Amino alcohol-derived chiral ionic liquids: structural investigations toward chiral recognition

From tentative beginnings, chiral ionic liquids have emerged into functionalized and tailor-made materials that provide novel input in classical asymmetric synthesis and separations. However, despite this broad application range the prediction of any chiral ionic liquids’ performance is difficult. We present a systematic study toward the chiral recognition properties of novel ionic liquids with an amino alcohol sub-structure derived from the chiral pool precursors ephedrine, prolinol, and phenylalaninol. The influence of different ionic head groups and core structures on the diastereomeric interactions between racemic Mosher’s acid carboxylate and enantiopure chiral ionic liquids was systematically investigated to provide insight into their recognition properties prior to application of these chiral ionic liquids in various fields.

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2-Chloro-N-([1R,2S]-1-hydroxy-1-phenylpropan-2-yl)-N-methylacetamideC12H16ClNO2[α]D20 = +30.3 (c 1.09, EtOH)Source of chirality: the precursorAbsolute configuration: (1R,2S)

1-(2-[[[1R,2S]-1-Hydroxy-1-phenylpropan-2-yl][methyl]amino]-2-oxoethyl)-3-methyl-1H-imidazol-3-ium chlorideC16H22ClN3O2[α]D20 = −6.05 (c 1.01, EtOH)Source of chirality: the precursorAbsolute configuration: (1R,2S)

1-(2-[[[1R,2S]-1-Hydroxy-1-phenylpropan-2-yl][methyl]amino]-2-oxoethyl)-3-methyl-1H-imidazol-3-ium bis(trifluoromethane)sulfonimideC18H22F6N4O6S2[α]D20 = −5.1 (c 1.48, EtOH)Source of chirality: the precursorAbsolute configuration: (1R,2S)

1-(2-[[[1R,2S]-1-Hydroxy-1-phenylpropan-2-yl][methyl]amino]-2-oxoethyl)pyridin-1-ium chlorideC17H21ClN2O2[α]D20 = −27.35 (c 1.02, EtOH)Source of chirality: the precursorAbsolute configuration: (1R,2S)

1-(2-[[[1R,2S]-1-Hydroxy-1-phenylpropan-2-yl][methyl]amino]-2-oxoethyl)pyridin-1-ium bis(trifluoromethane)sulfonimideC19H21F6[α]D20 = −15.55 (c 1.00, EtOH)Source of chirality: the precursorAbsolute configuration: (1R,2S)

1-(2-[[[1R,2S]-1-Hydroxy-1-phenylpropan-2-yl][methyl]amino]-2-oxoethyl)-2,3-dimethyl-1H-imidazol-3-ium chlorideC17H24ClN3O2[α]D20 = −7.4 (c 0.98, EtOH)Source of chirality: the precursorAbsolute configuration: (1R,2S)

1-(2-[[[1R,2S]-1-Hydroxy-1-phenylpropan-2-yl][methyl]amino]-2-oxoethyl)-2,3-dimethyl-1H-imidazol-3-ium bis(trifluoromethane)sulfonimideC19H24F6N4O6S2[α]D20 = −10.7 (c 1.07, EtOH)Source of chirality: the precursorAbsolute configuration: (1R,2S)

1-(2-[[[1R,2S]-1-Hydroxy-1-phenylpropan-2-yl][methyl]amino]-2-oxoethyl)-1-methylpyrrolidin-1-ium chlorideC17H27ClN2O2[α]D20 = −8.8 (c 1.04, EtOH)Source of chirality: the precursorAbsolute configuration: (1R,2S)

1-(2-[[[1R,2S]-1-Hydroxy-1-phenylpropan-2-yl][methyl]amino]-2-oxoethyl)-1-methylpyrrolidin-1-ium bis(trifluoromethane)sulfonimideC19H27F6N3O6S2[α]D20 = −17.5 (c 1.00, EtOH)Source of chirality: the precursorAbsolute configuration: (1R,2S)

Tributyl(2-[[[1R,2S]-1-hydroxy-1-phenylpropan-2-yl][methyl]amino]-2-oxoethyl)phosphonium chlorideC24H43ClNO2P[α]D25 = −16.0 (c 0.41, CHCl3)Source of chirality: the precursorAbsolute configuration: (1R,2S)

