Straightforward preparation of enantiopure 3-amino-4,4-dimethylpyrrolidin-2-one and its derivatives

An easy access to both enantiomers of 3-amino- and 3-(dimethylamino)-4,4-dimethylpyrrolidin-2-one from rac-pantolactam using (R)-α-methylbenzylamine as a chiral auxiliary is described.

Figure optionsDownload as PowerPoint slide

(R)-1-(p-Methoxybenzyl)-4,4-dimethyl-3-[(1-phenylethyl)imino]pyrrolidin-2-oneC22H26N2O2[α]D23=+39 (c 0.76, CH2Cl2)Source of chirality: (R)-1-phenylethylamineAbsolute configuration: (R)

(3S,1′R)-1-(p-Methoxybenzyl)-4,4-dimethyl-3-[(1-phenylethyl)amino]pyrrolidin-2-one·(2R,3R)-tartrateC22H28N2O2·C4H6O6[α]D23=+9 (c 1.10, MeOH)Source of chirality: diastereoselective reduction using (R)-1-phenylethylamineAbsolute configuration: (3S,1′R)(2R,3R)

(3S,1′R)-1-(p-Methoxybenzyl)-4,4-dimethyl-3-[(1-phenylethyl)amino]pyrrolidin-2-oneC22H28N2O2[α]D23=+14 (c 0.54, CH2Cl2)Source of chirality: diastereoselective reduction using (R)-1-phenylethylamineAbsolute configuration: (3S,1′R)

(S)-3-Amino-1-(p-methoxybenzyl)-4,4-dimethylpyrrolidin-2-oneC14H20N2O2[α]D23=-43 (c 0.90, CH2Cl2)Source of chirality: diastereoselective reduction using (R)-1-phenylethylamineAbsolute configuration: (S)

(S)-3-Amino-1-(p-methoxybenzyl)-4,4-dimethylpyrrolidin-2-one·mono-(2R,3R)-O,O′-di-(p-toluoyl)tartrateC14H20N2O2·C20H18O8[α]D23=-117 (c 0.95, MeOH)Source of chirality: diastereoselective reduction using (R)-1-phenylethylamineAbsolute configuration: (S)(2R,3R)

(S)-3-(Dimethylamino)-1-(p-methoxybenzyl)-4,4-dimethylpyrrolidin-2-oneC16H24N2O2[α]D23=-76 (c 0.58, CH2Cl2)Source of chirality: diastereoselective reduction using (R)-1-phenylethylamineAbsolute configuration: (S)

(S)-3-(Dimethylamino)-1-[(3-hydroxymethyl)-4-methoxybenzyl]-4,4-dimethylpyrrolidin-2-oneC17H26N2O3[α]D23=-40 (c 0.59, CH2Cl2)Source of chirality: diastereoselective reduction using (R)-1-phenylethylamineAbsolute configuration: (S)

(S)-3-(Dimethylamino)-1-(p-methoxybenzyl)-4,4-dimethylpyrrolidin-2-one·mono-(2R,3R)-O,O′-di-(p-toluoyl)tartrateC16H24N2O2·C20H18O8[α]D23=-105 (c 0.79, MeOH)Source of chirality: diastereoselective reduction using (R)-1-phenylethylamineAbsolute configuration: (S)(2R,3R)

Benzyl (S)-N-[1-(p-methoxybenzyl)-4,4-dimethyl-2-oxopyrrolidin-3-yl]carbamateC22H26N2O4[α]D23=+25 (c 0.62, CH2Cl2)Source of chirality: diastereoselective reduction using (R)-1-phenylethylamineAbsolute configuration: (S)

Benzyl (S)-N-[1-(p-methoxybenzyl)-4,4-dimethyl-2,5-dioxopyrrolidin-3-yl]carbamateC22H24N2O5[α]D23=-28 (c 0.46, CH2Cl2)Source of chirality: diastereoselective reduction using (R)-1-phenylethylamineAbsolute configuration: (S)

Benzyl (S)-N-[4,4-dimethyl-2-oxopyrrolidin-3-yl]carbamateC14H18N2O3[α]D23=-12 (c 0.30, CH2Cl2)Source of chirality: diastereoselective reduction using (R)-1-phenylethylamineAbsolute configuration: (S)

(S)-3-Amino-4,4-dimethylpyrrolidin-2-oneC6H12N2O[α]D23=-17 (c 0.53, CH2Cl2)Source of chirality: diastereoselective reduction using (R)-1-phenylethylamineAbsolute configuration: (S)

(R)-4,4-Dimethyl-3-[(1-phenylethyl)imino]pyrrolidin-2-oneC14H18N2O[α]D23=+44 (c 0.80, CH2Cl2)Source of chirality: (R)-1-phenylethylamineAbsolute configuration: (R)

(3S,1′R)-4,4-Dimethyl-3-[(1-phenylethyl)amino]pyrrolidin-2-oneC14H20N2O[α]D23=+26 (c 1.30, CH2Cl2)Source of chirality: diastereoselective reduction using (R)-1-phenylethylamineAbsolute configuration: (3S,1′R)

(3R,1′R)-4,4-Dimethyl-3-[(1-phenylethyl)amino]pyrrolidin-2-oneC14H20N2O[α]D23=+136 (c 0.70, CH2Cl2)Source of chirality: diastereoselective reduction using (R)-1-phenylethylamineAbsolute configuration: (3R,1′R)

(S)-3-(Dimethylamino)-4,4-dimethylpyrrolidin-2-oneC8H16N2O[α]D23=-20 (c 0.78, CH2Cl2)Source of chirality: diastereoselective reduction using (R)-1-phenylethylamineAbsolute configuration: (S)