Chiral diamides as efficient catalytic precursors for the borane-mediated asymmetric reduction of prochiral ketones

Chiral diamides [(2S)-5-oxo-2-(arylamino)carbonylpyrrolidines] derived from the abundantly available (S)-glutamic/(S)-pyroglutamic acids were successfully utilized as effective chiral catalytic precursors in the borane-mediated asymmetric reduction of prochiral ketones in refluxing toluene, to provide the corresponding secondary alcohols with up to 91% enantiomeric purities.

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(2S)-5-Oxo-2-(4-bromoanilino)carbonylpyrrolidineC11H11BrN2O2[α]D25=+13.0 (c 1.09, MeOH)Source of chirality: (S)-pyroglutamic acidAbsolute configuration: (S)

(2S)-5-Oxo-2-(4-chloroanilino)carbonylpyrrolidineC11H11ClN2O2[α]D25=+14.1 (c 1.04, MeOH)Source of chirality: (S)-pyroglutamic acidAbsolute configuration: (S)

(2S)-5-Oxo-2-(4-fluoroanilino)carbonylpyrrolidineC11H11FN2O2[α]D25=+14.0 (c 1.08, MeOH)Source of chirality: (S)-pyroglutamic acidAbsolute configuration: (S)

(2S)-5-Oxo-2-(4-nitroanilino)carbonylpyrrolidineC11H11N3O4[α]D25=+21.0 (c 0.60, MeOH)Source of chirality: (S)-pyroglutamic acidAbsolute configuration: (S)

(2S)-5-Oxo-2-(2,4-difluoroanilino)carbonylpyrrolidineC11H10F2N2O2[α]D25=+12.9 (c 1.02, MeOH)Source of chirality: (S)-pyroglutamic acidAbsolute configuration: (S)

(2S)-5-Oxo-2-(3,5-difluoroanilino)carbonylpyrrolidineC11H10F2N2O2[α]D25=+13.4 (c 1.08, MeOH)Source of chirality: (S)-pyroglutamic acidAbsolute configuration: (S)

(2S)-5-Oxo-2-[3,5-bis(trifluoromethyl)anilino]carbonylpyrrolidineC13H10F6N2O2[α]D25=+4.9 (c 2.09, MeOH)Source of chirality: (S)-pyroglutamic acidAbsolute configuration: (S)

(2S)-5-Oxo-2-(1-naphthylamino)carbonylpyrrolidineC15H14N2O2[α]D25=+15.0 (c 1.09, MeOH)Source of chirality: (S)-pyroglutamic acidAbsolute configuration: (S)