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Structurally defined anti-π-allyliridium complexes catalyse Z-retentive asymmetric allylic alkylation of oxindoles

Nature Catalysis volume 5, pages 1089–1097 (2022)Cite this article

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Abstract

The enantioselective synthesis of chiral Z-olefins is an important but challenging topic in organic chemistry. Iridium-catalysed Z-retentive asymmetric allylic substitution reactions have recently emerged as a promising strategy for trapping thermodynamically less stable anti-π-allyliridium intermediates. However, detailed mechanistic knowledge about this process has remained elusive. Here we report the structural characterization and transformations of the previously assumed putative anti-π-allyliridium intermediates. These complexes are highly efficient catalysts that enable Z-retentive asymmetric allylic alkylation of oxindoles accommodating a wide substrate scope. An iridium catalyst with a different metal-to-ligand ratio from that of a similar catalyst reported in the literature has been found to be crucial for regioselective nucleophilic attack at the less substituted allylic terminus. This simple yet powerful approach lays a solid foundation towards a general platform for the enantioselective synthesis of chiral Z-olefins.

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Fig. 1: Mechanism for transition metal-catalysed asymmetric allylic substitution.
Fig. 2: Synthesis of the π-allyliridium complexes.
Fig. 3: Isomerization of π-allyliridium complexes monitored by 31P NMR spectroscopy.
Fig. 4: Scope of the Ir-catalysed Z-retentive asymmetric allylic substitution.
Fig. 5: Optimized structures of key transition states.

Data availability

Detailed experimental procedures, characterizations of new compounds and computational results are provided in the Supplementary Information. Crystallographic data for the structures reported in this article have been deposited at the Cambridge Crystallographic Data Centre, under deposition numbers CCDC 2161348 (K1c-Cl), 2161343 (K1c-Br), 2161345 (K1c-I), 2161346 (K2a-Cl-H), 2161347 (K2a-I-H), 2161354 (K2c-Br-H), 2161350 (K2c-I-H), 2161340 (anti-K2c-Br-Me), 2161342 (anti-K2c-Br-Pr), 2161344 (anti-K2c-Br-Ph), 2161341 (exo-syn-K2c-Br-Me), 2161353 (endo-syn-K2c-Br-Pr), 2161349 (Z-3bA), 2161351 (Z-3a′A) and 2161352 (Z-3uA, structure shown in Supplementary Fig. 20). Copies of the data can be obtained free of charge via https://www.ccdc.cam.ac.uk/structures/. The output files of the theoretical calculations in this work have been deposited at Zenodo (https://doi.org/10.5281/zenodo.6817573). All other data are available from the corresponding authors upon reasonable request.

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Acknowledgements

We thank the National Key Research and Development Program of China (2021YFA1500100), the National Natural Science Foundation of China (21821002, 22031012, 22171282 and 91856201), the Youth Innovation Promotion Association of the Chinese Academy of Sciences (Y2021075) and the Science and Technology Commission of Shanghai Municipality (19590750400 and 21520780100) for generous financial support. We also thank X. Leng (SIOC) and L. Li (Shanghai Jiao Tong University) for X-ray crystallographic analysis, and R. Leveson-Gower (University of Groningen) for proofreading the manuscript. S.-L.Y. thanks the support of the Tencent Foundation through an XPLORER PRIZE.

Author information

Authors and Affiliations

  1. State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China

    Ru Jiang, Qing-Ru Zhao, Chao Zheng & Shu-Li You

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  1. Ru Jiang
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Contributions

S.-L.Y. conceived and supervised the project; R.J. synthesized and characterized the Ir complexes and developed the Ir-catalysed Z-retentive asymmetric allylic substitution reactions; Q.-R.Z. contributed to expanding the scope of the reaction; R.J. and C.Z. performed the electronic structure calculations; C.Z. wrote the manuscript with revisions suggested by all authors.

Corresponding authors

Correspondence to Chao Zheng or Shu-Li You.

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Peer review information

Nature Catalysis thanks Liqin Qiu and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary information

Supplementary Information

Supplementary Methods, Figs. 1–21, Tables 1–19, notes and references.

Supplementary Data 1

Cif file for K1c-I.

Supplementary Data 2

Cif file for K1c-Br.

Supplementary Data 3

Cif file for K1c-Cl.

Supplementary Data 4

Cif file for K2a-Cl-H.

Supplementary Data 5

Cif file for K2a-I-H.

Supplementary Data 6

Cif file for K2c-Br-H.

Supplementary Data 7

Cif file for K2c-I-H.

Supplementary Data 8

Cif file for anti-K2c-Br-Me.

Supplementary Data 9

Cif file for anti-K2c-Br-Pr.

Supplementary Data 10

Cif file for anti-K2c-Br-Ph.

Supplementary Data 11

Cif file for exo-syn-K2c-Br-Me.

Supplementary Data 12

Cif file for endo-syn-K2c-Br-Pr.

Supplementary Data 13

Cif file for Z-3bA.

Supplementary Data 13

Cif file for Z-3a′A.

Supplementary Data 13

Cif file for Z-3uA.

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Jiang, R., Zhao, QR., Zheng, C. et al. Structurally defined anti-π-allyliridium complexes catalyse Z-retentive asymmetric allylic alkylation of oxindoles. Nat Catal 5, 1089–1097 (2022). https://doi.org/10.1038/s41929-022-00879-z

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