Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Modular enantioselective assembly of multi-substituted boron-stereogenic BODIPYs

Nature Chemistry volume 17, pages 83–91 (2025)Cite this article

Subjects

Abstract

Boron dipyrromethenes (BODIPYs) are some of the most popular and indispensable tetracoordinate boron compounds and have found widespread applications owing to their excellent spectroscopic and photophysical properties. BODIPYs possessing boron-stereogenic centres are scarce, and strategies for the synthesis of enantioenriched boron-stereogenic BODIPYs with structural diversity remain underdeveloped. In theory, the BODIPY core skeleton has several sites that could be decorated with different substituents. However, due to the lack of general and efficient asymmetric synthetic methods, this potential diversity of chiral BODIPYs has not been exploited. Here we demonstrate a modular enantioselective assembly of multi-substituted boron-stereogenic BODIPYs in high efficiency with excellent enantioselectivities. Key to the success is the Pd-catalysed desymmetric Suzuki cross-coupling, enabling the precise discrimination of the two α C–Cl bonds of the designed prochiral BODIPY scaffold, giving access to a wide range of highly functionalized boron-stereogenic BODIPYs. Derivatizations, photophysical properties and applications in chiral recognition of the obtained optical BODIPYs are further explored.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Modular enantioselective assembly of multiply boron-stereogenic BODIPYs.
Fig. 2: Development of modular enantioselective construction of boron-stereogenic BODIPYs.
Fig. 3: Post-functionalization of boron-stereogenic 5-Cl-BODIPY.
Fig. 4: Photophysical properties investigations and application for chiral recognition.

Similar content being viewed by others

Data availability

The data that support the findings of this study are available within the Article and its Supplementary Information. Details about materials and methods, experimental procedures, characterization data, 1H, 13C, 19F, 11B NMR spectra and mass spectrometry data are available in Supplementary Information. Crystallographic data for the structures reported in this Article have been deposited at the Cambridge Crystallographic Data Centre, under deposition numbers CCDC 2278973 (3a), 2278972 (4a) and 2278967 (4l). Copies of the data can be obtained free of charge via https://www.ccdc.cam.ac.uk/structures/. Source data are provided with this paper.

References

  1. Treibs, A. & Kreuzer, F.-H. Difluorboryl-komplexe von di- und tripyrrylmethenen. Justus Liebigs Ann. Chem. 718, 208–223 (1968).

    CAS  Google Scholar 

  2. Bin-Kai, L., Kun-Xu, T., Li-Ya, N. & Qing-Zheng, Y. Progress in the synthesis of boron dipyrromethene (BODIPY) fluorescent dyes. Chin. J. Org. Chem. 42, 1265–1285 (2022).

    Google Scholar 

  3. Loudet, A. & Burgess, K. BODIPY dyes and their derivatives: syntheses and spectroscopic properties. Chem. Rev. 107, 4891–4932 (2007).

    CAS  PubMed  Google Scholar 

  4. Ulrich, G., Ziessel, R. & Harriman, A. The chemistry of fluorescent BODIPY dyes: versatility unsurpassed. Angew. Chem. Int. Ed. 47, 1184–1201 (2008).

    CAS  Google Scholar 

  5. Boens, N., Verbelen, B., Ortiz, M. J., Jiao, L. & Dehaen, W. Synthesis of BODIPY dyes through postfunctionalization of the boron dipyrromethene core. Coord. Chem. Rev. 399, 213024–213108 (2019).

    CAS  Google Scholar 

  6. Bañuelos, J. BODIPY dye, the most versatile fluorophore ever? Chem. Rec. 16, 335–348 (2016).

    PubMed  Google Scholar 

  7. Poddar, M. & Misra, R. Recent advances of BODIPY based derivatives for optoelectronic applications. Coord. Chem. Rev. 421, 213462–213483 (2020).

    CAS  Google Scholar 

  8. Nguyen, V.-N. et al. Recent developments of BODIPY-based colorimetric and fluorescent probes for the detection of reactive oxygen/nitrogen species and cancer diagnosis. Coord. Chem. Rev. 439, 213936–213952 (2021).

