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:

Hydrogen-bond-acceptor ligands enable distal C(sp3)–H arylation of free alcohols

Nature volume 622, pages 80–86 (2023)Cite this article

Subjects

Abstract

The functionalization of C–H bonds in organic molecules is one of the most direct approaches for chemical synthesis. Recent advances in catalysis have allowed native chemical groups such as carboxylic acids, ketones and amines to control and direct C(sp3)–H activation1,2,3,4. However, alcohols, among the most common functionalities in organic chemistry5, have remained intractable because of their low affinity for late transition-metal catalysts6,7. Here we describe ligands that enable alcohol-directed arylation of δ-C(sp3)–H bonds. We use charge balance and a secondary-coordination-sphere hydrogen-bonding interaction—evidenced by structure–activity relationship studies, computational modelling and crystallographic data—to stabilize L-type hydroxyl coordination to palladium, thereby facilitating the assembly of the key C–H cleavage transition state. In contrast to previous studies in C–H activation, in which secondary interactions were used to control selectivity in the context of established reactivity8,9,10,11,12,13, this report demonstrates the feasibility of using secondary interactions to enable challenging, previously unknown reactivity by enhancing substrate–catalyst affinity.

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: Value of, challenges in and strategy for enabling free-alcohol-directed C(sp3)–H activation.
Fig. 2: Model system and ligand optimization.
Fig. 3: Ligand optimization and scope for alcohol-directed δ-arylations of cyclobutanes.
Fig. 4: Evidence for hydrogen bonding.

Similar content being viewed by others

Data availability

Crystallographic data for compounds 4a, 4r, 4am, S21 and S22 are available in the Supplementary Information files and from the Cambridge Crystallographic Data Center under reference numbers CCDC 2115513, CCDC 2263719, CCDC 2263720, CCDC 2265739 and CCDC 2265740, respectively. The structures of Pd complexes C1–C3 (see Supplementary Information) are also provided under reference numbers CCDC 2236162, CCDC 2236161 and CCDC 2236160. All other data supporting the findings of this study are available in the Article and its Supplementary Information files.

References

  1. Chen, Z. et al. Transition metal-catalyzed C–H bond functionalizations by the use of diverse directing groups. Org. Chem. Front. 2, 1107–1295 (2015).

    Article  CAS  Google Scholar 

  2. Sambiagio, C. et al. A comprehensive overview of directing groups applied in metal-catalysed C–H functionalisation chemistry. Chem. Soc. Rev. 47, 6603–6743 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Uttry, A. & van Gemmeren, M. Direct C(sp3)–H activation of carboxylic acids. Synthesis 52, 479–488 (2020).

    Article  CAS  Google Scholar 

  4. Higham, J. I. & Bull, J. A. Transient imine directing groups for the C–H functionalisation of aldehydes, ketones and amines: an update 2018–2020. Org. Biomol. Chem. 18, 7291–7315 (2020).

    Article  CAS  PubMed  Google Scholar 

  5. Ertl, P. & Schuhmann, T. A systematic cheminformatics analysis of functional groups occurring in natural products. J. Nat. Prod. 82, 1258–1263 (2019).

    Article  CAS  PubMed  Google Scholar 

  6. Mo, F., Tabor, J. R. & Dong, G. Alcohols or masked alcohols as directing groups for C–H bond functionalization. Chem. Lett. 43, 264–271 (2014).

    Article  CAS  Google Scholar 

  7. Vicente, J. & Arcas, A. Aqua palladium complexes: synthesis, properties and applications. Coord. Chem. Rev. 249, 1135–1154 (2005).

    Article  CAS  Google Scholar 

  8. Kuninobu, Y., Ida, H., Nishi, M. & Kanai, M. A meta-selective C–H borylation directed by a secondary interaction between ligand and substrate. Nat. Chem. 7, 712–717 (2015).

    Article  CAS  PubMed  Google Scholar 

  9. Hoque, M. E., Bisht, R., Haldar, C. & Chattopadhyay, B. Noncovalent interactions in Ir-catalyzed C–H activation: L-shaped ligand for para-selective borylation of aromatic esters. J. Am. Chem. Soc. 139, 7745–7748 (2017).

    Article  CAS  PubMed  Google Scholar 

  10. Genov, G. R., Douthwaite, J. L., Lahdenperä, A. S. K., Gibson, D. C. & Phipps, R. J. Enantioselective remote C–H activation directed by a chiral cation. Science 367, 1246–1251 (2020).

