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Fused‐ring nitrogen and sulfur heterocycles by a tandem S N 2‐michael addition reaction
Author(s) -
Bunce Richard A.,
Kotturi Sharadsrikar V.,
Peeples Christopher J.,
Holt Elizabeth M.
Publication year - 2002
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.5570390531
Subject(s) - chemistry , isoindole , steric effects , tandem , thiophene , acetic acid , ring (chemistry) , sulfur , michael reaction , nitrogen , stereochemistry , medicinal chemistry , organic chemistry , catalysis , materials science , composite material
A tandem S N 2‐Michael addition reaction has been developed for the synthesis of cis ‐ and trans ‐fused nitrogen and sulfur heterocycles from the cis and trans isomers of ethyl (±)‐(2 E )‐3‐[2‐(iodomethyl)cyclo‐hexyl]‐2‐propenoate. Octahydro‐1 H ‐isoindole‐1‐acetic acid and octahydrobenzo[ c ]thiophene‐1‐acetic acid derivatives have been prepared and their stereochemistries elucidated using NMR and X‐ray crystallo‐graphic methods. Cyclization substrates for both the cis ‐ and the trans ‐fused rings are readily available in four steps from known compounds. Yields for the cyclization range from 80‐85% and stereochemical selec‐tivities with respect to the side chain vary from 12.5‐16:1 for the cis ‐fused structures to 6‐7.5:1 for the trans ‐fused structures. Steric interactions in the transition states for ring closure are proposed to rationalize the observed preferences.