Palladium(II)-catalyzed 1,4-oxidation of 2-aryl-1,3-cyclohexadienes. Application to the synthesis of (+/-)-epibatidine and analogues

Palladium(II)-catalyzed 1,4-chloroacetoxylation of 2-aryl-1,3-cyclohexadien es 2a and 2b resulted in a highly regio- and stereoselective reaction to gi ve cis-1-acetoxy-3-aryl-4-chloro-2-cyclohexenes 7a and 7b, respectively. Th e phenyl adduct 7a was subjected to the synthesis of exo- and endo-2-phenyl -7-azabicyclo[2.2.1]heptanes (exo-la and cndo-la). Stereoselective allylic nucleophilic substitution of the chloro group in 7a by tosylamide with eith er retention or inversion and hydrolysis to give 9a and 14a, respectively, followed by hydrogenation, cyclization, and deprotection afforded the targe t molecules. Interestingly, stereoselective hydrogenation of intermediates 9a and 14a afforded the required 1,2-cis and 1,2-trans relationships, respe ctively, between the nitrogen and the phenyl group. In an analogous manner, 7b was transformed to exo-12b, which previously has been converted to epib atidine.