1,2,3-Triazole-linked dendrimers as a support for functionalized and recoverable catalysts for asymmetric borane reduction of prochiral ketones

Article abstract of DOI:10.1016/j.tetasy.2008.03.019

A series of new, functionalized, and chiral catalysts have been synthesized based on 1,2,3-triazole-linked dendrimers. It has been found that dendrimer 7f is an efficient catalyst for the enantioselective borane reduction of both electron-deficient and electron-rich ketones, and high enantioselectivities were obtained (up to 96%). The catalyst can be recovered and reused four times without a significant loss of catalytic activity.

Full text of DOI:10.1016/j.tetasy.2008.03.019

Available online at www.sciencedirect.com
Tetrahedron: Asymmetry 19 (2008) 912–920
1,2,3-Triazole-linked dendrimers as a support for functionalized
and recoverable catalysts for asymmetric borane reduction
of prochiral ketones
Yan-Ning Niu,a Ze-Yi Yan,b Gao-Qiang Li,a Hai-Long Wei,a Guo-Lin Gao,a
Lu-Yong Wua and Yong-Min Lianga,c,
*
aState Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, PR China
bLaboratory of Radiochemistry, School of Nuclear Science and Technology, Lanzhou University,
Lanzhou 730000, PR China
cLanzhou Institute of Chemical Physics, Chinese Academy of Science, Lanzhou 730000, PR China
Received 23 January 2008; accepted 18 March 2008
Abstract—A series of new, functionalized, and chiral catalysts have been synthesized based on 1,2,3-triazole-linked dendrimers. It has
been found that dendrimer 7f is an efficient catalyst for the enantioselective borane reduction of both electron-deficient and electron-rich
ketones, and high enantioselectivities were obtained (up to 96%). The catalyst can be recovered and reused four times without a signif-
icant loss of catalytic activity.
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
ramide, although only 20% ee was obtained.8 Recently, Du
et al. also reported that chiral C3-symmetric tris(b-hydroxy
amide) ligands could be applied in the asymmetric addition
of aryl alkynes to various aldehydes (up to 92% ee) and the
asymmetric borane reduction of prochiral ketones with
high enantioselectivities (up to 98% ee).9
The development of well-defined dendritic catalysts that
can efficiently catalyze asymmetric organic reactions and
be separated completely from the product, still remains a
challenge. The very first attempt to carry out asymmetric
reaction using chiral dendritic ligand was reported by
Brunner et al.1 Since then, dendritic catalysts have been
attracting much attention in asymmetric organic synthesis.2
Recently, Bolm et al. reported optically active dendritic
amino alcohols, while Zhao et al. reported supported-den-
drimer prolinols for the asymmetric reduction of ketones
with borane.3 On the other hand, C3-symmetry is also
interesting in organic chemistry, and many C3-symmetric
compounds and their applications in asymmetric catalysis
being reported in the literature.4 The C3-symmetric trisox-
azoline compounds as chiral auxiliaries and ligands have
been successfully applied in asymmetric synthesis and
molecular recognition by Katsuki,5 Ahn,6 and Gade.7 As
an early example, Burns performed the enantioselective
borane reduction of ketones using C3-symmetric phospho-
The enantioselective reduction of prochiral ketones with
borane in the presence of a chiral ligand leading to enantio-
merically pure secondary alcohols plays an important role
in asymmetric synthesis.10 One of the most active research
fields of reduction of prochiral ketones to optically active
alcohols is to employ chiral oxaza-borolidine ligands as
catalysts. This method known as CBS reduction was pio-
neered by Itsuno et al.11 and further developed by Corey,
Bakshi, and Shibata.12 In order to find more effective cata-
lysts, a large number of studies have been reported with
many new ligands being prepared in the past few years.13
Recently, the study of chiral amino alcohols based on pro-
linol has become an interesting research area with new
derivatives such as sulfonyl prolinol,14 polymer-supported
sulfonamide,15 chiral phosphinamides,16 and chiral squaric
prolinols17 being reported and with high yields and with
good enantioselectivities being obtained. However, the
development of efficient methods to synthesize new
*
Corresponding author. E-mail: liangym@lzu.edu.cn
0957-4166/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2008.03.019

Y.-N. Niu et al. / Tetrahedron: Asymmetry 19 (2008) 912–920
913
recoverable catalysts still remains a challenging research
2. Results and discussion
field.
A series of new ligands 7a–f were synthesized from com-
mercially available trans-4-hydroxyl-L-proline as depicted
in Scheme 1. First, chiral trans-4-hydroxyl-L-proline 1
was reacted with ethyl chloroformate to give mixture 2.
The treatment of mixture 2 (without further purification)
with phenyl magnesium bromide furnished tertiary alcohol
3.23 Compound 3 was reacted with 4-toluenesulfonyl chlo-
ride in pyridine to give tosylate 4. Dis-placing the tosylate
with sodium azide in dry DMSO gave compound 5. The
hydrolysis of compound 5 resulted in the formation of
((2R,4S)-4-azidopyrrolidine-2-yl)diphenylmethanol 6. Var-
ious terminal alkynes 8a–f (Scheme 2) reacted with 6 using
Cu(I)-catalyzed 1,3-dipolar ‘click’ azide–alkyne cycloaddi-
tion condition to give the desired catalysts 7a–f.
Recently, Sharpless introduced ‘click chemistry’ as a new
way of categorizing organic reactions.18 In the past few
years, these reactions have been used in organic synthesis,
biological studies, material science, and so on,19 since the
special feature of this reaction is that it is completely spe-
cific, has quantitative yields, and almost perfect fidelity in
the presence of a wide variety of functional groups.20 We
were especially interested in the Cu(I)-catalyzed 1,3-dipolar
‘click’ azide–alkyne cyclo-addition for the construction of
1,2,3-triazoles.21 Very recently, we successfully prepared
pyrrolidine-based triazole derivatives via ‘click chemistry’,
which proved to be efficient catalysts for the highly diaste-
reoselective and enantioselective Michael addition of ke-
tones to nitroalkenes.22 As an ongoing study in ‘click
chemistry’, we herein report the utility of ‘click chemistry’
as a modular approach for the construction of C3-symmet-
ric 1,2,3-triazole-linked dendritic organocatalysts for the
asymmetric borane reduction of prochiral ketones.
It is well known that the enantioselectivity of borane reduc-
tion is greatly affected by solvent, temperature, and the
amount of catalyst.24 In order to evaluate the efficiency
of these ligands in the catalytic asymmetric reduction, in
HO
PhMgBr
THF, rt
HO
O
ClCOOEt
HO
O
OH
N
N
OMe
COOEt
Na2CO3, MeOH, rt
N
H
OH
COOEt
2
3
1
N3
TsO
NaN3
KOH
Pyridine
OH
OH
N
COOEt
N
DMSO, oC
MeOH, 80oC
0
DMSO, 60oC
COOEt
4
5
7a =
7b =
R
N3
+
8a-f
7a-f
OH
N
H
R
6
R
O
O
R
R
O
N
N
N
7d =
R=
7c =
OH
R
O
O
R
N
H
O
R
R
R
R
O
O
O
O
R
O
O
O
R
O
7e =
7f =
O
O
O
O
R
R
O
O
O
R
R
Scheme 1. Synthesis of new ligands.

