The proposed study will focus on the further development of a new synthetic method for the construction of nitrogen-to-arene carbon bonds by the nucleophilic addition of nitrogen anions to pi- arenechromium (O) tricarbonyl complexes. We have demonstrated the use of the Cr(CO)3 moiety to activate aromatic rings toward nucleophilic attack by certain nitrogen anions, and we propose to expand this method in the intramolecular sense toward the development of a general procedure for the preparation of nitrogen heterocycles such as indole, quinoline, and benzazepine derivatives. Specific methodology will be continued to determine the best method of preparation of the pi-((omega-amidoalkyl)arene)- chromium(O) tricarbonyl complexes which will serve as the substrates in these cyclization reactions. The recent, unexpected observation that N-alkylbenzamides do not add cleanly to pi-(arene) chromium tricarbonyl complexes must be studied and understood in order to develop the cyclization method in its most general sense. The effect of ring size as well as the presence of ring substitutents on the intramolecular addition must also be studied. A method of double substitution, with both amido and carbanionic termini, will also be investigated. After these preliminary studies are complete, an appropriate heterocyclic natural product will be chosen for total synthesis as an example of the utility of this method in natural product and drug synthesis. The development of new, relevant synthetic methods for the preparation of nitrogen heterocycles is of great importance in the pharmaceutical industry. The addition of such new methods of molecular construction is always needed to expand the flexibility of the synthetic chemist in being able to prepare new or modify existing physiologically active compounds. This particular study will provide the ability to cyclize nitrogen functionality directly onto aromatic rings in a nucleophilic sense in contrast to most known synthetic methods where such rings can only be formed after the nitrogen atom has been electrophilically ortho-substituted onto the arene ring. This method has the potential of being a very general route to some common, important heterocyclic ring systems.
Showing the most recent 10 out of 19 publications
