Cr(II)-promoted internal cyclization of acyclic enediynes fused to benzo[b]thiophene core: Macrocycles versus 2-methylenecycloalkan-1-ols formation

• Published in: Arabian journal of chemistry 2019-02, Vol.12 (2), p.151-167
• Main Authors: Kulyashova, A.E., Ponomarev, A.V., Selivanov, S.I., Khlebnikov, A.F., Popik, V.V., Balova, I.A.
• Format: Article
• Language: English
• ISSN: 1878-5352
• DOI: 10.1016/j.arabjc.2018.05.005

The utility of the intramolecular Nozaki-type coupling for the synthesis of macrocyclic benzo[b]thiophene-fused enediynes has been explored. The starting acyclic enediynes were prepared by the iodocyclization of 2-(buta-1,3-diynyl)thioanisoles followed by the Sonogashira cross-coupling of the resulting iodo-substituted benzo[b]thiophene with corresponding acetylenes. We found that Cr(II)-promoted intramolecular cyclization of 7-[2-(iodoethynyl)benzo[b]thiophen-3-yl]hept-6-ynal and 7-[3-(iodoethynyl)benzo-[b]thiophen-2-yl]hept-6-ynal resulted in the formation of 11-membered macrocyclic enediynes, while both expected 10-membered enediynes cannot be produced under the Nozaki-type reaction from corresponding 6-[3-(iodoethynyl)benzo[b]thiophen-2-yl]hex-5-ynal and 6-[2-(iodoethynyl)benzo[b]thiophen-3-yl]hex-5-ynal. In the case the reaction was catalyzed by Ni(II), the attack on a proximal triple bond led to the formation of 2-methylenecycloalkane-1-ol fragments, instead of macrocyclization. The DFT analysis of the ring strain in the benzo[b]thiophene-fused 10- and 11-membered enediyne-containing cycle provides the plausible explanation of the observed regioselectivity. Keywords: Enediynes, Diacetylenes, Iodocyclization, Intramolecular Nozaki‐Hiyama‐Kishi reactions, Benzothiophene, Allylic alcohols