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Construction of axial chirality via palladium/chiral norbornene cooperative catalysis

Nature Catalysis volume 3, pages 727–733 (2020)Cite this article

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Abstract

Axially chiral biaryls are common structural motifs in functional materials, bioactive natural products, pharmaceuticals and chiral catalysts/ligands. As such, efficient preparation of these privileged scaffolds is an important endeavour in organic chemistry. Herein we report a general and modular platform technology for the construction of axial chirality via palladium/chiral norbornene cooperative catalysis. It is a three-component cascade process that involves widely available aryl iodides, 2,6-substituted aryl bromides and olefins (or alkynes, boronic acids and so on) as the reactants. A wide variety of substrates bearing an assortment of functional groups (88 examples) are compatible with this method. Other features include a distinct stereoinduction model, excellent enantioselectivities, step economy and scalability. This method is also amenable for the synthesis of chiral fluorenols through axial-to-central chirality transfer in high stereochemical fidelity. We anticipate that this work will have broad synthetic utilities in chiral ligands and catalyst-design for asymmetric catalysis.

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Fig. 1: Axially chiral biaryl molecules and strategies for biaryl atropisomers synthesis.
Fig. 2: The proposed stereoinduction model and synthetic applications.

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Data availability

Data relating to the materials, optimization studies, experimental procedures and characterization of the new compounds are available in the Supplementary Information. Crystallographic data for 4g, 4da and 5j are available free of charge from the Cambridge Crystallographic Database Centre (CCDC) under reference numbers 1946138, 1946094 and 1946139, respectively. All other data are available from the authors on reasonable request.

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Acknowledgements

We are grateful to the National Natural Science Foundation of China (grant nos. 21871213 and 21801193), the China Postdoctoral Science Foundation (grant nos. 2016M602339 and 2018M642894) and the start-up funding from WHU for financial support. We thank H. Cong and W. Yan (Wuhan University) for X-ray crystallographic analysis assistance. We gratefully acknowledge P. Baran (TSRI), D. Ma and W. Tang (SIOC), H. Xu (Georgia State University), C. Wang and W.-B. Liu (Wuhan University), S. Yu (Nanjing University) and W. Xie (Northwest A&F University) for helpful discussions, H. Xu (Georgia State University) and M. Yan (Fish & Richardson) for help with preparation of the manuscript.

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Author notes

  1. These authors contributed equally: Yu Hua and Qianwen Gao.

Authors and Affiliations

  1. Sauvage Center for Molecular Sciences, Engineering Research Center of Organosilicon Compounds & Materials (Ministry of Education), College of Chemistry and Molecular Sciences and The Institute for Advanced Studies, Wuhan University, Wuhan, P. R. China

    Ze-Shui Liu, Yu Hua, Qianwen Gao, Yuanyuan Ma, Hua Tang, Yong Shang, Hong-Gang Cheng & Qianghui Zhou

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  1. Ze-Shui Liu
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Contributions

Q.Z. and Z.-S.L. conceived the idea. Q.Z. guided the project and wrote the manuscript. Z.-S.L., Y.H., Q.G., Y.M., H.T. and Y.S. performed the experiments and analysed the data. Z.-S.L. and H.-G.C. participated in the preparation of the manuscript.

Corresponding author

Correspondence to Qianghui Zhou.

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Supplementary information

Supplementary Information

Supplementary Methods, Figs. 1–11, Tables 1–17 and references.

Supplementary Data 1

Crystallographic Data of compound 4da.

Supplementary Data 2

Crystallographic Data of compound 4g.

Supplementary Data 3

Crystallographic Data of compound 5j.

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Liu, ZS., Hua, Y., Gao, Q. et al. Construction of axial chirality via palladium/chiral norbornene cooperative catalysis. Nat Catal 3, 727–733 (2020). https://doi.org/10.1038/s41929-020-0494-1

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