Mechanistic insight into difunctionalization of aryl chlorides via palladium/phosphine ligand/norbornene cooperative catalysis

Abstract

Density functional theory (DFT) calculations were performed to elucidate the mechanism of the palladium/XPhos/norbornene (NBE)-catalyzed ortho/ipso difunctionalization of aryl chlorides with alkyl bromides and acrylates. The reaction proceeds through a sequential pathway comprising: oxidative addition of Ar–Cl to Pd⁰, NBE insertion, Cs₂CO₃-assisted C–H activation, oxidative addition of alkyl bromide to Pd^II, C(sp²)–C reductive elimination from Pd^IV, NBE extrusion, alkene insertion, and β-H elimination. Among these steps, the oxidative addition of alkyl bromine is identified as the rate-determining step. The observed chemoselectivity favoring aryl chloride over alkyl bromide is attributed to stronger d(Pd) → σ*(C(sp²)–Cl) orbital interactions and higher stabilization energy E⁽²⁾. The NBE insertion is governed by both the C–H⋯π interaction and steric hindrance between NBE and the XPhos ligand. Furthermore, the suppression of the ipso-Heck side reaction is primarily attributed to electronic effects, whereas the formation of the benzocyclobutene by-product is inhibited by a combination of steric hindrance and ring strain in the corresponding transition state. Additionally, the NBE insertion process and the conformational flexibility of the XPhos ligand were also systematically exported, highlighting their critical roles throughout the catalytic cycle.