Zirconium oxo clusters as discrete molecular catalysts for the direct amide bond formation

Abstract

Zirconium compounds are prime catalysts in organic synthesis; however, their utility is often diminished by their moisture sensitivity. Here, we investigate zirconium oxo cluster (ZrOC) [Zr₆(OH)₄O₄(OAcr)₁₂]₂ (OAcr = acrylate) (Zr₁₂), as an air and moisture stable molecular catalyst for the atom economic formation of amide bonds directly from non-activated carboxylic acids and amines. The Zr₁₂ is readily prepared in one step from commercially available zirconium salts and carboxylic acids, and unlike the majority of metal complexes developed so far, it catalyzes the intermolecular formation of various amides in high yields without requiring water scavenging, inert or anhydrous reactions conditions, or any additives. Detailed mechanistic evaluation through control and NMR experiments suggests that the Zr₁₂ cluster, rather than a lower nuclearity species, is the catalytic active species involved in the reaction. Further, a comparison of Zr₁₂ performance with previously reported ZrCl₄ under the same conditions showcases several advantages of Zr₁₂ over conventional catalysts, underlining the potential of ZrOC as a new class of practical, readily available, and stable catalysts.