Chiral ligands for palladium-catalyzed asymmetric C–H activation

Chiral ligands enabled palladium-catalyzed regio- and enantioselective C–H activation represents one of the current frontiers in transition metal catalysis. It has been extensively developed over the past decade as an important method for the synthesis of chiral molecules. Functional molecules bearing central, axial or planar chirality can be efficiently generated in good to excellent optical purities through this method. It has also been used as one of the most efficient methods for the rapid construction of various C–C and C–X bonds. In this review, we highlight the development of some representative chiral ligands in Pd-catalyzed enantioselective C(sp2)–H and C(sp3)–H functionalization reactions. Specifically, critical features of these novel Pd-catalyzed transformations assisted by chiral ligands such as monodentate phosphoramidites, chiral phosphoric acids (CPAs) and bifunctional mono-N-protected amino acids (MPAAs) will be discussed. The recent advances and limitations in this rapidly growing research area and its application in the total synthesis of natural products and pharmaceutical molecules will also be presented and discussed.