Palladium-Catalyzed Reaction Of ?,?,?-Iododifluoromethyl Ketones

Since fluorine has the characteristics of small atomic radius and strong electronegativity,the introduction of fluorine atoms or fluorine-containing groups into organic molecules usually causes changes in physical and chemical properties,such as changing the fat solubility and metabolic stability of drugs and the thermal stability of the material.In recent years,more and more fluoroalkylation strategies have been developed.Among them,difluoroalkylation reaction has been one of the research hotspots.In this paper,?,?,?-iododifluoromethyl ketones building blocks are designed and synthesized,using methyl ketone as the raw material,and obtained through three-step reaction.At the same time,the difunctionalization reaction with terminal alkyne using ?,?,?-iododifluoromethyl ketones as raw materials was studied After the reaction through free radical addition and the subsequent Sonogashira coupling reaction,a series of di Fluoromethylene substituted 1,3-enyne compounds are synthesized.After that,we also conducted some research and exploration on the synthesis of optically active fluoroketone blocksThe first part introduces the synthesis of ?,?,?-iodine difluoroacetone building blocks,using methyl ketone as the raw material to synthesize ?,? through the three-step reaction with trifluoroacetate,Selectfluor fluorination and detrifluoroacetic acid,?-halogenated difluoroacetone block.Fifteen representative ?,?,?-iododifluoromethyl ketones blocks were prepared and synthesizedThe second part introduces the research on the difunctional reaction between ?,?,?-iododifluoromethyl ketones and alkyne.Using ?,?,?-iododifluoromethyl ketones and terminal alkyne as raw materials,the reaction system with catalyst,ligand,base,solvent,temperature and other conditions were screened to obtain the best reaction conditions:tetratriphenylphosphine palladium as the catalyst,no ligand added,potassium phosphate as the base,and toluene as the reaction solvent It is obtained by reacting with alkyne in oil bath at 80? for 4-8 hours.Under this optimal condition,substrate expansion was carried out to synthesize 25 1,3-enynes with different structures containing geminal difluoromethyl substitutionIn the third part,we carried out explorations on the synthesis of optically active fluorine-containing blocks,investigated the transition metal-catalyzed asymmetric cross-coupling,and carried out a preliminary exploration of the asymmetric fluorination reaction.