| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1343794 | Tetrahedron: Asymmetry | 2014 | 10 Pages |
Graphical abstract13 new chiral oxazoline-azaheteroaromatic ligands.Figure optionsDownload full-size imageDownload as PowerPoint slide
Enantiomerically pure oxazoline ligands with variously substituted 1,2,4-triazine rings have been synthesized using the Pd-catalysed cross-coupling amination of 3-halo-1,2,4-triazines. The catalytic efficiency of the ligands was studied in the asymmetric Henry reaction of nitromethane with several aldehydes. The appropriate β-nitro alcohols were formed in good yields (up to 93%) and with up to 78% ee. The impact of the substitution of the 1,2,4-triazine ring on the nitroaldol reaction is discussed. In order to investigate the influence of the 1,2,4-triazine ring on the catalytic activity of the ligands, ligands where the 1,2,4-triazine ring was replaced by a pyridine, pyrimidine, pyrazine or pyridine N-oxide ring were synthesized and applied to asymmetric nitroaldol reactions.
3-{2-[(4S)-4-Phenyl-4,5-dihydro-1,3-oxazol-2-yl]phenyl}amino-6-phenyl-1,2,4-triazineC24H19N5O[α]D20 = +33.4 (c 0.55, CH2Cl2)Absolute configuration: (4S)Source of chirality: (S)-phenylglycinol
3-{2-[(4S)-4-Isopropyl-4,5-dihydro-1,3-oxazol-2-yl]phenyl}amino-6-phenyl-1,2,4-triazineC21H21N5O[α]D20 = −7.1 (c 0.50, CH2Cl2)Absolute configuration: (4S)Source of chirality: (S)-valinol
3-{2-[(3aR,8aS)-8,8a-Dihydro-3aH-indeno[1,2-d]oxazol-2-yl]phenyl}amino-6-phenyl-1,2,4-triazineC25H19N5O[α]D20 = −487.6 (c 0.25, CH2Cl2)Absolute configuration: (3aR,8aS)Source of chirality: (1R,2S)-1-amino-2-indanol
3-{2-[(4S)-4-Phenyl-4,5-dihydro-1,3-oxazol-2-yl]phenyl}aminophenanthro[9,10-e]1,2,4-triazineC30H21N5O[α]D20 = +259.2 (c 0.25, CH2Cl2)Absolute configuration: (4S)Source of chirality: (S)-phenylglycinol
2-{2-[(4S)-4-Phenyl-4,5-dihydro-1,3-oxazol-2-yl]phenyl}aminopyrimidineC19H16N4O[α]D20 = +376.5 (c 1.0, CH2Cl2)Absolute configuration: (4S)Source of chirality: (S)-phenylglycinol
2-{2-[(4S)-4-Phenyl-4,5-dihydro-1,3-oxazol-2-yl]phenyl}aminopyrazineC19H16N4O[α]D20 = +351.5 (c 1.0, CH2Cl2)Absolute configuration: (4S)Source of chirality: (S)-phenylglycinol
2-{2-[(3aR,8aS)-8,8a-Dihydro-3aH-indeno[1,2-d]oxazol-2-yl]phenyl}aminopyridineC21H17N3O[α]D20 = −388.1 (c 0.52, CH2Cl2)Absolute configuration: (3aR,8aS)Source of chirality: (1R,2S)-1-amino-2-indanol
2-{2-[(3aR,8aS)-8,8a-Dihydro-3aH-indeno[1,2-d]oxazol-2-yl]phenyl}aminopyrimidineC20H16N4O[α]D20 = −408.2 (c 0.53, CH2Cl2)Absolute configuration: (3aR,8aS)Source of chirality: (1R,2S)-1-amino-2-indanol
2-{2-[(3aR,8aS)-8,8a-Dihydro-3aH-indeno[1,2-d]oxazol-2-yl]phenyl}aminopyrazineC20H16N4O[α]D20 = −363.6 (c 0.55, CH2Cl2)Absolute configuration: (3aR,8aS)Source of chirality: (1R,2S)-1-amino-2-indanol
2-Chloro-4-{2-[(4S)-4-phenyl-4,5-dihydro-1,3-oxazol-2-yl]phenyl}aminopyrimidineC19H15ClN4O[α]D20 = +268.7 (c 0.45, CH2Cl2)Absolute configuration: (4S)Source of chirality: (S)-phenylglycinol
