Introduction to Alkaloids

Abstract

Addition of secondary amino acid derivatives to (?/5-pentadienyl)tricarbonyliron cations gives (?74-diene)tricarbonyliron complexes in high yields with amino ester groups at the terminal position of the diene ligands. Treatments of the adducts containing a sarcosine, phenylalanine, or alanine moiety with lithium diisopropylamide (LDA), under an atmosphere of carbon monoxide, furnish fused 3-azabicyclo[3.3.0]octanecarboxylic acid derivatives. Under the same reaction conditions, intramolecular cyclizations of complexes containing a proline or pipecolinic acid derivative at the terminal position of the diene ligands give 6-azatricyclo-[6.3.0.02'6]undecane and 7-azatricyclo[7.3.0.02'7]dodecane ring systems, respectively, whereas treatment of the complex containing a nipecotic acid derivative provides a bridged 8-azatricyclo[6.3.1.02'6]dodecanecarboxylic acid derivative. Nitrogen-containing heterocyclic compounds have figured prominently in chemistry due to their useful pharmacological properties, their structural novelty, and their attendant rich chemistry.1 In spite of the numerous literature on the synthesis of nitrogen-containing heterobicyclic compounds,2 there have been few reports on the preparation of nitrogen-containing heterobicyclic and-tricyclic compounds promoted by transition metals. Of these reactions, however, formation of fused nitrogen-containing heterobicyclic compounds has so far been restricted to only cobalt-,3 chromium-,4 titanium-,5 nickel-,6 iron-,7 or palladium-promoted8 cyclization of ® Andree, G.; Seidel, A.; Schmickler, H.; Lex, J.; Kraka, E.; Haug, M.; Cremer, D.; Vogel, E. Angew. Chem., Int. Ed. Engl. 1985, 24, 592. (e) Kato, H.; Arikawa, Y.; Hashimoto, M.; Masuzawa, M. J. Chem. Soc., Chem. Commun. Í983, 938. (fi Tokitoh, N.; Okazaki, R. unsaturated molecules. Only limited examples of cobalt-mediated (the Pauson-Khand reaction) coupling reactions of alkyne to alkene followed by radical cyclization to give angularly fused triquinanes containing a nitrogen atom9a and a palladium-catalyzed cyclization of a polyenyne to give a linearly fused triquinane containing a nitrogen atom have been explored.91" In this paper, we report that nitrogen-containing fused bicyclic, linearly fused tricyclic, and bridged tricyclic skeletons can be constructed by the intramolecular cyclization of the diene-iron complexes bearing amino acid derivatives at the terminal position of the diene ligands. The addition of primary amines to the (?/5-pentadi-enyl)Fe(CO)s cation (la) is known to proceed by exo attack to produce (?74-cts-dienylamine)Fe(CO)3 complexes and the binuclear species obtained by further reaction with the cation.10 This has been confirmed in our preliminary investigations; the reaction of the primary amino ester derivative HaNCHaCC^Et with la provided the binuclear species as the major product in 51% yield. (6) Tamao, K.; Kobayashi, K.; I to, Y.