Synthesis of N-arylated 1,2-dihydroheteroaromatics through the three-component reaction of arynes with N-heteroaromatics and terminal alkynes or ketones

Article abstract of DOI:10.1002/asia.200900324

The reaction of benzynes with N-heteroaromatics including quinolines, isoquinolines, and pyridines and various terminal alkynes or ketones with an a-hydrogen in the presence of KF and 18-crown-6 in THF at room temperature for 8 h gave various N-arylated 1,2-dihydroheteroaromatics in good to moderate yields. Some of these product structures are found in various naturally occurring and biologically active heterocyclic compounds. The reaction involves an unusual multiple construction of new C - C, C - N, and C - H bonds and the cleavage of a C - H bond in one pot. It is likely that the three-component coupling proceeds through the nucleophilic addition of quinoline to benzyne, which generates a zwitterionic species. The latter then attracts a proton from terminal alkyne (or ketone) to generate an N-arylated quinolinium cation and an acetylide anion. Further reaction of these two ions provides the final substituted 1,2-dihydroquinolines. In the reaction, the terminal alkyne acts first as a proton donor and then as a nucleophile. The application of a three-component coupling reaction product, 1,2-dihydro-2-pyridinyl alkyne in a stereospecific [4+2] Diels-Alder cycloaddition reaction with N-phenyl maleimide to give an isoquinuclidine derivative, an important core present in various natural products, is demonstrated.