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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.

References

  1. Kumarasamy, E., Raghunathan, R., Sibi, M. P. & Sivaguru, J. Nonbiaryl and heterobiaryl atropisomers: molecular templates with promise for atropselective chemical transformations. Chem. Rev. 115, 11239–11300 (2015).

    Article  CAS  Google Scholar 

  2. Li, Q. et al. Reversible photoswitchable axially chiral dopants with high helical twisting power. J. Am. Chem. Soc. 129, 12908–12909 (2007).

    Article  CAS  Google Scholar 

  3. Smyth, J. E., Butler, N. M. & Keller, P. A. A twist of nature–the significance of atropisomers in biological systems. Nat. Prod. Rep. 32, 1562–1583 (2015).

    Article  CAS  Google Scholar 

  4. Clayden, J., Moran, W. J., Edwards, P. J. & LaPlante, S. R. The challenge of atropisomerism in drug discovery. Angew. Chem. Int. Ed. 48, 6398–6401 (2009).

    Article  CAS  Google Scholar 

  5. Noyori, R. & Takaya, H. BINAP: an efficient chiral element for asymmetric catalysis. Acc. Chem. Res. 23, 345–350 (1990).

    Article  CAS  Google Scholar 

  6. Chen, Y., Yekta, S. & Yudin, A. K. Modified BINOL ligands in asymmetric catalysis. Chem. Rev. 103, 3155–3211 (2003).

    Article  CAS  Google Scholar 

  7. Parmar, D., Sugiono, E., Raja, S. & Rueping, M. Complete field guide to asymmetric BINOL-phosphate derived Brønsted acid and metal catalysis: history and classification by mode of activation; Brønsted acidity, hydrogen bonding, ion pairing, and metal phosphates. Chem. Rev. 114, 9047–9153 (2014).

    Article  CAS  Google Scholar 

  8. Shirakawa, S., Wu, X. & Maruoka, K. Kinetic resolution of axially chiral 2-amino-1,1′-biaryls by phase-transfer-catalyzed N-allylation. Angew. Chem. Int. Ed. 52, 4312–4348 (2013).

    Article  CAS  Google Scholar 

  9. Chen, J. et al. Carbonyl catalysis enables a biomimetic asymmetric Mannich reaction. Science 360, 1438–1442 (2018).

    Article  CAS  Google Scholar 

  10. Wencel-Delord, J., Panossian, A., Leroux, F. R. & Colobert, F. Recent advances and new concepts for the synthesis of axially stereoenriched biaryls. Chem. Soc. Rev. 44, 3418–3430 (2015).

    Article  CAS  Google Scholar 

  11. Loxq, P., Manoury, E., Poli, R., Deydier, E. & Labande, A. Synthesis of axially chiral biaryl compounds by asymmetric catalytic reactions with transition metals. Coord. Chem. Rev. 308, 131–190 (2016).

    Article  CAS  Google Scholar 

  12. Yang, H., Yang, X. & Tang, W. Transition-metal catalyzed asymmetric carbon–carbon cross-coupling with chiral ligands. Tetrahedron 72, 6143–6174 (2016).

    Article  CAS  Google Scholar 

  13. Hazra, C. K., Dherbassy, Q., Wencel-Delord, J. & Colobert, F. Synthesis of axially chiral biaryls through sulfoxide-directed asymmetric mild C–H activation and dynamic kinetic resolution. Angew. Chem. Int. Ed. 53, 13871–13875 (2014).

    Article  CAS  Google Scholar 

  14. Gustafson, J. L., Lim, D. & Miller, S. J. Dynamic kinetic resolution of biaryl atropisomers via peptide-catalyzed asymmetric bromination. Science 328, 1251–1255 (2010).

    Article  CAS  Google Scholar 

  15. Ma, G. & Sibi, M. P. Catalytic kinetic resolution of biaryl compounds. Chem. Eur. J. 21, 11644–11657 (2015).

    Article  CAS  Google Scholar 

  16. Liao, G., Zhou, T., Yao, Q.-J. & Shi, B.-F. Recent advances in the synthesis of axially chiral biaryls via transition metal-catalysed asymmetric C–H functionalization. Chem. Commun. 55, 8514–8523 (2019).

    Article  CAS  Google Scholar 

  17. Giri, R., Shi, B.-F., Engle, K. M., Maugel, N. & Yu, J.-Q. Transition metal-catalyzed C–H activation reactions: diastereoselectivity and enantioselectivity. Chem. Soc. Rev. 38, 3242–3272 (2009).

    Article  CAS  Google Scholar 

  18. Hayashi, T., Hayashizaki, K., Kiyoi, T. & Ito, Y. Asymmetric synthesis catalyzed by chiral ferrocenylphosphine-transition-metal complexes. 6 Practical asymmetric synthesis of 1,1′-binaphthyls via asymmetric cross-coupling with a chiral [(alkoxyalkyl)ferrocenyl]monophosphine/nickel catalyst. J. Am. Chem. Soc. 110, 8153–8156 (1988).

    Article  CAS  Google Scholar 

  19. Shen, D., Xu, Y. & Shi, S.-L. A bulky chiral N‑heterocyclic carbene palladium catalyst enables highly enantioselective Suzuki–Miyaura cross-coupling reactions for the synthesis of biaryl atropisomers. J. Am. Chem. Soc. 141, 14938–14945 (2019).

    Article  CAS  Google Scholar 

  20. Qi, L.-W., Li, S., Xiang, S.-H., Wang, J. & Tan, B. Asymmetric construction of atropisomeric biaryls via a redox neutral cross-coupling strategy. Nat. Catal. 2, 314–323 (2019).

