L. Zhang et al. / Tetrahedron 69 (2013) 10644e10652
10649
Multiplicity was indicated as follows: s (singlet), d (doublet), t
4.3. General experimental procedure for Henry reaction
(triplet), q (quartet), m (multiplet), dd (doublet of doublet), br s
(broad singlet). Coupling constants were reported in Hertz (Hz).
Accurate mass data and routine mass data were obtained with an
Agilent Technologies 6520 Accurate-Mass Q-TOF LC/MS instrument
and a LCQ Advantage MAX instrument, respectively, under ESI
model. Optical rotations were measured with a PerkineElmer 341
polarimeter at 25 ꢀC. HPLC analysis was performed with a Shi-
madzu CTO-10 AS instrument and a Chiralpak AD-H column pur-
chased from Daicel Chemical Industries, LTD.
The mixture of L2 (7.5 mg, 0.015 mmol) and CuCl2$2H2O (2.1 mg,
0.0125 mmol) was stirred in THF/i-PrOH (1:1, 1 mL) at room tem-
perature under N2 protection for 1 h to form the complex. The
resulting mixture was cooled to 0 ꢀC, then nitroalkanes (2.5 mmol),
N-Meemorpholine (1.4 mL) and aldehydes (0.25 mmol) were added
and stirring continued for intend time at 0 ꢀC. The solvent was
removed under reduced pressure and the resulting mixture was
directly purified by column chromatography to afford the Henry
reaction product.
4.2. Synthesis of ligands L1eL3
(R)-2-Nitro-1-phenylethanol (5a, Table 4, entry 1).4d The title
compound was prepared according to the general procedure and
purified by column chromatography (petroleum ether/ethyl
acetate¼6:1). Enantiomeric excess (90% ee, Table 4, entry 1) was
determined by HPLC (Chiralcel OD-H), hexane/i-PrOH¼90:10,
1.0 mL/min, 254 nm, major enantiomer (R) tr¼12.847 min, minor
enantiomer (S) tr¼16.136 min; 1H NMR (400 MHz, CDCl3):
To a solution of NaH (5 equiv, 20 mmol) in 10 mL DMSO was
added quinine (4 mmol) and the mixture was stirred for 1 h at room
temperature. Then 2-bromo-1,10-phenanthroline 1 (6 mmol) or
2,9-dibromo-1,10-phenanthroline 2 (6 mmol) was added and the
reaction was kept for 5 h at 80e90 ꢀC under stirring. The mixture
was cooled to room temperature and 20 mL H2O was added care-
fully, following extracted with CH2Cl2 (3ꢂ20 mL). The organic
phases were combined, washed with brine, dried over anhydrous
Na2SO4, and evaporated in vacuo. The residue was purified by flash
d
7.43e7.29 (m, 5H), 5.39 (m, 1H), 4.56 (dd, J¼13.2, 9.6 Hz, 1H), 4.46
(dd, J¼13.2, 3.1 Hz, 1H), 3.27 (d, J¼3.6 Hz, 1H). 13C NMR (101 MHz,
CDCl3):
d 138.28, 129.04, 128.96, 126.01, 81.28, 71.01.
(R)-1-(3-Chlorophenyl)-2-nitroethanol (5b, Table 4, entry 2).19
The title compound was prepared according to the general pro-
cedure and purified by column chromatography (petroleum ether/
ethyl acetate¼6:1). Enantiomeric excess (73% ee, Table 4, entry 2)
was determined by HPLC (Chiralcel OD-H), hexane/i-PrOH¼90:10,
1.0 mL/min, 215 nm, major enantiomer (R) tr¼12.731 min, minor
enantiomer (S) tr¼16.514 min; 1H NMR (400 MHz, CDCl3):
chromatography to afford L1eL3.
