Abstract
Cross-coupling reactions are among the most important transformations in modern organic synthesis1,2,3. Although the range of reported (het)aryl halides and nucleophile coupling partners is very large considering various protocols, the reaction conditions vary considerably between compound classes, necessitating renewed case-by-case optimization of the reaction conditions4. Here we introduce adaptive dynamic homogeneous catalysis (AD-HoC) with nickel under visible-light-driven redox reaction conditions for general C(sp2)–(hetero)atom coupling reactions. The self-adjustive nature of the catalytic system allowed the simple classification of dozens of various classes of nucleophiles in cross-coupling reactions. This is synthetically demonstrated in nine different bond-forming reactions (in this case, C(sp2)–S, Se, N, P, B, O, C(sp3, sp2, sp), Si, Cl) with hundreds of synthetic examples under predictable reaction conditions. The catalytic reaction centre(s) and conditions differ from one another by the added nucleophile, or if required, a commercially available inexpensive amine base.
This is a preview of subscription content, access via your institution
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 / 30 days
cancel any time
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Data availability
The data supporting the findings of this study are available within the paper and its Supplementary Information and upon request from the corresponding authors.
References
Miyaura, N. & Suzuki, A. Palladium-catalyzed cross-coupling reactions of organoboron compounds. Chem. Rev. 95, 2457–2483 (1995).
Ruiz-Castillo, P. & Buchwald, S. L. Applications of palladium-catalyzed C–N cross-coupling reactions. Chem. Rev. 116, 12564–12649 (2016).
Ley, S. V. & Thomas, A. W. Modern synthetic methods for copper-mediated C(aryl)–O, C(aryl)–N, and C(aryl)–S bond formation. Angew. Chem. Int. Ed. 42, 5400–5449 (2003).
Dorel, R., Grugel, C. P. & Haydl, A. M. The Buchwald–Hartwig amination after 25 years. Angew. Chem. Int. Ed. 58, 17118–17129 (2019).
Diccianni, J. B. & Diao, T. N. Mechanisms of nickel-catalyzed cross-coupling reactions. Trends Chem. 1, 830–844 (2019).
Jana, R., Pathak, T. P. & Sigman, M. S. Advances in transition metal (Pd,Ni,Fe)-catalyzed cross-coupling reactions using alkyl-organometallics as reaction partners. Chem. Rev. 111, 1417–1492 (2011).
Zhang, J., Wang, S. Y., Zhang, Y. & Feng, Z. Iron-catalyzed cross-coupling reactions for the construction of carbon–heteroatom bonds. Asian J. Org. Chem. 9, 1519–1531 (2020).
Shaw, M. H., Twilton, J. & MacMillan, D. W. C. Photoredox catalysis in organic chemistry. J. Org. Chem. 81, 6898–6926 (2016).
Tellis, J. C., Primer, D. N. & Molander, G. A. Single-electron transmetalation in organoboron cross-coupling by photoredox/nickel dual catalysis. Science 345, 433–436 (2014).
Oderinde, M. S., Frenette, M., Robbins, D. W., Aquila, B. & Johannes, J. W. Photoredox mediated nickel catalyzed cross-coupling of thiols with aryl and heteroaryl iodides via thiyl radicals. J. Am. Chem. Soc. 138, 1760–1763 (2016).
Qin, Y. Z., Sun, R., Gianoulis, N. P. & Nocera, D. G. Photoredox nickel-catalyzed C–S cross-coupling: mechanism, kinetics, and generalization. J. Am. Chem. Soc. 143, 2005–2015 (2021).
Escobar, R. A. & Johannes, J. W. A unified and practical method for carbon–heteroatom cross-coupling using nickel/photo dual catalysis. Chem. Eur. J. 26, 5168–5173 (2020).
Kullmer, C. N. P. et al. Accelerating reaction generality and mechanistic insight through additive mapping. Science 376, 532–539 (2022).
Ahneman, D. T., Estrada, J. G., Lin, S. S., Dreher, S. D. & Doyle, A. G. Predicting reaction performance in C–N cross-coupling using machine learning. Science 360, 186–190 (2018).
Itoh, T. & Mase, T. Practical thiol surrogates and protective groups for arylthiols for Suzuki–Miyaura conditions. J. Org. Chem. 71, 2203–2206 (2006).
Wolfe, J. P., Ahman, J., Sadighi, J. P., Singer, R. A. & Buchwald, S. L. An ammonia equivalent for the palladium-catalyzed amination of aryl halides and triflates. Tetrahedron Lett. 38, 6367–6370 (1997).
Ghosh, A. K. & Brindisi, M. Organic carbamates in drug design and medicinal chemistry. J. Med. Chem. 58, 2895–2940 (2015).
Nakamura, Y., Maruya, K.-i. & Mizoroki, T. A study of the ligand-exchange of bromo(o-tolyl)bis(triphenylphosphine)nickel(II) with amine by means of 31P- spectroscopy and 13C-NMR spectroscopy. Bull. Chem. Soc. Jpn 53, 3089–3092 (1980).
