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).