Transition Metal-Catalyzed Alkynylation in Organic Synthesis

Transition metal-catalysed alkynylation has emerged as a cornerstone methodology for the efficient construction of carbon–carbon triple bonds in complex molecules. By harnessing the reactivity of late-transition metals such as palladium, rhodium, copper and nickel, chemists can form alkynylated scaffolds directly through C–H activation or cross-coupling pathways. These strategies enable atom-economical assembly of natural products, pharmaceuticals and functional materials under mild conditions, often circumventing the need for pre-functionalised substrates. Advances in catalyst design and mechanistic understanding have broadened substrate scope, improved regioselectivity and permitted enantioselective variants. Contemporary research emphasises sustainable protocols, including base-metal catalysis, electro- or photochemical activation, and radical processes, thereby enhancing the environmental profile of alkynylation. The global significance of these developments lies in their capacity to streamline synthetic routes, reduce waste and expand the chemist’s toolkit for late-stage functionalisation of complex targets.

Research from Nature Portfolio

Recent studies have demonstrated the power of multimetal-catalysed radical oxidative coupling to achieve direct alkynylation of unactivated C(sp3)–H bonds. By employing a cooperative copper–nickel–silver catalyst system, terminal alkynes and simple alkanes undergo selective C–H functionalisation to furnish substituted alkynes without prior activation. Mechanistic investigations point to radical intermediates and a rate-limiting hydrogen-atom abstraction step, offering a blueprint for controlling selectivity in challenging bond-forming events. This work exemplifies how synergistic metal combinations can unlock new reaction pathways and provides a versatile platform for deriving complex alkyne-containing frameworks from abundant feedstocks.

Transition Metal-Catalyzed Alkynylation in Organic Synthesis publication trend

The graph below shows the total number of articles in transition metal-catalyzed alkynylation in organic synthesis across all publications each year (not limited to Nature Index journals).

Technical terms

Alkynylation: Introduction of a carbon–carbon triple bond into an organic substrate, typically via transition metal catalysis.

C–H activation: Cleavage of a carbon–hydrogen bond by a metal centre to enable subsequent bond-forming reactions directly from C–H bonds.

Cross-coupling: Metal-catalysed formation of a carbon–carbon bond between two distinct coupling partners, often involving organohalides and organometallic reagents.

Sonogashira reaction: A classic palladium-copper-catalysed coupling of terminal alkynes with aryl or vinyl halides to form conjugated alkynes.

Directing group: A functional moiety that coordinates to a metal catalyst, guiding regioselective activation of adjacent C–H bonds.

References

1. Multimetallic catalysed radical oxidative C(sp3)–H/C(sp)–H cross-coupling between unactivated alkanes and terminal alkynes. Nature Communications (2016).
2. Broad-Scope Rh-Catalyzed Inverse-Sonogashira Reaction Directed by Weakly Coordinating Groups. ACS Catalysis (2018).
3. Rhodium-catalysed ortho -alkynylation of nitroarenes. Chemical Science (2021).
4. Selective Para‐C−H Alkynylation of Aniline Derivatives by Pd/S,O‐Ligand Catalysis. Chemistry - A European Journal (2022).