Dual-Catalytic Transition Metal Systems for Functionalization of Unreactive Sites of Molecules

<b>Catalytic reactions occur readily at 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 pre-activation steps or the use of highly reactive reagents. Herein, we report dual-catalytic transition metal systems that merge a reversible activation cycle with a functionalization cycle, together enabling functionalization of substrates at their inherently unreactive sites. By engaging the Ru- or Fe-catalyzed equilibrium between an alcohol and an aldehyde, Pd-catalyzed <i>b</i>-arylation of aliphatic alcohols and Rh-catalyzed <i>g</i>-hydroarylation of allylic alcohols were developed. The mild conditions, functional group tolerance and broad scope of the methodologies (81 examples) demonstrate the synthetic applicability of the dual-catalytic systems. In a broader context, this work highlights the potential of the multi-catalytic approach to address challenging transformations to circumvent the multi-step procedures and the use of highly reactive reagents in organic synthesis.</b>