Planar chiral imidazolium salts based on [2.2]paracyclophane in the asymmetric rhodium-catalyzed 1,2-addition of arylboronic acids to aldehydes

Article abstract of DOI:10.1016/j.tetasy.2010.01.025

A series of planar chiral imidazolium salts derived from [2.2]paracyclophane have been synthesized and characterized. By using these imidazolium salts as carbene precursors, the Rh-catalyzed 1,2-addition of arylboronic acids to aldehydes proceeded readily with low catalyst loadings (0.03-0.3 mol %) and gave a variety of chiral diarylmethanols in excellent yields and moderate enantioselectivities.

Full text of DOI:10.1016/j.tetasy.2010.01.025

Tetrahedron: Asymmetry 21 (2010) 292–298
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Planar chiral imidazolium salts based on [2.2]paracyclophane in the
asymmetric rhodium-catalyzed 1,2-addition of arylboronic acids to aldehydes
*
Qingshuang Ma, Yudao Ma , Xiao Liu, Wenzeng Duan, Bo Qu, Chun Song
Department of Chemistry, Shandong University, Shanda South Road No. 27, Jinan 250100, People’s Republic of China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 9 December 2009
Accepted 15 January 2010
A series of planar chiral imidazolium salts derived from [2.2]paracyclophane have been synthesized and
characterized. By using these imidazolium salts as carbene precursors, the Rh-catalyzed 1,2-addition of
arylboronic acids to aldehydes proceeded readily with low catalyst loadings (0.03–0.3 mol %) and gave
a variety of chiral diarylmethanols in excellent yields and moderate enantioselectivities.
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
cially with regard to the synthesis of new derivatives and their
applications in asymmetric catalysis.11,12 A series of planar chiral
The asymmetric arylation of aldehydes has recently received
considerable attention since chiral diarylmethanols are key struc-
tural elements in an array of pharmacologically active compounds
and are, for that reason, important synthetic targets.1 The asym-
metric Rh-catalyzed addition of organoboronic acids to aldehydes
is a general method for the synthesis of optically active diaryl-
methanols which have attracted much attention since Miyaura
et al. first reported in 1998.2 Due to the advantageous features of
organoboronic acids, such as low toxicity and easy manipulation,
considerable efforts have been made in this type of reaction.3
Complexes with N-heterocyclic carbenes (NHCs)4 have, during
recent years, gathered considerable interest from the organic
chemistry community and have been widely used in homogeneous
metal catalysis.5 Impressive progress has been made with regard to
their synthesis and application.5,6 The Rh-NHC-catalyzed addition
of arylboronic acid derivatives to aldehydes deserves particular
mention because these methods present high efficiency with a rea-
sonable tolerance towards polar substituents in the substrates.7 In
2005, Bolm reported the synthesis of a variety of chiral imidazoli-
um salts and their application in the asymmetric arylation of alde-
hydes.8 The protocol they reported can afford optically active
diarylmethanols in good yield. In spite of these efforts, examples
of the catalyzed addition with chiral N-heterocyclic carbene li-
gands remain scarce. Thus, it is still desirable to develop or find
more active chiral catalysts and efficient catalytic systems for
1,2-addition of organoboronic acids to aldehydes.
imidazoliniums derived from [2.2]paracyclophane have been pre-
pared by this group and their applications as rhodium or ruthe-
nium complexes in highly enantioselective transformations have
also been demonstrated.12 The above-mentioned findings and our
interests in NHCs and C–C forming reactions triggered our efforts
to develop new planar chiral imidazolium salts as NHC precursors
for application in homogeneous catalysis. We herein report the
synthesis of a new family of planar chiral imidazolium salts based
on [2.2]paracyclophane and their application in the asymmetric
rhodium-catalyzed 1,2-addition of arylboronic acids to aldehydes.
2. Results and discussion
Our straightforward synthetic pathway to the planar chiral imi-
dazolium salts is shown in Schemes 1 and 2. The synthesis of new
planar chiral imidazolium salts began with the known compounds
(Sp)-4-amino-12-bromo[2.2]paracyclophane 1a and (4Rp,13Sp)-4-
amino-13-bromo[2.2]paracyclophane 2a (Schemes 1 and 2).12
One of the important characteristics of 1a and 2a is the fact that
they are easily tunable in their steric profile.
Suzuki–Miyaura coupling with arylboronic acids under Pd-DPPF
catalysis gave the sterically hindered amino [2.2]paracyclophanes
in good to excellent yields (85–99%).12 Treatment of the substi-
tuted amino [2.2]paracyclophanes with aqueous glyoxal in THF
at room temperature gave the corresponding diimines in essen-
tially quantitative yield. In analogy to procedures for the transfor-
mation of glyoxal-derived diimines into imidazolium salts,13 we
treated diimines with chloromethyl ethyl ether in THF at 40 °C.
