DERACEMIZATION OF COMPOUNDS POSSESSING A SEC-ALCOHOL OR SEC-AMINO GROUP THROUGH A CYCLIC OXIDATION-REDUCTION SEQUENCE - A KINETIC TREATMENT

Deracemization of compounds bearing a chiral sec-hydroxy or -amino gro up can be achieved in a one- pot reaction via a novel process consisti ng of a cyclic oxidation-reduction sequence. Thus, in the first step, one enantiomer from the racemic starting material (R+S) is enantiosele ctively oxidized forming an achiral intermediate product (P, a ketone or imine, respectively). In the second step, the latter is non-selecti vely reduced to give al:ain R+S in racemic form. Cyclic repetition of this oxidation-reduction sequence leads to an overall chiral inversion of the faster reacting enantiomer from the racemic starting material to yield the slower reacting enantiomer as the final product in a theo retical 100% chemical and enantiomeric yield. Mathematical treatment o f the kinetics of this 'cyclo-process' allowed the estimation of the p ractical feasibility at hand of two crucial parameters: (i) the maxima l obtainable enantiomeric excess and (ii) the number of cycles require d (expressed as theoretical turnover) to reach equilibrium. A computer program for analysis and optimization of such processes was developed , which is available via the Internet. (C) 1998 Elsevier Science Ltd. All rights reserved.