Transition Metal-catalyzed The C-C/C-N/C-S Cross-coupling Reactions Of Pyrimidin-2-yl Phosphates

In recent years, aryl halides have aroused much attention among the researchers due to their higher reactivity towards transition-metal catalysis. However, aryl halides have many disadvantages, such as hard synthesis and high toxicity. The phosphates have been caused increasing attention in modern cross-coupling reactions owing to their own advantages. For example, the phosphates are always easily prepared, stable and can lead to lower the environmental impact of the cross-coupling process. Besides, phosphates can be involved in a series of reactions. Up to now, there are relatively few studies in the literature on the phosphates. Thus, the research on phosphates has a broad development space.This thesis reviewed the research advances of phosphates involved cross-coupling reactions. The coupling reactions between pyrimidin-2-yl phosphates were explored. Meanwhile, a series of multisubstituted pyrimidine derivatives were synthesized. The main contents were as follows:1. The research advances in C-C/C-N/C-S coupling reactions between phosphates with a variety of nucleophiles were reviewed.2. At first, we synthesized a series of pyrimidin-2-yl phosphates, and then we developed the iron-catalyzed Kumada cross-coupling reactions of pyrimidin-2-yl phosphates and Grignard reagents. And then, twenty-nine kinds of substituted pyrimidine derivatives were synthesized. Besides, the target products were confirmed by ¹H NMR?¹³C NMR and HRMS.3. Ni-catalyzed Suzuki-Miyaura cross-coupling reaction of pyrimidin-2-yl phosphates, tosylates and pivalates with arylboronic acids was described and twenty-four kinds of pyrimidine derivatives were synthesized. Besides, the reaction activity of three kinds of esters was also compared. Moreover, the target products were confirmed by ¹H NMR?¹³C NMR and HRMS.4. The cross-coupling reaction of pyrimidin-2-yl phosphates with amines and thiophenols was reported under the metal-free conditions and twenty-six kinds of pyrimidine derivatives were synthesized. Then, we succesfully achieved the CuSO₄·5H₂O-catalyzed NaAsc-mediated cross-coupling of pyrimidin-2-yl phosphates with amides. By using this method, we have successfully achieved the further functionalization of pyrimidin-2-yl phosphates.