Three-Component Cascasde Reactions Based On Zwitterionic Intermediates Trapping By Aliphatic Aldimines And β,γ-Unsaturated α-Keto Esters

Multi-component reactions (MCRs) mean three or more substrates react in a reaction vessel, and all or most of the substrate atoms contribute into the final product. Mul-ticomponent reaction is simple, efficient and atom economical, and attracts more and more attention in both academic and industrial area. In recent years, Professor Hu developed a multi-component reaction employing electrophiles to capture ylides or zwitterionic intermediates derived from nucleophiles attacking metal carbenes, and have achieved good results.Indole alkaloids spread widely in the nature. Since they have special biological activity in vivo, indole derivatives gain more and more attention in the medicine science. In 2012, Professor Hu reported a process for the trapping of zwitterionic intermediates derived from metal carbene and indole by imines, obtaining triptamine derivitives with excellent enantioselectivity and provided a new method to construct indole alkaloids efficiently. We go on our research based on the work mentioned above.Chapter 1 introduces the properties and reaction types of diazo compounds and metal carbenes, as well as the strategy of multi-component reactions and multi-component cascade reactions. In the meantime, the multi-component reactions of trapping ylide and zwitterionic intermediates by electrophiles and cross dehydrogenation coupling reactions were elaborated. Based on this, we propose designed strategies of this dissertation.Chapter 2 mentions the multi-component cascade reaction of trapping zwitterionic intermediates by aliphatic aldimines to provide tetrahydro-β-carboline derivatives. Based on our previous reaserach, we first propose N-benzylimines as electrophilic trapping species in the multi-component reaction, and studied the cyclization of products employing Pictet-Spengler intramolecular condensation reaction.Chapter 3 descends from chapter 2. Converting N-benzyl to steric N-benzhydryl imines, we can regulate diastereoselectivity by altering the type of chiral phosphoric acids providing α,β-substituted tryptamine derivatives with excellent enantioselectivity.Chapter 4 introduces the multi-component cascade reaction of trapping zwitterionic intermediates by β, γ-unsaturated-a-keto esters with subsequent dehydrogenation coupling to provide 1,2,3,4-tetrohydrocyclopent[b]indole derivatives. We firstly realized Michael reation of trapping zwitterionic intermediates by Michael receptors.