Trifluoroacetaldehyde: A useful industrial bulk material for the synthesis of trifluoromethylated amino compounds

Abstract

The synthesis of various trifluoromethylated amino compounds was studied using trifluoroacetaldehyde, an industrial bulk material, as a starting compound. One general application of trifluoroacetaldehyde is the preparation of trifluoroethylamino derivatives via reductive amination reaction. This synthesis includes the formation of the corresponding N,O-acetal intermediates followed by their reduction using NaBH 4 or 2-picoline borane complex, affording the target trifluoroethylamino compounds in moderate to good yields (47–87%). Another general application of trifluoroacetaldehyde is the synthesis of chiral α-substituted trifluoroethylamino compounds. In this synthesis, trifluoroacetaldehyde was first converted into the chiral trifluoromethyl tert-butyl sulfinimine, which was subjected to 1,2-nucleophilic addition reactions across its C N double bond. The addition of phenyllithium afforded α-(phenyl)trifluoroethylamino derivative in 83% yield and with 96% de. Allylation and Reformatsky reactions produced the corresponding α-substituted trifluoroethylamino derivatives in 82 and 58% yields and with 90 and 91% de, respectively.