Asymmetric Homogeneous Hydrogenation of Prochiral Substrates Mediated Through Carboxylic Acid and Carbamic Acid Metal-Binding Functional Groups

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Authors

de Winter, Tamara

Date

2016-01-11

Type

thesis

Language

eng

Keyword

Hydrogenation , Asymmetric

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Abstract

The need for enantiopure chiral compounds has driven the development of asymmetric synthesis, and more specifically asymmetric catalysis. The ability to selectively produce one enantiomer versus another has been a significant discovery for the production of natural products and pharmaceuticals, as both enantiomers may elicit very different interaction in living animals, either being therapeutic or toxic. This thesis investigates the structure of the substrate and its effect in the homogeneously-catalyzed asymmetric hydrogenation of C=C and C=O double bonds. In a study of the asymmetric hydrogenation of unsaturated carboxylic acids, the effects of the length of the linker between the unsaturation and the carboxylic acid functional group on the yield and selectivity of the asymmetric hydrogenation reaction were investigated. We selected Noyori’s Ru-binap catalysts and their derivatives as they are known to work well, in terms of high conversions and enantioselectivities, for the asymmetric hydrogenation of unsaturated carboxylic acids, such as atropic or tiglic acid. Other catalysts selected were a Rh-catalyst, and two Ir-catalysts reported to hydrogenate unsaturated carboxylic acids. In the subsequent chapter, this study was extended to ketoacids. The effect of the change in unsaturation, i.e. olefin to ketone, is discussed, as well as the effects of the length of the linker on the asymmetric hydrogenation. In these two studies, it was found that a gamma, delta-unsaturated carboxylic acid and a gamma-ketoacid could be asymmetrically hydrogenated in medium to high yield and enantioselectivity; however, the asymmetric hydrogenation of substrates with a greater distance between the unsaturation and the acid group had poor yield and selectivity. In the fifth chapter, a new methodology for the asymmetric hydrogenation of allylamines was developed. This new method takes advantage of a reversible reaction between amines and carbon dioxide (CO2) to suppress unwanted side reactions. The effects of various parameters on the enantioselectivity and conversion of the reaction were studied. It was found that the homogeneous-catalyzed asymmetric hydrogenation of 2-phenylprop-2-en-1-amine resulted in complete conversion and good enantioselectivity. Also, the presence of CO2(g) impeded the side reactions and the formation of unwanted byproducts. The best results found for 2-phenylprop-2-en-1-amine were implemented in the hydrogenation of its derivatives.

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Thesis (Ph.D, Chemistry) -- Queen's University, 2016-01-04 13:53:27.668

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