Design And Synthesis Of Organocatalysts And Their Applications In Asymmetric Mannich Reaction

Mannich reaction is one of the most important reactions for the formation of carbon-carbon bond and carbon-nitrogen bond. In recent years, asymmetric Mannich reactions catalyzed by small molecule organocatalysts have been studied widely and thoroughly, which have been successfully applied in the synthesis of some natural products and drug intermediates.In this thesis, several kinds of bifunctional small molecular organocatalysts with various hydrogen-bond donating ability have been designed and synthesized, their synthetic methodologies have been explored and synthetic routes have also been optimized. These organocatalysts were further applied to catalyze the asymmetric Mannich reactions of ketones or aldhydes with N-Boc, N-PMP protected imines and alpha amino sulphones. The results have demonstrated that thiourea organocatalyst could give excellent yield (90%), high enantioselectivity (up to 99% e.e.) and diastereoselectivity (up to 99:1) when the reaction proceeded in chloroform or 1,2-dichloroethane with 10 mol% or 5 mol% catalyst loading at the designation temperature.