Asymmetric synthesis of 1,4-amino alcohol ligands with a norbornene backbone for use in the asymmetric diethylzinc addition to benzaldehyde

Article abstract of DOI:10.1016/j.tetasy.2005.04.019

The asymmetric synthesis of cis-1,4-amino alcohols with a norbornene backbone was performed starting with (2S,3R)-(-)-cis-hemiester 2 (98% ee). Chemoselective amination with NH₄OH and HMPTA followed by LAH reduction afforded 5 and 7, respective

Full text of DOI:10.1016/j.tetasy.2005.04.019

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 16 (2005) 2039–2043
Asymmetric synthesis of 1,4-amino alcohol ligands with
a norbornene backbone for use in the asymmetric diethylzinc
addition to benzaldehyde
Cihangir Tanyeli* and Murat Sunbul
¨
¨
Department of Chemistry, Middle East Technical University, 06531 Ankara, Turkey
Received 8 April 2005; accepted 18 April 2005
Available online 23 May 2005
Abstract—The asymmetric synthesis of cis-1,4-amino alcohols with a norbornene backbone was performed starting with (2S,3R)-
(ꢀ)-cis-hemiester 2 (98% ee). Chemoselective amination with NH4OH and HMPTA followed by LAH reduction afforded 5 and 7,
respectively. Amido ester 6 was transformed into chiral ligand 9 with Grignard reaction followed by LAH reduction. The chiral
ligands 5, 7, and 9 were subjected to asymmetric diethylzinc addition to examine their effectiveness as chiral catalysts. Among these,
chiral ligand 7 exhibited the highest enantioselectivity (88% ee).
ꢀ 2005 Elsevier Ltd. All rights reserved.
1. Introduction
2. Asymmetric synthesis of 1,4-amino alcohols with a
norbornene backbone
Amino alcohols are versatile chiral building blocks for
organic synthesis1 and have also been used extensively
as chiral auxiliaries2 or ligands in asymmetric synthesis.3
In particular, the formation of C–C bonds has always
been one of the most challenging areas in organic syn-
thesis. Among these, the enantioselective addition of
diethylzinc to aldehydes in the presence of chiral ligands
was first reported by Noyori et al.4 Although different
types of chiral ligands, such as diamines,5 diols,6 amino-
thiols,7 and aminosulfides,7 were used in this reaction,
amino alcohols are the most common type of ligands
among them. Chiral 1,2-aminoalcohols are widely used
in diethylzinc addition reactions, however, there are
only just a few examples of chiral 1,4-amino alcohols
used in this reaction.1,8–12 1,4-Amino alcohols have
more flexible structures with respect to 1,2-amino alco-
hols for complexation with various types of metals and
thus may form more stable and selective catalysts in
the reaction. This prompted us to develop new chiral
1,4-amino alcohols including a norbornene backbone
and study their use in the alkylation of benzaldehyde
by diethylzinc.
In our synthetic strategy, cis-monoester (ꢀ)-2 was cho-
sen as the homochiral starting compound for the con-
struction of a norbornene backbone. Bolm et al.13
have recently reported a highly efficient method for the
enantioselective desymmetrizaton of meso-anhydrides
via an alkaloid-mediated opening with methanol. Qui-
nine and quinidine are used as the chiral directing agents
and both enantiomers of the corresponding cis-mono-
ester can be obtained with very high enantiomeric
excesses (up to 99% ee) and chemical yield.
Quinine-mediated desymmetrization of anhydride 1 with
methanol resulted in cis-monoester (ꢀ)-2 with a high
enantiomeric excess (98% ee) (Scheme 1). Monoester
(ꢀ)-2 was then reacted with p-bromophenol via DCC
coupling method to produce corresponding diester 3,
which was then analyzed by HPLC for enantiomeric
excess determination.
In our synthetic route, the carboxylic acid group of
monoester (ꢀ)-2 was chemoselectively activated with
ethyl chloroformate and then reacted with NH4OH to
afford the corresponding cis-monoester amide 4 with a
yield of 82%. One of the target cis-1,4-unsubstituted
amino alcohol derivatives 5 was obtained by subsequent
LiAlH4 reduction of 4 in ether with 73% yield.
