LE3 .A278 2015

2015

Jha, Amitabh

Acadia University

Master of Science

Masters

Chemistry

Chemistry

Fused heterocycles have received significant attention because of their diverse biological and pharmaceutical properties. For example, ()-nuevamine, which is the first known isoindoloisoquinoline alkaloid. Isoindolo[2,1-a]quinoline derivatives have attracted much interest because of their structural similarities with ()-nuevamine. In this study, diverse substituted 6,6a-dihydroisoindolo[2,1-a]quinolin-11(5H)-ones were successfully synthesized from N-aryl-3-hydroxyisoindolinones and substituted acetophenones including alkyl aryl cyclic ketones such as indanone and tetralone in three steps involving Lewis-acid-catalyzed C-C bond formation, NaBH4 reduction, and Lewis-acid-catalyzed intramolecular cyclization. First, 3-substituted-(2-oxo)-2-arylisoindolin-1-ones were obtained from fair to very good yields using Cu(OTf)2. The reaction involved N-acyliminium ion as the electrophile. To the best of our knowledge, acetophenones were used for the first time as nucleophiles for the reactions with N-acyliminium ions. Subsequent NaBH4 reduction afforded the corresponding 3-substituted-(2-hydroxy)-2-arylisoindolin-1-ones in excellent yields. Finally, BF3.OEt2-catalyzed intramolecular cyclization afforded substituted 6,6a-dihydroisoindolo[2,1-a]quinolin-11(5H)-ones from poor to excellent yields. All the products were well characterized by NMR and HRMS techniques. Some of the final products were unambiguously characterized by X-ray diffraction analysis. Pure diastereomers of the final products were obtained by recrystallization. Novel interesting tetracyclic and hexacyclic isoindoloquinolines were achieved by this method. The products have been submitted for biological activity as they have shown close structural resemblance with biologically active natural products.

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https://scholar.acadiau.ca/islandora/object/theses:396