Transition Metal Catalyzed C-H Activation Of 1,2,3-Triazoles

The 1,2,3-triazole heterocyclic system has been known for more than one hundred years. In the last two decades, the chemistry of 1,2,3-triazoles has gained a new impetus in its development due to the discovery of diverse biological activities of many triazole derivatives. A number of synthetic methods have been developed to prepare these heterocycles. However, the synthesis of N-2 substituted triazoles remains a challenge, especially for 2,4-disubstituted substrates. The aim of this thesis is to develop some synthetic strategies to construct C-C, C-N, C-S bonds by transition metal catalyzed C-H activation of 1,2,3-triazoles. The main results and observations from these studies are listed as follows.First, an efficient copper-catalyzed direct C-H amination of 2-aryl-1,2,3-triazole N-oxides with various amines has been developed in moderate to excellent yields with high regioselectivity. The general performance of our method was also demonstrated by the oxidative amination of thiazole and imidazole N-oxides. We were very pleased to find that the targeted N+-O-bond cleavage can be observed during the reaction, and thus obviate to use an additional deoxygenation step. The advantages of this new method are operational simplicity, high atom-economy, and use of inexpensive and environmentally friendly Cu(OAc)2 as the catalyst. In addition, this method avoids using any air-sensitive reagents, and the reaction can, therefore, be performed under relatively mild conditions, providing a powerful tool for the synthesis of 4-amino-2-aryl-1,2,3-triazole derivatives. Moreover, the high halogen compatibility of the process can provide a facile access to chloride-substituted 2-aryl-4-amino triazoles.Secondly, an efficient nickel-catalyzed method for C-S cross-coupling through direct functionalization of 2-aryl-1,2,3-triazole N-oxide C-H bonds with aryl or alky thiols, diaryl disulfide has been developed in moderate to excellent yields with high regioselectivity. We were very pleased to find that the targeted N+-O- bond cleavage can be observed during the reaction, and thus obviate to use an additional deoxygenation step. The advantages of this new method are broad substrate scope, operational simplicity, high atom-economy, and use of inexpensive NiSO4 as the catalyst. Moreover, the high halogen compatibility of the process can provide a facile access to halo-substituted 2-aryl-4-thio-substituted triazoles.Thirdly, a convenient and highly regioselective palladium-catalyzed direct C5-arylation of 1,2,3-triazole N-oxides was developed in the presence of silver carbonate and tripotassium phosphate. This protocol allowed use of sodium arylsulfinates, diphenylphosphine oxide and triphenylphosphine as arylating reagents to produce 2-aryl-5-aryl-1,2,3-triazole N-oxides in good to excellent yields, providing a complement to the existing methods for the direct arylation of 1,2,3-triazole N-oxides.In conclusion, we have developed some synthetic strategies to construct C-C, C-N, C-S bonds by transition metal catalyzed C-H activation of 1,2,3-triazoles. Therefore, the establishment of these synthetic strategies is beneficial to develop antischistosomal drugs.