Alkynyl

Alkynyl halides or haloalkynes are compounds whose molecules have one or more halogen atoms bonded to an alkynyl group. Various functionalized organic molecules can be synthesized from haloalkynes through different reaction processes such as cross-coupling reactions, nucleophilic additions and cycloadditions. The ability of halogenated alkynes to synthesize complex molecular structures allows for multiple bond-formation events in a single operation, which offers the opportunity to advance chemical synthesis and meets the growing demands for green and sustainable chemistry. It also offers a wide range of functionalized products, including many synthetically useful conjugated cyclic and acyclic structures that have potential applications in materials science, natural product and biochemical synthesis.

Applications

• Cycloaddition reaction: Intramolecular thermal and cationic Rh(I)-catalyzed [4+2] cycloaddition of alkynyl halides has been reported. The alkynyl halide moiety is compatible with Rh(I)-catalyzed [4+2] and the cycloaddition reaction smoothly undergoes at room temperature to give the halogenated cycloadducts in good yield. Halogenated cycloadducts obtained by this method have a wide range of uses, and can be converted into a variety of products that are difficult or impossible to obtain by direct cycloaddition. For example, these halogenated derivatives can be further functionalized by various metal-catalyzed coupling reactions.

  Fig.1. Rhodium-catalyzed intramolecular [4+2] cycloadditions of alkynyl halides

• Cross-coupling reaction: Carbon-carbon cross-coupling reactions are one of the most important and useful methods in organic synthesis, making it easy to access valuable compounds. Conjugated diynes are crucial multi-functional units in the synthesis of natural products, pharmaceutical and functional materials. Lee’s group reported a convenient method for constructing symmetric 1,3-diynes from 1-iodoalkynes with Pd catalysts and in the absence of any additives or other metal reagents. The reaction can be carried out under an inert atmosphere to avoid side reactions associated with the Glazer coupling reaction using O₂ as the oxidant.

  Fig.2. Pd-catalyzed homocoupling reactions of iodoalkynes

• Nucleophilic addition: Developing an effective and sustainable method of synthesizing heteroatom-containing olefins is an important task. Nucleophilic addition of haloalkynes to construct C(sp²)-heteroatom bonds represents a series of reactions with significant synthetic value. Different types of nucleophiles, including halide ions, acetates, isocyanides, phenols, thiols, imidazoles and sulfonamides, can readily undergo nucleophilic addition to the haloalkyne and genarate the corresponding haloalkenes, which could be used for the construction of polysubstituted alkenes and heterocyclic derivatives.

Fig.3. Nucleophilic additions to haloalkynes

References

1. Yoo W J, Allen A, Villeneuve K, et al. Rhodium-catalyzed intramolecular [4+2] cycloadditions of alkynyl halides[J]. Organic letters, 2005, 7(26): 5853-5856.
2. Damle, S. V.; Seomoon, D.; Lee, P. H. Palladium-Catalyzed Homocoupling Reaction of 1-Iodoalkynes: A Simple and Efficient Synthesis of Symmetrical 1,3-Diynes. J. Org. Chem. 2003, 68, 7085−7087.