Diphenylamine-derived bis-hydroxyamide catalyzed asymmetric borane reduction of prochiral ketones

Article abstract of DOI:10.1016/j.tetasy.2009.02.057

A series of bis-hydroxyamides were synthesized from diphenylamine-2,2′-dicarboxylic acid and chiral aminoalcohols. Their catalytic activity in asymmetric borane reduction was investigated. After the fine optimization of solvents, temperature, amount of borane complex, and the length of catalyst generating period, good to excellent yields (55-99%) and enantioselectivities (79-97% ee) can be achieved in the reduction of aromatic and alkyl prochiral ketones. A transition state structure was proposed on the basis of absolute configuration and controlled experiment.

Full text of DOI:10.1016/j.tetasy.2009.02.057

Tetrahedron: Asymmetry 20 (2009) 605–609
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Diphenylamine-derived bis-hydroxyamide catalyzed asymmetric borane
reduction of prochiral ketones
Jin Wang a, Han Liu a, Da-Ming Du a,b,
*
a Beijing National Laboratory for Molecular Sciences (BNLMS), Key Laboratory of Bioorganic Chemistry and Molecular Engineering,
College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, PR China
b School of Chemical Engineering and Environment, Beijing Institute of Technology, Beijing 100081, PR China
a r t i c l e i n f o
a b s t r a c t
A series of bis-hydroxyamides were synthesized from diphenylamine-2,20-dicarboxylic acid and chiral
aminoalcohols. Their catalytic activity in asymmetric borane reduction was investigated. After the fine
optimization of solvents, temperature, amount of borane complex, and the length of catalyst generating
period, good to excellent yields (55–99%) and enantioselectivities (79–97% ee) can be achieved in the
reduction of aromatic and alkyl prochiral ketones. A transition state structure was proposed on the basis
of absolute configuration and controlled experiment.
Article history:
Received 19 January 2009
Accepted 17 February 2009
Available online 22 April 2009
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
activity in the asymmetric borane reduction of prochiral ketones.
Herein, we would like to document the recent results.
Asymmetric borane reduction of prochiral ketones is one of the
most important methods for the construction of chiral secondary
alcohols.1 After Itsuno et al.’s pioneering work in this field in the
early 1980s,2 a plethora of catalytic systems have been investi-
gated. Among them, the CBS (Corey–Bakshi–Shibata) system devel-
oped by Corey et al. in 19873 attracts the most attention from the
scientific community, for its excellent enantioselectivity and easy
preparation from chiral amino alcohols. In addition to CBS system,
other active catalysts derived from amino alcohols, such as chiral
phosphinamido alcohols,4 phosphoramido alcohols,5 and sulfon-
amide alcohols,6 have also been developed.
N
H
N
H
HN
Ph
O
OH
O
HO
NH
Ph
HN
Ph
O
O
NH
Ph
OH HO
Ph
Ph
Ph
Ph
1
2
As important intermediates in the preparation of chiral oxazo-
line ligands,7 thiazoline ligands,8 and imidazoline ligands,9 many
chiral b-hydroxyamides have been synthesized from carboxylic
acids and amino alcohols. Considering the potential coordination
and H-bond donation ability of b-hydroxyamides, some of them
have been applied to asymmetric catalysis as ligands or catalysts.
A variety of enantioselective transformations, such as the alkyl-
ation of aldehydes,10 alkynylation of aldehdyes,11 Michael addi-
tions,12 Nozaki–Hiyama reaction,13 kinetic resolution of racemic
alcohols,14 conjugate radical addition,15 hydrosilylation of imine-
s,16and borane reduction of ketones,17 can be catalyzed by C1, C2,
or C3 symmetric b-hydroxyamides. As part of our project on the
development of diphenylamine-based chiral ligands,8b,18 we syn-
thesized chiral bis(b-hydroxyamide) compounds 1–4 (Fig. 1) from
commercially available amino alcohols and tested their catalytic
N
H
N
H
O
N
N
O
HN
O
O
NH
OH HO
HO
Ph
OH
Ph
Ph
Ph
3
4
Figure 1. Diphenylamine-based bis(b-hydroxyamide) ligands.
