Intramolecular Nicholas Reactions in the Synthesis of Heteroenediynes Fused to Indole, Triazole, and Isocoumarin

Natalia A. Danilkina, Alexander S. D’yachenko, Anastasia I. Govdi, Alexander F. Khlebnikov, Ilya V. Kornyakov

Research output

Abstract

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.
Original languageEnglish
JournalThe Journal of organic chemistry
DOIs
Publication statusE-pub ahead of print - 8 Jun 2020

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