*
Corresponding author. Tel.: +90 312 210 3222; fax: +90 312 210
1280; e-mail: tanyeli@metu.edu.tr
0957-4166/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2005.04.019

2040
C. Tanyeli, M. Su€nbu€l / Tetrahedron: Asymmetry 16 (2005) 2039–2043
O
b
a
COOH
COOMe
COO
COOMe
Br
O
O
1
2
3
98% ee
Scheme 1. Reagents and conditions: (a) quinine, MeOH, toluene/CCl4, ꢀ55 ꢁC; (b) 4-bromophenol, DCC, DMAP, CH2Cl2.
Substitution on norbornene based cis-1,4-amino alcohol
nitrogen and methylene bearing hydroxy group would
presumably cause an impact on the catalytic activity of
the resulting chiral ligands used in the asymmetric addi-
tion of diethylzinc to benzaldehyde. In the synthesis of
sterically and electronically modified chiral ligands,
monoester (ꢀ)-2 was reacted with hexamethylphospho-
rus triamide, which transformed the carboxylic acid
group into corresponding N,N-dimethyl amide deriva-
tive 6 with a yield of 88%.14 Subsequent reduction of 6
by LiAlH4 in ether afforded the N,N-dimethyl substi-
tuted cis-1,4-amino alcohol type chiral ligand 7 with a
yield of 90%. Using a Grignard method, the ester group
of 6 was functionalized with phenylmagnesium bromide
giving diphenyl substituted derivative 8. The reduction
of the N,N-dimethyl amide function was accomplished
by LiAlH4 in ether to afford chiral ligand 9 with a yield
of 94% (Scheme 2).
no effect on the stereocenters of the norbornene back-
bone, the absolute configuration of each ligand was
not changed during transformation reactions.
3. Enantioselective addition of diethylzinc to benzaldehyde
using 5, 7, and 9
The catalytic properties of the three new chiral 1,4-amino
alcohols 5, 7, and 9 were explored in asymmetric
diethylzinc addition to benzaldehyde. The results are
summarized in Table 1.
Table 1. Asymmetric diethylzinc addition to benzaldehyde using
norbornene based 1,4-aminoalcohol catalysts
O
H
HO
1. ZnEt2, L*
2. work-up
H
S
L* = 5, 7, 9
a
b
COOH
COOMe
NH2
OH
CONH2
COOMe
Entry
Liganda
Yield (%)b
15
ee (%)c
1
2
3
5
7
9
53
82
49
98
97
2
4
5
a 10 mol % of chiral catalysts were used. Toluene was used as solvent.
All reactions were done at 0 ꢁC.
c
b Yields were calculated after column chromatography.
c Enantiomeric ratios were determined by HPLC analysis using a chiral
column. The major product has an (S)-configuration.
f
e
CONMe2
OH
NMe2
OH
CONMe2
COOMe
Ph
Ph
Ph
Ph
All the ligands exhibited acceptable enantioselectivities
(up to 82% ee) and afforded 1-phenylpropanol in good
yields (up to 98%). The best result was obtained with
amino alcohol 7, which has dimethyl substituents on
the nitrogen atom (entry 2). Catalysts without any sub-
stituent on the nitrogen and hydroxymethylene carbon 5
and with dimethyl and diphenyl substituents on nitrogen
and hydroxymethylene carbon 9, respectively (entries 1
and 3) gave the products with lower ee values. These
results prompted us toward the investigation of the con-
ditions to improve the enantioselectivity of chiral catalyst
7. For this purpose, the temperature and solvent depen-
dence enantioselectivity of chiral ligand 7 was explored.
6
8
9
d
NMe2
OH
7
Scheme 2. Reagents and conditions: (a) (i) ClCO2Et, TEA, THF, (ii)
NH4OH; (b) LiAlH4, Et2O, reflux; (c) HMPTA, benzene, reflux; (d)
LiAlH4, Et2O, reflux; (e) (i) PhBr, Mg, Et2O, (ii) 1 M HCl; (f) LiAlH4,
Et2O, reflux.
The asymmetric diethylzinc addition reaction was car-
ried out in toluene with 10 mol % of chiral catalyst 7
at ꢀ10 and at 20 ꢁC and compared with the result given
in Table 1 (entry 2). At ꢀ10 ꢁC, catalyst 7 gave 76% ee
and afforded 1-phenylpropanol with a yield of 67%.