    CAS  Google Scholar 

  9. Yuan, L., Su, Y., Cong, H., Yu, B. & Shen, Y. Application of multifunctional small molecule fluorescent probe BODIPY in life science. Dyes Pigm. 208, 110851–110869 (2023).

    Google Scholar 

  10. Zhang, J. et al. BODIPY-based fluorescent probes for biothiols. Chem. Eur. J. 26, 4172–4192 (2020).

    CAS  PubMed  Google Scholar 

  11. Boens, N., Leen, V. & Dehaen, W. Fluorescent indicators based on BODIPY. Chem. Soc. Rev. 41, 1130–1172 (2012).

    CAS  PubMed  Google Scholar 

  12. Kolemen, S. & Akkaya, E. U. Reaction-based BODIPY probes for selective bio-imaging. Coord. Chem. Rev. 354, 121–134 (2018).

    CAS  Google Scholar 

  13. De Bonfils, P., Péault, L., Nun, P. & Coeffard, V. State of the art of BODIPY-based photocatalysts in organic synthesis. Eur. J. Org. Chem. 2021, 1809–1824 (2021).

    Google Scholar 

  14. Singh, P. K., Majumdar, P. & Singh, S. P. Advances in BODIPY photocleavable protecting groups. Coord. Chem. Rev. 449, 214193–214248 (2021).

    CAS  Google Scholar 

  15. Zhang, W. et al. Application of multifunctional BODIPY in photodynamic therapy. Dyes Pigm. 185, 108937–108950 (2021).

    CAS  Google Scholar 

  16. Kamkaew, A. et al. BODIPY dyes in photodynamic therapy. Chem. Soc. Rev. 42, 77–88 (2013).

    CAS  PubMed  Google Scholar 

  17. Kowada, T., Maeda, H. & Kikuchi, K. BODIPY-based probes for the fluorescence imaging of biomolecules in living cells. Chem. Soc. Rev. 44, 4953–4972 (2015).

    CAS  PubMed  Google Scholar 

  18. Pu, L. Simultaneous determination of concentration and enantiomeric composition in fluorescent sensing. Acc. Chem. Res. 50, 1032–1040 (2017).

    CAS  PubMed  Google Scholar 

  19. Pop, F., Zigon, N. & Avarvari, N. Main-group-based electro- and photoactive chiral materials. Chem. Rev. 119, 8435–8478 (2019).

    CAS  PubMed  Google Scholar 

  20. Zu, B., Guo, Y. & He, C. Catalytic enantioselective construction of chiroptical boron-stereogenic compounds. J. Am. Chem. Soc. 143, 16302–16310 (2021).

    CAS  PubMed  Google Scholar 

  21. Zhang, G. et al. Construction of boron-stereogenic compounds via enantioselective Cu-catalyzed desymmetric B–H bond insertion reaction. Nat. Commun. 13, 2624 (2022).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Zhang, G. et al. Cu(I)-catalyzed highly diastereo- and enantioselective constructions of boron/carbon vicinal stereogenic centers via insertion reaction. ACS Catal. 13, 9502–9508 (2023).

    CAS  Google Scholar 

  23. Zu, B., Guo, Y., Ren, L.-Q., Li, Y. & He, C. Catalytic enantioselective synthesis of boron-stereogenic BODIPYs. Nat. Synth. 2, 564–571 (2023).

    CAS  Google Scholar 

  24. Haefele, A., Zedde, C., Retailleau, P., Ulrich, G. & Ziessel, R. Boron asymmetry in a BODIPY derivative. Org. Lett. 12, 1672–1675 (2010).

    CAS  PubMed  Google Scholar 

  25. Gobo, Y., Matsuoka, R., Chiba, Y., Nakamura, T. & Nabeshima, T. Synthesis and chiroptical properties of phenanthrene-fused N2O-type BODIPYs. Tetrahedron Lett. 59, 4149–4152 (2018).

