Asymmetric Trinuclear Intermediates in Metal Oxo Cluster Formation: Kinetic Evidence for a Two-Step Esterification Mechanism

Metal oxo clusters are interesting catalysts and valuable building blocks for metal-organic frameworks (MOFs) and 3D-printing. Here, we study the nonaqueous formation mechanism of the prototypical M₆O₄(OH)₄(OOCR)₁₂ (M = Zr or Hf) clusters using a suite of <i>in situ</i> and <i>ex situ</i> characterization techniques. In the reaction of a metal alkoxide with excess carboxylic acid, an asymmetric trinuclear complex is transiently formed en route to the hexanuclear oxo cluster. The reaction produces ester as a byproduct, and we determine that precisely 4/3 equiv of ester is required for every Zr atom to reach full yield of the oxo cluster. The esterification can be divided into (i) a fast process, producing 1/3 equiv of ester and one μ₃-O linker, and (ii) a slow process, producing the remaining equivalent of ester to complete the condensation of the oxo cluster. The proposed mechanism is supported by kinetic modeling. These insights are crucial to retrosynthetically design routes to oxo clusters, including heterometallic oxo clusters with control over stoichiometry (see Parammal et al., <i>Angew. Chem., Int. Ed.</i> <b>2026</b>, accepted). Our results even provide insight into nanocrystal synthesis from an atomically precise perspective.