Sustainable protocol for Cu-catalysed A³-coupling under solvent-free conditions

Area of Science:

• Organic Chemistry
• Catalysis
• Green Chemistry

Background:

• Three-component reactions offer efficient pathways to complex molecules.
• Copper catalysis is a versatile tool in organic synthesis.

Purpose of the Study:

• To develop a novel copper-catalyzed cascade reaction for synthesizing diverse organic molecules.
• To explore a diversity-oriented methodology for library generation.

Main Methods:

• A copper(I) iodide (CuI)-catalyzed three-component cascade reaction.
• Utilizing ortho-alkynylaryl aldehydes, terminal alkynes, and amines/diamines.
• Employing an A3-coupling reaction strategy.

Main Results:

• Successfully synthesized a library of 72 diverse molecules with yields up to 99%.
• Demonstrated a green, solvent-free, open-air reaction with short reaction times (2 min-4 h).
• Produced biphenylacetylene tethered propargylamines, alkyne tethered dihydroisoquinolines, and N-fused benzimidazoles with excellent regioselectivity.

Conclusions:

• The developed methodology is efficient, versatile, and environmentally friendly.
• This approach provides a powerful tool for constructing complex heterocyclic scaffolds.
• The reaction's simplicity and mild conditions make it highly practical for organic synthesis.