Asyrometric Synthesis Of Pyrroloindolones And Fuylly Functionailzed Dihydropyranones Via N-Heterocyclic Carbene Catalysis

Synthesis of pharmaceutical compound and bioactive alkaloids scaffold via N-heterocyclic carbene catalysis is studied in this thesis which is composed of three parts:Chapter 1:This chapter firstly introduced the reaction of N-heterocyclic carbene (NHC) catalysis on the basis of electron properties of N-heterocyclic carbene and structure of substrates. Then the recent advances of Benzoin, Stetter reaction and a3-d3 umpolung in the field of NHC catalyzed asymmetric synthesis of pharmaceutical and bioactive scaffold were described, with an emphasis on a series of NHCs catalyzed novel reaction, such as hydroacylation of neutral olefin and cooperation with metal or other organocatalysts.Chapter 2:Pyrroloindolone, as an important scaffold of pyrrolo[1,2-α]indole, is ubiquitous and the ring system of which is common in a number of pharmaceutically important compounds and bioactive alkaloids. With very simple and readily available starting materials, we had successfully developed one-pot N-allylation/hydroacylation sequence to construct of quaternary pyrroloindolones by a combination of nucleophilic tertiary amine and NHC catalysis. Notably, the hydroacylation of active olefin which is similar to intramolecular anti-Stetter reaction is uncovered before. Therefore, this reaction not only provided a new access to construction of pyrroloindolones, but also established a novel reaction in NHC catalysis.Chapter 3:This chapter firstly described the recent advances of oxidative N-heterocyclic carbene catalysis. Then we represented a new chiral C1-symmetric NHC-catalyzed addition to a-aryl substituted α,β-disubstituted enals, which has been a longstanding and challenging issue for asymmetric catalysis. With a mild epoxidation process,δ-lactone epoxide, a scaffold widely existing in numerous biologically active compounds, was readily achieved with moderate yield but excellent diastereo- and enantioselectivity. Notably, the new chiral C1-symmetric NHCs were used as an organocatalyst for the first time.