Unlocking Diversity of Biologically Relevant Quinoline Scaffolds by Leveraging the Readily Available Feedstocks Under Cobalt‐NHC Catalysis
Year: 2025
Type: article
Abstract: Quinolines are privileged heterocycles with widespread applications in pharmaceuticals, agrochemicals, and materials science. However, sustainable and efficient one‐pot methods for synthesizing and functionalizing quinolines, e.g., 2‐methyl/aminoquinoline derivatives remained scarce. Herein, we report a unified, green, and operationally simple one‐pot strategy, which is enabled by a multitasking Co‐NHC catalyst ( Co3 ). Starting from 2‐aminobenzyl alcohol and acetone or benzyl nitrile as reactant, the present method achieves selective cyclization under open‐air conditions to afford 2‐methyl or 2‐aminoquinolines, respectively. Remarkably, the same catalytic system enables divergent C(sp 3 )‐H functionalization's, including alkenylation, alkylation, dimerization, and N ‐alkylation in a single pot, yielding six structurally distinct quinoline classes. The protocol features broad substrate scope, excellent chemoselectivity, and high step economy, generating water and/or H 2 as byproducts. Detailed mechanistic investigations, supported by control experiments, intermediate isolation, NMR/HRMS analysis, and DFT studies, reveal the dual catalytic role of the Co‐NHC complex in both cyclization and subsequent transformations. Overall, the current cobalt‐catalyzed platform paves the way for sustainable access to diverse quinoline architectures under mild and green conditions, relevant to drug discovery and advanced functional materials.
Source: Chemistry - A European Journal
Institution: Indian Institute of Technology Madras
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
Award: G5546836711
OpenAlex ID: W4415281810