Density functional theory investigation on Pd-catalyzed cross-coupling of azoles with aryl thioethers

Abstract

In the present study, a density functional theory (DFT) study has been carried out on the Pd-catalyzed coupling of azoles with aryl thioethers. Our effort is mainly put into identifying the most feasible catalytic cycle, and especially the origin of chemoselectivity for the exclusive aromatic C_sp²–S bond activation (in the presence of an alkyl C_sp³–S bond). The coupling mainly consists of three steps: C–S activation, NaO^tBu mediated C–H palladation, and reductive elimination. The C_sp²–S activation is favored over C_sp³–S activation, and thus di(hetero)aryls are the predicted products. This conclusion well reproduces Wang's recent experimental observations. The rate- and chemoselectivity determining steps of the C–H/C_sp²–S activation mechanism are C–H palladation and C–S activation steps, respectively. Analyzing the origin of chemoselectivity, we found that the easiness of Pd catalyzed C–S activation is independent of the C–S bond strengths in thioether substrates. By contrast, d–π* backdonation in C_sp²–S–Pd intermediates is the main driving force for the favorable C_sp²–S activation (over the C_sp³–S activation).