acid-catalyzed DKR has been reported by Bornscheuer [45]. Acyloins were racemized by using an acidic resin through the formation of enol intermediates. The enzymatic resolution was catalyzed by CALB. Since deactivation of this enzyme occurred in the presence of the acidic resin, they designed a simple reactor setup with two glass vials cormected via a pump to achieve a spatial separation between the acidic resin and the enzyme (Figure 4.20). 

In this section, dynamic kinetic resolution of substrates having a proton with low pKa is discussed. Racemization occurs by performing the DKR in the presence of a weak base. Enzyme- and base-catalyzed DKRs are categorized, according to the nature of the substrates, as being thioesters, -activated esters, oxazolones, hydan-toins or acyloins. 

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