Understanding the Through-Space Intermolecular Interactions of Isothiourea Catalysts in Acylation/Silylation Reactions of Secondary Alcohols

Through space interactions, including cation-π interaction, lone pair-πinteraction, steric hinderance etc. play a central role in organocatalytic reaction. They can control the reactivity or the selectivity of an organic reaction. Previous work in our group has already shown that the chiral isothiourea compounds can catalyze the acylation as well as silylation reaction of secondary alcohol with the possible cation-πinteraction between the catalyst and substrate. However, there is lack of study to understand how the delocalization of the positive charge would affect the reaction rate and whether some unexpected inter- or intramolecular interaction could help stabilize the cationic complex. This thesis is first going to introduce different types of the through space interactions and the physical organic methods to understand their basic properties. The Chapter 2 will show the evidence we found that can support the cation-πinteraction between the substrate and catalyst using linear free energy relationship (LFER) study. We will also discuss the extra through space interaction by multi-parameter fit and computational study. Chapter 3 will compare the intramolecular through space interactions in the silylated/acylated complexes that control the reactivity of isothiourea catalyst in the organic reaction using rate study, potentiometric titration and computational method. In general, this thesis will provide deeper insight into how the isothiourea based catalysts functioned in the acylation/silylation reaction of secondary alcohol and provide potential ideas for catalyst design to increase the selectivity of the reactions.