Perhydro-1,3-benzoxazines derived from (−)-8-aminomenthol as ligands for the catalytic enantioselective addition of diethylzinc to aldehydes

The catalytic potency of a series of perhydro-1,3-benzoxazines prepared from (−)-8-aminomenthol was examined in the enantioselective addition of diethylzinc to aldehydes. When (2R,3S,3aS,4aR,6R,8aS)-2-isopropyl-6,9,9-trimethyl-3-phenyldecahydro-4aH-pyrrolo[2,1-b][1,3]benzoxazin-3-ol 7b was used as a chiral ligand, 1-substituted propanols with an (R)-configuration were obtained in high yields and enantiomeric excesses up to >99%. The catalyst can be recovered and used without any loss in its activity.

Figure optionsDownload as PowerPoint slide

(2S,4aS,7R,8aR)-2-Isopropyl-4,4,7-trimethyloctahydro-2H-1,3-benzoxazineC14H27NO[α]D25=+7.8 (c 1.1, CHCl3)Source of chirality: (−)-8-aminomentholAbsolute configuration: (2S,4aS,7R,8aR)

(2S,4aS,7R,8aR,2′S,4a′S,7′R,8a′R)-Benzene-1,3-diylbis(4,4,7-trimethyloctahydro-2H-1,3-benzoxazine)C28H44N2O2[α]D25=+75.8 (c 1.2, CHCl3)Source of chirality: (−)-8-aminomentholAbsolute configuration: (2S,4aS,7R,8aR,2′S,4a′S,7′R,8a′R)

[(2S,4aS,7R,8aR)-4,4,7-Trimethyloctahydro-2H-1,3-benzoxazin-2-yl](diphenyl)methanolC24H31NO2[α]D25=+50.5 (c 1.0, CHCl3)Source of chirality: (−)-8-aminomentholAbsolute configuration: (2S,4aS,7R,8aR)

(2S,3R,3aS,4aR,6R,8aS)-2-Isopropyl-6,9,9-trimethyl 3-phenyldecahydro-4aH-pyrrolo[2,1-b][1,3]benzoxazin-3-olC23H35NO2[α]D25=-52.2 (c 1.0, CHCl3)Source of chirality: (−)-8-aminomentholAbsolute configuration: (2S,3R,3aS,4aR,6R,8aS)

(2S,3S,3aS,4aR,6R,8aS)-2,3-Diisopropyl-6,9,9-trimethyldecahydro-4aH-pyrrolo[2,1-b][1,3]benzoxazin-3-olC20H37NO2[α]D25=-36.8 (c 0.9, CHCl3)Source of chirality: (−)-8-aminomentholAbsolute configuration: (2S,3S,3aS,4aR,6R,8aS)

(2R,3S,3aS,4aR,6R,8aS)-2-Isopropyl-6,9,9-trimethyldecahydro-4aH-pyrrolo[2,1-b][1,3]benzoxazin-3-olC17H31NO2[α]D25=-45.9 (c 1.1, CHCl3)Source of chirality: (−)-8-aminomentholAbsolute configuration: (2R,3S,3aS,4aR,6R,8aS)

(2R,3S,3aS,4aR,6R,8aS)-2-Isopropyl-6,9,9-trimethyl-3-phenyldecahydro-4aH-pyrrolo[2,1-b][1,3]benzoxazin-3-olC23H35NO2[α]D25=-92.9 (c 1.1, CHCl3)Source of chirality: (−)-8-aminomentholAbsolute configuration: (2R,3S,3aS,4aR,6R,8aS)

(2R,3R,3aS,4aR,6R,8aS)-2, 3-Diisopropyl-6,9,9-trimethyldecahydro-4aH-pyrrolo[2,1-b][1,3]benzoxazin-3-olC20H37NO2[α]D25=-51.5 (c 0.7, CHCl3)Source of chirality: (−)-8-aminomentholAbsolute configuration: (2R,3R,3aS,4aR,6R,8aS)

(3R,4S)-1-{2-[1′S,2′R,4′R)-2′-Hydroxy-4′-methylcyclohexyl]propan-2-yl}-4-isopropyl-3-phenylpyrrolidin-3-olC23H37NO2[α]D25=-52.9 (c 1.1, CHCl3)Source of chirality: (−)-8-aminomentholAbsolute configuration: (3R,4S,1′S,2′R,4′R)

(3S,4R)-1-{2-[1′S,2′R,4′R)-2′-Hydroxy-4′-methylcyclohexyl]propan-2-yl}-4-isopropyl-3-phenylpyrrolidin-3-olC23H37NO2[α]D25=-12.2 (c 0.90, CHCl3).Source of chirality: (−)-8-aminomentholAbsolute configuration: (3S,4R,1′S,2′R,4′R)

(3R,4S)-3-Phenyl-4-(prop-1-en-2-yl)pyrrolidin-3-olC13H17NO[α]D25=+94.9 (c 0.7, MeOH)Source of chirality: (−)-8-aminomentholAbsolute configuration: (3R,4S)

(3R,4S)-1-Methyl-3-phenyl-4-(prop-1-en-2-yl)pyrrolidin-3-olC14H19NO[α]D25=+78.5 (c 0.3, CHCl3)Source of chirality: (−)-8-aminomentholAbsolute configuration: (3R,4S)

(3R,4S)-4-Isopropyl-1-methyl-3-phenylpyrrolidin-3-olC14H21NO[α]D25=-13.2 (c 1.1,CHCl3).Source of chirality: (−)-8-aminomentholAbsolute configuration: (3R,4S)