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.
Similar content being viewed by others
Acknowledgements
We gratefully acknowledge Rutgers University (M.S.) and Shandong University (D.Z.) for their support. Additional support for this project was provided by the Rutgers University–Newark Chancellor’s Research Office. P.G. acknowledges the China Scholarship Council (No. 201606240022) for a fellowship. We thank Pavel Kucheryavy for helpful discussions and assistance with NMR data analysis.
Funding
This work was supported by the National Institutes of Health (R35GM133326 to M.S.) and the National Natural Science Foundation of China (22273051 to D.Z. and 22303045 to Y.L.).
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Competing interests
The authors declare the following competing interests: Rutgers University has filed patent applications on the ligands and precatalysts described in this manuscript. Inventors: Szostak, M.; Gao, P. Applicant: Rutgers University. Heterobidentate imidazo[1,5-a]pyridine and imidazo[1,5-a]quinoline N-heterocyclic carbene (NHC) ligands, catalyst complexes thereof, and methods using the same. US 63/292,235, Dec. 21, 2021, PCT Filing. The patent claims the structures of ligands and catalysts covered in the manuscript. The remaining authors declare no competing interests.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary information
Source data
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
About this article
Cite this article
Gao, P., Wang, J., Chu, W. et al. Ligand-Controlled Oxidant-Free Gold(I)/(III)-Catalyzed Synthesis of Benzocyclobutenes via [2 + 2] Annulation. Nat Commun (2026). https://doi.org/10.1038/s41467-026-74372-7
Received:
Accepted:
Published:
DOI: https://doi.org/10.1038/s41467-026-74372-7
