MECHANISTIC INSIGHTS INTO ORGANOCATALYSIS - A COMPUTATIONAL STUDY

Abstract

In this thesis, modern density functional theory (DFT) methods were employed to shed light on the catalytic mechanisms and stereoselectivities of several important organocatalytic reactions. The investigation on a sulfa-Michael addition catalyzed by a cinchona alkaloid-squaramide catalyst revealed that more favorable cooperative noncovalent interactions in the preferred activation mode led to the stereoinduction. The inspection on asymmetric methanolysis of cyclic meso-anhydrides promoted by several amine-thiourea catalysts provided a general transition state model to predict and rationalize the reaction stereoselectivity. The origin of regioselectivity in a proline-tetrazole catalyzed N-nitroso aldol reaction was also elucidated by our survey on it. Finally, an in silico study on the catalyst-free 1,4-conjugate addition of methylamine to different Michael acceptors was performed to understand the reaction mechanism and to propose an effective organocatalyst for it. In summary, the theoretical exploration into these reactions in the thesis contributes to an insightful understanding of organocatalysis.