Both the enantioselectivity and the chemical yield were
lower than entry 2. When the temperature was raised
The absolute configurations of (ꢀ)-5, (+)-7, and (ꢀ)-9
were determined as (2S,3R) by comparing specific rota-
tion signs determined at equal concentration in the same
solvent with cis-monoester (+)-2, which had been re-
ported in the literature.13,15 Since transformation of
cis-monoester (ꢀ)-2 to chiral ligands 5, 7, and 9 has

C. Tanyeli, M. Su€nbu€l / Tetrahedron: Asymmetry 16 (2005) 2039–2043
2041
up to 20 ꢁC, no chemical yield change was observed. The
enantioselectivity decreased as in the former case (75%
ee). We also examined the effect of solvent using hexane,
DCM, and THF. All the results are given in Table 2.
The reactions were carried out at the optimized temper-
ature 0 ꢁC and among the solvents, the best result was
obtained in hexane (88% ee) (Table 2, entry 2). We ob-
tained very low ee with DCM and THF with 30% and
59% ee, respectively (entries 3 and 4).
at ꢀ55 ꢁC under argon. The reaction mixture was stirred
at this temperature for 60 h. Subsequently, the resulting
clear solution was concentrated in vacuo to dryness and
the resulting residue dissolved in ethyl acetate. The ethyl
acetate solution was washed with 2 M HCl, and after
phase separation, followed by extraction of aqueous
phase with ethyl acetate and the organic layer dried over
MgSO4 was filtered, and concentrated providing the
20
D
monoester 2 (2.17 g, 92%). ½aꢁ ¼ ꢀ7.8 (c 4.0, CCl4),
20
D
lit.15,16 ½aꢁ ¼ ꢀ7.9 (c 4.8, CCl4); mp 75–78 ꢁC, lit.15,16
74 ꢁC (racemic); 1H NMR: d 6.26 (dd, J = 2.96,
5.50 Hz, 1H), 6.16 (dd, J = 2.94, 5.53 Hz, 1H), 3.54 (s,
3H), 3.28 (dd, J = 3.22, 10.14 Hz, 1H), 3.22 (dd,
J = 3.13, 10.15 Hz, 1H), 3.14 (br s, 1H), 3.11 (br s,
1H), 1.43 (dt, J = 1.56, 8.67 Hz, 1H), 1.28 (d,
J = 8.69 Hz, 1H); 13C NMR: d 177.8, 173.1, 135.6,
134.4, 51.6, 48.8, 48.2, 47.9, 46.6, 46.1.
Table 2. The effect of solvent on the enantioselectivity of chiral ligand
7
Entrya
Solvent
Yield (%)b
ee (%)c
1
2
3
4
Toluene
Hexane
DCM
98
98
5
82
88
30
59
THF
15
a 10 mol % of chiral catalyst was used. All reactions were done at 0 ꢁC.
To recover the quinine, the acidic aqueous phase was
neutralized with Na2CO3 and extracted with CH2Cl2.
The combined organic phases were dried over MgSO4
and filtered. Evaporation of the solvent yielded the qui-
nine almost quantitatively.
b Yields were calculated after column chromatography.
c Enantiomeric ratios were determined by HPLC analysis using a chiral
column. The major product has S configuration.
4. Conclusion
5.2. Synthesis of (2S,3R)-2-(4-bromophenoxy)-3-meth-
oxycarbonylbicyclo[2.2.1]hept-5-ene 3
We have synthesized a series of chiral norbornene-based
1,4-amino alcohols (2S,3R)-5, (2S,3R)-7, and (2S,3R)-9.
These compounds were used as ligands in the asymmet-
ric diethylzinc addition to benzaldehyde. Ligand
(2S,3R)-7 showed the best enantioselectivity over the
others. We optimized the asymmetric diethylzinc addi-
tion condition. All the ligands directed the catalytic pro-
cess toward the formation of (1S)-1-phenylpropanol.
