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.

A heterogeneous iridium single-atom-site catalyst for highly regioselective carbenoid O–H bond insertion

Abstract

Transition-metal-catalysed carbenoid insertion of hydroxyl groups represents a robust and versatile method to forge C–O bonds. Achieving site-selective functionalization of alcohols using this transformation has undoubted synthetic value but remains challenging. Here we report a strategy for selective carbenoid O–H insertion that exploits an engineered heterogeneous iridium single-atom catalyst, thus providing opportunities for organic transformations by merging material science and catalysis. This catalytic protocol delivers excellent selectivities (up to 99:1) for the functionalization of aliphatic over phenolic O–H bonds, whereas the analogous homogeneous catalyst, Ir(ttp)COCl (ttp = 5,10,15,20-tetra-p-tolylporphyrinato), provided modest preferences. Density-functional-theory calculations suggest that the site-selectivity derives from the lower oxidation state of the iridium metal centre in the heterogeneous catalyst and its impact on the absorption energies of the reactants. These results showcase an example of a heterogeneous single-atom catalyst providing superior site-selectivity and provide a complementary strategy to address challenges in catalysis for organic synthesis.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

Fig. 1: Synthesis and structural characterizations.
Fig. 2: Atomic structural analysis of the Ir-SA catalyst.
Fig. 3: Performance of Ir-SA-catalysed O–H carbenoid insertion.
Fig. 4: Mechanistic studies by DFT calculations.

Similar content being viewed by others

Data availability

Data relating to the characterization data of materials (TEM, STEM, XANES, EXAFS, XPS, X-ray diffraction), general methods, experimental procedures, mechanistic studies, DFT computational studies, mass spectrometry and NMR spectra are available in the Supplementary Information or from the corresponding authors upon reasonable reuqest.

References

  1. Doyle, M. P. Catalytic methods for metal carbene transformations. Chem. Rev. 86, 919–939 (1986).

    Article  CAS  Google Scholar 

  2. Gillingham, D. & Fei, N. Catalytic X–H insertion reactions based on carbenoids. Chem. Soc. Rev. 42, 4918–4931 (2013).

    Article  CAS  PubMed  Google Scholar 

  3. Davies, H. M. L. & Manning, J. R. Catalytic C–H functionalization by metal carbenoid and nitrenoid insertion. Nature 451, 417–424 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Zhu, S. F. & Zhou, Q. L. Transition-metal-catalyzed enantioselective heteroatom–hydrogen bond insertion reactions. Acc. Chem. Res. 45, 1365–1377 (2012).

    Article  CAS  PubMed  Google Scholar 

  5. Davies, H. M. L. & Denton, J. R. Application of donor/acceptor-carbenoids to the synthesis of natural products. Chem. Soc. Rev. 38, 3061–3071 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Davies, H. M. L. & Hedley, S. J. Intermolecular reactions of electron-rich heterocycles with copper and rhodium carbenoids. Chem. Soc. Rev. 36, 1109–1119 (2007).

    Article  CAS  PubMed  Google Scholar 

  7. Qian, D. & Zhang, J. Gold-catalyzed cyclopropanation reactions using a carbenoid precursor toolbox. Chem. Soc. Rev. 44, 677–698 (2015).

    Article  CAS  PubMed  Google Scholar 

  8. Xia, Y., Qiu, D. & Wang, J. Transition-metal-catalyzed cross-couplings through carbene migratory insertion. Chem. Rev. 117, 13810–13889 (2017).

    Article  CAS  PubMed  Google Scholar 

  9. Xiang, Y., Wang, C., Ding, Q. & Peng, Y. Diazo compounds: versatile synthons for the synthesis of nitrogen heterocycles via transition metal-catalyzed cascade C–H activation/carbene insertion/annulation reactions. Curr. Org. Synth. 361, 919–944 (2019).

    CAS  Google Scholar 

  10. Gois, P. M. P. & Afonso, C. A. M. Stereo- and regiocontrol in the formation of lactams by rhodium–carbenoid C–H insertion of α-diazoacetamides. Eur. J. Org. Chem. 18, 3773–3788 (2004).

    Article  Google Scholar 

  11. Wee, A. G. H. Rhodium (ii)-catalyzed reaction of diazocompounds in the service of organic synthesis of natural and non-natural products. Curr. Org. Synth. 3, 499–555 (2006).

    Article  CAS  Google Scholar 

  12. Maas, G. Ruthenium-catalysed carbenoid cyclopropanation reactions with diazo compounds. Chem. Soc. Rev. 33, 183–190 (2004).

