The applicability of an intramolecular Nicholas reaction for the preparation of 10-membered O- and N-enediynes fused to indole, 1,2,3-triazole, and isocoumarin was investigated. The general approach to acyclic enediyne precursors fused to heterocycles includes inter- and intramolecular buta-1,3-diyne cyclizations with the formation of iodoethynylheterocycles, followed by Sonogashira coupling. The nature of both a heterocycle and a nucleophilic group affects the possibility of a 10-membered ring closure by the Nicholas reaction. Among oxacycles, an isocoumarin-fused enediyne was obtained. In the case of O-enediyne annulated with indole, instead of the formation of a 10-membered cycle, BF3-promoted addition of an OH-group to the proximal triple bond at the C3 position afforded dihydrofuryl-substituted indole. For 1,2,3-triazole-fused analogues, using NH-Ts as a nucleophilic functional group allowed obtaining 10-membered azaenediyne, while the substrate with a hydroxyl group gave only traces of the desired 10-membered oxacycle. An improved method for the deprotection of Co-complexes of cyclic enediynes using tetrabutylammonium fluoride in an acetone/water mixture and the investigation of the 10-membered enediynes' reactivity in the Bergman cyclization are also reported. In the solid state, all synthesized iodoethynylheterocycles were found to be involved in halogen bond (XB) formation with either O or N atoms as XB acceptors.