4-Bromophenol (0.088 g, 0.51 mmol) and monoester 2
(0.100 g, 0.51 mmol) were dissolved in CH2Cl2 (5 mL)
at 0 ꢁC under argon. Then, DCC (0.105 g, 0.51 mmol )
and DMAP (0.016 g, 0.13 mmol) were added simulta-
neously at 0 ꢁC. The mixture was stirred overnight at
room temperature. DCC precipitated as dicyclohexyl-
urea. The mixture was filtered and filtrate washed first
with 5% HOAc, then 1 M NaOH and finally brine.
The organic phase was dried over MgSO4 and evapora-
tion of the solvent afforded the compound 3 (0.16 g,
89%). HPLC-analysis of the methyl 4-bromophenyl
diester: Chiralcel OD-H at room temperature, n-hex-
ane/2-propanol = 98:2, 0.5 mL/min, 254 nm, t1 = 20.3
min (major), t2 = 23.2 min (minor); 1H NMR: d 7.37
(d, J = 8.72 Hz, 2H), 6.92 (d, J = 8.71 Hz, 2H), 6.32
(dd, J = 2.91, 5.39 Hz, 1H), 6.15 (dd, J = 2.92,
5.41 Hz, 1H), 3.55 (s, 3H), 3.39 (s, 2H), 3.20 (s, 1H),
3.17 (s, 1H), 1.40 (d, J = 8.70 Hz, 1H), 1.33 (d,
J = 8.61, 1H); 13C NMR: d 173.0, 171.2, 150.3, 135.9,
135.0, 132.7, 123.8, 119.0, 52.2, 49.1, 48.7, 48.5, 47.2,
46.6.
5. Experimental
1
The H and 13C NMR spectra were recorded in CDCl3
on a Brucker Spectrospin Avance DPX 400 spectro-
meter. Chemical shifts are given in parts per million
downfield from tetramethylsilane. Apparent splittings
are given in all cases. Infrared spectra were obtained
from KBr pellets on a Mattson 1000 FT-IR spectro-
photometer. Mass spectra were recorded on a Varian
MAT 212. Melting points are uncorrected. Optical rota-
tions were measured in a 1 dm cell using a Bellingham
and Stanley P20 polarimeter at 20 ꢁC. HPLC measure-
ments were performed with ThermoFinnigan Spectra
System instrument. Separations were carried out on
Chiralcel OD-H analytical column (250 · 4.60 mm) with
hexane/2-propyl alcohol as eluent. Column chromato-
graphy was performed on silica gel (60-mesh, Merck).
TLC was carried out on Merck 0.2-mm silica gel 60
F254 analytical aluminum plates.
5.3. Synthesis of (2S,3R)-2-carboxamido-3-methoxy-
carbonylbicyclo[2.2.1]hept-5-ene 4
Ethylchloroformate (0.97 mL, 10.2 mmol) was added to
a mixture of monoester 2 (2.00 g, 10.2 mmol) dissolved
in dry THF (15 mL) and triethylamine (1.42 mL,
10.2 mmol) over a period of 5 min at ꢀ7 ꢁC. The resul-
tant mixture was stirred for an additional 30 min at
ꢀ7 ꢁC and then the mixture filtered, and the cake
washed with THF (3 · 5 mL). NH4OH (3 mL) was
added to the filtrate in one portion and the mixture stir-
red for 1 h at 10 ꢁC, afterwards the mixture was concen-
trated. The solid residue was dissolved in CH2Cl2 and
washed with 1 M HCl. The organic phase was dried over
5.1. Synthesis of (2S,3R)-3-methoxycarbonylbicyclo-
[2.2.1]hept-5-ene-2-carboxylic acid 2
MeOH (1.48 mL, 36 mmol) was added dropwise to a
stirred solution of the meso-anhydride 1 (2.00 g,
12 mmol) and quinine (4.35 g, 13 mmol) in a 1:1 mixture
of toluene (120 mL) and carbon tetrachloride (120 mL)

2042
C. Tanyeli, M. Su€nbu€l / Tetrahedron: Asymmetry 16 (2005) 2039–2043
MgSO4 and the solvent evaporated. The crude product
was purified by column chromatography (5% MeOH/
95% CHCl3) to give compound 4 (1.63 g, 82%).
6 (0.50 g, 2.24 mmol) in dry THF (5 mL) at a rate, which
maintained gentle reflux. The mixture was then refluxed
for 3 h and hydrolized by the cautious addition of water
and 15% NaOH solution. The fine white precipitate,
which formed was washed with ether and discarded.
