Theoretical Insights into Mechanisms for Copper(I)-Catalyzed C–P Coupling of Diarylphosphines with Aryl Halides: A Combined Solvent and Ancillary Ligand Effect on the Identity of Active Catalyst and Reaction Mechanism

A theoretical study on reaction mechanisms for copper-catalyzed Ullmann-type C–P coupling of diphenylphosphine with aryl halides is reported herein. The equilibria and consequent relative concentrations of possible copper species in the reaction solution were evaluated to determine probable active catalytic species in the presence of several typical ancillary ligands in toluene and DMSO solvents. Subsequently, reactivity of these key copper species with aryl halides were studied in the context of commonly proposed mechanisms for copper­(I)-catalyzed Ullmann reactions, including oxidative addition/reductive elimination, σ-bond metathesis, single electron transfer (SET), and halogen atom transfer (HAT) mechanisms. On the basis of these studies, we propose that for phenanthroline and 1,2-ethylenediamine types of bidentate ligands, the active catalyst should be the neutral form LCu­(I)-PPh2 in nonpolar toluene, while the Cu­(PPh2)2– anion should be significant in highly polar DMSO. In contrast, for phosphine type ligands, the active catalytic species should be the neutral LCu­(I)-PPh2 complexes in both toluene and DMSO. More interestingly, for both neutral LCu­(I)-PPh2 and anionic Cu­(PPh2)2– complexes, HAT mechanism is proposed to be kinetically the most favorable in toluene. However, in DMSO, the operative reaction mechanism should be influenced by the ancillary ligand used. For phosphine ligand, HAT mechanism is still the most favored with the LCu­(I)-PPh2 as the active catalyst. For phen and diamine ligands, SET mechanism has been shown to be the most favored for anionic Cu­(PPh2)2– complex, and HAT mechanism is proposed for neutral LCu­(I)-PPh2 complexes; both contribute to the activation of aryl halides in reaction solution. Therefore, a combined effect of solvent polarity and ancillary ligand has been recognized on determining the identity of the active catalytic species and the operative reaction mechanism for Ullmann-type P-arylation reactions. These results and findings distinguish the reaction mechanism for Ullmann P-arylation reactions from the other type of Ullmann reactions, such as N- and O-arylation reactions.