Highly enantioselective synthesis of α-(perfluoroalkyl)amines via hydrogenation of enamide precursors in the presence of chiraphos-rhodium catalyst

Highly (up to 99% ee) enantio-enriched perfluoroalkyl amines can be synthesized by the perfluoroalkylation of nitriles with Lewis acidic perfluoroalkyl titanate reagents and catalytic asymmetric hydrogenation with the chiraphos-Rh catalyst of the resultant perfluoroalkyl enamides via base-mediated tautomerization.

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3-N-tert-Butoxycarbonylamino-1-phenyl-4,4,5,5,6,6,7,7,7-nonafluoroheptaneC18H20F9NO293% ee[α]D25=+14.4 (c 1.0, CHCl3)Source of chirality: Asymmetric HydrogenationAbsolute configuration: (S)

2-N-tert-Butoxycarbonylamino-3,3,4,4,5,5,6,6,6-nonafluoropentaneC14H14F9NO2[α]D25=-0.7 (c 1.0, CHCl3)Source of chirality: Asymmetric HydrogenationAbsolute configuration: (S)

1-Phenyl-4,4,5,5,6,6,7,7,7-nonafluoroheptane-3-amine hydrochorideC13H13F9N[α]D25=+10.8 (c 1.0, CHCl3)Source of chirality:Absolute configuration: (R)

2-N-Acetylamino-3,3,4,4,5,5,6,6,6-nonafluoropentaneC8H8F9NO[α]D25 = +1.9 (c 1.0, CHCl3)Source of chirality: Asymmetric HydrogenationAbsolute configuration: (S)

2-N-Acetylamino-3,3,4,4,5,5,5,-pentafluoropentaneC7H8F7NO[α]D25 = −2.6 (c 1.0, CHCl3)Source of chirality: Asymmetric HydrogenationAbsolute configuration: (S)

2-N-Acetylamino-3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorononaneC10H8F13NO[α]D25 = +2.0 (c 1.0, CHCl3)Source of chirality: Asymmetric HydrogenationAbsolute configuration: (S)

2-N-Acetylamino-1-phenyl-3,3,4,4,5,5,6,6,6-nonafluoroheptaneC14H12F9NO92% ee[α]D25 = +4.2 (c 1.0, CHCl3)Source of chirality: Asymmetric HydrogenationAbsolute configuration: (S)

5-N-Acetylamino-1,1,1,2,2,3,3,4,4-nonafluorononaneC11H14F9NO[α]D25 = −3.3 (c 1.0, CHCl3)Source of chirality: Asymmetric HydrogenationAbsolute configuration: (S)

4-N-Acetylamino-1,1,1,2,2,3,3-pentafluoroheptaneC9H12F7NO[α]D25 = −1.5 (c 1.0, CHCl3)Source of chirality: Asymmetric HydrogenationAbsolute configuration: (S)

7-N-Acetylamino-1,1,1,2,2,3,3,4,4,5,5-tridecafluorotridecaneC15H18F13NO[α]D25 = −1.2 (c 1.0, CHCl3)Source of chirality: Asymmetric HydrogenationAbsolute configuration: (S)

1-Phenyl-4,4,5,5,6,6,7,7,7-nonafluoroheptane-3-amine hydrochorideC13H13F9N[α]D25 = +10.8 (c 1.0, CHCl3)Source of chirality:Absolute configuration: (R)