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:

A general copper-catalysed enantioconvergent C(sp3)–S cross-coupling via biomimetic radical homolytic substitution

Nature Chemistry volume 16, pages 466–475 (2024)Cite this article

Subjects

Abstract

Although α-chiral C(sp3)–S bonds are of enormous importance in organic synthesis and related areas, the transition-metal-catalysed enantioselective C(sp3)–S bond construction still represents an underdeveloped domain probably due to the difficult heterolytic metal–sulfur bond cleavage and notorious catalyst-poisoning capability of sulfur nucleophiles. Here we demonstrate the use of chiral tridentate anionic ligands in combination with Cu(I) catalysts to enable a biomimetic enantioconvergent radical C(sp3)–S cross-coupling reaction of both racemic secondary and tertiary alkyl halides with highly transformable sulfur nucleophiles. This protocol not only exhibits a broad substrate scope with high enantioselectivity but also provides universal access to a range of useful α-chiral alkyl organosulfur compounds with different sulfur oxidation states, thus providing a complementary approach to known asymmetric C(sp3)–S bond formation methods. Mechanistic results support a biomimetic radical homolytic substitution pathway for the critical C(sp3)–S bond formation step.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Fig. 1: Motivation and design of Cu(I)-catalysed enantioconvergent C(sp3)–S cross-coupling via biomimetic radical homolytic substitution.
Fig. 2: Synthetic utility for the construction of valuable α-chiral alkyl organosulfur compounds.
Fig. 3: Mechanistic discussion.

Similar content being viewed by others

Data availability

Data relating to the materials and methods, optimization studies, experimental procedures, mechanistic studies, DFT calculations, HPLC spectra, NMR spectra, and mass spectrometry are available 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 2212974 (1), 2213037 (52) and 2213038 (83). Copies of the data can be obtained free of charge via https://www.ccdc.cam.ac.uk/structures/.

References

  1. Toru, T. & Bolm, C. (eds) Organosulfur Chemistry in Asymmetric Synthesis (Wiley, 2008).

  2. Dénès, F., Pichowicz, M., Povie, G. & Renaud, P. Thiyl radicals in organic synthesis. Chem. Rev. 114, 2587–2693 (2014).

    PubMed  Google Scholar 

  3. Dunbar, K. L., Scharf, D. H., Litomska, A. & Hertweck, C. Enzymatic carbon–sulfur bond formation in natural product biosynthesis. Chem. Rev. 117, 5521–5577 (2017).

    CAS  PubMed  Google Scholar 

  4. Wang, N., Saidhareddy, P. & Jiang, X. Construction of sulfur-containing moieties in the total synthesis of natural products. Nat. Prod. Rep. 37, 246–275 (2020).

    PubMed  Google Scholar 

  5. Scott, K. A. & Njardarson, J. T. Analysis of US FDA-approved drugs containing sulfur atoms. Top. Curr. Chem. 376, 5 (2018).

    Google Scholar 

  6. Lamberth, C. Sulfur chemistry in crop protection. J. Sulfur Chem. 25, 39–62 (2004).

    CAS  Google Scholar 

  7. Subramanian, H., Moorthy, R. & Sibi, M. P. Thiyl radicals: from simple radical additions to asymmetric catalysis. Angew. Chem. Int. Ed. 53, 13660–13662 (2014).

    CAS  Google Scholar 

  8. McGarrigle, E. M. et al. Chalcogenides as organocatalysts. Chem. Rev. 107, 5841–5883 (2007).

    CAS  PubMed  Google Scholar 

  9. Mellah, M., Voituriez, A. & Schulz, E. Chiral sulfur ligands for asymmetric catalysis. Chem. Rev. 107, 5133–5209 (2007).

    CAS  PubMed  Google Scholar 

  10. Margalef, J. et al. Evolution in heterodonor P–N, P–S and P–O chiral ligands for preparing efficient catalysts for asymmetric catalysis. From design to applications. Coord. Chem. Rev. 446, 214120 (2021).

    CAS  Google Scholar 

  11. Broderick, J. B., Duffus, B. R., Duschene, K. S. & Shepard, E. M. Radical S-adenosylmethionine enzymes. Chem. Rev. 114, 4229–4317 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Nakai, T. et al. The radical S-adenosyl-l-methionine enzyme QhpD catalyzes sequential formation of intra-protein sulfur-to-methylene carbon thioether bonds. J. Biol. Chem. 290, 11144–11166 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Chauhan, P., Mahajan, S. & Enders, D. Organocatalytic carbon–sulfur bond-forming reactions. Chem. Rev. 114, 8807–8864 (2014).