914
Y.-N. Niu et al. / Tetrahedron: Asymmetry 19 (2008) 912–920
8b =
8a =
O
O
O
8d =
8c =
O
O
O
O
O
O
O
8e =
8f =
O
O
O
O
O
O
O
O
O
O
O
Scheme 2. Various terminal alkynes.
preliminary experiments, we attempted to perform the
enantioselective reduction of acetophenone with BH3–
Me2S to explore the optimum reaction conditions. As
shown in Table 1, when the reaction was carried out at
the room temperature in THF, ligands 7a (Table 1, entry
1) and 7c (Table 1, entry 4) gave only very low enantio-
selectivity, less than 15% ee. This may be due to the
dimerization of the catalysts at the lower temperature.24e
When the reaction was carried out in refluxing THF
(70 °C) (Table 1, entries 2 and 5), the corresponding (R)-
1-phenylethanol was obtained in high enantioselectivities
(up to 90%). To our delight, all the ligands from 7a to 7f
gave excellent yields and high ee values (Table 1, entries
2, 3, and 5–8). In view of the slightly higher reactivity
and enantioselectivity of 7f, dendrimer 7f was chosen for
the following investigation (Table 1, entries 8–13). With
Table 1. Enantioselective borane reduction of acetophenonea
O
OH
ligand BH3 Me2S
solvent
Entry
Ligand (mol %)
Solvent
T (°C)
Yieldb (%)
eec (%)
Configd
1
2
3
4
5
6
7
8
9
10
11
12
13
7a (15)
7a (15)
7b (15)
7c (5.0)
7c (5.0)
7d (5.0)
7e (5.0)
7f (2.5)
7f (2.5)
7f (2.5)
7f (1.25)
7f (0.65)
7f (4.0)
THF
THF
THF
THF
THF
THF
THF
THF
Toluene
Toluene
THF
THF
THF
rt
92
98
95
94
96
97
96
98
92
93
94
92
97
5
89
90
13
90
91
92
94
86
85
87
84
95
—
70
70
rt
(R)
(R)
—
70
70
70
70
70
90
70
70
70
(R)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
a Reaction was carried out on a 0.5 mmol scale in 5 mL of solvent, molar ratio of PhCOCH3/BH3–Me2S = 1:1.5.
b Isolated yields by column chromatography.
c Ee determined by HPLC analysis using a Daicel Chiralcel OJ column.
d The absolute configuration was assigned by comparison of the sign of the specific rotation with that in the literature.

Y.-N. Niu et al. / Tetrahedron: Asymmetry 19 (2008) 912–920
Table 2. Catalytic asymmetric reduction of ketonesa
915
the exception of the reaction temperature and catalysts, the
reactivity and enantioselectivity were also affected by the
solvent. An attempt to employ the reduction in toluene at
70 °C caused a lower yield and the enantioselectivity to
be obtained. When the temperature was raised from
70 °C to 90 °C in toluene (Table 1, entries 9 and 10), the
enantioselectivity and yield had only a negligible change.
It was observed that a decrease in the catalyst loading from
2.5 mol % to 0.65 mol % using 7f resulted in a dramatic de-
crease in the enantioselectivity and a slight loss of the yield
(Table 1, entries 8, 11 and 12). Increasing the amount of the
catalyst further to 4.0 mol % (Table 1, entry 13) resulted in
a slight increase in the enantioselectivity.
7f
2.5 mol % , BH3 Me2S
O
OH
R1
R1
R2
R2
Configd
THF, Reflux
Entry
1
Product
Yieldb (%)
eec (%)
94
OH
95
(R)
(R)
9a
OH
2
91
90
O
9b
OH
98
9c
Under the optimum reaction conditions, using a catalytic
amount (2.5 mol %) of ligand 7f in refluxing THF, the
reduction of other prochiral ketones was investigated.
The results are summarized in Table 2. It has been shown
that both electron-deficient and electron-rich ketones and
all the reductions gave excellent yields and high ee values.
Comparison of the results (Table 2, entries 1–10) indicated
that electron-withdrawing groups were relatively beneficial
to the enantioselectivity. In order to understand the gener-
ality of this catalytic system, we also investigated the bor-
ane reduction of representative prochiral a-halo ketones
under the same conditions. High enantioselectivities were
thus obtained (Table 2, entries 11 and 12). The results dem-
onstrated that the steric effects had a significant impact on
the enantioselectivity, for example, the reactions of 3,4-
dihydronaphthalen-1(2H)-one (Table 2, entry 13) and pro-
piophenone (Table 2, entry 14) were completed in moder-
ate enantioselectivity due to the steric effect.
3
4
96
92
(R)
(R)
F
OH
97
9d
Cl
OH
93
9e
5
6
7
94
93
87
(R)
(R)
(R)
Br
OH
99
9f
O2N
OH
95
9g
OH
90
9h
8
9
89
92
93
(R)
(R)
(R)
Br
The recyclability and reusability of catalyst 7f were also
investigated (Table 3). The reduction of acetophenone
was chosen as a model study. When the first run of the
reduction was completed, the reaction was quenched with
water and extracted with CH2Cl2. After the removal of
the solvent under reduced pressure, diethyl ether was
added. The product was re-dissolved in ether, and catalyst
7f was precipitated. After removing the ether phase, the
catalyst was dried under vacuum for 12 h, and then reused
for the next cycle of the reaction. As can be seen from
Table 3, good enantioselectivities and yields were obtained
for four consecutive cycles with little to no loss of
performance.
OH
95
9i
O
OH
96
9j
10
O
OH
Cl
11
95
87
(S)
9k
9l
OH
OH
Br
12
13
93
98
92
81
(S)
(R)
3. Conclusion
In conclusion, a series of new chiral catalysts have been
synthesized from commercially available trans-4-hydro-
xyl-L-proline based on dendrimers as a support using ‘click
chemistry’. The catalytic borane reduction of ketones with
these new chiral catalysts was investigated, and high
enantioselectivities were obtained (up to 96%). The results
showed that dendrimer 7f is an efficient catalyst for the
enantioselective borane reduction of ketones. Meanwhile,
catalyst 7f can be recovered and reused four times without
any significant loss of activity. The development of other
asymmetric reactions using these C3-symmetric ligands is
currently ongoing in our group.
9m
OH
14
95
71
(R)
9n
a Reaction was carried out on a 0.5 mmol scale in 5 mL of solvent, molar
ratio of ketone/BH3–Me2S = 1:1.5.
b Isolated yield by column chromatography.
c Ee determined by HPLC analysis using a Daicel Chiralcel OJ column.
d The absolute configuration assigned by comparison with the literature.

