Study On Monofluoromethylation Of ?-ketoesters Compounds

Fluorochemicals are widely used in many fields such as pharmaceutical synthesis,special materials,and electronics.It has great research significance especially in the field of drug development.When a fluorine atom or a fluorine-containing group enters a drug molecule,it brings many effects such as enhancing metabolic stability,bioavailability,lipophilicity and membrane permeability.Due to the unique properties of monofluoromethyl groups that mimic biologically active molecules,exploring a simple and efficient method for the synthesis of monofluoromethyl compounds has become a research focus in the fluorochemical industry.?-ketoesters are a common class of compounds used to construct chiral centers,and they have great application prospects for study the control of C/O selective monofluoromethylation.The research of this topic is mainly divided into two parts.First,in this subject,fluoroiodomethane is used as a monofluoromethylation reagent,and?-ketoester compounds are monofluoromethylated at the?-position to synthesize?-ketoester compounds.The optimized reaction conditions are 1 equivalent of?-ketoesters,1.5equivalent of fluoroiodomethane,0.2 equivalent of sodium hydroxide,the reaction solvent is dimethylformamide,and the reaction temperature is room temperature.With a reaction time of 4 h,the product yield can reach 75%and the selectivity can reach40%.Secondly,using fluoroiodomethane as a monofluoromethylation reagent,O-CH₂F enoic acid compounds were synthesized by highly selective monofluoromethylation of O atoms with?-ketoesters.The optimized reaction conditions are 1 equivalent of di-substituted?-ketoesters,1.2 equivalent of fluoroiodomethane,0.5 equivalent of cesium fluoride,the reaction solvent is dimethylformamide,and the reaction temperature At room temperature and reaction time 4 h,the yield of the product can reach 75%and the selectivity can reach 100%.This paper uses fluoroiodomethane as a monofluoromethylation reagent,which is easy to operate,does not require metal catalysis,has high selectivity and high yield.A total of 26 new compounds were synthesized.The compounds were characterized by¹H NMR,¹³C NMR,¹⁹F NMR.