Sulfonyl‐PYBOX Ligands Enable Kinetic Resolution of α‐Tertiary Azides by CuAAC

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. We report the first highly selective kinetic resolution of racemic α‐chiral azides by Cu‐catalyzed azide‐alkyne cycloadditions (CuAAC), providing facile access to chiral α‐tertiary azides and 1,2,3‐triazoles with newly developed PYBOX ligands with a C4 sulfonyl group. The key role of the C4 sulfonyl in tuning the electronic and steric properties of the chiral catalysts to enhance enantiomer discrimination is rationalized by DFT calculations.