Catalytic Enantioselective Synthesis of Monosubstituted [<i>n</i>]Paracyclophane using a Desymmetrization/Kinetic Resolution Sequence
Jia Li, Ziyang Dong, S. Liu, Xinyu Liu, Changgui Zhao
Abstract
Optically pure monosubstituted [n]paracyclophanes are promising candidates for material synthesis, asymmetric catalysis, and drug discovery. Thus far, only a few catalytic asymmetric synthesis processes have been reported for assessing these strained atropisomers. In this study, we describe a highly enantioselective synthesis of monosubstituted [n]paracyclophanes by combining desymmetrization and kinetic resolution. The proposed protocol involves Pd-catalyzed atroposelective C-H bond olefination enabled by a monoprotected amino acid ligand, which affords a variety of monosubstituted [n]paracyclophanes with excellent enantioselectivity (≥99 %ee). Thermodynamic experiments are conducted to investigate the racemization barrier. The synthesized monosubstituted [n]paracyclophanes exhibit vivid fluorescence and impressive circularly polarized luminescence. Further, the emission color and dissymmetry factor can be tuned and controlled by switching the substituent on the benzene ring of the cyclophanes.