When Ligands Promote, Inhibit, or Disappear: Reaction-Dependent Roles in Au and Cu Catalysis

Abstract

Catalytic systems derived from Au(I) and Cu(I) precatalysts bearing phosphine and N-heterocyclic carbene (NHC) ligands are traditionally considered homogeneous. However, we demonstrate that under catalytically relevant conditions these systems undergo rapid and reversible metal–ligand bond cleavage, generating complex cocktails of molecular complexes, clusters, and nanoparticulate species. Using a combination of TEM analyses and poisoning experiments, we reveal that the identity of the dominant active species is not intrinsic to the metal/ligand pair but is critically reaction-dependent. For example, ligand-free nanoparticulate Cu species govern the Chan–Evans–Lam coupling, while molecular copper complexes dominate the Cu-AAC click reaction. In Au catalysis, ligandless nanoparticles are prevalent in A³-coupling and alkyne hydration, whereas in hydroamination the IMes ligand plays a striking promoting role within the cocktail, outperforming both phosphine-based and ligand-free systems. Inspired by this insight, we developed a simple, solvent- and silver-free Au/IMes protocol for alkyne hydroamination using bench-stable precursors. This study establishes the "cocktail of catalysts" paradigm as a fundamental concept in Au and Cu catalysis and highlights the need to reconsider traditional ligand design strategies when nanoparticulate species dynamically contribute to catalysis.