Theoretical investigation on Cu/Pd-catalyzed domino radical cyclization and C−H carbonylation of α-bromocarbonyl leading to carbonyl-containing quinolin-2(1H)‑one scaffold

Our DFT calculations provide the first theoretical investigation on Cu/Pd-catalyzed domino radical cyclization and C−H carbonylation of α-bromocarbonyl. The SET reduction was induced by CuI attacking C−Br of α-bromocarbonyl generating CuIIBr followed by intramolecular radical addition generating six-membered ring. The alkenyl bromide was formed assisted by CuIIBr together with CuI regeneration. Next, alkenyl PdII was giv-en via oxidative addition of Pd0 to C-Br. The five-membered cyclic PdII was obtained via intramolecular C−H activation. Finally, two paths are competitive to furnish six-membered acyl PdII via insertion of CO to C-Pd bond. The polycyclic carbonyl-containing quinolin-2(1H)-one was yielded via reductive elimination squeezing recovered Pd0 from six-membered ring. CO insertion is determined to be rate-limiting. The positive solvation effect is suggested by decreased absolute and activation energies in solution compared with in gas. These results are supported by Multiwfn analysis on FMO composition of specific TSs, and MBO value of vital bonding, breaking.