Asymmetric Alkynylation Strategies in Synthetic Organic Chemistry

Asymmetric alkynylation has emerged as a cornerstone in modern synthetic chemistry, enabling the enantioselective formation of carbon–carbon bonds by addition of alkynyl nucleophiles to carbonyls, iminium ions and related electrophiles. This strategy delivers chiral propargylic alcohols and heterocycles that serve as versatile intermediates in the assembly of natural products, agrochemicals and active pharmaceutical ingredients. Key advances hinge on the design of chiral ligands and organocatalysts that control stereochemistry through hydrogen bonding, π–π interactions and steric steering. Metal-mediated protocols—particularly those based on copper, silver and palladium—have been complemented by phase-transfer and organocatalytic approaches, each offering distinct advantages in terms of substrate scope, operational simplicity and environmental impact. Mechanistic insights from quantum-chemical studies have deepened understanding of transition-state organisation, guiding the development of more efficient and selective alkynylation methods. Collectively, these strategies underscore the global significance of asymmetric alkynylation in delivering structurally complex, enantioenriched molecules for research and industry.

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Asymmetric Alkynylation Strategies in Synthetic Organic Chemistry publication trend

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Technical terms

Alkynylation: The addition of an alkynyl (–C≡CR) unit to an electrophilic centre, forming a new carbon–carbon bond.

Enantioselectivity: The preference for formation of one enantiomer over its mirror image in a chiral reaction, usually expressed as enantiomeric excess.

Chiral ligand: An optically active molecule that coordinates to a metal centre to induce asymmetry in a catalytic transformation.

Propargylic alcohol: An alcohol functional group located on the carbon atom directly adjacent to a carbon–carbon triple bond.

Phase-transfer catalyst (PTC): A reagent that facilitates migration of a reactant between immiscible phases (e.g., aqueous to organic) to accelerate a reaction.

References

1. Enantiocontrol by assembled attractive interactions in copper-catalyzed asymmetric direct alkynylation of α-ketoesters with terminal alkynes: OH⋯O/sp 3 -CH⋯O two-point hydrogen bonding combined with dispersive attractions. Chemical Science (2018).
2. Enantioselective additions of copper acetylides to cyclic iminium and oxocarbenium ions. Beilstein Journal of Organic Chemistry (2015).
3. Theoretical Calculations on the Mechanism of Enantioselective Copper(I)-Catalyzed Addition of Enynes to Ketones. Catalysts (2018).
4. Enantioselective Trost alkynylation with 2E,4E-5-bromo-2,4-pentadienal. Tetrahedron Letters (2022).
5. Chiral Quaternary Ammoniums Derived from Dehydroabietylamine: Synthesis and Application to Alkynylation of Isatin Derivatives Catalyzed by Silver. Catalysts (2021).
6. Towards the Total Synthesis of Jerangolids – Synthesis of an Advanced Intermediate for the Pharmacophore Substructure. European Journal of Organic Chemistry (2020).