Semi-Synthesis Of The NH-Diamine,a(+)-Sparteine Mimic And Applications In Asymmetric Reactions In Aqueous Media

As the quinolizidine alkaloids,chiral bispidines including(–)-cytisine,(+)-sparteine and(–)-sparteine characterized by a bispidine core have important applications in the area of chemistry,pharmacy and biology.Thus,molecule design based on the bispidine core has always been the crucial point in discussion for many years.With our interest in transition-metal catalysis,we designed and synthesized a series of chiral diamines containing a skeleton of bispidine by analyzing the structure of natural product(–)-cytisine.Herein,we reported a highly efficient and economic semisynthetic pathway to a(+)-sparteine surrogate,NH-diamine,from(–)-cytisine in 4 steps with the overall yield of 94%.Besides,we also obtained methylated and arylated product derived from NH-diamine respectively by modifying the NH group.Modifications on(–)-cytisine for the purpose of preparing various types of chiral diamines with the NH group.With these chiral bispidines in hand,we explored their applications in the Pdcatalyzed kinetic oxidative resolution of secondary alcohols.When using water as the reaction solvent,NH-diamine delivered better enantioselectivity than(+)-sparteine and NMe-diamine.For a better understanding,a preliminary study on the reaction mechanism was made.The results indicated that a more stable complex resulted from the NH-diamine and Pd catalyst could be formed during the reaction,which could survive from water so that it was able to function as a chiral catalyst.In the presence of chiral diamines,Pd-catalyzed asymmetric addition reactions of arylboronic acids to cyclic N-sulfonyl imines in aqueous media were also investigated in the thesis.As a result,for the six-membered ring imines bearing various substituents,the NH-diamine afforded high yields and excellent enantioselectivities,while for the five-membered ring imines,the reactivity was very low possibly due to the poor watersolubility of the substrates.Phase transfer catalyst was under consideration to optimize the reaction conditions.From these preliminary discoveries,it could be assumed that the NH-diamine possessed great potential in promoting asymmetric reactions in aqueous media,and it was promising in the area of green asymmetric chemistry,encouraging more explorations on chiral bispidines in the aspect of new reactions and new bioactivities.