Ligand Design For Iron And Cobalt-Catalyzed Asymmetric Hydrofunctionalization Of Alkenes

Asymmetric metal catalysis is one of the most efficient methods for the preparation of chiral compounds,with huge significance in both industry and academia.Over the past four decades,this area is dominated by platinum group metals such as ruthenium,rhodium,palladium,iridium and platinum etc.However,all the platinum group metals are rare elements in the earth's crust,high and volatile in price.Furthermore,the toxicity of platinum group metals poses serious problems,especially in the pharmaceutical industry where toxic metal residues in the final products are strictly controlled to meet quality standards.In regard to green and sustainable chemistry,earth-abundant transition metals such as iron and cobalt can be excellent alternatives to the rare precious ones.In contrast to the two-electron redox chemistry of platinum group metal catalysts,iron and 'cobalt are known to undergo facile one electron oxidation redox pathway in the catalytic cycle.Thus,the highly efficient iron or cobalt catalysis is a challenge for asymmetric transformations,and also offers new catalytic reacticity for the existed problems.Catalytic alkene hydrofunctionalization with chiral metal catalysts is one of the most common and efficient methods to access enantiomerically enriched molecules.It is difficult for a chiral reagent or chiral metal complex to effectively distinguish the two enantiotopic faces of simple 1,1-disubstituted alkenes,which is a big challenge for asymmetric alkene hydrofunctionalization.This dissertation focuses on the ligand design for iron or cobalt-catalysed enantioselective hydrofunctionalization of 1,1-disubstituted alkenes.Part I:The design and preparation of Oxazoline-Imine-Pyridine(OIP)ligand.The OIP ligand was designed based on the one electron redox chemistry of iron and cobalt catalysts,bionics and 'hard and soft(Lewis)acids and bases'.Two synthetic routes were developed for the synthesis of OIP ligand from readily available starting materials.Part II:Asymmetric iron and cobalt-catalysed hydroboration of 1,1-disubstituted alkenes.With the OIP-iron catalyst,an efficient asymmetric alkene hydroboration was realized.The OIP ligand was found to be more efficient for cobalt-catalysed enantioselective anti-Markovnikov hydroboration of 1,1-disubstituted styrenes.Part III:Iron-catalysed enantioselective hydrosilylation of 1,1-disubstituted alkenes.Employing the OIP-iron complex,a highly enantioselective anti-Markovnikov hydrosilylation of 1,1-disubstituted styrenes was developed.A series of chiral organosilanes could be easily prepared from simple alkenes.Part IV:Mechanistic studies on iron-catalysed asymmetric hydroboration and hydrosilylation of alkenes.The enantioselectivity was found to be opposite between the alkene hydroboration and hydrosilylation reactions with the same OIP-iron catalyst.To explain this unique phenomenon,a detailed mechanistic investigation was conducted.By the means of EPR spectroscopy,the possible catalytic resting states were detected for both reactions,respectively.Based on the data of deuterium labeling experiments,catalytic cycles were proposed for the two reactions,respectively.Part V:Cobalt-catalysed asymmetric hydrogenation of 1,1-disubstituted alkenes.Employing the OIP-cobalt catalyst,a highly enantioselective hydrogenation of 1,1-diarylethenes was developed under one atmosphere of hydrogen at room temperature.The a-alkyl styrenes were also suitable without alkene isomerization.Moreover,a possible catalytic cycle was proposed on the basis of preliminary mechanistic studies.Part VI:Experimemtal section.The general procedures for the experiments and compounds characterization in this dissertation were described.In addition,the EPR reactions in Part IV were completed together with Renfeng Du and Yongtao Wang in Haoran Li group.