Bifunctional Catalyst For The Asymmetric Construction Of Quaternary Carbon Centers Synthesis Of Indole Derivative

Indole alkaloids containing quaternary stereogenic centers present unique biological activity and special spatial structure, so that they were recognized as potential drug molecules and had attracted much attention. So research on simple and effective methods of synthesis of this class of molecules has a very important significance.The emergence of bifunctional organocatalysts has made great progress in organic synthetic chemistry, which has greatly enriched the methodology of organic synthesis, promoted the discovery of many new reactions, and simplified steps to promote the development of the domino reactions.In this dissertation, we established two kinds of bifunctional chiral catalysts catalyzed reactions to construct indole alkaloids with quaternary stereogenic centers. First, we disclosed a highly enantioselective formal [4+2] cycloaddition reaction between methylenein-dolinones and Nazarov Reagents catalyzed by Bransted acid-Lewis base binfunctional organocatalysts.This reaction is accomplished via sequential double Michael addition reactions in which the bifunctional chiral catalyst activates each reaction component by hydrogen bonding interactions. This protocol holds great potential in the synthesis of biologically active spiro[cyclohexane-1,3’-indoline]-2’,4-dionederivativest in high enantiomeric purity. Second, We have developed an enantioselective selenofunctionalization of tryptamine derivatives reaction with N-phenylselenophthalimide (N-PSP) catalyzed by chiral phosphoric acids as bifunctional catalyst(up to89%ee), and we used this protocol to prepare the key chiral precursor of the (+)-alline.