However, all imidazolium chlorides could not be purified by chro-
matography and recrystallization except for 3a (54% yield). Follow-
ing another literature method,14 the treatment of diimines with
paraformaldehyde and hydrogen chloride in toluene gave very
similar results. We were pleased to find that a reagent formed from
The element of planar chirality plays an increasingly important
role in modern organometallic chemistry.9 The field of [2.2]paracy-
clophane chemistry has expanded considerably since these com-
pounds first attracted the interest of chemists in the middle of
the last century.10 Recently, there has been notable progress, espe-
* Corresponding author. Tel.: +86 531 88361869; fax: +86 531 88565211.
E-mail address: ydma@sdu.edu.cn (Y. Ma).
0957-4166/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2010.01.025

Q. Ma et al. / Tetrahedron: Asymmetry 21 (2010) 292–298
293
NH2
N
N
i)
O
O
Cl
ii) ClCH2OCH2CH3
R
R
R
R
3
1
3a: 54%; 3b: 23%; 3c: 28%
NH2
N
N
i)
O
O
Cl
ii) (CH2O)n / HCl
R
R
3
1
3a: 60%; 3b: 0; 3c: 0
Figure 1. ORTEP diagram of the molecular structure of 4a. Ellipsoids are drawn at
the 50% probability level. Hydrogen atoms have been removed for clarity.
OCH3
c:
a: Br
b:
R =
of potassium tert-butoxide/phenylboronic acid (1:2) was examined
in different solvents at 80 °C for 2 h. As can be seen from Table 1,
no products were obtained in dioxane or DME if no water was in-
volved. The rate and enantioselectivity of the reaction was influ-
enced by the amount of water in the DME/water system (Table 1,
entries 2–5). In DME/water (5:1), the ligand showed good activity
(64% yield) and moderate enantioselectivity (36% ee). However, the
complexes were unstable in this solvent system and this cause led
to relatively low yield. Our efforts indicated that MeOH/DME (5:1)
was the most suitable, affording the desired product in 99% yield
and 41% ee (Table 1, entry 7). Therefore, MeOH/DME (5:1) was se-
lected as the reaction solvent in the following reactions. Different
rhodium sources were also investigated with ligand 4a (Table 1,
entries 9–11); [Rh(OAc)2]2 emerged as the best choice of catalyst
precursors.
Scheme 1. Synthesis of the imidazolium chlorides.
NH2
N
i)
N
O
O
O
OTf
ii) AgOTf
R
R
R
ClCH2OCC(CH3)3
1
4a: 91%; 4b: 76%;
4c: 85%:4d: 83%; 4e: 78%
i)
O
O
O
OTf
N
N
NH2
ii) AgOTf
R
R
R
We chose MeOH/DME (5:1) as the solvent system and other li-
gands were screened in the arylation of aldehydes (Table 2).
Diarylmethanol 8ab was obtained in high yield (95–99%) with each
of the imidazolium salts 3a, 4a–e and 5a–f. The ligands 4a and 5a
ClCH2OCC(CH3)3
5a: 78%: 5c:58%;
5d: 54%; 5f: 72%.
2
OCH3
c:
a: Br
b:
R =
Table 1
Optimization of the reaction conditionsa
e:
d:
f: H
HO
OCH3
4a (3 mol %)
[Rh(OAc)2]2 (3 mol %)
CHO
B(OH)2
+
KOBu-t
Solvent
Scheme 2. Synthesis of the imidazolium triflates.
7b
8ab
6a
equal amounts of silver triflate and chloromethyl pivalate15 re-
sulted in the formation of the desired imidazolium triflates in mod-
erate to good yields (54–91%). The imidazolium salts 3a, 4a–e and
5a–f were purified, and fully characterized by NMR, mass spec-
trometry, and, in the case of 4a, single-crystal X-ray diffraction
analysis (Fig. 1).
The imidazolium salts 3a, 4a–e and 5a–f thus obtained were
then used as precursors for rhodium–NHC complexes, which were
applied in the catalytic addition of arylboronic acids to aromatic
aldehydes.
We began by optimizing the reaction conditions using 4a as li-
gand, a number of parameters were varied using phenylboronic
acid and 1-naphthaldehyde as model substrates.
The reaction conditions were evaluated with a particular
emphasis on solvent effects. The 1,2-addition of phenylboronic
acid to 1-naphthaldehyde with 3.0 mol % of catalyst generated
in situ from imidazolium salt 4a and [Rh(OAc)2]2 in the presence
Entry
Solvent
Yieldb (%)
eec (%)
1
2
3
4
5
6
7
8
Dioxane
DME
0
0
—
—
DME/H2O (10:1)
DME/H2O (5:1)
DME/H2O (3:1)
MeOH
MeOH/DME (5:1)
Ethanol/DME (5:1)
MeOH/DME (5:1)
MeOH/DME (5:1)
MeOH/DME (5:1)
58
64
70
99
99
99
90
89
83
36 (R)
36 (R)
0
30 (R)
41 (R)
37 (R)
34 (R)
11 (R)
30 (R)
9d
10e
11f
a
Reaction conditions: [Rh(OAc)2]2 (3 mol %), 4a (3 mol %), KOBu-t (1 equiv),
arylboronic acids (2 equiv), N2, 80 °C, 2 h.
b
Isolated yield.
c
Determined by chiral HPLC (CHIRALPAK IA Column) analysis.