    CAS  PubMed  Google Scholar 

  14. Kikuchi, J. & Terada, M. Enantioconvergent substitution reactions of racemic electrophiles by organocatalysis. Chem. Eur. J. 27, 10215–10225 (2021).

    CAS  PubMed  Google Scholar 

  15. Zhang, X. & Tan, C.-H. Stereospecific and stereoconvergent nucleophilic substitution reactions at tertiary carbon centers. Chem 7, 1451–1486 (2021).

    CAS  Google Scholar 

  16. Yu, J.-S. et al. Catalytic enantioselective construction of sulfur-containing tetrasubstituted carbon stereocenters. ACS Catal. 6, 5319–5344 (2016).

    CAS  Google Scholar 

  17. Zhu, C., Cai, Y. & Jiang, H. Recent advances for the synthesis of chiral sulfones with the sulfone moiety directly connected to the chiral center. Org. Chem. Front. 8, 5574–5589 (2021).

    CAS  Google Scholar 

  18. Cheng, Q. et al. Iridium-catalyzed asymmetric allylic substitution reactions. Chem. Rev. 119, 1855–1969 (2019).

    ADS  CAS  PubMed  Google Scholar 

  19. Choi, J., Martín-Gago, P. & Fu, G. C. Stereoconvergent arylations and alkenylations of unactivated alkyl electrophiles: catalytic enantioselective synthesis of secondary sulfonamides and sulfones. J. Am. Chem. Soc. 136, 12161–12165 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. He, S.-J. et al. Nickel-catalyzed enantioconvergent reductive hydroalkylation of olefins with α-heteroatom phosphorus or sulfur alkyl electrophiles. J. Am. Chem. Soc. 142, 214–221 (2020).

    CAS  PubMed  Google Scholar 

  21. Xia, X. & Wang, Z. Cr-catalyzed diastereo- and enantioselective synthesis of β-hydroxy sulfides and selenides. ACS Catal. 12, 11152–11158 (2022).

    CAS  Google Scholar 

  22. Sundaravelu, N., Sangeetha, S. & Sekar, G. Metal-catalyzed C–S bond formation using sulfur surrogates. Org. Biomol. Chem. 19, 1459–1482 (2021).

    CAS  PubMed  Google Scholar 

  23. Hegedus, L. L. & McCabe, R. W. Catalyst poisoning. Catal. Rev. Sci. Eng. 23, 377–476 (2007).

    Google Scholar 

  24. Evans, D. A., Miller, S. J., Lectka, T. & von Matt, P. Chiral bis(oxazoline)copper(II) complexes as Lewis acid catalysts for the enantioselective Diels–Alder reaction. J. Am. Chem. Soc. 121, 7559–7573 (1999).

    CAS  Google Scholar 

  25. Trost, B. M., Krische, M. J., Radinov, R. & Zanoni, G. On asymmetric induction in allylic alkylation via enantiotopic facial discrimination. J. Am. Chem. Soc. 118, 6297–6298 (1996).

    CAS  Google Scholar 

  26. Cai, A. & Kleij, A. W. Regio‐ and enantioselective preparation of chiral allylic sulfones featuring elusive quaternary stereocenters. Angew. Chem. Int. Ed. 58, 14944–14949 (2019).

    CAS  Google Scholar 

  27. Khan, A., Zhao, H., Zhang, M., Khan, S. & Zhao, D. Regio- and enantioselective synthesis of sulfone-bearing quaternary carbon stereocenters by Pd-catalyzed allylic substitution. Angew. Chem. Int. Ed. 59, 1340–1345 (2020).

    CAS  Google Scholar 

  28. Zhang, Q., Dong, D. & Zi, W. Palladium-catalyzed regio- and enantioselective hydrosulfonylation of 1,3-dienes with sulfinic acids: scope, mechanism, and origin of selectivity. J. Am. Chem. Soc. 142, 15860–15869 (2020).

    CAS  PubMed  Google Scholar 

  29. Li, M.-M., Cheng, L., Xiao, L.-J., Xie, J.-H. & Zhou, Q.-L. Palladium-catalyzed asymmetric hydrosulfonylation of 1,3-dienes with sulfonyl hydrazides. Angew. Chem. Int. Ed. 60, 2948–2951 (2021).

