CuI/DMAP-Catalyzed Oxidative Alkynylation of 7-Azaindoles: Synthetic Scope and Mechanistic Studies

An efficient and practical method for the N-alkynylation of 7-azaindoles has been established by using CuI/DMAP catalytic system at room temperature and in open air. This simple protocol has been successfully employed in the synthesis of a wide range of N-alkynylated 7-azaindoles with good yields. Also, this approach is well-suited for large-scale N-alkynylation reactions. The designed N-alkynylated 7-azaindoles were further subjected to Cu-/Ir-catalyzed alkyne-azide cycloaddition (CuAAC/IrAAC) or "click" reaction for the rapid synthesis of 1,4-/1,5 disubstituted 1,2,3-triazole decorated 7-azaindoles. A mechanistic study based on density functional theory (DFT) calculations and ultraviolet-visible (UV) spectroscopic studies revealed that the CuI and DMAP combination formed a [CuII(DMAP)2I2] species, which acts as an active catalyst. The DFT method was used to assess the energetic viability of an organometallic in the C-N bond formation pathway originating from the [CuII(DMAP)2I2] complex. We expect that the newly designed Cu/DMAP/alkyne system will offer valuable insights into the field of Cu-catalyzed transformations. Using a new CuI/DMAP catalytic system, oxidative N-alkynylation of 7-azaindole has been discussed. A detailed mechanistic study has been performed based on the reactive intermediate [CuII(DMAP)2I2], supported by both DFT calculations and UV-visible spectroscopy. Further several 7-azaindole decorated 1,4 and 1,5 disubstituted 1,2,3-triazole derivatives has been synthesized via click chemistry. image