24
L1: White powder, mp 101e103 ꢀC; [
a
]
þ3.0 (c 1.4, CH2Cl2);
D
IR (KBr) nmax: 2927, 1618, 1504, 1454, 1349, 1260, 1076, 1027, 993,
850 cmꢁ1. 1H NMR (400 MHz, CDCl3):
d
9.06 (d, J¼3.1 Hz, 1H), 8.73
(d, J¼4.5 Hz, 1H), 8.36 (s, 1H), 8.13 (m, J¼7.1 Hz, 2H), 8.04e7.92 (m,
2H), 7.73 (d, J¼4.4 Hz, 1H), 7.65 (d, J¼8.7 Hz, 1H), 7.61e7.51 (m,
2H), 7.36 (dd, J¼9.1, 2.0 Hz, 1H), 7.28 (d, J¼8.5 Hz, 1H), 5.81e5.68
(m, 1H), 5.06e4.88 (m, 2H), 4.21 (s, 3H), 3.50 (t, J¼8.3 Hz, 1H),
3.40e3.22 (m, 2H), 2.87 (d, J¼13.3 Hz, 1H), 2.77e2.66 (m, 1H),
2.37 (s, 1H), 2.17e2.07 (m, 1H), 1.91 (s, 1H), 1.85e1.66 (m, 2H), 1.55
d
7.50e7.12 (m, 4H), 5.34 (dd, J¼9.1, 3.5 Hz, 1H), 4.46 (m, J¼13.3,
6.3 Hz, 2H), 3.65 (s, 1H). 13C NMR (101 MHz, CDCl3):
130.37, 129.01, 126.23, 124.23, 80.95, 70.28.
d 140.31, 134.77,
(R)-1-(2, 4-Dichlorophenyl)-2-nitroethanol (5c, Table 4, entry
3).6n The title compound was prepared according to the general
procedure and purified by column chromatography (petroleum
ether/ethyl acetate¼6:1). Enantiomeric excess (77% ee, Table 4,
entry 3) was determined by HPLC (Chiralcel AD-H), hexane/i-
PrOH¼90:10, 0.5 mL/min, 254 nm, major enantiomer (R)
tr¼14.592 min, minor enantiomer (S) tr¼17.432 min; 1H NMR
(s, 1H). 13C NMR (101 MHz, CDCl3):
d 161.35, 158.54, 149.48, 147.16,
144.48, 143.89, 140.96, 139.86, 136.27, 131.33, 129.12, 126.86,
125.97, 125.18, 124.23, 123.00, 122.60, 118.52, 115.00, 113.69,
101.67, 73.20, 59.68, 56.72, 42.85, 39.26, 29.70, 27.60, 26.99, 21.34.
HRMS: calculated for [MþH]þ C32H30N4O2 503.2442, found
503.2443.
24
L2: White yellow powder, mp 205e206 ꢀC; [
a
]
þ178.2 (c
(400 MHz, CDCl3):
d
7.61 (d, J¼8.4 Hz, 1H), 7.40 (d, J¼2.0 Hz, 1H),
D
0.7, CH2Cl2); IR (KBr) nmax: 3389, 2926, 1618, 1504, 1454, 1354,
7.34 (dd, J¼8.4, 2.0 Hz, 1H), 5.79 (m, J¼9.4, 3.9, 2.4 Hz, 1H), 4.64 (dd,
J¼13.7, 2.3 Hz, 1H), 4.42 (dd, J¼13.7, 9.5 Hz, 1H), 3.20 (d, J¼4.2 Hz,
1251, 1134, 1026, 918, 848 cmꢁ1 1H NMR (400 MHz, CDCl3):
.
d
9.05 (s, 1H), 8.77 (d, J¼4.2 Hz, 1H), 8.13 (dd, J¼28.8, 8.3 Hz, 3H),
1H). 13C NMR (101 MHz, CDCl3):
128.60, 127.99, 79.09, 67.44.
d 135.24, 134.16, 132.09, 129.51,
7.95 (m, J¼10.2 Hz, 2H), 7.76e7.48 (m, 5H), 7.37 (d, J¼8.8 Hz, 1H),
5.74 (dd, J¼17.1, 6.7 Hz, 1H), 5.24e5.03 (m, 2H), 4.13 (d,
J¼26.2 Hz, 3H), 3.88e3.75 (m, 1H), 3.27 (s, 2H), 2.72 (s, 1H), 2.02
(d, J¼17.1 Hz, 2H), 1.71 (d, J¼11.0 Hz, 1H), 1.53 (s, 1H), 1.35e1.17
(R)-1-(4-Fluorophenyl)-2-nitroethanol (5d, Table 4, entry 4).4d
The title compound was prepared according to the general pro-
cedure and purified by column chromatography (petroleum ether/
ethyl acetate¼6:1). Enantiomeric excess (76% ee, Table 4, entry 4)
was determined by HPLC (Chiralcel OD-H), hexane/i-PrOH¼90:10,
0.8 mL/min, 215 nm, major enantiomer (R) tr¼13.513 min, minor
enantiomer (S) tr¼115.837 min; 1H NMR (400 MHz, CDCl3):
(m, 3H). 13C NMR (101 MHz, CDCl3):
d 160.57, 158.40, 149.23,
147.36, 144.93, 143.13, 139.60, 137.70, 136.31, 131.63, 128.98,
127.71, 126.32, 125.52, 124.07, 122.65, 122.31, 116.90, 115.15,
102.63, 58.02, 56.35, 54.12, 41.70, 37.03, 30.92, 29.68, 26.76,
24.79. HRMS: calculated for [MþH]þ C32H30N4O2 503.2442,
d
7.43e7.29 (m, 2H), 7.14e7.00 (m, 2H), 5.41 (dd, J¼9.5, 3.2 Hz, 1H),
found 503.2443.
4.56 (dd, J¼13.2, 9.5 Hz, 1H), 4.47 (dd, J¼13.2, 3.2 Hz, 1H), 3.27 (d,
24
L3: White yellow powder, mp 195e197 ꢀC; [
a
]
ꢁ103.7 (c 0.5,
J¼66.4 Hz, 1H). 13C NMR (101 MHz, CDCl3):
d 164.09, 134.03, 127.84,
D
CH2Cl2); IR (KBr) nmax: 2927, 1619, 1579, 1490, 1449, 1364, 1267,
116.07, 81.15, 70.34.
1232, 1109, 1026, 970, 852 cmꢁ1. 1H NMR (400 MHz, CDCl3):
d
8.75
(R)-2-Nitro-1-(4-nitrophenyl)ethanol (5e, Table 4, entry 5).4d
The title compound was prepared according to the general pro-
cedure and purified by column chromatography (petroleum ether/
ethyl acetate¼5:1). Enantiomeric excess (71% ee, Table 4, entry 5)
was determined by HPLC (Chiralcel OD-H), hexane/i-PrOH¼85:15,
1.0 mL/min, 215 nm, major enantiomer (R) tr¼15.571 min, minor
(d, J¼4.4 Hz, 1H), 8.08 (d, J¼8.7 Hz, 1H), 8.00e7.84 (m, 4H), 7.73 (d,
J¼4.3 Hz, 1H), 7.64 (dd, J¼18.4, 8.5 Hz, 2H), 7.53 (d, J¼8.6 Hz, 1H),
7.34 (dd, J¼9.1, 2.1 Hz, 1H), 7.20 (d, J¼8.6 Hz, 1H), 5.90e5.78 (m, 1H),
5.00 (m, J¼12.7 Hz, 2H), 4.04 (s, 3H), 3.66e3.55 (m, 1H), 3.44 (d,
J¼11.6 Hz, 1H), 3.23e3.10 (m, 1H), 2.74 (d, J¼12.6 Hz, 2H), 2.34 (s,
1H), 1.91 (d, J¼31.7 Hz, 4H), 1.60 (s, 1H). 13C NMR (101 MHz, CDCl3):
enantiomer (S) tr¼19.195 min; 1H NMR (400 MHz, CDCl3):
d 8.26 (d,
d
161.61,158.14,147.36,145.39,144.71,143.02,141.80,139.50,138.04,
J¼8.7 Hz, 2H), 7.63 (d, J¼8.7 Hz, 2H), 5.61 (d, J¼4.3 Hz, 1H),
131.45, 127.85, 127.39, 126.45, 125.37, 123.38, 122.22, 119.83, 114.57,
114.01, 101.76, 74.49, 59.41, 58.31, 56.77, 56.34, 42.77, 39.69, 30.94,
27.78. HRMS: calculated for [MþH]þ C32H29BrN4O2 581.1547, found
581.1548.
4.69e4.50 (m, 2H), 3.45 (s, 1H). 13C NMR (101 MHz, CDCl3):
d 148.10,
145.14, 126.98, 124.19, 80.68, 69.98.
(R)-1-(2-Methoxyphenyl)-2-nitroethanol (5f, Table 4, entry 6).4d
The title compound was prepared according to the general