    Article  CAS  PubMed  Google Scholar 

  13. Ye, T. & McKervey, M. A. Organic synthesis with α-diazo carbonyl compounds. Chem. Rev. 94, 1091–1160 (1994).

    Article  CAS  Google Scholar 

  14. DeAngelis, A., Panish, R. & Fox, J. M. Rh-catalyzed intermolecular reactions of α-alkyl-α-diazo carbonyl compounds with selectivity over β-hydride migration. Acc. Chem. Res. 49, 115–127 (2016).

    Article  CAS  PubMed  Google Scholar 

  15. Xiao, Q., Zhang, Y. & Wang, J. B. Diazo compounds and N-tosylhydrazones: novel cross-coupling partners in transition-metal-catalyzed reactions. Acc. Chem. Res. 46, 236–247 (2013).

    Article  CAS  PubMed  Google Scholar 

  16. Padwa, A., Krumpe, K. E., Gareau, Y. & Chiacchio, U. Rhodium (ii)-catalyzed cyclization reactions of alkynyl-substituted α-diazo ketones. J. Org. Chem. 56, 2523–2530 (1991).

    Article  CAS  Google Scholar 

  17. Padwa, A., Cheng, B. & Zou, Y. Natural product synthesis via the rhodium carbenoid-mediated cyclization of α-diazo carbonyl compounds. Aust. J. Chem. 67, 343–353 (2014).

    Article  CAS  Google Scholar 

  18. Doyle, M. P. Chiral catalysts for enantioselective carbenoid cyclopropanation reactions. Rec. Trav. Chim. Pays-Bas 110, 305–316 (1991).

    Article  CAS  Google Scholar 

  19. DeAngelis, A., Dmitrenko, O. & Fox, J. M. Rh-catalyzed intermolecular reactions of cyclic α-diazocarbonyl compounds with selectivity over tertiary C−H bond migration. J. Am. Chem. Soc. 134, 11035–11043 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Che, J., Niu, L., Jia, S., Xing, D. & Hu, W. Enantioselective three-component aminomethylation of α-diazo ketones with alcohols and 1,3,5-triazines. Nat. Commun. 11, 1511 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Yang, J., Ke, C., Zhang, D., Liu, X. & Feng, X. Enantioselective synthesis of 2,2,3-trisubstituted indolines via bimetallic relay catalysis of α-diazoketones with enones. Org. Lett. 20, 4536–4539 (2018).

    Article  CAS  PubMed  Google Scholar 

  22. Li, M.-L., Yu, J.-H., Li, Y.-H., Zhu, S.-F. & Zhou, Q.-L. Highly enantioselective carbene insertion into N–H bonds of aliphatic amines. Science 366, 990–994 (2019).

    Article  CAS  PubMed  Google Scholar 

  23. Garlets, Z. J. et al. Enantioselective C–H functionalization of bicyclo[1.1.1]pentanes. Nat. Catal. 3, 351–357 (2020).

    Article  CAS  Google Scholar 

  24. Chamni, S. et al. Diazo reagents with small steric footprints for simultaneous arming/SAR studies of alcohol-containing natural products via O–H insertion. ACS Chem. Biol. 6, 1175–1181 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Wu, J. et al. Site-selective and stereoselective O‑alkylation of glycosides by Rh (ii)-catalyzed carbenoid insertion. J. Am. Chem. Soc. 141, 19902–19910 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Liu, L. & Corma, A. Metal catalysts for heterogeneous catalysis: from single atoms to nanoclusters and nanoparticles. Chem. Rev. 118, 4981–5079 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Wang, A., Li, J. & Zhang, T. Heterogeneous single-atom catalysis. Nat. Rev. Chem. 2, 65–81 (2018).

    Article  CAS  Google Scholar 

  28. Cui, X., Li, W., Ryabchuk, P., Junge, K. & Beller, M. Bridging homogeneous and heterogeneous catalysis by heterogeneous single-metal-site catalysts. Nat. Catal. 1, 385–397 (2018).

    Article  CAS  Google Scholar 

  29. Yang, X. et al. Single-atom catalysts: a new frontier in heterogeneous catalysis. Acc. Chem. Res. 46, 1740–1748 (2013).

    Article  CAS  PubMed  Google Scholar 

  30. Zhu, W. & Chen, C. Reaction: open up the era of atomically precise catalysis. Chem 5, 2737–2739 (2019).

    Article  CAS  Google Scholar 

  31. Guo, X. et al. Direct, nonoxidative conversion of methane to ethylene, aromatics, and hydrogen. Science 344, 616–619 (2014).

    Article  CAS  PubMed  Google Scholar 

  32. Hwang, K. C. & Sagadevan, A. One-pot room-temperature conversion of cyclohexane to adipic acid by ozone and UV light. Science 346, 1495–1498 (2014).

    Article  CAS  PubMed  Google Scholar 

  33. Liu, P. et al. Photochemical route for synthesizing atomically dispersed palladium catalysts. Science 352, 797–801 (2016).