    CAS  Google Scholar 

  26. Ray, C. et al. Dissimilar-at-boron N-BODIPYs: from light-harvesting multichromophoric arrays to CPL-bright chiral-at-boron BODIPYs. Org. Chem. Front. 10, 5834–5842 (2023).

    CAS  Google Scholar 

  27. Lu, H., Mack, J., Nyokong, T., Kobayashi, N. & Shen, Z. Optically active BODIPYs. Coord. Chem. Rev. 318, 1–15 (2016).

    CAS  Google Scholar 

  28. Li, X., Zhang, G. & Song, Q. Recent advances in the construction of tetracoordinate boron compounds. Chem. Commun. 59, 3812–3820 (2023).

    CAS  Google Scholar 

  29. Abdou-Mohamed, A. et al. Stereoselective formation of boron-stereogenic organoboron derivatives. Chem. Soc. Rev. 52, 4381–4391 (2023).

    CAS  PubMed  Google Scholar 

  30. Vedejs, E. et al. Asymmetric memory at labile, stereogenic boron: enolate alkylation of oxazaborolidinones. J. Am. Chem. Soc. 121, 2460–2470 (1999).

    CAS  Google Scholar 

  31. Charoy, L. et al. Synthesis of benzylcyanoborane adducts of amines and separation of their enantiomers; S2 substitution at boron atom. Chem. Commun. 2275–2276 (2000).

  32. Imamoto, T. & Morishita, H. An enantiomerically pure tetracoordinate boron compound: stereochemistry of substitution reactions at the chirogenic boron atom. J. Am. Chem. Soc. 122, 6329–6330 (2000).

    CAS  Google Scholar 

  33. Toyota, S., Ito, F., Nitta, N. & Hakamata, T. Substituent effects on configurational stabilities at tetrahedral boron atoms in intramolecular borane–amine complexes: structures, enantiomeric resolution, and rates of enantiomerization of [2-(dimethylaminomethyl)phenyl]phenylboranes. Bull. Chem. Soc. Jpn. 77, 2081–2088 (2004).

    CAS  Google Scholar 

  34. Braun, M., Schlecht, S., Engelmann, M., Frank, W. & Grimme, S. Boron-based diastereomerism and enantiomerism in imine complexes—determination of the absolute configuration at boron by CD spectroscopy. Eur. J. Org. Chem. 2008, 5221–5225 (2008).

    Google Scholar 

  35. Kaiser, P. F., White, J. M. & Hutton, C. A. Enantioselective preparation of a stable boronate complex stereogenic only at boron. J. Am. Chem. Soc. 130, 16450–16451 (2008).

    CAS  PubMed  Google Scholar 

  36. Schlecht, S., Frank, W. & Braun, M. Stereogenic boron in 2-amino-1,1-diphenylethanol-based boronate-imine and amine complexes. Beilstein J. Org. Chem. 7, 615–621 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Jiménez, V. G. et al. Circularly polarized luminescence of boronic acid-derived salicylidenehydrazone complexes containing chiral boron as stereogenic unit. J. Org. Chem. 83, 14057–14062 (2018).

    PubMed  Google Scholar 

  38. Aupic, C. et al. Highly diastereoselective preparation of chiral NHC-boranes stereogenic at the boron atom. Chem. Sci. 10, 6524–6530 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Stöckl, Y. et al. Enantioenriched boron C,N-chelates via chirality transfer. Chem. Eur. J. 29, e202301324 (2023).

    PubMed  Google Scholar 

  40. Braun, M. Boron-based enantiomerism. Eur. J. Org. Chem. 27, e202400052 (2024).

    CAS  Google Scholar 

  41. Guo, Y., Zu, B., Chen, C. D. & He, C. Boron-stereogenic compounds: synthetic developments and opportunities. Chin. J. Chem. https://doi.org/10.1002/cjoc.202400130 (2024).

