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Catalytic atroposelective synthesis

Nature Catalysis (2024)Cite this article

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Abstract

Atropisomeric architectures are increasingly encountered in modern materials and medicinally important compounds. More importantly, they are now a characteristic of broadly useful chiral ligands and organocatalysts. Over the past decade, substantial advancements have been made in enhancing the accessibility of major classes of atropisomers through the refinement of existing strategies and the introduction of contemporary concepts for catalytic atroposelective synthesis. This synthetic capability enables the expansion of chemical space and facilitates the preparation of valuable atropisomeric scaffolds. Here we review the state of the art in the asymmetric synthesis of atropisomers with the help of selected examples. Focus will be placed on the strategies that have emerged rapidly in recent years, and that are characterized by high versatility and modularity. Additionally, the incorporation of emerging synthetic tools and representative scaffolds are discussed, alongside future directions in this research domain.

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Fig. 1: Discovery and importance of axial chirality.
Fig. 2: Catalytic asymmetric synthesis of atropisomers through C–H functionalization.
Fig. 3: Synthesis of atropisomeric biaryls through atroposelective ring-opening reactions.
Fig. 4: Atroposelective direct arylation enabled by organocatalytic arene umpolung.
Fig. 5: Catalytic asymmetric synthesis of atropisomers involving axially chiral VQM.
Fig. 6: Catalytic asymmetric synthesis of atropisomers involving emerging synthetic tools.
Fig. 7: Axially chiral alkenes and stereogenic axis involving heteroatom(s).
Fig. 8: Atropisomers with a stereogenic C(sp3)–X axis or multiple axes.

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Acknowledgements

We are grateful for financial support from the National Natural Science Foundation of China (21825105, 22231004, 22271135 and 22301125), the National Key R&D Program of China (2022YFA1503703 and 2021YFF0701604), Guangdong Innovative Program (2019BT02Y335) and Shenzhen Science and Technology Program (KQTD20210811090112004, JCYJ20210324120205016 and JCYJ20210324105005015). We appreciate assistance from SUSTech Core Research Facilities.

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  1. Shenzhen Grubbs Institute and Department of Chemistry, Southern University of Science and Technology, Shenzhen, China

    Shao-Hua Xiang, Wei-Yi Ding, Yong-Bin Wang & Bin Tan

  2. Academy for Advanced Interdisciplinary Studies, Southern University of Science and Technology, Shenzhen, China

    Shao-Hua Xiang

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B.T. and W.-Y.D. supervised the study. S.-H.X. and W.-Y.D. conducted the literature search. B.T., S.-H.X., W.-Y.D. and Y.-B.W. wrote the manuscript.

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Correspondence to Wei-Yi Ding or Bin Tan.

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Xiang, SH., Ding, WY., Wang, YB. et al. Catalytic atroposelective synthesis. Nat Catal (2024). https://doi.org/10.1038/s41929-024-01138-z

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