Tributyl(2-[[[1R,2S]-1-hydroxy-1-phenylpropan-2-yl][methyl]amino]-2-oxoethyl)phosphonium bis(trifluoromethane)sulfonimideC26H43F6N2O6PS2[α]D20 = −13.7 (c 1.10, EtOH)Source of chirality: the precursorAbsolute configuration: (1R,2S)

2-([[1R,2S]-1-Hydroxy-1-phenylpropan-2-yl][methyl]amino)-N,N,N-trimethyl-2-oxoethanaminium chlorideC15H25ClN2O2[α]D20 = −9.4 (c 1.02, MeOH)Source of chirality: the precursorAbsolute configuration: (1R,2S)

2-([[1R,2S]-1-Hydroxy-1-phenylpropan-2-yl][methyl]amino)-N,N,N-trimethyl-2-oxoethanaminium bis(trifluoromethane)sulfonimideC17H25F6N3O6S2[α]D20 = −15.0 (c 1.03, EtOH)Source of chirality: the precursorAbsolute configuration: (1R,2S)

(S)-1-(2-[2-[Hydroxymethyl]pyrrolidin-1-yl]-2-oxoethyl)pyridin-1-ium chlorideC12H17ClN2O2[α]D20 = −53.1 (c 0.62, MeOH)Source of chirality: the precursorAbsolute configuration: (S)

(S)-1-(2-[2-[Hydroxymethyl]pyrrolidin-1-yl]-2-oxoethyl)pyridin-1-ium bis(trifluoromethane)sulfonimideC14H17F6N3O6S2[α]D20 = −29.0 (c 0.77, MeOH)Source of chirality: the precursorAbsolute configuration: (S)

(S)-1-(2-[2-[Hydroxymethyl]pyrrolidin-1-yl]-2-oxoethyl)-3-methyl-1H-imidazol-3-ium chlorideC11H18ClN3O2[α]D20 = −29.0 (c 0.77, MeOH)Source of chirality: the precursorAbsolute configuration: (S)

(S)-1-(2-[2-[Hydroxymethyl)pyrrolidin-1-yl]-2-oxoethyl]-3-methyl-1H-imidazol-3-ium bis(trifluoromethane)sulfonimideC13H18F6N4O6S2[α]D20 = −28.2 (c 1.09, MeOH)Source of chirality: the precursorAbsolute configuration: (S)

(S)-1-(2-[2-[Hydroxymethyl]pyrrolidin-1-yl]-2-oxoethyl)-2,3-dimethyl-1H-imidazol-3-ium chlorideC12H20ClN3O2[α]D20 = −46.85 (c 1.05, MeOH)Source of chirality: the precursorAbsolute configuration: (S)

(S)-1-(2-[2-[Hydroxymethyl]pyrrolidin-1-yl]-2-oxoethyl)-2,3-dimethyl-1H-imidazol-3-ium bis(trifluoromethane)sulfonimideC14H20F6N4O6S2[α]D20 = −17.6 (c 0.83, MeOH)Source of chirality: the precursorAbsolute configuration: (S)

(S)-1-(2-[2-[Hydroxymethyl]pyrrolidin-1-yl]-2-oxoethyl)-1-methylpyrrolidin-1-ium chlorideC12H23ClN2O2[α]D20 = −34.1 (c 0.75, MeOH)Source of chirality: the precursorAbsolute configuration: (S)

(S)-1-(2-[2-[Hydroxymethyl]pyrrolidin-1-yl]-2-oxoethyl)-1-methylpyrrolidin-1-ium bis(trifluoromethane)sulfonimideC14H23F6N3O6S2[α]D20 = −23.1 (c 0.96, MeOH)Source of chirality: the precursorAbsolute configuration: (S)

(S)-Tributyl(2-[2-[hydroxymethyl]pyrrolidin-1-yl]-2-oxoethyl)phosphonium chlorideC19H39ClNO2P[α]D20 = −25.85 (c 0.79, MeOH)Source of chirality: the precursorAbsolute configuration: (S)

(S)-Tributyl(2-[2-[hydroxymethyl]pyrrolidin-1-yl]-2-oxoethyl)phosphonium bis(trifluoromethane)sulfonimideC21H39F6N2O6PS2[α]D20 = −17.85 (c 1.01, MeOH)Source of chirality: the precursorAbsolute configuration: (S)

(S)-2-(2-[Hydroxymethyl]pyrrolidin-1-yl)-N,N,N-trimethyl-2-oxoethanaminium chlorideC10H21ClN2O2[α]D20 = −35.4 (c 0.89, MeOH)Source of chirality: the precursorAbsolute configuration: (S)

