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.
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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.
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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.
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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.
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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.
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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
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DOI: https://doi.org/10.1038/s41586-023-06087-4
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