X. Ma et al. / Tetrahedron: Asymmetry 20 (2009) 1419–1424
1423
146.4, 145.2, 139.7 129.2, 127.7 127.3, 126.8, 126.5 126.2, 126.1
4.3.6. (S,S)-2-Amino-N-(1-hydroxy-4-methyl-1,1-
126.0 80.1 58.5, 50.1, 21.5; HRMS calcd for (C23H24N2O2+H)+
361.1911, found 361.1904. Anal. Calcd for C23H24N2O2: C, 76.64;
H, 6.71; N, 7.77. Found: C, 76.68; H, 6.80; N, 7.71.
diphenylpentan-2-yl)-4-methylpentanamide 1f
Yield 54%; mp 180ꢀ182 °C; ½a D20
¼ ꢀ44 (c 1.0, DMSO); FT-IR
ꢁ
3389, 3347, 2953, 2297, 2868, 1643, 1518, 1447, 1167, 1135,
1062, 745, 699 cmꢀ1 1H NMR (400 MHz, DMSO-d6) d 7.63 (d, 1H,
;
4.3.2. (S,S)-2-Amino-N-(1-hydroxy-1,1,3-triphenylpropan-2-
J = 9.6 Hz), 7.50 (d, 4H, J = 7.6 Hz), 7.29 (t, 2H, J = 7.6 Hz),
7.12ꢀ7.20 (m, 3H), 7.06ꢀ7.09 (t, 1H, J = 7.2 Hz), 5.91 (s, 1H),
4.93ꢀ4.98 (m, 1H), 2.86ꢀ2.89 (dd, 1H, J = 5.6 Hz, J = 8.8 Hz),
1.49ꢀ1.54 (m, 4H), 1.33ꢀ1.39 (m, 1H), 0.98ꢀ1.04 (m, 2H),
0.89ꢀ0.97 (m, 1H), 0.87 (d, 3H, J = 6.8 Hz), 0.76 (d, 3H, J = 6.4 Hz),
0.68 (d, 6H, J = 7.2 Hz); 13C NMR (100 MHz, DMSO-d6) d 175.4,
146.9, 146.4, 128.0, 127.4, 126.1, 125.9, 125.6, 125.3, 80.1, 53.0,
52.5, 44.1, 39.2, 24.1, 23.8, 23.1, 21.7, 21.6; HRMS calcd for
(C24H34N2O2+H)+ 383.2693, found 383.2696. Anal. Calcd for
C24H34N2O2: C, 75.35; H, 8.96; N, 7.32. Found: C, 75.49; H, 9.11;
N, 7.24.
yl)propanamide1b
Yield 53%; mp 203ꢀ204 °C; ½a D20
¼ ꢀ18 (c 1.0, DMSO); FT-IR
ꢁ
3405, 3290, 1711, 1645, 1524, 1447, 1154, 1061, 752, 699 cmꢀ1
;
1H NMR (400 MHz, DMSO-d6) d 7.77 (d, 1H, J = 9.6 Hz), 7.62 (d,
2H, J = 7.2 Hz), 7.53 (d, 2H, J = 7.6 Hz), 7.35 (t, 2H,
J = 7.4 Hz),7.07ꢀ7.21 (m, 9H), 6.23 (s, 1H), 5.08 (t, 1H, J = 9.0 Hz),
2.86ꢀ2.91 (dd, 1H, J = 6.8 Hz, J = 13.2 Hz), 2.58ꢀ2.71 (m, 2H),
1.46 (s, 2H), 0.62 (d, 3H, J = 6.8 Hz); 13C NMR (100 MHz, DMSO-
d6) d 174.8, 146.5, 146.3, 139.2, 129.2, 128.2, 127.8, 127.4, 126.3,
126.1, 125.8, 125.7, 125.5, 80.1, 56.1, 50.0, 36.0, 21.2; HRMS calcd
for (C24H26N2O2+H)+ 375.2067, found 375.2061. Anal. Calcd for
C24H26N2O2: C, 76.98; H, 7.00; N, 7.48. Found: C, 77.05; H, 7.21;
N, 7.54.
