Calixarene-based chiral primary amine thiourea promoted highly enantioselective asymmetric Michael reactions of α,α-disubstituted aldehydes with maleimides

Calix[4]arene based chiral bifunctional thiourea-primary amines have been shown to act as effective catalysts for the Michael addition of aldehydes to maleimides for the first time. The corresponding adducts were generally obtained preferentially in (R)- or (S)-forms with high yields (up to 99%) and with high to excellent enantioselectivities (up to 98% ee).

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25,27-Bis[1-((1S,2S)-2--(1,3-dioxoisoindolin-2-yl)cyclohexyl)-3-propoxy)thiourea]-26,28-dihydroxy-5,11,17,23-tetra(tert-butyl)-calix[4]areneC80H98N6O4S2[α]D25=-2.7 (c 0.6, CHCl3)Source of chirality: (1S,2S) cyclohexane-1,2-diamineAbsolute configuration: (S,S,S,S)

1-(2-(4-tert-Butylphenoxy)ethyl)-3-((1S,2S)-2-(1,3-dioxoisoindolin-2-yl)cyclohexyl)thioureaC27H33N3O3S[α]D25=-2.1 (c 0.6, CHCl3)Source of chirality: (1S,2S) cyclohexane-1,2-diamineAbsolute configuration: (S,S)

25,27-Bis[1-((1S,2S)-2-aminocyclohexyl)-3-propoxy)thiourea]-26,28-dihyd-roxy-5,11,17,23-tetra(tert-butyl)-calix[4]areneC64H94N6O4S2[α]D25=-4.9 (c 0.9, CHCl3)Source of chirality: (1S,2S) cyclohexane-1,2-diamineAbsolute configuration: (S,S,S,S)

1-((1S,2S)-2-Aminocyclohexyl)-3-(2-(4-tert-butylphenoxy)ethyl)thioureaC19H31N3OS[α]D25=-1.1 (c 2.0, CHCl3)Source of chirality: (1S,2S) cyclohexane-1,2-diamineAbsolute configuration: (S,S)

(S)-2-(2,5-Dioxo-1-phenylpyrrolidin-3-yl)-2-methylpropanalC14H15NO3[α]D25=-3.2 (c 0.8, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-2-Methyl-2-(1-(4-nitrophenyl)-2,5-dioxopyrrolidin-3-yl)propanalC14H14N2O5[α]D25=-2.9 (c 0.9, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-2-(1-Benzyl-2,5-dioxopyrrolidin-3-yl)-2-methylpropanalC15H17NO3[α]D25=+11.9 (c 0.8, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-2-(1-(4-Chlorophenyl)-2,5-dioxopyrrolidin-3-yl)-2-methylpropanalC14H14ClNO3[α]D25=-2.4 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-2-(1-(4-Bromophenyl)-2,5-dioxopyrrolidin-3-yl)-2-methylpropanalC14H14BrNO3[α]D25=-3.1 (c 0.9, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-1-(2,5-Dioxo-1-phenylpyrrolidin-3-yl)cyclohexanecarbaldehydeC17H19NO3[α]D25=-0.7 (c 0.8, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-1-(1-Benzyl-2,5-dioxopyrrolidin-3-yl)cyclohexanecarbaldehydeC18H21NO3[α]D25=+1.6 (c 0.9, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-1-(2,5-Dioxo-1-phenylpyrrolidin-3-yl)cyclopentanecarbaldehydeC16H17NO3[α]D25=+18.2 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-1-(1-Benzyl-2,5-dioxopyrrolidin-3-yl)cyclopentanecarbaldehydeC17H19NO3[α]D25=-0.7 (c 0.5, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-1-(1-(4-Bromophenyl)-2,5-dioxopyrrolidin-3-yl)cyclopentanecarbaldehydeC16H16BrNO3[α]D25=+1.9 (c 0.6, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-1-(1-(4-Nitrophenyl)-2,5-dioxopyrrolidin-3-yl)cyclopentanecarbaldehydeC16H16N2O5[α]D25=+2.3 (c 0.8, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-1-(1-(4-Chlorophenyl)-2,5-dioxopyrrolidin-3-yl)cyclopentanecarbaldehydeC16H16ClNO3[α]D25=+1.9 (c 1.1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-2-(2,5-Dioxo-1-phenylpyrrolidin-3-yl)-2-ethylbutanalC16H19NO3[α]D25=-6.3 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-2-(1-(4-Bromophenyl)-2,5-dioxopyrrolidin-3-yl)-2-ethylbutanalC16H18BrNO3[α]D25=-2.1 (c 0.9, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-2-(1-Benzyl-2,5-dioxopyrrolidin-3-yl)-2-ethylbutanalC17H21NO3[α]D25=-2.9 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-2-Ethyl-2-(1-(4-Nitrophenyl)-2,5-dioxopyrrolidin-3-yl)butanalC16H18N2O5[α]D25=-1.7 (c 0.6, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-2-(1-(4-Chlorophenyl)-2,5-dioxopyrrolidin-3-yl)-2-ethylbutanalC16H18ClNO3[α]D25=-1.9 (c 0.7, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-2-(2,5-Dioxo-1-phenylpyrrolidin-3-yl)-2-methylpentanalC16H19NO3[α]D25=-1.3 (c 0.6, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S,S)