2. Results and discussion
Chiral bis(b-hydroxyamide) ligands 1–3 have already been pub-
lished.8b,18c,d Considering the privileged structure of (S)-2-diph-
enylhydroxymethylpyrrolidine in the CBS and related systems,
we synthesized ligand 4 in two steps in 80% yield, as illustrated
in Scheme 1.
* Corresponding author. Tel./fax: +86 10 68914985.
E-mail addresses: dudm@bit.edu.cn, dudm@pku.edu.cn (D.-M. Du).
0957-4166/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2009.02.057

606
J. Wang et al. / Tetrahedron: Asymmetry 20 (2009) 605–609
Ph
Ph
OH
N
H
N
H
SOCl2
N
O
O
N
N
H
reflux 4h
5 eq. TEA
DCM
OH
Ph
HO
Ph
CO2H
CO2H
rt 7 days
Ph
Ph
4
80% for two steps
Scheme 1. Synthesis of ligand 4 from diphenyl-2,20-dicarboxylic acid.
With the desired ligands in hand, we tested their catalytic activ-
Table 2
Optimization of solvents and reaction temperaturea
ity in the asymmetric borane reduction of prochiral ketone. The
reaction was conducted in toluene at 50 °C under the catalysis of
10 mol % ligand, using 1.2 equiv of BH3–THF complex and 1-acetyl-
naphthalene 5a as model substrate. The ligand and borane com-
plex were stirred together under argon for 1 h at 50 °C in order
to generate the active catalyst. The effect of the length of this per-
iod on enantioselectivity will be discussed later (vide infra). Full
conversion of the substrate can be achieved in 3 h. As shown in
Table 1, ligand 4 gave much better enantioselectivity as well as
comparable yield, and was chosen for further optimization.
Entry
Solvent
Temp (°C)
Yieldb (%)
eec (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
THF
DCM
50
50
50
0
25
50
70
90
0
25
50
65
0
25
50
65
93
100
95
89
90
92
90
73
90
94
94
95
90
91
89
92
84
83
90
67
91
91
93
90
88
94
97
96
92
97
97
96
Benzene
Toluene
Toluene
Toluene
Toluene
Toluene
c-Hexane
c-Hexane
c-Hexane
c-Hexane
n-Hexane
n-Hexane
n-Hexane
n-Hexane
Table 1
Screening of ligandsa
HO
O
CH3
CH3
1.2 eq. BH3 THF
a
All the reactions were conducted on a 0.5 mmol scale using 10 mol % of 4 as
10 mol% cat.
ligand and 1-acetylnaphthalene as model substrate.
b
50 ºC toluene
Isolated yield.
c
5a
Determined by HPLC on Chiracel OJ-H column with n-hexane and 2-propanol
6a
70:30 as eluents at 254 nm.
Entry
Ligand
Yieldb (%)
eec (%)
1
2
3
4
1
2
3
4
87
93
92
92
23
51
46
91
complex and the catalyst loading in the reaction, as well as the
reaction temperature that we had optimized before. As depicted
in Table 3, when the catalyst loading was reduced from 10 mol %
to 5 mol % and 1 mol %, the enantioselectivity decreased drastically
from 97% to 87% and 37%. Increasing the amount of borane com-
plex from 1.2 to 1.4 equiv also caused a lower ee. The behavior of
our system is in accord with the predictable effect of background
reduction.
a
All the reactions were conducted on a 0.5 mmol scale in toluene at 50 °C using
10 mol % of ligand and 1-acetylnaphthalene as model substrate.
b
Isolated yield.
c
Determined by HPLC on Chiracel OJ-H column with n-hexane and 2-propanol
70:30 as eluents at 254 nm.
