Recently, Professor Yan Hailong group at the School of Pharmaceutical Science of Chongqing University has published an article on Angewandte Chemie International Edition entitled "Atroposelective Construction of Nine-Membered Carbonate Bridged Biaryls".
Atropoisomeric biaryls are among the most common chiral skeletons and abundantly presented as key contributing blocks of diverse bioactive natural products or catalytic ligands in enantioselective synthesis. As an important subclass of this category, axially chiral bridged biaryls have attracted enormous attention due to their unique architectures and significant utility. Limited by existing knowledge on the axially chiral bridged biaryls, however, the stereochemically pure synthesis of configurationally stable biaryls with medium-sized (7-11) rings remains a great challenge in organocatalysis. The construction of these ring systems not only requires a highly stereoselective formation of the stereogenic axis during the reaction process, but also confronts unfavorable transannular interactions as well as entropy and enthalpy factors existing in the synthesis of medium-sized rings. We herein demonstrated an efficient method for the atroposelective construction of nine-membered carbonate bridged biaryls through vinylidene ortho-quinone methide (VQM) intermediates. Diverse products with desirable pharmacological features were synthesized in satisfying yields and good to excellent enantioselectivities. In subsequent bioassays, several agents showed considerable antiproliferative activity via the mitochondrial-related apoptosis mechanism. Further transformations produced more structural diversity and may inspire new ideas for developing functional molecules.
This study was supported by National Natural Science Foundation of China (Grant Nos.: 21922101, 21772018, and 22001025) and the Fundamental Research Funds for the Central Universities (Project No. 2020CDJQY-Z002). We thank Mr. Gong Xiangnan (Analytical and Testing Center of Chongqing University) for X-ray crystallographic analysis, and Wang Pengfei for pharmacological research.
