Fused-ring nitrogen and sulfur heterocycles by a tandem SN2-michael addition reaction

✍ Scribed by Richard A. Bunce; Sharadsrikar V. Kotturi; Christopher J. Peeples; Elizabeth M. Holt

• Publisher: Journal of Heterocyclic Chemistry
• Year: 2002
• Tongue: English
• Weight: 69 KB
• Volume: 39
• Category: Article
• ISSN: 0022-152X
• DOI: 10.1002/jhet.5570390531

✦ Synopsis

Abstract

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.