[Rh(nbd)Cl]2 was used as the rhodium source.
[Rh(cod)Cl]2 was used as the rhodium source.
RhCl3 was used as the rhodium source.
d
e
f

294
Q. Ma et al. / Tetrahedron: Asymmetry 21 (2010) 292–298
Table 3
gave the product with 41% and 31% ee, respectively (Table 2, en-
tries 2 and 7). It is well-known that an increase in the bulkiness
of chiral groups may lead to increased enantiocontrol in asymmet-
ric reactions. In the hope of increasing the enantioselectivity to
appreciable levels, steric bulk was introduced to the ligands 4a
and 5a. These sterically hindered ligands 4b–e, 5c, and 5d gave
inferior enantioselectivities in contrast to ligands 4a and 5a.
Imidazolium chloride 3a gave almost the same activity with the
corresponding imidazolium triflate 4a and a slightly inferior
enantioselectivity. Better results were obtained with imidazolium
salts 4a and 5f as ligands, however, the analogous imidazolinium
tetrafluoroborate L1 and L2 exhibited very poor catalytic abilities
(Scheme 3, Table 2, entries 11 and 12).
Scope of the methodologya
4a (0.3 mol %)
[Rh(OAc)2]2 (0.3 mol %)
O
OH
Ar2
+
Ar2 B(OH)2
Ar1
H
Ar1
KOBu-t
MeOH / DME
8
6
7
Entry
Ar1
Ar2
Yieldb (%)
eec (%)
1
2
3
4
5
1-Naphthyl 6a
1-Naphthyl 6a
1-Naphthyl 6a
Phenyl 6b
Phenyl 6b
Phenyl 6b
Phenyl 7b
94 8ab
97 8ac
97 8ad
94 8ba
97 8bc
97 8bd
96 8ca
95 8cb
99 8cd
92 8da
95 8db
93 8dd
41 (R)
52 (ꢀ)
34 (+)
41 (S)
46 (S)
28 (S)
52 (+)
46 (R)
40 (+)
45 (R)
42 (ꢀ)
38 (R)
2-MeOC6H4 7c
3-MeOC6H4 7d
1-Naphthy 7a
2-MeOC6H4 7c
3-MeOC6H4 7d
1-Naphthy 7a
Phenyl 7b
3-MeOC6H4 7d
1-Naphthyl 7a
2-MeOC6H4 7c
3-MeOC6H4 7d
6
7
8
9
10
11
12
2-MeOC6H4 6c
2-MeOC6H4 6c
2-MeOC6H4 6c
4-ClC6H4 6d
4-ClC6H4 6d
4-ClC6H4 6d
Br
Br
BF4
BF4
N
N
N
N
a
L1
L2
Reaction conditions: [Rh(OAc)2]2 (0.3 mol %), 4a (0.3 mol %), KOBu-t (1 equiv),
arylboronic acids (2 equiv), N2, MeOH/DME (5:1), reflux, 6 h.
b
Isolated yields.
Scheme 3. Imidazolinium salts L1 and L2.
c
Determined by chiral HPLC (CHIRALPAK IA Column) analysis.
Table 2
Ligand evaluation studya
enantioselectivity (up to 52%) with only 0.3 mol % catalyst. The
substitution pattern of the substrates had an important effect on
the enantioselectivity of the products. The aromatic aldehyde or
arylboronic acid bearing an ortho-substituent afforded the chiral
diarylmethanols with higher enantiomeric excess. An interesting
feature of this methodology is that both enantiomers of a given
diarylmethanol can be easily prepared with the same chiral ligand,
just by the appropriate choice of the reaction partners: arylboronic
acid or aldehyde.
HO
CHO
B(OH)2
Ligand (3 mol %)
[Rh(OAc)2]2 (3 mol %)
+
KOBu-t
MeOH / DME
8ab
6a
7b
Entry
Ligand
Yieldb (%)
eec (%)
3. Conclusion
1
2
3
4
5
6
7
8
9
3a
4a
4b
4c
4d
4e
5a
5c
5d
5f
99
99
95
95
99
97
99
95
99
99
9
37 (R)
41 (R)
10 (R)
3 (R)
14 (R)
30 (R)
31 (S)
3 (S)
In conclusion, a series of planar chiral imidazolium salts based
on [2.2]paracyclophane have been prepared. Their applicability in
rhodium-catalyzed asymmetric additions of arylboronic acids
to aromatic aldehydes has been demonstrated. Even with
0.03 mol % of the catalyst, the reactions could be carried out
quickly and gave the chiral diarylmethanols in excellent yields.