  42. Suzuki, S., Segawa, Y., Itami, K. & Yamaguchi, J. Synthesis and characterization of hexaarylbenzenes with five or six different substituents enabled by programmed synthesis. Nat. Chem. 7, 227–233 (2015).

    CAS  PubMed  Google Scholar 

  43. Aiken, S. G. et al. Iterative synthesis of 1,3-polyboronic esters with high stereocontrol and application to the synthesis of bahamaolide A. Nat. Chem. 15, 248–256 (2023).

    CAS  PubMed  Google Scholar 

  44. Lyu, H. et al. Modular synthesis of 1,2-azaborines via ring-opening BN-isostere benzannulation. Nat. Chem. 16, 269–276 (2024).

    CAS  PubMed  Google Scholar 

  45. Rohand, T., Dolusic, E., Ngo, T. H., Maes, W. & Dehaen, W. Efficient synthesis of aryldipyrromethanes in water and their application in the synthesis of corroles and dipyrromethenes. Arkivoc 307–324 (2007).

  46. Willis, M. C., Powell, L. H. W., Claverie, C. K. & Watson, S. J. Enantioselective Suzuki reactions: catalytic asymmetric synthesis of compounds containing quaternary carbon centers. Angew. Chem. Int. Ed. 43, 1249–1251 (2004).

    CAS  Google Scholar 

  47. Urbaneja, X., Mercier, A., Besnard, C. & Kündig, E. P. Highly efficient desymmetrisation of a tricarbonylchromium 1,4-dibromonaphthalene complex by asymmetric Suzuki–Miyaura coupling. Chem. Commun. 47, 3739–3741 (2011).

    CAS  Google Scholar 

  48. Hedouin, G., Hazra, S., Gallou, F. & Handa, S. The catalytic formation of atropisomers and stereocenters via asymmetric Suzuki–Miyaura couplings. ACS Catal. 12, 4918–4937 (2022).

    CAS  Google Scholar 

  49. Lou, Y., Wei, J., Li, M. & Zhu, Y. Distal ionic substrate–catalyst interactions enable long-range stereocontrol: Access to remote quaternary stereocenters through a desymmetrizing Suzuki–Miyaura reaction. J. Am. Chem. Soc. 144, 123–129 (2022).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Pearce-Higgins, R. et al. An enantioselective Suzuki–Miyaura coupling to form axially chiral biphenols. J. Am. Chem. Soc. 144, 15026–15032 (2022).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Zhang, M., Lee, P. S., Allais, C., Singer, R. A. & Morken, J. P. Desymmetrization of vicinal bis(boronic) esters by enantioselective Suzuki–Miyaura cross-coupling reaction. J. Am. Chem. Soc. 145, 8308–8313 (2023).

    CAS  Google Scholar 

  52. Höpfl, H. The tetrahedral character of the boron atom newly defined—a useful tool to evaluate the N→B bond. J. Organomet. Chem. 581, 129–149 (1999).

    Google Scholar 

  53. Satyanarayana, T., Abraham, S. & Kagan, H. B. Nonlinear effects in asymmetric catalysis. Angew. Chem. Int. Ed. 48, 456–494 (2009).

    CAS  Google Scholar 

  54. Imbos, R., Minnaard, A. J. & Feringa, B. L. Monodentate phosphoramidites; versatile ligands in catalytic asymmetric intramolecular heck reactions. Dalton Trans. 2017–2023 (2003).

  55. Barder, T. E., Walker, S. D., Martinelli, J. R. & Buchwald, S. L. Catalysts for Suzuki–Miyaura coupling processes: scope and studies of the effect of ligand structure. J. Am. Chem. Soc. 127, 4685–4696 (2005).

    CAS  PubMed  Google Scholar 

  56. Bodio, E. & Goze, C. Investigation of B-F substitution on BODIPY and aza-BODIPY dyes: development of B-O and B-C BODIPYs. Dyes Pigm. 160, 700–710 (2019).

