Metal‐Free A ³ Coupling for the Synthesis of Propargylamines Under Mild Basic Conditions and Their Biological Evaluation

ABSTRACT Propargylamines are valuable nitrogen‐containing building blocks widely used in medicinal chemistry and heterocycle synthesis. Herein, we report a metal‐free aldehyde–alkyne–amine (A 3 ) coupling protocol for the synthesis of tertiary propargylamines using a cooperative K 2 CO 3 /Et 3 N base system. The reaction proceeds in acetonitrile at 60°C and enables the one‐pot coupling of terminal alkynes, secondary amines, and formaldehyde to afford tertiary propargylamines in moderate to good yields (42%–82%). The methodology accommodates a range of cyclic and acyclic secondary amines, as well as both aryl and aliphatic terminal alkynes, providing access to structurally diverse products through an operationally simple, metal‐free protocol that employs inexpensive, readily available bases under mild reaction conditions. The synthesized derivatives exhibited antimicrobial activity against representative bacterial and fungal strains (MIC = 20–80 µg/mL) and were further evaluated by molecular docking and in silico drug‐likeness analyses.