Chromatographic Enantioseparation And Asymmetric Reaction Of Chiral Sulfinamides

Chromatographic enantioseparation of twelve kinds of structure closely related chiral sulfinamide derivatives were examined on three chiral columns OD-H,AD-H and AS-H.The effects of mobile phase composition and temperature on enantioselectivity have been investigated.It was shown that the resolution of the chiral recognition ability of OD-H and AD-H chiral stationary phases(CSPs)to sulfinamide derivatives is stronger than that of AS-H CSP under the same condition.The enantioseparations of the N-phenyl cyclic sulfinamide derivatives and the N-(benzylidene)-sulfinamide derivatives in the stationary phase reveals that the "space suitability" of the enantiomers is also an important factor in the identification of chiral stationary phases.According to the above results,we chose AD-H column as chiral stationary phase to investigate the effect of mobile phase polarity on the chiral separation.It is found that the selectivity factor increases with the increase of the polar fractions at the beginning.However,when the polar fractions reaches a certain value,selectivity factor decreases with the increase of the polar fractions.As suggests that the polar component in the mobile phase participates in chiral recognition of enantiomers in a specific way.The effects of temperature on enantioselectivity is also investigated.And the chiral recognition mechanisms is discussed based on the experimental data of the relative thermodynamic parameters.It is found that the enantioseparation of sulfinamide derivatives in OD-H chiral stationary phase is mainly controlled by enthalpy of intermolecular interactions.We synthesize a series of chiral sulfinamide-olefin ligands with a novel chiral cyclic sulfinamide as a chiral skeleton,and then investigated the catalytic activity and enantioselectivity of these ligands.Among these ligands,N-cinnamyl-2,3-dihydro-1,2-benzisothiazole-1-oxide is the best ligand for highly enantioselective rhodiumcatalyzed asymmetric 1,4-additions of ?,?-unsaturated cyclic carbonyl compounds and 1,2-addition of benzil.Chiral addition products are obtained in high yields(up to 98%).The enantiomeric excess values of all the products were determined by high performance liquid chromatography(HPLC).The OD-H,AD-H and AS-H chiral column were used.Chiral addition products are obtained excellent enantioselectivities(up to 98%ee),minimum is 86%.HPLC can well determine the enantioselectivity of asymmetric reactions.