Asymmetric addition of diethylzinc to aldehydes catalyzed by a camphor-derived β-amino alcohol

Article abstract of DOI:10.1016/j.tetasy.2009.06.009

The asymmetric addition of diethylzinc to aromatic and aliphatic aldehydes, including linear aliphatic ones, catalyzed by 2 mol % of β-amino alcohol (1S, 2R)-7,7-dimethyl-1-morpholin-4-yl-bicyclo[2.2.1]heptan-2-ol 10 gave the corresponding secondary alcohols in high yields and with up to 94% ee at ambient temperature after 15 min.

Full text of DOI:10.1016/j.tetasy.2009.06.009

Tetrahedron: Asymmetry 20 (2009) 1556–1560
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Tetrahedron: Asymmetry
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Asymmetric addition of diethylzinc to aldehydes catalyzed by a
camphor-derived b-amino alcohol
*
Zhi-Long Wu, Hsyueh-Liang Wu, Ping-Yu Wu, Biing-Jiun Uang
Department of Chemistry, National Tsing Hua University, Hsinchu, Taiwan 30013
a r t i c l e i n f o
a b s t r a c t
Article history:
The asymmetric addition of diethylzinc to aromatic and aliphatic aldehydes, including linear aliphatic
ones, catalyzed by 2 mol % of b-amino alcohol (1S, 2R)-7,7-dimethyl-1-morpholin-4-yl-bicyclo[2.2.1]hep-
tan-2-ol 10 gave the corresponding secondary alcohols in high yields and with up to 94% ee at ambient
temperature after 15 min.
Received 18 May 2009
Accepted 13 June 2009
Available online 14 July 2009
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
O
NMe2
OH
N
OH
The enantioselective addition of organozincs1,2 to carbonyl
compounds in the presence of chiral catalysts has attracted the
attention of synthetic organic chemists owing to its mild reaction
conditions, wide functional group tolerance, and the low toxicity
of the zinc metal. The concomitant construction of an asymmetric
C–C bond and a new stereogenic center in the reaction has led to its
application in the synthesis of optically active alcohols for the
further synthesis of natural products and biologically active
components.3 Among the naturally occurring chiral substances,
camphor and its derivatives are not only good chiral auxiliaries4,5
in asymmetric synthesis, but also useful chiral scaffolds for
asymmetric catalysts.6,7 Chiral b-amino alcohol 1 (DAIB)8 showed
impressive results during catalytic organozinc addition reactions,
while its modified analogue MIB 2,9 which bears a larger amino
coordinator, gave better catalytic activities in the addition of dieth-
ylzinc, alkenylzincs, and arylzincs to aldehydes (Fig. 1).10,11 In con-
trast, b-amino alcohol 3 was inferior in catalyzing the ethylation
reaction (23% ee).6b However, an independent study of the chiral
ligand 3 by our group in the asymmetric diethylzinc addition reac-
tion with benzaldehyde gave as high as 82% ee of the correspond-
ing adduct. The improved ee presumably arose from the use of less
diethylzinc and lower reaction temperatures (Table 1, entry 1).
Encouraged by these results and our early efforts on camphor-de-
rived rigid ligands in asymmetric reactions,7 we decided to develop
a more effective and easily prepared ligand bearing a norbornane
structure by enlarging the amino moiety of known b-amino alcohol
3 in an asymmetric organozinc addition reaction. Here, we report
our findings on 1-N,N-dialkylamino-2-hydroxynorbornane as
catalysts in the asymmetric addition of diethylzinc to aldehydes.
OH
Me2N
DAIB 1
MIB 2
3
Figure 1. Some isoborneol-based b-amino alcohols.
2. Results and discussion
The b-amino alcohol ligands 8–10 were synthesized from the
corresponding amino ketone 412 in two steps (Scheme 1). Treat-
ment of amine 4 with 1,4-butane dibromide, 1,5-pentane dibro-
mide, and bis-(2-bromoethyl)ether gave amino ketones 5–7,
respectively, in good yields. Finally, the diastereoselective reduc-
tion of ketones 5–7 with NaBH4/CeCl3 in methanol at ꢀ78 °C then
slowly to 25 °C yielded the corresponding exo-alcohols 8–10,
respectively.13
The application of 10 mol % of b-amino alcohols 3 and 8–10 in
the asymmetric addition of diethylzinc with benzaldehydes was
initially tested at 0 °C, and good yields along with excellent ee were
obtained (Table 1).
