Tunable Unsymmetrical Chiral N-Heterocyclic Carbene Ligands for Highly Diastereo- and Enantioselective Copper-Catalyzed Tandem Borylative Cyclization: Ligand Controlled Diastereoselectivity Reversal

A distinct class of C1-symmetric N-heterocyclic carbene (NHC) ligands possessing a chiral fused tetrahydroquinoline ring and a chiral N-arylmethyl group was designed and synthesized via an asymmetric catalytic synthesis strategy. Their copper(I) complexes were successfully applied to asymmetric borylation/cyclization tandem reactions, providing facile access to a broad range of chiral borylated 2,3-trans- 3,4-cis-trisubstituted tetrahydroquinolines, which are synthetically important and otherwise difficult to access, in high yields with excellent enantioselectivities and diastereoselectivities. The single-crystal X-ray diffraction analyses of the Cu(I) complexes of L3 and L6 indicate that a crowded chiral pocket around the Cu(I)metal center is created that is beneficial for the chiral induction in this asymmetric tandem reaction. In addition, chiral all -cis 2,3,4-trisubstituted tetrahydroquinolines were also prepared by using a less bulky C2-symmetric chiral NHC ligand. A plausible catalytic cycle and transition states were proposed to account for the observed diastereoselectivity reversal.