[organic] Professor Huang Hanmin from the Institute of Lanhua and the University of science and technology and researcher Hu bin from the Institute of Lanhua worked together to realize the alkylation of active olefins and benzylamines through the activation of C-N bonds catalyzed by nickel

As an important intermediate, benzyl radicals have been widely used in organic chemistry At present, it is a mainstream method to prepare benzyl radicals by stoichiometric strong oxidants (such as TBHP or NSFI) to oxidize the SP 3 C-H bond of alkylaromatics However, this method usually requires a large amount of alkylaromatics as a source of free radicals or even as a solvent Therefore, it is of great significance to develop efficient methods for the formation of benzyl radicals In recent years, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Professor Huang Hanmin of University of science and technology of China and researcher Hu bin of Lanzhou Institute of chemical physics have made a series of important research progress in the field of transition metal catalyzed C-N bond activation In 2017, the team developed an iodine mediated C-N bond activation reaction of benzylamine, and realized the C-N bond insertion reaction of carbon monoxide (scheme 1a) using nickel catalyst Recently, the team realized the conversion of benzylamine to benzyl radical by nickel catalyzed C-N bond activation on the basis of previous research, and successfully applied it to the synthesis of alkyl substituted indolones and dihydroquinolinones (scheme 1b and 1c) Relevant research results were published in Chem EUR J (DOI: 10.1002/chem 201800543) (source: chem EUR J.) firstly, the reaction conditions were screened with N, n-diisopropylbenzylamine (1a) and n-methyl-n-phenylmethylacrylamide (2a) as model substrates (Table 1) Using 10 mol% nii2 and 20 mol% iodine as catalysts and xantphos as ligands, the target product 3A (entry5) with a separation yield of 92% was obtained at 150 ℃ for 24 hours The results show that the activation of C-N bond of benzylamine by iodine and nickel is necessary (source: chem EUR J.) later, the author investigated the substrate applicability of benzylamine (Table 2) Only when the substituent is isopropyl or benzyl, the reaction can get a good yield The electric properties of substituents on benzene ring and the position of substituents have no obvious effect on the reaction, and the better yield can be obtained Other aromatic rings such as naphthalene ring, thiophene ring and furan ring have good tolerance in the reaction (source: chem EUR J.) next, the author examined the substrate range of active olefins (Table 3) Both electron rich and electron deficient aromatic substituted α - substituted acrylamide have good reactivity M-methyl substituted substrate 2C can react with 1a to form a mixture of two isomers 3aC When the substituents on nitrogen atom are acetyl, phenyl and benzyl, the reaction can also proceed smoothly (source: chem EUR J.) in addition to α - substituted acrylamide, β - substituted acrylamide 2q is also suitable for this type of conversion (Table 4) When the amount of iodine increases to 40 mol%, 2q can react with aromatic amines and heteroaromatic amines containing different substituents, and the corresponding target products can be obtained in good yields Two enantiomers in the product can be separated and purified by column chromatography (source: chem EUR J.) conclusion: Professor Huang Hanmin from the Institute of Langhua and the University of science and technology and researcher Hu bin from the Institute of Langhua have developed a new type of nickel catalyzed C-N bond activation reaction of benzylamine, and a series of biologically active indolones and dihydroquinolinones have been synthesized by the free radical addition / cyclization reaction of benzylamine with α or β - substituted acrylamide The reaction does not need oxidant and has good substrate applicability.