Diastereoselective Synthesis of β-Amino-α-(trifluoromethyl) Alcohols
FULL PAPER
J ϭ 13.1 Hz, 2 H, CHHPh), 3.91 (d, J ϭ 13.1 Hz, 2 H, CHHPh),
4.02 (m, 1 H, CHOH), 5.38 (br. s, 1 H, OH), 7.20Ϫ7.40 (m, 10 H,
[α]2D0 ϭ Ϫ11.9 (c ϭ 1.0, CHCl3). IR (KBr): ν˜ ϭ 3550, 1270, 1140,
1
1110, 745, 700 cmϪ1. H NMR (CDCl3): δ ϭ 2.89 (dd, J ϭ 14.4,
Harom) ppm. 13C NMR (CDCl3): δ ϭ 19.6 (CH3), 22.3 (CH3), 27.0 J ϭ 5.3 Hz, 1 H, CHHCHN), 3.08 (dd, J ϭ 14.4, J ϭ 9.2 Hz, 1 H,
2
[CH(CH3)2], 54.4 (CH2Ph), 60.8 (CHN), 66.6 (q, JC,F ϭ 30.3 Hz, CHHCHN), 3.34 (ddd, J ϭ 9.2, J ϭ 5.3, J ϭ 2.3 Hz, 1 H, CHN),
CHOH), 127.6, 128.6, 129.2 (CHarom), 137.8 (Carom) ppm. 19F 3.54 (d, J ϭ 13.9 Hz, 2 H, CHHN), 3.80 (d, J ϭ 13.9 Hz, 2 H,
3
NMR (CDCl3): δ ϭ Ϫ76.74 (d, 3 F, JF,H ϭ 7.5 Hz, CF3) ppm. CHHN), 4.20 (m, 1 H, CHOH), 7.10Ϫ7.35 (m, 15H. Harom) ppm.
C20H24F3NO (351.4): calcd. C 68.36, H 6.88, N 3.99; found C
68.08, H 6.70, N 4.12.
13C NMR (CDCl3): δ ϭ 31.7 (CH2CH), 54.4 (CH2N), 58.8 (CHN),
68.1 (q, 2JC,F ϭ 29.5 Hz, CHOH), 126.2, 127.1, 128.3, 128.7, 129.5
(CHarom), 138.8, 139.1 (Carom) ppm. 19F NMR (CDCl3): δ ϭ
(2S,3S)-3-(Dibenzylamino)-1,1,1-trifluoro-4-methyl-2-pentanol (anti-
2b): Colorless oil. [α]2D0 ϭ ϩ3.8 (c ϭ 0.9, CHCl3). [α]2D0 ϭ Ϫ22.0
3
Ϫ76.07 (d, 3 F, JF,H ϭ 7.6 Hz, CF3) ppm. C24H24F3NO (399.4):
calcd. C 72.16, H 6.06, N 3.51; found C 71.39, H 5.77, N 3.98.
