Highly Enantioselective Syntheses of β-Amino Alcohols
(1S,2S)-2-(4-Chlorophenylamino)-1,2-diphenylethanol (6e):[7f] The ti-
(1S,2S)-2-(2-Methoxyphenylamino)cyclohexan-1-ol (11b):[7e,7f] The
tle compound was isolated by column chromatography (hexane/
title compound was isolated by column chromatography (hexane/
AcOEt, 90:10) as a white solid; m.p. 95 °C; ee Ͼ99% on HPLC AcOEt, 90:10) as a white solid; m.p. 68–70 °C; ee 83% on HPLC
(Chiralpak AD Column) mobile phase 85:15 hexane/iPrOH; flow (Chiralpak OJ column) mobile phase, 80:20 hexane/iPrOH; flow
rate 1 mLmin–1, λ = 247 nm, retention time (1S,2S) 15.58 min, rate 0.5 mLmin–1, λ = 247 nm, retention time (1S,2S): 17.1 min,
(1R,2R): 17.37 min. Only one diastereomer was observed by NMR
and HPLC analysis. H NMR (500 MHz, CDCl3): δ = 2.38 (br. s,
(1R,2R): 19.2 min. [α]rDt = +49.6 (c = 3.0, CH2Cl2, 63% ee). 1H
NMR (500 MHz, CDCl3): δ = 0.97–1.15 (m, 1 H), 1.24–1.50 (m, 3
H), 1.68–1.78 (m, 2 H), 2.04–2.16 (m, 2 H), 2.85 (br. s, 1 H), 3.07–
3.19 (m, 1 H), 3.34–3.46 (m, 1 H), 3.83 (s, 3 H), 6.63–6.89 (m, 4
1
1 H), 4.47 (d, J = 5.6 Hz, 1 H), 4.70 (br. s, 1 H, NH), 4.86 (d, J =
5.6 Hz, 1 H), 6.41 (d, J = 8.8 Hz, 2 H), 6.98 (d, J = 8.0 Hz, 2 H),
7.15–7.30 (m, 10 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 64.7, H) ppm. 13C NMR (125 MHz, CDCl3): δ = 24.2, 25.0, 31.5, 33.0,
77.9, 126.4, 127.2, 127.6, 128.0, 128.3, 128.6, 139.8, 140.1, 140.4,
55.4, 55.6, 74.5, 109.7, 111.4, 117.2, 121.2, 137.5, 147.5 ppm. IR
145.8 ppm. IR (in KBr): ν = 3396, 3063, 3031, 2960, 2929, 2860,
(in KBr): ν = 3616, 3429, 3067, 2964, 1602, 1511, 1456, 1430, 1341,
˜
˜
1812, 1722, 1599, 1496, 1268, 1073, 820, 739, 700 cm–1. LC-MS:
m/z 324 [M + H]+, 347 [M + Na]+, 306 [M – OH]+, 289 [M –
Cl]+, 271(base peak) [M – OH – Cl]+.
1247, 1180, 1121, 1050, 1030, 977, 945 cm–1.
(1S,2S)-2-(4-Methoxyphenylamino)cyclohexan-1-ol
(11c):[9a,7b,7f]
The title compound was isolated by column chromatography (hex-
ane/AcOEt, 85:15) as a white solid; m.p. 62–64 °C; ee on HPLC
(Chiralpak OD column) mobile phase, 80:20 hexane/iPrOH; flow
rate 0.5 mLmin–1, λ = 247 nm, retention time (1S,2S): 16.2 min,
(1R,2R): 24.3 min. [α]rDt = +40.1 (c = 3.2, CH2Cl2, 48% ee). 1H
NMR (500 MHz, CDCl3): δ = 0.85–1.10 (m, 1 H), 1.12–1.40 (m, 3
H), 1.60–1.80 (m, 2 H), 2.0–2.18 (m, 2 H), 2.92–3.04 (m, 1 H), 2.60
(br. s, 1 H), 3.24–3.55 (m, 1 H), 3.73 (s, 3 H), 6.66 (d, J = 8.8 Hz,
2 H), 6.76 (d, J = 8.8 Hz, 2 H) ppm. 13C NMR (125 MHz, CDCl3):
δ = 24.2, 25.0, 31.4, 33.0, 55.6, 61.6, 74.3, 114.7, 116.3, 141.5,
(2S,3S)-3-(Phenylamino)butan-2-ol (10a):[5b] The title compound
was isolated by column chromatography (hexane/AcOEt, 90:10) as
an oil; ee 68% on HPLC (Chiralpak OD column) mobile phase,
97.56:2.44 hexane/iPrOH; flow rate 1 mLmin–1, λ = 247 nm, reten-
tion time (2S,3S): 34.56 min, (2R,3R): 36.21 min. 1H NMR
(500 MHz, CDCl3): δ = 1.14 (d, J = 6.8 Hz, 1 H), 1.25 (d, J =
6.8 Hz, 3 H), 2.61 (br. s, 1 H), 3.31 (m, 1 H), 3.62 (m, 2 H), 6.66–
6.74 (m, 3 H), 7.15–7.18 (m, 2 H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 17.3, 19.5, 56.1, 71.4, 114.3, 118.2, 129.3, 147.7 ppm.