916
Y.-N. Niu et al. / Tetrahedron: Asymmetry 19 (2008) 912–920
Table 3. Recycling of catalyst 7f (reduction of acetophenone)a
1.12 (t, J = 6.3 Hz, 3H); 13C NMR (75 MHz, CDCl3):
d = 158.0, 145.2, 143.1, 127.8, 127.6, 127.3, 127.2, 127.1,
Cycle
Yieldb (%)
eec (%)
81.4, 69.5, 65.4, 61.9, 56.0, 39.0, 14.4. IR (KBr, cmꢀ1
)
1
2
3
4
97
95
96
93
94
92
90
90
3417, 2950, 1682, 1416, 1198, 1107, 984, 700. Anal. Calcd
for C20H23NO4: C, 70.36; H, 6.79; N, 4.10. Found: C,
70.32; H, 6.78; N, 4.12.
a Reaction was carried out on a 1 mmol scale in 10 mL of solvent, molar
ratio of PhCOCH3/BH3–Me2S = 1:1.5.
4.2.2. Synthesis of (2S,4R)-ethyl-2-(hydroxydiphenylmeth-
yl)-4-(tosyloxy)pyrrolidine-1-carboxylate 4. To an ice-cold
solution of 3 (3.41 g, 10.0 mmol) in pyridine (20 mL) was
added 4-toluenesulfonyl chloride (2.29 g, 12.0 mmol). The
reaction mixture was stirred for 6 h and then diluted with
ethyl acetate (100 mL). The organic phase was washed with
10% HCl (3 ꢂ 50 mL), saturated NaHCO3 solution
(3 ꢂ 50 mL), and saturated NaCl solution (2 ꢂ 50 mL).
The organic phase was dried over Na2SO4 and the solvent
was evaporated under reduced pressure. The crude product
was subjected to flash chromatography on silica gel (eluent:
b Isolated yield by column chromatography.
c Ee determined by HPLC analysis using a Daicel Chiralcel OJ column.
4. Experimental
4.1. General
Column chromatography was carried out on silica gel
(200–300 mesh). 1H NMR spectra were recorded on
300 MHz or 400 MHz in CDCl3, chemical shifts are re-
ported in ppm using TMS as the internal standard. 13C
NMR spectra were recorded on a Varian 75 MHz or Var-
ian 100 MHz spectrometers with complete proton decou-
pling. IR spectra were recorded on a FT-IR spectrometer
and only major peaks are reported in cmꢀ1. High resolu-
tion mass spectra (HRMS) were obtained by the ESI ioni-
zation sources. Melting points were determined on a
microscopic apparatus and are uncorrected. All new com-
pounds were further characterized by elemental analysis
or HRMS. HPLC analysis was performed on Varian-Pro-
Star using a ChiralPak OJ columns purchased from Daicel
Chemical Industries, Ltd. Optical rotations were measured
pentane/EtOAc 1:1). Yield: 4.36 g (88%). White solid,
20
mp 77–79 °C, ½aꢁD ¼ þ46:5 (c 1.0, CH2Cl2); 1H NMR
(300 MHz, CDCl3): d = 7.63 (d, J = 8.1 Hz, 2H), 7.29–
7.20 (m, 12H), 5.00 (dd, J = 6.3 Hz, 8.1 Hz, 1H), 4.42
(br, 1H), 4.09–3.96 (m, 1H), 3.68–3.64 (m, 1H), 3.07 (br,
1H), 2.40 (s, 3H), 2.22–2.12 (m, 2H), 1.16 (m, 3H); 13C
NMR (75 MHz, CDCl3): d = 155.7, 144.9, 144.8, 133.4,
129.8, 127.9, 127.8, 127.7, 127.4, 127.1, 81.3, 79.3, 64.5,
62.0, 53.1, 36.2, 21.6, 14.3. IR (KBr, cmꢀ1) 3446, 2921,
1688, 1416, 1371, 1342, 1175, 1096, 887, 746, 649. Anal.
Calcd for C27H29NO6S: C, 65.44; H, 5.90; N, 2.83. Found:
C, 65.40; H, 5.94; N, 2.80.
using a 1 mL cell with a 1 dm path length on a digital
20
polarimeter and are reported as follows: ½aꢁD (c in g per
4.2.3. Synthesis of (2S,4S)-ethyl-4-azido-2-(hydroxydiphen-
yl-methyl)pyrrolidine-1-carboxylate
100 mL of solvent). Commercially available reagents and
solvents were used without further purification. Toluene
and tetrahydrofuran were distilled with sodium under
nitrogen. Other solvents used were purified and dried by
standard procedures. Borane-dimethyl sulfide complex
was purchased from Aldrich.
5. Compound
4
(4.1 g, 8.4 mmol) was dissolved in dry DMSO (50 mL),
and sodium azide (1.63 g, 25.2 mmol) was added. The reac-
tion mixture was heated to 60 °C for 20 h, allowed to cool to
room temperature and diluted with ethyl acetate (100 mL).
The organic phase was washed with H2O (3 ꢂ 100 mL) and
saturated brine (2 ꢂ 50 mL), dried with Na2SO4, and the
solvent was evaporated. The crude product was subjected
to flash chromatography using 2:1 hexanes/EtOAc to afford
4.2. Synthesis of catalysts 7a–7f
2.77 g (90% yield) of the indicated compound 5 as a white
4.2.1. Synthesis of trans-4-hydroxyl-a,a-bisphenyl-L-prolinol
carbamate ester 3.23 To a solution of trans-4-hydroxyl-L-
proline 1 in methanol was slowly added ethyl chlorofor-
mate. The reaction mixture was stirred for 24 h at room
temperature, and then filtered. The filtrate was extracted
with ethyl acetate and concentrated to give product 2 as
a colorless oil. To a solution of 2 (5.0 g, 23.0 mmol) in
dry THF (100 mL) was added phenyl magnesium bromide
(1 M in THF, 138 mL, 138.0 mmol) at 0 °C under an argon
atmosphere. After being stirred for 5 h, the reaction solu-
tion was diluted with saturated aqueous NH4Cl and ex-
tracted with CH2Cl2 (2 ꢂ 50 mL). The organic layer was
dried over anhydrous Na2SO4 and filtered. The filtrate
was concentrated under reduced pressure to give a residue,
which was chromatographed on silica gel (eluent: hexanes/
20
solid. White solid, mp 116–118 °C, ½aꢁD ¼ þ87:6 (c 1.2,
CH2Cl2); 1H NMR (300 MHz, CDCl3): d = 7.50 (d,
J = 7.8 Hz, 2H), 7.39–7.19 (m, 8H), 4.94 (dd, J = 6.6 Hz,
8.1 Hz, 1H), 4.09–3.90 (m, 3H), 3.75 (br, 1H), 2.93 (br,
1H), 2.47–2.39 (m, 1H), 1.96–1.87 (m, 1H), 1.04 (t,
J = 6.6 Hz, 3H); 13C NMR (75 MHz, CDCl3): d = 156.0,
144.5, 143.3, 127.8, 127.7, 127.2, 127.1, 127.1, 127.0,
127.1, 81.4, 65.1, 61.7, 57.8, 51.6, 35.2, 14.2. IR (KBr,
cmꢀ1) 3379, 2981, 2104, 1667, 1439, 1343, 1229, 761, 700.