    Article  CAS  PubMed  Google Scholar 

  34. Ji, S. et al. Rare-earth single erbium atoms for enhanced photocatalytic CO2 reduction. Angew. Chem. Int. Ed. 59, 10651–10657 (2020).

    Article  CAS  Google Scholar 

  35. Tian, S. et al. Single-atom Fe with Fe1N3 structure showing superior performances for both hydrogenation and transfer hydrogenation of nitrobenzene. Sci. China Mater. 64, 642–650 (2020).

    Article  Google Scholar 

  36. Ji, S. et al. Chemical synthesis of single atomic site catalysts. Chem. Rev. 120, 11900–11955 (2020).

    Article  CAS  PubMed  Google Scholar 

  37. Jones, J. et al. Thermally stable single-atom platinum-on-ceria catalysts via atom trapping. Science 353, 150–154 (2016).

    Article  CAS  PubMed  Google Scholar 

  38. Qiao, B. et al. Single-atom catalysis of CO oxidation using Pt1/FeOx. Nat. Chem. 3, 634–641 (2011).

    Article  CAS  PubMed  Google Scholar 

  39. Lin, L. et al. Low-temperature hydrogen production from water and methanol using Pt/α-MoC catalysts. Nature 544, 80–83 (2017).

    Article  CAS  PubMed  Google Scholar 

  40. Malta, G. et al. Identification of single-site gold catalysis in acetylene hydrochlorination. Science 355, 1399–1403 (2017).

    Article  CAS  PubMed  Google Scholar 

  41. Li, X., Rong, H., Zhang, J., Wang, D. & Li, Y. Modulating the local coordination environment of single-atom catalysts for enhanced catalytic performance. Nano Res. 13, 1842–1855 (2020).

    Article  CAS  Google Scholar 

  42. Fernández, E. et al. Base-controlled Heck, Suzuki, and Sonogashira reactions catalyzed by ligand-free platinum or palladium single atom and sub-nanometer clusters. J. Am. Chem. Soc. 141, 1928–1940 (2019).

    Article  PubMed  Google Scholar 

  43. Sun, T., Xu, L., Wang, D. & Li, Y. Metal organic frameworks derived single atom catalysts for electrocatalytic energy conversion. Nano Res. 12, 2067–2080 (2019).

    Article  CAS  Google Scholar 

  44. Beniya, A. & Higashi, S. Towards dense single-atom catalysts for future automotive applications. Nat. Catal. 2, 590–602 (2019).

    Article  Google Scholar 

  45. Xu, Q. et al. Coordination structure dominated performance of single-atomic Pt catalyst for anti-Markovnikov hydroboration of alkenes. Sci. China Mater. 63, 972–981 (2020).

    Article  CAS  Google Scholar 

  46. Daelman, N., Capdevila-Cortada, M. & Lopez, N. Dynamic charge and oxidation state of Pt/CeO2 single-atom catalysts. Nat. Mater. 18, 1215–1221 (2019).

    Article  CAS  PubMed  Google Scholar 

  47. DeRita, L. et al. Structural evolution of atomically dispersed Pt catalysts dictates reactivity. Nat. Mater. 18, 746–751 (2019).

    Article  CAS  PubMed  Google Scholar 

  48. Lu, Y. et al. Identification of the active complex for CO oxidation over single-atom Ir-on-MgAl2O4 catalysts. Nat. Catal. 2, 149–156 (2018).

    Article  Google Scholar 

  49. Zhuang, Z., Kang, Q., Wang, D. & Li, Y. Single-atom catalysis enables long-life, high-energy lithium-sulfur batteries. Nano Res. 13, 1856–1866 (2020).

    Article  CAS  Google Scholar 

  50. Shang, H. et al. Engineering isolated Mn–N2C2 atomic interface sites for efficient bifunctional oxygen reduction and evolution reaction. Nano Lett. 20, 5443–5450 (2020).

    Article  CAS  PubMed  Google Scholar 

  51. Lee, B.-H. et al. Reversible and cooperative photoactivation of single-atom Cu/TiO2 photocatalysts. Nat. Mater. 18, 620–626 (2019).

    Article  CAS  PubMed  Google Scholar 

  52. Mao, J. et al. Isolated Ni atoms dispersed on Ru nanosheets: high-performance electrocatalysts toward hydrogen oxidation reaction. Nano Lett. 20, 3442–3448 (2020).

    Article  CAS  PubMed  Google Scholar 

  53. Cao, L. et al. Identification of single-atom active sites in carbon-based cobalt catalysts during electrocatalytic hydrogen evolution. Nat. Catal. 2, 134–141 (2019).

