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.