Nucleophilic reactions with α-trifluoromethyl imine and N,O-disubstituted aminal: synthesis of β-trifluoromethyl β-anilino esters

The Reformatsky reaction with 4-methoxy-N-(2,2,2-trifluoroethylidene)aniline (1) proceeds under mild conditions to yield ethyl 4,4,4-trifluoro-3-(N-4-methoxyphenyl)amino-2-alkylbutyrate (5) and 4-trifluoromethyl-3-alkyl-1-(4-methoxyphenyl)-2-azetidinone (6) as the main products. Similarly, the reaction of diethyl malonate with 1 in the presence of sodium hydride affords a high yield of ethyl 4,4,4-trifluoro-3-(N-4-methoxyphenyl)amino-2-carbethoxybutyrate (5d), which is also provided in the reaction of diethyl malonate with 4-methoxy-N-(1-ethoxy-2,2,2-trifluoroethyl)aniline (2). The Reformatsky reactions of 4a–c with N-(1-ethoxy-2,2,2-trifluoroethyl)aniline (3) also proceed to give the corresponding ethyl 4,4,4-trifluoro-3-(N-phenyl)amino-2-alkylbutyrates (11a–c).