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Carolina Hurricanes ShirtAromatic nitrile compounds are widely used in pharmaceutical molecules and agrochemicals because of their good biological activity (figure 1).In addition, aromatic nitrile compounds can also be hydrolyzed, reduced, nucleophilic reactions to obtain aromatic carboxylic acid, benzylamine, ketone/imine and other molecules with potential drug activity.The traditional synthesis methods of aromatic nitrile compounds mainly include Sandmeyer reaction of diazo salt and coupling reaction of aryl halides catalyzed by transition metal.In recent years, a few literatures have reported the preparation of aryl nitrile compounds by Rh or Co catalyzed c-h bond activation.However, this kind of reaction requires specific guiding group and strong basic lithium reagent, and the by-product is obvious and the selectivity is not ideal.Recently, David a. Nicewicz's group from the university of north Carolina at chapel hill reported direct cyanoylation of aromatic hydrocarbons by c-h bonds over organic photoredox catalysts.The reaction condition is mild, the substrate is universal and no transition metal is needed.Figure 1. Aryl nitrile compounds and their preparation.More recently, the authors found that the excited state of acridine salt by illumination allows aromatic hydrocarbon cation radicals to be generated by electron transfer, which can be followed by c-h bond amination.This reaction has good substrate universality, and does not require the introduction of additional guiding groups, and has good selectivity for the para-position of mono-substituted benzene.Considering the extensive synthetic value of aryl nitrile compounds, they wanted to apply the process to the reaction of cyano-containing nucleophiles with aromatic hydrocarbons.First they imagine, with a high reduction potential of 3, 6-2 tertiary butyl - 9 - all three methyl phenyl - 10 - phenyl acridine four fluorine boric acid salt (1, 2 E1 / red * = + 2.15 V vs. SCE) may be an ideal catalyst, excited state of aromatics oxidation can contain a variety of functional groups 1, get the key of aromatic hydrocarbon cation radical intermediates (figure 1 b), after reaction with cyano nucleophilic reagent for aromatic nitriles products.FIG. 2. Screening of reaction conditions.The authors selected diphenyl ether as the substrate for conditional screening (figure 2).We use 5 molar of 1 as a catalyst, and we use KCN or Bu4N+CN- as a source of cyanogens.The reaction was performed by adding TEMPO free radical blocker and no target reaction occurred (figure 2, entries 1-2).Using a polar solvent, trace product 3a could be detected in the GMS (figure 2, entries 3).The NaHCO3 saturated solution was then added to the reaction system and different cyanoyl sources were replaced, resulting in a higher reaction yield (figure 2, entries 4-6).When phosphate buffer solution was used as the co-solvent and TMSCN as the source of cyano, the reaction yield was significantly increased (figure 2, entries 7-9).When the buffer pH value is 9, the product can be obtained at a yield of 69% (p/o isomer ratio is 1.6:1).TMSCN can release cyanide negative ions slowly during the reaction process, effectively reducing the concentration of cyanide ions in the reaction system.Figure 3. Response universality study.After obtaining the optimal conditions, they also examined the substrate universality of the reaction (figure 3).First, for mono-substituted aromatic substrates, both phenoxy and alkoxy substituted benzenes and naphthalenes have high yields and good selectivity (3a-3c, 3f-3g).Under standard conditions, the silicoether-protected group would obtain the unprotected p-cyanophenol products (3d-3e).For tri-substituted aromatic hydrocarbons, a unique cyanidation product (3h) can be obtained by trimethylbenzene at a yield of 35%.3, 5-dimethyl phenyl ether yields the products of the 2- and 4- reactions at an overall yield of 89% (3i).For ortho-disubstituting aromatic hydrocarbons, substituents containing alkoxy, double bonds, cyclopropane, and even electron-absorbing carbonyl, ester, halogen, etc., can be obtained at a medium to excellent yield (3i-3n, 3p-3s).For intermediate disubstituted aromatic hydrocarbons, the product will appear isomers (3o).The corresponding products (3t-3w) can also be obtained under standard reaction conditions for substrates containing aromatic heterocycles.The reaction was further applied to bioactive molecules with complex structures, and corresponding cyanylation products could also be obtained, and most of the reactions obtained products with single site substitution, indicating that this method has important application value in drug synthesis and full synthetic chemistry (3x-3zb, 3aa).Figure 4. Possible mechanism of the reaction.Finally, the mechanism of the reaction was investigated (figure 4).Photocatalyst 1 is excited by blue light irradiation in the transition state of mes-acr +*, which is highly oxidized (e1/2red *=+ 2.15v vs. SCE), and can oxidize aromatic hydrocarbon 2 to the corresponding free radical cation 5, while the catalyst is reduced to mes-acr catalyst (6).TMSCN reacts with 5 to obtain cyclohexadiene radical 7, the intermediate can be oxidized by oxygen atoms to obtain the target product 3, while producing hydrogen peroxide radical (or oxygen) oxidized radical 6 to obtain reduced photocatalyst 1, thus completing the catalytic cycle.Nicewicz group has developed a catalytic C-H - bond cyanoylation of (hybrid) aromatic hydrocarbons using acridine salt as a photoredox catalyst.This reaction is mild, has good substrate universality, and avoids side reactions at high active benzyl sites. It has good application value in full synthesis and drug synthesis chemistry.Original text (scan or long press the qr code, after recognition, direct to the original page, or click here to view the original) :Direct C Cyanation of Arenes via Organic Photoredox Catalysis.J. am. Chem. Soc., 2017, 139, 2880-2883, DOI: 10.1021/jacs. 6b12708x-mol Organic field academic discussion QQ group (450043083)The copyright of this article belongs to x-mol.com if the source is not specified. Please do not reprint without permission.

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