The N-alkylation Reaction Based On Hydrogen Borrowing Strategy Catalyzed By Cheap Metal Nickel

The N-alkylation based on the borrowing-hydrogen strategy is an atom-economic and stepeconomic environment reaction.In recent years,this reaction has attracted a lot of attention in the field of organic synthesis.Compared to other N-alkylation methods,this reaction has three outstanding advantages: firstly,alcohols as the alkylating agents are cheaper and greener than the conventional halogenated hydrocarbons;Secondly,the proton in the alcohols that can be used directly as a hydrogen source,without added additional hydrogenation reagents.Thirdly,dehydrogenation,condensation,and hydrogenation can be achieved in one step,with water as the only by-product.This is an atom-economic and step-economic reaction,which fits well with the concept of green chemistry.In the past years,the borrowing-hydrogen reaction mainly employs expensive and highly toxic iridium and ruthenium as catalyst.As society's requirements increasing for sustainable synthetic chemistry,it is necessary to develop an earth abundant,inexpensive and lowly toxic metal catalyst.In response to this situation,in this paper,we developed a series of inexpensive nickel catalysts that achieved the following three parts of research:(I)Nickel-catalyzed N-alkylation of hydrazides and arylaminesIn this chapter,we achieved the N-alkylation of hydrazides and arylamines with racemic alcohols by using nickel(II)trifluoromethanesulfonate(Ni(OTf)2)and an electron-rich and bulky biphosphines(dcpp).It had good yields and had tolerance to various functional groups.By using this method,we further synthesized Piribedil,a drug for the treatment of Parkinson's disease.(II)Nickel-catalyzed asymmetric N-alkylation hydrazidesIn this chapter,we achieved asymmetric N-alkylation of hydrazides with racemic alcohols by using Ni(OTf)2 and an electron-rich and bulky chiral biphosphines(S-Binapine).The reaction had good yields and high enantioselectivity.In addition,we also verified the mechanism using deuterium labeling experiments.(III)Nickel-catalyzed synthesis of saturated N-heterocycles based on borrowing-hydrogen annulationIn this chapter,we synthesized tetrahydroquinoxalines,quinoxalines,5-7 membered Nheterocycles,tetrahydro-?-carbolines,and tetrahydrogens by using nickel catalysts that has wide catalytic range.The reaction has a high yield.In addition,we synthesized the natural product Komavine using this method.The above three parts of work,on the one hand,efficiently synthesize a large number of nitrogen-containing compounds,heterocyclic compounds and chiral amines,which are very important in the fields of medicine and chemical industry,have important value of practical application.On the other hand,these works have deepened people's understanding of the catalytic properties of cheap metals,and provided theoretical guidance and experimental support for the development of more cheap metal catalysis,have certain theoretical and innovative significance.