4.4. General procedure for the aldol reaction
The following procedure for the reaction of cyclohexanone with
4-nitrobenzaldehyde in brine is representative.
4.3.3. (S,S)-2-Amino-N-(1-hydroxy-4-methyl-1,1-diphenylpentan-
2-yl)propanamide 1c
In a typical experiment, a mixture of 4-nitrobenzaldehyde
(0.2 mmol), 1f (usually 5 mol %), cyclohexanone (2.0 mmol) and
DNP (usually 5 mol %) were stirred in brine (1.0 mL) at room tem-
perature until the reaction was completed as judged by TLC. This
solution was quenched in aqueous NH4Cl (4 mL) and extracted
thrice with AcOEt (4 mL). Then the organic layers were combined,
dried with anhydrous Na2SO4, concentrated to dryness under
reduced pressure, purified by preparative TLC or column to achieve
the aldol product. The absolute configuration was analyzed with
HPLC and 1H NMR.
Yield 46%; mp 172ꢀ173 °C; ½a D20
¼ ꢀ54 (c 1.0, DMSO); FT-IR
ꢁ
3428, 3307, 2956, 2930, 1645, 1525, 1449, 1140, 1061, 750,
702 cmꢀ1 1H NMR (400 MHz, DMSO-d6) d 7.55 (d, 1H, J = 9.6 Hz),
;
7.45ꢀ7.47 (m, 4H), 7.25 (t, 2H, J = 7.4 Hz), 7.03ꢀ7.17 (m, 4H),
5.88 (d, 1H, J = 3.6 Hz), 4.91 (t, 1H, J = 9.6 Hz), 2.94ꢀ2.96 (m, 1H),
1.55 (s, 2H), 1.43ꢀ1.49 (m, 2H), 0.89ꢀ0.94 (m, 1H), 0.81 (d, 3H,
J = 5.6 Hz), 0.73 (d, 3H, J = 6.4 Hz), 0.72 (d, 3H, J = 5.6 Hz); 13C
NMR (100 MHz, DMSO-d6) d 175.5, 146.9, 146.3, 128.0, 127.4,
126.2, 126.0, 125.6, 125.3, 80.2, 52.4, 50.1, 24.1, 21.6; HRMS calcd
for (C21H28N2O2+H)+ 341.2224, found 341.2218. Anal. Calcd for
C21H28N2O2: C, 74.08; H, 8.29; N, 8.23. Found: C, 73.94; H, 8.61;
N, 8.17.
All the known aldol adducts matched the reported characteris-
tics.9,11,12,14,17 Characterization data for selected examples are
given below.
4.3.4. (S,S)-2-Amino-N-(1-hydroxy-4-methyl-1,1-diphenylpentan-
4.4.1. (2S,1R)-2-[Hydroxy-(4-nitrophenyl)-methyl]-cyclohexan-
2-yl)-3-methylbutanamide 1d
1-one 2a
Yield 51%; mp 177ꢀ178 °C; ½a D20
ꢁ
¼ ꢀ49 (c 1.0, DMSO); FT-IR
Yield 95%; ½a 2D0
ꢁ
¼ þ37 (c 1.0, CHCl3); 1H NMR (200 MHz, CDCl3)
3428, 3383, 3325, 2956, 2928, 2871, 1645, 1511, 1447, 1165,
d 8.19ꢀ8.24 (m, 2H), 7.46ꢀ7.52 (m, 2H), 4.89ꢀ4.93 (d, 1H,
J = 8.4 Hz), 4.1 (s, 1H), 2.29ꢀ2.47 (m, 3H), 2.08ꢀ2.18 (m, 1H),
1.48ꢀ1.86 (m, 5H). anti/syn = 11/1, determined by chiral HPLC.
Ee = 97%. The enantiomeric excess was determined by HPLC with
an AD-H column (hexane/i-PrOH = 80/20), 0.5 mL/min; tR = 24.71
(minor), tR = 31.52 (major).
