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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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.
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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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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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DOI: https://doi.org/10.1038/s44160-022-00201-6
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