Nickel-Catalyzed Functionalization of Alkenes

Nickel-catalysed functionalisation of alkenes has emerged as a versatile strategy for constructing complex molecules with high efficiency and selectivity. Owing to the earth-abundance and unique catalytic properties of nickel, this approach enables the installation of diverse functional groups across carbon–carbon double bonds under relatively mild conditions. Key advances include redox-neutral dicarbofunctionalisation, reductive hydrocarbonation and migratory hydrofunctionalisation, each leveraging nickel’s capacity to mediate radical or organometallic pathways. The resulting protocols afford access to a wide array of value-added products, from chiral amines and ketones to heterocycles and fluorinated motifs, with broad substrate scope and often excellent regio- and stereocontrol. Operational simplicity, compatibility with unactivated alkenes and the avoidance of stoichiometric organometallic reagents underpin the practical appeal of these methods for pharmaceutical and agrochemical synthesis. Recent innovations in charge-relocation strategies, photochemical C–H activation and ligand-relay catalysis have further extended the reach of nickel systems, enabling late-stage diversification and new retrosynthetic disconnections that streamline the assembly of complex targets.

Research from Nature Portfolio

Recent studies have introduced stereodivergent 1,3-difunctionalisation protocols that employ a charge-relocation concept to access either syn- or anti-configured products directly from unactivated alkenes, obviating the need for directing groups and demonstrating applicability in the synthesis of complex natural toxins. In a complementary development, an enantioselective three-component dicarbofunctionalisation uses photochemical C(sp3)–H activation in tandem with nickel catalysis to install two vicinal carbon–carbon bonds with high enantio-, regio- and chemoselectivity. This approach harnesses hydrogen-atom transfer for radical generation and delivers chiral α-aryl and alkenyl carbonyls, phosphonates and diarylalkanes from simple alkanes, ethers and alcohols, showcasing operational simplicity and broad functional-group tolerance.

Nickel-Catalyzed Functionalization of Alkenes publication trend

The graph below shows the total number of articles in nickel-catalyzed functionalization of alkenes across all publications each year (not limited to Nature Index journals).

Technical terms

Alkene: An unsaturated hydrocarbon featuring a carbon–carbon double bond, serving as a versatile reactive handle for functionalisation.

Dicarbofunctionalisation: The simultaneous formation of two carbon–carbon bonds across an alkene, enabling rapid molecular complexity.

Regioselectivity: The preference for bond formation at one position over others on an unsymmetrical substrate.

Enantioselectivity: The preferential formation of one enantiomer over another in a chiral reaction, crucial for bioactive molecules.

Photoredox catalysis: A technique using light-activated catalysts to generate radicals or reactive intermediates under mild conditions.

Ligand relay catalysis: A strategy employing dynamic exchange of different ligands during distinct steps of a catalytic cycle to optimise activity and selectivity.

References

1. Stereodivergent 1,3-difunctionalization of alkenes by charge relocation. Nature (2024).
2. Nickel-catalysed enantioselective alkene dicarbofunctionalization enabled by photochemical aliphatic C–H bond activation. Nature Catalysis (2024).
3. Dual Nickel/Photoredox-Catalyzed Asymmetric Carbosulfonylation of Alkenes. Journal of the American Chemical Society (2023).
4. Ligand Relay Catalysis Enables Asymmetric Migratory Hydroarylation for the Concise Synthesis of Chiral α‐(Hetero)Aryl‐Substituted Amines. Advanced Science (2024).
5. Nickel-catalyzed difunctionalization of allyl moieties using organoboronic acids and halides with divergent regioselectivities. Chemical Science (2018).