228
T. I. Danilova et al. / Tetrahedron: Asymmetry 15 (2004) 223–229
(
CHDA), 1.62–2.95 (m, 3H, –CH
m, 4H, –CH
),
.16–2.22 (m, 1H, –CH –CHH–), 2.30–2.40 (m, 1H,
2
– CHDA), 1.50–1.60 (m, 1H, –CH
– CHDA, 2H, NH
2
–
cooled to 0 ꢁC and 0.12 ml (0.102 mmol) of Et
2
Zn (15%
2
2
solution in hexane, d ¼ 0.720) was added in one aliquot.
After 5 min, 0.051 mmol of aldehyde was added drop-
wise and the mixture was warmed to room temperature
and then allowed to stir for an additional 15 h. The
2
–
2
2
CHH–CH
2
2
–), 2.50–2.60 (m, 1H, –CHH–CH –), 2.78–
.86 (m, 1H, –CHH–CH –), 2.96–3.06 (m, 1H, –CHH–
2
CH –), 3.14–3.22 (m, 2H, –CHH–CH –), 3.33–3.52 (m,
2
excess Et Zn was hydrolyzed with 0.25 ml of 1 N HCl.
2
2
3
7
8
2
6
H, –CHH–CH
.40–6.48 (m, 3H, PC arom H), 6.52 (dd, 1H, J ¼ 7:8,
2
–), 6.02 (d, 1H, J ¼ 7:8 Hz, H or H ),
The reaction mixture was then diluted with 4 ml of ether
and 3 ml of water. The organic layer was separated and
aqueous fraction was additionally extracted with Et O
3
4
15
16
3
J ¼ 1:8 Hz, H or H ), 7.04 (dd, 1H, J ¼ 7:8,
2
4
12
13
J ¼ 1:8 Hz, H or H ), 7.40–7.50 (m, 5H, arom H).
Anal. Calcd for C29 (447.22): C,
2.61; H, 7.54; N, 6.26. Found: C, 82.90; H, 7.68; N,
(5 · 4 ml) or CH
2
Cl
were washed with brine (2 ml) and dried over Na
2
. The combined organic fractions
4
SO .
H
32
N
2
Oꢁ0.25C
7
H
8
2
8
6
After solvent removal, the oily residue was subjected to
the GC and Chiral GC, without further purification, for
the conversion and enantiomeric excess analysis. The
conversion was determined by GC (Hewlett–Packard
HP 5890 Series II gas chromatograph) on HP-1
þ
.05; MS (70 eV): m=z (%) ¼ 424 (M , 29), 320 (69), 312
(
20), 104 (100).
From combined fractions with R 0.25, 0.12 g (75%) of
f
[
(S)-BHPC](1R,2R)-CHDA 16a was collected as orange
);
(12 m · 0.25 mm) with N
2
as carrier gas. Split tempera-
2
2
semisolid compound. ½aꢀ ¼ )642.9 (c 0.316, CHCl
3
ture 200 ꢁC, detector FID 250 ꢁC, temperature program:
40 ꢁC (1 min), flow rate 30 ꢁC/min, end temperature
250 ꢁC (10 min). Enantiomeric analysis of secondary
product alcohols was performed by GC (Hewlett–
Packard HP 5890 Series II gas chromatograph) on CP-
D
1
H NMR (CDCl ): d 0.90–1.02 (m, 1H, –CH – CHDA),
3
2
1
.23–1.50 (m, 2H, –CH
2
– CHDA, 2H, NH
2
), 1.68–1.78
(
CHDA), 2.02–2.12 (m, 1H, –CH – CHDA), 2.15–2.40
m, 2H, –CH
2 2
– CHDA), 1.82–1.95 (m, 3H, –CH –
2
(
(
2
–
m, 1H, –CHH–CH
m, 1H, –CHH–CH –), 2.78–2.92 (m, 2H, –CHH–CH
.93–3.25 (m, 3H, –CHH–CH –), 3.40–3.52 (m, 1H,
2
–, 1H, –CH
2
– CHDA), 2.50–2.60
Chirasil-Dex CB (25 m · 0.25 mm) with N
2
as carrier
2
2
–),
gas. Temperature data for 1-phenylpropanol: split tem-
perature 200 ꢁC, detector FID 250 ꢁC, temperature
program: 40 ꢁC (1 min), flow rate 5 ꢁC/min, end tem-
perature 190 ꢁC (20 min); the retention times (min) were
26.94 (S) and 27.20 (R). Temperature data for 1-cyclo-
hexylpropan-ol: split temperature 200 ꢁC, detector FID
250 ꢁC, temperature program: 40 ꢁC (10 min), flow rate
20 ꢁC/min, end temperature 100 ꢁC (35 min), flow rate
20 ꢁC/min, end temperature 190 ꢁC (5 min); the retention
times (min) were 44.90 (S) and 45.50 (R).