For further improvement of the enantioselectivity, we finely
optimized the solvents and reaction temperature. 1-Acetylnaph-
thalene was also used as model substrate in this screening. The
results are depicted in Table 2. Toluene, benzene, n-hexane, and
c-hexane gave good yields and enantioselectivities (higher than
90%) at 50 °C. Though hexane isomers gave better results than tol-
uene, the temperature optimization was conducted with all the
three solvents. Benzene was abandoned for its toxicity. The tem-
perature of the reaction mixture was raised or reduced to desired
value after the 1 h catalyst generating period at 50 °C before the
addition of substrate. When the temperature was varied from
0 °C to 65 °C (to 90 °C for toluene), the enantioselectivity was not
affected significantly, except for the case of toluene at 0 °C. Gener-
ally, n- and c-hexane gave better results than toluene, and the best
result can be achieved at 50 °C. Considering the better solubility of
the substrates and ligands in c-hexane, it became the solvent of
choice. No further optimization was observed when the borane
source was changed to BH3ꢀSMe2 complex (90% yield and 86%
ee). Another factor that can affect the enantioselectivity is the
background reduction,19 which is related to the amount of borane
Table 3
Effect of catalyst loading and amount of borane complexa
Entry
Loading (mol %)
Borane amount (equiv)
Yieldb (%)
eec (%)
1
2
3
4
10
5
1
1.2
1.2
1.2
1.4
94
93
93
97
97
87
37
88
10
a
All the reactions were conducted on a 0.5 mmol scale at 50 °C in c-hexane using
10 mol % of 4 as ligand and 1-acetylnaphthalene as a model substrate.
b
Isolated yield.
c
Determined by HPLC on Chiracel OJ-H column with n-hexane and 2-propanol
70:30 as eluents at 254 nm.
We also tested the effect of the catalyst generating period. As
shown in Table 4, when the length of the period was prolonged
to 1.5 h or shortened to 0.5 h, the results were not affected, thus
indicating the rapid generation of the active catalyst in our system.
With the optimized conditions in hand, we tested ligand 4 in
the asymmetric borane reduction of differently substituted aro-
matic ketones. The results are listed in Table 5. Excellent yields

J. Wang et al. / Tetrahedron: Asymmetry 20 (2009) 605–609
607
Table 4
cated the synergetic mode of interaction between the two pyrrol-
idine subunits. On the basis of the absolute configuration and our
knowledge about the diphenylamine skeleton, a transition state
was postulated to interpret the origin of the enantioselectivity.
As illustrated in Figure 3, the active catalyst is generated from
1 equiv of borane and ligand 4. Two equivalents of H2 are extruded
during this process. A molar of ketone and another molar of borane
coordinate to the catalyst to form the reactive complex. In the tran-
sition state, the large group RL directs to the outer side and the hy-
dride attacks the carbonyl group from the Si face.
Effect of the length of catalyst generating perioda
Entry
Catalyst generating period (h)
Yieldb (%)
eec (%)
1
2
3
0.5
1
1.5
94
94
95
95
97
94
a
All the reactions were conducted in 0.5 mmol scale at 50 °C after the catalyst
generating period in c-hexane, using 10 mol % of 4 as ligand and 1-acetylnaph-
thalene as model substrate.
b
Isolated yield.
c
Determined by HPLC on Chiracel OJ-H column with n-hexane and 2-propanol
70:30 as eluents at 254 nm.
Ph
Ph
OH
N
and enantioselectivities can be achieved in the cases of both elec-
tron-donating groups and electron-withdrawing groups substi-
tuted onto the aromatic ketones. Generally, electron-deficient
ketones gave better results than electron-rich ketones. Such a ten-
dency can be interpreted through Hammond’s hypothesis. Higher
N
H
N
O
O
N
O
OH
Ph
HO
Ph
Ph
Ph
7
electron deficiency will cause larger ꢁDH for the hydride transfer
4
20 mol %
process, which is considered to be the rate-determining step. Thus,
a starting-material-like transition state will be favored and the
transfer of stereochemical information between material (the com-
plex containing ligand 4, ketone, and borane) and product will be
better. In the case of propiophenone, 90% ee can still be obtained,
although the stereochemical differences between phenyl and ethyl
are smaller. The diaryl ketone and dialkyl ketone were also tested
in this reaction. Moderate enantioselectivities were obtained. The
absolute configuration of the products was determined to be (R)
in most cases through comparison of the specific rotation values
with the literature data.5,6 The opposite configuration of diaryl-
10 mol %
97% ee
92% ee
Figure 2. Control experiment using mono-b-hydroxyamide ligand.
N
H
RL
RS
BO
N
H
H2
H
O
O
B
O
O
methanol 6m may be attributed to the p–p stacking effect between
the naphthyl and the ligand skeleton which overwhelm the steric
N
effect.
