Smart Palladium-Chiral Diamine Catalytic System with a Crown Ether Side Arm: Supramolecularly Controlled Asymmetric Suzuki-Miyaura Coupling Reactions

Herein, we disclose the rational design and synthesis of a new type of tunable C₁-symmetric diamine ligands bearing a crown ether side arm with a single chiral carbon center. Highly efficient and enantioselective palladium-catalyzed Suzuki-Miyaura coupling reactions were achieved with these chiral diamine ligands, which providing an efficient strategy for the synthesis of three series of axially chiral biaryl compounds bearing alkoxyl-, formyl- or triflate-groups (44 examples and up to 95% ee). Control experiments reveal that the assembled crown ether-K⁺ motif acts as the key factor for obtaining excellent enantiomeric excesses. Density functional theory calculations were further used to determine the origin of enantioselectivity during the reductive elimination step of the coupling of 1-naphthylboronic acid with 2-methoxyl-1-naphthyl iodide. A 1.6 kcal/mol difference in Gibbs free energy is calculated from the favorable transitions states TS1 (R) and TS16 (S), and a corresponding 87% ee by distribution analysis is in good agreement with the experimental result (84% ee). In addition, these studies indicate that an interesting pendulous swapping coordination of ligand with palladium might occur, which possibly facilitate multiple noncovalent secondary interactions with substrates from both side arms of the ligand.