B. Erd e´ lyi et al. / Tetrahedron: Asymmetry 17 (2006) 268–274
273
1
3
7
5
1
.13–7.20 (2H, m, Ar4,6–H); C NMR: 23.37, 40.88,
5.68, 70.70, 111.13, 121.22, 124.80, 128.00, 129.50,
57.79. Anal. Calcd for C H O : C, 72.26, H, 8.49.
4.3.11. Racemic 1-(4-chlorophenyl)propan-2-ol rac-2h.
Yield: 70%; IR: 3368, 2968, 1492, 1408, 1088, 1016,
1
936, 800; H NMR: 1.22 (2H, d, J = 6.25 Hz, CH ),
1
0
14
2
3
Found: C, 72.03, H, 8.55.
1.94 (1H, s, OH), 2.63–2.77 (2H, m, CH ), 3.95–4.02
2
(
1H, m, CH), 7.15 (2H, d, J = 8.4 Hz, Ar2,6–H), 7.28
1
3
4
7
.3.4. (S)-1-(2-Methoxyphenyl)propan-2-ol (S)-2c. Yield:
(2H, d, J = 8.4 Hz, Ar3,5–H); C NMR: 22.97, 45.09,
68.85, 128.72, 130.89, 132.39, 137.20. Anal. Calcd for
C H ClO: C, 63.35, H, 6.50, Cl, 20.78. Found: C,
25
1
7%; ee: >99% (GC); ½aꢁ ¼ þ39:8 (c 1.0, CHCl ); H
D
3
1
2
NMR spectrum agreed with the reported data. The
IR, H and C NMR spectra of (S)-2c were indistin-
guishable from that of rac-2c.
9
11
1
13
63.18, H, 6.48, Cl, 20.91.
4
.3.12. (S)-1-(4-Chlorophenyl)propan-2-ol (S)-2h. Yield:
25
4
2
1
.3.5. Racemic 1-(3-methoxyphenyl)propan-2-ol rac-
d. Yield: 76%; IR: 3384, 2968, 1584, 1488, 1260,
152, 1044, 944, 780; H NMR: 1.25 (3H, d,
70%; ee: >99% (GC); ½aꢁ ¼ þ31:0 (c 1.0, CHCl ); The
D
3
1
13
IR, H and C NMR spectra of (S)-2h were undistin-
guishable from that of rac-2h.
1
J = 6.0 Hz, CH ), 1.87 (1H, br s, OH), 2.64–2.80
3
(
2H, m, CH ), 3.81 (1H, s, O–CH ), 3.99–4.05 (1H, m,
4.4. Synthesis of the (S)-1-phenylbutan-2-ol (S)-4a by ring
opening of (S)-propylene oxide 7 with benzylmagnesium
bromide
2
3
O–CH), 6.78–6.83 (3H, m, Ar2,4,6–H), 7.21–7.27 (1H,
m, Ar –H); C NMR: 22.95, 46.00, 55.31, 68.95,
1
3
5
1
11.98, 115.27, 121.88, 129.69, 140.31, 159.91. Anal.
Calcd for C H O : C, 72.26, H, 8.49. Found: C,
To a stirred solution of (6 mmol, 146 mg) magnesium,
and one drop of 1,2-dibromoethane in diethyl ether
1
0
14
2
7
2.11, H, 8.54.
(5 ml), benzyl bromide (6 mmol, 1.03 g) in 5 ml diethyl
4
7
.3.6. (S)-1-(3-Methoxyphenyl)propan-2-ol (S)-2d. Yield:
ether was added dropwise, and the reaction mixture stir-
red under reflux until the magnesium dissolved. Then
(S)-propylene oxide (S)-7 (3 mmol, 0.17 g, 0.21 ml)
was added under ꢀ30 ꢁC and the mixture stirred at this
temperature for 20 min. Then, the temperature was
raised up to room temperature (about 30 min), and then
stirred for 1 h. The reaction mixture was quenched by
25
13
4%; ee: >99% (GC); ½aꢁ ¼ þ30:3 (c 1.0, CHCl ) {lit.:
D 3
D
3
1
13
[a] = +31.8 (c 1.53, CHCl )}; The IR, H and C NMR
spectra of (S)-2d were indistinguishable from that of rac-
2
d.