7 (S)
10
11
12
40 (S)
13 (S)
5 (S)
L1
L2
14
4. Experimental
a
Reaction conditions: [Rh(OAc)2]2 (3 mol %), ligand (3 mol %), KOBu-t (1 equiv),
4.1. General remarks
arylboronic acids (2 equiv), N2, MeOH/DME (5:1), reflux, 2 h.
b
Isolated yield.
c
Determined by chiral HPLC (CHIRALPAK IA Columns) analysis.
Commercially available reagents were used without further
purification unless otherwise noted. Solvents were reagent grade
and purified by standard techniques. (Sp)-4-Amino-12-bromo[2.2]
paracyclophane 1a, Sp-4-amino-12-(2-methoxyphenyl)[2.2]para-
cyclophane 1b, Sp-4-amino-12-phenyl[2.2] paracyclophane 1c,
(4Rp,13Sp)-4-amino-13-bromo[2.2]paracyclophane 2a, (4Rp,13Sp)-
4-amino-13-phenyl[2.2] paracyclophane 2c, (4Rp,13Sp)-4-amino-
In view of the high activity of these ligands, the low catalyst
loading conditions were carried out with 4a as the carbene pre-
cursor. The 1,2-addition of phenylboronic acid to 1-naphthalde-
hyde with 0.3 and 0.1 mol % of the catalyst, under our
optimized reaction conditions, led to product 8ab in 98% yield/
41% ee and in 94% yield/32% ee, respectively. In contrast to the
3 mol % catalyst loading, the reaction rate was slower but the
enantioselectivity did not diminish with 0.3 mol % catalyst. Even
with 0.03 mol % of the catalyst, the reaction proceeded readily
and gave the desired product in 91% yield and 21% ee after
12 h.
13-(3-methoxyphenyl)[2.2]paracyclophane
2d,
(Rp)-4-amino
[2.2]paracyclophane 2f, N,N0-Bis[Rp-(ꢀ)-12-bromo-4-[2.2]paracy-
clophanyl] imidazolinium Tetrafluoroborate L1 and N,N0-bis
[(Rp-(ꢀ)-4-[2.2]paracyclophanyl] imidazolinium tetrafluoroborate
L2 were prepared according to published procedures. Melting
points were recorded on a melting point apparatus and are
uncorrected. 1H and 13C spectra were recorded on 400 and
300 MHz spectrometers. Mass spectra were recorded on an Agilent
100 ABI-API14000 spectrometer. Optical rotations were taken on a
polarimeter with a wavelength of 589 nm. The concentration ‘c’
has units of g/100 mL (or 10 mg/mL) unless otherwise noted.
As shown in Table 3, the optimized protocol was tested in the
asymmetric arylation of aldehydes with different steric and elec-
tronic properties. In most cases, the reaction proceeded with nota-
ble efficiency (up to 99% isolated yield) and moderate

Q. Ma et al. / Tetrahedron: Asymmetry 21 (2010) 292–298
295
4.2. General procedures for the synthesis of (Sp)-4-amino-12-
aryl[2.2]paracyclophane 1
and a yellow precipitate appeared. After completion of the reaction
as indicated by TLC, the yellow precipitate was collected by filtra-
tion and washed with 2.0 mL water. The desired diimine was iso-
lated as a yellow solid (594.8 mg, 95% yield).
(Sp)-4-Amino-12-bromo [2.2]paracyclophane 1a (501.3 mg,
1.66 mmol), arylboronic acid (2.49 mmol), KF (289.7 mg,
4.98 mmol) and Pd-DPPF (13.6 mg, 1.66 ꢁ 10ꢀ2 mmol) in 1,4-diox-
ane (5.0 mL) were stirred at 80 °C for about 4 h under a slight
positive pressure of nitrogen. After completion of the reaction as
indicated by TLC, the mixture was cooled to the room temperature;
water (5.0 mL) was added and filtered. The solution was extracted
by dichloromethane (10.0 mL ꢁ 3), and the solvent was removed
on a rotary evaporator. The residue was purified by chromatogra-
phy on silica gel (hexanes/ethyl acetate = 20:1), and pure product
was isolated.