1
(c ϭ 0.9, MeOH).). IR (film): ν˜ ϭ 3440, 745, 695 cmϪ1. H NMR
(CDCl3): δ ϭ 0.97 (d, J ϭ 6.5 Hz, 3 H, CH3), 1.23 (d, J ϭ 6.6 Hz,
3 H, CH3), 2.34 [m, 1 H, CH(CH3)2], 2.75 (dd, J ϭ 9.6, J ϭ 3.9 Hz,
1 H, CHN), 3.19 (br. s, 1 H, OH), 3.72 (d, J ϭ 13.5 Hz, 2 H,
CHHPh), 3.78 (d, J ϭ 13.5 Hz, 2 H, CHHPh), 4.05 (m, 1 H,
CHOH), 7.20Ϫ7.40 (m, 10 H, Harom) ppm. 13C NMR (CDCl3):
δ ϭ 21.1 (CH3), 22.8 (CH3), 27.6 [CH(CH3)2], 55.2 (CH2Ph), 64.2
(2S,3R)-3-(Dibenzylamino)-1,1,1-trifluoro-3-phenyl-2-propanol (ent-
syn-2e): Colorless solid, m.p. 104Ϫ105 °C (from hexane). IR (KBr):
ν˜ ϭ 3325, 1270, 1160, 770, 750, 700 cmϪ1. 1H NMR (CDCl3): δ ϭ
3.07 (d, J ϭ 13.2 Hz, 2 H, CHHPh), 3.89 (d, J ϭ 13.2 Hz, 2 H,
CHHPh), 3.96 (d, J ϭ 10.3 Hz, 1 H, CHN), 4.55 (dq, J ϭ 10.3,
J ϭ 5.8 Hz, 1 H, CHOH), 7.20Ϫ7.50 (m, 15 H, Harom) ppm. 13C
2
2
(CHN), 67.9 (q, JC,F ϭ 29.5 Hz, CHOH), 127.3, 128.5, 129.2
NMR (CDCl3): δ ϭ 53.4 (CH2Ph), 61.0 (CHN), 67.4 (q, JC,F
ϭ
(CHarom), 139.0 (Carom) ppm. 19F NMR (CDCl3): δ ϭ Ϫ73.48 (d,
29.8 Hz, CHOH), 127.7, 128.5, 128.6, 128.8, 129.0, 129.8 (CHarom),
132.0, 137.4 (Carom) ppm. 19F NMR (CDCl3): δ ϭ Ϫ76.49 (d, 3 F,
3JF,H ϭ 6.9 Hz, CF3) ppm. C23H22F3NO (385.4): calcd. C 71.67, H
5.75, N 3.63; found C 71.25, H 5.44, N 3.81.
3
3 F, JF,H ϭ 7.8 Hz, CF3) ppm. C20H24F3NO (351.4): calcd. C
68.36, H 6.88, N 3.99; found C 68.22, H 6.80, N 4.08.
(2R,3S)-3-(Dibenzylamino)-1,1,1-trifluoro-5-methyl-2-hexanol (syn-
2c): Colorless oil. [α]2D0 ϭ ϩ33.4 (c ϭ 1.0, CHCl3). IR (film): ν˜ ϭ
(2R,3R)-3-(Dibenzylamino)-1,1,1-trifluoro-3-phenyl-2-propanol (ent-
anti-2e): Colorless solid, m.p. 119Ϫ121 °C (from hexane/EtOAc).
3435, 1150, 750, 700 cmϪ1 1H NMR (CDCl3): δ ϭ 0.96 (d, J ϭ
.
IR (KBr): ν˜ ϭ 3455, 1275, 1170, 1140, 765, 745, 700 cmϪ1 1H
.
6.6 Hz, 3 H, CH3), 0.98 (d, J ϭ 6.5 Hz, 3 H, CH3), 1.30 (m, 1 H,
CHHCHN), 1.82 (m, 2 H, CHHCHN and CH(CH3)2], 3.04 (m, 1
H, CHN), 3.55 (d, J ϭ 13.2 Hz, 2 H, CHHPh), 3.63 (dq, J ϭ 8.3,
J ϭ 6.6 Hz, 1 H, CHOH), 3.85 (d, J ϭ 13.2 Hz, 2 H, CHHPh),
7.20Ϫ7.40 (m, 10 H, Harom) ppm. 13C NMR (CDCl3): δ ϭ 22.2
(CH3), 23.3 (CH3), 25.5 [CH(CH3)2], 37.8 (CH2CHN), 54.2
NMR (CDCl3): δ ϭ 3.11 (d, J ϭ 13.7 Hz, 2 H, CHHPh), 3.95 (d,
J ϭ 13.7 Hz, 2 H, CHHPh), 4.10 (d, J ϭ 8.0 Hz, 1 H, CHN), 4.66
(m, 1 H, CHOH), 7.20Ϫ7.55 (m, 15 H, Harom) ppm. 13C NMR
(CDCl3): δ ϭ 54.6 (CH2Ph), 62.7 (CHN), 69.9 (q, 2JC,F ϭ 29.2 Hz,
CHOH), 127.1, 128.2, 128.3, 128.7, 129.0, 130.0 (CHarom), 132.4,
138.7 (Carom) ppm. 19F NMR (CDCl3): δ ϭ Ϫ75.28 (d, 3 F, 3JF,H ϭ
6.6 Hz, CF3) ppm. C23H22F3NO (385.4): calcd. C 71.67, H 5.75, N
3.63; found C 71.40, H 5.52, N 3.74.
