KINETIC RESOLUTION OF MESO DL STEREOISOMERIC MIXTURES - THEORY AND PRACTICE/

A mathematical model, based on reactions of independent functional gro ups, is derived to describe kinetic resolutions of bifunctional meso/d l stereoisomeric mixtures. The model indicates that only the slow reac ting enantiomer can be obtained (as recovered starting material) with high stereoisomeric purity in these processes; the products from the f ast reacting enantiomer and the meso diastereomer are predicted to hav e limited diastereoisomeric purity. Recycling strategies are presented that can serve to enhance the purity of the these products. In partic ular, if recycling can be performed using a reaction with selectivity opposite to that in the first cycle, it is predicted that all three co mponents of a meso/dl mixture (or their derived products) can be obtai ned with high stereoisomeric purity, even from a process with modest e nantiotopic group selectivity. These predictions were tested by Sharpl ess epoxidation. of a 1:1 mixture of meso and racemic stereoisomers of 6,6-ethylenedioxy-1,10-undecadiene-3,9-d (1) under conditions of high (40:1) and modest (9:1) selectivity. In both scenarios, the two C-2 e nantiomers and the monoepoxide derivative of the meso diastereomer of 1 were obtained with high stereoisomeric purity (greater than or equal to 97% dp, >99% ee) from an initial L-tartarate mediated epoxidation of the mixture followed by recycling of the mono- and diepoxide fracti ons by deoxygenation (KSeCN) and reepoxidation using a D-tartarate der ived catalyst. The results are in reasonable agreement with those calc ulated with the mathematical model.