Synthesis of 5- and 6-(6-Chloro-3-pyridyl)-2-azabicyclo[2.2.0]hexanes. Epibatidine Analogs

Synthetic routes to vicinal-6-(6-Cl-3-pyridyl)- and distal-5-(6-Cl-3-pyridyl)-2-azabicyclo-[2.2.0]hexane analogs of the potent nicotinic receptor agonist epibatidine are described. Both exo-regioisomers are available from a readily available 2-azabicyclo[2.2.0]hex-5-ene by way of stereoselective reductive Heck addition of the 6-Cl-3-pyridyl moiety. Stereochemical inversion of the 6- and 5-aryl groups provides entry to the endo isomers.