The addition reaction conditions were then optimized with li-
gand 10, which gave the best yield and ee in the ethylation of benz-
aldehyde. Various reaction parameters, such as ligand loadings
(Table 2, entries 1–3), addition methods (entries 4 and 5), and
the amount of diethylzinc (entry 6) were examined. In general,
excellent enantioselectivities (94% ee) were observed using
1.5 equiv of diethylzinc in the presence of 5 mol % of b-amino alco-
hol 10 at 0 °C. The use of less than 1.5 equiv of diethylzinc dimin-
ished the enantioinduction (entry 6).
The optimization was later focused on the solvent effect (Table
3). Reactions in pentane and heptane were studied at 0 °C, and
* Corresponding author. Tel.: +886 3 5721224; fax: +886 3 5711082.
E-mail address: bjuang@mx.nthu.edu.tw (B.-J. Uang).
0957-4166/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2009.06.009

Z.-L. Wu et al. / Tetrahedron: Asymmetry 20 (2009) 1556–1560
1557
Table 1
Table 2
Asymmetric diethylzinc addition with benzaldehyde catalyzed by b-amino alcohols 3
and 8–10
Optimization of the reaction conditions with b-amino alcohol 10a
OH
Et
O
10, hexane
Et2Zn
(1.0 M in hexane)
+
OH
Et
O
Ph
H
Ph
0 ºC, time
Ligand (10 mol %)
hexane, 0 ºC, 2 h
Et2Zn (1.5 equiv)
(1.0 M in hexane)
+
(R)
Ph
Ph
H
(R)
Entry
10 (mol %)
Et2Zn (equiv)
Time (h)
Yieldb (%)
eec (%)
Entry
Ligand
Yielda (%)
eeb (%)
1
2
3
5
2
1
5
5
5
1.5
1.5
1.5
1.5
1.5
1.05
6
18
36
6
6
6
92
86
75
90
92
85
94
84
47
94
94
85
1
2
3
4
3
8
9
91
89
91
95
82
94
95
95
4d
5e
6
10
a
Isolated yield after column chromatography.
Determination by HPLC on the OD-H chiral column.
a
The reaction was carried out on a 1.0 mmol scale of benzaldehyde and 1.0 mL of
b
hexane.
b
c
Isolated yield after column chromatography.
Determination by HPLC on the OD-H chiral column.
Reverse addition sequence of diethylzinc and benzaldehyde.
Benzaldehyde was slowly added over 10 min.
d
e
showed excellent ee (entries 1 and 2). When the reaction was con-
ducted in the presence of 5 mol % of b-amino alcohol 10 without
solvent it showed no loss of enantioselectivity (entry 3). However,
when 2 mol % of ligand was used, the ee value dropped to 78% (en-
try 4). Interestingly, when the reaction was carried out at ambient
temperature, the presence of 2 mol % of ligand led to the corre-
sponding adduct with 93% ee and 90% yield in 15 min (entry 5).
There was no improvement in enantioselectivity when diethylzinc
in toluene was used, or the reaction was carried out at either 40 °C
or ꢀ10 °C (entries 6–8). Good enantioselectivity (91% ee) was ob-
tained with 1 mol % of b-amino alcohol 10 at the expense of a long-
er reaction time (entry 9). Therefore the reaction conditions in
entry 5 were utilized to study the scope of the reaction.
aromatic and aliphatic aldehydes, including linear aliphatic ones,
in 89–94% ee with 2 mol % of chiral ligand. The reaction required
only equimolar amounts of diethylzinc, and was completed in
15 min at ambient temperature. The development of b-amino alco-
hol 10 offers a simple and effective chiral induction in the diethyl-
zinc addition reaction for the preparation of chiral secondary
alcohols.
4. Experimental
In order to understand the application and limitation of the cat-
alytic system, aldehydes 11a–k were carefully examined (Table 4).
Optically active secondary alcohols with >91% ee were obtained in
the cases of aromatic aldehydes (entries 1–6). Alkenyl (entry 7) and
aliphatic aldehydes (entries 8–11) were also applicable in the sys-
tem. It is noteworthy that this methodology could be applied to
linear aliphatic aldehydes (entries 10 and 11).
