Studies on guanidinyl pyrrolidine catalyzed conjugate additions and synthesis of (-)-pancracine and (+)-ipalbidine

Lingampally, Rajinikanth (2011) Studies on guanidinyl pyrrolidine catalyzed conjugate additions and synthesis of (-)-pancracine and (+)-ipalbidine. Doctoral (PhD) thesis, Memorial University of Newfoundland.

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The organocatalytic, asymmetric conjugate addition of carbon nucleophiles and heteroatom nucleophiles to enones is of interest because the products are useful synthetic intermediates. We have observed that these reactions are catalyzed by proline-derived guanidines. The present study examines the enantioselective addition of malonates, nitroalkanes and heteroatom nucleophiles to a variety of enones in order to provide the corresponding Michael adducts. The observations from this study provide some insight into the reactivity of amine-guanidine bifunctional catalyst motifs and lay the foundation for designing second generation catalysts having modulated nucleophilic and basic character. -- Enantiomerically pure γ-nitroketones and their derivatives are an important class of organic compounds due to their utility as building blocks for the asymmetric synthesis of natural products and biologically active molecules. In the present study, the organocatalytic Michael addition of a monoprotected cyclohexane 1,3-dione and selected β-nitro styrenes in the presence of a proline-derived triamine catalyst provided the conjugate addition products in good yield (83-90%), with high enantiomeric excess (89-99%) and high diastereoselectivity (≥19/1). These Michael adducts were utilized in a stereoselective synthesis of cis and trans-3-aryloctahydroindoles. Application of this methodology is presented in a short formal total synthesis of the methanomorphanthridine alkaloid (-)-pancracine. -- Enantiomerically enriched γ-nitroketones obtained from the triamine catalyzed organocatalytic Michael addition were also utilized as starting materials in an efficient synthesis of indolizidines. The utility of this methodology is highlighted by its application in a short total synthesis of the arylindolizidine alkaloid (+)-ipalbidine. The synthetic strategy has potential applications in the preparation of congeners and analogs of several arylindolizidine alkaloids.

Item Type: Thesis (Doctoral (PhD))
Item ID: 9544
Additional Information: Includes bibliographical references.
Department(s): Science, Faculty of > Chemistry
Date: 2011
Date Type: Submission
Library of Congress Subject Heading: Alkaloids--Synthesis; Asymmetric synthesis; Pyrrolidine; Catalysts

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