20
½aꢁ ¼ ꢀ2.5 (c 2.77, MeOH); mp 130–131 ꢁC; IR
D
(KBr): 3325, 3198, 1738, 1671 cmꢀ1
;
1H NMR: d
6.45 (dd, J = 3.04, 5.44 Hz, 1H), 6.11 (dd, J = 2.97,
5.48 Hz, 1H), 5.54 (s, 2H), 3.54 (s, 3H), 3.23 (dd,
J = 3.04, 10.45 Hz, 1H), 3.18 (dd, J = 2.83, 10.49 Hz,
1H), 3.07 (m, 2H), 1.44 (d, J = 8.61 Hz, 1H), 1.28 (d,
J = 8.59, 1H); 13C NMR: d 174.3, 173.6, 137.0, 133.3,
51.5, 49.8, 49.3, 49.0, 47.2, 45.7.
The filtrate was concentrated to give amino alcohol 7
20
(0.37 g, 90%). ½aꢁ ¼ þ15.1 (c 1.16, MeOH); mp
D
1
90–92 ꢁC; IR (KBr): 3131, 2959, 2361, 1507 cmꢀ1; H
NMR: d 5.98 (m, 2H), 3.43 (dd, J = 2.12, 11.61 Hz,
1H), 3.13 (t, J = 11.32 Hz, 1H), 2.64 (s, 1H), 2.61 (s,
1H), 2.42 (m, 2H), 2.24 (t, J = 12.49 Hz, 1H), 2.16 (s,
6H), 2.03 (dd, J = 1.79, 12.42 Hz, 1H), 1.33 (m, 2H);