(S)-2-(2-[Hydroxymethyl]pyrrolidin-1-yl)-N,N,N-trimethyl-2-oxoethanaminium bis(trifluoromethane)sulfonimideC12H21F6N3O6S2[α]D20 = −17.6 (c 1.01, MeOH)Source of chirality: the precursorAbsolute configuration: (S)

(S)-1-(2-((1-Hydroxy-3-phenylpropan-2-yl)amino)-2-oxoethyl)pyridin-1-ium chlorideC16H19ClN2O2[α]D20 = −14.3 (c 1.00, MeOH)Source of chirality: the precursorAbsolute configuration: (S)

(S)-1-(2-((1-Hydroxy-3-phenylpropan-2-yl)amino)-2-oxoethyl)pyridin-1-ium bis(trifluoromethane)sulfonimideC18H19F6N3O6S2[α]D20 = −17.5 (c 1.05, CH2Cl2)Source of chirality: the precursorAbsolute configuration: (S)

(S)-1-(2-[[1-Hydroxy-3-phenylpropan-2-yl]amino]-2-oxoethyl)-3-methyl-1H-imidazol-3-ium chlorideC15H20ClN3O2[α]D20 = −7.5 (c 0.85, MeOH)Source of chirality: the precursorAbsolute configuration: (S)

(S)-1-(2-[[1-Hydroxy-3-phenylpropan-2-yl]amino]-2-oxoethyl)-3-methyl-1H-imidazol-3-ium bis(trifluoromethane)sulfonimideC17H20F6N4O6S2[α]D20 = −12.95 (c 0.98, CH2Cl2)Source of chirality: the precursorAbsolute configuration: (S)

(S)-1-(2-[[1-Hydroxy-3-phenylpropan-2-yl]amino]-2-oxoethyl)-2,3-dimethyl-1H-imidazol-3-ium chlorideC16H22ClN3O2[α]D20 = −6.8 (c 1.06, MeOH)Source of chirality: the precursorAbsolute configuration: (S)

(S)-1-(2-[[1-Hydroxy-3-phenylpropan-2-yl]amino]-2-oxoethyl)-2,3-dimethyl-1H-imidazol-3-ium bis(trifluoromethane)sulfonimideC18H22F6N4O6S2[α]D20 = −12.9 (c 1.07, CH2Cl2)Source of chirality: the precursorAbsolute configuration: (S)

(S)-1-(2-[[1-Hydroxy-3-phenylpropan-2-yl]amino]-2-oxoethyl)-1-methylpyrrolidin-1-ium chlorideC16H25ClN2O2[α]D20 = −29.15 (c 1.02, MeOH)Source of chirality: the precursorAbsolute configuration: (S)

(S)-1-(2-[[1-Hydroxy-3-phenylpropan-2-yl]amino]-2-oxoethyl)-1-methylpyrrolidin-1-ium bis(trifluoromethane)sulfonimideC18H25F6N3O6S2[α]D20 = −23.0 (c 1.06, CH2Cl2)Source of chirality: the precursorAbsolute configuration: (S)

(S)-Tributyl(2-[[1-hydroxy-3-phenylpropan-2-yl]amino]-2-oxoethyl)phosphonium chlorideC23H41ClNO2P[α]D20 = −14.8 (c 1.04, MeOH)Source of chirality: the precursorAbsolute configuration: (S)

(S)-Tributyl(2-[[1-hydroxy-3-phenylpropan-2-yl]amino]-2-oxoethyl)phosphonium bis(trifluoromethane)sulfonimideC25H41F6N2O6PS2[α]D20 = −13.7 (c 1.10, CH2Cl2)Source of chirality: the precursorAbsolute configuration: (S)

(S)-2-([1-Hydroxy-3-phenylpropan-2-yl]amino)-N,N,N-trimethyl-2-oxoethanaminium chlorideC14H23ClN2O2[α]D20 = −31.1 (c 0.85, MeOH)Source of chirality: the precursorAbsolute configuration: (S)

(S)-2-([1-Hydroxy-3-phenylpropan-2-yl]amino)-N,N,N-trimethyl-2-oxoethanaminium bis(trifluoromethane)sulfonimideC16H23F6N3O6S2[α]D20 = −23.7 (c 1.03, CH2Cl2)Source of chirality: the precursorAbsolute configuration: (S)