Construction Of Axial Chiral Biaryls Through Palladium Catalyzed Asymmetric C-H Transformation

Axial chiral biaryl backbone as one of the most important structural units is widely present in natural products and drugs,and is often found in chiral ligands.Therefore,great efforts have been paid for the efficient synthesis of these chiral frameworks.Recently,transition-metal catalyzed enantioselective C-H functionalization has emerged as a novel and powerful manner for the asymmetric catalysis&synthesis with its nature of atom and step economy.With a careful review of the documented strategies,this thesis has developed the diversity-oriented synthesis of functional axial chiral biaryl compounds via palladium-catalyzed asymmetric C-H transformation.The main research contents include the following two aspects:First,palladium/amino acid-catalyzed the construction of N-C axial chirality through atroposelective C-H olefination of N-arylindoles.Initially,we chose the asymmetric C-H bond alkenylation of N-phenylindole-2-carboxaldehyde with n-butyl acrylate in the presence of catalytic chiral amino acids as the model reaction to investigaing the reaction conditions.Under the optimal conditions,various indole derivatives and functional olefins,even bulky internal and tri-substituted olefins,can be tolerated.This reaction features mild reaction conditions,excellent regio-and enantioselectivity,broad substrate scope,and readily available chiral ligand.The product can be further transformed into kinds of valuable chiral functional molecules.All the products were characterized by ¹H NMR,¹³C NMR,HRMS,HPLC,etc.Second,diversity-oriented synthesis of functional axial chiral scaffolds enabled by palladium-catalyzed asymmetric C-H annulation of biaryl aldehydes with alkynes.A series of biaryl axial chiral compounds were synthesized with good to excellent yields and excellent enantioselectivity by the palladium-catalyzed asymmetric cyclization of biphenylaldehyde and diphenylacetylene via dual C-H activation.In this reaction,a wide range of functional groups are well tolerated.With the derivatization of products,the diversity-oriented synthesis of axial chiral aldehyde catalysis,carboxylic acid and phosphine ligands can be easily achieved and their application for asymmetric catalysis has been performed.All the products were characterized by ¹H NMR,¹³C NMR,HRMS,HPLC,etc.