A C-H Arylation-Based Enantioselective Synthesis of Planar Chiral Cyclophanes

Abstract

Despite the growing importance of planar chiral macrocyclophanes owing to their unique properties in different areas of chemistry, methods that are effective in controlling their planar chirality are restricted to certain molecular scaffolds. Herein, we report the first Pd(0)-catalyzed enantioselective intermolecular C-H arylation that induces planar chirality by installing bulky aryl groups through dynamic kinetic resolution (DKR). A computer-assisted approach allowed a fine-tuning of the structure of the employed chiral bifunctional phosphine-carboxylate ligands to achieve high enantioselectivities. A range of planar chiral macrocyclophanes were successfully synthesized from configurationally labile macrocyclic precursors via C-H arylation with various perfluoroarenes. Mechanistic investigations indicated that the reaction proceeds via reversible oxidative addition and enantiodetermining C-H activation. Selected macrocyclophane products showed interesting photophysical and chiroptical properties, which depended on both the nature of the ansa chains and the aromatic moieties.

Keywords: C−H activation; asymmetric catalysis; cyclophanes; dynamic kinetic resolution; planar chirality.