Anal. Calcd for C20H22N4O3: C, 65.56; H, 6.05; N, 15.29.
Found: C, 65.52; H, 6.04; N, 15.32.
4.2.4. Synthesis of ((2S,4S)-4-azidopyrrolidin-2-yl)diphenyl-
methanol 6. Compound 5 (2.5 g, 6.8 mmol) and KOH
(3.0 g, 53.5 mmol) in methanol (25 mL) were heated at
80 °C for 8 h. After the reaction was complete, and cooled
to room temperature, the methanol was removed under re-
duced pressure. Water (50 mL) was added to the reaction
mixtures, the mixtures were extracted with CH2Cl2
EtOA = 2:1) to give the product as a white foam (4.55 g,
20
58% yield). White solid, mp 174–176 °C, ½aꢁD ¼ ꢀ43:2 (c
1
1.1, CH2Cl2); H NMR (300 MHz, CDCl3): d = 7.40–7.20
(m, 10H), 5.06 (t, J = 7.2 Hz, 1H), 4.03–3.86 (m, 3H),
3.52–3.48 (m, 1H), 2.97–2.94 (m, 1H), 2.19–1.97 (m, 3H),

Y.-N. Niu et al. / Tetrahedron: Asymmetry 19 (2008) 912–920
917
(3 ꢂ 20 mL). The organic layer was washed with saturated
NaCl solution (2 ꢂ 30 mL), dried with Na2SO4, and the
solvent was evaporated and the residue was chromato-
graphed using 4:1 hexanes/EtOAc to afford 1.72 g (86%
4.2.7. Synthesis of (2S,20S,200S,4S,40S,400S)-4,40,400-(4,40,
400-(benzene-1,3,5-triyltris(oxy))tris(methylene)tris(1H-1,2,3-
triazole-4,1-diyl))tris(pyrrolidine-4,2-diyl)tris(diphenyl meth-
anol) 7c. A solution of 8c (120 mg, 0.5 mmol),25a com-
pound 6 (529 mg, 1.8 mmol), N,N-diisopropylethylamine
(516 mg, 4.0 mmol), and Cu(PPh3)3Br (139.2 mg, 0.15
mmol) was prepared in tetrahydrofuran (10 mL). The reac-
tion mixture was then stirred at room temperature for ca.
72 h. The solvent was removed under reduced pressure.
The crude product was purified by column chromatogra-
phy, eluting with a 30:1 mixture of dichloromethane and
yield) of the indicated compound 6 as a white solid. White
20
solid, mp 82–84 °C, ½aꢁD ¼ ꢀ62:7 (c 1.5, CH2Cl2); 1H
NMR (300 MHz, CDCl3): d = 7.57–7.47 (m, 4H), 7.30–
7.24 (m, 4 H), 7.22–7.13 (m, 2H), 4.28 (t, J = 7.5 Hz,
1H), 3.97–3.90 (m, 1H), 3.09–2.97 (m, 2H), 1.97–1.76 (m,
3H); 13C NMR (75 MHz, CDCl3): d = 147.1, 144.6,
128.3, 128.0, 126.6, 126.5, 125.7, 125.3, 76.5.0, 63.8, 60.3,
51.9, 32.3. IR (KBr, cmꢀ1) 3345, 2938, 2100, 1267, 703.
Anal. Calcd for C17H18N4O: C, 69.37; H, 6.16; N, 19.03.
Found: C, 69.40; H, 6.12; N, 19.01.
methanol to give 7c as a white solid (527 mg, 94% yield).
20
White solid, mp 135–136 °C, ½aꢁD ¼ ꢀ160:7 (c 1.0,
1
CH2Cl2); H NMR (300 MHz, CDCl3): d = 7.80 (s, 3H),
7.55 (d, J = 6.9 Hz, 6H), 7.46–7.43 (m, 6H), 7.28–7.10
(m, 18H), 6.28 (s, 1H), 5.07 (s, 9H), 4.38 (t, J = 7.8 Hz,
3H), 3.42 (dd, J = 7.2 Hz, 10.5 Hz, 3H), 3.22 (dd,
J = 3.6 Hz, 11.1 Hz, 3H), 2.24–2.05 (m, 6H), 1.96 (s, 3H);
13C NMR (75 MHz, CDCl3): d = 160.0, 146.5, 144.4,
143.6, 128.3, 128.1, 126.8, 126.6, 125.7, 125.1, 121.3, 95.0,
76.5, 64.4, 61.9, 59.7, 52.9, 33.6. IR (KBr, cmꢀ1) 3338,
2869, 1596, 1447, 1151, 1054, 749, 700. Anal. Calcd for
C66H66N12O6: C, 70.57; H, 5.92; N, 14.96. Found: C,
70.53; H, 5.94; N, 14.99. HRMS (ESI, M+H+), calcd,
1123.5031; found 1123.5031.
4.2.5. Synthesis of diphenyl((2S,4S)-4-(4-phenyl-1H-1,2,3-
triazol-1-yl)pyrrolidin-2-yl)methanol 7a. A solution of eth-
ynylbenzene (122 mg, 1.2 mmol), compound 6 (294 mg,
1 mmol), N,N-diisopropylethyl-amine (51.6 mg, 0.4 mmol),
and Cu(PPh3)3Br (92.8 mg, 0.1 mmol) was prepared in tet-
rahydrofuran (5 mL). The reaction mixture was then stir-
red at room temperature for ca. 48 h. The solvent was
removed under reduced pressure. The crude product was
purified by column chromatography, eluting with EtOAc
to give 7a as a white solid (380 mg, 96% yield). White solid,
20
1
mp 157–158 °C, ½aꢁD ¼ ꢀ150:2 (c 1.2, CH2Cl2); H NMR
(300 MHz, CDCl3): d = 7.94 (s, 1H), 7.80 (d, J = 8.1 Hz,
2H), 7.60–7.57 (m, 2H), 7.48 (d, J = 7.8 Hz, 2H), 7.41–
7.13 (m, 11H), 5.14 (br, 1H), 4.42 (t, J = 7.5 Hz, 1H),
3.48 (m, 1H ), 3.30 (m, 1H), 2.31–2.12 (m, 2H), 2.01 (br,
1H); 13C NMR (75 MHz, CDCl3): d = 147.7, 146.5,
144.3, 130.5, 128.7, 128.4, 128.1, 128.0, 126.9, 126.7,
125.7, 125.6, 125.1, 117.8, 76.5, 64.5, 59.6, 53.1, 33.5. IR
(KBr, cmꢀ1) 3418, 3083, 1442, 1256, 972, 694. Anal. Calcd
for C25H24N4O: C, 75.73; H, 6.10; N, 14.13. Found: C,
75.70; H, 6.07; N, 14.15. HRMS (ESI, M+H+), calcd,
397.2023; found 397.2021.