To obtain more information about the catalytic system, we pre-
pared
(S)-N-benzoyl-2-diphenylhydroxymethylpyrro-lidine
7
(Fig. 2). When this compound was used as a ligand (20 mol %
was added to keep an equal amount of the pyrrolidine subunit to
the original system) in the reduction of 1-acetylnaphthalene under
the same conditions, the ee value decreased to 92%, which indi-
Figure 3. Proposed transition state of the reaction.
3. Conclusion
In conclusion, we have developed a novel diphenylamine-de-
rived bis(b-hydroxyamide) ligand 4 which can be easily prepared
fromdiphenylamine-2,20-dicarboxylicacidand(S)-2-diphenylhydr-
oxymethylpyrrolidine in two steps. This ligand show high catalytic
activity in the asymmetric borane reduction of aromatic prochiral
ketones. Excellent yields and enantioselectivities can be achieved
after the optimization solvent, reaction temperature, amount of
borane complex, and the length of catalyst generating period.
The transition state of the hydride transfer step was postulated
on the basis of absolute configuration of the products, and the re-
sult of control experiment using ligand 7. Further development of
diphenylamine derived chiral ligands is ongoing in our laboratory.
Table 5
Asymmetric borane reduction of aromatic ketonesa
OH
O
1.2 eq. BH3 THF
R1
R1
R2
R2
10 mol% 4
º
50 C, c-hexane
Entry
R1
R2
Product
Yieldb (%)
eec (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
1-Naphthyl
C6H5
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Et
6a
6b
6c
6d
6e
6f
6g
6h
6i
94
87
93
93
95
95
85
90
84
96
99
85
86
55
97 (R)
96 (R)
90 (R)
93 (R)
95 (R)
90 (R)
97 (R)
95 (R)
97 (R)
90 (R)
91 (R)
90 (R)
81 (S)
79 (R)
4-MeC6H4
4-MeOC6H4
3-MeOC6H4
2-MeOC6H4
4-FC6H4
4-ClC6H4
4-BrC6H4
2-BrC6H4
4-NO2C6H4
C6H5
4. Experiment
4.1. General
6j
6k
6l
Commercially available compounds were used without further
purification. Solvents were dried according to standard procedures.
Column chromatography was carried out using silica gel (200–300
mesh). Melting points were measured on a Yanaco melting point
apparatus and were uncorrected. The 1H NMR spectra were re-
corded on Bruker 300 MHz spectrometer, while the 13C NMR spec-
tra were recorded at 75 MHz. Infrared spectra were obtained on a
Nicolet AVATAR 330 FT-IR spectrometer. Mass spectra were
obtained on a Bruker Apex IV (ESI) mass spectrometer. Optical
1-Naphthyl
c-C6H11
C6H5
Me
6m
6n
a
All the reactions were conducted on a 0.5 mmol scale at 50 °C in c-hexane under
the catalysis of 10 mol % 4.
b
Isolated yield.
c
Determined by HPLC on Chiracel columns with chiral stationary phase. For 6n,
transformation to its carbamate is needed for HPLC analysis.

608
J. Wang et al. / Tetrahedron: Asymmetry 20 (2009) 605–609
rotations were measured on a Perkin–Elmer 341 LC spectrometer.
The enantiomeric excesses (ee) of the products were determined
by chiral HPLC analysis using Aglient HP 1100 instrument (n-hex-
ane/2-propanol as eluent).
Product 6e was obtained as a colorless oil (72 mg, 95% yield).
The ee was determined by HPLC on Chiracel OB column (n-hexane:
2-propanol 95:5, 1.0 mL/min, 254 nm, tminor = 15.1 min, tmajor
=
20.1 min). ½a 2D0
¼ þ27:2 (c 3.8, DCM, 95% ee).
ꢂ
Product 6f was obtained as a colorless oil (72 mg, 95% yield).
The ee was determined by HPLC on Chiracel OB column (n-hexane:
4.2. Synthesis of 1,10-(diphenylamine-2,20-dicarbonyl)-bis[(2S)-
a
,
a
-diphenyl-2-pyrrolidinemethanol] 4
2-propanol 98:2, 0.8 mL/min, 254 nm, tminor = 15.0 min, tmajor =
15.6 min). ½a 2D0
¼ þ20:3 (c 3.0, DCM, 90% ee).
