Construction Of Several Kinds Of Nitrogen - Containing Heterocyclic Compounds Based On Isocyanate Insertion Reaction

N-containing compounds, which are always found in many natural products and medicines commercially available, are very important object of deep investigation due to their broad ranges of promising bio-activities. According to the statistical data on top 200 medicinal sales in America in 2009, about 80 percent is N-containing architectures.Isocyanides derivatives are versatile synthetic intermediates. We design two kinds of isocyanides-based imidolylation reaction to produce N-heterocyclic compounds with high efficiency. Based on the developed two kinds of reactions, we have achieved that quinazolines, fused-quinazolines, imidazoloquinazolines, imidazoloimidazoles, cyanative indoles, and cyanative isoquinolines.In this regard, this dissertation is divided into four parts according to these different structural motifs.In the first part, we develop a palladium-catalyzed three-component reaction of carbodiimide, amines, and isocyanides, resulting in 2-amino-4-iminoquinazolines with high efficiency. In the process, palladium acetate is employed as metal catalyst. PCy3 is used as mono-dentate ligand, and Cs2CO3 is utilized as a base. What’s more, tandem nucleophilic addition, imidolylation of isocyanides, and palladium-caltayzed C-N bonds formation are involved, and the tandem reactions proceed smoothly with high bond-forming efficiency due to the formation of several new chemical bonds in one-pot procedure. Interestingly, phosphites are demonstrated as efficient participants in the reactions of carbodiimides with isocyanides. In the reactions, the use of Lewis acid FeCl3 as activator of carbodiimides secure the formation of 2-phosphated 4-iminoquinazolines. Furthermore, the palladium-catalyzed three-component tandem reactions of carbodiimides, secondary amies, and isocyanides in the absence of phosphine ligands are described, leading to the fuzed quinazolines with high efficiency. The mechanistical studies indicate that the reactions undergo nucleophilic addition, double imidolylation of isocyanides, and double palldium-catalyzed C-N bonds formation. Addition of 3 equivalents isocyanides into the reaction is crucial for the synthesis of fused quinazolines. Interestingly, a distinctive compound named imidazoloquinazolines is observed by decreasing amount of isocyanides to about 1.1 equivalents. In the process for the synthesis of imidazoloquinazolines, only one imidolylation is involved.In the second part, we describe a copper-catalyzed tandem reaction for the sythesis of benzoimidazoloimidazales. The reactions start with carbodiimides and isocyanoacetates in the presence of CuI as catalyst, DMEDA as ligand, and K3PO4 as base. In the transformations, [3+2] cyclization and copper-catalyzed C-N bonds formation are involved. The studies on the reaction generality indicate the reactions perform well with high efficiency and good group tolerance. Interestingly, the prepared products could go through further structural elaboration. In the standard conditions of Suzuki reactions and Sonogashira reactions, the corresponding products afford in moderate to good yields.In the three part, our interest is focused on the palladium(II)-triggered imidolylation of isocyanides. N, N-dimethyl-2-alkynylbenzamines are selected as the starting matericals in the presence of palladium acetate as catalyst, silver acetate as oxidant, and potassium acetate as additive, leading to 3-amidylindoles with high efficiency and excellent substrates tolerance. In the process, intramolecular 6-endo cyclization, imidolylation of isocyanides, reductive elimination with acetate ion, and rearrangement are involved. From the mechanistic studies, it seems that indole palladium species are recognized as the key intermediates.In the last part, we disclose two cyanations using isocyanides as nonmetallic cyano source. Based on the developed cyanative reactions,3-cyanoindoles and 4-cyanoquinolines are obtained. In the access to 3-cyanoindoles, we select N, N-dimethyl-2-alkynylbenzamines as the substrates. In the presence of palladium trifluoroacetate as catalyst and silver trifluoroacetate as oxidant, the desired 3-cyanoindoles afford in moderate to excellent yields. Notably, isocyanides derived from secondary amines are compatible for the above cyanative reactions, leading to the desired 3-cyanindoles with high efficiency. Particularly, the use of anhydrous 1, 2-dichloroethane as solvent is one of the most important results-affecting factors, and excess trifluoroacetate ion in the reactions is critical for the isocyanides-based cyanations. In the reactions, tandem intramolecular cyclization, imidolylation of isocyanides, removal of tert-butyl cation, and cyanation are involved. Interestingly, when tetrahydrofuran is employed as solvent, a distinctive product 3-amidylindole is observed. The control experiments tell us that moisture in solvent play a role of starting material, being incorporating into the targeted product. Furthermore, the developed cyanative reaction using isocyanides as nonmetallic cyano source is expanded to the reactions of 2-alkynyl-benaldimines with isocyanides. Similar results with that of N, N-dimethyl-2-alkynylbenzamines, the desired 4-cyanoisoquinolines afford in good to excellent yields and good groups tolerance. In the reactions, tandem 6-endo cyclization, imidolylation of isocyanides, removal of tert-butyl cation, and cyanation are involved. As expected, the use of anhydrous acetonitrile secures the formation of 4-cyanoquinolines. When analytic reagent acetonitrile is used as solvent, 4-amidylquinolines are furnished with high efficiency as expected. The control experiments demonstrate that the formation of 4-amidylisoquinolines depends on the moisture in solvent. In the process,2-alkynyl-benaldimines undergo a 6-endo cyclization to produce a isoquinoline palladium species. Isocyanides would occur to insert into palladium-carbon bonds in the isoquinoline palladium species to form a isoquinoline imidolylative palladium intermediate, which go through a ligand exchange with moisture in solvent, followed by reductive elimination to afford the desired 4-amidylquinolines.