The effect of the enantiomeric excess of the chiral ligand on the
enantiomeric excess of the adducts has been demonstrated to
show a positive non-linearity with either 5 mol % or 2 mol % of b-
amino alcohol 10 (Fig. 2).14 A higher level of (+)-non-linearity with
5 mol % of b-amino alcohol 10 was rationalized by the concentra-
tion of both the effective catalyst and the inactive dimer, which
are proportional to ligand loading.14d
4.1. General experimental procedure for the synthesis of
amino ketones 5–7
a-
A 10 mL round-bottomed flask containing
a-amino ketone 4
(0.10 g, 0.65 mmol) and potassium carbonate (0.20 g, 1.45 mmol)
was filled with argon and acetonitrile (2.5 mL) was added. After
the mixture was added to the corresponding dibromide
(0.70 mmol) and stirred at room temperature for 10 min, the mix-
ture was heated under reflux for 12 h, and the reaction was
stopped by the addition of water (5 mL). The mixture was then ex-
tracted with CH2Cl2 (5 mL ꢁ 3), and the combined organic solution
was dried over Na2SO4 and concentrated to give the crude product,
which was purified via column chromatography to yield the de-
sired a-amino ketone.
3. Conclusion
4.1.1. (1S)-7,7-Dimethyl-1-pyrrolidin-1-yl-bicyclo[2.2.1]
heptan-2-one 5
a 2D4
ꢂ
¼ þ45:2 (c 1.0, CHCl3); 1H NMR (400 MHz, CDCl3) d 3.08–
In conclusion, an effective chiral b-amino alcohol 10 for the
catalytic asymmetric addition of diethylzinc to aldehydes has been
demonstrated. The catalytic system could be applied to both
½
3.03 (m, 2H), 2.85–2.81 (m, 2H), 2.41–2.34 (m, 1H), 2.13 (dt,
J = 12.8, 3.2 Hz, 1H), 2.05–1.98 (m, 1H), 1.91 (t, J = 4.6 Hz, 1H),
.
CeCl3 7H2O (25 mol %)
dibromide
NaBH4, MeOH
K2CO3, MeCN
O
O
OH
(CH2)2
−78 ºC to −20 ºC to rt
reflux, 12 h
dibromide
H2N
N
X
N
(H2C)2
(H2C)2
(CH2)2
4
X
Br
5
6
7
X = - (85%)
8 X = - (78%)
Br
Br
X = CH2 (83%)
X = O (88%)
9 X = CH2 (86%)
10 X = O (88%)
Br
Br
O
Br
Scheme 1. Synthesis of b-amino alcohols bearing the isoborneol skeleton.

1558
Z.-L. Wu et al. / Tetrahedron: Asymmetry 20 (2009) 1556–1560
Table 3
(CH2), 22.0 (CH3), 19.7 (CH3); IR (neat) 2963 (s), 2876 (m), 1742
(s) cmꢀ1; HRMS calcd for C13H21NO 207.1623, found 207.1620.
Optimization of reaction conditions with b-amino alcohol 10 in different solventsa
OH
O
10
, solvent
Et2Zn (1.05 equiv)
(1.0 M in hexane)
+
4.1.2. (1S)-7,7-Dimethyl-1-piperidin-1-yl-bicyclo[2.2.1]heptan-
Ph
Et
Ph
H
temp, time
2-one 6
(R)
½
a 2D4
ꢂ
¼ þ91:4 (c 1.0, CHCl3); mp 78.0–79.0 °C; 1H NMR
Entry
10(mol %)
Solvent
Temp
(°c)
Time
(h)
Yieldb
(%)
eec
(%)
(400 MHz, CDCl3) d 2.90–2.82 (m, 2H), 2.78–2.70 (m, 2H), 2.42–
2.32 (m, 1H), 2.15 (dt, J = 12.6, 3.6 Hz, 1H), 2.00–1.90 (m, 1H),
1.88–1.78 (m, 2H), 1.58–1.46 (m, 5H), 1.45–1.39 (m, 2H), 1.36–
1.28 (m, 1H), 1.11 (s, 6H); 13C NMR (100 MHz, CDCl3) d 217.5 (C),
79.2 (C), 49.0 (CH2), 47.4 (C), 43.6 (CH), 43.0 (CH2), 26.8 (CH2),
26.3 (CH2), 25.7 (CH2), 24.5 (CH2), 23.3 (CH3), 21.1 (CH3); IR (neat)
2971 (w), 2926 (m), 1739 (s) cmꢀ1; HRMS calcd for C14H23NO
221.1780, found 221.1792.
