Ligand-Controlled Oxidant-Free Gold(I)/(III)-Catalyzed Synthesis of Benzocyclobutenes via [2 + 2] Annulation

Abstract

Abstract Benzocyclobutenes (BCBs) represent a highly strained, privileged structural motif with significant applications in drug discovery, medicinal chemistry, organic synthesis, polymers and materials science, yet efficient synthetic methods remain limited. Here, we report an oxidant-free Au(I)/Au(III)-catalyzed [2 + 2] annulation strategy for the synthesis of BCBs leveraging a unique class of rationally designed hemilabile C,N-bidentate N-heterocyclic carbene ligand (NHC). This approach employs readily available aryl halides and olefins under mild conditions, demonstrating broad functional group compatibility and the applications in late-stage functionalization. The ligand tunes the electronic and steric environment of gold center to promote selective migratory insertion while suppressing undesired β-hydride elimination. Density functional theory (DFT) calculations elucidate the reaction pathway and underscore the critical role of electron-withdrawing substituents within the C,N-carbene framework. This work establishes an efficient strategy for BCBs synthesis and highlights the potential of NHC ligands in advancing oxidant-free gold catalysis.