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

Robert Glaser, Gregory J. Tarrant, John B. Bremner

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

The stereochemistry of bicyclic oxazepane-type intermediates for the synthesis of hydroxylated tropane alkaloids was determined by 1H NMR spectroscopy. Thermolysis of the 3α-tert-butyldimethylsiloxy-8-methyl-8-azabicyclo[3.2.1]oct-6-ene axial N-oxide diastereomer (1) in butyronitrile afforded 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 afforded 5, having a less sterically demanding 3-hydroxy substituent, and resulted in an equilibrium between the boat and chair oxazepane ring conformations.

Original languageEnglish
Pages (from-to)389-394
Number of pages6
JournalMagnetic Resonance in Chemistry
Volume35
Issue number6
DOIs
StatePublished - 1 Jan 1997

Keywords

  • Meisenheimer rearrangement
  • NMR
  • Physoperuvine
  • Stereochemistry
  • Tropane alkaloid

ASJC Scopus subject areas

  • Chemistry (all)
  • Materials Science (all)

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