    Article  ADS  CAS  PubMed  Google Scholar 

  11. Li, G., Yan, Y., Zhang, P., Xu, X. & Jin, Z. Palladium-catalyzed meta-selective C–H functionalization by noncovalent H-bonding interaction. ACS Catal. 11, 10460–10466 (2021).

    Article  CAS  Google Scholar 

  12. Goswami, N. et al. Distal meta-alkenylation of formal amines enabled by catalytic use of hydrogen-bonding anionic ligands. Chem 9, 989–1003 (2023).

    Article  CAS  Google Scholar 

  13. Mondal, A., Díaz-Ruiz, M., Deufel, F., Maseras, F. & van Gemmeren, M. Charge-controlled Pd catalysis enables the meta-C–H activation and olefination of arenes. Chem 9, 1004–1016 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Abrams, D. J., Provencher, P. A. & Sorensen, E. J. Recent applications of C–H functionalization in complex natural product synthesis. Chem. Soc. Rev. 47, 8925–8967 (2018).

    Article  CAS  PubMed  Google Scholar 

  15. Lam, N. Y. S., Wu, K. & Yu, J.-Q. Advancing the logic of chemical synthesis: C–H activation as strategic and tactical disconnections for C–C bond construction. Angew. Chem. Int. Ed. 60, 15767–15790 (2021).

    Article  CAS  Google Scholar 

  16. Shao, Q., Wu, K., Zhuang, Z., Qian, S. & Yu, J.-Q. From Pd(OAc)2 to chiral catalysts: The discovery and development of bifunctional mono-N-protected amino acid ligands for diverse C–H functionalization reactions. Acc. Chem. Res. 53, 833–851 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Lucas, E. L. et al. Palladium-catalyzed enantioselective β-C(sp3)–H activation reactions of aliphatic acids: A retrosynthetic surrogate for enolate alkylation and conjugate addition. Acc. Chem. Res. 55, 537–550 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Park, H., Chekshin, N., Shen, P.-X. & Yu, J.-Q. Ligand-enabled, palladium-catalyzed β-C(sp3)–H arylation of Weinreb amides. ACS Catal. 8, 9292–9297 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Hoveyda, A. H., Evans, D. A. & Fu, G. C. Substrate-directable chemical reactions. Chem. Rev. 93, 1307–1370 (1993).

    Article  CAS  Google Scholar 

  20. Terao, Y., Wakui, H., Satoh, T., Miura, M. & Nomura, M. Palladium-catalyzed arylative carbon–carbon bond cleavage of α,α-disubstituted arylmethanols. J. Am. Chem. Soc. 123, 10407–10408 (2001).

    Article  CAS  PubMed  Google Scholar 

  21. Terao, Y. et al. Palladium-catalyzed arylation of α,α-disubstituted arylmethanols via cleavage of a C–C or a C–H bond to give biaryls. J. Org. Chem. 68, 5236–5243 (2003).

    Article  CAS  PubMed  Google Scholar 

  22. Lu, Y., Wang, D.-H., Engle, K. M. & Yu, J.-Q. Pd(II)-catalyzed hydroxyl-directed C–H olefination enabled by monoprotected amino acid ligands. J. Am. Chem. Soc. 132, 5916–5921 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Wang, X., Lu, Y., Dai, H.-X. & Yu, J.-Q. Pd(II)-catalyzed hydroxyl-directed C–H activation/C–O cyclization: Expedient construction of dihydrobenzofurans. J. Am. Chem. Soc. 132, 12203–12205 (2010).

    Article  CAS  PubMed  Google Scholar 

  24. Lu, Y., Leow, D., Wang, X., Engle, K. M. & Yu, J.-Q. Hydroxyl-directed C–H carbonylation enabled by mono-N-protected amino acid ligands: an expedient route to 1-isochromanones. Chem. Sci. 2, 967–971 (2011).

    Article  CAS  Google Scholar 

  25. Wen, Z.-K., Xu, Y.-H. & Loh, T.-P. Palladium-catalyzed cross-coupling of unactivated alkenes with acrylates: Application to the synthesis of the C13–C21 fragment of Palmerolide A. Chem. Eur. J. 42, 13284–13287 (2012).

    Article  Google Scholar 

  26. Kandukuri, S. R., Jiao, L.-Y., Machotta, A. B. & Oestreich, M. Diastereotopic group selection in hydroxy-directed intramolecular C–H alkenylation of indole under oxidative palladium(II) catalysis. Adv. Synth. Catal. 356, 1597–1609 (2014).

    Article  CAS  Google Scholar 

  27. Liang, Q.-J. et al. Chelation versus non-chelation control in the stereoselective alkenyl sp2 C–H bond functionalization reaction. Angew. Chem. Int. Ed. 56, 5091–5095 (2017).

