Studies On The Condensation Reaction Of Alpha-Fluorocarbonyl Compounds

In this paper,the aldol condensation reactions of thiofluoroacetate andα-fluoroxindole with carbonyl compound were developed respectively under the condition of Mg Br₂·OEt₂/N,N-diisopropylethylamine,a series ofα-fluoro-β-hydroxythioester compounds andα-fluoro-β-hydroxyoxindole compounds containing C-F bonds were synthesized,and for specific details you have to look at the following two parts:In the first part,the stereoselective aldol reaction of thiofluoroacetate andaldehyde was developed.By screening different lewis acid catalysts,it was found that under the reaction condition of Mg Br₂·OEt₂/N,N-diisopropylethylamine/dichloromethane,S-（2,4,6-triisopropylphenyl）2-fluoroethanethioate and S-（2,6-dimethylphenyl）2-fluoroethanethioate can react with different aromatic aldehydes and cinnamaldehyde at25°C,and the expectedα-fluoro-β-hydroxythioester compounds could also be obtained in relatively good yields and diastereoselectivity.Condensation product can also be converted at 0°C with methanol as the solvent,theα-fluoro-β-hydroxythioester compound reacted smoothly with methylamine and benzylamine,andα-fluoro-β-hydroxyamide compound was obtained.In the second part,a highly stereoselective aldol reaction with highly activeα-fluoroxindole and aromatic aldehydes was developed.Under the reaction condition of N,N-diisopropylethylamine and lewis acid Mg Br₂·OEt₂,α-fluoroxindole can undergo aldol reactions with aromatic aldehydes,with good to excellent yields to get theα-fluoro-β-hydroxyoxindole compounds.The reaction has a good substrate range:N-alkyl,N-phenyl,N-propargyl and N-allyl-α-fluoroxindoles,andα-fluoroxindoles with a substituent at the 4-6 position all reacted smoothly.