2,4-Di-{[2-((4S)-4-phenyl-4,5-dihydro-1,3-oxazol-2-yl)phenyl]amino}pyrimidineC34H28N6O2[α]D20 = +349.7 (c 0.45, CH2Cl2)Absolute configuration: (4S)Source of chirality: (S)-phenylglycinol
2-{2-[(4S)-4-Phenyl-4,5-dihydro-1,3-oxazol-2-yl]phenyl}aminopyridine 1-oxideC20H17N3O2[α]D20 = +279.8 (c 0.50, CH2Cl2)Absolute configuration: (4S)Source of chirality: (S)-phenylglycinol
2-{2-[(4S)-4-Isopropyl-4,5-dihydro-1,3-oxazol-2-yl]phenyl}aminopyridine 1-oxideC17H19N3O2[α]D20 = +43.2 (c 0.54, CH2Cl2)Absolute configuration: (4S)Source of chirality: (S)-valinol
(S)-2-Nitro-1-(3-nitrophenyl)ethanolC8H8N2O5ee = 41%[α]D25 = +17.1 (c 1.25, CH2Cl2)Absolute configuration: (S)Source of chirality: asymmetric nitroaldol reaction
(S)-2-Nitro-1-phenylethanolC8H9NO3ee = 60%[α]D25 = +28.1 (c 1.00, CH2Cl2)Absolute configuration: (S)Source of chirality: asymmetric nitroaldol reaction
(S)-2-nitro-1-(2-nitrophenyl)ethanolC8H8N2O5ee = 43%[α]D25 = −98.5 (c 1.05, CH2Cl2)Absolute configuration: (S)Source of chirality: asymmetric nitroaldol reaction
(S)-2-Nitro-1-(4-nitrophenyl)ethanolC8H8N2O5ee = 42%[α]D25 = +18.2 (c 1.00, CH2Cl2)Absolute configuration: (S)Source of chirality: asymmetric nitroaldol reaction
(S)-1-(2-Chlorophenyl)-2-nitroethanolC8H8ClNO3ee = 55%[α]D25 = +55.6 (c 1.03, CH2Cl2)Absolute configuration: (S)Source of chirality: asymmetric nitroaldol reaction
(S)-1-(3-Chlorophenyl)-2-nitroethanolC8H8ClNO3ee = 29%[α]D25 = +17.4 (c 0.53, CH2Cl2)Absolute configuration: (S)Source of chirality: asymmetric nitroaldol reaction
(R)-1-(4-Chlorophenyl)-2-nitroethanolC8H8ClNO3ee = 78%[α]D25 = −36.4 (c 1.02, CH2Cl2)Absolute configuration: (R)Source of chirality: asymmetric nitroaldol reaction
(S)-1-(4-Chlorophenyl)-2-nitroethanolC8H8ClNO3ee = 65%[α]D25 = +30.9 (c 1.01, CH2Cl2)Absolute configuration: (S)Source of chirality: asymmetric nitroaldol reaction
(S)-1-(2-Bromophenyl)-2-nitroethanolC8H8BrNO3ee = 77%[α]D25 = +38.2 (c 0.90, CH2Cl2)Absolute configuration: (S)Source of chirality: asymmetric nitroaldol reaction
(S)-1-(2-Methylphenyl)-2-nitroethanolC9H11NO3ee = 63%[α]D25 = +30.8 (c 1.01, CH2Cl2)Absolute configuration: (S)Source of chirality: asymmetric nitroaldol reaction
(S)-1-(3-Methylphenyl)-2-nitroethanolC9H11NO3ee = 61%[α]D25 = +23.2 (c 0.5, CH2Cl2)Absolute configuration: (S)Source of chirality: asymmetric nitroaldol reaction
(S)-1-(2-Methoxylphenyl)-2-nitroethanolC9H11NO4ee = 56%[α]D25 = +29.2 (c 1.04, CH2Cl2)Absolute configuration: (S)Source of chirality: asymmetric nitroaldol reaction
(S)-1-(3-Methoxylphenyl)-2-nitroethanolC9H11NO4ee = 22%[α]D25 = +10.7 (c 0.60, CH2Cl2)Absolute configuration: (S)Source of chirality: asymmetric nitroaldol reaction
(S)-1-(4-Methoxyphenyl)-2-nitroethanolC9H11NO3ee = 30%[α]D25 = +15.3 (c 0.50, CH2Cl2)Absolute configuration: (S)Source of chirality: asymmetric nitroaldol reaction
(S)-1-(1-Naphthyl)-2-nitroethanolC12H11NO3ee = 41%[α]D25 = +26.8 (c 1.00, CH2Cl2)Absolute configuration: (S)Source of chirality: asymmetric nitroaldol reaction
(S)-1-Nitro-4-phenylbutan-2-olC10H13NO3ee = 50%[α]D25 = −4.8 (c 1.00, CH2Cl2)Absolute configuration: (S)Source of chirality: asymmetric nitroaldol reaction