    CAS  Google Scholar 

  57. Lu, H., Mack, J., Yang, Y. & Shen, Z. Structural modification strategies for the rational design of red/NIR region BODIPYs. Chem. Soc. Rev. 43, 4778–4823 (2014).

    CAS  PubMed  Google Scholar 

  58. Teng, K.-X., Niu, L.-Y., Li, J., Jia, L. & Yang, Q.-Z. An unexpected coupling–reduction tandem reaction for the synthesis of alkenyl-substituted BODIPYs. Chem. Commun. 55, 13761–13764 (2019).

    CAS  Google Scholar 

  59. Wang, Z. et al. Organotrifluoroborate salts as complexation reagents for synthesizing BODIPY dyes containing both fluoride and an organo substituent at the boron center. J. Org. Chem. 84, 2732–2740 (2019).

    CAS  PubMed  Google Scholar 

  60. Niu, L.-Y. et al. BODIPY-based ratiometric fluorescent sensor for highly selective detection of glutathione over cysteine and homocysteine. J. Am. Chem. Soc. 134, 18928–18931 (2012).

    CAS  PubMed  Google Scholar 

  61. Wang, S.-Y., Niu, L.-Y. & Yang, Q.-Z. Fluorescent probes for detection of bioactive molecules based on ‘aromatic nucleophilic substitution-rearrangement’ mechanism. Sci. Sin. Chim. 52, 893–912 (2022).

    Google Scholar 

Download references

Acknowledgements

We are grateful for financial support from the National Natural Science Foundation of China (22122102, 22101120 and 22271134), Guangdong Provincial Key Laboratory of Catalysis (2020B121201002), Guangdong Pearl River Talent Program (2019QN01Y628) and Shenzhen Science and Technology Innovation Committee (RCJC20221008092723013 and JCYJ20230807093104009). We acknowledge the assistance of SUSTech Core Research Facilities (SUSTech CRF) for obtaining photophysical properties and chiral recognition data.

Author information

Author notes

  1. These authors contributed equally: Li-Qing Ren, Baoquan Zhan.

Authors and Affiliations

  1. Shenzhen Grubbs Institute and Department of Chemistry, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen, China

    Li-Qing Ren, Baoquan Zhan, Jiayi Zhao, Yonghong Guo, Bing Zu, Yingzi Li & Chuan He

Authors
  1. Li-Qing Ren
    View author publications

    Search author on:PubMed Google Scholar

  2. Baoquan Zhan
    View author publications

    Search author on:PubMed Google Scholar

  3. Jiayi Zhao
    View author publications

    Search author on:PubMed Google Scholar

  4. Yonghong Guo
    View author publications

    Search author on:PubMed Google Scholar

  5. Bing Zu
    View author publications

    Search author on:PubMed Google Scholar

  6. Yingzi Li
    View author publications

    Search author on:PubMed Google Scholar

  7. Chuan He
    View author publications

    Search author on:PubMed Google Scholar

Contributions

C.H. and L.-Q.R. conceived the project. L.-Q.R., B.Zhan, J.Z., Y.G. and B.Zu designed and performed the synthetic experiments. Y.L. performed the computational studies. C.H. and L.-Q.R. prepared the paper.

Corresponding author

Correspondence to Chuan He.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer review information

Nature Chemistry thanks Olivier Chuzel, Erhong Hao and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplementary Information

Supplementary figures, discussion and tables.

Supplementary Data 1

Crystallographic data for compound 3a; CCDC reference 2278973.

Supplementary Data 2

Crystallographic data for compound 4a; CCDC reference 2278972.

Supplementary Data 3

Crystallographic data for compound 4l; CCDC reference 2278967.

Source data

Source Data Fig. 4

Excel file for Fig. 4.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ren, LQ., Zhan, B., Zhao, J. et al. Modular enantioselective assembly of multi-substituted boron-stereogenic BODIPYs. Nat. Chem. 17, 83–91 (2025). https://doi.org/10.1038/s41557-024-01649-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Version of record:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41557-024-01649-z

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing