Homogeneous Metal Catalysts with Inorganic Ligands: Probing Ligand Effects in Lewis Acid Catalyzed Direct Amide Bond Formation

Inorganic clusters have large potential in the development of effective and robust catalysts due to their tunable electronic and structural properties and the ability to bind and stabilize catalytic metals. However, they have been rarely used as ligands in homogeneous metal catalysis, and the effect of the ligand structure on the catalyst's reactivity has been scarcely investigated. By using well-defined and soluble inorganic clusters such as polyoxometalates (POMs) as representative inorganic ligands for a Hf(IV) Lewis acid metal, we illustrate how the interplay between the dielectric constant of the medium and the ligand structure can be used to convert a poorly active Hf-Keggin 2:2 complex ((Et2NH2)8[Hf(μ-O)(H2O)(PW11O39)]2) into an effective catalyst for a water-tolerant and atom-economic direct amide bond formation. By studying a model reaction between phenylacetic acid and benzylamine, direct catalytic amide formation was observed only in polar aprotic solvents, with yields inversely related to the dielectric constant of the solvents. More interestingly, while a clear improvement was observed for the Hf-Keggin catalyst upon changing the medium from dimethyl sulfoxide (ε = 46.7) to N-methyl-2-pyrrolidone (ε = 32.2), changing the dielectric constant had a minimal effect on the reactivity of the Hf-Wells–Dawson 2:2 complex ((Me2NH2)14[Hf(μ-O)(H2O)(α2-P2W17O61)]2), which gave quantitative yields in both solvents. Detailed mechanistic and spectroscopic analyses revealed that the dielectric constant of the medium plays a key role in providing the optimal balance between formation and stability of the monomeric catalytically active Hf-POM 1:1 species, thereby enabling efficient amide bond formation.