Chemoselective Catellani Ortho-Arylation Of Indopyrroles:Total Synthesis Of Rhazinal

Catellani Reaction was a type of domino coupling reaction which was catalyzed by Pd and mediated by norbornene, and it received more and more attentions for the construction of the1,2,3-trisubstituted aromatic skeletons with high efficiency. Currently, the catellani reaction substrates was limited to halogenated benzenes and their derivatives, while heterocycle especially pyrrole compounds was rare. Besides, pyrrole skeleton is a structure which was common in natural products and pharmaceutical moleculars, and the efficient functionalization on it has an important significance. There are few examples that the Catellani reaction was applied to the synthesis of natural products. The rhazinilam family of natural products share a tetracyclic framework which contains an axial chiral pyrrole aniline biaryl fragment and a strained nine-membered lactam bearing a quaternary carbon center, and there are many syntheses about it has been reported. Here, we applized the catellani reaction of indopyrroles to construct the core structure of Rhazinilam family moleculars, and completed the total synthesis the Rhazinal rapidly.Chapter one introduced the process and mechanism of catellani reaction, in which a carbopalladacycle was formed and take the oxidative addition with another halogenated hydrocarbon. The review was focus on four aspects:the first was decribed based on different new bonds formed by using different trapping reagents; the second based on different ortho-substituents of halogen formed by the oxidative addition of carbopalladacycle with the second molecular halogenated hydrocarbon then reductive elimination; the third is about the synthetic applications of Catellani reaction on phermaceutical chemistry, materials and natural products; the forth based on other research progress.Chapter two introduced the experiments and discussions about the Catellani reaction of indopyrrole and the total synthesis of Rhazinal in two parts. The first part is about the choose and synthesis of model substrate based on the core structure of Rhazinilam family; The substrate reacted smoothly giving the core structure in one step efficiently, and the optimal conditions was screened with the catalyst PdCl2and PPh3, the base Cs2CO3, the solvent dioxane, giving the best results; The teminal alkene double bond of the model reaction product was functioned to try to finish the total synthesis. The second part dicussed the total synthesis of Rhazinal by the redesigned approch, including the synthesis of the substrate, the effect of remote substituent on the key reaction; the optimization of hydrogenation reaction conditions and the other steps of the total synthesis; the reaction of other halogenated pyrrole was also studied to come to a conclusion that the indopyrroles with a with-drawing substituent give better results. In one word, the total synthesis of Rhazinal was completed with the overall yield13.4%in11steps, and the Catellani reaction of indoprroles was also developed.