Synthesis of Bifunctional Organocatalysts and Application to Asymmetric Reaction

Author:Yuan Yong Hai

Supervisor:tu yong qiang


Degree Year:2019





The metal-free organocatalysis based on the dual activation of proline has been displaying versatile utilities in the asymmetric reactions and the synthesis of natural products and pharmaceuticals.In previous reports,the spirocyclic pyrrolidine(SPD)derived organocatalysts have proved to be well enantio-induceable toward several reactions.In this thesis,a novel kind of chiral bifunctional organocatalyst,the SPD backbone-derived fluoro-alkyl and-aryl sulphonamides are designed,prepared and examined toward the asymmetric Mannich/acylation/Wittig sequent reaction.As a practical application,the organo-catalyzed asymmetric formal synthesis of tetrahydroalstonine and the first asymmetric total synthesis of naucleofficine I and II,have been accomplished.This thesis might contain the following three aspects:1.We initially designed and synthesized a new type of chiral bifunctional organocatalysts by deriving SPD-backbone with various substituted sulfonamides.2.These catalysts were examined toward the cross dehydrogenative coupling (CDC)reaction and Mannich/acylation/Wittig sequent reaction.As a result,the SPD-TfNH(trifluoromethanesulfonamide)catalyst can facilitate Mannich sequence well in excellent enantioselectivity,as well as moderate to good yields.3.It’s one of the hot research areas for organic chemists to synthesize the monoterpenoid indole alkaloids with multi-substituents and stereocenters,and we focus on the synthesis of the alkaloids(+)-naucleofficine I and (-)-naucleofficine II,which are isolated from Nauclea genus.The synthetic utility of Mannich sequence and O-hetero-Diels-Alder cycloaddition have been exemplified through the formal synthesis of(+)-tetrahydroalstonine and the first asymmetric total synthesis of(+)-naucleofficine I and(-)-naucleofficine II in a concise way.