Sulfonyl‐PYBOX Ligands Enable Kinetic Resolution of α‐Tertiary Azides by CuAAC
Yi Gong, Cai Wang, Feng Zhou, Kui Liao, Xiyu Wang, Xi‐Yu Wang, Ying Sun, Yan‐Xue Zhang, Zhi Tu, Xin Wang, Xin Wang, Jian Zhou
Abstract
We report the first highly selective kinetic resolution of racemic α-chiral azides via Cu-catalyzed azide-alkyne cycloaddition (CuAAC). Newly developed pyridine-bisoxazoline (PYBOX) ligands, bearing a C4 sulfonyl group, enable effective kinetic resolution of racemic azides derived from privileged scaffolds such as indanone, cyclopentenone, and oxindole, and their asymmetric CuAAC to afford α-tertiary 1,2,3-triazoles with high to excellent ee values. DFT calculations and control experiments reveal that the C4 sulfonyl group decreases the Lewis basicity of the ligand and increases the electrophilicity of the copper center for better recognition of azides, and functions as a shielding group to make the chiral pocket of the catalyst more effective.