    Article  CAS  Google Scholar 

  54. Chung, H. T. et al. Direct atomic-level insight into the active sites of a high-performance PGM-free ORR catalyst. Science 357, 479–484 (2017).

    Article  CAS  PubMed  Google Scholar 

  55. Gu, J., Hsu, C. S., Bai, L., Chen, H. M. & Hu, X. Atomically dispersed Fe3+ sites catalyze efficient CO2 electroreduction to CO. Science 364, 1091–1094 (2019).

    Article  CAS  PubMed  Google Scholar 

  56. Chen, Z. et al. A heterogeneous single-atom palladium catalyst surpassing homogeneous systems for Suzuki coupling. Nat. Nanotechnol. 13, 702–707 (2018).

    Article  CAS  PubMed  Google Scholar 

  57. Xiao, M. et al. A single-atom iridium heterogeneous catalyst in oxygen reduction reaction. Angew. Chem. Int. Ed. 58, 9640–9645 (2019).

    Article  CAS  Google Scholar 

  58. Cui, H. et al. A stable and porous iridium(iii)–porphyrin metal–organic framework: synthesis, structure and catalysis. CrystEngComm 18, 2203–2209 (2016).

    Article  CAS  Google Scholar 

  59. Anding, B. J., Dairo, T. O. & Woo, L. K. Reactivity comparison of primary aromatic amines and thiols in E–H insertion reactions with diazoacetates catalyzed by iridium(iii) tetratolylporphyrin. Organometallics 36, 1842–1847 (2017).

    Article  CAS  Google Scholar 

  60. Ravel, B. & Newville, M. ATHENA, ARTEMIS, HEPHAESTUS: data analysis for X-ray absorption spectroscopy using IFEFFIT. J. Synchrotron Radiat. 12, 537–541 (2005).

    Article  CAS  PubMed  Google Scholar 

  61. Ankudinov, A. L., Ravel, B. & Rehr, S. D. Real-space multiple-scattering calculation and interpretation of X-ray-absorption near-edge structure. Phys. Rev. B 58, 7565–7576 (1998).

    Article  CAS  Google Scholar 

  62. Zhang, Y. K. & Yang, W. Comment on ‘Generalized gradient approximation made simple’. Phys. Rev. Lett. 80, 890 (1998).

    Article  CAS  Google Scholar 

  63. Henkelman, G., Uberuaga, B. P. & Hannes, J. A climbing image nudged elastic band method for finding saddle points and minimum energy paths. J. Chem. Phys. 113, 9901–9904 (2000).

    Article  CAS  Google Scholar 

  64. Cao, X. M., Burch, R., Hardacre, C. & Hu, P. An understanding of chemoselective hydrogenation on crotonaldehyde over Pt(111) in the free energy landscape: the microkinetics study based on first-principles calculations. Catal. Today 165, 71–79 (2011).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

J.Z. acknowledges support from the Shanghai Municipal Science and Technology Major Project (2018SHZDZX03) and the Program of Introducing Talents of Discipline to Universities (B16017). S.J., D.W. and Y L. acknowledge the National Key R&D Program of China (2018YFA0702003) and the National Natural Science Foundation of China (21890383). They thank the BL14W1 station in Shanghai Synchrotron Radiation Facility (SSRF). J.D. acknowledges the Youth Innovation Promotion Association of Chinese Academy of Sciences (2018017). F.D.T. acknowledges support by the Director, Office of Science, Office of Basic Energy Science and the Division of Chemical Sciences, Geosciences, and Bioscience of the US Department of Energy at Lawrence Berkeley National Laboratory (grant DE-AC0205CH1123). We thank B. Ye from ShanghaiTech University for helpful discussions.

Author information

Authors and Affiliations

Authors

Contributions

J.Z., S.J. and P.G. performed most of the experiments, analysed the experimental data and co-wrote the paper. C.G. performed computational studies, analysed the computational data and co-wrote the paper. H.L. and J.D. helped to collect and analyse the XAFS data. J.Z., D.W., Y.L. and F.D.T. designed and guided the research, and co-wrote the paper. All the authors discussed the results and contributed to writing the manuscript.

Corresponding authors

Correspondence to Jie Zhao, Dingsheng Wang or F. Dean Toste.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Peer review information Nature Catalysis thanks T. Shishido, J. Wang and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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

Supplementary information

Supplementary Information

Supplementary Figs. 1–41, Tables 1–6, methods, discussions, NMR spectra, references.

Supplementary Data

DFT coordinates for optimized structures

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhao, J., Ji, S., Guo, C. et al. A heterogeneous iridium single-atom-site catalyst for highly regioselective carbenoid O–H bond insertion. Nat Catal 4, 523–531 (2021). https://doi.org/10.1038/s41929-021-00637-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41929-021-00637-7

This article is cited by

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