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Dual-catalytic transition metal systems for functionalization of unreactive sites of molecules

A Publisher Correction to this article was published on 29 January 2019

This article has been updated


Catalytic reactions occur readily at the sites of starting materials that are both innately reactive and sterically accessible, or that are predisposed by a functional group amenable to direct a catalyst. However, selective reactions at unbiased sites of substrates remain challenging and typically require additional preactivation steps or the use of highly reactive reagents. Here we report dual-catalytic transition metal systems that merge a reversible activation cycle with a functionalization cycle, which together enable the functionalization of substrates at their inherently unreactive sites. By engaging the Ru- or Fe-catalysed equilibrium between an alcohol and an aldehyde, methods for Pd-catalysed β-arylation of aliphatic alcohols and Rh-catalysed γ-hydroarylation of allylic alcohols were developed. The mild conditions, functional group tolerance and broad scope (81 examples) demonstrate the synthetic applicability of the dual-catalytic systems. This work highlights the potential of the multicatalytic approach to address challenging transformations to circumvent multistep procedures and the use of highly reactive reagents in organic synthesis.

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Fig. 1: TM-catalysed functionalization of starting materials.
Fig. 2: Reaction design and development.
Fig. 3: Mechanistic studies.
Fig. 4: Pd-/Ru-catalysed arylation of the β-C–H bond of alcohols.
Fig. 5: γ-selective hydroarylation of allylic alcohols.

Data availability

The crystallographic data for compound 7a have been deposited at the Cambridge Crystallographic Data Centre (CCDC) as CCDC 1821986 and can be obtained free of charge from the CCDC via All the other data are available from the authors upon reasonable request.

Change history

  • 29 January 2019

    In the version of this Article originally published, some compounds in Fig. 4 had incorrect footnote notation: for 5b 47%*,b should be 47%ab; for 6w 65%‡§¶ should be 65%cdf; for 6x 50%‡§¶,” should be 50%cdf and for 6y 59%‡§¶ should be 59%cdf. Furthermore, in Fig. 2b, for the arylation reaction the text read “H–Base+ X–” but should be H-Base+X; in Fig. 3d, the reaction arrow was labelled “Doxane-d8” but should be Dioxane-d8; and in Fig. 1c there was an extraneous horizontal line at top right. All these errors have now been amended.


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This work was financially supported by the University of Strasbourg, the French National Research Agency (‘Investments for the future’ programme of the IdEx Unistra framework), FRC & LabEx Chemistry of Complex Systems, the Polish National Science Centre (Etiuda fellowship no. 2016/20/T/ST5/00494 to D.L.), the European Union (Marie Curie Actions, PCOFUND-GA-2013-609102) through the Campus France (Prestige fellowship no. PRESTIGE-2017-4-0022 to D.L.), the Polish Ministry of Science and Higher Education (Mobilnosc Plus fellowship no. 1672/l/MOB/V/l 7/2018/0 to K.H.) and the Foundation for Polish Science (Start fellowship no. START-036.2018 to K.H.). We thank L. Karmazin for the crystallographic measurements, E. Richmond for help with the initial high-performance liquid chromatography analysis and W. Dzik for helpful discussions.

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Authors and Affiliations



D.L. and P.D. conceived, designed and performed the initial experiments. D.L., Y.Z. and P.D. designed and performed subsequent experiments. D.L., Y.Z. and K.H. performed the experiments during the revision. P.D. conceived the concept and prepared the manuscript with feedback from D.L.

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Correspondence to Paweł Dydio.

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Supplementary Information

Supplementary Methods, Supplementary Figures 1–19, Supplementary Tables 1–4, Supplementary References

Compound 7a

Crystallographic data for compound 7a

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Lichosyt, D., Zhang, Y., Hurej, K. et al. Dual-catalytic transition metal systems for functionalization of unreactive sites of molecules. Nat Catal 2, 114–122 (2019).

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