Metal Free Aryl C-N Bond-forming Reaction And Its Application In The Synthesis Of Naturally Occurring Carbazole Alkaloids

Aromatic amine compounds are widely used in medicine, dye, pesticide, daily chemicals and materials. In the past20years, transition metal catalyzed C-N coupling reaction has been developed rapidly, but there are still some notable limitations. Palladium catalyzed coupling reaction need the phosphorus ligands with complex structure and expensive metal palladium. Copper catalyzed reactions often require large amounts of copper salt, and less reactive but more economically attractive aryl chlorides does not occur. Both of them have metal contamination problem, particularly in the pharmaceutical industry, where metal contamination to the products may cause serious problems. In this dissertation, we studied the construction of aryl C-N bond under metal-free condition and its application in the synthesis of naturally occurring carbazole alkaloids, some important results are obtained as follows:1. We have developed a new method for the construction of aryl C-N bond under metal-free condition. The research showed that the new method for synthesis of anilines were from aryloxyamides through Smiles rearrangement-amide hydrolysis tandem reaction. This process represents a practical method for the facile construction of anilines with a broad substrate scope and wide functional group tolerance in moderate to excellent yields. Aryloxyamides as the starting material which are easily prepared from phenols, successfully conversion to anilines via tandem reaction; Compare with palladium, copper or other transition metal catalyzed synthesis of aniline, this method showed more environmentally friendly, low cost and only need simple operation. Moreover, on the basis of mechanism proposals in previous studies and our experiment results, a plausible mechanism for the reaction was given.2. We have developed a new method for the phenols directly transform to arylamines under metal-free conditions:arylamines were synthesized from phenols and amination reagent through the tandem reaction of alkylation-Smiles rearrangement-amide hydrolysis under one-pot procedure. The transformation affords structurally diverse arylamines such as diarylamines, alkylarylamines and primary arylamines in good to excellent yields. In particular, a variety of halogenated arylamines or containing alkali sensitive functional groups arylamines were also readily produced using this method. In addition, the tandem reaction has also been successfully applied in the synthesis of laser dye coumarin (120) and scale up to gram scale, the yield will not fall.3. We have developed a new method of two step synthesis of naturally occurring carbazole alkaloids, using commercially available phenols as starting material, it was easy to convert into the corresponding diarylamines via the amination reactions, followed by Pd(Ⅱ)-catalyzed oxidative coupling reactions to afford Murrayafoline A, Mukonine and Clausenine. Also, a series of halogenated carbazoles were synthesized by the same method. The method for the two step synthesis of carbazole has the advantages of short steps, simple operation and reliable.