TY - JOUR

T1 - Intramolecular Nicholas Reactions in the Synthesis of Heteroenediynes Fused to Indole, Triazole, and Isocoumarin

AU - Danilkina, Natalia A.

AU - Дьяченко, Александр Сергеевич

AU - Govdi, Anastasia I.

AU - Khlebnikov, Alexander F.

AU - Kornyakov, Ilya V.

AU - Bräse, S.

AU - Balova, I.A.

N1 - Funding Information: This study was supported by RFBR (18-33-01213)—synthesis of triazole-fused enediynes (A.I.G.), Saint Petersburg state university (event no. 6, 2019)—other synthetic work (A.S.D.), and RSF (19-73-10077)—halogen bonding in iodoheterocycles (A.I.G.). The research was carried out with the equipment of the SPbU Research Park: Magnetic Resonance Research Centre, Thermogravimetric and Calorimetric Research Centre, Chemical Analysis and Materials Research Centre, Educational Resource Centre of Chemistry, Centre for X-ray Diffraction Studies, and Computer Centre. The authors are thankful to Dr. Mikhail Chislov (SPbU) for the help with DSC measurements, staff of the Magnetic Resonance Research Centre for the measurement of NMR spectra of Co complexes, Dr. Alexander D. Misharev (SPbU) for the measurements of HRMS spectra of Co-complexes and enediynes, Dr. Galina L. Starova (SPbU) and Vitalii V. Suslonov (SPbU) for X-ray diffraction studies, and Prof. Vadim Y. Kukushin (SPbU) for valuable comments.

PY - 2020/7/17

Y1 - 2020/7/17

N2 - 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.

AB - 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.

KW - ACTIVATION

KW - BENZOTHIOPHENE

KW - BERGMAN CYCLIZATION

KW - CYCLOADDITIONS

KW - CYCLOAROMATIZATION

KW - ELECTROPHILIC CYCLIZATION

KW - ENEDIYNE COMPOUNDS

KW - MEDIATED SYNTHESIS

KW - PHOTOCHEMICAL GENERATION

KW - REACTIVITY

UR - http://www.scopus.com/inward/record.url?scp=85089262166&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/23a3af9a-197c-38c7-99f2-c56e63228f4e/

U2 - 10.1021/acs.joc.0c00930

DO - 10.1021/acs.joc.0c00930

M3 - Article

VL - 85

SP - 9001

EP - 9014

JO - Journal of Organic Chemistry

JF - Journal of Organic Chemistry

SN - 0022-3263

IS - 14

ER -