    CAS  Google Scholar 

  30. Pritzius, A. B. & Breit, B. Asymmetric rhodium-catalyzed addition of thiols to allenes: synthesis of branched allylic thioethers and sulfones. Angew. Chem. Int. Ed. 54, 3121–3125 (2015).

    CAS  Google Scholar 

  31. Yang, X.-H., Davison, R. T. & Dong, V. M. Catalytic hydrothiolation: regio- and enantioselective coupling of thiols and dienes. J. Am. Chem. Soc. 140, 10443–10446 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Han, X., Wang, M., Liang, Y., Zhao, Y. & Shi, Z. Regio- and enantioselective nucleophilic addition to gem-difluoroallenes. Nat. Synth. 1, 227–234 (2022).

    ADS  Google Scholar 

  33. Ueda, M. & Hartwig, J. F. Iridium-catalyzed, regio- and enantioselective allylic substitution with aromatic and aliphatic sulfinates. Org. Lett. 12, 92–94 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. He, Z.-T. & Hartwig, J. F. Enantioselective α-functionalizations of ketones via allylic substitution of silyl enol ethers. Nat. Chem. 11, 177–183 (2019).

    CAS  PubMed  Google Scholar 

  35. Roggen, M. & Carreira, E. M. Enantioselective allylic thioetherification: the effect of phosphoric acid diester on iridium-catalyzed enantioconvergent transformations. Angew. Chem. Int. Ed. 51, 8652–8655 (2012).

    Google Scholar 

  36. Xu, B. et al. Highly enantioselective S–H bond insertion cooperatively catalyzed by dirhodium complexes and chiral spiro phosphoric acids. Chem. Sci. 5, 1442–1448 (2014).

    CAS  Google Scholar 

  37. Cavell, K. J., Hill, J. O. & Magee, R. J. Standard enthalpy of formation of bis(diethyldithiocarbamato)copper(II) at 298 K and the copper–sulphur bond energy. J. Chem. Soc. Dalton Trans. 1638–1640 (1980).

  38. Jarrett, J. T. The biosynthesis of thiol- and thioether-containing cofactors and secondary metabolites catalyzed by radical S-adenosylmethionine enzymes. J. Biol. Chem. 290, 3972–3979 (2015).

    CAS  PubMed  Google Scholar 

  39. Taylor, A. M., Farrar, C. E. & Jarrett, J. T. 9-Mercaptodethiobiotin is formed as a competent catalytic intermediate by Escherichia coli biotin synthase. Biochemistry 47, 9309–9317 (2008).

    CAS  PubMed  Google Scholar 

  40. Cicchillo, R. M. et al. Escherichia coli lipoyl synthase binds two distinct [4Fe–4S] clusters per polypeptide. Biochemistry 43, 11770–11781 (2004).

    CAS  PubMed  Google Scholar 

  41. Grove, T. L. et al. Structural insights into thioether bond formation in the biosynthesis of sactipeptides. J. Am. Chem. Soc. 139, 11734–11744 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. MacMahon, T. J., Jackson, T. C. & Freiser, B. S. A gas-phase study of FeSn+ (n = 1–6). J. Am. Chem. Soc. 111, 421–427 (2002).

    Google Scholar 

  43. He, J. et al. Catalytic decarboxylative radical sulfonylation. Chem 6, 1149–1159 (2020).

    CAS  Google Scholar 

  44. Choi, J. & Fu, G. C. Transition metal–catalyzed alkyl-alkyl bond formation: another dimension in cross-coupling chemistry. Science 356, eaaf7230 (2017).

    PubMed  PubMed Central  Google Scholar 

  45. Cherney, A. H., Kadunce, N. T. & Reisman, S. E. Enantioselective and enantiospecific transition-metal-catalyzed cross-coupling reactions of organometallic reagents to construct C–C bonds. Chem. Rev. 115, 9587–9652 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Dong, X.-Y., Li, Z.-L., Gu, Q.-S. & Liu, X.-Y. Ligand development for copper-catalyzed enantioconvergent radical cross-coupling of racemic alkyl halides. J. Am. Chem. Soc. 144, 17319–17329 (2022).

    CAS  PubMed  Google Scholar 

  47. Dong, X.-Y. et al. A general asymmetric copper-catalysed Sonogashira C(sp3)–C(sp) coupling. Nat. Chem. 11, 1158–1166 (2019).