4.2.8. Synthesis of (2S,20S,200S,4S,40S,400S)-4,40,400-(4,40,
400-(4,40,400-(ethane-1,1,1-triyl)tris(benzene-4,1-diyl))tris(oxy)-
tris(methylene)tris(1H-1,2,3-triazole-4,1-diyl))tris(pyrrolidi-
ne-4,2-diyl)tris(diphenylmethanol) 7d. A solution of 8d
(210 mg, 0.5 mmol),25a,b compound 6 (529 mg, 1.8 mmol),
N,N-diisopropylethylamine (516 mg, 4.0 mmol), and
Cu(PPh3)3Br (139.2 mg, 0.15 mmol) was prepared in tetra-
hydrofuran (10 mL). The reaction mixture was then stirred
at room temperature for ca. 72 h. The solvent was removed
under the reduced pressure. The crude product was purified
by column chromatography, eluting with a 20:1 mixture of
dichloromethane and methanol to give 7d as a white solid
20
4.2.6. Synthesis of ((2S,4S)-4-(4-pentyl-1H-1,2,3-triazol-1-
yl)pyrrolidin-2-yl)diphenylmethanol 7b.
(592 mg, 91% yield). White solid, mp 145–146 °C, ½aꢁD ¼
A
solution of
ꢀ92:1 (c 1.0, CH2Cl2); 1H NMR (300 MHz, CDCl3):
d = 7.78 (s, 3H), 7.56 (d, J = 7.5 Hz, 6H), 7.46 (d, J =
7.5 Hz, 6H), 7.31–7.11 (m, 18H), 7.11–7.00 (d, J =
9.0 Hz, 6H), 6.97–6.84 (d, J = 9.0 Hz, 6H), 5.11–5.07 (d,
9H), 4.41 (t, J = 8.1 Hz, 3H), 3.44 (dd, J = 7.2 Hz,
11.1 Hz, 3H), 3.25 (dd, J = 3.6 Hz, 11.1 Hz, 3H), 2.27–
2.10 (m, 9H), 1.95 (br, 3H); 13C NMR (75 MHz, CDCl3):
d = 156.2, 146.5, 144.3, 144.0, 142.1, 129.5, 128.3, 128.1,
126.8, 126.7, 125.6, 125.1, 121.0, 113.8, 76.5, 64.4, 61.8,
59.6, 52.9, 50.5, 33.5, 30.6. IR (KBr, cmꢀ1) 3362, 3055,
1503, 1180, 1006, 829, 698. Anal. Calcd for
C80H78N12O6: C, 73.71; H, 6.03; N, 12.89. Found: C,
73.74; H, 6.04; N, 12.92. HRMS (ESI, M+H+), calcd,
1303.6240; found 1303.6229.
hept-1-yne (115 mg, 1.2 mmol), compound 6 (294 mg,
1 mmol), N,N-diisopropylethylamine (51.6 mg, 0.4 mmol),
and Cu(PPh3)3Br (92.8 mg, 0.1 mmol) was prepared in tet-
rahydrofuran (5 mL). The reaction mixture was then stirred
at room temperature for ca. 48 h. The solvent was removed
under reduced pressure. The crude product was purified by
column chromatography (eluent: pentane/EtOAc = 1:2) to
give 7b as a white solid (359 mg, 92% yield). White solid, mp
20
100–102 °C, ½aꢁD ¼ ꢀ103:9 (c 1.2, CH2Cl2); 1H NMR
(400 MHz, CDCl3): d = 7.67–7.58 (m, 2H), 7.55–7.43 (m,
4H), 7.33–7.14 (m, 5H), 5.13–5.10 (m, 1H), 4.45 (d,
J = 8.8 Hz, 1H), 3.48 (dd, J = 7.2 Hz, 10.8 Hz, 1H), 3.25
(dd, J = 3.6 Hz, 10.8 Hz, 1H), 2.69 (t, J = 7.6 Hz, 1H),
2.26–2.09 (m, 2H), 1.94 (s, 1H), 1.69–1.61 (m, 2H), 1.35–
1.31 (m, 4H), 0.90 (t, J = 6.4 Hz, 3H); 13C NMR
(100 MHz, CDCl3): d = 148.5, 146.6, 144.4, 132.0, 131.9,
131.8, 128.3, 128.1, 126.8, 126.7, 125.7, 125.1, 118.6, 76.6,
64.5, 59.4, 53.0, 33.5, 31.4, 29.0, 25.6, 22.3, 13.9. IR (KBr,
cmꢀ1) 3447, 3119, 2926, 2858, 1443, 1173, 1119, 973, 697.
Anal. Calcd for C24H30N4O: C, 73.81; H, 7.74; N, 14.35.
Found: C, 73.85; H, 7.71; N, 14.32. HRMS (ESI,
M+H+), calcd, 391.2492; found 391.2490.
4.2.9. Synthesis of (2S,20S,200S,4S,40S,400S)-4,40,400-(4,40,400-
(4,40,400-(4,40,400-(ethane-1,1,1-triyl)tris(benzene-4,1-diyl))tris-
(oxy)tris(methylene)tris(benzene-4,1-diyl))tris(oxy)tris(meth-
ylene)tris(1H-1,2,3-triazole-4,1-diyl))tris(pyrrolidine-4,2-diyl)-
tris(diphenylmethanol) 7e. To a stirred solution of 1-(bro-
momethyl)-4-(prop-2-ynloxy)benzene (742 mg 3.3 mmol)25c
and 1,1,1-tris(4-hydroxyphenyl)ethane (306 mg, 1 mmol) in
acetone (20 mL) added potassium carbonate (450 mg,

918
Y.-N. Niu et al. / Tetrahedron: Asymmetry 19 (2008) 912–920
3.3 mmol) and 18-crown-6 (10 mg, 0.04 mmol). The reac-
tion mixture was stirred in refluxing acetone under a nitro-
gen atmosphere for 36 h, filtered, and evaporated to
dryness. The crude material was then as purified by column
chromatography, eluting with dichloromethane to give
compound 8e as a white solid (612 mg, yield 83%). White
solid, White solid, mp 70–72 °C, 1H NMR (300 MHz,
CDCl3): d = 7.34 (d, J = 8.7 Hz, 6H), 6.98 (t, J = 7.5 Hz,
12H), 6.83 (d, J = 8.7 Hz, 6H), 4.92 (s, 6H), 4.66 (d,
J = 2.4 Hz, 6H), 2.51 (t, J = 2.4 Hz, 3H), 2.09 (s, 3H);
13C NMR (75 MHz, CDCl3): d = 157.2, 156.7, 141.8,
129.9, 129.5, 129.1, 114.8, 113.8, 78.4, 75.5, 69.4, 55.6,
50.5, 30.6. IR (KBr, cmꢀ1) 1607, 1509, 1238, 1220, 1175,
1007, 823, 683. Anal. Calcd for C50H42O6: C, 81.28; H,
5.73. Found: C, 81.26; H, 5.72.
CDCl3): d = 159.5, 156.5, 146.5, 144.4, 143.5, 141.9,
139.7, 129.5, 128.2, 128.0, 126.7, 126.6, 125.7, 125.1,
121.3, 113.9, 106.5, 101.3, 76.6, 69.6, 64.3, 61.9, 59.6,
52.7, 50.5, 33.5, 30.6. IR (KBr, cmꢀ1) 3416, 2925, 1598,
1449, 1241, 1155, 1049, 1009, 832, 700. Anal. Calcd for
C161H156N24O15: C, 72.50; H, 5.90; N, 12.60. Found: C,
72.52; H, 5.88; N, 12.64.
