Copper‐Catalyzed Glaser‐Hey‐Type Cross Coupling of 9‐Ethynyl‐α‐Noscapine Leading to Unsymmetrical 1,3‐Diynyl Noscapinoids

Cu(I)‐catalyzed Glaser‐Hey‐type cross coupling of 9‐ethynylnoscapine with terminal alkynes has been described that enables synthesis of unsymmetrical noscapine 1,3‐diynes in very good yields in the presence of base and amines as ligands. The symmetrical dimer of 9‐ethynylnoscapine was also isolated as by‐product. Outcome of these couplings critically depends on the choice of ligands and base as well as employed reaction conditions. The synthesized 1,3‐diyne analogues were evaluated for their antiproliferative activity. Dumbbell‐like noscapinoids and noscapine dimers bearing 1,3‐diyne moiety at the C‐9 position were synthesized by employing Cu(I)‐catalyzed Glaser‐Hey‐type cross coupling of 9‐ethynylnoscapine with terminal alkynes.