Approaches to syn-7-substituted 2-azanorbornanes as potential nicotinic agonists; synthesis of syn- and anti-isoepibatidine.
[reaction: see text] Coupling of N-Boc-7-bromo-2-azabicyclo[2.2.1]heptane with aryl and pyridyl boronic acids incorporates aryl and heterocyclic substituents at the 7-position and leads to a preference for syn over anti stereoisomers. Incorporation of a chloropyridyl group followed by N-deprotection gives syn-isoepibatidine. Facial selectivity in attack on 7-keto-2-azanorbornanes depends heavily on the N-protecting group leading to the first syn-7-hydroxy-2-azabicyclo[2.2.1]heptane derivative.
Malpass
John R
JR
Department of Chemistry, University of Leicester, Leicester LE1 7RH, United Kingdom. jrm@le.ac.uk
Handa
Sandeep
S
White
Richard
R
D001372:Aza Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D001384:Azetidines / Q000138:chemical synthesis / Q000737:chemistry; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000737:chemistry; D018360:Crystallography, X-Ray; D008968:Molecular Conformation; D015394:Molecular Structure; D018722:Nicotinic Agonists / Q000138:chemical synthesis* / Q000737:chemistry; D009636:Norbornanes / Q000138:chemical synthesis* / Q000737:chemistry; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
C109763:5-(2-azetidinylmethoxy)-2-chloropyridine; D001372:Aza Compounds; D001384:Azetidines; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018722:Nicotinic Agonists; D009636:Norbornanes; D011725:Pyridines; C082748:epibatidine