Halogenation and Functionalization of Alkynes in Organic Synthesis

Halogenation and functionalization of alkynes constitute a cornerstone of contemporary synthetic chemistry, offering versatile pathways to access a wide array of halogenated building blocks and elaborated molecular frameworks. Alkynes, characterised by their carbon–carbon triple bond, can undergo electrophilic addition, radical-mediated transformations or metal-catalysed processes to furnish vinyl halides, haloalkynes and dihalogenated adducts with high regiochemical and stereochemical control. These halogenated motifs serve as pivotal intermediates in cross-coupling reactions, cycloadditions and late-stage modifications of complex targets, including pharmaceuticals, agrochemicals and advanced materials. Recent developments have emphasised mild and sustainable reaction conditions, novel halogen sources and increased functional-group tolerance, enabling both terminal and internal alkynes to be transformed with exceptional efficiency and selectivity. The integration of photochemical techniques and transfer reagents has further broadened the scope, allowing precise incorporation of chlorine, bromine or iodine under metal-free or earth-abundant catalyst systems. Such innovations not only streamline synthetic sequences but also open avenues for radiolabelling and isotopic labelling in medicinal chemistry, demonstrating the enduring global significance of alkyne halogenation strategies.

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Halogenation and Functionalization of Alkynes in Organic Synthesis publication trend

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

Technical terms

Alkyne: A hydrocarbon containing a carbon–carbon triple bond, used as a versatile substrate in addition and coupling reactions.

Electrophilic addition: A reaction in which an electrophile adds to an unsaturated carbon–carbon bond, forming a new covalent bond.

Radical functionalization: The incorporation of a substituent onto a substrate via radical intermediates, often under photochemical or thermal initiation.

Halogen-Atom Transfer (XAT): A photochemical process in which a halide radical is generated through abstraction of a halogen atom from a dihalide precursor, enabling downstream radical additions.

Transfer hydrochlorination: A method that employs a surrogate reagent to deliver hydrogen chloride to unsaturated substrates, often under Lewis acid catalysis and without direct use of gaseous HCl.

References

1. Highly Efficient 1-Iodination of Terminal Alkynes Catalyzed by Inorganic or Organic Bases. Catalysts (2024).
2. Metal-free transfer hydrochlorination of internal C–C triple bonds with a bicyclo[3.1.0]hexane-based surrogate releasing two molecules of hydrogen chloride. Chemical Communications (2022).
3. Photo‐Induced Halogen‐Atom Transfer: Generation of Halide Radicals for Selective Hydrohalogenation Reactions. Chemistry - A European Journal (2022).