13C NMR: d 135.8, 134.8, 63.5, 61.0, 50.4, 48.0, 47.3,
46.5, 45.6, 40.2; HRMS calcd for C11H20NO (M+H)+,
182.1546. Found 182.1550.
5.4. Synthesis of (2S,3R)-2-aminomethyl-3-hydroxy-
methylbicyclo[2.2.1]hept-5-ene 5
To a suspension of LiAlH4 (0.11 g, 3.0 mmol) in dry THF
(10 mL) was added a solution of amido ester 4 (0.20 g,
1.0 mmol) in THF (5 mL) at a rate, which maintained
gentle reflux. The mixture was then refluxed for 1 day
and hydrolized by the cautious addition of water and
15% NaOH solution. The fine white precipitate which
formed was washed with ether and discarded. The filtrate
was concentrated and purified by column chromatogra-
5.7. Synthesis of (2S,3R)-2-(N,N-dimethylcarboxamido)-
3-(diphenylhydroxymethyl)-bicyclo[2.2.1]hept-5-ene 8
Bromobenzene (3.2 g, 20.4 mmol) was dissolved in
10 mL of anhydrous diethyl ether and put into the addi-
tion funnel. This solution was added to magnesium
(0.6 g, 25.0 mmol) turnings. Once the reaction had be-
gun, the rest of the bromobenzene solution was added
dropwise at a rate that maintained gentle reflux. When
the addition of the bromobenzene solution was com-
plete, the mixture was refluxed for 20 min. Compound
6 (1.51 g, 6.78 mmol) was dissolved in 15 mL of anhy-
drous diethyl ether and added to the prepared Grignard
mixture. After all of compound 6 solution had been
added, the reaction mixture was refluxed for 2 h. The
resultant mixture was poured into the mixture of ice
(25 g) and 3 M H2SO4 (30 mL). The organic phase was
washed with 5% NaHCO3 and then brine. This was
dried over MgSO4, the solvent evaporated and the crude
product purified by column chromatography (5%
phy (8% MeOH/2% NH4OH/90% CHCl3) to afford com-
20
pound 5 (1.11 g, 73%). ½aꢁ ¼ ꢀ8.9 (c 0.56, MeOH); mp
D
1
102–104 ꢁC; IR (KBr): 3378, 3077, 2665, 1608 cmꢀ1; H
NMR: d 6.06 (dd, J = 3.00, 5.39 Hz, 1H), 6.02 (dd,
J = 2.39, 5.80 Hz, 1H), 3.74 (br s, 2H), 3.55 (dd,
J = 3.23, 11.61 Hz, 1H), 3.32 (t, J = 11.42 Hz, 1H), 2.98
(dd, J = 2.57, 11.76 Hz, 2H), 2.77 (t, J = 1.42 Hz, 2H),
2.56–2.60 (m, 1H), 2.44 (t, J = 11.95 Hz, 1H), 2.28–2.35
(m, 1H), 1.40 (d, J = 1.83 Hz, 1H), 1.39 (d, J = 1.87 Hz,
1H); 13C NMR: d 135.3, 134.4, 63.2, 49.8, 47.6, 46.9,
46.2, 44.5, 42.2; HRMS calcd for C9H16NO (M+H)+,
154.1232. Found 154.1240.
5.5. Synthesis of (2S,3R)-2-(N,N-dimethylcarboxamido)-
3-methoxycarbonylbicyclo[2.2.1]hept-5-ene 6
MeOH, 95% CHCl3) to give compound 8 (1.96 g,
20
83%). ½aꢁ ¼ þ8.3 (c 0.7, CHCl3); mp 203–204 ꢁC; IR
D
1
(KBr): 3479, 3217, 1605 cmꢀ1; H NMR: 7.45–7.50 (m,
4H), 7.16–7.21 (m, 4H), 7.02–7.08 (m, 2H), 6.53 (dd,
J = 3.40, 5.20 Hz, 1H), 5.87 (dd, J = 3.00, 5.42 Hz,
1H), 3.56 (dd, J = 3.22, 9.58 Hz, 1H), 3.46 (dd,
J = 2.56, 9.57 Hz, 1H), 2.86 (s, 1H), 2.84 (s, 3H), 2.56
(s, 1H), 2.30 (s, 3H), 1.29 (s, 2H); 13C NMR: 175.3,
150.8, 148.5, 138.8, 131.0, 128.2, 128.1, 128.0, 126.4,
126.3, 126.2, 78.1, 58.7, 50.5, 47.8, 46.4, 45.1, 38.5,
36.4; HRMS calcd for C23H26NO2 (M+H)+, 348.1964.
Found 348.1977.
To the solution of monoester 2 (2.00 g, 10.2 mmol) in
benzene (5 mL) was added hexamethylphosphorus tria-
mide (1.85 mL, 5.1 mmol) at a rate which maintained
reflux of the reaction. After 2 h, the resulting cloudy
solution was allowed to cool to room temperature and
a saturated NaHCO3 solution was added. The aqueous
layer was extracted with DCM. The organic solutions
were combined, dried over MgSO4, and concentrated
20
D
to give compound 6 (2.01 g, 88%). ½aꢁ ¼ ꢀ35.7 (c
1.16, CHCl3); mp 78–79 ꢁC; IR (KBr): 2998, 1742,
1637 cmꢀ1
;
1H NMR: d 6.30 (dd, J = 3.03, 5.34 Hz,
5.8. Synthesis of (2S,3R)-2-(dimethylaminomethyl)-3-
(diphenylhydroxymethyl)bicyclo[2.2.1]hept-5-ene 9
1H), 6.12 (dd, J = 2.93, 5.39 Hz, 1H), 3.52 (s, 3H),
3.35 (dd, J = 3.16, 9.91 Hz, 1H), 3.19 (dd, J = 3.48,
9.92 Hz, 1H), 3.12 (s, 1H), 3.04 (s, 1H), 2.95 (s, 3H),
2.81 (s, 3H), 1.38 (d, J = 8.5 Hz, 1H), 1.27 (d,
J = 8.5 Hz, 1H); 13C NMR: 173.3, 172.4, 136.6, 133.9,
51.9, 49.2, 48.9, 47.3, 47.0, 46.9, 37.3, 36.0; HRMS calcd
for C12H18NO3 (M+H)+, 224.1287. Found 224.1277.