    Article  CAS  Google Scholar 

  21. Link, A. & Sparr, C. Stereoselective arene formation. Chem. Soc. Rev. 47, 3804–3815 (2018).

    Article  CAS  Google Scholar 

  22. Zhao, K. et al. Enhanced reactivity by torsional strain of cyclic diaryliodonium in Cu-catalyzed enantioselective ring-opening reaction. Chem 4, 599–612 (2018).

    Article  CAS  Google Scholar 

  23. Wang, Y.-B. & Tan, B. Construction of axially chiral compounds via asymmetric organocatalysis. Acc. Chem. Res. 51, 534–547 (2018).

    Article  CAS  Google Scholar 

  24. Yamaguchi, K., Yamaguchi, J., Studer, A. & Itami, K. Hindered biaryls by C–H coupling: bisoxazoline-Pd catalysis leading to enantioselective C–H coupling. Chem. Sci. 3, 2165–2169 (2012).

    Article  CAS  Google Scholar 

  25. Jia, Z.-J. et al. General enantioselective C–H activation with efficiently tunable cyclopentadienyl ligands. Angew. Chem. Int. Ed. 56, 2429–2434 (2017).

    Article  CAS  Google Scholar 

  26. Jang, Y.-S., Woźniak, Ł., Pedroni, J. & Cramer, N. Access to P‐ and axially chiral biaryl phosphine oxides by enantioselective Cpx IrIII atalyzed C–H arylations. Angew. Chem. Int. Ed. 57, 12901–12905 (2018).

    Article  CAS  Google Scholar 

  27. Catellani, M., Frignani, F. & Rangoni, A. A complex catalytic cycle leading to a regioselective synthesis of o,o′‐disubstituted vinylarenes. Angew. Chem. Int. Ed. 36, 119–122 (1997).

    Article  CAS  Google Scholar 

  28. Kim, D.-S., Park, W.-J. & Jun, C.-H. Metal–organic cooperative catalysis in C–H and C–C bond activation. Chem. Rev. 117, 8977–9015 (2017).

    Article  CAS  Google Scholar 

  29. Catellani, M., Motti, E. & Ca’, N. D. Catalytic sequential reactions involving palladacycle-directed aryl coupling steps. Acc. Chem. Res. 41, 1512–1522 (2008).

    Article  CAS  Google Scholar 

  30. Ding, L., Sui, X. & Gu, Z. Enantioselective synthesis of biaryl atropisomers via Pd/norbornene-catalyzed three-component cross-couplings. ACS Catal. 8, 5630–5635 (2018).

    Article  CAS  Google Scholar 

  31. Zhao, Y.-B. et al. Exploiting the divergent reactivity of aryl–palladium intermediates for the rapid assembly of fluorene and phenanthrene derivatives. Angew. Chem. Int. Ed. 48, 1849–1852 (2009).

    Article  CAS  Google Scholar 

  32. Yang, L. et al. Palladium-catalyzed dynamic kinetic asymmetric transformation of racemic biaryls: axial-to-central chirality transfer. J. Am. Chem. Soc. 137, 4876–4879 (2015).

    Article  CAS  Google Scholar 

  33. Shi, H., Herron, A. N., Shao, Y., Shao, Q. & Yu, J.-Q. Enantioselective remote meta-C–H arylation and alkylation via a chiral transient mediator. Nature 558, 581–585 (2018).

    Article  CAS  Google Scholar 

  34. Li, R., Liu, F. & Dong, G. Palladium-catalyzed asymmetric annulation between aryl iodides and racemic epoxides using a chiral norbornene cocatalyst. Org. Chem. Front. 5, 3108–3112 (2018).

    Article  CAS  Google Scholar 

  35. Cao, Z. et al. Pd-catalyzed asymmetric allylic alkylation of indoles and pyrroles by chiral alkene-phosphine ligands. Org. Lett. 13, 2164–2167 (2011).

    Article  CAS  Google Scholar 

  36. Shintani, R., Duan, W.-L., Okamoto, K. & Hayashi, T. Palladium/chiral phosphine–olefin complexes: X-ray crystallographic analysis and the use in catalytic asymmetric allylic alkylation. Tetrahedron Asymmetry 16, 3400–3405 (2005).

    Article  CAS  Google Scholar 

  37. Liu, Z. & Du, H. Development of chiral terminal-alkene-phosphine hybrid ligands for palladium-catalyzed asymmetric allylic substitutions. Org. Lett. 12, 3054–3057 (2010).

    Article  CAS  Google Scholar 

  38. Lam, F. L. et al. Palladium–(S,pR)-ferroNPS-catalyzed asymmetric allylic etherification: electronic effect of nonconjugated substituents on benzylic alcohols on enantioselectivity. Angew. Chem. Int. Ed. 47, 1280–1283 (2008).

    Article  CAS  Google Scholar 

  39. Wen, W. et al. Chiral aldehyde catalysis for the catalytic asymmetric activation of glycine esters. J. Am. Chem. Soc. 140, 9774–9780 (2018).

    Article  CAS  Google Scholar 

  40. Witzig, R. M., Fäseke, V. C., Häussinger, D. & Sparr, C. Atroposelective synthesis of tetra-ortho-substituted biaryls by catalyst-controlled non-canonical polyketide cyclizations. Nat. Catal. 2, 925–930 (2019).

    Article  CAS  Google Scholar 

Download references

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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