转自：康龙化成

Access to Terminal Alkynes via Palladium-Catalyzed Coupling of ArCl with a Low Catalyst Loading of 0.08 mol %

Lei Xu, Gen-Qiang Chen,* and Xumu Zhang* 

Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Department of Chemistry and Medi-X Pingshan, Southern University of Science and Technology, Shenzhen 518055, People’s Republic of China;

Academy for Advanced Interdisciplinary Studies and Shenzhen Grubbs Institute, Southern University of Science and Technology, Shenzhen 518000, People’s Republic of China;

Guangdong Laboratory of Chemistry and Fine Chemical Engineering, Shantou 515031, People’s Republic of China;

—J. Org. Chem. 2025, 90, 23, 7938–7946

Recommended by Chunlei Lu_ MC2

KEY WORDS:Heck−Cassar-Sonogashira reaction, Pd catalysis (反应类型), C(sp2)-C(sp) (成键类型), Aryl chlorides. (triisopropylsilyl)-acetylene (原料), Aryl alkynes (产物) 

ABSTRACT: The synthesis of terminal alkynes from inexpensive aryl chlorides remains a challenging task in organic synthesis. Here, a Heck−Cassar reaction of aryl chlorides with (triisopropylsilyl)-acetylene catalyzed by low loadings of palladium (0.08 mol %) has been developed. Through subsequent desilylation, aryl-substituted terminal alkynes can be readily prepared. This reaction features robustness and good functional group compatibility, making it suitable for the late-stage modification of drug molecules.

Synthesis of Terminal Alkyne from Aryl Halides

Scope of Aryl Chlorides (Selected)

Scope of Terminal Alkyne

Late-Stage Modification of Drug Molecules

In summary, apractical Heck−Cassar reaction for synthesizing terminal alkynes from aryl chlorides, catalyzed by low loading of palladium (0.08 mol %), has been developed. The transformation is completed in two steps (which can be performed in one pot): the palladium-catalyzed Heck−Cassar reaction of aryl chlorides with (triisopropylsilyl)acetylene, followed by subsequent desilylation. The reaction shows good generality and excellent functional group compatibility and can be used for the late-stage modification of drug molecules on a gram scale.

（转自：康龙化成）