F. Liu et al. / Journal of Molecular Catalysis A: Chemical 379 (2013) 163–168
165
2869, 2781, 1613, 1588, 1516, 1463, 1254, 1181, 1031, 829 cm−1;
DACH), 2.94–3.15 (m, 2H, NHCH CH ), 3.45–3.57 (m, 2H, NHCH),
2
2
1
◦
H NMR (300 MHz, D O, 25 C) ı 0.84–0.86 (d, J = 6.2 Hz, 3H,
2
4
.23–4.51 (dd, J = 13.1 Hz, 2H, NHCH C H ), 7.49–7.53 (m, 4H, H
2
6
◦
4
1
3
of benzyl); C NMR (125 MHz, D O, 25 C) ı 15.5, 23.8, 23.8, 23.9,
CH CHCH ), 0.91–0.93 (d, J = 6.4 Hz, 3H, CH CHCH ), 1.25–1.31 (d,
2
2 3 2 3
2
7.5, 27.6, 27.9, 32.5, 47.9, 50.7, 59.0, 59.3, 131.6, 133.8; HRMS
J = 6.2 Hz, 3H, NHCHCH ), 1.44–2.46 (m, 11H, CH of DACH and
3 2
+
(
ESI) calcd for C19H32ClN2 [M+H] 323.2249, found 323.2234.
(CH ) CHCH ), 3.54 (s, 3H, NHCH), 3.85 (s, 3H, OCH ), 4.18–4.49
3
2
2
3
1
2
(
1R,2R)-N -(Hexan-2-yl), N -(4-chlorobenzyl)cyclohexane-1,2-
(dd, J = 13.0 Hz, 2H, NHCH ), 7.06–7.09 (d, J = 8.0 Hz, 2H, H of ben-
2
13
diamine dihydrochloride (4f·2HCl): White powder; yield: 1.62 g,
zyl), 7.46–7.49 (d, J = 8.1 Hz, 2H, H of benzyl); C NMR (75 MHz,
2
5
◦
4
1%; [˛] = −55.0 (c 0.59, H O); IR (KBr) ꢀ 400, 2936, 2866,
D O, 25 C) ı 17.1, 19.1, 23.0, 24.3, 25.1, 26.7, 28.3, 44.8, 51.3, 54.1,
D
2
2
−
1
2
770, 1597, 1493, 1453, 1413, 1390, 1092, 1015, 810, 509 cm
;
56.9, 58.1, 59.5, 117.4, 125.1, 134.3, 162.6; HRMS (ESI) calcd for
1
◦
+
H NMR (500 MHz, D O, 25 C) ı 0.87 (t, 3H, CH CH ), 1.26–1.27
C20H35N O [M+H] 319.2743, found 319.2719.
2
2
3
2
1
2
(
d, J = 6.2 Hz, 3H, CHCH ), 1.31–2.45 (m, 14H, CH CH CH CH and
(1R,2R)-N -(4-Methylpentan-2-yl), N -(biphenyl-4-ylmethyl)cy-
3
3
2
2
2
CH2 of DACH), 3.50–3.54 (m, 3H, NHCH), 4.21–4.51 (dd, J = 13.1 Hz,
clohexane-1,2-diamine dihydrochloride (4l·2HCl): White powder;
13
25
D
2
H, NHCH ), 7.48–7.51 (m, 4H, H of benzyl); C NMR (125 MHz,
yield: 3.05 g, 78%; [˛] = −55.7 (c 0.47, H O); IR (KBr) ꢀ 3386,
2
2
◦
D O, 25 C) ı 15.7, 17.0, 24.2, 28.4, 29.4, 35.6, 51.0, 55.6, 57.0, 60.1,
2955, 2869, 2770, 1597, 1487, 1451, 1254, 1392, 1157, 1041, 1007,
2
31.9, 134.1; HRMS (ESI) calcd for C19H32ClN2 [M+H]+ 323.2249,
−1
1
◦
H NMR (300 MHz, D O, 25 C) ı 0.82–0.86 (d,
2
1
764, 698 cm
;
found 323.2234.
J = 5.1 Hz, 3H, CH CHCH ), 0.90–0.92 (d, J = 5.9 Hz, 3H, CH CHCH ),
1.26–1.31 (d, J = 6.5 Hz, 3H, NHCHCH ), 1.41–2.48 (m, 11H, CH of
3 2
2
3
2
3
1
2
(
1R,2R)-N -(4-Methylpentan-2-yl), N -(4-chlorobenzyl)cyclohe-
xane-1,2-diamine dihydrochloride (4g·2HCl): White powder; yield:
DACH and (CH ) CHCH ), 3.58 (s, 3H, NHCH), 3.85 (s, 3H, OCH ),
4.27–4.58 (dd, J = 13.1 Hz, 2H, NHCH ), 7.45–7.63 (m, 5H, H of C H ),
2 6
5
3 2 2 3
2
5
1
2
8
.66 g, 42%; [˛] = −57.0 (c 0.56, H O); IR (KBr)
ꢀ
3406,
D
2
956, 2869, 2769, 1598, 1494, 1454, 1396, 1369, 1092, 1016,
7.73–7.75 (d, J = 7.6 Hz, 2H, H of C H ), 7.78–7.81 (d, J = 7.7 Hz, 2H, H
6
4
−1
1
◦
13
◦
of C H ); C NMR (75 MHz, D O, 25 C) ı 17.1, 19.1, 22.9, 24.3, 25.1,
6 4 2
11, 508 cm
;
H NMR (500 MHz, D O, 25 C) ı 0.85–0.87 (d,
2
J = 6.3 Hz, 3H, CH CHCH ), 0.91–0.93 (d, J = 6.6 Hz, 3H, CH CHCH ),
26.7, 28.2, 44.8, 51.4, 54.1, 56.8, 59.7, 119.7, 129.6, 130.3, 130.8,
131.8, 133.2, 142.2, 144.6; HRMS (ESI) calcd for C25H37N2 [M+H]+
365.2951, found 365.2870.
