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).