Study On Visible-Light-Enabled Decarboxylative Di-and Monofluoromethylation Of Cinnamic Acids Under Metal-Free Conditions

After the fluoroalkylation of organic compound molecules,exhibited significantly enhanced its metabolic stability,lipophilicity and cell membrane permeability,target protein binding capacity and bioavailability compare to their parent compounds.However,the amount of naturally occurring fluorine-containing organic compounds is extremely rare in nature.Therefore,since the development of organofluorine chemistry,the study of a series of fluoroalkylation of organic compounds has attracted a wide attention from organic chemists.Since the di-and monofluoroalkylation can not only introduce fluorine atom(s)into a molecule,but also introduce other organic functional groups at the same time,this has a distinct advantage over the perfluoroalkylation reaction in the economical efficiency of the synthesis step.Allyl fluorides as an important class of molecular skeleton.Especially,di-and monofluoroalkyl-substituted alkenes that exist in many biologically active compounds and drugs.Significant progress has been made in the field of transition-metal-mediated decarboxylative fluoroalkylation of ?,?-unsaturated carboxylic acids.However,there still exist several inherent limitations in the research of these fluoroalkylation reactions,which not only require harsh reaction conditions but also lead to metal residues and environmental toxicity.Therefore,it is still necessary to develop a green and efficient metod in the synthesis of alkene fluorides,which is very significant for application potential.In this paper,several new mono-and difluoromethylalion reactions of cinnamic acids using an Eosin Y catalytic under metal-free conditions are reported.In this paper,under the catalysis of the organic photocatalyst Eosin Y,we used 4-methylcinamic acid and ethyl bromodifluoroacetate as the model substrates.A series of reaction conditions were explored.The types and equivalent of the hypervalent iodine reagents,catalyst and its amount,solvents,base,light sources and reaction time on the reaction.Ultimately,the optimized conditions were screened as the folowing:2 equiv BI-OH,5 mol%Eosin Y,2 equiv iPr2NEt and DCE/H2O(1:1,2 mL)as solvents irradiation for 15 house bulbs at room temoerature for 12 h.Under the optimized reaction conditions,A series of cinnamic acids were subjected to the present reaction conditions and synthesized the corresponding mono-and difluoroalkyl-substituted alkenes in good yields.Based on the previous literature,Simultaneously,experimental results proved that the ethyl a-fluoroacetate radical is in the reaction by use of a radical-trapping reagent TEMPO(2,2,6,6-tetramethyl-1-oxylpiperidine).We proposed that the possible reaction mechanism is first to remove CO2 after fluoroalkyl radical addition.