Studies on selected organocatalytic Mannich, vinylogous and conjugate addition reactions and the stereoselective synthesis of selected aspulvinones

Annadate, Ritesh (2020) Studies on selected organocatalytic Mannich, vinylogous and conjugate addition reactions and the stereoselective synthesis of selected aspulvinones. Doctoral (PhD) thesis, Memorial University of Newfoundland.

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Abstract

The functionalized γ-butenolide (2-(5H) furanone) motif is found in various natural products and hence the synthesis of butenolides is of considerable interest. The organocatalytic direct Mannich reaction of γ-crotonolactone with cyclic imines or in-situ generated iminium ions, to provide the functionalized butenolides is not reported. Several new bifunctional thiourea catalysts incorporating a chiral phosphoramide functionality, were prepared and examined in these reactions. These furanones are potential precursors for the synthesis of functionalized quinolizidines such as the homopumiliotoxins and indolizidines such as the pumiliotoxins. Details of these studies are described in Chapter 1. The organocatalytic Michael addition of cyclic ketones and aldehydes to -nitrostyrenes, generated in-situ from the corresponding nitroacetates, was investigated. The use of pyrrolidine-based amine catalysts in the presence of a protonic acid was found to be optimal and provided enantiomerically enriched -nitro ketones or -nitro aldehydes in good yield. The utility of -nitro aldehydes in the synthesis of pyrrolidines was also established. Details of these studies are described in Chapter 2. The aspulvinones, 3-aryl-5-arylidene tetronic acids, are a major group of fungal metabolites which have attracted considerable interest due to their biological activity. A modular synthesis of aspulvinones B, D and the recently isolated aspulvinone Q was developed. The methodology features a stereoselective aldol condensation of diazotetronic acid with aldehydes to provide the 5-arylidene diazotetronates. A catalytic, intermolecular C-H insertion reaction of 5-arylidene diazotetronates with arenes provides the aspulvinones. Variation of the aldehyde and the arene components furnishes synthetic analogues of the aspulvinones. These results are presented in Chapter 3. The first organocatalytic asymmetric direct vinylogous aldol reaction of isatin with -angelicalactone for the construction of 3-substituted-3-hydroxyindoles by using various phosphoramide-thiourea catalysts was developed. Details of these studies are described in Chapter 4.

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