Synthesis and X-ray crystal structures of chiral, nonracemic 5,6-dihydro-4H-1,3,4-oxadiazines

✍ Scribed by Shawn R. Hitchcock; Melissa A. Dean; Christopher J. Kelley; Kate L. Edler; Gregory M. Ferrence

• Publisher: Journal of Heterocyclic Chemistry
• Year: 2010
• Tongue: English
• Weight: 501 KB
• Volume: 47
• Category: Article
• ISSN: 0022-152X
• DOI: 10.1002/jhet.402

✦ Synopsis

Abstract

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A series of chiral, nonracemic oxadiazines have been prepared from (1__R__,2__S__)‐ephedrine, (1__R__,2__S__)‐norephedrine, and L‐phenylalaninol. The synthesis of the Ephedra‐based oxadiazines was accomplished by a process of N‐nitrosation, reduction, acylation, and acid‐catalyzed cyclization. The trans‐ and cis‐diastereomeric oxadiazines derived from (1__R__,2__S__)‐ephedrine were analyzed by ^1^H NMR spectroscopy and by single crystal X‐ray crystallographic analysis. The stereochemistry of the (1__R__,2__S__)‐norephedrine–derived oxadiazines was assigned based on ^1^H NMR spectroscopy and by analogy with the X‐ray crystal structure of the (1__R__,2__S__)‐ephedrine–based oxadiazines. In addition, L‐phenylalaninol was used as a template to prepare a series of oxadiazines substituted at the N~4~‐nitrogen with an isopropyl group. This was accomplished by a reductive alkylation of L‐phenylalaninol with acetone and subsequent hydrazide formation. These hydrazides were reacted with methanesulfonyl chloride to yield the corresponding oxadiazines by a base‐mediated cyclization. J. Heterocyclic Chem., (2010).