Chiral 1,2-Cyclohexane-Bridged Bis-NHC Palladium Catalysts for Asymmetric Suzuki–Miyaura Coupling: Synthesis, Characterization, and Steric Effects on Enantiocontrol

Abstract

The series of chiral 1,2-cyclohexane-bridged bis-N-heterocyclic carbene ligand precursors H 2 [(1 R,2 R )-( 1a – i )]Br with different substituent groups and their neutral and cationic diaqua palladium complexes, namely {Pd[(1 R,2 R )-( 1a – i )]Br 2 } ( 2a – i ), {Pd[(1 R,2 R )-( 1a )]X 2 } (X = Cl ( 3 ), OAc ( 4-OAc ), OC(O)CF 3 ( 4-OCH(O)CF 3 )), and {Pd[(1 R,2 R )-( L OMe )](OH 2 ) 2 }X 2 (X = OTf ( 5-OTf ), SbF 6 ( 5-SbF 6 )) have been prepared in moderate to good yields. These chiral palladium complexes were fully characterized by elemental analysis, high-resolution mass spectra, 1 H and 13 C NMR, and optical rotation determinations. The crystal structures of the chiral complexes 2a and 5-OTf were further confirmed to adopt a distorted-square-planar coordination geometry around the palladium center. The obtained chiral NHC-Pd compounds were able to catalyze the asymmetric Suzuki–Miyaura couplings of aryl halides with arylboronic acids in good yields (up to 96%) and moderate enantioselectivities (up to 64% ee). The coligand and steric effects were studied carefully. The coligands, including Br –, Cl –, AcO –, CF 3 COO –, and water molecules, have little influence on the catalytic results. However, a strong steric effect of the two aromatic substituents R on the enantiocontrol has been proved in the catalytic asymmetric Suzuki–Miyaura coupling reaction. The highest enantioselectivity of 64% ee could be achieved under the standard reaction conditions.