Pd-catalyzed acylation and allylation of 2-alkynylanilines with 1,2-diphenylcyclopropenones and gem-difluorinated cyclopropanes: a DFT study†

We reported the mechanism of Pd-catalyzed 2-alkynylaniline synthesis into indoles by acylation and allylation using density functional theory. Firstly, we believed that the reaction process of 2-alkynylaniline and 1,2-diphenylcyclopropenone mainly includes N–H deprotonation, C–N cyclization, oxidative addition of Pd(ii) intermediate to cyclopropenone, cleavage of the four-membered palladacycle intermediate, protonation of ketonate palladium intermediate, and catalyst regeneration. Secondly, the reaction process of 2-alkynylaniline and naphthyl difluorinated cyclopropane mainly includes oxidative insertion of Pd(0) center to difluorinated cyclopropane then produces a cyclopallada(ii)-butane intermediate, β-F elimination, Pd(ii) catalyst-assisted N–H deprotonation, C–N cyclization, and reductive elimination, leading to catalyst regeneration. The redox reaction plays an important role in promoting the Pd-catalyzed activation of cyclopropenones and cyclopropanes. In the acylation reaction, we computationally compared the prioritization of the neutral Pd catalyst (path A), the cationic Pd catalyst (path C) on the oxidative addition step, and the neutral Pd catalyst (path B) on migratory insertion, and proved that the neutral Pd catalyst (path A) on oxidative addition was the most favorable path. We also demonstrated this conclusion through distortion–interaction, noncovalent interaction (NCI), reduced density gradient (RDG), and extended transition state-natural orbitals for chemical valence (ETS-NOCV) analyses using the Multiwfn program. The palladium(ii) catalyst underwent the catalytic cycle process of Pd(ii) → Pd(iv) → Pd(ii) in acylation. The allylation reaction was catalyzed by Pd(0) → Pd(ii) → Pd(0). We also studied the effects of four designed catalysts, such as Pd(0)-EtOAc, Pd(0)-^tBuPPh₂, [Pd(0)(^tBuPPh₂)Cl]⁻, and [Pd(ii)(allyl)Cl]₂, on the allylation reaction. Theoretical results show that the coordination of solvent EtOAc as a ligand with Pd(0) catalyst is most beneficial to stabilize some key structures.