Gold Catalysis in Organic Synthesis

Gold catalysts have revolutionised organic synthesis over the past two decades, offering unique reactivity profiles compared with traditional transition‐metal systems. The propensity of gold to engage in π-activation alongside its capacity to undergo redox cycling between Au(I) and Au(III) oxidation states has given rise to novel bond-forming strategies for the functionalisation of alkynes, alkenes and arenes. The high polarizability and relativistic effects inherent to gold confer exceptional π-acidic character, facilitating selective activation of unsaturated substrates under mild conditions. Advances in ligand design and mechanistic insight have overcome longstanding challenges associated with oxidative addition at gold centres, enabling cross-coupling reactions analogous to those long established for palladium. Dual catalytic processes—often merging gold with photoredox or hypervalent iodine-mediated systems—have expanded the toolkit for carbon–carbon and carbon–heteroatom bond formation. The global impact of gold catalysis is evident in the late-stage modification of natural products, pharmaceuticals and complex fine chemicals, where its tolerance to sensitive functional groups and operational simplicity are highly prized. Control of chemo-, regio- and stereoselectivity has cemented gold catalysis as an indispensable component of modern synthetic strategy.

Research from Nature Portfolio

Recent studies have demonstrated the power of gold-catalysed redox cycles in enabling multifunctionalisation protocols that were previously unattainable. A four-component transformation of internal alkynes achieves oxo-arylfluorination or oxo-arylalkenylation through an Au(I)/Au(III) cycle, forging four new bonds in a single operation with outstanding chemo- and regioselectivity. Divergence of the reaction pathway is controlled by site-directing functional groups, streamlining access to densely substituted ketones. In parallel, electrophilic cyclopropenyl–gold(III) species have been employed as equivalents of σ-type cyclopropenium cations, enabling the efficient synthesis of highly functionalised cyclopropenes under mild oxidative conditions. This strategy uses cyclopropenyl hypervalent iodine reagents to effect concomitant gold(I) oxidation and cyclopropenyl transfer, and has been applied to the late-stage modification of complex bioactive scaffolds.

Gold Catalysis in Organic Synthesis publication trend

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

Technical terms

Au(I)/Au(III) redox cycle: Interconversion between gold in oxidation states +1 and +3 during catalysis, enabling oxidative addition and reductive elimination steps.

Oxidative addition: A bond-forming step in which a metal inserts into a covalent bond (for example C–X), increasing its oxidation state by two units.

Reductive elimination: The reverse of oxidative addition, a step in which two ligands on a metal centre couple and are released, reducing the metal’s oxidation state.

Trans effect: The influence exerted by a ligand on the lability and reactivity of ligands positioned trans to it in a coordination complex.

Photoredox catalysis: A strategy that uses visible light to excite a photocatalyst, which then enables single-electron transfer processes in conjunction with a co-catalyst.

Cyclopropenium cation: A three-membered cyclic carbocation with aromatic character, which can be mimicked in gold-catalysed cyclopropene synthesis.

References

1. Cyclometalated (N,C) Au(III) Complexes: The Impact of Trans Effects on Their Synthesis, Structure, and Reactivity. Accounts of Chemical Research (2023).
2. Gold-catalyzed four-component multifunctionalization of alkynes. Nature Communications (2023).
3. Accessing elusive σ-type cyclopropenium cation equivalents through redox gold catalysis. Nature Chemistry (2024).
4. Oxidative additions of alkynyl/vinyl iodides to gold and gold-catalyzed vinylation reactions triggered by the MeDalphos ligand. Chemical Science (2021).