    Article  CAS  Google Scholar 

  28. Li, L., Liu, Q., Chen, J. & Huang, Y. Alcohol-directed ortho-C–H alkenylation. Synlett 30, 1366–1370 (2019).

    Article  CAS  Google Scholar 

  29. Meng, K. et al. Geminal group-directed olefinic C–H functionalization via four- to eight-membered exo-metallocycles. Nat. Commun. 10, 5109 (2019).

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  30. Ghiringhelli, F., Uttry, A., Ghosh, K. K. & van Gemmeren, M. Direct β- and γ-C(sp3)–H alkynylation of free carboxylic acids. Angew. Chem. Int. Ed. 59, 23127–23131 (2020).

    Article  CAS  Google Scholar 

  31. Bryndza, H. E. & Tam, W. Monomeric metal hydroxides, alkoxides, and amides of the late transition metals: Synthesis, reactions, and thermochemistry. Chem. Rev. 88, 1163–1188 (1988).

    Article  CAS  Google Scholar 

  32. Fernández-Rivas, C. et al. Synthesis and structure of new oxapalladacycles with a Pd–O bond. Organometallics 20, 2998–3006 (2001).

    Article  Google Scholar 

  33. Sigman, M. S. & Schultz, M. J. The renaissance of palladium(II)-catalyzed oxidation chemistry. Org. Biomol. Chem. 2, 2551–2554 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Xia, G. et al. Reversing conventional site-selectivity in C(sp3)–H bond activation. Nat. Chem. 11, 571–577 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Tanka, K., Ewing, W. R. & Yu, J.-Q. Hemilabile benzyl ether enables γ-C(sp3)–H carbonylation and olefination of alcohols. J. Am. Chem. Soc. 2019, 15494–15497 (2019).

    Article  Google Scholar 

  36. Xia, G. et al. Ligand-enabled β-methylene C(sp3)–H arylation of masked aliphatic alcohols. Angew. Chem., Int. Ed. 59, 7783–7787 (2020).

    Article  CAS  Google Scholar 

  37. Salamanca, V., Toledo, A. & Albéniz, A. C. [2,2’-Bipyridin]-6(1H)-one, a truly cooperating ligand in the palladium-mediated C–H activation step: experimental evidence in the direct C-3 arylation of pyridine. J. Am. Chem. Soc. 140, 17851–17856 (2018).

    Article  CAS  PubMed  Google Scholar 

  38. Li, Z. et al. A tautomeric ligand enables directed C–H hydroxylation with molecular oxygen. Science 372, 1452–1457 (2021).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  39. Li, Z., Park, H. S., Qiao, J. X., Yeung, K.-S. & Yu, J.-Q. Ligand-enabled C–H hydroxylation with aqueous H2O2 at room temperature. J. Am. Chem. Soc. 144, 18109–18116 (2022).

    Article  CAS  PubMed  Google Scholar 

  40. Saint-Denis, T. G. et al. Mechanistic study of enantioselective Pd-catalyzed C(sp3)–H activation of thioethers involving two distinct stereomodels. ACS Catal. 11, 9738–9753 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Drover, M. W. A guide to secondary coordination sphere editing. Chem. Soc. Rev. 51, 1861–1880 (2022).

    Article  CAS  PubMed  Google Scholar 

  42. Wimmer, F. L., Wimmer, S., Afcharian, A., Castan, P. & Fabre, P. L. Acid dissociation and dimerization constants of some cis-diaqua complexes of palladium(II) with chelating N, N’ and N, C’ ligands. J. Chem. Res. Synop. 194–195 (1999).

  43. Alsters, P. L., Boersma, J., Smeets, W. J. J., Spek, A. L. & van Koten, G. Arylpalladium compounds containing an alcohol functionality: Hindered rotation around the Pd–C bond and reactivity toward styrene and carbon monoxide. Comments on carbon–oxygen bond shortening in late-transition-metal alkoxides. Organometallics 12, 1639–1647 (1993).

    Article  CAS  Google Scholar 

  44. Jie, S., Ai, P., Zhou, Q. & Li, B.-G. Nickel and cationic palladium complexes bearing (imino)pyridyl alcohol ligands: Synthesis, characterization and vinyl polymerization of norbornene. J. Organomet. Chem. 696, 1465–1473 (2011).

