Z.-L. Wei et al. / Bioorg. Med. Chem. 8 (2000) 1129±1137
1135
(S)-(+)-N-(4-(1,2-Dihydroxyethyl)phenyl)methanesulfon-
amide (2h). Obtained from 1h: white solid, mp 135±
136 ꢀC; [a]d25 +35 (c 1.0, CH3COCH3). IR (KBr) 3250,
(AB, 4H, J=8.7 Hz), 5.10 (dd, 1H, J=7.8, 3.3 Hz), 4.36
(dd, 1H, J=11.7, 3.3 Hz), 4.16 (dd, 1H, J=11.7,
7.8 Hz), 2.8 (br s, 1H), 2.12 (s, 3H). MS m/z (rel. inten-
sity): 226 ([M+1]+, 3.7), 208 (73.4), 165 (13.1), 153
(30.7), 135 (12.9), 106 (14.6), 74 (22.5), 43 (100).
1630, 1510, 1390, 1320, 1215, 1150, 1080, 1050, 990,
1
765 cm
.
1H NMR (300 MHz, CD3COCD3) d 7.37,
7.28 (AB, 4H, J=8.5 Hz), 4.68 (dd, 1H, J=7.6, 4.4 Hz),
3.60 (dd, 1H, J=11.0, 4.4 Hz), 3.52 (dd, 1H, J=11.0,
7.6 Hz), 3.41 (s, 2H), 2.94 (s, 3H). MS m/z (rel. inten-
sity): 231 (M+, 1.1), 200 (100), 184 (12.6), 121 (30.9),
120 (14.8), 106 (10.5), 92 (24), 77 (9.6). Anal. calcd for
C9H13NO4S: C, 46.74; H, 5.67; N, 6.06; S, 13.87.
Found: C, 46.58; H, 5.65; N, 5.95; S, 14.15.
(S)-(+)-N-(4-(2,2-Dimethyl-1,3-dioxolan-4-yl)phenyl)-
methanesulfonamide (3). A mixture of 2h (50 mg,
0.22 mmol), acetone (0.5 mL), 2,2-dimethoxypropane
(0.5 mL, 4.1 mmol) and p-toluene sulfonic acid (5 mg)
was stirred at room temperature for 16 h. After that,
30 mL of ethyl acetate was added. The organic phase
was washed with aqueous sodium bicarbonate, satu-
rated brine, dried, ®ltered and evaporated under
reduced pressure. The residue was puri®ed by chroma-
tography with petroleum ether:ethyl acetate (5:2) to give
3 (52 mg, 89%) as a white solid, mp 81±82 ꢀC; [a]d25 +59
(c 0.7, CH3COCH3). IR (KBr) 3350, 2980, 1635, 1515,
(S)-(+)-2-Acetoxy-1-phenylethanol (10a). Obtained from
9a: colorless oil; [a]2d5 +28 (c 1.1, CH3COCH3) {lit.6
[a]d +28 (c 2.0, CH3COCH3), 94% ee, (S)}. IR (®lm)
1
3400, 1730 cm 1. H NMR (300 MHz, CDCl3) d 7.40±
7.35 (m, 5H), 4.95 (dd, 1H, J=8.5, 3.3 Hz), 4.28 (dd,
1H, J=11.7, 3.3 Hz), 4.15 (dd, 1H, J=11.7, 8.5 Hz),
2.75 (br s, 1H), 2.09 (s, 3H).
1460, 1400, 1330, 1290, 1220, 1150, 1070, 980, 920, 870,
1
830 cm
.
1H NMR (300 MHz, CD3COCD3) d 7.39,
7.32 (AB, 4H, J=8.5 Hz), 5.06 (dd, 1H, J=7.7, 6.4 Hz),
4.29 (dd, 1H, J=8.1, 6.4 Hz), 3.60 (t, 1H, J=7.9 Hz),
2.96 (s, 3H), 1.46 (s, 3H), 1.39 (s, 3H). Anal. calcd for
C12H17NO4S: C, 53.12; H, 6.32; N, 5.16. Found: C,
53.09; H, 6.38; N, 5.03. The enantiomeric excess was
99.5%, determined by HPLC analysis using Chiralpak
AD column (eluent, hexane:2-propanol=9:1) using the
racemic 3 as comparison.
(R)-( )-2-Acetoxy-1-(2-chlorophenyl)ethanol (10b).
Obtained from 9b: colorless oil; [a]2d5 19.3 (c 1.2,
CHCl3). IR (®lm) 3450, 1730 cm 1. 1H NMR (300 MHz,
CDCl3) d 7.63 (dd, 1H, J=7.6, 1.7 Hz), 7.4±7.2 (m, 3H),
5.39 (dd, 1H, J=7.9, 2.9 Hz), 4.33 (dd, 1H, J=11.6,
2.9 Hz), 4.17 (dd, 1H, J=11.6, 7.9 Hz), 2.4 (br s, 1H),
2.11 (s, 3H). Anal. calcd for C10H11ClO3: C, 55.96; H,
5.16. Found: C, 55.57; H, 5.01.
(S)-(+)-1-(4-Aminophenyl)-1,2-ethanediol (4). A mixture
of (S)-2g (150 mg, 0.82 mmol), ethanol (10 mL) and
(S)-(+)-2-Acetoxy-1-(3-chlorophenyl)ethanol (10c).
