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A Diels–Alder/Ene Cascade Leading to 5‐(Pyrrolidin‐3‐yl)thieno[3,2‐ e ]isoindoles from Ketone‐derived 2‐Vinylthiophenes and N ‐Phenylmaleimide
Author(s) -
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.,
Ratanaya 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.
Publication year - 2018
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.3327
Subject(s) - chemistry , thiophene , ketone , diels–alder reaction , cycloaddition , ene reaction , organic chemistry , indole test , raney nickel , medicinal chemistry , stereochemistry , catalysis
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.