Recent Progress on Transition-Metal-Catalyzed Asymmetric C-H Bond Functionalization for the Synthesis of Biaryl Atropisomers

Abstract

Axial chirality is of significant importance in chiral molecules. Axially chiral biaryls are existed in numerous natural products and biologically active molecules. Moreover, they have been extensively used as chiral catalysts and chiral ligands in asymmetric catalysis. Due to the importance of these privileged scaffolds, considerable attention has been attracted to develop novel, efficient and practical methods for their asymmetric synthesis by utilizing chiral transition-metal catalysis or chiral organocatalysis. Among those reported elegant achievements, asymmetric C-H bond functionalization reactions are the most concise and efficient methods for the synthesis of axial chiral biaryls in terms of atom and step economies. With the advancement of transition-metal-catalyzed asymmetric C-H bond functionalization reactions, they largely promote the field of asymmetric synthesis of axially chiral biaryls. Recent progress on the development of synthesis of axially chiral biaryls via transition metal (Pd-, Rh-, and Ir-) catalyzed asymmetric C-H bond functionalization reactions are summarized in this review. Those mainly include:Rh-catalyzed enantioselective C(sp2)-H bond alkylation and arylation reactions with the combination of rhodium (I) catalyst precursors and chiral phosphine ligands; Rh-catalyzed enantioselective C(sp2)-H bond alkenylation, arylation and annulation reactions with well-defined chiral rhodium (Ⅲ)-Cp(SCp) complexes; Ir-catalyzed enantioselective C(sp2)-H bond arylation reactions with chiral iridium (Ⅲ)-Cp complex and chiral amino acid as co-catalyst; Pd-catalyzed diastereoselective C(sp2)-H bond alkenylation, iodination, and arylation reactions using chiral p-tolyl sulfoxide auxiliary or menthyl phenylphosphate group as a directing group; Pd-catalyzed intramolecular enantioselective C(sp2)-H bond arylation reaction with Pd(0) catalyst precursors and chiral TADDOL-phosphoramidites; Pd-catalyzed intermolecular enantioselective C(sp2)-H bond iodination, alkenylation, alkynylation, allylation and arylation reactions with Pd(Ⅱ) catalyst precursors and mono-N-protected amino acids (MPAAs). In addition, preparation of varieties of novel axially chiral ligands by utilizing these methods and their applications in catalytic asymmetric reactions are also covered. Meanwhile, applications of these methods as key steps in the synthesis of natural products are also discussed.