Diels-Alder/Ene Reactivities of 2-(1′-Cycloalkenyl)thiophenes and 2-(1′-Cycloalkenyl)benzo[ b]thiophenes with N-Phenylmaleimides: Role of Cycloalkene Ring Size on Benzothiophene and Dibenzothiophene Product Distributions

Wayland E. Noland, Honnaiah Vijay Kumar, Yernaidu Reddi, Christopher J. Cramer, Alexei V. Novikov, Hyejin Kim, Yumeng Zhu, Yoke Ching Chin, Yuqi Zhou, Predrag Radakovic, Anjola Uprety, Jun Xie, Grant C. Flick

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Abstract

Scaffolds of thiophene and benzothiophene are the important class of bioactive compounds found abundant in nature. The Diels-Alder reactions of 2-(1′-cycloalkenyl)thiophenes and 2-(1′-cycloalkenyl)benzo[b]thiophenes having the alkene groups present in five-, six-, seven-, eight-, and twelve-membered rings with substituted N-phenylmaleimides are characterized. The size of the cycloalkene rings plays a critical role in dictating the product distributions of expected and isomerized Diels-Alder adducts. 2D NMR studies indicate that the isolated isomers for 2-(1′-cycloalkenyl)thiophenes having five-, six-, and seven-membered rings are aromatized benzothiophene products, whereas eight- and twelve-membered rings are un-rearranged adducts. In addition, the product of subsequent ene-reaction with the N-phenylmaleimide is isolated for the five- and six-membered ring cases. Interestingly, in the 2-(1′-cycloalkenyl)benzo[b]thiophene having five-, six-, seven-, eight-, and twelve-membered rings, the un-rearranged dibenzothiophene Diels-Alder adduct is isolated in every instance. Molecular mechanics and density functional theory (M06-2X and PBE0-D3) calculations are performed to understand the differential reactivity of the various dienes for both the initial Diels-Alder reaction and a possible, subsequent ene reaction.

Original languageEnglish (US)
Pages (from-to)5265-5287
Number of pages23
JournalJournal of Organic Chemistry
Volume85
Issue number8
DOIs
StatePublished - Apr 17 2020

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