Studies On The Enantioselective Mannich Reactions Of Alpha-fluorooxindoles

?-Fluorooxindole fragments are both important structures of many bioactive molecules and pharmaceuticals and valuable synthetic blocks which can be easily converted into fluorinated compounds.Due to the effect of fluorine atoms on the acidity/basicity of vicinal amines.to construct the vicinal fluoroamine is important to drug discovery and organic synthesis.However,compared with their non-fluorinated analogs,the use of?-fluorooxindole and their derivatives in the asymmetric synthesis of?-fluoro-?-aminooxindoles remained limited.In this paper,a new method for synthesizing?-fluoro-?-aminooxindoles through the enantioselective Mannich reaction between N-sulfonyl aldimines and 3-fluorooxindoles is introduced.Through the examination with a series of organocatalysts,including tertiary amine-thiourea catalysts,bifunctional cinchona alkaloid catalysts and their derivatives cinchonidine proved to be the best catalyst.Under the effect of effect of cinchonidine in toluene at-5 ~oC,3-fluorooxindoles can successfully react with N-Ts aldimines to give fully substituted 3-fluorooxindoles bearing vicinal fluoroamine motifs with high efficiency and good stereoselectivity.We have checked the substrate scope:3-fluorooxindole derivatives with substituents at the 1-,4-,5-,6-,7-positions and with electron-withdrawing/electron-donating are successfully reacted.With regard to the aldimine substrates,with substitutions at 2-,3-,4-,5-and 6-positions can also react well,giving the corresponding products in excellent yields.This reaction uses readily available reactants and cheap organocatalysts,which enables the construction of?-fluoro-?-aminooxindoles in good to excellent yields in good to excellent yield with very good enantiomeric excess(up to 96%yield and 94%ee).This paper provides applications of 3-fluorooxindoles as fluorinated blocks,and is able to provide assistance for the synthesis of related fluoro-active molecules.