Gold-Catalyzed Transformations in Organic Synthesis

Gold catalysis has emerged as a versatile platform for the activation of π‐systems and the generation of reactive carbene intermediates, enabling a wide array of bond-forming processes under remarkably mild conditions. The unique ability of gold(I) and gold(III) complexes to coordinate alkynes, allenes and alkenes with high π-affinity facilitates nucleophilic addition, cycloaddition and rearrangement pathways that were previously challenging to realise. Central to these advances is the capacity of gold to stabilise cationic intermediates and access gold carbene species without the need for stoichiometric diazo precursors, thereby enhancing atom economy. This mechanistic flexibility has been harnessed in the rapid construction of cyclic frameworks, including oxazoles, pyrroles and azepines, through formal [3+2], [4+2] and [4+3] annulations. Moreover, the design of tailored ligands and counterions has permitted control over regio- and stereoselectivity, unlocking enantioselective variants of key transformations. Collectively, gold-catalysed methods now underpin the synthesis of complex natural products, pharmaceutical scaffolds and functional materials, underscoring their global significance and practical potential in streamlining synthetic routes for fine chemicals and advanced intermediates.

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Gold-Catalyzed Transformations in Organic Synthesis publication trend

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

Technical terms

Gold carbene: A reactive species in which a gold centre is formally bound to a divalent carbon atom bearing two nonbonding electrons, capable of facilitating carbene‐type insertions and cycloadditions.

π-Activation: The process by which a transition metal coordinates to a π-bond (such as an alkyne or alkene), lowering its energy and rendering it more susceptible to nucleophilic attack.

Ynamide: An alkyne bearing an adjacent nitrogen substituent (amide), which increases the electron density of the triple bond and directs reactivity under gold catalysis.

Electrocyclization: A pericyclic reaction that converts a conjugated π-system into a cyclic product through a concerted cyclic redistribution of π-electrons, often initiated or stabilised by metal coordination.

References

1. Gold(I)-Catalyzed Activation of Alkynes for the Construction of Molecular Complexity. Chemical Reviews (2015).
2. Atom-economic generation of gold carbenes: gold-catalyzed formal [3+2] cycloaddition between ynamides and isoxazoles. Chemical Science (2015).
3. Gold-catalyzed [4+3]- and [4+2]-annulations of 3-en-1-ynamides with isoxazoles via novel 6π-electrocyclizations of 3-azahepta trienyl cations. Chemical Science (2018).