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Synthesis of axially chiral alkenylboronates through combined copper- and palladium-catalysed atroposelective arylboration of alkynes

Nature Synthesis volume 2, pages 140–151 (2023)Cite this article

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Abstract

The incorporation of alkenylboronates into axially chiral compounds increases their structural diversity and provides a synthetic handle for late-stage functionalizations. Despite advances made in the synthesis of axially chiral acyclic alkenes, catalytic enantioselective synthesis of tetrasubstituted axially chiral acyclic alkenylboronates still remains a challenge. Here, we report a combined copper- and palladium-catalysed atroposelective arylboration of alkynes, providing access to tetrasubstituted axially chiral alkenylboronates. The process can tolerate a broad range of functional groups and substrates, including unsymmetrical alkynes, providing products with excellent Z-/E-selectivity, regiocontrol and enantiocontrol. The synthetic use of the products has been demonstrated through onwards synthetic transformations to generate various new axially chiral olefins including axially chiral 1,3-enynes. Mechanistic experiments reveal a potential combined copper and palladium catalytic cycle, with the observed stereocontrol originating from a higher-order active palladium catalyst.

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Fig. 1: Background and our strategy.
Fig. 2: Downstream applications and transformations.
Fig. 3: Mechanism experiments and possible catalytic cycle.

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Data availability

The data that support the findings of this study are available within the article and its Supplementary Information files. Crystallographic data for the structures reported in this Article have been deposited at the CCDC, under deposition numbers CCDC 2171042 (3), 2171044 (12), 2171040 (17), 2171047 (36), 2171041 (51), 2171043 (70), 2171046 (126) and 2171045 (ent-3). Copies of the data can be obtained free of charge via https://www.ccdc.cam.ac.uk/structures.

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Acknowledgements

Financial support came from National Natural Science Foundation of China (grant nos. 21931013 to Q.S. and 22001038 to K.Y.), the Natural Science Foundation of Fujian Province (grant no. 2022J02009 to Q.S.) and Open Research Fund of School of Chemistry and Chemical Engineering, Henan Normal University (to Q.S.) is gratefully acknowledged.

Author information

Authors and Affiliations

  1. Key Laboratory of Molecule Synthesis and Function Discovery, Fujian Province University, College of Chemistry at Fuzhou University, Fuzhou, China

    Wangyang Li, Shanglin Chen, Jinhui Xie, Zhenwei Fan, Kai Yang & Qiuling Song

  2. Institute of Next Generation Matter Transformation, College of Material Sciences Engineering, Huaqiao University, Xiamen, China

    Qiuling Song

  3. School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, China

    Qiuling Song

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  1. Wangyang Li
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Contributions

Q.S. designed and directed the project. W.L. performed the experiments and developed the reactions. S.C., J.X., Z.F. and K.Y. helped collecting some experimental data. Q.S. and W.L. wrote the manuscript. All authors discussed the results and commented on the manuscript.

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Correspondence to Qiuling Song.

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Nature Synthesis thanks the anonymous reviewers for their contribution to the peer review of this work. Primary Handling Editor: Thomas West, in collaboration with the Nature Synthesis team.

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Supplementary information

Supplementary information

Supplementary Tables 1–14, Figs. 1–9 and starting material preparation, experimental procedures, synthetic transformations, mechanistic studies and product characterization.

Supplementary Data 1

Crystallographic data of complex 3 (CCDC 2171042).

Supplementary Data 2

Crystallographic data of complex 12 (CCDC 2171044).

Supplementary Data 3

Crystallographic data of complex 17 (CCDC 2171040).

Supplementary Data 4

Crystallographic data of complex 36 (CCDC 2171047).

Supplementary Data 5

Crystallographic data of complex 51 (CCDC 2171041).

Supplementary Data 6

Crystallographic data of complex 70 (CCDC 2171043).

Supplementary Data 7

Crystallographic data of complex 126 (CCDC 2171046).

Supplementary Data 8

Crystallographic data of complex ent-3 (CCDC 2171045).

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Li, W., Chen, S., Xie, J. et al. Synthesis of axially chiral alkenylboronates through combined copper- and palladium-catalysed atroposelective arylboration of alkynes. Nat. Synth 2, 140–151 (2023). https://doi.org/10.1038/s44160-022-00201-6

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