[organic] angelw: old reaction new method, no photoreaction of photosensitizer

In recent years, the combination of photo redox and transition metal catalysis has opened a new way for the construction of C (SP 3) - C (SP 2) bond In general, rare metals such as Ru or IR are used as photocatalysts in this dual catalysis mode, which is difficult to realize large-scale application In traditional Negishi cross coupling, iodine or brominated aromatics are often used as coupling reagents, while chloroaromatics are difficult to undergo Negishi cross coupling due to their poor activity (Figure 1) Recently, Baran reported the coupling reaction of organic zinc reagent and C (SP 3) - C (SP 2) induced by Photo Double catalysis, but the reaction is only a pure thermal process, and light has no special effect on the reaction (j.am Chem SOC., 2016, 138, 2174) In addition, the application of organic zinc reagents in photochemical reactions has not been reported Recently, Dr Jes ú s ALC á Zar from the R & D Department of Janssen cilag, a Johnson & Johnson company, reported a case of Negishi cross coupling reaction catalyzed by light and nickel The reaction was carried out in the form of flow reaction, with a wider substrate range than the traditional Negishi cross coupling reaction, and without the addition of exogenous photosensitizers The relevant research results were published on angelw Chem Int ed (DOI: 10.1002 / anie 201802656) (source: angelw Chem Int ED) at first, the author optimized the flow reaction conditions with methyl 4-bromobenzoate (2) and zinc benzyl bromide (1) as substrates Under the action of 1 mol% fac IR (PPy) 3 and 2 mol% NiCl2 · glyme, the target product (entry 1) can be obtained in 64% yield The results showed that the coupling reaction can also take place without Photocatalyst (entry 2) When the temperature is increased to 60 ℃ without light, the conversion can also reach 78%, which indicates that heat can promote the reaction to a certain extent (entry 5) The coupling reaction between 4-Bromoanisole (3) and commercial zinc benzyl bromide could not take place under the condition of light and 60 ℃ (entry 6), while the in-situ preparation of zinc benzyl bromide could be successfully coupled with 3 (entry 7) (source: angelw Chem Int ED) next, the authors compared the thermal and photoinduced Negishi coupling reactions (Figure S1) The experimental results show that the reaction rate can be significantly increased by light (source: angelw Chem Int ED) then, the author studied the substrate application range of coupling reaction (Figure 2) In order to make the experimental results comparable, each reaction was carried out under the same conditions under light or no light The bromoaromatics with electron withdrawing or electron donating substituents in benzene ring can react with aryl zinc reagent Negishi When brominated aromatic hydrocarbons are replaced by strong electron donating groups (8, 10), light can produce a strong acceleration effect Alkylzinc reagents can also be coupled with brominated aromatic hydrocarbons (6, 7, 12) It has been found that chlorinated aromatic hydrocarbons (23) with very low activity can be efficiently coupled with alkyl or aryl zinc reagents under light conditions Pyridyltriazole derivatives are allosteric modulators of metabotropic glutamate receptor 2 Compounds 25 and 26 were prepared from pyridyltriazole, which further proved the application value of this method in pharmaceutical chemistry In addition, the flow synthesis method was used to prepare compound 16 in gram scale The experimental results show that the flow reaction has higher reaction efficiency than batch reaction (source: angelw Chem Int ED) the author recorded the UV / Vis spectra of each component and different mixtures in the reaction (Figure 3) The experimental results show that the bivalent nickel complex in the system can absorb part of visible light (source: angelw Chem Int ED) although the photocatalytic process usually involves single electron transfer or free radical formation, the author is not sure whether the reaction undergoes the reaction mechanism of free radicals Through 19F NMR monitoring, it was found that the reduction of NiII to Ni0 was accelerated by light, and the dimerization rate of compound 27 was further accelerated (Figure 4) (source: angelw Chem Int ED) conclusion: Dr Jes ouls ALC á Zar, Janssen Pharmaceutical Group of Johnson & Johnson company, reported the Negishi cross coupling reaction catalyzed by light and nickel The reaction was carried out in the form of flow reaction, with a wider range of substrates than the traditional Negishi cross coupling reaction, and no need to add exogenous photosensitizers This discovery opens up a new way for cross coupling chemistry and provides a new perspective for the study of photocatalysis.