Organocatalytic Michael addition reactions of nitrostyrenes and application in the synthesis of selected indolizidine and quinolizidine alkaloids

Nagamyian Vengada Guru, Moorthy (2017) Organocatalytic Michael addition reactions of nitrostyrenes and application in the synthesis of selected indolizidine and quinolizidine alkaloids. Doctoral (PhD) thesis, Memorial University of Newfoundland.

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Abstract

The organocatalytic asymmetric conjugate addition of carbon nucleophiles and heteroatom nucleophiles to electron deficient nitroalkenes is an important tool for the synthesis of highly functionalized building blocks for applications in medicinal and synthetic organic chemistry. Although the enantioselective conjugate addition reactions of -nitrostyrenes are well known, the corresponding conjugate addition reactions of - nitrostyrenes are not reported. The present study examines the organocatalytic asymmetric, enamine-mediated conjugate addition reaction of aldehydes or cyclic ketones to -nitrostyrenes that were generated in situ from the corresponding nitroacetates. The details of this study are described in Chapter 2 of this thesis. The utility of the above methodology was demonstrated by application in the formal total synthesis of 4-aryl indolizidine alkaloids, (+)-lasubine II and (-)-subcosine II. The organocatalytic Michael addition of 1,4-cyclohexanedione monoethylene ketal to an appropriate -nitrostyrene which were generated in situ from the corresponding nitroacetate gave the key -nitroketone which was used as the starting material in the alkaloid synthesis. The details of this study are described in Chapter 3. Finally, an enantiomerically enriched -nitroketone obtained from the organocatalytic Michael addition of 1,4-cyclohexanedione monoethylene ketal to a - nitrostyrene has been utilized in the synthesis of a recently isolated indolizidine alkaloid, (+)-fistulopsine B, which is of interest due to its anticancer activity. Details of this investigation are described in Chapter 4.

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