    CAS  PubMed  Google Scholar 

  48. Wang, F.-L. et al. Mechanism-based ligand design for copper-catalysed enantioconvergent C(sp3)–C(sp) cross-coupling of tertiary electrophiles with alkynes. Nat. Chem. 14, 949–957 (2022).

    CAS  PubMed  Google Scholar 

  49. Zhang, Y.-F. et al. Enantioconvergent Cu-catalyzed radical C–N coupling of racemic secondary alkyl halides to access α-chiral primary amines. J. Am. Chem. Soc. 143, 15413–15419 (2021).

    CAS  PubMed  Google Scholar 

  50. Chen, J.-J. et al. Enantioconvergent Cu-catalysed N-alkylation of aliphatic amines. Nature 618, 294–300 (2023).

  51. Wang, L.-L. et al. A general copper-catalysed enantioconvergent radical Michaelis–Becker-type C(sp3)–P cross-coupling. Nat. Synth. 2, 430–438 (2023).

    ADS  Google Scholar 

  52. Lin, Q. et al. Efficient C(sp3alkyl)–SCF3 bond formations via copper-mediated trifluoromethylthiolation of alkyl halides. Org. Biomol. Chem. 12, 5500–5508 (2014).

  53. Bulman Page, P. C., Wilkes, R. D. & Reynolds, D. in Comprehensive Organic Functional Group Transformations (eds Katritzky, A. R., Meth-Cohn, O., & Rees, C. W.) 113–275 (Elsevier, 1995).

  54. Sladojevich, F., Trabocchi, A., Guarna, A. & Dixon, D. J. A new family of cinchona-derived amino phosphine precatalysts: application to the highly enantio- and diastereoselective silver-catalyzed isocyanoacetate aldol reaction. J. Am. Chem. Soc. 133, 1710–1713 (2011).

    CAS  PubMed  Google Scholar 

  55. Mampuys, P., McElroy, C. R., Clark, J. H., Orru, R. V. A. & Maes, B. U. W. Thiosulfonates as emerging reactants: synthesis and applications. Adv. Synth. Catal. 362, 3–64 (2020).

    CAS  Google Scholar 

  56. Zilbeyaz, K., Oztekin, A. & Kutluana, E. G. Design and synthesis of garlic-related unsymmetrical thiosulfonates as potential Alzheimer’s disease therapeutics: in vitro and in silico study. Bioorg. Med. Chem. 40, 116194 (2021).

    CAS  PubMed  Google Scholar 

  57. Trost, B. M. & Li, C.-J. (eds) Modern Alkyne Chemistry: Catalytic and Atom-Economic Transformations (Wiley, 2015).

  58. Gómez, J. E., Cristòfol, À. & Kleij, A. W. Copper-catalyzed enantioselective construction of tertiary propargylic sulfones. Angew. Chem. Int. Ed. 58, 3903–3907 (2019).

    Google Scholar 

  59. Gao, X., Xiao, Y.-L., Zhang, S., Wu, J. & Zhang, X. Copper-catalyzed enantioselective trifluoromethylthiolation of secondary propargyl sulfonates. CCS Chem. 3, 1463–1471 (2021).

    CAS  Google Scholar 

  60. Liu, L. et al. Copper-catalyzed intermolecular enantioselective radical oxidative C(sp3)–H/C(sp)–H cross-coupling with rationally designed oxazoline-derived N,N,P(O)-ligands. Angew. Chem. Int. Ed. 60, 26710–26717 (2021).

    CAS  Google Scholar 

  61. Su, B., Lee, T. & Hartwig, J. F. Iridium-catalyzed, β-selective C(sp3)–H silylation of aliphatic amines to form silapyrrolidines and 1,2-amino alcohols. J. Am. Chem. Soc. 140, 18032–18038 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Cheng, X., Lu, H. & Lu, Z. Enantioselective benzylic C–H arylation via photoredox and nickel dual catalysis. Nat. Commun. 10, 3549 (2019).

    ADS  PubMed  PubMed Central  Google Scholar 

  63. Kainz, Q. M. et al. Asymmetric copper-catalyzed C–N cross-couplings induced by visible light. Science 351, 681–684 (2016).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  64. Wang, Z., Yin, H. & Fu, G. C. Catalytic enantioconvergent coupling of secondary and tertiary electrophiles with olefins. Nature 563, 379–383 (2018).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  65. Wang, Z., Yang, Z.-P. & Fu, G. C. Quaternary stereocentres via catalytic enantioconvergent nucleophilic substitution reactions of tertiary alkyl halides. Nat. Chem. 13, 236–242 (2021).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  66. Deng, Q.-H., Melen, R. L. & Gade, L. H. Anionic chiral tridentate N-donor pincer ligands in asymmetric catalysis. Acc. Chem. Res. 47, 3162–3173 (2014).