4.3. General procedure for asymmetric borane reduction of
prochiral ketones
Under an argon atmosphere, BH3–Me2S (0.75 mmol) was
added to a solution of catalyst 7f (0.025 mmol) in dry
THF (5 mL). The suspension was stirred and refluxed for
1 h. Then, a THF (2 mL) solution of ketone (0.5 mmol)
was added by syringe pump over a period of 1 h, and the
reaction mixture stirred for an additional 1 h. The reaction
mixture was cooled and quenched by the dropwise addition
of water (5 mL) and extracted with CH2Cl2 (3 ꢂ 5 mL).
The organic layer was treated with saturated brine, and
then dried over anhydrous Mg2SO4. After concentration
by rotatory evaporation, diethyl ether was added. The
product was dissolved in the ether, and catalyst 7f was pre-
cipitated. After removing the ether phase, the catalyst was
dried under vacuum for 12 h, and then reused for the next
cycle of the reaction. After the solvent was removed from
the ether phase under the reduced pressure, the residue
was purified by column chromatography on silica gel
(petroleum ether/ethyl acetate 8:1) to afford the corre-
sponding secondary alcohol. The ee value was determined
by Chiralcel OJ column (eluent: hexane/2-propanol = 90/
10).
A solution of 8e (369 mg, 0.5 mmol), compound 6 (529 mg,
1.8 mmol), N,N-diisopropylethylamine (516 mg, 4.0
mmol), and Cu(PPh3)3Br (139.2 mg, 0.15 mmol) was pre-
pared in tetrahydrofuran (10 mL). The reaction mixture
was then stirred at room temperature for ca. 72 h. The sol-
vent was removed under the reduced pressure. The crude
product was purified by column chromatography, eluting
with a 10:1 mixture of dichloromethane and methanol to
give 7e as a white solid (712 mg, 88% yield). White solid,
20
1
mp 121–123 °C, ½aꢁD ¼ ꢀ105:6 (c 1.3, CH2Cl2); H NMR
(300 MHz, CDCl3): d = 7.78 (s, 3H), 7.56 (d, J = 8.1 Hz,
6H), 7.45 (d, J = 8.4 Hz, 6H), 7.34–7.13 (m, 24H), 6.99–
6.95 (m, 12H), 6.85–6.82 (m, 6H), 5.13–5.06 (m, 9H),
4.92 (s, 3H), 4.39 (t, J = 7.5 Hz, 3H), 3.46–3.39 (m, 3H),
3.27–3.22 (m, 3H), 2.21–2.01 (m, 12H); 13C NMR
(75 MHz, CDCl3): d = 157.9, 156.7, 146.5, 144.3, 143.8,
141.8, 129.6, 129.5, 129.1, 128.3, 128.1, 126.8, 126.7,
125.6, 125.1, 121.1, 114.7, 113.8, 76.5, 69.5, 64.4, 61.9,
59.6, 52.8, 50.5, 33.5, 30.6. IR (KBr, cmꢀ1) 3414, 2926,
1613, 1508, 1236, 1174, 1005, 823, 699. Anal. Calcd for
C101H96N12O9: C, 74.79; H, 5.79; N, 10.36. Found: C,
74.83; H, 5.78; N, 10.37. HRMS (ESI, M+H+), calcd,
1621.7496; found 1621.7491.
4.3.1. (R)-1-Phenyl-ethanol 9a.26a Colorless oil; 95%
yield. 94% ee. Determined by HPLC analysis (Daicel Chiral-
cel OB column, hexane/isopropanol = 90:10, 0.5 mL/min,
254 nm). Retention time: tmajor = 16.04 and tminor = 14.64 -
20
1
min. ½aꢁD ¼ þ29:6 (c 1.3, MeOH). H NMR (300 MHz,
CDCl3): d = 7.33–7.21 (m, 5H), 4.82 (q, J = 6.3 Hz, 1H),
2.27 (br, 1H), 1.45 (d, J = 6.6 Hz, 3H). 13C NMR
4.2.10. Synthesis of (2S,20S,200S,2000S,20000S,200000S,4S,40S,
400S,4000S,40000S,400000S)-4,40,400,4000,40000,400000-(4,40,400,4000,40000,400000-(5,
50,500-(4,40,400-(ethane-1,1,1-triyl)tris(benzene-4,1-diyl))tris-
(oxy)tris(methylene)tris(benzene-5,3,1-triyl))hexakis(oxy)-
hexakis(methylene)hexakis(1H-1,2,3-triazole-4,1-diyl))hexa-
kis(pyrrolidine-4,2-diyl)hexakis (diphenyl methanol) 7f. To
a solution of 8f (225 mg, 0.25 mmol),25b compound 6
(529 mg, 1.8 mmol), N,N-diisopropylethylamine (516 mg,
4.0 mmol), and Cu(PPh3)3Br (139.2 mg, 0.15 mmol) in tet-
rahydrofuran (10 mL) were added. The reaction mixture
was then stirred at room temperature for ca. 72 h. The sol-
vent was removed under reduced pressure. The crude prod-
uct was purified by column chromatography, eluting with a
10:1 mixture of dichloromethane and methanol to give 7f
(75 MHz, CDCl3): d = 145.7, 128.3, 127.3 125.3, 70.2,
20
25.0. lit.26a ½aꢁD ¼ þ28:4 (c 1.2, MeOH); 97% ee.
