5,6-DEHYDROISOQUINUCLIDINES AS SYNTHONS FOR NATURAL PRODUCTS (KETO FUNCTIONALIZATION, IBOGAMINE, ELECTROPHILIC ADDITION, PEDUNCULANNE, 593A)

5,6-Dehydroisoquinuclidines in which the nitrogen is protected by a carboalkoxy group have been prepared by Lewis acid catalyzed Diels-Alder cycloaddition of alkylidene bisurethanes with cyclohexadiene. Regioselective oxy mercuration using mercuric nitrate followed by Jones oxidation of the isomeric alcohols afforded exclusively 5-ketoisoquinuclidines. Baeyer-Villiger oxidation of 5 ketoisoquinuclidines using buffered peracetic acid afforded the lactone resulting from bridgehead migration exclusively. Acid catalyzed methanolysis afforded 2,5-cis-disubstituted piperidines.;Treatment of 5-substituted 5,6-dehydroisoquinuclidines with Br(,2) under a variety of conditions leads only to unrearranged products resulting from 1,2 addition of bromine. A mechanism consistent with these results is described.;Reaction of 5,6-dehydroisoquinuclidines with N-bromosuccinimide in aqueous dimethyl sulfoxide afforded rearranged bromohydrins (resulting from 1,2-shift of the C(,1)-N bonds). Reduction with tri-n-butyl tin hydride followed by pyridinium chlorochromate oxidation afforded N-carboalkoxy 7-azabicuclo 3.2.1 octan-2-one. Treatment of 3-exo or 3-endo substituted 5,6-dehydroisoquinuclidines with NBS in wet DMSO again afforded rearranged bromohydrins.;An approach to the alkaloid peduncinlavine utilizing this novel rearrangement is described.;Treatment of 5,6-dehydroisoquinuclidines with bromine in CH(,2)Cl(,2) at -78(DEGREES)C afforded rearranged products resulting from 1,2 shift of the C(,1)-N bond. Specifically, treatment of N-carboethoxy-2-azabicyclo 2.2.2 oct-5-ene under the above conditions afforded N-carboethoxy-2,8-dibromo-7-azabicyclo 3.2.1 octane.;Treatment of N-carboalkoxy-5,6-dehydroisoquinuclidines with phenylselenyl chloride in methylene chloride afforded regioselectively 5-chloro-6-phenylselenenyl isoquinuclidines. Treatment of N-carboethoxy-5-chloro-6-phenylselenenyl-2-azabicyclo 2.2.2 octane with neat DBU cleanly effected elimination of HCl aqueous. Acid hydrolysis of the resulting vinyl selenide cleanly afforded N-carboethoxy 6-ketoisoquinuclidines. The generality of the reaction was explored by carrying out the described sequence on a series of 3-exo and 3-endo substituted 5,6-dehydroisoquinuclidines.;Utilization of this method in a synthesis of epi-ibogamine is described. (Abstract shortened with permission of author.)...