RESUMO
Cu/ligand-mediated coupling reactions have been widely investigated in the recent past. However, activation of cheaper aryl chlorides is still a great limitation of these reactions. During the course of present investigations efforts have been made to develop a normal and facile CuI/ligand pair protocol for arylation of phthalimide using aryl chlorides. The protocol has also been extended for arylation of amines. On the basis of experimental and theoretical results, a catalytic cycle has also been proposed and it has been established that these reactions follow oxidative addition-reductive elimination (OA-RE) pathway. These studies have indicated that tetracoordinated [Cu(L1)(L2)]+ complex is active catalytic species in these reactions.
RESUMO
Decarboxylative A3-coupling of ortho-hydroxybenzaldehydes, secondary amines, and alkynoic acids is performed under catalyst and solvent-free conditions. The developed methodology provided a waste-free method for the synthesis of hydroxylated propargylamines which are versatile precursors for various bioactive heterocyclic scaffolds. The experimental and density functional theory studies revealed that the in situ-formed ortho-quinonoid intermediate (formed from ortho-hydroxybenzaldehyde and amine) undergoes a concerted Eschweiler-Clarke type decarboxylation with alkynoic acids. The synthesized compounds were evaluated for MAO-A, MAO-B, and AChE inhibitory activities as potential drug candidates for the treatment of various neurological disorders. Compound 4f was found to be the most potent and selective MAO-B (high selectivity over MAO-A) and AChE inhibitor in the series with IC50 values of 4.27 ± 0.07 and 0.79 ± 0.03 µM, respectively.