To a solution of diimine (413 mg, 0.66 mmol) in toluene (5.0 ml)
was added 20.0 mg (0.66 mmol) of paraformaldehyde in solid
form. The reaction mixture was heated to 100 °C until most of
paraformaldehyde was dissolved. It was then cooled to 40 °C and
0.17 ml of HCl (0.66 mmol, 4 M in dioxane) was syringed in. The
reaction mixture was heated to 70 °C for 5 h during which time
the color of the reaction mixture turned brown and a white precip-
itate appeared. It was then allowed to stir at rt for 36 h. The off-
white precipitate was collected by filtration and washed with
THF. Then the resulting solid was chromatographed on silica gel
(CH2Cl2/MeOH 50:1–10:1) and the pure product was isolated
(312.0 mg, 60% yield).
(Sp)-4-Amino-12-(3-methoxyphenyl) [2.2]paracyclophane 1d
was obtained as a crystalline white solid (99% yield). Mp 100–
101 °C; Rf 0.54 (hexanes/ethyl acetate = 5:1); ½a D20
ꢂ
¼ ꢀ62 (c 1.0,
N,N0-Bis[(Sp)-(+)-12-bromo-4-[2.2]paracyclophanyl]imidazoli-
um chloride 3a was obtained as a solid; Mp >260 °C; Rf 0.4 (CH2Cl2/
CHCl3); 1H NMR (400 MHz, CDCl3, rt): d 7.30–7.27 (m, 1H), 7.20
(d, J = 1.4 Hz, 1H), 7.10 (t, J = 7.6 Hz, 2H), 6.86 (d, J = 7.8 Hz, 1H),
6.69 (d, J = 7.6 Hz, 1H), 6.43 (d, J = 7.56 Hz, 2H), 6.23 (s, 1H), 5.67
(s, 1H), 3.86 (s, 3H), 3.64–3.45 (m, 2H),3.13–3.11 (m, 3H), 2.89–
2.74 (m, 3H), 2.45–2.38 (m, 1H); 13C NMR (75 MHz, CDCl3, rt): d
159.1, 142.5, 140.9, 140.2, 138.5, 135.8, 134.5, 134.4, 131.8,
128.9, 127.3, 121.5, 115.0, 111.2, 54.8, 33.7, 33.5, 31.9, 31.7. HRMS
(ESI): calcd for C23H24NO (M+H)+ 330.1858, found 330.1868.
(Sp)-4-Amino-12-(1-naphthyl) [2.2]paracyclophane 1e was ob-
tained as a crystalline white solid (98% yield). Mp 185–187 °C, Rf
ethanol = 15:1); ½a D20
ꢂ
¼ þ26:7 (c 0.50, CHCl3); 1H NMR (300 MHz,
CDCl3, rt): d 11.36 (s, 1H), 8.38 (s, 2H), 7.20 (s, 2H), 6.88 (d,
J = 3.9 Hz, 2H), 6.71 (s, 6H), 6.60 (s, 2H), 3.58–3.55 (m, 4H), 3.22–
3.19 (m, 6H), 2.99–2.91 (m, 4H), 2.64–2.57 (m, 2H); 13C NMR
(75 MHz, CDCl3, rt): d 141.4, 141.0, 138.3, 137.5, 135.3, 135.0,
132.8, 132.8, 131.8, 125.6, 122.2, 122.1, 35.0, 33.4, 32.4, 31.8.
HRMS (ESI): calcd for C35H31Br2N2 (MꢀCl)+ 639.0834, found
639.0851.
0.58 (hexanes/ethyl acetate = 5:1); ½a D20
ꢂ
¼ ꢀ333:5 (c 1.0, CHCl3);
4.4. General procedures for the synthesis of imidazolium
triflates 4 and 5
1H NMR (400 MHz, CDCl3, rt): d 7.92 (d, J = 8.5 Hz, 1H), 7.85 (t,
J = 7.4 Hz, 2H), 7.77–7.75 (m, 1H), 7.64 (d, J = 7.8 Hz, 1H), 7.44 (s,
1H), 7.36 (d, J = 7.1 Hz, 1H), 7.20 (d, J = 1.6, Hz, 1H), 6.74 (d,
J = 7.7 Hz, 1H), 6.59–6.29 (m, 2H), 6.28 (s, 1H), 5.86 (s, 1H), 3.21–
3.16 (m, 3H), 2.82–2.77 (m, 2H), 2.69–2.65 (m, 2H), 2.42–2.32
(m, 1H); 13C NMR (75 MHz, CDCl3, rt): d 141.6, 139.9, 139.1,
138.9, 137.2, 134.9, 133.6, 133.6, 133.0, 131.8, 129.3, 128.1,
127.4, 126.6, 126.0, 125.9, 125.6, 125.6, 34.3, 34.0, 32.58, 32.2.
HRMS (ESI): calcd for C26H24N (M+H)+ 350.1909, found 350.1907.
Compound 1 or 2 (1.0 mmol) and 40% glyoxal (174.0 mg,
1.2 mmol) in 1.0 mL THF was stirred at room temperature for
5 h, during which time the color of the reaction mixture turned yel-
low and a yellow precipitate appeared. After completion of the
reaction as indicated by TLC, the yellow precipitate was collected
by filtration and washed with 2.0 mL water. The desired diimine
was isolated as yellow solid.
