Palladium-Catalyzed Sonogashira Coupling of a Heterocyclic Phosphonium Salt with a Terminal Alkyne

• DOI: 10.1021/acs.orglett.2c01800
• Publication Date: 2022-06-30T16:24:57Z
• Authors: Qing-Dong Wang; Si-Xuan Zhang; Zhuo-Wen Zhang; Ying Wang; Mengtao Ma; Xue-Qiang Chu; Zhi-Liang Shen
• Keywords: Alkynes; 01 natural sciences; Catalysis; Copper; Palladium; 0104 chemical sciences

An efficient Sonogashira coupling of a heterocyclic phosphonium salt with a terminal alkyne via C-P bond cleavage was developed. The reactions proceeded smoothly in the presence of palladium catalyst, copper(I) iodide, and N,N-diisopropylethylamine (DIPEA) in N-methyl-2-pyrrolidone (NMP) at 100 °C for 12 h, producing the corresponding alkynyl-substituted pyridine, quinoline, pyrazine, and quinoxaline in moderate to good yields with wide substrate scope and broad functional group tolerance. In addition, gram-scale synthesis could also be achieved, and the reaction could be applied to the functionalization of alkyne-containing complex molecules derived from sugars and pharmaceutical and naturally occurring products (e.g., estrone, d-galactopyranose, menthol, and ibuprofen).