SYNTHESIS OF (+)-N-BOC-7-AZABICYCLO[2.2.1]HEPTAN-2-ONE AND (-)-N-BOC-7-AZABICYCLO[2.2.1]HEPTAN-2-ONE VERSATILE INTERMEDIATES FOR THE ENANTIOSPECIFIC SYNTHESIS OF (+)-EPIBATIDINE AND (-)-EPIBATIDINE AND ANALOGS

(+)- and (-)-Epibatidine, nonopiate antinociceptive alkaloids, have been prepared from (-)- and (+)-N-BOC-7-azabicyclo[2.2.1]heptan-2-one which were produced by resolution of the racemic mixture of the corresponding alcohols obtained in the previous racemic synthesis. In the present work, we report the enantiospecific synthesis of(-)- and (+)-N-BOC-7-azabicyclo[2.2.1]heptan-2-one from L-glutamic acid and levulinic acid. Also, this report describes the selective formation of trans-2,3-disubstituted-7-azabicyclo[2.2.1]heptanes from N-benzyl-5-(1'-methoxycarbonyl-3'-oxobutyl)proline via a decarbonylation/iminium ion cyclization process. These functionalized intermediates are of potential value for the enantiospecific synthesis of epibatidine analogues.