H-1-NMR STUDY OF CONFORMATIONAL DIFFERENCES IN 3-TERT-BUTYLDIMETHYLSILOXY AND 9-METHYL-8-OXA-9-AZABICYCLO[3.2.2]NON-6-EN-3-OL INTERMEDIATESFOR BRIDGEHEAD HYDROXYLATED TROPANE ALKALOID DERIVATIVES

The stereochemistry of bicyclic oxazepane-type intermediates for the s ynthesis of hydroxylated tropane alkaloids was determined by H-1 NMR s pectroscopy, Thermolysis of the 3 rt-butyldimethylsiloxy-8-methyl-8-az abicyclo[3.2.1 ]oct-6-ene axial N-oxide diastereomer (1) in butyronitr ile afforded the Meisenheimer rearrangement product, (1R, 3S*, t-buty ldimethylsiloxy)-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 substi tuent 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 mo iety in the starting material 1. Removal of the bulky tert-butyldimeth ylsilyl protecting group afforded 5, having a less sterically demandin g 3-hydroxy substituent, and resulted in an equilibrium between the bo at and chair oxazepane ring conformations. (C) 1997 by John Wiley & So ns, Ltd.