Asymmetric Synthesis with Chiral Nucleophilc Catalysts

点击翻译按钮获取中文摘要

A chiral nucleophilic catalyst, 4-pyrrolidinopyridine (PPY) analogue, has been developed which could effectively catalyze the acylative kinetic resolution racemic amino alcohol derivatives with selectivity factors of 10 to 54. Kinetic studies of acylation indicated that the observed high enantioselectivity of the acylation promoted by the catalyst is due to the rate acceleration of acylation of one enantiomer rather than the rate deceleration of the other. The origin of the acceleration was revealed to be due to the transition state-hydrogen bonding between a substrate and the catalyst.Chiral PPY analogues were also readily prepared from L-proline. Although these catalysts do not possess chiral elements near the catalytically active pyridine-nitrogen, they promote kinetic resolution of racemic alcohols highly selectively. Contrary to the mechanism of enantioselective acylation by the previously PPY analogue, π-π interaction between an aromatic ring and pyridinium π-system is critical in the chiral nucleophilic catalysts derived from L-proline. A new generation of chiral nucleophilic catalysts with dual functional side chains was successfully prepared from 4-hydroxy-L-proline. These catalysts showed superior chemo- and enantioselectivity in asymmetric desymmetrization of meso-diols.