To a suspension of LiAlH4 (0.033 g, 0.86 mmol) in
anhydrous ether (10 mL) was added a solution of amide
alcohol 8 (0.15 g, 0.43 mmol) in dry THF (5 mL) at a
rate, which maintained gentle reflux. The mixture was
then refluxed for 3 h and hydrolized by the cautious
addition of water and 15% NaOH solution. The fine
white precipitate which formed was washed with ether
5.6. Synthesis of (2S,3R)-2-dimethylaminomethyl-3-
hydroxymethylbicyclo[2.2.1]hept-5-ene 7
and discarded. The filtrate was concentrated to give
20
D
amino alcohol 9 (0.135 g, 94%). ½aꢁ ¼ ꢀ17.8 (c 0.56,
To a suspension of LiAlH4 (0.26 g, 6.72 mmol) in anhy-
drous ether (1 mL) was added a solution of amido ester
MeOH); mp 133–136 ꢁC; IR (KBr): 3528, 1976, 1653
cmꢀ1
;
1H NMR: 7.55 (d, J = 7.72 Hz, 2H), 7.39

C. Tanyeli, M. Su€nbu€l / Tetrahedron: Asymmetry 16 (2005) 2039–2043
2043
J. Organomet. Chem. 1990, 382, 19–37; (b) Noyori, R.;
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Am. Chem. Soc. 1989, 111, 4028–4036.
(d, J = 7.73 Hz, 2H), 7.27 (m, 4H), 7.15 (m, 2H), 6.33
(m, 2H), 3.53 (dd, J = 2.67, 9.85 Hz, 1H), 3.06 (br s,
1H), 2.75 (m, 1H), 2.35 (br s, 1H), 2.13 (t,
J = 10.65 Hz, 1H), 1.98 (s, 6H), 1.89 (dd, J = 4.14,
12.78 Hz, 1H), 1.39 (br s, 2H); 13C NMR: 149.3,
148.7, 137.4, 135.7, 128.1, 127.9, 126.4, 125.9, 125.3,
79.6, 60.6, 52.2, 50.6, 47.3, 46.6, 45.8, 42.8; HRMS calcd
for C23H28NO (M+H)+, 334.2172. Found 334.2161.
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1999, 10, 3791.
5.9. General procedure for diethylzinc addition reactions
8. (a) Genov, M.; Dimitrov, V.; Ivanova, V. Tetrahedron:
Asymmetry 1997, 8, 3703–3706; (b) Genov, M.; Kostova,
K.; Dimitrov, V. Tetrahedron: Asymmetry 1997, 8, 1869–
1876.
9. Scarpi, D.; Galbo, F.; Occhiato, E.; Guarna, A. Tetrahe-
dron: Asymmetry 2004, 15, 1319–1324.
10. (a) Hanyu, N.; Aoki, T.; Mino, T.; Sakamoto, M.; Fujita,
T. Tetrahedron: Asymmetry 2000, 11, 2971–2979; (b)
Hanyu, N.; Aoki, T.; Mino, T.; Sakamoto, M.; Fujita,
T. Tetrahedron: Asymmetry 2000, 11, 4127–4136; (c)
Hanyu, N.; Mino, T.; Sakamoto, M.; Fujita, T. Tetra-
hedron Lett. 2000, 41, 4587–4590.
11. Martinez, A. G.; Vilar, E. T.; Fraile, A. G.; de la Moya
Cerero, S.; Maroto, B. L. Tetrahedron: Asymmetry 2003,
14, 1959–1963.
The ligand (0.05 mmol) was dissolved in hexane (or tol-
uene) (3 mL) at room temperature under an argon atmo-
sphere and diethyl zinc (1.0 mmol, 1 M in hexane) then
added to this solution. The mixture was stirred for
30 min and then cooled to 0 ꢁC. Benzaldehyde
(0.5 mmol) was added to the mixture and the reaction
mixture stirred for 48 h at 0 ꢁC. After adding 1 M HCl
(10 mL), it was extracted with ethyl acetate (25 mL).
Then the organic phase was dried over MgSO4 and the
solvent evaporated to give the corresponding alcohol.
HPLC-analysis of 1-phenyl-1-propanol: Chiralcel OD-H
at room temperature, n-hexane/2-propanol = 98:2,
1.0 mL/min, 254 nm, t1 = 26.3 min (R), t2 = 31.5 min (S).
12. Faux, N.; Razafimahefa, D.; Picart-Goetgheluck, S.;
Brocard, J. Tetrahedron: Asymmetry 2005, 16, 1189–
1197.
References
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¨
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¨
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