2
610
P. Salehi et al. / Tetrahedron: Asymmetry 20 (2009) 2609–2611
ison with previous imino alcohols9 that have been used for this
purpose.
OH
Chiral Catalyst 3
Et2Zn
+ C6H5CHO
Toluene, n-Hexane
C6H5
4
4
. Experimental
Scheme 2.
.1. General
Mass spectra were recorded on a FINNIGAN-MAT8430 mass
Table 1
Enantioselective addition of Et
different conditions
2
Zn to C
H
6 5
CHO catalyzed by chiral catalyst 3 under
spectrometer operating at an ionization-potential of 70 eV. Ele-
mental analysis was performed using a Gmbh varioEL instrument.
IR spectra were recorded on KBr pellets on a Nicolet Impact 400D
spectrophotometer. Conversions were determined with a Hewlett–
Packard HP-5890 GC instrument equipped with a flame ionization
detector and a 30 m HP-1 capillary column, using nitrogen (2 mL/
min) as carrier gas. The enantiomeric ratios were determined with
the aforementioned apparatus using a 30 m WCOT-fused silica
Yielda (%)
eeb,c (%)
Entry
Mol % of ligand
T (°C)
Time (h)
1d
2
3
10
10
5
ꢁ10
ꢁ10
ꢁ10
ꢁ10
+5
24
24
24
24
20
20
20
38
67
71
12
73
73
74
8
99
99
0
99
99
99
4
1
5
5
6
7
10
5
+5
rt
1
13
capillary column (HP-chiral). H and CNMR spectra were deter-
mined on a Bruker 300 DRX Avance instrument at 300.13 and
a
b
c
GC yield of the mixture of the two enantiomers.
ee was determined by GC using a chiral capillary column (HP-Chiral).
The absolute configuration of the major enantiomer was determined by com-
7
5.47 MHz, respectively.
0
0
0
0
0
parison with an authentic sample. The major enantiomer in all cases had an (R)-
4.2. (1S,1 S,2S,2 S,3E,3 E,5S,5 S)-3,3 -(Ethane-1,2-diylbis(azan-1-
configuration.
yl-1-ylidene))bis(2,6,6-trimethylbicyclo[3.1.1]heptan-2-ol) 3
d
i
With 120 mol % of Ti(O Pr)
4
.
To a solution of (1S,2S,5S)-(ꢁ)-2-hydroxypinan-3-one (1.0 equiv)
in dry toluene (20 mL) was added 2 mol % of BF
3
ꢀEt
2
O and ethylene-
i
the absence of Ti(O Pr)4. The amount of the catalyst and reaction
temperature was optimized in subsequent reactions. As shown in
Table 1, the best result (74% yield and 99% ee) was obtained when
diamine (0.5 equiv). After heating at reflux for 18 h (TLC monitoring)
with stirring, the solvent was distilled off under vacuum and the res-
idue was purified by recrystallization from n-heptane to give 70%
yield of the ligand 3 as a colorless solid. 70% Yield as colorless crys-
5
mol % of 3 was used at room temperature (Table 1, entry 7).
After optimizing the best conditions for the reaction of diethyl-
ꢁ1
+
tals; IR (KBr) 3340, 2909, 1647, 1390, cm ; Ms (EI) 361 (M +1,
1
zinc with benzaldehyde, we applied the same conditions to other
aromatic aldehydes. The results for the addition of diethylzinc in
the presence of 3 are summarized in Table 2.
For the substituted aromatic aldehydes as shown in Table 2,
high ees were obtained. In general, the introduction of substituents
at the ortho-position led to a slight decrease in the enantioselectiv-
ity. The best enantioselectivity of up to 98% was obtained with p-
fluorobenzaldehyde (Table 2, entry 1).
60), 343 (32), 289 (19), 195 (25), 71 (41), 43 (100); H NMR (CDCl )
d 0.81 (6H, s), 1.28 (6H, s), 1.42 (6H, s), 1.52–1.56 (2H, m), 2.00–
3
2.02 (4H, m), 2.25–2.31 (2H, m), 2.55 (4H, s), 3.25 (2H, br s), 3.56
1
3
(4H, m); C NMR (CDCl ) d 176.4, 51.3, 50.4, 38.39, 38.32, 33.7,
3
28.2, 28.1, 27.3, 22.89, 22.82 (C22H36N O requires: C, 73.3; H,
2
2
10.0; N, 7.7. Found: C, 73.6; H, 10.0; N, 7.7).
4
.3. General procedure for the enantioselective addition of
diethylzinc to aryl aldehydes
3
. Conclusion
The ligand (0.055 mmol) was placed in a test tube and dissolved
in dry toluene (2 mL). The solution was stirred for 5 min. A 1.0 M
solution of diethylzinc in n-hexane (2.2 mmol, 2.2 mL) was then
added, and after the mixture was stirred for 5 min, a solution of
the aldehyde (1.11 mmol) in dry toluene (1 mL) was added by a
syringe. The mixture was stirred at the appropriate temperature,
In conclusion, we have shown that imino alcohol 3, which is
easily prepared from the reaction of 2-hydroxy-3-pinanone with
ethylenediamine can be successfully used as a ligand in the high
yield enantioselective addition of diethylzinc to aryl aldehydes.
The method offers the use of a cheap and stable ligand in compar-
4
for the time reported in Table 1. Saturated aqueous NH Cl was
added (10 mL) and the mixture was extracted with ethyl acetate
Table 2
(3 ꢂ 20 mL). The collected organic phases were washed with water,
Enantioselective addition of diethylzinc to aromatic aldehydes by chiral imino alcohol
2 4
dried over Na SO , and analyzed by GC, after suitable dilution.
a
3
Entry
1
Aldehyde
Yieldb (%)
eec,d (%)
Acknowledgments
p-FC
p-FC
6
H
H
4
CHO
CHO
98
98
100
98
100
100
100
94
98
94
92
93
95
92
91
72
71
e
2
6
4
Financial support from the Research Council of Shahid Beheshti
University and Catalyst Center of Excellence (CCE) is gratefully
acknowledged.
3
4
5
p-ClC
p-BrC
6
H
4
CHO
CHO
6 4
H
p-MeC
p-MeC
6
H
4
CHO
CHO
e
6
6
H
4
7
8
9
p-MeOC
o-MeOC
o-ClC
6
H
H
4
CHO
4
CHO
CHO
References
6
6
H
4
81
1.
(a) Soai, K.; Niwa, S. Chem. Rev. 1992, 92, 833–856; (b) Pu, L.; Bin Yu, H. Chem.
Rev. 2001, 101, 757–824.
a
b
c
Condition: rt, 20 h and 5 mol % of 3.
Measured as conversion% by GC.
Determined by capillary chiral GC analysis using a chiral column (HP-chiral).
The absolute configuration was determined by comparing the sign of specific
2. (a) Kitamura, M.; Suga, S.; Kawai, K.; Noyori, R. J. Am. Chem. Soc. 1986, 108, 6071–
6072; (b) Noyori, R.; Kitamura, M. Angew. Chem., Int. Ed. Engl. 1991, 30, 49–
69.
d
3.
(a) Soai, K.; Yokoyama, S.; Hayasaka, T. J. Org. Chem. 1991, 56, 4264–4268; (b)
Dabiri, M.; Salehi, P.; Kozehgary, G.; Heydari, S.; Heydari, A.; Esfandyari, M.
Tetrahedron: Asymmetry 2008, 19, 1970–1972.
11
rotation. The major enantiomer in all cases had an (R)-configuration.
e
With 10 mol % of 3.