4.3.2. (R)-1-(4-Methoxy-phenyl)-ethanol 9b.9b Colorless
oil; 91% yield. 90% ee. Determined by HPLC analysis (Dai-
cel Chiralcel OJ column, hexane/isopropanol = 90:10,
0.5 mL/min, 254 nm). Retention time: tmajor = 29.36 and
20
tminor = 27.54 min. ½aꢁ ¼ þ37:9 (c 1.2, CH2Cl2). 1H
D
NMR (300 MHz, CDCl3): d = 7.26 (d, J = 8.4 Hz, 2H),
6.87–6.84 (m, 3H), 4.81 (q, J = 6.6 Hz, 1H), 3.77 (s, 1H),
2.15 (br, 1H), 1.46 (d, J = 6.6 Hz, 3H); 13C NMR
(75 MHz, CDCl3): d = 158.7, 138.0, 126.6, 113.6, 69.6,
20
55.1, 24.8. lit.9b ½aꢁD ¼ þ49:4 (c 2.3, CH2Cl2); 93% ee.
as a white solid (566 mg, 85% yield). White solid, mp
4.3.3. (R)-1-(4-Fluoro-phenyl)-ethanol 9c.9b Colorless oil;
98% yield. 96% ee. Determined by HPLC analysis (Daicel
Chiralcel OJ column, hexane/2-propanol = 95:5, 0.5 mL/
min, 254 nm). Retention time: tmajor = 15.82 and tmi-
20
124–126 °C, ½aꢁD ¼ ꢀ54:8 (c 1.2, CH2Cl2); 1H NMR
(400 MHz, CDCl3): d = 7.77 (s, 6H), 7.54 (d, J = 7.6 Hz,
12H), 7.48–7.42 (m, 12H), 7.26–7.10 (m, 36H), 6.96–6.93
(m, 6H), 6.81–6.79 (m, 6H), 6.67 (d, J = 8.4 Hz, 6H),
6.59 (s, 3H), 5.15–5.05 (m, 18H), 4.95 (s, 6H), 4.37 (t,
J = 8.8 Hz, 6H), 3.41–3.40 (m, 6H), 3.23–3.20 (m, 6H),
2.18–2.06 (m, 15H), 1.91 (br, 6H); 13C NMR (100 MHz,
20
1
nor = 15.18 min. ½aꢁD ¼ þ39:8 (c 1.0, CH2Cl2). H NMR
(300 MHz, CDCl3): d = 7.36–7.32 (m, 2H), 7.06–7.00 (m,
2H), 4.89 (q, J = 6.6 Hz, 1H), 1.74 (br, 1H), 1.48 (d,
J = 6.6 Hz, 3H); 13C NMR (75 MHz, CDCl3): d = 162.0,

Y.-N. Niu et al. / Tetrahedron: Asymmetry 19 (2008) 912–920
919
20
141.5, 127.0, 126.9, 114.9, 69.3, 24.9. lit.9b ½aꢁD ¼ þ34:1 (c
0.5 mL/min, 254 nm). Retention time: tmajor = 25.30 and
20
2.0, CH2Cl2); 95% ee.
tminor = 23.51 min. ½aꢁD ¼ þ38:5 (c 1.2, CHCl3). 1H
NMR (300 MHz, CDCl3): d = 7.26–7.20 (m, 1H), 6.91
(m, 2H), 6.79–6.76 (m, 1H), 4.81 (q, J = 6.6 Hz, 1H),
3.77 (s, 3H), 2.34 (br, 1H), 1.45 (d, J = 6.6 Hz, 3H); 13C
4.3.4. (R)-1-(4-Chloro-phenyl)-ethanol 9d.9b Colorless oil;
97% yield. 92% ee. Determined by HPLC analysis (Daicel
Chiralcel OJ column, hexane/2-propanol = 90:10, 0.5 mL/
NMR (75 MHz, CDCl3): d = 159.6, 147.5, 129.3, 117.6,
28
min, 254 nm). Retention time: tmajor = 14.53 and
112.7, 110.8, 70.1, 55.1, 25.0. lit.26b ½aꢁD ¼ þ39 (c 1.0,
20
D
tminor = 13.61 min. ½aꢁ ¼ þ39:5 (c 1.2, CH2Cl2). 1H
CHCl3); 96% ee.
NMR (400 MHz, CDCl3): d = 7.32–7.26 (m, 4H), 4.85 (q,
J = 6.8 Hz, 1H), 2.10 (br, 1H), 1.45 (d, J = 6.4 Hz, 3H);
4.3.10. (R)-1-(2-Methoxy-phenyl)-ethanol 9j.9b Colorless
oil; 96% yield. 93% ee. Determined by HPLC analysis (Dai-
cel Chiralcel OJ column, hexane/2-propanol = 90:10,
13C NMR (100 MHz, CDCl3): d = 144.4, 133.2, 128.8,
20
126.0, 69.9 25.4. lit.9b ½aꢁD ¼ þ47:2 (c 1.8, CH2Cl2); 94%
ee.
0.5 mL/min, 254 nm). Retention time: tmajor = 20.65 and
20
tminor = 20.05 min. ½aꢁD ¼ þ45:8 (c 1.4 CH2Cl2). 1H
4.3.5. (R)-1-(4-Bromophenyl)-ethanol 9e.9b Colorless oil;
93% yield. 94% ee. Determined by HPLC analysis (Daicel
Chiralcel OJ column, hexane/2-propanol = 90:10, 0.5 mL/
NMR (300 MHz, CDCl3): d = 7.33 (d, J = 7.2 Hz, 1H),
7.26–7.20 (m, 1H), 6.97–6.92 (m, 1H), 6.88–6.85 (d,
J = 8.4 Hz, 1H), 5.08 (q, J = 6.3 Hz, 1H), 3.84 (s, 3H),
2.72 (br, 1H), 1.49 (d, J = 6.6 Hz, 3H). 13C NMR
min, 254 nm). Retention time: tmajor = 15.52 and tminor
=
20
14.49 min. ½aꢁD ¼ þ17:6 (c 1.4, CH2Cl2). 1H NMR
(300 MHz, CDCl3): d = 7.47–7.43 (m, 2H), 7.26–7.21 (m,
2H), 4.83 (q, J = 6.3 Hz, 1H), 2.16 (br, 1H), 1.44 (d,
(75 MHz, CDCl3): d = 156.4, 133.3, 128.2, 126.0, 120.7,
20
110.3, 66.3, 55.1, 22.8. lit.9b ½aꢁD ¼ þ53:0 (c 1.5, CH2Cl2);
87% ee.
J = 6.6 Hz, 3H); 13C NMR (75 MHz, CDCl3): d = 144.7,
20
131.3, 127.0, 121.0, 69.4, 25.0. lit.9b ½aꢁD ¼ þ16:8 (c 2.1,
4.3.11. (S)-2-Chloro-1-phenyl-ethanol 9k.26c Colorless oil;
95% yield. 87% ee. Determined by HPLC analysis (Daicel
Chiralcel OJ column, hexane/2-propanol = 90:10, 0.5 mL/
CH2Cl2); 91% ee.
