Mandana Gruber-Khadjawi et al.
FULL PAPERS
analyses were performed on an Agilent 1100 with autosam-
pler and multi wave detector (MWD).
by HPLC with a Chiralpack AD-H column (heptane/2-prop-
anol, 9:1, 1.3 mLminÀ1, 208C, l=210 nm): tr =27.3 min and
37.2 min (major); 64% ee; [a]2D0: +22.2 (c 1.0, CH2Cl2).[11a]
(S)-1-Nitroheptan-2-ol (2d):[12] Pale yellow oil; 1H NMR
3
General Procedure for HbHNL-Catalyzed Nitroaldol
(500 MHz, CDCl3): d=0.84 (t, J=6.8 Hz, 3H, -CH3), 1.27–
1.39 (m, 5H, H3CCH2CH2CHH-), 1.45–1.57 (m, 3H,
-CHHCH2-) 2.76 (br, -CHOH-), 4.25 (br, 1H, -CHOH-),
Reaction (Products 1, 3–6, 8–14)
Wt-HbHNL (2.0 mL), McIlvaine buffer (45 mM citrate
buffer and 110 mM phosphate buffer) (pH 5.5, 100 mL) and
tert-butyl methyl ether (4.2 mL) were stirred until an emul-
sion was established. To the mixture aldehyde (1.0 mmol)
was added. After stirring for 5 min nitroalkane (10.0 mmol)
was added. The reaction mixture was stirred at room tem-
perature for 48 h. The reaction mixture was extracted three
times with 20 mL of ethyl acetate. The combined extracts
were dried over anhydrous Na2SO4 and the solvent was re-
moved under reduced pressure. The crude products were
purified by column chromatography with cyclohexane/ethyl
acetate 16:1 as eluent.
2
3
4.32 (dd, J=13.2 Hz, J=8.3 Hz, 1H, -CHHNO2), 4.36 (dd,
3J=13.2 Hz, 3J=2.9 Hz, 1H, -CHHNO2); 13C NMR
(125 MHz, CDCl3): d=14.1, 22.7, 25.0, 31.7, 33.9, 68.9, 80.9.
The enantiomeric excess (ee) was determined by HPLC
with a Chiralpack AD-H column (heptane/2-propanol, 9:1,
0.9 mLminÀ1, 208C, l=210 nm): tr =8.9 min and 11.6 min
(major); 96% ee; [a]2D0: +12.0 (c 1.1, CH2Cl2).
(S)-1-Nitro-4-phenylbutan-2-ol (2e):[7g,11c] Colorless nee-
1
dles; mp 96–988C; H NMR (500 MHz, CDCl3): d=1.80 (m,
1H, -CH2CHHCHOH-), 1.85 (m, 1H, -CH2CHHCHOH-),
2.75 (m, 1H, Aryl-CHH-CH2-), 2.76 (s, -CHOH-), 2.87 (m,
1H, Aryl-CHHCH2-), 4.31 (m, 1H, -CHOH-), 4.40 (m, 2H,
-CH2NO2), 7.20–7.26 (m, 3H), 7.32 (t, 2H); 13C NMR
(125 MHz, CDCl3): d=31.6, 35.3, 68.0, 80.8, 126.6, 128.7,
128.9, 140.9. The enantiomeric excess was determined by
HPLC with a Chiralpack AD-H column (heptane/2-propa-
nol, 9:1, 0.9 mLminÀ1, 208C, l=210 nm): tr =13.0 min and
16.2 min (major); 66% ee; [a]2D0: À6.8 (c 0.8, CH2Cl2).[13a]
(R)-1-(2-Furyl)-2-nitroethanol (2f):[12a] Pale yellow oil;
1H NMR (500 MHz, CDCl3): d=3.10 (br, -CHOH-), 4.66
(dd, 2J=13.7 Hz, 3J=3.4 Hz, 1H, -CHHNO2), 4.77 (dd,
2J=13.2 Hz, 3J=9.3 Hz, 1H, -CHHNO2), 5.46 (dd, 3J=
9.3 Hz, 3J=3.4 Hz, 1H, -CHOH-), 6.38 (m, 2H), 7.41 (d,
1H); 13C NMR (125 MHz, CDCl3): d=65.0, 78.6, 108.4,
110.9, 143.4, 150.9. The enantiomeric excess was determined
by HPLC with a Chiralpack AD-H column (heptane/2-prop-
anol, 98:2, 1.5 mLminÀ1, 208C, l=210 nm): tr =45.4 min and
48.5 min (major); 88% ee; [a]20: +27.7 (c 1.1, CH3OH).
(R)-2-Nitro-1-thien-2-ylethaDnol (2h): Pale yellow oil;
1H NMR (500 MHz, CDCl3): d=2.93 (d, -CHOH-), 4.58
In the case of benzaldehyde the reaction was also per-
formed on an up to 500-mmol scale in a biphasic system
with phosphate buffer pH 7.0 using nitromethane and nitro-
ethane, respectively. The yields and ees were reproducible.
