New Efficient Synthetic Routes to Enantiomerically Pure Fluoroalkyl (Arylsulfinyl)methyl Imines and Amines

The synthesis of N-aryl and N-alkyl fluoroalkyl (arylsulfinyl)methyl imines (R)-1, new chiral and enantiomerically pure fluoro- and nitrogen substituted templates, has been efficiently accomplished by two different methods, both consisting in two steps, from cheap fluoroacetic acids or esters. Route A consists in the addition of N-substituted trifluoro- and chlorodifluoroacetimidoyl chlorides 2 to α-lithium methyl-p-tolylsulfoxide (R)-3, and Route B in the aza-Wittig reaction between N-aryl iminophosphoranes 4 and γ-fluoro-β-ketosulfoxides (R)-5. Preliminary investigations on the reduction of 1 to the corresponding fluoroalkyl (arylsulfinyl)methyl amines 6, and the exploitation of this method in the synthesis of 3,3,3-trifluoroalanine (R)-8 is described.

fluoroacetimidoyl chlorides - aza-Wittig - sulfoxides - imines - trifluoroalanine