1
2
3
5
5
5
2
2
2
2
2
1.0 mL of pentane
1.0 mL of heptane
0
0
0
0
25
25
40
ꢀ10
25
25
2
2
2
6
92
91
86
82
90
87
85
85
88
84
94
94
94
78
93
91
81
69
91
18
—
—
—
—
—
—
—
—
4
5
15 min
15 min
5 min
1
1
12
6d
7
8
9
10
1
0.5
4.1.3. (1S)-7,7-Dimethyl-1-morpholin-4-yl-bicyclo[2.2.1]-
a
heptan-2-one 7
The reaction was carried out on a 1.0 mmol scale of benzaldehyde.
Isolated yield after column chromatography.
Determination by HPLC on the OD-H chiral column.
Et2Zn (1.0 M in toluene) was used.
½
a 2D4
ꢂ
¼ þ82:5 (c 1.0, CHCl3); mp 89.5–90.5 °C; 1H NMR
b
c
(400 MHz, CDCl3) d 3.63 (t, J = 4.8 Hz, 4H), 3.00–2.90 (m, 2H),
2.81–2.76 (m, 2H), 2.39–2.33 (m, 1H), 2.08 (dt, J = 12.4, 3.6 Hz,
1H), 2.00–1.92 (m, 1H), 1.85–1.80 (m, 2H), 1.57–1.50 (m, 1H),
1.34–1.31 (m, 1H), 1.09 (s, 3H), 1.08 (s, 3H); 13C NMR (100 MHz,
CDCl3) d 217.1 (C), 78.6 (C), 67.7 (CH2), 48.5 (CH2), 47.5 (C), 43.8
(CH), 43.1 (CH2), 26.0 (CH2), 25.8 (CH2), 23.3 (CH3), 21.0 (CH3); IR
(neat) 2958 (s), 2889 (m), 2850 (s), 1743 (s) cmꢀ1; HRMS calcd
for C13H21NO2 223.1572, found 223.1567.
d
Table 4
Asymmetric addition of diethylzinc to aldehydes catalyzed by b-amino alcohol 10
OH
O
10 ( 2 mol %)
Et2Zn
+
R
H
25 ºC, 15 min
R
Et
12a−k
Yielda (%)
(1.0 M in hexane)
11a−k
4.2. General experimental procedure for the synthesis of
Entry
R
eeb (%)
a
-amino alcohols 8–10
1
2
3
4
5
6
7
8
9
3-F-Ph 11a
3-Cl-Ph 11b
2-Me-Ph 11c
3-Me-Ph 11d
95
93
95
94
97
94
96
89
90
90
96
93
92
92
91
94
91
92
92
93c
94d
89d
A 25 mL round-bottomed flask containing the
a-amino ketone
.
(0.45 mmol), CeCl3 7H2O (0.11 mmol), and methanol (3 mL) was
cooled to ꢀ78 °C. Following the addition of NaBH4 (2.11 mmol),
the flask was slowly warmed to ꢀ20 °C. After 2 h at ꢀ20 °C, the
flask was slowly warmed to room temperature, and was kept at
ambient temperature for 6 h. The solvents were then removed in
vacuo, and to the residue was added water (15 mL) and extracted
with CH2Cl2 (15 mL ꢁ 3). The organic solution was combined, dried
over Na2SO4, and concentrated to give the crude product, which
was purified by column chromatography to yield the pure b-amino
alcohol.
3-MeO-Ph 11e
1-Naphthyl 11f
(2-Me-cinnamaldehyde) 11g
(Hydrocinnamaldehyde) 11h
Cyclohexyl 11i
10-Decenyl 11j
Pentyl 11k
10
11
a
Isolated yield after column chromatography.
Determination by chiral HPLC.
The ee was determined via its benzoyl ester.