152.8 ppm. IR (in KBr): ν = 3677, 3529, 3366, 3021, 3013, 2938,
˜
IR (KBr): ν = 3398, 3053, 2974, 2926, 1922, 1602, 1505, 1439, 1376,
˜
1318, 1254, 1005, 902, 751, 692 cm–1. LC-MS: m/z 166 [M + H]+,
2861, 2836, 1612, 1512, 1465, 1450, 1401, 1296, 1239, 1221, 1180,
1136, 1067, 1038 cm–1.
(2S,3S)-3-(2-Methoxyphenylamino)butan-2-ol (10b):[5b] The title
compound was isolated by column chromatography (hexane/Ac-
OEt, 90:10) as an oil; ee Ͼ99% on HPLC (Chiralpak OD column)
mobile phase, 95:5 hexane/iPrOH; flow rate 1 mLmin–1, λ =
(1S,2S)-2-(Phenylamino)cyclooctan-1-ol (12a):[7b] The title com-
pound was isolated by column chromatography (hexane/AcOEt,
90:10) as a white solid. Melting point 55–56 °C; ee 72% on HPLC
(Chiralpak OD column) mobile phase, 95:5 hexane/iPrOH; flow
rate 0.8 mLmin–1, λ = 247 nm, retention time (1S,2S): 27.12 min,
(1R,2R) 29.34 min: 1H NMR (500 MHz, CDCl3): δ = 1.05–1.45
(m, 4 H), 1.50–2.15 (m, 8 H), 3.40–3.50 (m, 1 H), 3.60–3.70 (m, 1
1
247 nm, retention time (2S,3S): 23.34 min, (2R,3R): 29.31 min. H
NMR (500 MHz, CDCl3): δ = 1.21 (d, J = 8.3 Hz, 3 H), 1.33 (d,
J = 6.0 Hz, 3 H), 2.78 (s, 1 H), 3.40 (m, 1 H), 3.74 (m, 1 H), 3.91
(s, 3 H), 4.13 (s, 1 H), 6.75–6.80 (m, 2 H), 6.85–6.87 (m, 1 H), 6.91–
6.96 (m, 1 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 17.2, 19.4,
55.4, 55.8, 71.4, 109.7, 111.4, 117.2, 121.2, 137.5, 147.5 ppm. IR
H), 4.50 (br., 1 H), 6.70–7.20 (m, 6 H) ppm. IR (KBr): ν = 3315,
˜
3107, 3054, 3027, 2941, 1923, 1690, 1604, 1498, 1465, 1306,
1256 cm–1. LC-MS: m/z = 218 [M + H]+.
(KBr): ν = 3414, 2970, 1602, 1510, 1456, 1249, 1220, 1110, 1025,
˜
902, 737 cm–1. LC-MS: m/z 196 [M + H]+.
(1S,2S)-2-(2-Methoxyphenylamino)cyclooctan-1-ol (12b): The title
compound was isolated by column chromatography (hexane/Ac-
OEt, 90:10) as an oil; ee 78% on HPLC (Chiralpak OJ column)
mobile phase, 95:5 hexane/iPrOH; flow rate 0.4 mLmin–1, λ =
(2S,3S)-3-(4-Methoxyphenylamino)butan-2-ol (10c):[5b] The title
compound was isolated by column chromatography (hexane/Ac-
OEt, 90:10) as an oil; ee 75% on HPLC (Chiralpak AD column)
mobile phase, 95:5 hexane/iPrOH; flow rate 1 mLmin–1, λ =
1
220 nm, retention time (1S,2S): 40.39 min, (1R,2R): 42.10 min. H
1
NMR (500 MHz, CDCl3): δ = 1.27–1.30 (m, 4 H), 1.44–1.70 (m, 8
H), 2.14–2.17 (m, 1 H), 2.90–2.93 (m, 1 H), 3.84 (s, 3 H), 4.47 (br.,
1 H), 6.71–7.17 (m, 5 H) ppm. 13C NMR (125 MHz, CDCl3): δ =
24.43, 25.60, 26.29, 26.49, 26.56, 55.75, 75.75, 110.50, 116.07,
121.38, 147.86, 150.63 ppm. LC-MS: m/z = 250 [M + H]+.
