Overcoming limitations in non-activated alkene cross-coupling with nickel catalysis and anionic ligands

Abstract

Multicomponent cross-coupling reactions involving alkenes represent a compelling strategy for accessing three-dimensional molecules, a key pursuit in contemporary medicinal chemistry. Transition metal-catalysed processes predominantly necessitate the use of conjugated alkenes or non-activated alkenes equipped with specific auxiliary functional groups, for example, 8-aminoquinoline. However, it remains a huge challenge to directly use unmodified native functional groups, such as alcohols and ethers, as directing groups. Here, by utilizing an anionic bidentate ligand such as acac, we have successfully addressed the challenge of employing weakly coordinating native functional groups as directing groups in a nickel-catalysed cross-coupling of non-activated alkenes. This reaction enables the simultaneous introduction of an sp2 fragment and an sp3 fragment to two carbons of the alkenes with high chemo- and regioselectivity. This work demonstrates the advantages and potential of anionic bidentate ligands in the cross-coupling of non-activated alkenes. The transition metal-catalysed multicomponent cross-coupling of alkenes currently relies on strongly coordinating groups to direct the reactivity. Now Wu et al. present a nickel catalyst that enables the installation of sp2 and sp3 fragments on alkenes using alcohols and ethers as directing groups.