The ee was determined via its p-nitrobenzoyl ester.
b
c
d
4.2.1. (1S, 2R)-7,7-Dimethyl-1-pyrrolidin-1-yl-bicyclo[2.2.1]-
heptan-2-ol 8
½
a 2D4
ꢂ
¼ þ1:2 (c 1.0, CHCl3); 1H NMR (400 MHz, CDCl3) d 3.97
(br, 1H), 3.66 (dd, J = 7.8, 3.0 Hz, 1H), 2.67–2.62 (m, 2H), 2.55–
2.50 (m, 2H), 1.90–1.85 (m, 1H), 1.81–1.60 (m, 7H), 1.51 (t,
J = 4.4 Hz, 1H), 1.16–1.06 (m, 1H), 1.10 (s, 3H), 1.03–0.96 (m,
1H), 0.99 (s, 3H); 13C NMR (100 MHz, CDCl3) d 75.1 (CH), 70.1
(C), 47.0 (CH2), 46.3 (C), 45.7 (CH), 38.4 (CH2), 26.1 (CH2), 22.9
(CH2), 22.8 (CH3), 20.7 (CH2), 20.1 (CH3); IR (neat) 3422 (br),
2958 (s), 2877 (s), 2821 (m) cmꢀ1; HRMS calcd for C13H23NO
209.1780, found 209.1774.
4.2.2. (1S, 2R)-7,7-Dimethyl-1-piperidin-1-yl-bicyclo[2.2.1]-
heptan-2-ol 9
½
a 2D4
ꢂ
¼ þ14:2 (c 1.0, CHCl3); mp 88.5–89.5 °C; 1H NMR
(400 MHz, CDCl3) d 3.72 (d, J = 5.2 Hz, 1H), 2.58 (br, 4H), 1.90–
1.70 (m, 3H), 1.68–1.36 (m, 8H), 1.18–0.98 (m, 2H), 1.14 (s, 3H),
1.07 (s, 3H); 13C NMR (100 MHz, CDCl3) d 73.6 (CH), 72.8 (C),
48.4 (CH2), 46.7 (CH), 45.9 (C), 37.9 (CH2), 26.7 (CH2), 26.3 (CH2),
24.4 (CH2), 24.0 (CH3), 22.3 (CH2) 20.3 (CH3); IR (neat) 3329 (br),
2958 (s), 2932 (s), 2805 (w) cmꢀ1; HRMS calcd for C14H25NO
223.1936, found 223.1945.
Figure 2. Nonlinear effect study of b-amino alcohol 10.
1.86–1.67 (m, 6H), 1.40–1.33 (m, 1H), 1.08 (s, 3H), 1.06 (s, 3H);
13C NMR (100 MHz, CDCl3) d 217.4 (C), 77.0 (C), 48.0 (CH2),
46.9 (C), 42.8 (CH), 42.6 (CH2), 27.7 (CH2), 25.9 (CH2), 24.1

Z.-L. Wu et al. / Tetrahedron: Asymmetry 20 (2009) 1556–1560
1559
4.2.3. (1S, 2R)-7,7-Dimethyl-1-morpholin-4-yl-
4.3.10. 4-Nitro-benzoic acid1-ethyl-undec-10-enyl ester (4-nitro-
benzoyl ester of alcohol 12j)
Chiracel OB, UV 254 nm, isopropanol/hexanes (1:400), 0.5 mL/
min. tR = 25.7 min (2.9% for S), 30.6 min (97.1% for R); 94% ee.
bicyclo[2.2.1]heptan-2-ol 10
½
a 2D4
ꢂ
¼ þ11:0 (c 1.0, CHCl3); mp 35.0–36.0 °C; 1H NMR
(400 MHz, CDCl3) d 3.74–3.66 (m, 5H), 2.67–2.61 (m, 2H), 2.57–
2.50 (m, 2H), 1.92–1.76 (m, 3H), 1.69–1.62 (m, 1H), 1.52 (t,
J = 4.6 Hz, 1H), 1.18–1.00 (m, 2H), 1.14 (s, 3H), 1.06 (s, 3H); 13C
NMR (100 MHz, CDCl3) d 72.8 (CH), 71.8 (C), 66.7 (CH2), 47.2
(CH2), 46.0 (CH), 45.3 (C), 37.5 (CH2), 25.7 (CH2), 23.3 (CH3),
21.7 (CH2), 19.8 (CH3); IR (neat) 3415 (br), 2956 (s), 2884 (s),
2850 (m) cmꢀ1; HRMS calcd for C13H23NO2 225.1729, found
225.1713.
