Metal-catalyzed Asymmetric Synthesis Of Axially Chiral Biaryls&Study On Bromination Mechanism Of Aryl-olefins

Atropisomeric biaryls are the core scaffolds of many dominant ligands.They also widely exist in natural products and pharmaceutically active molecules.Although transition-metal catalyzed synthesis of axially chiral biaryls has been developed rapidly in recent years,it is highly desirable,yet still challenging to explore new catalytic systems to adapt to the diversity of molecular structures and functional group compatibility.This thesis mostly focuses on transition-metal catalyzed asymmetric synthesis of axially chiral biaryls and study on bromination mechanism of axially chiral aryl-olefins.The research work of thesis focus on three parts:In the first part,we developed a Cu/bisoxazoline-catalyzed N-arylation reaction of cyclic diaryliodoniums and oximes.Nucleophilic reagent oxime has the potential to react with cyclic diaryliodonium salts to form N-attack or O-attack products.After extensive investigations,the asymmetric ring-opening reaction with selective Narylation was realized and provides an effective protocol for synthesis of nitrones bearing atropisomeric biaryl skeletons.The optically active N-arylnitrones are versatile synthetic precursors.Further studies on synthetic applications transformed them into a variety of functional chiral scaffolds,i.e.:N-arylhydroxylamine,heterocyclic compounds,indoles,chiral anilines derivatives.The enantiopurity can be well maintained in the conversion process.In the second part,we developed a dirhodium(Ⅱ)/[(R)-BTFM-Garphos]catalyzed asymmetric arylation of isatin derivatives.Asymmetric carbonyl addition to prochiral C3 of isatin derivatives provided a series of axially chiral 3-hydroxy-3-aryl-oxindoles bearing both atropisomeric axis and tertiary chiral carbon center.We realized highly enantioselective carbonyl addition reaction of bulky isatins bearing 4-nonhydrogen substituent based on dirhodium(Ⅱ)catalysis.The reaction usually completed within a few minutes and excellent enantioselectivity was obtained.In addition,Rh2(O2CCF3)4/(R)-BTFM-Garphos complex was investigated by XRD,UV-Vis and NMR.On the basis of above results,a brief catalytic mechanism of dirhodium(Ⅱ)phosphine catalyzed 1,2-addition reaction was proposed.The last part focused on the study on the bromination mechanism of axially chiral 1,2-dihydronaphthenes.In our previous work,the synthesis of axially chiral aryl-olefins was achieved.Olefins can be conveniently functionalized to bromoalkenes.We observed phosphine oxide mediated alkene bromination along with the formation of unexpected intermediate which easily transformed to the final bromoalkene products.By changing the skeleton of starting material,the key intermediates were isolated,characterized by single crystal X-ray analysis,NMR tracking.The formation mechanism of intermediate is proposed,and the experimental conditions regarding intermediate transformation to bromoalkenes are also explored.