    CAS  PubMed  Google Scholar 

  67. Dong, J., Krasnova, L., Finn, M. G. & Sharpless, K. B. Sulfur(VI) fluoride exchange (SuFEx): another good reaction for click chemistry. Angew. Chem. Int. Ed. 53, 9430–9448 (2014).

    CAS  Google Scholar 

Download references

Acknowledgements

The authors highly appreciate the help of C. Yu and S. Chen from SUSTech in preparing the image of protein CteB in Fig. 1a and the assistance of SUSTech Core Research Facilities. Financial support from the National Natural Science Foundation of China (22025103, 92256301 and 21831002), the National Key R&D Program of China (2021YFF0701604 and 2021YFF0701704), Guangdong Innovative Program (2019BT02Y335), Shenzhen Science and Technology Program (KQTD20210811090112004 and JCYJ20220818100604009), and Shenzhen Special Funds (JCYJ20200109141001789) is gratefully acknowledged. We appreciate the assistance of SUSTech Core Research Facilities. Calculations were performed on the high‐performance computing system at the Department of Chemistry, Zhejiang University.

Author information

Author notes

  1. These authors contributed equally: Yu Tian, Xi-Tao Li, Ji-Ren Liu, Jian Cheng, Ang Gao.

Authors and Affiliations

  1. Shenzhen Grubbs Institute and Department of Chemistry, Southern University of Science and Technology, Shenzhen, China

    Yu Tian, Xi-Tao Li, Ji-Ren Liu, Jian Cheng, Ning-Yuan Yang, Wei Zhang & Xin-Yuan Liu

  2. Shenzhen Key Laboratory of Cross-Coupling Reactions, Southern University of Science and Technology, Shenzhen, China

    Yu Tian & Xin-Yuan Liu

  3. School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, Guangdong, P. R. China

    Xi-Tao Li

  4. Center of Chemistry for Frontier Technologies, Department of Chemistry, State Key Laboratory of Clean Energy Utilization, Zhejiang University, Hangzhou, China

    Ji-Ren Liu & Xin Hong

  5. Academy for Advanced Interdisciplinary Studies and Department of Chemistry, Southern University of Science and Technology, Shenzhen, China

    Ang Gao, Zhuang Li, Kai-Xin Guo, Han-Tao Wen, Zhong-Liang Li & Qiang-Shuai Gu

Authors
  1. Yu Tian
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xi-Tao Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ji-Ren Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jian Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ang Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ning-Yuan Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Zhuang Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kai-Xin Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Wei Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Han-Tao Wen
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Zhong-Liang Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Qiang-Shuai Gu
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Xin Hong
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Xin-Yuan Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Y.T., X.-T.L., J.C. and A.G. designed the experiments and analysed the data. Y.T., X.-T.L., J.C., A.G., N.-Y.Y., Z.L., K.-X.G., W.Z. and H.-T.W. performed the experiments. X.H. designed the DFT calculations. J.-R.L. performed the DFT calculations. Y.T., Z.-L.L., Q.-S.G., and X.-Y.L. wrote the manuscript. X.-Y.L. conceived and supervised the project.

Corresponding author

Correspondence to Xin-Yuan Liu.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer review information

Nature Chemistry thanks Chaozhong Li 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 Figs. 1–17 and Tables 1–13, experimental procedures, synthetic procedures, characterization data, DFT calculations, and mechanistic discussion.

Supplementary Data 1

Crystallographic data for compound 1; CCDC reference 2212974.

Supplementary Data 2

Crystallographic data for compound 52; CCDC reference 2213037.

Supplementary Data 3

Crystallographic data for compound 83; CCDC reference 2213038.

Supplementary Data 4

Tables of energies and coordinates in xyz format.

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

Tian, Y., Li, XT., Liu, JR. et al. A general copper-catalysed enantioconvergent C(sp3)–S cross-coupling via biomimetic radical homolytic substitution. Nat. Chem. 16, 466–475 (2024). https://doi.org/10.1038/s41557-023-01385-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41557-023-01385-w

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