2
3
2
3
1
.26–1.27 (d, 3H, NHCHCH ), 1.31–2.45 (m, 8H, CH of DACH and
3
2
CHCH CH), 3.52–3.54 (m, 3H, NHCH), 4.19–4.49 (dd, J = 13.0 Hz, 2H,
2
13
1
2
NHCH C H ), 7.49–7.50 (m, 4H, H of benzyl); C NMR (125 MHz,
(1R,2R)-N -(Anthracen-10-ylmethyl),
N -(4-methylpentan-2-
2
6
◦
4
D O, 25 C) ı 17.0, 19.1, 22.9, 24.1, 25.0, 26.7, 28.3, 44.9, 51.1, 54.7,
yl)cyclohexane-1,2-diamine dihydrochloride (4m·2HCl): Yellow
2
6.9, 60.0, 132.0, 134.0; HRMS (ESI) calcd for C19H32ClN2 [M+H]+
25
5
3
powder; yield: 2.86 g, 62%; [˛]D = −46.6 (c 0.53, H O); IR (KBr) ꢀ
2
−
1
23.2249, found 323.2247.
3416, 2954, 2868, 2690, 1715, 1624, 1585, 1449, 1390, 734 cm
;
1
2
1
◦
H NMR (500 MHz, D O, 25 C) ı 0.69–0.71 (d, J = 6.5 Hz, 6H,
2
(
1R,2R)-N -(Heptan-2-yl), N -(4-chlorobenzyl)cyclohexane-1,2-
diamine dihydrochloride (4h·2HCl): White powder; yield: 2.01 g,
CH CHCH ), 0.74–0.76 (d, J = 6.5 Hz, 6H, CH CHCH ), 1.00–1.02 (d,
3H, J = 6.3 Hz, NHCHCH ), 1.19–2.60 (m, 11H, CH of DACH and
3 2
2 3 2 3
2
5
4
2
9%; [˛] = −52.6 (c 0.54, H O); IR (KBr) ꢀ 3422, 2935, 2863,
D
2
−
1 1
764, 1598, 1494, 1455, 1391, 1092, 1016, 810, 510 cm
;
H NMR
(CH ) CHCH ), 3.3–3.54 (m, 3H, NHCH), 4.93–5.17 (dd, J = 13.9 Hz,
3 2 2
◦
(
300 MHz, D O, 25 C) ı 0.85–0.87 (d, 3H, CHCH ), 0.91–0.93 (d,
2H, NHCH ), 7.50–7.55 (t, 2H, J = 7.7 Hz, H of anthracene), 7.60–7.65
2
3
2
3
H, CHCH ), 1.26–1.27 (d, 3H, NHCHCH ), 1.31–2.45 (m, 8H, CH
(t, 2H, J = 6.8 Hz, H of anthracene), 8.02–8.11 (d, J = 8.8 Hz, 4H, H
3
3
2
13
of DACH), 3.52–3.54 (m, 3H, NHCH), 4.19–4.49 (dd, J = 13.0 Hz, 2H,
NHCH C H ), 7.49–7.50 (m, 4H, H of benzyl); C NMR (75 MHz,
D O, 25 C) ı 17.1, 23.0, 24.4, 24.5, 25.1, 26.7, 28.3, 28.4, 44.9, 51.1,
of anthracene), 8.52 (s, 1H, H of anthracene); C NMR (125 MHz,
13
◦
2
6
◦
4
D O, 25 C) ı 13.7, 17.0, 20.8, 23.0, 24.1, 24.5, 25.8, 27.8, 41.7, 43.3,
2
2
124.2, 125.5, 137.7, 128.8, 131.0; HRMS (ESI) calcd for C24H31N2
[M+H]+ 389.2951, found 389.2946.
5
[
4.1, 57.0, 60.2, 132.0, 134.0; HRMS (ESI) calcd for C19H32ClN2
M+H]+ 323.2249, found 323.2247.