Obtained from 9c: colorless oil; [a]2d0 +29 (c 1.3,
CHCl3). IR (®lm) 3400, 1720 cm 1. 1H NMR (300 MHz,
CDCl3) d 7.5±7.1 (m, 4H), 4.92 (dd, 1H, J=8.1, 3.4 Hz),
4.23 (dd, 1H, J=11.7, 3.4 Hz), 4.11 (dd, 1H, J=11.7,
8.1 Hz), 2.9 (br s, 1H), 2.07 (s, 3H). Anal. calcd for
C10H11ClO3: C, 55.96; H, 5.16. Found: C, 55.71; H,
5.30.
.
PtO2 2H2O (20 mg) was stirred at room temperature
under atmospheric hydrogen for 5 h. After ®ltration
the solvent was removed under reduced pressure and the
residue was puri®ed by chromatography with methylene
chloride:acetone (3:1) to give 4 (123 mg, 98%) as a light
yellow solid, mp 107±108 ꢀC; [a]d25 +39 (c 1.5, CH3
COCH3) {lit.24 mp 98±99 ꢀC}. 1H NMR (300 MHz,
CD3COCD3) d 7.08, 6.63 (AB, 4H, J=8.5 Hz), 4.54 (dd,
1H, J=7.9, 4.4 Hz), 3.52 (dd, 1H, J=11.0, 4.4 Hz), 3.45
(dd, 1H, J=11.0, 7.9 Hz), 3.25 (s, 4H). MS m/z (rel.
intensity): 153 (M+, 9.9), 122 (100), 106 (10.4), 94 (42),
77 (30).
(S)-(+)-2-Acetoxy-1-(4-chlorophenyl)ethanol (10d).
Obtained from 9d: colorless oil; [a]2d0 +33 (c 1.9,
CHCl3). IR (®lm) 3400, 1730 cm 1. 1H NMR (300 MHz,
CDCl3) d 7.6±7.1 (m, 4H), 4.92 (dd, 1H, J=8.2, 3.4 Hz),
4.22 (dd, 1H, J=11.5, 3.4 Hz), 4.10 (dd, 1H, J=11.5,
8.2 Hz), 2.7 (br s, 1H), 2.08 (s, 3H). Anal. calcd for
C10H11ClO3: C, 55.96; H, 5.16. Found: C, 55.67; H,
5.14.
Conversion of (S)-4 to (S)-2h. 75 mg (0.5 mmol) of (S)-4
was dissolved in methylene chloride (1 mL) and pyridine
(0.2 mL). The mixture was cooled to
10 ꢀC and
methanesulfonyl chloride (40 mL, 0.51 mmol) was added
slowly. The mixture was stirred at 10 ꢀC for 1 h, then
warmed to room temperature and stirred for further 4 h.
After that 50 mL of ethyl acetate was added and the
mixture was washed with brine and dried. After ®ltra-
tion the solvent was removed under reduced pressure
and the residue was puri®ed by chromatography with
methylene chloride:acetone (4:1) to give (S)-2h (71 mg,
63%), [a]2d6 +32 (c 0.8, CH3COCH3).
(S)-(+)-2-Acetoxy-1-(3-nitrophenyl)ethanol (10f).
Obtained from 9f: white solid, mp 74±76 ꢀC; [a]d20
1
+40.3 (c 1.1, CHCl3). IR (®lm) 3300, 1720 cm 1. H
NMR (300 MHz, CDCl3) d 8.30 (t, 1H, J=1.7 Hz), 8.18
(d, 1H, J=8.1 Hz), 7.75 (d, 1H, J=7.7 Hz), 7.56 (t, 1H,
J=8.0 Hz), 5.09 (dd, 1H, J=7.8, 3.3 Hz), 4.33 (dd, 1H,
J=11.6, 3.3 Hz), 4.16 (dd, 1H, J=11.6, 7.8 Hz), 2.65 (br
s, 1H), 2.12 (s, 3H). Anal. calcd for C10H11NO5: C,
53.34; H, 4.92; N, 6.22. Found: C, 53.17; H, 5.01; N,
6.40.
Determination of the absolute con®guration of 2e and 2f.
To a mixture of 2e (2f) (120 mg, 0.66 mmol), DMAP
(10 mg) and CH2Cl2 (3 mL) was added slowly at 0 ꢀC
(S)-(+)-2-Acetoxy-1-(4-nitrophenyl)ethanol (10g).
Obtained from 9g: white solid; [a]2d3 +27 (c 1.4,
CHCl3) {lit.24 mp 121±122 ꢀC}. IR (®lm) 3400,
a
solution of p-toluenesulfonyl chloride (170 mg,
0.9 mmol) in 2 mL of CH2Cl2. After that the mixture
was stirred at 10 ꢀC for a day. The solvent was removed
1
1710 cm 1. H NMR (300 MHz, CDCl3) d 8.24, 7.60