To a suspension of AgOTf (0.33 g, 1.3 mmol) in CH2Cl2 (2.0 mL)
was added chloromethyl pivalate (0.16 ml, 1.1 mmol) and the
resulting suspension was stirred for 45 min. After filtration the fil-
trate was added to the above diimine (1.0 mmol) and the solution
was stirred in a sealed tube in the dark at 40 °C for 8 h. After the
solution was cooled to room temperature MeOH (1.0 mL) was
added, the solvent was removed in vacuo and the resulting oil
was chromatographed on silica gel (CH2Cl2/MeOH 50:1–10:1)
and pure product was isolated.
4.3. General procedures for the synthesis of imidazolium
chloride 2
4.3.1. Method A
Compound 1a (604.4 mg, 2.0 mmol) and 40% glyoxal (348.0 mg,
2.4 mmol) in 2.0 mL THF were stirred at room temperature for 5 h,
during which time the color of the reaction mixture turned yellow
and a yellow precipitate appeared. After completion of the reaction
as indicated by TLC, the yellow precipitate was collected by filtra-
tion and washed with 2.0 mL water. The desired diimine was iso-
lated as yellow solid (594.8 mg, 95% yield).
4.4.1. N,N0-Bis[(Sp)-(+)-12-bromo-4-
[2.2]paracyclophanyl]imidazolium trifluoromethanesulfonate
4a
A
5 mL single-necked flask was charged with 90.0 mg
(0.91 mmol) of chloromethylethyl ether (95%) in 0.30 ml THF. To
this colorless solution was added solution of 575 mg
Compound 4a was obtained as a white solid (91% yield). Mp
>260 °C; Rf 0.4 (CH2Cl2/ethanol = 20:1); ½a D20
ꢂ
¼ þ18 (c 1.3, CHCl3);
a
1H NMR (300 MHz, DMSO, rt): d 9.50 (s, 1H), 8.31 (d, J = 1.5 Hz,
2H), 7.40 (d, J = 1.5 Hz, 2H), 7.00 (d, J = 8.1 Hz, 2H), 6.89–6.83 (m,
6H), 6.78 (s, 2H), 3.42–2.96 (m, 14H), 2.77–2.50 (m, 2H); 13C
NMR (75 MHz, DMSO, rt): d 147.1, 146.6, 143.7, 142.5, 140.9,
140.7, 140.0, 138.5, 137.9, 137.7, 137.6, 130.9, 128.5, 128.1, 39.9,
38.1, 36.7, 36.5, 35.8. HRMS (ESI): calcd for C35H31Br2N2 (MꢀOTf)+
639.0834, found 639.0939.
(0.91 mmol), of the above diimine in 2.0 ml THF and two drops
of water. The flask was sealed under nitrogen with a septum and
the mixture stirred at 40 °C. A solid began to appear after 1 h of
stirring. Stirring at 40 °C was continued for 16 h and then the mix-
ture was allowed to cool to 23 °C and the precipitated solids were
collected by filtration. The off-white precipitate was collected by
filtration and washed with THF. Then the resulting solid was chro-
matographed on silica gel (CH2Cl2/MeOH 50:1–10:1) and pure
product was isolated (387.0 mg, 54% yield).
4.4.2. N,N0-Bis[(Sp)-(+)-12-(2-methoxyphenyl)-4-
[2.2]paracyclophanyl]imidazolium trifluoromethanesulfonate
4b
4.3.2. Method B
Compound 1a (604.4 mg, 2.0 mmol) and 40% glyoxal (348.0 mg,
2.4 mmol) in 2.0 mL THF was stirred at room temperature for 5 h,
during which time the color of the reaction mixture turned yellow
Compound 4b was obtained as a slight yellow solid (76% yield).
Mp 168–170 °C; Rf 0.4 (CH2Cl2/ethanol = 20:1); ½a D20
¼ þ83:2 (c
ꢂ

296
Q. Ma et al. / Tetrahedron: Asymmetry 21 (2010) 292–298
0.50, CHCl3); 1H NMR (300 MHz, CDCl3, rt): d 8.73 (s, 1H), 7.92 (d,
J = 1.4 Hz, 2H), 7.28–7.26 (m, 2H), 7.08–7.07 (m, 4H), 6.98–6.95 (m,
8H), 6.73 (d, J = 7.5 Hz, 2H), 6.62–6.57 (m, 4H), 3.69 (s, 6H), 3.50–
3.29 (m, 4H), 3.23–3.15 (m, 4H), 3.10–2.88 (m, 6H), 2.65–2.49
(m, 2H); 13C NMR (75 MHz, CDCl3, rt): d 156.3, 143.2, 138.8,
137.4, 137.2, 135.8, 135.8, 135.1, 134.1, 133.0, 132.7, 132.5,
130.4, 129.4, 129.2, 128.6, 126.3, 123.7, 120.9, 111.7, 65.8, 55.4,
34.2, 34.0, 33.6, 32.6. HRMS (ESI): calcd for C49H45N2O2 (MꢀOTf)+
693.3481, found 693.3607.