2
(CH2Ph), 54.9 (CHN), 70.1(q, JC,F ϭ 29.4 Hz, CHOH), 127.6,
128.6, 129.0 (CHarom), 137.9 (Carom) ppm. 19F NMR (CDCl3): δ ϭ
3
Ϫ76.26 (d, 3 F, JF,H ϭ 6.4 Hz, CF3) ppm. C21H26F3NO (365.4):
calcd. C 69.02, H 7.17, N 3.83; found C 68.68, H 7.01, N3.70.
(2R,3S)-4-(tert-Butyldimethylsilyloxy)-3-(dibenzylamino)-1,1,1-tri-
fluoro-2-butanol (syn-2f): Colorless solid, m.p. 89Ϫ90 °C (from hex-
ane). [α]2D0 ϭ ϩ56.3 (c ϭ 0.8, CHCl3). IR (KBr): ν˜ ϭ 3465, 1280,
1165, 750, 700 cmϪ1. 1H NMR (CDCl3): δ ϭ 0.13 (s, 3 H, CH3Si),
0.15 (s, 3 H, CH3Si), 0.98 [s, 9 H, (CH3)3C], 3.09 (ddd, J ϭ 9.5,
J ϭ 7.1, J ϭ 3.0 Hz, 1 H, CHN), 3.70 (d, J ϭ 13.2 Hz, 2 H,
CHHPh), 3.88 (dd, J ϭ 11.4, J ϭ 7.1 Hz, 1 H, CHHO), 3.91 (m,
1 H, CHOH), 3.98 (d, J ϭ 13.2 Hz, 2 H, CHHPh), 4.00 (dd, J ϭ
11.4, J ϭ 3.0 Hz, 1 H, CHHO), 5.24 (br. s, 1 H, OH), 7.20Ϫ7.40
(m, 10 H, Harom) ppm. 13C NMR (CDCl3): δ ϭ Ϫ5.9 (CH3Si),
Ϫ5.7 (CH3Si), 18.1 [C(CH3)3], 25.8 [(CH3)3C], 54.6 (CH2Ph), 57.2
(2S,3S)-3-(Dibenzylamino)-1,1,1-trifluoro-5-methyl-2-hexanol (anti-
2c): Colorless oil. [α]2D0 ϭ Ϫ12.3 (c ϭ 1.0, CHCl3). IR (film): ν˜ ϭ
3460, 1145, 750, 700 cmϪ1 1H NMR (CDCl3): δ ϭ 0.51 (d, J ϭ
.
6.5 Hz, 3 H, CH3), 0.91 (d, J ϭ 6.5 Hz, 3 H, CH3), 1.20 (m, 1 H,
CHHCHN), 1.70 (m, 1 H, CHHCHN), 1.85 [m, 1 H, CH(CH3)2],
3.05 (ddd, J ϭ 9.5, J ϭ 4.5, J ϭ 2.0 Hz, 1 H, CHN), 3.43 (d, J ϭ
13.6 Hz, 2 H, CHHPh), 3.82 (d, J ϭ 13.2 Hz, 2 H, CHHPh), 4.26
(m, 1 H, CHOH), 7.20Ϫ7.40 (m, 10 H, Harom) ppm. 13C NMR
(CDCl3): δ ϭ 21.3 (CH3), 23.6 (CH3), 24.1 [CH(CH3)2], 34.5
2
(CH2CHN), 54.2 (CHN), 54.4 (CH2Ph), 67.8 (q, JC,F ϭ 29.4 Hz,
CHOH), 127.2, 128.3, 129.1 (CHarom), 139.3 (Carom) ppm. 19F
2
(CHN), 59.7 (CH2OTBDMS), 65.1 (q, JC,F ϭ 30.9 Hz, CHOH),
3
127.5, 128.6, 129.1 (CHarom), 137.9 (Carom) ppm. 19F NMR
NMR (CDCl3): δ ϭ Ϫ76.50 (d, 3 F, JF,H ϭ 8.2 Hz, CF3) ppm.
