Theoretical Study Of Mechanisms Of C(sp~2)-H Bond Functionalization Of Diazo Compounds Via Copper Catalysis

The efficient construction of new C-C bonds is of interest in the field of chemistry,and one of the effective methods is the C（sp²）-H bond functionalization of diazo compounds catalyzed by transition metal.Due to its step economy and atom economy,it has been widely used in the fields of chemical industry,pharmaceutical,energy and materials,and has opened new paths for the design and synthesis of biologically active molecules,natural products,and pharmaceuticals.Therefore,it is important to clarify the reaction mechanism of this process for efficient C（sp²）-H bond functionalization.The combination of theoretical calculations and experimental studies is a powerful tool to study the reaction mechanisms and provide guidance for the design and development of new reaction systems.Herein,combining with the experimental data of the highly selective ortho-C（sp²）-H bond functionalization of 1-naphthol with diazo compounds catalysed by transition metal Cu,this paper systematically studied and compared the mechanism of para-and ortho-C（sp²）-H bond functionalization of1-naphthol andα-phenyl-α-diazoacetate methyl ester catalyzed by Cu（I）and Cu（II）using density functional theory（DFT）,and revealed the fundamental origin of the site-selectivity.The resluts showed that CuCl-catalyzed ortho-selective C-H bond functionlization of naphthol due to the bimetallic Cu carbene,while the key to the reaction catakyzed by CuCl₂ is the monometallic Cu carbene.Moreover,the hydrogen bond interactions in the rate-determining transition state structure of the ortho-C-H bond functionalization of naphthol was beneficial to lower the reaction energy barrier,so it preferred to obtain the ortho-substituted product of naphthol.In addition,the mechanism of the C-H bond functionalization of 1-naphthalene methyl ether andα-phenyl-α-diazoacetate methyl ester was calculated under the same conditions.And the results showed that it was difficult to obtain the product of the C-H bond insertion,which was consistent with the experimental results and again verified the important role of phenolic hydroxyl groups.Morever,we systematically investigated the mechanism of the para-C（sp²）-H functionalization of inactive aromatic compound toluene and differentα-aryl-α-diazoesters catalyzed by gold and analysed the effect of different electrical substituents on the reaction yields.The calculation results showed that the substituents with electron-withdrawing effect favored the formation of C-H bond functionalization products,while the substituents with electron-donating effects inhibited the formation of the products.