Professor Pan Yi's research group of Nanjing University and Professor Liang Yong have made new achievements in the field of decarboxylation free radical fluorination

Trifluoromethyl (CF3) group is a kind of very important fluorine-containing functional group In the past decade, chemists have developed a variety of efficient trifluoromethylation reagents, but most of them are complex in synthesis and expensive in price, and have some limitations in large-scale application Trifluoroacetic acid (TFA) and anhydrides (tfaa) are cheap industrial sources of trifluoromethyl, but due to the strong electron absorption effect of CF 3, the trifluoroacetate ion has a very high oxidation potential, so it is difficult to produce oxidative decarboxylation to release trifluoromethyl radicals (CF 3 ·) Therefore, the previously reported methods usually need high temperature, excessive strong oxidants or metal reagents and other harsh reaction conditions to activate (Figure 1a) The NHPI type redox active ester (Raes) developed by Baran group is a good method to activate carboxylic acid compounds, and the decarboxylation functionalization derived from Raes is developing rapidly However, due to the electrical properties, the existing methods can not activate trifluoroacetic acid CF 3-nhpi ester reported by Sanford group can selectively generate phthn · and CF 3co2 - Recently, Stephenson's group has realized the trifluoromethylation of aromatics by using the strategy of in situ activation of tfaa with pyridine N-oxide However, the development of stable and cheap fluorinated alkylation reagents with redox activity still has great challenges and urgent needs Reaction design (source: angelw Chem Int ed.) Recently, Professor Pan Yi's research group of Nanjing University was inspired by the N-O bond breaking of oxime esters to produce imine radicals It is assumed that the weak N-O bond can be selectively broken by controlling the electron affinity of oxime esters, and oxygen radicals and imine radicals can be produced By introducing a good halogen leaving group into oxime ester, the electron rich imine can be stabilized and used to resist the strong electron absorption effect of CF 3 group in the active ester Under the condition of photocatalysis, the N-O bond of the nhbc ester breaks to form trifluoroacetoxy radical (cf3co2 ·), which is further decarboxylated to obtain CF3 · In this new strategy, nhbc ester is used to decarboxylate trifluoroacetic acid and release trifluoromethyl radicals under mild photocatalytic conditions It also has a good activation effect on other fluorine-containing groups Moreover, it has been applied to hydrofluoroalkylation and fluorination migration of inactive olefins The reaction conditions are mild and the substrate can adapt to a wide range In addition, Professor Liang Yong, the collaborator, also proved that nhbc is easier to pull electrons than NHPI through DFT theoretical calculation, which is more conducive to the generation of various fluorine-containing alkyl radicals and imine anions in thermodynamics At the same time, the departure of chlorine also reduces the entropy of the whole system This achievement was published on angel.chem.int.ed (DOI: 10.1002 / anie 201812192) under the title of "a general learning group assisted strategy for photoinduced fluoroskylations using n-hydroxybenzimidoyl chloride esters" This work was jointly completed by Zhang Weigang and Zou Zhenlei Under the guidance of Professor Pan Yi and Associate Professor Wang Yi, Professor Liang Yong made full thermodynamic calculation for this work Researchers Qing Fengling and Hu Jinbo from Shanghai organic Research Institute provided valuable suggestions for the paper The above work was supported by the National Natural Science Foundation of China, the youth thousand talents program of the central organization department and the natural science foundation of Jiangsu Province.