Thiourea-catalyzed asymmetric conjugate addition of α-substituted cyanoacetates to maleimides

Chiral isosteviol-derived tertiary amine-thiourea was proven to be effective in catalyzing the asymmetric conjugate addition between α-substituted cyanoacetate and maleimides. Diverse succinimides bearing vicinal quaternary-tertiary stereocenters were obtained in excellent yields, excellent diastereoselectivities, and with good to high enantioselectivities. This catalytic system can be used efficiently in large-scale reactions with the yields and stereoselectivities being maintained at the same level.

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1-(Ethyl ent-beyeran-19-oate-16-yl) -3-((1S,2S)-2-(dimethyl amino)cyclohexyl) thioureaC31H53N3O2S[α]D20=-70.8 (c 2.0, CHCl3)Source of chirality: Ethyl ent-16β-aminobeyeran-19-oate 1,2-diaminocyclohexaneAbsolute configuration: (4R,8R,10S,13S,16R), (1′S,2′S)

1-(Ethyl ent-beyeran-19-oate-16-yl)-3-((1R,2R)-2-(dimethyl amino)cyclohexyl) thioureaC31H53N3O2S[α]D20=-149.5 (c 2.0, CHCl3)Source of chirality: Ethyl ent-16β-aminobeyeran-19-oate 1,2-diaminocyclohexaneAbsolute configuration: (4R,8R,10S,13S,16R), (1′R,2′R)

1-(Ethyl ent-beyeran-19-oate-16-yl)-3-((1S,2S)-2-(diethyl amino)cyclohexyl) thioureaC33H57N3O2S[α]D20=-34.9 (c 1.0, CHCl3)Source of chirality: Ethyl ent-16β-aminobeyeran-19-oate 1,2-diaminocyclohexaneAbsolute configuration: (4R,8R,10S,13S,16R), (1′S,2′S)

1-(Ethyl ent-beyeran-19-oate-16-yl)-3-((1S,2S)-2-(pyrrolidin-1-yl)cyclohexyl) thioureaC33H55N3O2S[α]D20=-24.0 (c 1.0, CHCl3)Source of chirality: Ethyl ent-16β-aminobeyeran-19-oate 1,2-diaminocyclohexaneAbsolute configuration: (4R,8R,10S,13S,16R), (1′S,2′S)

(R)-Ethyl 2-cyano-2-((S)-2,5-dioxo-1-phenylpyrrolidin-3-yl)-2-phenylacetateC21H18N2O4[α]D20=-51.4 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R,S)

(R)-Ethyl 2-((S)-1-(3-bromophenyl)-2,5-dioxopyrrolidin-3-yl)-2-cyano-2-phenylacetateC21H17BrN2O4[α]D20=-54.8 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R,S)

(R)-Ethyl 2-((S)-1-(4-bromophenyl)-2,5-dioxopyrrolidin-3-yl)-2-cyano-2-phenylacetateC21H17BrN2O4[α]D20=-51.9 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R,S)

(R)-Ethyl 2-((S)-1-(3-chlorophenyl)-2,5-dioxopyrrolidin-3-yl)-2-cyano-2-phenylacetateC21H17ClN2O4[α]D20=-57.4 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R,S)

(R)-Ethyl 2-((S)-1-(4-chlorophenyl)-2,5-dioxopyrrolidin-3-yl)-2-cyano-2-phenylacetateC21H17ClN2O4[α]D20=-54.0 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R,S)

(R)-Ethyl 2-cyano-2-((S)-1-(4-fluorophenyl)-2,5-dioxopyrrolidin-3-yl)-2-phenylacetateC21H17FN2O4[α]D20=-49.8 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R,S)

(R)-Ethyl 2-cyano-2-((S)-1-(3-nitrophenyl)-2,5-dioxopyrrolidin-3-yl)-2-phenylacetateC21H17N3O6[α]D20=-52.8 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R,S)

(R)-Ethyl 2-cyano-2-((S)-2,5-dioxo-1-(p-tolyl)pyrrolidin-3-yl)-2-phenylacetateC22H20N2O4[α]D20=-54.6 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R,S)

(R)-Ethyl 2-cyano-2-((S)-1-(4-methoxyphenyl)-2,5-dioxopyrrolidin-3-yl)-2-phenylacetateC22H20N2O5[α]D20=-50.6 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R,S)

(R)-Ethyl 2-cyano-2-((S)-1-(naphthalen-1-yl)-2,5-dioxopyrrolidin-3-yl)-2-phenylacetateC25H20N2O4[α]D20=-49.0 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R,S)

(R)-Ethyl 2-((S)-1-benzyl-2,5-dioxopyrrolidin-3-yl)-2-cyano-2-phenylacetateC22H20N2O4[α]D20=-11.8 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R,S)

(R)-Ethyl 2-cyano-2-((S)-2,5-dioxo-1-phenylpyrrolidin-3-yl)-2-(p-tolyl)acetateC22H20N2O4[α]D20=-52.4 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R,S)

(R)-Methyl 2-cyano-2-((S)-2,5-dioxo-1-phenylpyrrolidin-3-yl)-2-phenylacetateC20H16N2O4[α]D20=-38.5 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R,S)

(R)-Ethyl 2-(4-chlorophenyl)-2-cyano-2-((S)-2,5-dioxo-1-phenylpyrrolidin-3-yl)acetateC21H17ClN2O4[α]D20=-46.2 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R,S)

(R)-Ethyl 2-(4-bromophenyl)-2-cyano-2-((S)-2,5-dioxo-1-phenylpyrrolidin-3-yl)acetateC21H17BrN2O4[α]D20=-49.0 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R,S)

(R)-Ethyl 2-cyano-2-((S)-2,5-dioxo-1-phenylpyrrolidin-3-yl)-2-(4-methoxyphenyl)acetateC22H20N2O5[α]D20=-56.0 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R,S)