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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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 www.ccdc.cam.ac.uk/getstructures. All the other data are available from the authors upon reasonable request.
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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.
The authors declare no competing interests.
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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). https://doi.org/10.1038/s41929-018-0207-1
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