Copper Catalyzes The Formation Of Nitro Cations And Is Used In The Nitration And Chloronitration Of Olefins

As an important functional group,nitro group is widely present in various drug molecular skeletons.There have been lots of reports about the synthesis of nitroaryl derivatives.Nitroalkene is a very important organic synthon,but its synthesis method has hardly made any breakthrough from 1895 to 2010.With the development of free radical chemistry,several excellent work on direct nitration of olefins via free radical processes has been reported in the past decade.However,due to the high reactivity of the free radical reaction,the disadvantages of using expensive reagents and excessive addition of oxidizing agents,the practicality of these methods is greatly limited,and in particular,it cannot be applied to large-scale production preparation.In order to circumvent these shortcomings of the free radical reaction,it has become important to study the nitration reaction via the nitro cation mechanism,especially the method of generating active nitro cation by catalysis.TMSONO₂ is a promising source of nitrocation.However,since the intramolecular N-O bond is not easily broken,the nitrocation cannot be produced well.As we known,single electron transfer process is an effective way to activate inert bonds;copper salts are good single electron transfer catalysts.Here,we use the inexpensive nitrate and trimethylchlorosilane to generate TMSONO₂ in situ,and then use the cheap copper salt to catalyze the single-electron oxidation of TMSONO₂ to generate radical cations.Because the cleavage energy of N-O bond in radical cations is much lower than neutral molecules,it is easy to break the N-O bond,and efficiently produce nitrocation.On the one hand,we have achieved the direct nitration of olefins using this method.And this methodology has a very broad substrate suitability.Either electron-rich olefins,or electron-deficient olefins,even or heterocyclic aryl olefins can work well.Moreover,we have accomplished the nitration of estrone derivative with a good yield.It demonstrates the excellent application potential of this methodology in organic synthesis and complex molecular late modification.It is particularly worth mentioning that the methodology can be scaled up to a level above ten grams under laboratory conditions.The reagents we used are inexpensive;the reaction conditions are extremely mild;the operation is very simple;and the conversion efficiency is very high.We firmly believe that the method can be applied to industrial applications.On the other hand,there is an increasing number reports of the difunctionalization of olefins due to the high efficiency of such reactions.However,there are only a few cases in which a nitro group is introduced into the molecule by a method of difunctionalizating of an olefin.Chlorine-nitration of olefins can also be achieved using the methods.