    Article  CAS  Google Scholar 

  45. Reek, J. N. H. et al. Transition metal catalysis controlled by hydrogen bonding in the second coordination sphere. Chem. Rev. 122, 12308–12369 (2022).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  46. Farizyan, M., Mondal, A., Mal, S., Deufel, F. & van Gemmeren, M. Palladium-catalyzed nondirected late-stage C–H deuteration of arenes. J. Am. Chem. Soc. 143, 16370–16373 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. van der Kolk, M. R., Janssen, M. A. C. H., Rutjes, F. P. J. T. & Blanco-Ania, D. Cyclobutanes in small-molecule drug candidates. ChemMedChem 17, e202200020 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  48. Frank, N. et al. Synthesis of meta-substituted arene bioisosteres from [3.1.1]propellane. Nature 611, 721–726 (2022).

    Article  ADS  CAS  PubMed  Google Scholar 

  49. Wang, Z. et al. Ligand-controlled divergent dehydrogenative reactions of carboxylic acids via C–H activation. Science 374, 1281–1285 (2021).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  50. Cockroft, S. L. & Hunter, C. A. Chemical double-mutant cycles: dissecting non-covalent interactions. Chem. Soc. Rev. 36, 172–188 (2007).

    Article  CAS  PubMed  Google Scholar 

  51. Brazzolotto, D., Bogart, J. A., Ross, D. L., Ziller, J. W. & Borovik, A. S. Stabilizing a NiII-aqua complex via intramolecular hydrogen bonds: synthesis, structure, and redox properties. Inorg. Chim. Acta 495, 118960 (2019).

    Article  CAS  Google Scholar 

  52. Knowles, R. R. & Jacobsen, E. N. Attractive noncovalent interactions in asymmetric catalysis: Links between enzymes and small molecule catalysts. Proc. Natl Acad. Sci. USA 107, 20678–20685 (2010).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  53. Davis, H. J. & Phipps, R. J. Harnessing non-covalent interactions to exert control over regioselectivity and site-selectivity in catalytic reactions. Chem. Sci. 8, 864–877 (2017).

    Article  CAS  PubMed  Google Scholar 

  54. Neel, A. J., Hilton, M. J., Sigman, M. S. & Toste, F. D. Exploiting non-covalent π interactions for catalyst design. Nature 543, 637–646 (2017).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  55. Hwang, J., Mercado, B. O. & Miller, S. J. Chirality-matched catalyst-controlled macrocyclization reactions. Proc. Natl Acad. Sci. USA 118, e2113122118 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank the Scripps Research Institute, the NIH (National Institute of General Medical Sciences grants R01 GM084019 and F32 GM143921) and the Jennifer and Dallas Luttrell Endowed Fellowship in the Skaggs Graduate School of Chemical and Biological Sciences for their financial support. The content is solely our responsibility and does not necessarily represent the official views of the National Institutes of Health. We thank K. Wu for assistance with automated conformational searches and for numerous discussions throughout the course of this project; M. Gembicky, J. Bailey, E. Samolova and the UCSD Crystallography Facility for X-ray crystallographic analysis; L. Pasternack, D.-H. Huang and G. Kroon of the Nuclear Magnetic Resonance Facility of the Scripps Researcher Services for their assistance with NMR analysis; B. Webb and E. Billings of the Scripps Center for Metabolomics and Mass Spectrometry and J. Chen, B. Sanchez and Q. N. Wong of the Scripps Automated Synthesis Facility for assistance with mass spectrometry. We acknowledge the group of M. van Gemmeren for taking the time to independently verify the reproducibility of the results obtained in this study.

Author information

Author notes

  1. These authors contributed equally: Daniel A. Strassfeld, Chia-Yu Chen

Authors and Affiliations

  1. Department of Chemistry, The Scripps Research Institute, La Jolla, CA, USA

    Daniel A. Strassfeld, Chia-Yu Chen, Han Seul Park, D. Quang Phan & Jin-Quan Yu

Authors
  1. Daniel A. Strassfeld
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chia-Yu Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Han Seul Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. D. Quang Phan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jin-Quan Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

D.A.S. and J.-Q.Y. conceived of the project. D.A.S. developed the arylation of benzylic C–H bonds. D.A.S. and C.-Y.C. developed the arylation of cyclobutyl substrates and C.-Y.C. performed scope studies for the cyclobutyl system. H.S.P. developed the pyridone–sulfonamide ligands and performed scope studies on the benzylic arylation. D.Q.P. developed the acyl-sulfonamide ligands. D.A.S. performed the DFT studies. D.A.S. and J.-Q.Y. prepared the paper. J.-Q.Y. directed the project.

Corresponding author

Correspondence to Jin-Quan Yu.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer review information

Nature thanks Manuel van Gemmeren and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Peer reviewer reports are available.

