Air-Compatible Indole-Based NHC–Copper Catalysts for A3 Coupling Reaction
Cai-Wei Cheng, Chia-Chen Lin, Po-Yu Chen, Wei-Cen Chen, Bo-Heng Chen, Chu-Ting Huang, Dong-Sheng Lee, Ta-Jung LuAbstract
A series of indole-based N-heterocyclic carbene (NHC) copper complexes has been developed as air-compatible catalysts for A3 coupling reactions. The optimized catalytic system efficiently promotes the three-component coupling of aldehydes, amines, and alkynes under aerobic conditions with catalyst loadings as low as 0.1 mol %. Systematic evaluation of ligand structure reveals that both electronic and steric features of the indole-derived NHC framework play key roles in modulating catalytic activity and stability under air. Notably, differences in time-dependent catalytic behavior are correlated with the air stability of the Cu–NHC complexes, providing insight into catalyst deactivation pathways. These results demonstrate the potential of indole-based NHC–copper complexes as efficient catalysts for A3 coupling reactions under operationally simple conditions.