A Diels–Alder/Ene Cascade Leading to 5‐(Pyrrolidin‐3‐yl)thieno[3,2‐e]isoindoles from Ketone‐derived 2‐Vinylthiophenes and N‐Phenylmaleimide

A Diels–Alder/Ene Cascade Leading to 5‐(Pyrrolidin‐3‐yl)thieno[3,2‐e]isoindoles from Ketone‐derived 2‐Vinylthiophenes and N‐Phenylmaleimide

In an extension of our prior work with indoles and pyrroles, the Diels–Alder chemistry of substituted 2‐vinylthiophenes was explored, using N‐phenylmaleimide as the dienophile. The dienes were prepared from thiophene in two steps by addition to various ketones, followed by dehydration (40–60% overal...

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Bibliographic Details
Published in:Journal of heterocyclic chemistry Vol. 55; no. 12; pp. 2698 - 2714
Main Authors: Noland, Wayland E., Huisenga, Matthew P., Herzig, Ryan J., Rosenow, John A., Kim, Hoyeon, Kroll, Neil J., Nesmelov, Andrei, Johnson, Benjamin T., Duncan, Nathan S., Ratanayanon, Jidapa, Yue, Ruixian A., Xiong, Kenny, Ong, Bee K., Vo, Diane T., Klein, Nathan D., Lang, Simon B., Riley, Jacob K., Daniels, Steven P., Tritch, Kenneth J.
Format: Journal Article
Language:English
Published: Hoboken Wiley Subscription Services, Inc 01-12-2018
Subjects:
Biological activity
Catalysts
Cycloaddition
Dehydration
Dienes
Indoles
Ketones
Organic chemistry
Pyrroles
Yield
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Summary:In an extension of our prior work with indoles and pyrroles, the Diels–Alder chemistry of substituted 2‐vinylthiophenes was explored, using N‐phenylmaleimide as the dienophile. The dienes were prepared from thiophene in two steps by addition to various ketones, followed by dehydration (40–60% overall yields). Although most dienes were obtained as regioisomeric mixtures, the Diels–Alder‐derived products were easily purified by chromatography. The main cycloaddition pathway was endo Diels–Alder addition followed by exo ene addition of a second molecule of dienophile (19–33% yields). Several products were desulfurized with Raney nickel (48–62% yields). Unfortunately, no thiophene‐derived products showed the promising biological activity of the previously reported indole analogs.
ISSN:0022-152X
1943-5193
DOI:10.1002/jhet.3327