Additional information

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

Extended data figures and tables

Extended Data Fig. 1 Aryl iodide scope with quaternized cyclobutane alcohol 3q.

Reactions were run according to General Procedure B. The reported yields are for isolated and purified products.

Extended Data Fig. 2 Poorly performing aryl iodides and alcohol substrates.

Due to the extremely low yields or lack of detectable product formation in most of these reactions, we were unable to isolate analytically pure samples of products except where specifically noted A) Poorly performing aryl iodides. Reactions were run according to General Procedure B with modifications as indicated. Aryl iodide screening was performed using either alcohol 3q (for 1-chloro-2-iodobenzene and 1-bromo-2-iodobenzene) or alcohol 3a (for the remaining aryl iodides) as the substrate. B) Poorly performing alcohol substrates. Alcohol screening was performed using methyl-4-iodobenzoate as the coupling partner. Bolded bonds indicate relative stereochemistry. C) Products isolated in low yields from reactions run with linear alcohols. §12 mol% L27 used. &Reaction run at 0.1 M. #Reactions were run according to General Procedure A using L24 as the ligand. ^Based on crude NMR vs. CH2Br2 internal standard. *Reaction run using 0.1 mmol of methyl-4-iodobenzoate as the limiting reagent (0.1 M in DCE) with 10 equivalents of the alcohol substrate.

Extended Data Fig. 3 Logic of double mutant cycle experiments.

Double mutant cycles are a classic tool used to quantify the energy of a non-covalent interaction of interest in a complex setting, including enzyme-substrate binding and fully synthetic systems such as molecular balances and zippers50. The interaction under investigation is perturbed by removing each interacting partner (here the HBD and HBA) both individually (affording a pair of single mutants) and simultaneously (to give the double mutant). Each of these modifications will affect more than just the proposed H-bonding interaction, but the non-cooperative effects can be cancelled by adding and subtracting the energies of the four species using the equation in the figure above. The resulting energy will reflect differences in cooperative interactions between the two interacting partners across the four structures. Ideally, each mutation would fully knock out the interaction under investigation without creating any new interactions with the other partner, in which case the equation would directly report the (de)stabilization due to the interaction under investigation in the parent system. In practice, however, it can be difficult to design modifications which meet these criteria since there are many ways in which the mutated substituents could still interact cooperatively (e.g., other non-covalent interactions like dipole-dipole interactions or steric clash, or via through-bond effects, such as changes in the Lewis acidity of the metal center). Thus, double mutant cycles must be designed carefully to ensure that they provide information about the interaction of interest rather than other cooperative interactions. To address the potential for confounding factors, we have calculated four double mutant cycles each for TS-1, TS-δ-1, TS-cis-γ-1, and TS-trans-γ-1 (see Extended Data Fig. 4 and Figs. S78, S83, and S88 for details, discussion, and tabulated energies and Figs. 4e and S71–S77, S79–S82, and S84–S87 for the actual cycles) employing different mutations designed to have very different potential confounding factors. The qualitative agreement between these models provides strong support for significant stabilization by the proposed H-bonding interaction.

Extended Data Fig. 4 Summary of computational double mutant cycles examined for benzylic C–H activation.

A) The HBA can be knocked out by replacing the acyl sulfonamide with a carboxylate or an amidate. The amidate preserves the identity of the chelating atom, but may significantly alter the electronics at Pd, whereas the carboxylate is more similar to the acyl sulfonamide electronically but changes the atom bound to Pd. B) The HBD can be knocked out by replacing the directing group with a methyl ether or an alkoxide. The methyl ether preserves the charge and nature of the directing group, but significantly alters the steric properties of the directing group, whereas the alkoxide significantly alters the electronic character of the directing group, but presents a similar steric profile to the alcohol. C) Tabulated data for the four cycles generated by the pairwise combinations of the ligand and substrate mutations described above (the tabulated data is taken from the cycles shown in Figs. 4e and S71–S73). While there are modest quantitative differences in the interaction energy measured for each cycle, they are all in qualitative agreement on the stabilization afforded by the interaction between the alcohol and the sulfonamide. Since the four cycles were chosen to have different potential confounding factors, the qualitative agreement strongly suggests that the observed stabilization is due at least in large part to the proposed H-bonding interaction.

Supplementary information

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

Strassfeld, D.A., Chen, CY., Park, H.S. et al. Hydrogen-bond-acceptor ligands enable distal C(sp3)–H arylation of free alcohols. Nature 622, 80–86 (2023). https://doi.org/10.1038/s41586-023-06485-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41586-023-06485-8

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

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