Studies Towards The Synthesis Of Multi-substituted Butyrolactonimidates And Synthesis Of The Corynanthe And Heteroyohimbine Family Alkaloids By Photocatalytic Radical Cascade Reaction

Heterocyclic structures are widely found in the core of natural products.Preparations of heterocyclic compounds through cascade reactions are of great significance to the syntheses of natural products and their derivatives.This thesis focuses on the development of novel and efficient cascade reactions,which can be employed to construct the core skeletons of natural products.Taking the asymmetric Michael addition reaction of(R)-N-tert-butanesulfinyl imidates and the photocatalytic nitrogen radical reaction as the key points,this work consists of two parts:(1)Studies towards the synthesis of multi-substituted butyrolactonimidates via a highly efficient cascade reaction;(2)Syntheses of the corynanthe and heteroyohimbine family alkaloids through photocatalytic radical cascade reaction.(1)Chiral multi-substituted butyrolactones,as important intermediates in natural product synthesis,food chemistry and medicinal chemistry,have attracted considerable synthetic interest.We have developed a new method for synthesis of multi-substituted chiral butyrolactonimidates via a one-pot,three-step cascade reation,in which(R)-N-tert-butanesulfinyl imidates 166 and ?,?-unsaturated diesters 167 underwent highly stereoselective Michael addition,anion oxidative hydroxylation and cyclization.The butyrolactonimidate products are versatile intermediates for preparation of substituted butyrolactones and furans.The usefulness of this cascade reaction is demonstrated by the concise total synthesis of natural product(?)-nephrosteranic acid.(2)Monoterpenoid indole alkaloids have attracted widespread attention from the synthetic community,for their diverse skeletons and potent biological activities.It is important to develop a highly efficient method to construct corynanthe-type and heteroyohimbin-type skeleton,which enrichs the species of monoterpene indole alkaloids analogues,and has significance for drug development and organic synthesis as well.In this work,we have developed a photocatalytic radical cascade reaction by using Ir(dtbby)(ppy)2PF6/KHCO3 as a dual oxidant/base catalyst system for synthesis of corynanthe-type and heteroyohimbin-type skeleton,which underwent generating nitrogen-centered radicals under photocatalysis,intermolecular Michael addition reaction and intramolecular addition.Subsequently,we have applied this reaction as a key step to accomplish the syntheses of corynanthe-type monoterpenoid indole alkaloids in 9-10 steps,such as(+)-corynantheidol,(+)-hirsutinol,(+)-isocorynantheol,and syntheses of heteroyohimbin-type monoterpenoid indole alkaloids in 12 steps such as(+)-rauniticine,(+)-tetrahydroalstonine,(?)-3-isoajmalicine,(+)-19-epi-3-isoajmalicine.