ꢂ
To a 50 mL round-bottomed flask were added diphenylamine-
Product 6g was obtained as a colorless oil (59 mg, 85% yield).
The ee was determined by HPLC on Chiracel OB column (n-hexane:
2,20-dicarboxylic acid (2.57 g, 10 mmol) and thionyl chloride
(10 mL). After being refluxed for 4 h, the excess thionyl chloride
was removed under vacuum. The yellowish solid residue (diphe-
nylamine-2,20-dicarbonyl dichloride) was dissolved in dichloro-
methane (DCM) (70 mL). To another 250 mL round-bottomed
flask were added (S)-2-diphenylhydroxymethylpyrrolidine (6.08
g, 24 mmol), Et3N (7.0 mL, 50 mmol), and DCM (30 mL). After being
cooled to 0 °C, the solution of the dichloride in DCM was added
dropwise. After the addition, the temperature was allowed to reach
25 °C and the mixture was stirred at this temperature for further
7 days for the full conversion of material (monitored by TLC). The
reaction was quenched by water. The mixture was washed with
satd NaHCO3 (aq) and water, dried with Na2SO4, and concentrated
under vacuum. The product was purified by column chromatogra-
phy using DCM/methanol 400:1 (V/V) as eluent. The pure bis(b-
hydroxyamide) 4 was obtained as a white solid (5.82 g, 80% yield).
2-propanol 98:2, 0.8 mL/min, 254 nm, tminor = 13.5 min, tmajor
=
14.4 min). ½a 2D0
¼ þ26:5 (c 3.2, DCM, 97% ee).
ꢂ
Product 6h was obtained as a colorless oil (70 mg, 90% yield).
The ee was determined by HPLC on Chiracel OB column (n-hexane:
2-propanol 98:2, 0.8 mL/min, 254 nm, tminor = 14.2 min, tmajor
=
14.6 min). ½a 2D0
¼ þ36:6 (c 2.6, DCM, 96% ee).
ꢂ
Product 6i was obtained as colorless oil (84 mg, 84% yield). The
ee was determined by HPLC on Chiracel OB column (n-hexane:
2-propanol 98:2, 0.8 mL/min, 254 nm, tminor = 15.2 min, tmajor
=
15.6 min). ½a 2D0
¼ þ31:6 (c 3.9, DCM, 97% ee).
ꢂ
Product 6j was obtained as a colorless oil (97 mg, 96% yield).
The ee was determined by HPLC on Chiracel OB column (n-hexane:
2-propanol 98:2, 0.8 mL/min, 254 nm, tminor = 11.2 min, tmajor
=
13.8 min). ½a 2D0
¼ þ39:3 (c 4.3, DCM, 90% ee).
ꢂ
Product 6k was obtained as colorless oil (83 mg, 99% yield). The
ee was determined by HPLC on Chiracel OB column (n-hexane:
Mp 178–180 °C. ½a D20
ꢂ
¼ ꢁ98:0 (c 0.5, DCM). 1H NMR (300 MHz,
CDCl3): d = 1.30–1.40 (m, 2H), 1.46–1.58 (m, 2H), 1.92–2.02 (m,
2H), 2.14–2.20 (m, 2H), 2.84 (dd, J1 = 17.1 Hz, J2 = 9.9 Hz, 2H),
3.33 (t, J = 8.1 Hz, 2H), 5.53 (t, J = 8.1 Hz, 2H), 6.64 (s, 2H), 6.76–
6.83 (m, 4H), 7.16–7.37 (m, 16H), 7.49 (d, J = 6.9 Hz, 4H), 7.63 (d,
J = 6.3 Hz, 4H), 8.52 (s, 1H). 13C NMR (75 MHz, CDCl3): d = 24.2,
29.5, 51.7, 66.7, 82.4, 117.6, 120.0, 125.0, 127.1, 127.2, 127.4,
127.8, 127.9, 128.0, 128.5, 130.4, 140.5, 143.1, 145.2, 172.0. IR:
3289, 3058, 1613, 1580, 1508, 1448, 1411, 1306, 1200, 1161,
1031, 751, 702 cmꢁ1. HRMS (ESI) calcd for C48H46N3O4 (M+H):
728.34828, found: 728.35103.
