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1 H 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
Author(s) -
Glaser Robert,
Tarrant Gregory J.,
Bremner John B.
Publication year - 1997
Publication title -
magnetic resonance in chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.483
H-Index - 72
eISSN - 1097-458X
pISSN - 0749-1581
DOI - 10.1002/(sici)1097-458x(199706)35:6<389::aid-omr103>3.0.co;2-8
Subject(s) - chemistry , tropane , stereochemistry , bicyclic molecule , substituent , moiety , diastereomer , ring (chemistry) , nuclear magnetic resonance spectroscopy , steric effects , organic chemistry
The stereochemistry of bicyclic oxazepane‐type intermediates for the synthesis of hydroxylated tropane alkaloids was determined by 1 H 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, (1 R *, 3 S *, 5 S *)‐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. © 1997 John Wiley & Sons, Ltd.