Studies On Phosphine-catalyzed [4+1] Annulations Of Electron-deficient 4π-conjugated Systems With Maleimides

Five-membered ring skeleton is an important molecular structure unit and widely exists in many important biologically active molecular structures. In recent years, the synthesis methods of construction of five-membered ring compounds by using phosphine, amine and other lewis base as catalysts have attracted great attention from chemists. Generally, there are three reaction modes for the construction of five-membered cycles by using tertiary phosphine as catalyst, which are [3+2] reaction mode, [4+1] reaction mode and [2+2+1] reaction mode. There also emerged many outstanding reports according to these three reaction modes. In the reported literatures, phosphine-catalyzed [4+1] annulations were all initiated by the in situ generated allylic P-ylides from MBH derivatives and phosphines, however, the non-allylic P-ylides initiated [4+1] annulation has not been reported before. This dissertation mainly focuses on the construction of five-membered cycles, providing a novel [4+1] annulation initiated by non-allylic P-ylides. The research in this dissertation includes the following three parts:In chapter 1, the recently advanves in phosphine or amine catalyzed cyclization reaction types of electron-deficient 4π-conjugated systems, maleimides and salicylaldehyde imine (salicylic aldehyde or salicylic ketone ester) compounds are briefly reviewed. On the basis of the findings in literatures, we put forward our research projects.In chapter 2, the background of common ylides of nitrogen, sulfur, and phosphorus initiated [4+1] annulation has been briefly introduced. A novel phosphine-catalyzed [4+1] annulation reaction of 1,3-dienes or 1,3-azadienes with maleimides have been developed for the first time. This reaction represents the first example of [4+1] cyclization between electron-deficient 4π-conjugated systems and non-allylic phosphorus ylides. Among them, the maleimides serves as C1 synthons. Mechanistic investigation implies that this cyclization takes place by the Michael addition-intramolecular SN2 substitution mode. These annulations provide a convenient and highly efficient method for the construction of important C-N spiro skeleton and N-N spiro skeleton.In chapter 3, on the basis of the previous work, the in situ generated non-allylic P-ylides initiated [4+1] annulation has been further explored. Phosphine-catalyzed [4+1] annulation between salicyl N-tosylimines and maleimides has been successfully developed by the optimization of reaction conditions. With mild reaction conditions and readily-prepared raw materials, this reaction can provide a simple and efficient method for the synthesis of O-N spiro skeleton compounds. Besides, the application of the in situ generated non-allylic P-ylides in [4+1] annulation has been enriched and developed by this work.