2-propanol 98:2, 0.8 mL/min, 254 nm, tminor = 54.0 min, tmajor =
55.6 min). ½a 2D0
¼ þ23:8 (c 3.5, DCM, 91% ee).
ꢂ
Product 6l was obtained as a colorless oil (57 mg, 85% yield).
The ee was determined by HPLC on Chiracel OD-H column (n-hex-
ane: 2-propanol 95:5, 1.0 mL/min, 254 nm, tmajor = 7.1 min, tminor
=
8.4 min). ½a 2D0
¼ þ20:2 (c 1.0, DCM, 90% ee).
ꢂ
Product 6m was obtained as a colorless oil (100 mg, 86% yield).
The ee was determined by HPLC on Chiracel OD-H column (n-hex-
ane: 2-propanol 90:10, 1.0 mL/min, 254 nm, tmajor = 12.0 min,
tminor = 24.5 min). ½a D20
¼ ꢁ46:0 (c 1.0, DCM, 90% ee).
ꢂ
Product 6n was obtained as colorless oil (35 mg, 55% yield). The
ee was determined by HPLC on Chiracel OD-H column (n-hexane:
2-propanol 98:2, 1.0 mL/min, 254 nm, tmajor = 7.0 min, tminor = 7.8 -
min) after being transformed to the carbamate using phenylisothi-
ocyanate in the presence of stoichiometric amount of NaH in THF
4.3. General procedure for the asymmetric borane reduction of
prochiral ketones 5a–k
To a flame-dried Schlenk tube were added ligand 4 (36 mg,
0.05 mmol), BH3–THF complex (1 M solution in THF, 0.6 mL,
0.6 mmol), and anhydrous cyclohexane (c-hexane) (1.5 mL). The
mixture was heated to 50 °C and was stirred at this temperature
for 1 h. Then, the solution of prochiral ketone (0.5 mmol) in c-hex-
ane (1.5 mL) was added in one portion. After being stirred at the
same temperature for a further 3 h, the reaction was quenched
by methanol. After removing the solvent, the product was purified
by column chromatography using petroleum ether/ethyl acetate
5:1 (V:V) as eluent. The ee value was determined by HPLC.
for 10 h. ½a 2D0
¼ ꢁ7:2 (c 1.0, DCM, 79% ee).
ꢂ
Acknowledgments
This project was partially supported by National Natural Sci-
ence Foundation of China (Grant Nos: 20572003, 20772006), the
Program for New Century Excellent Talents in University (NCET-
07-0011).
Product 6a was obtained as a colorless oil (81 mg, 94% yield). The
ee was determined by HPLC on Chiracel OJ-H column (n-hexane:
References
2-propanol 70:30, 1.0 mL/min, 254 nm, tminor = 6.8 min, tmajor
=
7.9 min). ½a 2D0
¼ þ34:9 (c 2.3, DCM, 97% ee).
ꢂ
1. For reviews, see: (a) Wallbaum, S.; Martens, J. Tetrahedron: Asymmetry 1992, 3,
1475; (b) Singh, V. K. Synthesis 1992, 605; (c) Deloux, L.; Srebnik, M. Chem. Rev.
1993, 93, 763; (d) Corey, E. J.; Helal, C. J. Angew. Chem., Int. Ed. 1998, 37, 1976.
2. (a) Hirao, A.; Itsuno, S.; Nakahama, S.; Yamazaki, N. J. Chem. Soc., Chem.
Commun. 1981, 315; (b) Itsuno, S.; Hirao, A.; Nakahama, S. J. Chem. Soc., Perkin
Trans. 1 1984, 2887; (c) Itsuno, S.; Ito, K.; Hirao, A.; Nakahama, S. J. Org. Chem.
1984, 49, 555.
3. (a) Corey, E. J.; Bakshi, R. K.; Shibata, S. J. Am. Chem. Soc. 1987, 109, 5551; (b)
Corey, E. J.; Bakshi, R. K.; Shibata, S.; Chen, C-P.; Singh, V. K. J. Am. Chem. Soc.
