Studies On Selective Metal-catalvzed Carbenoid Tandem Reactions Of C-C/C-X Formation

Accessing high and precise selectivity of targeting products（stereo-selectivity,chemo-selectivity and regio-selectivity）is a powerful tool to build complicated and diversified backbones of organic molecules in organic synthetic chemistry.Currently,scientists have developed a series of synthetic methodologies to achieve regio-selectivity,chemo-selectivity,enantio-selectivity and diastereoselectivity in chemical reactions via selecting different transition-metal catalysts.However,transition metal catalysts controlled high selectivity of tandem reaction is rarely reported due to the number and order of multi-step bond forming and bond breaking.It is challenging to control pathway selectivity of multi-steps tandem reactions under the same reaction substrates and condition.To achieve this,it is essential to choose suitable starting substrates and catalytic system.Metal carbenoid,an active chemical species,can effectively construct C-C/C-X bond.Due to flexible reactivity of metal carbenoid,it is possible to achieve the high pathway selectivity of multi-steps tandem reactions which can be used to efficiently synthesize diversified chemical bonds,complicated natural products,drug molecules by using different transition metal catalysts.In this dissertation,we will comprehensively introduce the development of high selectivity pathway of tandem reactions by choosing different transition metal catalysts and utilizing the flexible reactivity of metal carbenoid and its application in organic synthetic methodology and synthesis of complicated molecules.This dissertation including 4 chapters.The first chapter introduced the recent progress of transition metal controlled divergent pathway selectivity（regio-selectivity,chemo-selectivity,enantioselectivity and diastereoselectivity）in organic reactions and metal carbenoid involved C-C/C-X bond formation.In the second chapter,epoxypyrrolidines were proved to be efficiently and stereo-selectively synthesized from diazoesters and heterocyclic ketene aminals（HKAs）under combination of rhodium acetate and chiral ligand catalytic system.By conducting mechanism experiments,it was demonstrated that the tandem reaction including C-H insertion/cyclization addition/auto oxidation steps.This tandem reaction featured high atom-economic,high chemo-selectivity and high efficiency which can construct C-C/C-N/C-O bonds in one step.It is worthy to mention this substrate-controlled C（sp³）-C（sp³）epoxidation reaction can be achieved by using air as external oxidant.In the third chapter,we efficiently prepared multisubstituted pyrroles in Ag OTf catalyzed[4+1C]insertion reaction by using diazoesters or N-tosylhydrazones and enaminones.By mechanistic study,this tandem reaction included C-C insertion/cyclization condensation/[1,5]selective migration.The reaction featured that the bond formation and chemo-,region-selectivity were controlled by silver catalyst.Except that,the substrate scope was proved to be broad including donor–acceptor diazoesters and donor–donor N-tosylhydrazones.Most importantly,this tandem reaction can be applied to high efficiently synthesis of the precursor of Lamellarin L which displayed promising application in natural products total synthesis.Based on the conclusion of previous work,in the fourth chapter,we proposed to synthesize multiple backbones of products by only changing transition metal catalysts starting from same substrates（diazoesters and enaminones）and conditions in these tandem reactions.By screen a series of catalysts,we finally discovered two new tandem reaction pathways of diazoesters and enaminones which catalyzed by Pd（cod）Cl₂or Rh₂（oct）₄,and the furopyrrole derivatives or 1,4-iminones can be divergently and concisely synthesized in a highly efficient way.For these new tandem reactions,the metal catalysts showed different selectivity in C-C/C-O/C-N bonding formation and different numbers of new bonds.We proposed the possible mechanism pathway and the related theory to explain the highly tandem pathway selectivity was under investigation by using DFT computations.