Convenient enantioselective synthesis of β-trifluoromethyl-β-aminoketones by organocatalytic asymmetric Mannich reaction of aryl trifluoromethyl ketimines with acetone

The l-proline-catalyzed asymmetric Mannich reaction has been performed between aryl trifluoromethyl ketimines and acetone to provide, for the first time, chiral β-aryl-β-trifluoromethyl-β-aminoketones in high yields and with 74–92% enantiomeric excesses.

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4-Amino-4-phenyl-5,5,5-trifluoro-2-pentanoneC11H12F3NOEe = 80%[α]D20=+26.6 (c 1.80, MeOH)Chiral source: (S)-prolineAbsolute configuration: (S)

4-Amino-4-(4-methylphenyl)-5,5,5-trifluoro-2-pentanoneC12H14F3NOEe = 74%[α]D20=+15.4 (c 0.75, MeOH)Chiral source: (S)-prolineAbsolute configuration: (S)

4-Amino-4-(3-methylphenyl)-5,5,5-trifluoro-2-pentanoneC12H14F3NOEe = 92%[α]D20=+24.8 (c 0.81, MeOH)Chiral source: (S)-prolineAbsolute configuration: (S)

4-Amino-4-(4-methoxyphenyl)-5,5,5-trifluoro-2-pentanoneC12H14F3NO2Ee = 78%[α]D20=+10.3 (c 0.39, MeOH)Chiral source: (S)-prolineAbsolute configuration: (S)

4-Amino-4-(4-fluorophenyl)-5,5,5-trifluoro-2-pentanoneC11H12F4NOEe = 83%[α]D20=+30.1 (c 0.63, MeOH)Chiral source: (S)-prolineAbsolute configuration: (S)