Alkyne Metathesis Catalysis in Organic Synthesis

Alkyne metathesis has emerged as a powerful method for the formation and reorganisation of carbon–carbon triple bonds, enabling the efficient assembly of complex molecular architectures. Central to this process is a catalytic cycle involving [2+2] cycloaddition of an alkylidyne complex with a terminal or internal alkyne to form a metallacyclobutadiene intermediate, followed by cycloreversion to exchange alkyne fragments. Advances in ligand design—most notably silanolate and tripodal frameworks—have dramatically enhanced catalyst stability, functional-group tolerance and operational simplicity. These developments have broadened the scope of alkyne metathesis from macrocycle and polymer synthesis to dynamic covalent chemistry, solid-phase synthesis and natural-product construction. Challenges such as air and moisture sensitivity, narrow substrate compatibility and catalyst deactivation have been addressed through tailored steric and electronic tuning, delivering systems that combine high activity with bench-top handling and storage. Today, alkyne metathesis stands as a strategic tool in both academic and industrial settings, offering unique disconnections for complex targets and sustainable routes to advanced materials.

Research from Nature Portfolio

Recent studies have introduced user-friendly alkyne metathesis catalysts that operate under open air conditions without sacrificing efficiency. These systems employ multidentate tris(2-hydroxyphenyl)methane ligands bearing electron-withdrawing substituents to achieve high turnover at ambient temperature and tolerate a wide range of functional groups including alcohols, aldehydes, nitro and heterocycles. Remarkably, the most active variants deliver yields above 90% in air and retain activity after dispersion in paraffin wax under ambient storage. This work paves the way for broader adoption of alkyne metathesis in synthetic routes where rigorous exclusion of moisture and oxygen has previously been prohibitive.

Alkyne Metathesis Catalysis in Organic Synthesis publication trend

The graph below shows the total number of articles in alkyne metathesis catalysis in organic synthesis across all publications each year (not limited to Nature Index journals).

Technical terms

Alkyne metathesis: A catalytic reaction exchanging alkynyl fragments through a sequence of [2+2] cycloaddition and cycloreversion steps.

Alkylidyne: A metal‒carbon triple bond complex that initiates alkyne metathesis by engaging substrate alkynes.

Metallacyclobutadiene: A four-membered metallacyclic intermediate formed by [2+2] cycloaddition in the alkyne metathesis cycle.

Metallatetrahedrane: A tetrahedral metal–carbon cluster intermediate that can interconvert with metallacyclobutadiene during isomerisation.

Ligand denticity: The number of coordinating atoms through which a ligand binds to a metal centre, influencing catalyst stability and reactivity.

References

1. Metallacyclobutadienes: Intramolecular Rearrangement from Kinetic to Thermodynamic Isomers. Advanced Science (2024).
2. Rhenium Alkyne Catalysis: Sterics Control the Reactivity. Inorganic Chemistry (2024).
3. Highly active alkyne metathesis catalysts operating under open air condition. Nature Communications (2021).
4. Molybdenum Alkylidyne Complexes with Tripodal Silanolate Ligands: The Next Generation of Alkyne Metathesis Catalysts. Angewandte Chemie International Edition (2019).
5. “Canopy Catalysts” for Alkyne Metathesis: Molybdenum Alkylidyne Complexes with a Tripodal Ligand Framework. Journal of the American Chemical Society (2020).