4.3.11. 4-Nitro-benzoic acid 1-ethyl-hexyl ester (4-nitro-benzoyl
ester of alcohol 12k)
Chiracel OJ, UV 254 nm, isopropanol/hexanes (1:400), 0.5 mL/
min. tR = 14.3 min (5.6% for S), 16.0 min (94.4% for R); 89% ee.
Acknowledgment
We thank the National Science Council, Republic of China, for
the financial support.
4.3. General procedure for the asymmetric addition of
diethylzinc with aldehydes catalyzed by b-amino alcohol 10
To a 10 mL round-bottomed flask containing ligand 10 (4.5 mg,
0.02 mmol) was added diethylzinc solution (1.05 mmol, 1.0 M in
hexane) at room temperature. After being stirred at room temper-
ature for 5 min, the aldehyde (1.0 mmol) was added to the mixture.
The reaction was stopped after 15 min by the addition of aqueous
NH4Cl (3 mL, 1 M solution). The mixture was extracted with ether
(10 mL ꢁ 3), and the combined organic solution was dried over
Na2SO4, and concentrated to give the crude product, which was
purified by column chromatography to yield the corresponding
secondary alcohol. The ee value was determined by HPLC on a chi-
ral stationary phase.
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4.3.2. 1-(3-Chloro-phenyl)-propan-1-ol 12b
Chiracel OD-H, UV 254 nm, isopropanol/hexanes (1:99), 0.5 mL/
min. tR = 38.7 min (4.2% for S), 40.5 min (95.8% for R); 92% ee.
4.3.3. 1-o-Tolyl-propan-1-ol 12c
Chiracel OB, UV 254 nm, isopropanol/hexanes (1:99), 0.5 mL/
min. tR = 12.0 min (3.8% for S), 13.5 min (96.2% for R); 92% ee.
6. For recent examples of using norbornane based ligands in diethylzinc addition
reactions: (a) Hari, Y.; Aoyama, T. Synthesis 2005, 583; (b) García Martínez, A.;
Teso Vilar, E.; García Fraile, A.; de la Moya Cerero, S.; Martínez-Ruiz, P.; Villas, P.
C. Tetrahedron: Asymmetry 2002, 13, 1; (c) García Martínez, A.; Teso Vilar, E.;
García Fraile, A.; de la Moya Cerero, S.; Lora Maroto, B. Tetrahedron: Asymmetry
2003, 14, 1959; (d) García Martínez, A.; Teso Vilar, E.; García Fraile, A.; de la
Moya Cerero, S.; Lora Maroto, B. Tetrahedron: Asymmetry 2004, 15, 753; (e)
García Martínez, A.; Teso Vilar, E.; García Fraile, A.; de la Moya Cerero, S.; Lora
Maroto, B. Tetrahedron 2005, 61, 3055; (f) García Martínez, A.; Teso Vilar, E.;
García Fraile, A.; de la Moya Cerero, S.; Martínez-Ruiz, P.; Díaz Morillo, C.
Tetrahedron: Asymmetry 2007, 18, 742; (g) de Oliveira, L. F.; Costa, V. E. U.
Tetrahedron: Asymmetry 2004, 15, 2583; (h) Martins, J. E. D.; Mehlecke, C. M.;
Gamba, M.; Costa, V. E. U. Tetrahedron: Asymmetry 2006, 17, 1817.
7. For examples of using norbornane based ligands catalyzed asymmetric
reactions developed by our group: (a) Chang, C.-W.; Yang, C.-T.; Hwang, C.-
D.; Uang, B.-J. Chem. Commun. 2002, 54; (b) Wu, H.-L.; Uang, B.-J. Tetrahedron:
Asymmetry 2002, 13, 2625; (c) Uang, B.-J.; Fu, I.-P.; Hwang, C.-D.; Chang, C.-W.;
Yang, C.-T.; Hwang, D.-R. Tetrahedron 2004, 60, 10479; (d) Wu, P.-Y.; Wu, H.-L.;
Uang, B.-J. J. Org. Chem. 2006, 71, 833; (e) Wu, H.-L.; Wu, P.-Y.; Uang, B.-J. J. Org.
