Theoretical study on Pd-catalyzed reaction of aryl iodide with unsymmetrical alkyne

•DFT calculations elucidate the mechanistic details of Pd(0)-catalyzed reaction of aryl iodide with unsymmetric alkyne.•The alkyne insertion is predicted to be rate-determinant.•The energetics for forming P3(47.2%), P4(9.8%) and P5(39.0%) is probed.•Influence of bulky vs unbulky phosphine ligand on the reaction feasibility is elucidated based on calculations.

With the aid of density functional theory (DFT) calculations, the Pd-catalyzed reactions of aryl iodide with unsymmetrical alkyne leading to two products containing C(sp3)−I bond (P3 and P4) and one product containing a three-membered carbocyclic unit (P5), have been studied theoretically. It is found that both the alkyne insertion and the subsequent CC bond insertion involved in the reaction are the major thermodynamic driving forces. The alkyne insertion instead of the C(sp3)−I reductive elimination is predicted to be rate-determinant. Similar barrier heights calculated for the two insertion modes of unsymmetrical internal alkyne (TS3-4 and TS3′-4′) lead to the products P3 (47.2%) and P4 + P5 (48.8%) having similar product yields. The intriguing formation of the product containing a three-membered carbocyclic unit (P5) was investigated in details. The second alkene insertion is found to be kinetically more favored than the C(sp3)−I reductive elimination, leading to product P5 (39.0%) more productive than P4 (9.8%). The remarkably thermodynamically favored β−H elimination is the key factor enabling formation of P5. Why significant bulky phosphine ligand such as P(t-Bu)3 instead of small one such as P(Me)3 was employed experimentally have also been rationalized based on our calculation results.

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