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-diynes cyclizations with the formation of iodoethynylheterocycles, followed by a Sonogashira coupling. The nature of both a heterocycle and a nucleophilic group affected the possibility of a 10-membered cycle closure by the Nicholas reaction. Among oxacycles, only isocoumarin-fused enediyne was obtained. In the case of O-enediyne annulated with indole, instead of 10-membered cycle formation, BF3-promoted addition of OH-group to the proximal triple bond at C3 position afforded dihydrofuryl-substituted indole. For 1,2,3-triazole-fused analogues, NH-Ts group was suitable for the synthesis of 10-membered azaenediyne as opposed to OH function, which gave only traces of desired 10-membered oxacycle. The improved method for deprotection of Co-complexes of cyclic enediynes using tetrabutylammonium fluoride in acetone/water mixture and investigation of the 10-membered enediynes’ reactivity in the Berman cyclization are also reported. In solid state all iodoethynylheterocycles synthesized were found to be involved in halogen bond (XB) formation with either O or N atoms as XB acceptors.