Studies On The Total Synthesis Of (�)-Crinine And The Asymmetric Organocatalytic Intramolecular Aza-Michael Reaction

This thesis mainly describes the progress of catalytic asymmetric aza-Michael addition reactions over the past decade, total synthesis of amaryllidaceae alkaloid (�)-crinine, and the asymmetric organocatalysis aza-Michael addition of enones. The following three chapters as follows:The First Chapter:Recent Progress of Catalytic Asymmetric Aza-Michael AdditionThis chapter reviews the recent progress of catalytic asymmetric aza-Michael reaction and its applications in natural products synthesis. According to the substrate combination of donors and acceptors, the intermolecular aza-Michael reaction and the intramolecular aza-Michael reaction in catalytic asymmetric fashion were included. Besides, the tandem reaction involving asymmetric aza-Michael reaction was also presented.The Second Chapter:Total Synthesis of Amaryllidaceae Alkaloid (�)-crinineThis chapter describes total synthesis of amaryllidaceae alkaloid (�)-crinine, which was featured by the effective construction of the key arylic quaternary carbon through semipinacol rearrangement of allylic alcohols. Commenced with the acyclic allyl alcohol, the total synthesis of (�)-crinine was successfully accomplished by 10 steps in 24% overall yield, and also the alkaloid 6-epi-(�)-crinine was achieved.The Third Chapter:Catalytic Asymmetric Intramolecular aza-Michael Addition of EnonesThis chapter mainly concentrates on the development of asymmetric intramolecular aza-Michael addition of enones catalyzed by quinine-derived primary amine catalyst. Upon the screening of catalysts, acid additives and solvents, a series of substituted piperidine compounds were accessed in high yield (up to 98% yield) with excellent enantioselectivity (up to 99% ee), leading to a novel route for the synthesis of the structurally related 2-substituted piperidine alkaloids.