1H NMR Study of Conformational Differences in 3-tert-Butyldimethylsiloxy- and 9-Methyl-8-oxa-9-azabicyclo[3.2.2]non-6-en-3-ol Intermediates for Bridgehead Hydroxylated Tropane Alkaloid Derivatives
✍ Scribed by Robert Glaser; Gregory J. Tarrant; John B. Bremner
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- English
- Weight
- 275 KB
- Volume
- 35
- Category
- Article
- ISSN
- 0749-1581
No coin nor oath required. For personal study only.
✦ Synopsis
The stereochemistry of bicyclic oxazepane-type intermediates for the synthesis of hydroxylated tropane alkaloids was determined by 1H NMR spectroscopy. Thermolysis of the 3a-tert-butyldimethylsiloxy-8-methyl-8azabicyclo [ 3.2.1 ] oct-6-ene axial N-oxide diastereomer (1) in butyronitrile a †orded the Meisenheimer rearrangement product, (1R*, 3S*, 5S*)-3-(tert-butyldimethylsiloxy)-9-methyl-8-oxa-9-azabicyclo [ 3.2.2 ] non-6-ene (2). NMR techniques have shown that this product experiences a conformational bias favoring occupancy of the bulky 3-tert-butyldimethylsiloxy substituent in an exo-disposed equatorial position on a boat oxazepane ring. It was found the tert-butyldimethylsiloxycycloheptenylamino fragment in 2 retained the same relative stereochemistry as ascribed to this moiety in the starting material 1. Removal of the bulky tert-butyldimethylsilyl protecting group a †orded 5, having a less sterically demanding 3-hydroxy substituent, and resulted in an equilibrium between the boat and chair oxazepane ring conformations.