2
3
7
8
CHH–CH –), 6.01 (d, 1H, J ¼ 7:8 Hz, H or H ),
2
3
6
.40–6.48 (m, 3H, PC arom H), 6.52 (dd, 1H, J ¼ 7:8,
4
15
16
3
J ¼ 1:8 Hz, H or H ), 7.04 (dd, 1H, J ¼ 7:8,
4
12
13
J ¼ 1:8 Hz, H or H ), 7.24–7.33 (m, 2H, arom H),
.40 (m, 3H, arom H). Anal. Calcd for
OÆ0.38C (459.22): C, 82.95; H, 7.64; N,
7
C
6
29
H
32
N
2
8 7
H
.10. Found: C, 83.22; H, 7.68; N, 6.07; MS (70 eV): m=z
þ
(
%) ¼ 424 (M , 15), 320 (79), 312 (13), 104 (100). The
absolute configurations of the diastereomers of 16a and
b were determined by chemical transformation of (R)-3
to [(R)-BHPC](1R,2R)-CHDA 16b, which was found
having positive rotation, and hence the configuration of
the diastereomer 16a with negative rotation angle was
assigned as [(S)-BHPC](1R,2R)-CHDA.
4.3. Enantioselective diethylzinc addition to aldehydes
catalyzed by hemisalens 14a, 15, and 16
4.3.1. Typical experimental procedure. To a solution of
hemisalen (0.007 mmol) in 0.28 ml of toluene, 0.140 ml
2
(0.142 mmol) of Et Zn (1 M solution in hexane) was
4.1.3. Preparation of hemisalen [(R)-BHPC](1R,2R)-
CHDA 16b. The dark orange suspension of 0.050 g
added in one portion at 0 ꢁC followed by the dropwise
addition of the aldehyde (0.071 mmol). The resulting
yellow solution was warmed to room temperature and
allowed to stir for additional 15 h. The excess Et Zn was
2
hydrolyzed with 0.25 ml of 1 N HCl. The reaction mix-
16
(
0.125 mmol) of (R)-BHPC
0.565 mmol) (1R,2R)-CHDA, and 0.063 ml (0.100 g,
.570 mmol) of TiCl in 5 ml of toluene was refluxed
(ee 92%), 0.065 g
(
2
4
equipped with Dean–Stark trap filled with anhydrous
MgSO for 12 h. After solvent removal, the crude red oil
ture was then diluted with 4 ml of Et
Organic layer was separated and the aqueous fraction
was additionally extracted with Et
O (5 · 4 ml) or
CH Cl . The combined organic fractions were washed
with brine (2 ml) and dried over Na SO . After solvent
2 2
O and 3 ml of H O.
4
was passed from short column filled with SiO
EtOH 20/1) to remove the traces of corresponding salen.
2
(toluene/
2
2
2
The resulted hemisalen [(R)-BHPC](1R,2R)-CHDA
(
2
4
de 92%) 0.030 g (75%) was collected as orange oil.
removal, the oily residue, without further purification,
was subjected to the GC and Chiral GC for the con-
version and enantiomeric excess analysis. The conver-
sion was determined by GC (Hewlett–Packard HP 5890
Series II gas chromatograph) on HP-1 (12 m · 0.25 mm)
2
D
2
½
aꢀ ¼ +195.3 (c 0.32, CHCl
3
).
4.2. Enantioselective diethylzinc addition to aldehydes
catalyzed by salens 4–10
with N
2
as carrier gas. Split temperature 200 ꢁC, detec-
tor FID 250 ꢁC, temperature program: 40 ꢁC (1 min),
flow rate 30 ꢁC/min, end temperature 250 ꢁC (10 min).
Enantiomeric analysis of the secondary alcohols product
was performed by GC (Hewlett–Packard HP 5890 Series
II gas chromatograph) on CP-Chirasil-Dex CB (25 m ·
4.2.1. Typical experiment procedure. To a suspension of
salen (0.005 mmol) in 0.2 ml of toluene, 0.005 mmol of
Et Zn (15% solution in hexane, d ¼ 0.720) was added
2
and the resulting yellow or orange mixture was stirred
for 1 h at room temperature. The resulting mixture was
2
0.25 mm) with N as the carrier gas. Temperature data