Studies On Copper Mediated Synthesis Of N,N-disubstituted Phosphonamides

In recent years,protocols for building C-N bond have been reported in succession with rapid development of chelation-assisted transition-metal catalysis.Synthesis of N,N-disubstituted phosphinamides is a research hotspot.N,N-disubstituted phosphinamides are important organic synthetic raw materials(or intermediates)and have been widely used in organic synthesis,catalysis,medicine,materials,pesticides and other fields due to their unique chemical properties.Traditional methods for synthesizing N,N-disubstituted phosphinamides has disadvantages of harsh reactions,high production cost,environmentally unfriendly coupling reagents and low yield of target product.It is very urgent to develop new methods for preparation of N,N-disubstituted phosphinamides and much progresses have been achieved over the years.However,most of these efforts were achieved by using noble metal catalysts,ligands,acids and alkali.Synthesis of N,N-disubstituted phosphinamides compounds by transition-metal assistance has rarely been reported.Thus,It has significant academic and application value to develop a new synthetic method with mild reaction conditions and environment-friendly catalytic system.In this dissertation,a series of phosphinamides that containing N,N-disubstituted skeletons were synthesized with cheap copper salts under chelation-assistance.The structure and physicochemical properties of desired products were characterized by GC-MS,HRMS and NMR analysis.To explore the substrate scopes of this strategy,the electronic and steric hindrance effects of the phosphinamide and coupling reagents were investigated.In addition,the reaction mechanism was explored through systematic control experiments and XPS analysis of active metal species.The main innovative research results and conclusions obtained are listed as follows:(1)An efficient copper powder promoted,aminoquinoline-assisted phosphonamides with arylboronic acid derivatives for the preparation of N,N-disubstituted phosphonamides at room temperature was developed.This method does not require the addition of ligands and bases,and oxygen is the sole oxidant.This method has excellent functional group tolerance.A diverse of unstable functional groups on the benzene ring of aryl boronic acid such as vinyl,formyl,acetyl,sulfonyl,acetylamino,cyano,nitro,and trifluoromethyl can be accommodated.From the results of the control experiments,it can be understood that the chelation of the 8-aminoquinoline group is crucial for copper mediated synthesis of N,N-disubstituted phosphonamides.The XPS data indicates that the active metal species of the reaction is Cu(?)species.(2)A copper-promoted methylation strategy for for the preparation of N,N-disubstituted phosphonamides was developed.This strategy innovatively uses di-tert=butyl peroxide as a methylating agent to efficiently prepare N,N-methylated disubstituted phosphonamides.From the results of the control experiments,it is found that the reaction undergoes via a free radical pathway.This strategy does not require external ligands,has the advantages of high atom economy and simple operation,providing a new idea for the synthesis of N-methylated N,N-disubstituted phosphonamides.