4
2
1
.3.7. Racemic 1-(4-methoxyphenyl)propan-2-ol rac-
e. Yield: 88%; IR: 3360, 2968, 1616, 1512, 1248,
the addition of NH Cl (8 ml) and diethyl ether
4
1
148, 1036, 944, 808; H NMR: 1.24 (3H, d,
(30 ml). The mixture was washed with water (8 ml),
and brine (8 ml). The organic solution was dried over
Na SO and concentrated under reduced pressure. The
J = 6.3 Hz, CH ), 2.63–2.78 (2H, m, CH ), 2.96 (1H,
br s, OH), 3.81 (1H, s, O–CH ), 3.96–4.05 (1H, m,
3
2
3
2
4
CH), 6.87 (2H, d, J = 8.7 Hz, Ar2,6–H), 7.14 (2H, d,
residue was purified by column chromatography (silica
gel; hexane–acetone 10:1) to yield the secondary alcohol
(S)-4a.
1
3
J = 8.7 Hz, Ar3,5–H); C NMR: 22.73, 44.92, 55.92,
9.22, 114.13, 116.21, 130.50, 158.41. Anal. Calcd
for C H O : C, 72.26, H, 8.49. Found: C, 72.15, H,
6
1
0
14
2
8
.38.
The corresponding racemic alcohol rac-4a was syn-
thesized from benzyl bromide, magnesium and race-
mic propylene oxide rac-7 (3 mmol) in a similar
reaction.
4
.3.8.
(S)-1-(4-Methoxyphenyl)propan-2-ol
(S)-2e.
25
Yield: 84%; ee: >99% (GC); ½aꢁ ¼ þ34:9 (c 1.0,
D
1
4
1
CHCl ) {lit.: [a] = +27.0 (c 4.4, CHCl )}; H NMR
3
D
3
1
5
1
spectrum agreed with the reported data. The IR, H
and C NMR spectra of (S)-2e were undistinguishable
from that of rac-2e.
4.4.1. Racemic 1-phenylbutan-2-ol rac-4b. Yield: 57%;
1
3
1
IR: 3344, 2968, 1496, 1456, 1076, 1032, 760, 680; H
NMR: 1.18 (3H, d, J = 6.9 Hz, CH ), 1.55–1.99 (2H,
3
m, CH ), 2.23 (1H, br s, OH), 2.55–2.87 (2H, m,
2
4
2
1
.3.9. Racemic 1-(2,4-dimethoxyphenyl)propan-2-ol rac-
g. Yield: 41%; IR: 3387, 2968, 1580, 1475, 1268,
166, 1043, 944, 793; H NMR: 1.21 (2H, d,
CH ), 3.61–3.92 (1H, m, O–CH), 7.25–7.39 (5H, m,
2
1
3
Ar–H); C NMR: 10.83, 29.19, 43.2, 74.07, 126.63,
128.67, 129.55, 138.62. Anal. Calcd for C H O: C,
1
1
0
14
J = 6.3 Hz, CH ), 1.81 (1H, br s, OH), 2.64–2.8 (2H,
79.96, H, 9.39. Found: C, 79.83, H, 9.44.
3
m, CH ), 3.8 (3H, s, O–CH ), 3.81 (3H, s, O–CH ),
2
3
3
6
.45 (2H, dd, J = 7.8 Hz, J = 2.2 Hz, Ar –H), 6.45
4.4.2. (S)-1-Phenylbutan-2-ol (S)-4b. Yield: 57%;
1 2 5
25
17
(
1H, br s, Ar –H), 7.05 (1H, d, J = 7.8 Hz, Ar –H);
C NMR: 23.10, 39.97, 55.53, 55.59, 68.27, 98.92,
04.35, 119.52, 131.80 158.69, 159.95. Anal. Calcd
ee: >98% (GC); ½aꢁ ¼ þ12:3 (c 1.0, CHCl ) {lit.:
3
6
D
3
1
3
1
[a] = +17.2 (c 1.0, CHCl )}; H NMR spectrum agreed
D 3
1 1 13
17
1
with the reported data H data. The IR, H and
C
for C H O : C, 67.32, H, 8.22. Found: C, 67.35, H,
NMR spectra of (S)-4b were indistinguishable from that
of rac-4b.
1
1
16
3
8
.24.
4
.3.10. (S)-1-(2,4-Dimethoxyphenyl)propan-2-ol(S)-2g.
4.5. Chiral HPLC and GC analysis and absolute config-
uration of the secondary alcohols 2b–e,g,h and 4a
25
Yield: 38%; ee: >99% (GC); ½aꢁ ¼ þ19:7 (c 1.0,
D
1
CHCl ); H NMR spectrum agreed with the reported
3
6
1
1
13
data. The IR, H and C NMR spectra of (S)-2g were
indistinguishable from that of rac-2g.
The enantiomeric compositions of the secondary
alcohols from bioreductions (2a–h and 4a,b and 6;