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R. Kowalczyk, J. Skarzewski / Tetrahedron: Asymmetry 20 (2009) 2467–2473
2472
C-2 as well as methyl groups were in agreement with those reported
in the literature.5d
crystallization from cyclohexane/dichloromethane gave the desired
product with 99.8% ee and 99% dr (163 mg, 53% recovery), colorless
crystals, mp 99–100 °C, [
Syn-(1S,2S)-(1-Naphthalene-1-yl)-2-nitropropan-1-ol: Light yel-
low oil, [ D = +30.4 (c 0.3, CHCl3, 84% ee); IR (film, max): 3535,
3053, 2992, 1551, 1389, 1360, 1053, 804, 781 cmꢀ1 1H NMR
(300 MHz, CDCl3): d = 8.26 (d, J = 8.1 Hz, 1H, ArH), 7.87 (t,
J = 9.0 Hz, 2H, ArH), 7.45–7.59 (m, 4H, ArH), 5.77 (d, J = 9.3 Hz,
1H, CHOH), 5.06–5.16 (m, 1H, CHNO2), 2.74 (br s, 1H, OH), 1.24
(d, J = 6.6 Hz, 3H, CH3). 13C NMR (75 MHz, CDCl3): d = 134.0 (CIV°Ar),
133.97 (CIV°Ar), 130.8 (CIV°Ar), 129.8 (CAr), 129.2 (CAr), 126.8 (CAr),
126.1 (CAr), 125.6 (CAr), 125.4 (CAr), 123.2 (CAr), 88.5 (COH), 73.7
(CNO2), 16.8 (CH3). HRMS (ESI, [M+Na]+) calcd for [C13H13NO3+Na]+
254.0788; found 254.0791.
a
]
D = ꢀ37.8 (c 0.5, CHCl3, 99% ee).
4.3.1.2. 1-(4-Chlorophenyl)-2-nitropropan-1-ol. Chiralpak AD-
H, n-hexane/i-PrOH, 95:5, 1.0 mL/min, k = 225 nm, antimajor
(1S,2R) tr = 15.2 min, antiminor (1R,2S) tr = 16.6 min, synminor
(1R,2R) tr = 21.9 min, synmajor (1S,2S) tr = 24.4 min (lit.:5d anti
(1S,2R) tr = 15.0 min, anti (1R,2S) tr = 16.4 min, syn (1R,2R)
tr = 21.9 min, syn (1S,2S) tr = 24.0 min). The chemical shifts of pro-
tons adjacent to carbons C-1, C-2 as well as the methyl groups
were in agreement with those reported in the literature.5d
a]
m
.
4.3.1.3. 1-(4-Chlorophenyl)-2-nitrobutan-1-ol. Chiralpak AD-H,
n-hexane/i-PrOH, 95:5, 1.0 mL/min, k = 225 nm, antimajor (1S,2R)
tr = 12.0 min, antiminor (1R,2S) tr = 13.0 min, synminor (1R,2R)
tr = 17.1 min, synmajor (1S,2S) tr = 21.1 min (lit.:5d anti (1S,2R)
tr = 12.4 min, anti (1R,2S) tr = 13.3 min, syn (1R,2R) tr = 17.8 min,
syn (1S,2S) tr = 21.6 min). The chemical shifts of protons adjacent
to carbons C-1, C-2 as well as the methyl groups were in agreement
with those reported in the literature.5d
4.3.1.7. 1-Cyclohexyl-2-nitropropan-1-ol. Chiralpak AD-H, n-
hexane/i-PrOH, 97:3, 1.0 mL/min, k = 210 nm, antiminor tr = 16.0 min,
antimajor tr = 18.7 min, synmajor tr = 17.1 min, synminor tr = 25.7 min.