Noel, T. et al. Palladium-catalyzed amination reactions in flow: overcoming the challenges of clogging via acoustic irradiation. Chem. Sci. 2, 287–290 (2011).
Sun, R., Qin, Y. Z. & Nocera, D. G. General paradigm in photoredox nickel-catalyzed cross-coupling allows for light-free access to reactivity. Angew. Chem. Int. Ed. 59, 9527–9533 (2020).
Till, N. A., Tian, L., Dong, Z., Scholes, G. D. & MacMillan, D. W. C. Mechanistic analysis of metallaphotoredox C–N coupling: photocatalysis initiates and perpetuates Ni(I)/Ni(III) coupling activity. J. Am. Chem. Soc. 142, 15830–15841 (2020).
Holland, P. L., Andersen, R. A. & Bergman, R. G. Application of the E–C approach to understanding the bond energies thermodynamics of late-metal amido, aryloxo and alkoxo complexes: an alternative to pπ/dπ repulsion. Comments Inorg. Chem. 21, 115–129 (1999).
Vitaku, E., Smith, D. T. & Njardarson, J. T. Analysis of the structural diversity, substitution patterns, and frequency of nitrogen heterocycles among US FDA approved pharmaceuticals. J. Med. Chem. 57, 10257–10274 (2014).
Lavagnino, M. N., Liang, T. & MacMillan, D. W. C. HARC as an open-shell strategy to bypass oxidative addition in Ullmann–Goldberg couplings. Proc. Natl Acad. Sci. USA 117, 21058–21064 (2020).
Vinogradova, E. V., Park, N. H., Fors, B. P. & Buchwald, S. L. Palladium-catalyzed synthesis of N-aryl carbamates. Org. Lett. 15, 1394–1397 (2013).
Acknowledgements
I.G. thanks R. Mandal for encouragement for this project. We thank R. Hoheisel for the CV measurements and A. N. Fakhrutdinov for NMR spectra checking. This project received funding from the Deutsche Forschungsgemeinschaft (TRR 325 – 444632635) and the Russian Science Foundation (RSF projects 21-13-00193, 22-13-00247). N.S. thanks Bayhost for a PhD stipend. T.A.K. thanks the Deutsche Bundesstiftung Umwelt (DBU) for a PhD scholarship. J.D. gratefully acknowledges Elitenetzwerk Bayern ‘IDK Chemical Catalysis with photonic or electric energy input’ for financial support.
Author information
Authors and Affiliations
Contributions
I.G. and B.K. conceived the project. I.G. designed experiments with valuable and critical inputs from N.S. and B.K. I.G., N.S., T.A.K., J.D. and M.N. performed experiments and analysed the results. J.V.B. performed mass spectrometric experiments. J.V.B., N.S. and V.P.A. analysed the mass spectrometry results. V.P.A. contributed to the mechanistic concept description. I.G. and B.K. prepared the paper with input from all authors.
Corresponding authors
Ethics declarations
Competing interests
The authors declare no competing interests.
Peer review
Peer review information
Nature thanks the anonymous reviewers 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 Additional electrophiles and nucleophiles scope in C(sp2)–Br cross–coupling reactions.
Isolated yields are reported unless noted otherwise. aFor an all-inclusive-examples figure see section 4 in the Supplementary Information. bThe compounds were isolated as their respective oxides.
Extended Data Fig. 2 Additional examples of cross–coupling reactions with amino acids and drugs as nucleophiles and drugs as electrophiles.
Isolated yields are reported unless noted otherwise. aFor an all-inclusive-examples figure see section 4 in the Supplementary Information.
Extended Data Fig. 3 Additional examples of cross–coupling reactions for the synthesis of drug and pesticide intermediates (electrophile and nucleophile scopes are demonstrated).
Isolated yields are reported unless noted otherwise. aFor an all-inclusive-examples figure see section 4 in the Supplementary Information.
Extended Data Fig. 4 Additional examples of cross–coupling reactions for two-step transformations– either in tandem or one-pot.
Isolated yields are reported unless noted otherwise. For compound 270, the formation of the desired product was confirmed by GC and GC–MS analysis with an authentic sample, and no attempts were made for the purification of the desired product. The synthesis of 277 can directly be performed with 4CzIPN. aFor an all-inclusive-examples figure see section 4 in the Supplementary Information.
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.
About this article
Cite this article
Ghosh, I., Shlapakov, N., Karl, T.A. et al. General cross-coupling reactions with adaptive dynamic homogeneous catalysis. Nature 619, 87–93 (2023). https://doi.org/10.1038/s41586-023-06087-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41586-023-06087-4
This article is cited by
-
A review on copper-based nanoparticles as a catalyst: synthesis and applications in coupling reactions
Journal of Materials Science (2024)
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.
