Pd-Catalyzed Amidations of Aryl Chlorides Using Monodentate Biaryl Phosphine Ligands: A Kinetic, Computational, and Synthetic Investigation

We present results on the amidation of aryl halides and sulfonates utilizing a monodentate biaryl
phosphine-Pd catalyst. Our results are in accord with a previous report that suggests that the formation of
κ2-amidate complexes is deleterious to the effectiveness of a catalyst for this transformation and that their
formation can be prevented by the use of appropriate bidentate ligands. We now provide data that suggest
that the use of certain monodentate ligands can also prevent the formation of the κ2-amidate complexes
and thereby generate more stable catalysts for the amination of aryl chlorides. Furthermore, computational
studies shed light on the importance of the key feature(s) of the biaryl phosphines (a methyl group ortho
to the phosphorus center) that enable the coupling to occur. The use of ligands that possess a methyl
group ortho to the phosphorus center allows a variety of aryl and heteroaryl chlorides with various amides
to be coupled in high yield.