Enzymatic resolution of 2,2,2-trifluoro-1-arylethylamine derivatives by Pseudomonas fluorescens lipase in organic solvents

Amination of phenyl trifluoromethyl ketone with ammonium formate (Leuckart-Wallach reaction) in a one-pot reaction gave 2,2,2-trifluoro-1-phenylethylamine (3a) in high yield (81%). Other fluorinated 1-arylethylamine derivatives were obtained from their corresponding aryl ketones in moderate to good yields (55–81%). Enzymatic resolution of racemic 3a was done with Pseudomonas fluorescens lipase (Amano lipase AK) via enantioselective alcoholysis of its chloroacetamide (4a) with n-amyl alcohol in diisopropyl ether giving good enantioselectivity (E-value = 44). Other amines also were resolved by lipase AK under similar conditions (E-values = 25 to >100).