7-substituted 2-azabicyclo[2.2.1]heptanes as key intermediates for the synthesis of novel epibatidine analogues; synthesis of syn-and anti-isoepiboxidine.
Neighboring group participation by the 2-nitrogen in anti-7-bromo-2-benzyl-2-azabicyclo[2.2.1]heptane allows ready nucleophilic substitution at the 7-position by C, N, O, and halogen nucleophiles and opens the way to a range of novel 7-substituted 2-azabicyclo[2.2.1]heptanes. Conversion of an anti-7-ethoxycarbonyl group into a methylisoxazole ring provides anti-isoepiboxidine, a conversion that is possible even without protection of the secondary bicyclic nitrogen. Successful base-induced epimerization alpha to the carbonyl of the anti-7-ethoxycarbonyl derivative gives the syn-stereoisomer and hence syn-isoepiboxidine.
Department of Chemistry, University of Leicester, Leicester LE1 7RH, United Kingdom. jrm@le.ac.uk
John R
JR
Malpass
Richard
R
White
D001372:Aza Compounds / Q000737:chemistry*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000737:chemistry; D006536:Heptanes / Q000737:chemistry*; D008956:Models, Chemical; D015394:Molecular Structure; D018722:Nicotinic Agonists / Q000138:chemical synthesis* / Q000737:chemistry; D019906:Nuclear Magnetic Resonance, Biomolecular; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D001372:Aza Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D006536:Heptanes; D018722:Nicotinic Agonists; D011725:Pyridines; C082748:epibatidine