CHCl3); 1H NMR (300 MHz, CDCl3, rt): d 8.93 (s, 1H), 7.37 (s, 2H),
7.31(d, J = 7.5 Hz, 4H), 7.01–6.85 (m, 8H), 6.81–6.69 (m, 8H), 6.67
(d, J = 6.3 Hz, 2H), 3.50–3.36 (m, 6H), 3.29–2.99 (m, 8H), 2.83–
2.74 (m, 2H); 13C NMR (75 MHz, CDCl3, rt): d 144.1, 140.7, 140.2,
138.6, 137.5, 136.0, 135.2, 134.8, 133.6, 132.7, 132.4, 131.0,
129.7, 128.7, 128.3, 127.1, 125.4, 122.2, 34.7, 34.6, 34.4, 32.8.
HRMS (ESI): calcd for C47H41N2 (MꢀOTf)+ 633.3270, found
633.3241.
4.4.8. N,N0-Bis[(4Rp,13Sp)-13-(3-methoxyphenyl)-4-[2.2]-
paracyclophanyl]imidazolium trifluoromethanesulfonate 5d
Compound 5d was obtained as a slight yellow solid (54% yield).
4.4.3. N,N0-Bis[(Sp)-(+)-12-phenyl-4-[2.2]paracyclophanyl]-
imidazolium trifluoromethanesulfonate 4c
Compound 4c was obtained as a white solid (85% yield). Mp 156–
Mp 196–198 °C; Rf 0.4 (CH2Cl2/ethanol = 20:1); ½a D20
¼ þ210:3 (c
ꢂ
158 °C; Rf 0.4 (CH2Cl2/ethanol = 20:1); ½a D20
ꢂ
¼ þ64:7 (c 0.50, CHCl3);
0.4, CHCl3); 1H NMR (300 MHz, CDCl3, rt): d 8.69 (s, 1H), 7.36 (s,
2H), 7.14 (d, J = 7.8 Hz, 4H), 6.99 (s, 2H), 6.92–6.80 (m, 6H), 6.70
(d, J = 7.5 Hz, 2H), 6.65–6.6.56 (m, 4H), 6.50 (d, J = 8.1 Hz, 2H),
3.59 (s, 6H), 3.33–3.22 (m, 8H), 3.14–3.04 (m, 2H), 2.97–2.72 (m,
6H); 13C NMR (75 MHz, CDCl3, rt): d 155.6, 144.2, 139.3, 137.5,
136.6, 136.3, 134.7, 134.3, 132.8, 132.4, 131.2, 130.1, 128.8,
127.6, 127.0, 123.1, 122.2, 121.0, 111.8, 55.6, 35.0, 34.6, 34.1,
33.6. HRMS (ESI): calcd for C49H45N2O2 (MꢀOTf)+ 693.3481, found
693.3452.
1H NMR (300 MHz, CDCl3, rt): d 7.92 (s, 1H), 7.45 (t, J = 7.5 Hz, 5H),
7.35–7.26 (m, 7H), 6.90–6.65 (m, 10H), 6.46 (s, 2H), 3.56–3.48 (m,
2H), 3.25–3.06 (m, 12H), 2.82–2.75 (m, 2H); 13C NMR (75 MHz,
CDCl3, rt): d 142.6, 140.1, 139.8, 139.7, 139.1, 137.4, 137.1, 136.1,
135.6, 134.1, 132.9, 132.9, 132.6, 130.0, 129.1, 128.3, 127.4,
124.54, 124.5, 123.3, 122.8, 34.3, 34.2, 33.4, 31.8. HRMS (ESI): calcd
for C47H41N2 (MꢀOTf)+ 633.3270, found 633.3241.
4.4.4. N,N0-Bis[(Sp)-(+)-12-(3-methoxyphenyl)-4-[2.2]paracyclo-
phanyl]imidazolium Trifluoromethanesulfonate 4d
4.4.9. N,N0-Bis[(Rp)-(ꢀ)-4-[2.2]paracyclophanyl]imidazolium
trifluoromethanesulfonate 5f
Compound 4d was obtained as a white solid (83% yield). Mp
170–172 °C, Rf 0.4 (CH2Cl2/ethanol = 20:1); ½a D20
ꢂ
¼ þ78:5 (c 0.50,
Compound 5f was obtained as a white solid (72% yield).