1987, 109, 7925.
4. For examples, see: (a) Hulst, R.; Heres, H.; Peper, N. C. M. W.; Kellogg, R. M.
Tetrahedron: Asymmetry 1996, 7, 1373; (b) Gamble, M. P.; Studley, J. R.; Wills,
M. Tetrahedron Lett. 1996, 37, 2853; (c) Gamble, M. P.; Studley, J. R.; Wills, M.
Tetrahedron: Asymmetry 1996, 7, 3071; (d) Gamble, M. P.; Smith, A. R. C.; Wills,
M. J. Org. Chem. 1998, 63, 6068; (e) Burns, B.; King, N. P.; Tye, H.; Studley, J. R.;
Gamble, M.; Wills, M. J. Chem. Soc., Perkin Trans. 1 1998, 1027; (f) Li, K. Y.; Zhou,
Z. H.; Wang, L. X.; Zhou, Q. L.; Tang, C. C. Main Group Met. Chem. 2002, 25, 663;
Product 6b was obtained as a colorless oil (53 mg, 87% yield).
The ee was determined by HPLC on Chiracel OB column (n-hexane:
2-propanol 95:5, 0.8 mL/min, 254 nm, tminor = 10.0 min, tmajor
=
12.7 min). ½a 2D0
¼ þ44:1 (c 2. 2, DCM, 96% ee).
ꢂ
Product 6c was obtained as a colorless oil (63 mg, 93% yield).
The ee was determined by HPLC on Chiracel OB column (n-hexane:
2-propanol 95:5, 1.0 mL/min, 254 nm, tminor = 9.0 min, tmajor
=
12.9 min). ½a 2D0
¼ þ18:5 (c 4.0, DCM, 90% ee).
ꢂ
Product 6d was obtained as a colorless oil (71 mg, 93% yield).
The ee was determined by HPLC on Chiracel OB column (n-hexane:
2-propanol 95:5, 1.0 mL/min, 254 nm, tminor = 15.1 min, tmajor
=
16.8 min). ½a 2D0
¼ þ34:4 (c 3.4, DCM, 93% ee).
ꢂ

J. Wang et al. / Tetrahedron: Asymmetry 20 (2009) 605–609
609
(g) Li, K.; Zhou, Z.; Wang, L.; Chen, Q.; Zhao, G.; Zhou, Q.; Tang, C. Tetrahedron:
Asymmetry 2003, 14, 95.
Chem. 2007, 269, 179; (c) Huang, L.-N.; Hui, X.-P.; Chen, Z.-C.; Yin, C.; Xu, P.-F.;
Yu, X.-X.; Cheng, S.-Y. J. Mol. Catal. A: Chem. 2007, 275, 9; (d) Hui, X.-P.; Yin, C.;
Chen, Z.-C.; Huang, L.-N.; Xu, P.-F.; Fan, G.-F. Tetrahedron 2008, 64, 2553.
12. (a) Kobayashi, S.; Ogawa, C.; Kawamura, M.; Sugiura, M. Synlett 2001, 983; (b)
Fuerte, A.; Corma, A.; Sanchez, F. Catal. Today 2005, 107–108, 404.
13. Sugimoto, K.; Aoyagi, S.; Kibayashi, C. J. Org. Chem. 1997, 62, 2322.
14. (a) Dálaigh, C. Ó.; Hynes, S. J.; Maher, D. J.; Connon, S. J. Org. Biomol. Chem. 2005,
3, 981; (b) Dálaigh, C. Ó.; Hynes, S. J.; O’Brien, J. E.; McCabe, T.; Maher, D. J.;
Watson, G. W.; Connon, S. J. Org. Biomol. Chem. 2006, 4, 2785; (c) Dálaigh, C. Ó.;
Connon, S. J. J. Org. Chem. 2007, 72, 7066.
