This paper describes Sonogashira cross-coupling of functionalized 2-, 4-, and 5-trifloyl oxazoles and thiazoles with terminal alkynes. This methodology has been extended to 2, 4- ditrifloylthiazoles, which results in regioselective cross-coupling at the C2-position of the thiazole. The resulting 2-alkynyl-4-trifloylthiazoles are effective electrophiles in a second palladium (0)-mediated cross-coupling reaction.