247 nm, retention time (2S,3S): 48.87 min, (2R,3R): 49.20 min. H
NMR (500 MHz, CDCl3): δ = 1.18 (d, J = 6.4 Hz, 3 H), 1.32 (d,
J = 6.0 Hz, 3 H), 3.23 (t, J = 6.9 Hz, 1 H), 3.63 (t, J = 6.6 Hz, 1
H), 3.81 (s, 3 H), 6.71–6.75 (m, 2 H), 6.83–6.86 (m, 2 H) ppm. 13C
NMR (125 MHz, CDCl3): δ = 17.1, 19.4, 55.7, 58.0, 71.4, 114.9,
116.3, 141.0, 152.9 ppm. IR (KBr): ν = 3394, 2970, 1617, 1512,
˜
(1S,2S)-2-(4-Methoxyphenylamino)cyclooctan-1-ol (12c): The title
compound was isolated by column chromatography (hexane/Ac-
OEt, 90:10) as an oil; ee 56% on HPLC (Chiralpak OD column)
mobile phase, 95:5 hexane/iPrOH; flow rate 0.8 mLmin–1, λ =
1455, 1377, 1236, 1037, 822 cm–1. LC-MS: m/z 196 [M + H]+.
(1S,2S)-2-(Phenylamino)cyclohexene-1-ol (11a):[7e,7f,9a] The title
compound was isolated by column chromatography (hexane/Ac-
OEt, 90:10) as a white solid; m.p. 58–60 °C; ee 67% on HPLC
(Chiralpak OD column) mobile phase, 95:5 hexane/iPrOH; flow
rate 0.4 mLmin–1, λ = 247 nm, retention time (1S,2S): 62.95 min,
(1R,2R): 65.41 min. 1H NMR (500 MHz, CDCl3): δ = 1.03–1.41
(m, 4 H), 1.71–1.77 (m, 2 H), 2.09–2.15 (m, 2 H), 2.89 (m, 2 H),
3.13 (ddd, J = 3.9, J = 10.0, J = 10.1 Hz, 1 H), 3.33 (ddd, J = 4.2,
J = 10.4, J = 10.5 Hz, 1 H), 6.7–7.2 (m, 2 H), 7.21–7.25 (m, 5
H) ppm. 13C NMR (125 MHz, CDCl3): δ = 24.2, 24.9, 31.5, 33.1,
1
220 nm, retention time (1S,2S): 27.32 min, (1R,2R) 39.59 min: H
NMR (500 MHz, CDCl3): δ = 1.26–1.29 (m, 4 H), 1.44–1.63 (m, 8
H), 2.12–2.16 (m, 1 H), 2.89–2.91 (m, 1 H), 4.48 (br., 1 H), 3.74 (s,
3 H), 6.66–6.75 (m, 5 H) ppm. 13C NMR (125 MHz, CDCl3): δ =
25.74, 26.43, 26.70, 55.82, 72.71, 114.91, 116.93, 139.26, 151.53,
153.09, 155.72 ppm. LC-MS: m/z = 250 [M + H]+.
Recycling of the Catalyst: At the end of the catalytic run (checked
on TLC) the solvent was completely removed under reduced pres-
sure. The residue was extracted with hexane to remove the reac-
tants. The remaining solid was further washed with hexane
(10 mL), dried under reduced pressure for 1–2 h, and was used as
60.1, 74.4, 114.3, 118.3, 129.3, 147.8 ppm. IR (in KBr): ν = 3354,
˜
2931, 2858, 1602, 1501, 1448, 1320, 1067, 748 cm–1. LC-MS: m/z =
192 [M + H]+, 214 [M + Na]+.
Eur. J. Org. Chem. 2008, 3118–3128
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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