5. Du, D.-M.; Fang, T.; Xu, J.; Zhang, S.-W. Org. Lett. 2006, 8, 1327.
6. For examples, see: (a) Yang, G.-S.; Hu, J.-B.; Zhao, G.; Ding, Y.; Tang, M.-H.
Tetrahedron: Asymmetry 1999, 10, 4307; (b) Hu, J.-B.; Zhao, G.; Yang, G.-S.; Ding,
Z.-D. J. Org. Chem. 2001, 66, 303; (c) Hu, J.-B.; Zhao, G.; Ding, Z.-D. Angew. Chem.,
Int. Ed. 2001, 40, 1109; (d) Zhao, G.; Hu, J.-B.; Qian, Z.-S.; Yin, W.-X. Tetrahedron:
Asymmetry 2002, 13, 2095; (e) Yang, S.-D.; Shi, Y.; Sun, Z.-H.; Zhao, Y.-B.; Liang,
Y.-M. Tetrahedron: Asymmetry 2006, 17, 1895; (f) Li, G.-Q.; Yan, Z.-Y.; Niu, Y.-N.;
Wu, L.-Y.; Wei, H.-L.; Liang, Y.-M. Tetrahedron: Asymmetry 2008, 19, 816.
7. For reviews of oxazoline preparation, see: Desimoni, G.; Faita, G.; Jørgensen, K.
A. Chem. Rev. 2006, 106, 3561.
8. For examples, see: (a) Fu, B.; Du, D.-M.; Xia, Q. Synthesis 2004, 221; (b) Lu, S.-F.;
Du, D.-M.; Zhang, S.-W.; Xu, J. Tetrahedron: Asymmetry 2004, 15, 3433.
9. For examples, see: (a) Boland, N. A.; Casey, M.; Hynes, S. J.; Matthews, J. W.;
Smith, M. P. J. Org. Chem. 2002, 67, 3919; (b) Menges, F.; Neuburger, M.; Pfaltz,
A. Org. Lett. 2002, 4, 4713.
15. Sibi, M. P.; Manyem, S. Org. Lett. 2002, 4, 2929.
16. Onomura, O.; Kouchi, Y.; Iwasaki, F.; Matsumura, Y. Tetrahedron Lett. 2006, 47,
3751.
17. (a) Zhou, H.; Lu, S.; Xie, R.; Chan, A. S. C.; Yang, T.-K. Tetrahedron Lett. 2001, 42,
1107; (b) Zhou, H.-B.; Zhang, J.; Lü, S.-M.; Xie, R.-G.; Zhou, Z.-Y.; Choi, M. C. K.;
Chan, A. S. C.; Yang, T.-K. Tetrahedron 2001, 57, 9325; (c) Zou, H.-H.; Hu, J.;
Zhang, J.; You, J.-S.; Ma, D.; Lü, D.; Xie, R.-G. J. Mol. Catal. A: Chem. 2005, 242, 57;
(d) Fang, T.; Xu, J.; Du, D.-M. Synlett 2006, 1559.
18. (a) Du, D.-M.; Lu, S.-F.; Fang, T.; Xu, J. J. Org. Chem. 2005, 70, 3712l; (b) Lu, S.-F.;
Du, D.-M.; Xu, J.; Zhang, S.-W. J. Am. Chem. Soc. 2006, 128, 7418; (c) Lu, S.-F.; Du,
D.-M.; Xu, J. Org. Lett. 2006, 8, 2115; (d) Liu, H.; Xu, J.; Du, D.-M. Org. Lett. 2007,
9, 4725; (e) Liu, H.; Lu, S.-F.; Xu, J.; Du, D.-M. Chem. Asian J. 2008, 3, 1111.
19. Xu, J.; Wei, T.; Zhang, Q. J. Org. Chem. 2003, 68, 10146.
10. (a) Takahashi, H.; Kawabata, A.; Higashiyama, K. Chem. Pharm. Bull. 1987, 35,
1604; (b) Blay, G.; Fernandez, I.; Hernandez-Olmas, V.; Marco-Aleixandre, A.;
Pedro, J. R. Tetrahedron: Asymmetry 2005, 16, 1207; (c) Fang, T.; Xu, J.; Du, D.-M.
Lett. Org. Chem. 2006, 3, 780.
11. (a) Fang, T.; Du, D.-M.; Lu, S.-F.; Xu, J. Org. Lett. 2005, 7, 2081; (b) Chen, Z.-C.;
Hui, X.-P.; Yin, C.; Huang, L.-N.; Xu, P.-F.; Yu, X.-X.; Cheng, S.-Y. J. Mol. Catal. A: