Metal mediated transesterification

Liquid-liquid phase segregation has been accomplished using two immiscible solvents (i.e., phase transfer DCC) by several laboratories. For example, the Morrow group has reported on imine [73] and acylhydrazone [74] DCLs targeting extraction of metal ions from aqueous to halogenated solutions. As discussed above in the context of Pd-mediated transesterification, the Miller group has also contributed to this area. 

In 2002, the asymmetric synthesis of 3-substituted 3-hydroxy-p-lactams has been reported to be realized by metal-mediated l,3-butadien-2-ylation reactions between 1,4-dibromo-2-butyne and optically pure azetidine-2,3-diones [64]. This latter starting material was prepared via Staudinger reaction followed by sequential transesterification and Swem oxidation (Scheme 15), [65]. 

There are basically two approaches to the synthesis of enantiomerically pure alcohols (i) kinetic resolution of the racemic alcohol using a hydrolase (lipase, esterase or protease) or (ii) reduction mediated by a ketoreductase (KRED). Both of these processes can be performed as a cascade process. The first approach can be performed as a dynamic kinetic resolution (DKR) by conducting an enzymatic transesterification in the presence of a redox metal [e.g. a Ru(ll) complex] to catalyze in situ racemization of the unreacted alcohol isomer [11] (Scheme 6.1). We shall not discuss this type of process in any detail here since it forms the subject of Chapter 1. 

DYKAT is a dynamic system closely related to DKR. Although four types of DYKAT have been reported in the literature, all the examples reviewed here are included in DYKAT type 111. They focus on the asymmetric transformation of a diastereomeric mixture of enantiomeric pairs of acyclic and cyclic diols by means of lipase-catalyzed transesterification and epimerization of the chiral centers mediated by the Ru catalyst 3a. The major differences with respect to DKR reside in the formation of chiral intermediates (hydroxyketones) during the metal-catalyzed epimerization as well as the involvement of two successive enzymatic transformations with different selectivities. An additional complexity originates from possible intramolecular acyl-migrations. Nevertheless, if similar requirements to those described for an efficient DKR are fulfilled, the result of these DYKATs could be the formation of only one stereoisomer of the diacylated product. 

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