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-pyridy l)-2-azabicyclo-[2.2.0]hexane analogs of the potent nicotinic receptor agon ist epibatidine are described. Both exo-regioisomers are available from a r eadily available 2-azabicyclo[2.2.0]hex-5-ene by way of stereoselective red uctive Heck addition of the 6-Cl-3-pyridyl moiety. Stereochemical inversion of the 6- and 5-aryl groups provides entry to the endo isomers. (C) 2000 E lsevier Science Ltd. All rights reserved.