The Discovery of Multifunctional Chiral P Ligands for the Catalytic Construction of Quaternary Carbon/Silicon and Multiple Stereogenic Centers

• Published in: Accounts of chemical research Vol. 54; no. 2; pp. 452 - 470
• Main Authors: Ye, Fei, Xu, Zheng, Xu, Li-Wen
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 19.01.2021
• ISSN: 0001-4842; 1520-4898; 1520-4898
• DOI: 10.1021/acs.accounts.0c00740

Conspectus The development of highly effective chiral ligands is a key topic in enhancing the catalytic activity and selectivity in metal-catalyzed asymmetric synthesis. Traditionally, the difficulty of ligand synthesis, insufficient accuracy in controlling the stereoselectivity, and poor universality of the systems often become obstacles in this field. Using the concept of nonequivalent coordination to the metal, our group has designed and synthesized a series of new chiral catalysts to access various carbon/silicon and/or multiple stereogenic centers containing products with excellent chemo-, diastereo-, and enantioselectivity. In this Account, we summarize a series of new phosphine ligands with multiple stereogenic centers that have been developed in our laboratory. These ligands exhibited good to excellent performance in the transition-metal-catalyzed enantioselective construction of quaternary carbon/silicon and multiple stereogenic centers. In the first section, notable examples of the design and synthesis of new chiral ligands by non-covalent interaction-based multisite activation are described. The integrations of axial chirality, atom-centered chirality, and chiral anions and multifunctional groups into a single scaffold are individually highlighted, as represented by Ar-BINMOLs and their derivative ligands, HZNU-Phos, Fei-Phos, and Xing-Phos. In the second, third, and fourth sections, the enantioselective construction of quaternary carbon stereocenters, multiple stereogenic centers, and silicon stereogenic centers using our newly developed chiral ligands is summarized. These sections refer to detailed reaction information in the chiral-ligand-controlled asymmetric catalysis based on the concept of nonequivalent coordination with multisite activation. Accordingly, a wide array of transition metal and main-group metal catalysts has been applied to the enantioselective synthesis of chiral heterocycles, amino acid derivatives, cyclic ketones, alkenes, and organosilicon compounds bearing one to five stereocenters. This Account shows that this new model of multifunctional ligand-controlled catalysts exhibits excellent stereocontrol and catalytic efficiency, especially in a stereodivergent and atom-economical fashion. Furthermore, a brief mechanistic understanding of the origin of enantioselectivity from our newly developed chiral catalyst systems could inspire further development of new ligands and enhancement of enantioselective synthesis by asymmetric metal catalysis.