Ligand and solvent effects on the aromatic trifluoromethylation via reductive elimination from palladium

The incorporation of trifluoromethyl groups in aromatic compounds via nucleophilic substitution faces the problem of the high reactivity of this species as a base and its decomposition to form difluorocarbene. Although palladium-catalyzed trifluoromethylation was developed for aryl chloride substrates using biaryl monophosphines as ligands, the scope of reaction and the availability of effective ligands are yet limited. In this work, we have investigated the direct reductive elimination step of the catalytic cycle. The study involved 11 ligands, including several biaryl monophosphines and the most effective BrettPhos ligand. The solvent effect was also evaluated, including up to 20 solvents. We have found that several biaryl monophosphine ligands are as effective as BrettPhos in the reductive elimination step. The solvent effect evaluated with the openCOSMO-RS model indicates that there is a better correlation of the induced free energy barrier with the dipole moment of the solvent molecule than with the Onsager function. • Simple monophosphine ligands react via T-shaped complexes. • Several biaryl phosphine ligands are effective in the reductive elimination step. • Solvent dipole moment is a good predictor of solvent effect.