(S)-1-Phenyl-2-nitroethanol
(2a):[7g]
Colorless
oil;
1H NMR (500 MHz, CDCl3):[11a] d=2.86 (br, 1H, -OH), 4.49
2
3
2
(dd, J=13.2 Hz, J=2.9 Hz 1H, -CHHNO2), 4.58 (dd, J=
13.2 Hz, 3J=9.8 Hz, 1H, -CHHNO2), 5.43 (dd, 3J=9.8 Hz,
3J=2.9 Hz, 1H, -CHOH-), 7.33–7.39 (m, 5H); 13C NMR
(125 MHz, CDCl3):[7c] d=71.2, 81.4, 126.2, 129.2, 129.3,
138.3. The enantiomeric excess was determined by HPLC
with
a Chiralcel OD-H column (heptane/ethanol 9:1,
0.7 mLminÀ1, 208C, l=210 nm): tr =18.0 min and 21.0 min
(major); 97% ee; [a]2D0: +26.9 (c 1.2, CH2Cl2).[7h]
(S)-1-(3-Hydroxyphenyl)-2-nitroethanol (2b): Wt-HbHNL
(1.0 mL), phosphate buffer (pH 7, 50 mM, 0.67 mL) and tert-
butyl methyl ether (1.3 mL) were stirred vigorously in a 10-
mL round-bottom flask until an emulsion was established
(10 min). To the mixture 3-hydroxybenzaldehyde (122 mg,
1.0 mmol) was added. After stirring for 5 min. nitromethane
(0.51 mL, 10.0 mmol) was added in one portion. The reac-
tion mixture was stirred at room temperature for 48 h and
then extracted three times with 4 mL of diethyl ether. The
combined extracts were dried over anhydrous Na2SO4 and
the solvent removed under reduced pressure. The yellow oil
was purified by column chromatography (cyclohexane/ethyl
acetate 10:1) to afford a light yellow solid; yield:76.5 mg
2
3
2
(dd, J=13.2 Hz, J=3.4 Hz, 1H, -CHHNO2), 4.69 (dd, J=
13.7 Hz, 3J=9.3 Hz, 1H, -CHHNO2), 5.70 (dd, 3J=9.3 Hz,
3J=4.4 Hz, 1H, -CHOH-), 6.99 (1H), 7.04 (1H), 7.31 (1H);
13C NMR (125 MHz, CDCl3): d=67.4, 81.0, 125.4, 126.5,
127.5, 141.4. The enantiomeric excess was determined by
HPLC with a Chiralpack AD-H column (heptane/2-propa-
nol, 98:2, 1.5 mLminÀ1, 308C, l=210 nm): tr =43.5 min and
45.4 min (major); 98% ee; [a]2D0: +33.2 (c 1.1, CH2Cl2).
(S)-1-(3-Furyl)-2-nitroethanol (2i): Pale yellow oil;
1H NMR (500 MHz, CDCl3): d=2.88 (s, -CHOH-), 4.50 (dd,
2J=13.7 Hz, 3J=3.4 Hz, 1H, -CHHNO2), 4.59 (dd, 2J=
13.2 Hz, 3J=9.3 Hz, 1H, -CHHNO2), 5.40 (d, 3J=8.3 Hz,
1
(46%); mp 64–698C; H NMR (500 MHz, DMSO): d=4.48
(dd, 2J=12.7 Hz, 3J=10.3 Hz, 1H, -CHHNO2), 4.79 (dd,
2J=13.2 Hz, 3J=2.4 Hz 1H, -CHHNO2), 5.16 (m, 3J=
3.9 Hz, 1H, -CHOH-), 6.01 (d, 1H, -OH), 6.67–6.82 (m,
3H), 7.11–7.15 (m, 1H), 9.45 (s, 1H, Aryl-OH); 13C NMR
(125 MHz, DMSO): d=70.6, 82.7, 113.7, 115.5, 117.3, 130.1,
142.6, 158.1. the enantiomeric excess was determined by
HPLC with a Chiralpack AD-H column (heptane/2-propa-
nol, 95:5, 1.5 mLminÀ1, 308C, l=210 nm): tr =47.4 min
(major) and 50.8 min; 18% ee; [a]2D0:+1.2 (c 1.0, CH3OH).
(S)-2-Nitro-1-(4-nitrophenyl)ethanol (2c):[7d,g,h] Pale yellow
solid; mp 798C; 1H NMR[11a] (500 MHz, DMSO): d=4.62
(1H); 13C NMR
1H, -CHOH-), 6.37 (1H), 7.40 (1H), 7.45 ACHTREUNG
(125 MHz, CDCl3): d=64.4, 80.5, 108.2, 123.6, 140.2, 144.4.
The enantiomeric excess was determined by HPLC with a
Chiralpack AD-H column (heptane/2-propanol, 9:1,
1.0 mLminÀ1, 208C, l=210 nm): tr =14.9 min and 20.0 min
(major); 89% ee; [a]2D0: +17.5 (c 1.3, CH2Cl2).
(S)-1-(2-Chlorophenyl)-2-nitroethanol (2j):[11b] Colorless
1
oil; H NMR[11a] (500 MHz, CDCl3): d=3.14 (br, 1H, -OH),
4.44 (dd, 2J=13.7 Hz, 3J=9.8 Hz, 1H, -CHHNO2), 4.65
(dd, 2J=13.7 Hz, 3J=2.4 Hz, 1H, -CHHNO2), 5.82 (br,
2
3
2
(dd, J=12.7 Hz, J=9.8 Hz, 1H, -CHHNO2), 4.94 (dd, J=
12.7 Hz, 3J=2.9 Hz, 1H, -CHHNO2), 5.43 (m, 3J=3.9 Hz,
13C NMR[13a]
3
-CHOH-),
7.28–7.38
(3H)
7.62
A
-CHOH-), 6.42 (d, J=4.9 Hz, 1H, -OH),7.72 (d, 2H) 8.21-
(d, 2H); 13C NMR (125 MHz, DMSO): d=69.7, 81.9, 124.1,
(125 MHz, CDCl3): d=68.0, 79.5, 127.7, 127.8, 129.9, 130.1,
128.3, 147.8, 148.7. The enantiomeric excess was determined
131.7, 135.7. The enantiomeric excess was determined by
1448
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2007, 349, 1445 – 1450