1063, 747, 700 cmꢀ1 1H NMR (400 MHz, DMSO-d6) d 7.68 (d, 1H,
;
J = 9.2 Hz), 7.49ꢀ7.53 (m, 4H), 7.28 (t, 2H, J = 7.4 Hz), 7.05ꢀ7.20
(m, 4H), 5.96 (s, 1H), 4.94ꢀ4.99 (t, 1H, J = 10.0 Hz), 2.71 (s, 1H),
1.67ꢀ1.70 (m, 1H), 1.48ꢀ1.54 (m, 2H), 1.43 (s, 2H), 0.92ꢀ0.98
(m, 1H), 0.85 (d, 3H, J = 6.0 Hz), 0.75 (d, 3H, J = 6.4 Hz), 0.65 (d,
3H, J = 6.8 Hz), 0.50 (d, 3H, J = 6.4 Hz); 13C NMR (100 MHz,
DMSO-d6) d 174.1, 146.9, 146.4, 128.0, 127.5, 126.1, 126.0, 125.6,
125.3, 80.1, 59.7, 52.7, 39.2, 30.6, 24.2, 24.1, 21.5, 19.5, 16.1; HRMS
calcd for (C23H32N2O2+H)+ 369.2537, found 369.2529. Anal. Calcd
for C23H32N2O2: C, 74.96; H, 8.75; N, 7.60. Found: C, 75.07; H,
8.92; N, 7.48.
4.4.2. (R)-4-Hydroxy-4-(4-nitrophenyl)butan-2-one 4a
Yield 70%; ½a 2D0
ꢁ
¼ þ45 (c 1.0, CHCl3); 1H NMR (200 MHz, CDCl3)
d 8.16ꢀ8.23 (m, 2H), 7.52ꢀ7.58 (m, 2H), 5.24ꢀ5.30 (m, 1H), 3.62
(br, 1H), 2.84ꢀ2.88 (m, 2H), 2.23 (s, 3H). Ee = 90%, determined by
chiral HPLC with AS-H column (hexane/i-PrOH = 70/30), 1.0 mL/
min, tR = 14.4 (major), tR = 19.9 (minor).
4.3.5. (S,S)-2-Amino-N-(2-hydroxy-1,2,2-triphenylethyl)-4-
methylpentanamide 1e
Acknowledgement
Yield 56%; mp 204ꢀ205 °C; ½a D20
¼ ꢀ155 (c 1.0, DMSO); FT-IR
ꢁ
3400, 3330, 3298, 2953, 2926, 1643, 1516, 1448, 1161, 1061,
We are grateful for the financial support from NSFC (No.
20672051).
748, 734, 699 cmꢀ1 1H NMR (400 MHz, DMSO-d6) d 8.40 (d, 1H,
;
J = 9.6 Hz), 7.52 (d, 2H, J = 8.0 Hz), 7.25ꢀ7.28 (t, 2H, J = 7.2 Hz,
J = 8.0 Hz), 7.17ꢀ7.20 (t, 3H, J = 7.2 Hz, J = 6.0 Hz), 6.98ꢀ7.08 (m,
8H), 6.08 (s, 1H), 5.80 (d, 1H, J = 8.8 Hz), 2.96ꢀ3.00 (dd, 1H,
J = 5.2 Hz, J = 8.8 Hz), 1.53 (br, 1H), 1.39ꢀ1.46 (m, 1H), 1.01ꢀ1.08
(m, 1H), 0.92ꢀ0.93 (m, 1H), 0.68 (d, 3H, J = 6.4 Hz); 13C NMR
(100 MHz, DMSO-d6) d 146.4, 145.2, 139.7, 129.2, 127.7, 127.3,
126.7, 126.4, 126.2, 126.0, 80.1, 63.4, 58.6, 44.0, 40.1, 23.8, 23.0,
21.7; HRMS calcd for (C26H30N2O2+H)+ 403.2380, found 403.2378.
Anal. Calcd for C26H30N2O2: C, 77.58; H, 7.51; N, 6.96. Found: C,
77.82; H, 7.69; N, 7.06.
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