Palladium-catalyzed Fluoroallylation Of Difluoroalkenes And C-F Bond Activation Reaction

Trifluoromethyl compounds are widely used in the synthesis of bioactive small molecules due to their high lipid solubility,high electronegativity and good metabolic stability.In the past,trifluoromethylation methods mainly focused on the introduction of trifluoromethyl as a whole,which has a narrow range of substrates,expensive trifluoromethylation reagents and low atomic economy.Therefore,this paper attempts to realize a new palladium-catalyzed trifluoromethyl synthesis mode-"2F+1F=3F"reaction for the first time,based on the transition metal palladium catalysis,using a less studied class of allyl fluorides and gem difluoroalkenes as the reaction module,through activation of the C-F bond,precise regulation of the C-F bond breaking site and selective addition,to obtain the product containing trifluoromethyl.This is a new way of constructing CF₃,which can prepare novel trifluoromethyl compounds with high efficiency,and the trifluoromethylated products are equivalent to the allylation of fluorine negative ions of difluoroolefins.The whole reaction process can achieve high atomic economy and does not require expensive trifluoromethylation reagents.The main results obtained in this thesis are as follows:1.More than 40 kinds of substrates have been expanded,and the best yield can reach 96%,and the system is compatible with a wide range of substrates;it can also be modified to synthesize some trifluoromethyl compounds with natural product skeletons.The isocratic expansion of the template reaction to 5 mmol and the reduction of the catalyst to 2.5 mol%still gives 90%yield and enables large-scale production;the derivatization of products is versatile and can broaden the application of the reaction system.2.The mechanism investigation experiments proved the existence of palladium positive-fluorine negative ionic intermediates in the system,and the control and kinetic experiments showed that the activation of the C-F bond of allyl fluoride was not involved in the decisive step;the reaction rate was only related to the concentration of difluoroolefin,and the larger its concentration,the faster the reaction rate.3.The method has simple reaction conditions,easy operation,and can precisely regulate the position of C-F bond breaking without additional additives,and the region selectivity of C-F bond addition to difluoro-olefin is good,which can synthesize the target product efficiently and realize the high value-added conversion and recycling of C-F bond,and also provides a new idea for the treatment and degradation of organic fluoride waste,which is in line with the concept of green chemistry.