Deracemization chiral secondary alcohols

Kroutil et al. have recently reported [18] an elegant one-pot oxidation/reduction sequence for the deracemization of a chiral secondary alcohol using a single biocatalyst. LyophiUzed cells of a Rhodococcus sp. CBS IVJ.Ti converted racemic 2-decanol into the (S)-enantiomer in 82% yield and 92% enantiomeric excess (e.e.). via a non-specific oxidation followed sequentially by an (S)-selective reduction (Scheme 6.5). Acetone was used as the hydrogen acceptor in the first step and isopropanol as the hydrogen donor in the second step. 

Deracemization. In this type of process, one enantiomer is converted to the other, so that a racemic mixture is converted to a pure enantiomer, or to a mixture enriched in one enantiomer. This is not quite the same as the methods of resolution previously mentioned, although an outside optically active substance is required. To effect the deracemization two conditions are necessary (7) the enantiomers must complex differently with the optically active substance (2) they must interconvert under the conditions of the experiment. When racemic thioesters were placed in solution with a specific optically active amide for 28 days, the solution contained 89% of one enantiomer and 11 % of the other. In this case, the presence of a base (Et3N) was necessary for the interconversion to take place. Biocatalytic deracemization processes induce deracemization of chiral secondary alcohols. In a specific example, Sphingomonas paucimobilis NCIMB 8195 catalyzes the efficient deracemization of many secondary alcohols in up to 90% yield of the (R)-alcohol. ... 

The term deracemization covers reactions in which two enantiomers are inter-converted by a stereoinversion process such that a racemate can be transformed to a non-racemic mixture without any net change in the composition of the molecule. Deracemization reactions usually involve a redox process, for example, the interconversion of chiral secondary alcohols via the ketone or alternatively the interconversion of amino acids/amines via the corresponding imine (Scheme 4.37). 

Relatively little attention has been paid to the conversion of racemic compounds into their enantiomerically pure versions in a single process, in other words a deracemization. For certain classes of chiral compounds such as secondary alcohols, this approach should provide many benefits, particularly to the pharmaceutical industry. Existing routes to high value intermediates in their racemic form may be modified to provide the equivalent homochiral product, thus reducing the extent of development chemistry required. In addition, the... 

The chiral synthesis of allylic alcohols has been the focus of many research works due to the high versatility of these molecules in the preparation of many active com-poimds [58,82], Allen and Williams reported the first example of DKR of allylic alcohols via lipase-palladium catalyst coupling deracemization of cyclic allylic acetates [83]. However, the accumulation of secondary products, as well as the long reaction times required, limited the use of this strategy. 

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