In(OTf)₃-catalyzed cyclization of nitrogen- and oxygen-tethered acetylenic malonic esters provided various five to seven-membered heterocycles in moderate to excellent yield, and the reaction proceeded with no racemization and complete E-selectivity in the case of chiral and nonterminal alkynes. The synthetic utility was demonstrated by the total synthesis of (−)-salinosporamide A, a highly potent 20S proteasome inhibitor, and (+)-neooxazolomycin, a member of the oxazolomycin family of antibiotics.