1
2
(
1R,2R)-N -Benzyl,
N -(4-methylpentan-2-yl)cyclohexane-1,2-
2.3. General procedure for the Henry reaction
diamine dihydrochloride (4i·2HCl): White powder; yield: 3.25 g,
2
5
9
2
0%; [˛] = −63.5 (c 0.49, H O); IR (KBr) ꢀ 3427, 2956, 2869,
1 1
D
2
The test tube with a stirring bar was charged with a ligand
−
771, 1587, 1456, 1391, 1042, 751, 699 cm
; H NMR (300 MHz,
(
0.06 mmol, 12 mol%), 4, free diamine (prepared from the cor-
responding hydrochlorides 4·2HCl), copper(II) acetate hydrate
10.0 mg, 0.05 mmol, 10 mol%), and i-PrOH (1.0 mL). The result-
◦
D O, 25 C) ı 0.84–0.86 (t, J = 6.1 Hz, 3H, CH CHCH ), 0.91–0.92 (d,
J = 6.6 Hz, 3H, CH CHCH ), 1.25–1.30 (dd, J = 6.5 Hz, 3H, NHCHCH ),
2
2
3
2
3
3
(
1
.40–2.48 (m, 11H, CH2 of DACH and (CH ) CHCH ), 3.55 (s, 3H,
3 2 2
ing suspension was gently heated for 30 s and stirred for 1 h to
ensure completion of the complex formation. Then a solution of
NHCH), 4.22–4.54 (dd, J = 13.2 Hz, 2H, NHCH ), 7.51 (s, 5H, H of
benzyl); C NMR (75 MHz, D O, 25 C) ı 17.1, 19.2, 23.0, 24.2,
2
1
3
◦
2
◦
aldehyde (0.5 mmol, 1 equiv) in i-PrOH (0.3 mL) was added at 25 C,
2
1
4.5, 25.1, 26.7, 28.3, 42.2, 44.9, 51.7, 54.3, 57.0, 60.0, 131.9, 132.0,
◦
the whole mixture was cooled to −20 C for 15 min, treated with
32.5, 132.8; HRMS (ESI) calcd for C19H33N2 [M+H]+ 289.2638,
nitromethane (5.0 mmol, 10 equiv) via a syringe. After 5 min, a solu-
found 289.2639.
tion of i-Pr NEt (5.0 mg, 7.70 mol%) in i-PrOH (0.2 mL) was added
1
2
2
(
1R,2R)-N -(4-Methylpentan-2-yl), N -(4-methylbenzyl)cyclo-
◦
via a syringe. The mixture was stirred for 24 h at −20 C. Purifica-
hexane-1,2-diamine dihydrochloride (4j·2HCl): White powder; yield:
2
5
tion by flash chromatography on silica gel (30 g, n-hexane/AcOEt,
3
2
.00 g, 80%; [˛] = −54.6 (c 0.52, H O); IR (KBr) ꢀ 3378, 2956,
1 1
D
2
4
:1, v/v) afforded the desired ˇ-nitroalcohols.
−
869, 2781, 1588, 1454, 1392, 1042, 808 cm
; H NMR (300 MHz,
◦
D O, 25 C) ı 0.85–0.87 (d, J = 6.2 Hz, 3H, CH CHCH ), 0.91–0.93 (d,
2
2
3
J = 6.4 Hz, 3H, CH CHCH ), 1.25–1.31 (d, J = 6.2 Hz, 3H, NHCHCH ),
2.4. HPLC conditions
2
3
3
1
.41–2.45 (m, 14H, CH of DACH, (CH ) CHCH and C H CH ), 3.55
2 3 2 2 6 4 3
(
s, 3H, NHCH), 4.19–4.50 (dd, J = 12.8 Hz, 2H, NHCH ), 7.32–7.35 (d,
Enantiomeric excess was determined using HPLC on Chiralpak
IC, Chiracel OD-H, or Chiralpak AD-H chiral columns. Reported val-
ues are listed below:
2
J = 7.4 Hz, 2H, H of benzyl), 7.40–7.43 (d, J = 7.6 Hz, 2H, H of benzyl);
1
3
◦
C NMR (75 MHz, D O, 25 C) ı 17.1, 19.1, 23.0, 24.0, 24.2, 25.1,
2
2
(
6.7, 28.3, 44.8, 51.5, 54.1, 56.8, 59.7, 129.5, 132.5, 143.1; HRMS
2-Nitro-1-phenylethanol (5a): Chiralpak IC, n-hexane/i-PrOH,
9:1, 0.8 mL/min, ꢁ = 220 nm, tminor = 12.0 min, tmajor = 12.6 min.
1-(2-Methoxyphenyl)-2-nitroethanol (5b): Chiracel OD-H, n-
hexane/i-PrOH = 90:10, 0.8 mL/min, ꢁ = 215 nm, tminor = 13.3 min,
tmajor = 15.2 min.
ESI) calcd for C20H35N2 [M+H]+ 303.2794, found 303.2751.
1
2
(
1R,2R)-N -(4-Methylpentan-2-yl), N -(4-methoxybenzyl)cyclo-
hexane-1,2-diamine dihydrochloride (4k·2HCl): White powder;
2
5
yield: 3.05 g, 78%; [˛] = −59.2 (c 0.49, H O); IR (KBr) ꢀ 2955,
D
2