Opposite stereopreference

Deracemization by stereoinversion is a process in which one form (S of the racemic starting material (Rf -i- Sf) is enantioselectively transformed into an intermediate (Si) which can in turn react to give the form of opposite configuration (Rf). An example of this method could be the selective oxidation of one enantiomer of a racemic secondary alcohol and the subsequent reduction with a catalyst of opposite stereopreference [2]. 

A Subtilisin-catalyzed process was developed for the kilogram-scale continuous production of the drug intermediate (R)-l-aminoindan (R)-19e and of the chiral resolving agent (R)-l-(l-naphthyl)ethylamine (R)-19fin PBR [110]. Note the opposite stereopreference of the protease [110] and Upase-catalysis [111-113]. 

In this case, a reaction temperature of 50°C was needed to increase the racemization rate of the substrate and achieve an efficient DKR. Ru catalyst 3a in combination with CAL-B or subtilin Carlsberg has been used to carry out the DKR of the allylic alcohol rac-49, which is a precursor of the pharmacologically important 2-arylpropionic acids. Bearing in mind that these two enzymes display opposite stereopreference, both enantiomers could be prepared. Scheme 57.12 shows the reaction conditions. DKR with CAL-B was conducted at 80°C to obtain an acceptable rate of product formation, the corresponding acetate (R)-50... 

Unhke a kinetic resolution process, where in principle both enantiomers of the same compound can be obtained, a deracemization process gives access to one single enantiomer. The possibihty of securing the enantiomer of opposite configuration depends on the availability of the enzymes involved frequently enzymes with complementary stereopreferences are not available. 

The absolute stereopreference observed in the Diels-Alder reaction catalyzed by (/ )-8 is opposite to that found with catalysis by (/ )-19a. This implies that the presence of the 3,5-bis(trifluoromethyI)phenyl group greatly affects the asymmetric induction of BLAs. In fact, the use ofBLAs 19a and 9, prepared from the same chiral tetraol, in Diels-Alder reactions leads to the opposite enantiomers with high selectivity (eq 14) (21). 

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