Design And Synthesis Of Bifunctional Organocatalysts And Their Organocatalysis In Asymmetric Aldol Reactions

Asymmetric organocatalysis has developed rapidly in recent years, and hasalready achieved remarkable results in the exploration of novel organocatalysts,organocatalytic mechanisms, organocatalytic systems and reaction types etc. Ingeneral, organocatalysts have the function of enzymatic catalysis, which feature someunique properties such as simplicity, efficiency and environmental friendliness.Organocatalysis has found many applications in the asymmetric synthesis of manynatural products and bioactive molecules, and served as an important protocol toconstruct a wide variety of optically active chemical entities.Organocatalytic asymmetric Aldol reaction represents one of the most importantstrategies for the formation of C-C bonds, and is widely utilized in the asymmetricsynthesis of biologically active natural products and chiral drugs. On the basis ofvarious organocatalytic mechanisms, a large number of organocatalysts, which differin chemical structural features, have been developed for the direct catalyticasymmetric Aldol reaction. Being a family member of organocatalysts, thebifunctional organocatalysts are able to activate both electrophilic and nucleophilicreactants simultaneously in the organcatalytic direct Aldol reactions, thus deliveringhigh organocatalytic efficiencies and stereocontrols.Based on the Lewis base-Brondsted acid dual activation mechanism, wedesigned and synthesized different types of bifunctional organocatalysts with the useof axially unfixed biphenyl as scaffold and enantiopure α-amino acids as chiral source.The reaction conditions were optimized systematically by screening different factorsassociated with chiral induction. It was found that bifunctional organocatalyst50performed with high efficiencies and showed excellent enantioselectives anddiastereoselectives in asymmetric Aldol reactions (up to100%yield,97:3dr,98%ee).On the basis of control experiments and structure-activity relationship analysis ofsome organocatalysts designed in this work, we proposed a plausible mechanism forthe chiral induction observed with oragnocatalyst50.In summary, we designed and synthesized some bifunctional organocatalystswith different structural features, and studied their organocatalytic performace in thedirect asymmetric Aldol reactions; it was found the title bifunctional organocatalystsexhibited high reactivities and excellent stereoselectivities in the organocatalyticdirect Aldol reactions.