Multiple Atropo Selectivity by κ2-N,O-Oxazoline Urea Ligands in Cobaltaelectro-Catalyzed C–H Activations: Decoding Selectivity with Data Science Integration

Enantioselective catalysis is one of the most prominent strategies in organic synthesis to access chiral bioactive compounds and advanced organic materials. Particularly the development of chiral ligands has significantly advanced the efficiency and selectivity of transition metal-catalyzed enantioselective transformations. Over recent decades, numerous chiral ligand classes with distinct geometrical and electronic properties were established. Despite these advances, the demand for novel, tunable, and highly effective chiral ligands persist, driven by the need for structurally diverse chiral molecules and the pursuit of greener, more sustainable catalytic processes. Herein, we introduce a novel class of chiral oxazoline ureas and demonstrate their potential as k2-N,O-preligands in enantioselective transition metal catalysis. The chiral oxazoline urea ligands were featurized and compared with amide and enol derivatives using the physical organic descriptors. A multivariate linear regression model was constructed to quantitatively describe the effect of the quinoline fragment from the substrate and the ligand on enantioselectivity. Moreover, the model was effectively applied to atropo-enantioselective cobaltaelectro-catalyzed C–H annulations of 1-alkynyl indoles.