Study Based On Diazoamides Participated Reactions Of Trapping Active Zwitterionic Intermediates By Electrophiles

Diazo compound is one of the most important species in organic chemistry and they are widely used in organic synthesis due to their special reactivity. Recently, our group successively reported a series of diazos participated multi-component reactions based on trapping active ylide intermediates. However, the scope of diazos is just limited to diazo esters and diazo ketones.As an important part of diazo compounds, diazo amides are widely utilized in transition metal catalyzed C-H insertion reactions, cyclopropanation and aziridination. So far, there is no report focus on using electrophilic reagents to capture active zwitterionic intermediates derived by diazo amides. In this dissertation, we realized these transformations for the first time. This methodology is potentially valuable because it can construct highly substituted oxindole derivatives which are proverbially existed in substructures of natural products and synthetic intermediates of bioactive molecules.Chapter1is the short review of relevant literatures including diazo compounds, carbine, yilde chemistry and creativities of diazo amides. It also brief introduces the design strategies and content of this dissertation.In chapter2, we firstly achieved diazo amides involved three-component reactions based on trapping active ylide intermediates. The research showed diazoacetamide was decomposed by Rh2(OAc)4and formed carbenoid. In the presence of aniline as nucleophile, the carbenoid was transferred to ammonium ylide intermediate which is thus trapped by active carbonyl compound isatin to complete the transformation. This methodology can build up the framework of3-hydroxy-3-substituted oxindole derivatives in a single step with good yield and moderate diastereoselectivity.The research of chapter3was based on the rhodium catalyzed intramolecular C-H insertion of.N-methyl diazoacetamide. We designed to use imine as electrophile to trap the proposed zwitterionic intermediate and thus change the reaction pathway. Meanwhile, BINOL derived phosphoric acid played a role of co-catalyst to achieve asymmetric catalysis. The enantiomerically enriched3-mono-substitued oxindoles could be synthesized with good diastereoselectivity and enantioselectivity.Based on the research of chapter3, the work in chapter4broadened the scope of diazo amides to a-alkyl-N-methyl-diazoacetamide. We achieved Rh2(OAc)4and chiral Br(?)nsted Acid co-catalyzed trapping of zwitterionic intermediate by imines to obtained3-disubstituted oxindole derivatives with over99:1dr and up to98%ee. We also proposed the possible reaction pathway and "indirect proton transfer" process by conducting controlled deuterium-labeling experiment.In chapter5, we further expanded the electrophiles to active carbonyl compound isatins which were also capable of trapping the zwitterionic intermediates generated by diazo amides. The obtained bis-oxindole derivatives are useful intermediates in synthesizing alkaloids. The reaction can achieve good yield and diastereoselectivity. In addition, β,γ-unsaturated-a-ketoester can also be used as an electrophile to trap the zwitterionic intermediates and two types of oxindole derivatives can be generated from the same starting material by selective1,2and1,4-addition reactions.