α,α-Diarylprolinol-derived chiral ionic liquids: recoverable organocatalysts for the domino reaction between α,β-enals and N-protected hydroxylamines

Chiral ionic liquids bearing α,α-diarylprolinol units were synthesized and applied for the first time as organocatalysts for the domino reaction between α,β-enals and N-protected hydroxylamines involving aza-Michael and intramolecular acetalization steps. Corresponding 5-hydroxy-3-arylisoxazolidines with either an (S)- or (R)-configuration at C-3 were obtained in excellent yields (up to 94%) and with moderate to high enantioselectivities (64 to >99% ee). The ionic liquid supported catalyst can be easily recycled and reused for at least four times without a significant loss of chemical yield or enantioselectivity.

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1-(5-((3R,5S)-5-(bis(3,5-Dimethylphenyl)(trimethylsilyloxy)methyl)pyrrolidin-3-yloxy)-5-oxopentyl)-3-methyl-1H-imidazol-3-ium hexafluorophosphateC33H48F6N3O3PSi[α]D28=-19.5 (c 1.0, CHCl3)Source of chirality: (2S,4R)-4-hydroxypyrrolidine-2-carboxylic acidAbsolute configuration: (3R,5S)

1-(5-((3R,5S)-5-(bis(3,5-bis(Trifluoromethyl)phenyl)(trimethylsilyloxy)methyl)pyrrolidin-3-yloxy)-5-oxopentyl)-3-methyl-1H-imidazol-3-ium hexafluorophosphateC33H36F18N3O3PSiαD24=-2.9 (c 2.0, CHCl3)Source of chirality: (2S,4R)-4-hydroxypyrrolidine-2-carboxylic acidAbsolute configuration: (3R,5S)

3-((3S,5S)-5-(Diphenyl(trimethylsilyloxy)methyl)pyrrolidin-3-yl)-1-methyl-5-pentyl-1H-1,2,3-triazol-3-ium hexafluorophosphateC28H41F6N4OPSi[α]D28=-23.6 (c 1.0, CHCl3)Source of chirality: (2S,4R)-4-hydroxypyrrolidine-2-carboxylic acidAbsolute configuration: (3S,5S)

(3S,5S)-Benzyl 3-(4-chlorophenyl)-5-hydroxyisoxazolidine-2-carboxylateC17H16ClNO4[α]D28=-20.7 (c 1.0, CHCl3)Source of chirality: asymmetric domino reactionAbsolute configuration: (3S,5S)

(3S,5S)-Benzyl 3-(4-fluorophenyl)-5-hydroxyisoxazolidine-2-carboxylateC17H16FNO4[α]D28=+0.3 (c 1.0, CHCl3)Source of chirality: asymmetric domino reactionAbsolute configuration: (3S,5S)

(3S,5S)-Benzyl 3-(4-methoxyphenyl)-5-hydroxyisoxazolidine-2-carboxylateC18H19NO5[α]D28=-4.6 (c 1.0, CHCl3)Source of chirality: asymmetric domino reactionAbsolute configuration: (3S,5S)

(3S,5S)-Benzyl 3-(3-cyclopentyloxy-4-methoxyphenyl)-5-hydroxyisoxazolidine-2-carboxylateC23H27NO6[α]D28=-5.6 (c 1.0, CHCl3)Source of chirality: asymmetric domino reactionAbsolute configuration: (3S,5S)

(3S,5S)-Benzyl 3-(4-nitrophenyl)-5-hydroxyisoxazolidine-2-carboxylateC17H16N2O6[α]D28=-21.7 (c 1.0, CHCl3)Source of chirality: asymmetric domino reactionAbsolute configuration: (3S,5S)