Diastereoselective preparation of (S)-(1,4,4-trimethylpyrrolidin-3-yl)amine, a new chiral 1,2-diamine for thiourea-type organocatalysts

The enantioselective synthesis of the title compound, its conversion into a thiourea-type organocatalyst and the behavior of this organocatalyst in several enantioselective Michael reactions are described.

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(R)-1,4,4-Trimethyl-3-[(1-phenylethyl)imino]pyrrolidin-2-oneC15H20N2O[α]D24=+62 (c 0.81, CH2Cl2)Source of chirality: (R)-1-phenylethylamineAbsolute configuration: (R)

(3S,1′R)-1,4,4-Trimethyl-3-[(1-phenylethyl)amino]pyrrolidin-2-one·(S)-mandelateC15H22N2O·C8H8O3[α]D22=+171 (c 0.65, MeOH)Source of chirality: Diastereoselective reduction using (R)-1-phenylethylamine as a chiral auxiliaryAbsolute configuration: (3S,1′R) (S)

(3R,1′R)-1,4,4-Trimethyl-3-[(1-phenylethyl)amino]pyrrolidin-2-one·(S)-mandelateC15H22N2O·C8H8O3[α]D22=+148 (c 1.04, MeOH)Source of chirality: Diastereoselective reduction using (R)-1-phenylethylamine as a chiral auxiliaryAbsolute configuration: (3R,1′R) (S)

(3S,1′R)-1,4,4-Trimethyl-3-[(1-phenylethyl)amino]pyrrolidin-2-oneC15H22N2O[α]D22=+144 (c 0.74, CH2Cl2)Source of chirality: Diastereoselective reduction using (R)-1-phenylethylamine as a chiral auxiliaryAbsolute configuration: (3S,1′R)

(3R,1′R)-1,4,4-Trimethyl-3-[(1-phenylethyl)amino]pyrrolidin-2-oneC15H22N2O[α]D22=+139 (c 1.10, CH2Cl2)Source of chirality: Diastereoselective reduction using (R)-1-phenylethylamine as a chiral auxiliaryAbsolute configuration: (3R,1′R)

(S)-3-Amino-1,4,4-trimethylpyrrolidin-2-oneC7H14N2O[α]D22=+41 (c 0.90, CH2Cl2)Source of chirality: Diastereoselective synthesis using (R)-1-phenylethylamine as a chiral auxiliaryAbsolute configuration: (S)

(S)-3-Amino-1,4,4-trimethylpyrrolidin-2-one mono-O,O-di-p-toluoyl-(2R,3R)-tartrateC7H14N2O·C20H18O8[α]D22=-106 (c 0.54, MeOH)Source of chirality: Diastereoselective synthesis using (R)-1-phenylethylamine as a chiral auxiliaryAbsolute configuration: (S) (2R,3R)

(S)-(1,4,4-Trimethylpyrrolidin-3-yl)amine dihydrochlorideC7H16N2·2HCl[α]D22=-12 (c 1.03, H2O)Source of chirality: Diastereoselective synthesis using (R)-1-phenylethylamine as a chiral auxiliaryAbsolute configuration: (S)

(S)-(1,4,4-Trimethylpyrrolidin-3-yl)amineC7H16N2[α]D23=-3 (c 0.73 CH2Cl2)Source of chirality: Diastereoselective synthesis using (R)-1-phenylethylamine as a chiral auxiliaryAbsolute configuration: (S)

(S)-N-1,4,4-Trimethylpyrrolidin-3-yl-N′-[3,5-bis(trifluoromethyl)phenyl]thioureaC16H19N3F6S[α]D25=-23 (c 0.53, CH2Cl2)Source of chirality: Diastereoselective synthesis using (R)-1-phenylethylamine as a chiral auxiliaryAbsolute configuration: (S)