C21H26F3NO (365.4): calcd. C 69.02, H 7.17, N 3.83; found C
68.74, H 7.12, N 3.94.
3
(CDCl3): δ ϭ Ϫ77.52 (d, 3 F, JF,H ϭ 6.3 Hz, CF3) ppm.
C24H34F3NO2Si (453.6): calcd. C 63.55, H 7.55, N 3.09; found C
63.16, H 6.90, N 3.22.
(2R,3S)-3-(Dibenzylamino)-1,1,1-trifluoro-4-phenyl-2-butanol (syn-
2d): Colorless solid, m.p. 76Ϫ77 °C (from hexane). [α]2D0 ϭ ϩ30.5
(2S,3S)-4-(tert-Butyldimethylsilyloxy)-3-(dibenzylamino)-1,1,1-tri-
fluoro-2-butanol (anti-2f): Colorless oil. [α]2D0 ϭ ϩ33.1 (c ϭ 1.3,
CHCl3). IR (film): ν˜ ϭ 3430, 1260, 1115, 745, 700 cmϪ1. 1H NMR
(CDCl3): δ ϭ 0.13 (s, 3 H, CH3Si), 0.14 (s, 3 H, CH3Si), 0.94 [s, 9
H, (CH3)3C], 3.12 (m, 1 H, CHN), 3.86 (m, 4 H, CH2N), 4.12 (d,
J ϭ 5.0 Hz, 2 H, CH2OTBDMS), 4.37 (dq, J ϭ 7.9, J ϭ 3.9 Hz, 1
H, CHOH), 7.25Ϫ7.50 (m, 10 H, Harom) ppm. 13C NMR (CDCl3):
δ ϭ Ϫ5.8 (CH3Si), 17.9 [C(CH3)3], 25.7 [(CH3)3C], 55.3 (CH2Ph),
(c ϭ 1.0, CHCl3).). IR (KBr): ν˜ ϭ 3425, 1270, 1135, 745, 700 cmϪ1
.
1H NMR (CDCl3): δ ϭ 2.96 (dd, J ϭ 14.6, J ϭ 3.8 Hz, 1 H,
CHHCHN), 3.12 (dd, J ϭ 14.6, J ϭ 9.6 Hz, 1 H, CHHCHN), 3.37
(m, 3 H, CHN and CHHN), 3.80 (m, 3 H, CHOH and CHHN),
5.20 (br. s, 1 H, OH), 7.05Ϫ7.45 (m, 15 H, Harom) ppm. 13C NMR
(CDCl3): δ ϭ 34.3 (CH2CH), 54.0 (CH2N), 57.7 (CHN), 69.2 (q,
2JC,F ϭ 29.4 Hz, CHOH), 126.8, 127.6, 128.5, 128.8, 129.1, 129.3
(CHarom), 137.5, 138.9 (Carom) ppm. 19F NMR (CDCl3): δ ϭ
2
55.7 (CHN), 62.9 (CH2OTBDMS), 71.4 (q, JC,F ϭ 29.7 Hz,
3
Ϫ76.10 (d, 3 F, JF,H ϭ 6.0 Hz, CF3) ppm. C24H24F3NO (399.4):
CHOH), 127.2, 128.3, 128.6 (CHarom), 139.1 (Carom) ppm. 19F
calcd. C 72.16, H 6.06, N 3.51; found C 71.64, H 5.76, N 3.54.
3
NMR (CDCl3): δ ϭ Ϫ77.53 (d, 3 F, JF,H ϭ 7.6 Hz, CF3) ppm.
(2S,3S)-3-(Dibenzylamino)-1,1,1-trifluoro-4-phenyl-2-butanol (anti-
C24H34F3NO2Si (453.6): calcd. C 63.55, H 7.55, N 3.09; found C
2d): Colorless solid, m.p. 108Ϫ110 °C (from hexane/EtOAc). 63.22, H 7.04, N 3.18.
Eur. J. Org. Chem. 2004, 1558Ϫ1566
2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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