Ruthenium(0)-Catalyzed Selective Carbon-Fluorine Bond Arylation Of Polyfluoroarenes

Multifluorinated bi-or triaryls are widely used in pharmaceuticals,functional materials and agrochemicals due to their unique properties of C-F bonds.The synthesis of multifluorinated bi-or triaryls by general methods is difficult due to the lack of preparation methods and the difficulty of precise selection of fluorine substitution sites.However,the selective C-F activation of transition metalcatalyzed poly-or perfluorinated compounds is a proven synthetic method for the synthesis of multifluorinated bi-or triaryls in high yields.The directing strategy can accelerate the oxidative addition step of C-F bonds with transition metals while improving the yield and regioselectivity of the reaction.In this paper,a method system was developed for Ru3(CO)12-catalyzed iminedirected fluorosubstituted Schiff bases to undergo an ortho-selective C-F arylation,in which aryl boronic esters were used as coupling partners.Under optimal reaction conditions,a series of experiments were conducted to explore the suitability of reaction substrates,intermolecular competition,in situ synthesis,DFT calculations,integrated C-F/C-H activation and applied transformation of products.The suitability of the reaction substrates was explored experimentally,showing that aryl boronic esters with different substituents and Schiff base substrates with different degrees of fluorination were capable of synthesizing multifluorinated bi-or triaryl aldehydes in excellent yields.Intermolecular competition experiments have shown that electron-deficient fluorinated Schiff bases and electron-rich aryl borate substrates are more favorable for the reaction.Complete catalytic cycle was illustrated in the DFT calculations,which undergoes four reaction steps:two metal coordination,oxidative addition,transmetallation and reductive elimination before finally generating the diarylated imine product.Precise C-H and C-F activation on aromatic rings of Schiff base substrates with different degrees of fluorination was shown in the integrated C-F/C-H activation reaction.Futhermore,the successful synthesis of polyfluorinated ligands,heterocycles,drugs and porphyrin analogs highlights the effective application of this method for conversion,demonstrating the great potential of the method in many fields of medicinal chemistry,functional materials and electrochemical catalysis.The catalyst system for this reaction is the mildest of among all the reported carbon-fluorine bond activation reactions of polyfluorinated aromatics.The advantages of this reaction are a wide range of substrate applicability,good functional group tolerance,and the ability to obtain multifluorinated bi-or triaryl aldehydes in highly superior yields,which are difficult to achieve by other methods for the synthesis of this type of compounds.Integrated C-F/C-H activation used the same ruthenium(0)catalyst system to precisely activate the CH and C-F bonds in different fluorosubstituted Schiff base substrates and successfully synthesize the high value asymmetric multifluorinated bi-or triaryl aldehydes.