A Versatile and Efficient Palladium-meta-Terarylphosphine Catalyst for the Copper-Free Sonogashira Coupling of (Hetero-)Aryl Chlorides and Alkynes

• Published in: European journal of organic chemistry 2014-11, Vol.2014 (32), p.7184-7192
• Main Authors: Yang, Yong, Chew, Xinying, Johannes, Charles W., Robins, Edward G., Jong, Howard, Lim, Yee Hwee
• Format: Article
• Language: English
• Subjects: Alkynes; C-C cou­pling; Cross-coupling; Ligands; Palladium; Phosphane ligands; Synthetic methods
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201402699

A novel meta‐terarylphosphine ligand, Cy*Phine, was developed and found to be a highly active promoter of copper‐free Sonogashira cross‐coupling reactions when combined in situ with a palladium source. The evolutionary m‐terarylphosphine ligand architecture was able to impose significant performance advantages over its biarylphosphine congeners. An expedient and versatile protocol was also devised with an emphasis on substrates applicable to the fine‐chemicals industry by featuring a diverse range of challenging, electron‐rich aryl chlorides and terminal alkynes. The Pd–Cy*Phine catalyst was able to deliver products in excellent yields with efficient substrate utilization, which minimizes the generation of commonly formed byproducts, and the reaction is tolerant of a variety of substrates with unprotected functional groups. A protocol is devised for the cross‐coupling of electron‐rich aryl chlorides with terminal alkynes by using Pd–Cy*Phine, which is a highly active in situ catalyst containing a novel meta‐terarylphosphine ligand. Excellent yields are achieved with minimal generation of byproducts. The versatility of this reaction is demonstrated by its tolerance of a range of unprotected functional groups.