4.3.6. (R)-1-(4-Nitro-phenyl)-ethanol 9f.9b Colorless oil;
99% yield. 93% ee. Determined by HPLC analysis (Daicel
Chiralcel OJ column, hexane/2-propanol = 90:10, 0.5 mL/
min, 254 nm). Retention time: tmajor = 28.79 and tminor =
20
26.68 min. ½aꢁD ¼ þ41:8 (c 1.4, C6H12). 1H NMR
(300 MHz, CDCl3): d = 7.36–7.22 (m, 5H), 4.85 (dd,
J = 3.6 Hz, 8.4 Hz, 1H), 3.73–3.58 (m, 2H), 2.82 (br, 1H);
min, 254 nm). Retention time: tmajor = 38.04 and tminor
=
20
34.61 min. ½aꢁD ¼ þ29:0 (c 1.2, CH2Cl2). 1H NMR
(400 MHz, CDCl3): d = 8.17 (d, J = 9.2 Hz, 2H), 7.54 (d,
J = 8.4 Hz, 2H), 5.01 (q, J = 6.8, 1H), 2.48 (br, 1H), 1.51
(d, J = 6.4 Hz, 3H); 13C NMR (100 MHz, CDCl3):
13C NMR (75 MHz, CDCl3): d = 139.8, 128.5, 128.3,
25
125.9, 73.9, 50.7. lit.26c ½aꢁD ¼ þ42:8 (c 1.5, C6H12); 87% ee.
4.3.12. (S)-2-Bromo-1-phenyl-ethanol 9l.26c Colorless oil;
93% yield. 92% ee. Determined by HPLC analysis (Daicel
Chiralcel OJ column, hexane/2-propanol = 90:10, 0.5 mL/
d = 153.1, 147.0, 126.0, 123.6, 69.3, 25.3. lit.9b
20
½aꢁD ¼ þ27:1 (c 2.1, CH2Cl2); 98% ee.
min, 254 nm). Retention time: tmajor = 28.40 and tminor
=
20
4.3.7. (R)-1-Naphthalen-2-yl-ethanol 9g.26a White solid;
95% yield. 87% ee. Determined by HPLC analysis (Daicel
Chiralcel OJ column, hexane/2-propanol = 90:10, 0.5 mL/
26.30 min. ½aꢁD ¼ þ38:8 (c 1.1, CHCl3). 1H NMR
(400 MHz, CDCl3): d = 7.36–7.30 (m, 5H), 4.87 (dd,
J = 3.2 Hz, 6.4 Hz, 1H), 3.60–3.48 (m, 2H ), 2.97 (br,
min, 254 nm). Retention time: tmajor = 40.46 and tminor
=
1H); 13C NMR (100 MHz, CDCl3): d = 140.3, 128.6,
20
25
31.05 min. ½aꢁD ¼ þ29:8 (c 1.3, CHCl3). 1H NMR
(400 MHz, CDCl3): d = 7.83–7.79 (m, 4H), 7.50–7.24 (m,
3H), 4.81 (q, J = 6.6 Hz, 1H), 2.06 (br, 1H), 1.45 (d,
J = 6.6 Hz, 3H). 13C NMR (100 MHz, CDCl3):
128.3, 125.9, 73.7, 39.9. lit.26d ½aꢁD ¼ þ40:1 (c 1.8, CHCl3);
92% ee.
4.3.13. (R)-1,2,3,4-Tetrahydronaphthalen-1-ol 9m.26e Col-
orless oil; 98% yield. 81%, ee. Determined by HPLC anal-
ysis (Daicel Chiralcel OJ column, hexane/2-propanol =
90:10, 0.5 mL/min, 254 nm). Retention time: tmajor = 14.64
d = 143.4. 133.5, 133.1, 128.5, 128.1, 127.8, 126.3, 126.0,
20
124.0, 70.7, 29.9. 25.3. lit.26a ½aꢁD ¼ þ30:4 (c1.4, CHCl3);
93% ee.
20
1
and tminor = 12.97 min. ½aꢁ ¼ ꢀ28:3 (c 1.1, CHCl3). H
NMR (300 MHz, CDCl3):Dd = 7.41–7.39 (m, 1H), 7.38–
7.15 (m, 2H), 7.08–7.06 (m, 1H), 4.72 (s, 1H), 2.76–2.65
(m, 2H), 2.13 (s, 1H); 1.99–1.71 (m, 4H); 13C NMR
4.3.8. (R)-1-(3-Bromophenyl)-ethanol 9h.26a Colorless oil;
90% yield. 87% ee. Determined by HPLC analysis
(Daicel Chiralcel OJ column, hexane/2-propanol = 90:10,
0.5 mL/min, 254 nm). Retention time: tmajor = 14.73 and
(75 MHz, CDCl3): d = 138.7, 137.0, 128.8, 128.5, 127.4,
20
20
tminor = 13.22 min. ½aꢁD ¼ þ39:2 (c 1.4, CHCl3). 1H
126.0, 67.9, 32.1, 29.1, 18.7. lit.26e ½aꢁD ¼ ꢀ28:6 (c 0.5,
NMR (300 MHz, CDCl3): d = 7.53 (s, 1H), 741–7.38 (m,
2H), 7.30–7.18 (m, 2H), 4.86 (q, J = 6.3 Hz, 1H), 1.90
(br, 1H), 1.48 (d, J = 6.6 Hz, 3H); 13C NMR (75 MHz,
CHCl3); 82% ee.
4.3.14. (R)-1-Phenylpropan 9n.26e Colorless oil; 95%,
yield. 71% ee. Determined by HPLC analysis (Daicel Chi-
ralcel OJ column, hexane/2-propanol = 90:10, 0.5 mL/min,
254 nm). Retention time: tmajor = 14.49 and tminor = 13.82
CDCl3): d = 148.0, 130.3, 129.9, 128.4, 123.9, 122.4, 69.5,
20
25.1. lit.26a ½aꢁD ¼ þ45:4 (c 1.0, CHCl3); 96% ee.
20
1
4.3.9. (R)-1-(3-Methoxy-phenyl)-ethanol 9i.26b Colorless
oil; 95% yield. 92% ee. Determined by HPLC analysis (Dai-
cel Chiralcel OJ column, hexane/2-propanol = 90:10,
min. ½aꢁD ¼ þ27:6 (c 1.4, CHCl3). H NMR (300 MHz,
CDCl3): d = 7.34–7.23 (m, 5H), 4.53 (t, J = 4.8 Hz, 1H),
2.26 (br, 1H), 1.82–1.69 (m, 2H), 0.88 (t, J = 6.6 Hz, 3H);

920
Y.-N. Niu et al. / Tetrahedron: Asymmetry 19 (2008) 912–920
13C NMR (75 MHz, CDCl3): d = 144.5, 128.3, 127.3,
13. (a) Mathre, S. A.; Thompson, A. W.; Douglas, K.; Hoogs-
teen, J. D.; Carroll, E. G.; Corey, E. J.; Grabowski, J. J. Org.
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Woodall, T. W. J. Am. Chem. Soc. 1994, 116, 8516–8525; (c)
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20
125.9, 75.8, 31.7, 10.0. lit.26e ½aꢁD ¼ þ29:0 (c 1.0, CHCl3);
77% ee.
Acknowledgments
We thank the NSF (NSF-20021001, NSF-20672049) and
the ‘Hundred Scientists Program’ from the Chinese Acad-
emy of Science for financial support.
14. Yang, G. Sh.; Hu, J. B.; Zhao, G.; Ding, Y.; Tang, M. H.
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