Diastereomeric ratios (anti/syn) were determined by 1H NMR. The
chemical shifts of protons adjacent to carbons C-1, C-2 as well as
the methyl groups were in agreement with those reported in the
literature.4b,d
4.3.1.4. 2-Nitro-1-(4-nitrophenyl)propan-1-ol. Chiralpak AD-H,
n-hexane/i-PrOH, 9:1, 1.0 mL/min, k = 225 nm, anti tr = 19.5 min,
synminor tr = 29.5 min, synmajor tr = 36.5 min; Chiralcel OD-H, n-hex-
ane/i-PrOH, 9:1, 1.0 mL/min, k = 225 nm, antiminor tr = 19.7 min,
antimajor tr = 26.2 min, syn tr = 24.5 min. Diastereomeric ratios
(anti/syn) were determined by 1H NMR. The chemical shifts of pro-
tons adjacent to carbons C-1, C-2 as well as the methyl groups
were in agreement with those reported in the literature.5d
4.3.1.8. 1-Cyclohexyl-2-nitrobutan-1-ol. Chiralpak AD-H, n-hex-
ane/i-PrOH, 97:3, 0.5 mL/min, k = 210 nm, synmajor tr = 29.2 min,
synminor tr = 46.6 min.
Syn-(1S,2S)-1-Cyclohexyl-2-nitrobutan-2-ol: Colorless oil, [
ꢀ9.2 (c 0.7, MeOH, 99% ee). IR (film, max): 3452, 2929, 2974,
1554, 1451, 1378, 1112, 811 cmꢀ1 1H NMR (300 MHz, CDCl3):
a] =
D
m
.
d = 4.55 (ddd, J = 10.5 Hz, J = 6.3 Hz, J = 4.5 Hz, 1H, CHNO2), 3.56–
3.63 (m, 1H, CHOH), 2.11 (d, J = 8.4 Hz, 1H, OH), 1.99–2.07 (m,
1H, CHCHCH3), 1.64–1.88 (m, 6H, CHCHCH3 and HCy), 1.32–1.38
(1H, m, HCy), 1.14–1.28 (5H, m, HCy), 0.97 (t, J = 7.5 Hz, 3H, CH3).
13C NMR (75 MHz, CDCl3): d = 91.9 (CNO2), 75.9 (COH), 40.2 (CH),
29.8 (CH2), 26.8 (CH2), 26.1 (CH2), 26.0 (CH2), 25.7 (CH2), 24.0
(CH2), 10.2 (CH3). 1H NMR and 13C NMR spectroscopic data were
identical to those reported in the literature.4e
4.3.1.5. 2-Nitro-(4-nitrophenyl)butan-1-ol. Chiralpak AD-H, n-
hexane/i-PrOH, 9:1, 1.0 mL/min, k = 225 nm, anti tr = 12.4 min,
synminor (1R,2R) tr = 19.3 min, synmajor (1S,2S) tr = 30.4 min; Chiralcel
OD-H, n-hexane/i-PrOH, 9:1, 1.0 mL/min, k = 225 nm, antiminor
(1R,2S) tr = 13.5 min, antimajor (1S,2R) tr = 14.9 min, syn
tr = 18.9 min (lit.:5d Chiralpak AD-H anti tr = 12.8 min, syn (1R,2R)
tr = 19.1 min, syn (1S,2S) tr = 29.2 min; Chiralcel OD-H, anti
(1R,2S) tr = 12.2 min, anti (1S,2R) tr = 13.1 min, syn tr = 16.0 min).
Diastereomeric ratios (anti/syn) were determined by 1H NMR.
The chemical shifts of protons adjacent to carbons C-1, C-2 as well
as the methyl groups were in agreement with those reported in the
literature.5d
4.3.1.9. (1S,2S)-2-Nitro-1,2-diphenylethanol. Chiralpak AD-H,
n-hexane/i-PrOH, 97:3, 0.5 mL/min, k = 210 nm minor isomer
tr = 110.2 min, major tr = 115.6 min; waxy light yellow solid,
[
a
]
D = ꢀ35.7 (c 0.7, MeOH, 62% ee). IR (film,
mmax): 3440, 3035,
2925, 1554, 1364, 1055, 725, 696 cmꢀ1. 1H NMR (300 MHz, CDCl3):
d = 7.23–7.29 (m, 5H, ArH), 7.17–7.20 (m, 3H, ArH), 7.10–7.14 (m,
2H, ArH), 5.35–5.61 (m, 2H, CHNO2 and CHOH), 2.68 (br s, 1H,
OH). 13C NMR (75 MHz, CDCl3): d = 137.5 (CIV°Ar), 131.3 (CIV°Ar),
130.0 (CAr), 128.9 (CAr), 128.8 (CAr), 128.6 (CAr), 128.2 (CAr), 127.1
(CAr), 96.8 (CHNO2), 75.9 (CHOH). HRMS (ESI, [M+Na]+) calcd for
[C14H13NO3+Na]+ 266.0788; found 266.0793.
4.3.1.6. 1-(Naphthalen-1-yl)-2-nitropropan-1-ol. Chiralpak AD-
H, n-hexane/i-PrOH, 9:1, 0.5 mL/min, k = 210 nm, antimajor
tr = 16.8 min, antiminor tr = 20.8 min, synmajor tr = 28.1 min, synminor
tr = 32.7 min. The mixture of diastereomers was separated using
flash chromatography (silica gel, 30 g, n-hexane/AcOEt, 8:1, v/v)
giving diastereomerically pure nitroaldols:
Anti-(1S,2R)-1-(Naphthalene-1-yl)-2-nitropropan-1-ol: Colorless
solid, mp 83.5–85 °C (75% ee), [
a
]
D = ꢀ30.4 (c 0.6, CHCl3, 75% ee);
4.3.1.10. 1-Cyclohexyl-2-nitro-2-phenylethanol. Chiralpak AD-
H, n-hexane/i-PrOH, 97:3, 1.0 mL/min, k = 210 nm, antimajor
tr = 23.7 min, antiminor tr = 36.9 min, synmajor tr = 27.7 min, synminor
tr = 32.0 min. Diastereomeric ratios (anti/syn) were determined by
1H NMR. The chemical shifts of protons adjacent to carbons C-1,
C-2 as well as methyl groups were in agreement with those re-
ported in the literature.4b
IR (KBr,
m
max): 3547, 3068, 1543, 1319, 809, 777 cmꢀ1
.
1H NMR
(300 MHz, CDCl3): d = 7.99 (d, J = 8.4 Hz, 1H, ArH), 7.90 (d,
J = 7.8 Hz, 1H, ArH), 7.83 (d, J = 8.4 Hz, 1H, ArH), 7.77 (d,
J = 7.2 Hz, 1H, ArH), 7.48–7.59 (m, 3H, ArH), 6.26 (br s, 1H, CHOH),
4.90 (dq, J = 6.7 Hz, J = 2.4 Hz, 1H, CHNO2), 2.70 (s, 1H, OH), 1.42 (d,
J = 6.7 Hz, 3H, CH3). 13C NMR (75 MHz, CDCl3): d = 133.8 (CIV°Ar),
133.6 (CIV°Ar), 129.38 (CIV°Ar), 129.30 (CAr), 129.1 (CAr), 127.0 (CAr),
125.9 (CAr), 125.4 (CAr), 124.0 (CAr), 121.7 (CAr), 85.6 (COH), 70.9
(CNO2), 11.0 (CH3). HRMS (ESI, [M+Na]+) calcd for [C13H13NO3+Na]+
254.0788; found 254.0793. This compound is described in the lit-
erature,5a however the spectroscopic data were not reported.
Reaction performed according to the general procedure on
2.5 mmol scale of aldehyde, followed by purification using column
chromatography (silica gel, 100 g, n-hexane/AcOEt, 8:1, v/v), led to
the first fraction (anti/syn 93:7 dr, 78% ee, 306 mg, 56% yield). Single
4.3.1.11. 2-Nitro-1,3-diphenylpropan-1-ol. Chiralcel OD-H, n-hex-
ane/i-PrOH, 9:1, 1.0 mL/min, k = 210 nm, antiminor (1R,2S)tr =11.0 min,
antimajor (1S,2R) tr = 19.8 min, synminor (1R,2R) tr = 13.1 min, synmajor
(1S,2S) tr = 14.8 min (lit.:5d anti (1R,2S) tr = 10.1 min, anti (1S,2R)
tr = 14.9 min, syn (1R,2R) tr = 11.1 min, syn (1S,2S) tr = 12.7 min). Our
analysis of the corresponding racemates suggested that the reported
peak5d of 14.9 min was previously ascribed to the (1S,2R) enantiomer.
Perhaps, it could resultfrom some impurityinstead. Diastereomericra-