Chem. 2007, 72, 5935; (f) Wu, H.-L.; Wu, P.-Y.; Uang, B.-J. J. Org. Chem. 2008, 73,
6445.
8. (a) Kloetzing, R. J.; Thaler, T.; Knochel, P. Org. Lett. 2006, 8, 1125; (b) Oppolzer,
W.; Radinov, R. N.; El-Sayed, E. J. Org. Chem. 2001, 66, 4766; (c) Dosa, P. I.; Fu, G.
C. J. Am. Chem. Soc. 1998, 120, 445; (d) Oppolzer, W.; Radinov, R. N.; De
Brabander, J. Tetrahedron Lett. 1995, 36, 2607; (e) Oppolzer, W.; Radinov, R. N. J.
Am. Chem. Soc. 1993, 115, 1593.
9. (a) Kim, J. G.; Walsh, P. J. Angew. Chem., Int. Ed. 2006, 45, 4175; (b) Kelly, A. R.;
Lurain, A. E.; Walsh, P. J. J. Am. Chem. Soc. 2005, 127, 14668; (c) Jeon, S.-J.; Chen,
Y. K.; Walsh, P. J. Org. Lett. 2005, 7, 1729; (d) Lurain, A. E.; Carroll, P. J.; Walsh, P.
J. J. Org. Chem. 2005, 70, 1262; (e) Lurain, A. E.; Maestri, A.; Kelly, A. R.; Carroll,
P. J.; Walsh, P. J. J. Am. Chem. Soc. 2004, 126, 13608; (f) Lurain, A. E.; Walsh, P. J. J.
Am. Chem. Soc. 2003, 125, 10677; (g) García, C.; Libra, E. R.; Carroll, P. J.; Walsh,
P. J. J. Am. Chem. Soc. 2003, 125, 3210; (h) Chen, Y. K.; Lurain, A. E.; Walsh, P. J. J.
Am. Chem. Soc. 2002, 124, 12225; (i) Nugent, W. A. Chem. Commun. 1999, 1369.
4.3.4. 1-m-Tolyl-propan-1-ol 12d
Chiracel OD-H, UV 254 nm, isopropanol/hexanes (1:99), 0.5 mL/
min. tR = 9.4 min (95.6% for R), 11.9 min (4.4% for S); 91% ee.
4.3.5. 1-(3-Methoxy-phenyl)-propan-1-ol 12e
Chiracel OD-H, UV 254 nm, isopropanol/hexanes (2:98), 0.5 mL/
min. tR = 21.5 min (97.0% for R), 24.0 min (3.0% for S); 94% ee.
4.3.6. 1-Naphthalen-1-yl-propan-1-ol 12f
Chiracel OD-H, UV 254 nm, isopropanol/hexanes (2:98), 1.0 mL/
min. tR = 21.7 min (4.3% for S), 42.7 min (95.7% for R); 91% ee.
4.3.7. 2-Methyl-1-phenyl-pent-1-en-3-ol 12g
Chiracel OD-H, UV 254 nm, isopropanol/hexanes (2:98), 1.0 mL/
min. tR = 12.6 min (95.9% for R), 14.1 min (4.1% for S); 92% ee.
4.3.8. 1-Phenyl-pentan-3-ol 12h
Chiracel OD-H, UV 254 nm, isopropanol/hexanes (2:98), 1.0 mL/
min. tR = 16.5 min (96.2% for R), 27.8 min (3.8% for S); 92% ee.
4.3.9. Benzoic acid 1-cyclohexyl-propyl ester (benzoyl ester of
alcohol 12i)
Chiracel AD-H, UV 254 nm, isopropanol/hexanes (1:99), 0.3 mL/
min. tR = 14.1 min (96.5% for R), 17.0 min (3.5% for S); 93% ee.

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2008, 19, 19; (b) Parrott, R. W., II; Dore, D. D.; Chandrashekar, S. P.;
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19, 607; (c) Szatmári, I.; Sillanpää, R.; Fülöp, F. Tetrahedron: Asymmetry
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Tetrahedron: Asymmetry 2008, 19, 1572; (e) Yang, X.-F.; Hirose, T.; Zhang,
G.-Y. Tetrahedron: Asymmetry 2008, 19, 1670; (f) Grach, G.; Reboul, V.;
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