Gold-Catalyzed Cycloaddition Reactions of Allenamides

Gold-catalysed cycloaddition reactions of allenamides have emerged as a powerful strategy to construct complex cyclic frameworks with high atom economy and selectivity. Allenamides, characterised by an allenic system adjacent to an amide moiety, serve as versatile π-components that can engage in various cycloaddition pathways under gold(I) activation. The unique electrophilic activation mode of gold(I) complexes enables the polarisation of the allene, promoting nucleophilic attack and subsequent ring closure to afford cyclobutanes, tetrahydropyrans, tetrahydrocarbazoles and other heterocycles in a single step. By fine-tuning ligand environment and reaction parameters, chemists can switch between [2+2], [4+2] and [2+2+2] cycloaddition manifolds, achieve high regio- and enantioselectivity and access scaffolds of direct relevance to medicinal chemistry. Mechanistic studies supported by density functional theory have elucidated key intermediates, including gold-stabilised carbocationic species and 1,3-dipolar transition states, guiding the rational design of catalysts. Recent advances have extended the substrate scope to include unactivated alkenes, alkenols and aldehydes, while enabling tandem processes that increase molecular complexity. As a result, gold-catalysed cycloaddition of allenamides now stands as an essential tool for streamlined synthesis of bioactive molecules and natural product frameworks, emphasising its global significance and practical potential in sustainable organic synthesis.

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Gold-Catalyzed Cycloaddition Reactions of Allenamides publication trend

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

Technical terms

Allenamide: An organic compound featuring an allene (cumulene) directly conjugated to an amide, serving as a versatile π-component in cycloaddition reactions.

Cycloaddition: A pericyclic reaction in which two or more unsaturated molecules unite to form a cyclic adduct, often classified by the number of atoms involved in the new ring.

Gold(I) catalyst: A monovalent gold complex, typically coordinated to phosphine or phosphite ligands, that activates π-systems through soft Lewis acid interactions.

Regioselectivity: The preference for bond formation at specific positions on a substrate, leading to one constitutional isomer over others.

Enantioselectivity: The selective formation of one enantiomer over its mirror image in a chiral reaction, often quantified by enantiomeric excess.

References

1. Enantioselective gold-catalyzed intermolecular [2+2] versus [4+2]-cycloadditions of 3-styrylindoles with N -allenamides: observation of interesting substituent effects. Chemical Science (2015).
2. Gold( i )-catalyzed [2 + 2 + 2] cycloaddition of allenamides, alkenes and aldehydes: a straightforward approach to tetrahydropyrans. Chemical Science (2015).