CHCl3); 1H NMR (300 MHz, CDCl3, rt): d 7.96 (s, 1H), 7.50 (d,
J = 1.2 Hz, 2H), 7.39–7.34 (t, J = 7.8 Hz, 2H), 6.97 (d, J = 7.5 Hz,
2H), 6.87–6.83 (m, 6H), 6.77–6.45 (m, 8H), 6.47 (s, 2H), 3.77 (s,
6H), 3.59–3.51 (m, 2H), 3.30–3.02 (m, 14H), 2.87–2.80 (m, 2H):
13C NMR (75 MHz, CDCl3, rt): d 159.9, 142.5, 141.5, 139.6, 139.3,
137.4, 137.1, 136.1, 135.7, 133.8, 133.0, 132.8, 130.0, 129.8,
124.4, 123.6, 120.4, 114.9, 112.3, 55.2, 34.3, 34.2, 33.5, 31.8. HRMS
(ESI): calcd for C49H45N2O2 (MꢀOTf)+ 693.3481, found 693.3453.
Mp138–141 °C; Rf 0.4 (CH2Cl2/ethanol = 20:1); ½a D20
¼ ꢀ26:4 (c
ꢂ
0.4, CHCl3); 1H NMR (300 MHz, CDCl3, rt): d 9.30 (s, 1H), 7.93 (s,
2H), 6.78 (d, J = 7.5 Hz, 2H), 6.68–6.51 (m, 13H), 3.51–2.66 (m,
16H); 13C NMR (75 MHz, CDCl3, rt): d143.5, 140.3, 138.3, 137.4,
135.6, 134.7, 133.5, 133.3, 133.2, 132.6, 132.0, 128.4, 126.9,
123.7, 65.8, 34.9, 34.4, 32.5, 15.2. HRMS (ESI): calcd for C35H33N2
(MꢀOTf)+ 481.2644, found 481.2660.
4.4.10. N,N0-Bis[(Rp)-(ꢀ)-12-bromo-4-[2.2]paracyclophanyl]
imidazolinium tetrafluoroborate L1
4.4.5. N,N0-Bis[(Sp)-(+)-12-(1-Naphthyl)-4-[2.2]paracyclophanyl]
imidazolium trifluoromethanesulfonate 4e
Compound L1 was obtained as a white solid (80% yield). Mp
Compound 4e was obtained as a white solid (78% yield). Mp
>260 °C; Rf 0.4 (CH2Cl2/ethanol = 20:1);
½
a 2D0
ꢂ
¼ ꢀ52:0 (c 0.12,
192–194 °C; Rf 0.4 (CH2Cl2/ethanol = 20:1); ½a D20
ꢂ
¼ þ121:3 (c 0.50,
CHCl3); 1H NMR (300 MHz, DMSO, rt): d 8.93 (s, 1H), 7.08 (s, 2H),
6.89 (s, 2H), 6.84–6.79 (m, 6H), 5.06–5.04 (m, 2H), 4.56 (m,2H),
3.37–2.99 (m, 16H); 13C NMR (75 MHz, DMSO, rt): d156.1, 141.9,
140.7, 138.2, 137.2, 135.4, 134.7, 133.6, 133.5, 132.1, 131.3,
125.6, 120.3, 49.5, 34.7, 32.9, 32.3, 31.7. HRMS (ESI): calcd for
C35H33Br2N2 (MꢀBF4)+ 641.0990, found 641.0982.
CHCl3); 1H NMR (300 MHz, CDCl3, rt): d 8.33 (s, 1H), 7.84–7.80
(m, 4H), 7.66–7.60 (m, 3H), 7.43–7.37 (m, 3H), 7.25–7.22 (m,
2H), 7.20–7.14 (m, 7H), 6.93 (d, J = 7.8 Hz, 2H), 6.86–6.80 (m,
4H), 6.68 (d, J = 6.3 Hz, 2H), 6.43 (d, J = 1.5 Hz, 2H), 3.23–2.94 (m,
12H), 2.78–2.48 (m, 2H), 2.46–2.41 (m, 12H); 13C NMR (75 MHz,
CDCl3, rt): d 143.1, 139.0, 137.9, 137.4, 136.2, 136.0, 135.4, 134.3,
134.1, 133.2, 132.8, 132.5, 132.3, 130.3, 128.2, 128.1, 125.9,
125.8, 125.4, 124.0, 123.4, 34.4, 34.0, 33.3, 31.9. HRMS (ESI): calcd
for C55H45N2 (MꢀOTf)+ 733.3583, found 733.3564.
4.5. General procedure for the solvent effect over the arylation
of aldehyde (Table 1)
At first, Rh2(OAc)4 (3.3 mg, 7.5 ꢁ 10ꢀ3 mmol, 3 mol %) was
weighed into a flamed dried tube equipped with a condenser and
under an argon atmosphere. The solvent (0.50 mL) was added
and the suspension was stirred at room temperature for 5 min.
Then, NHC ligand 4a (5.9 mg, 7.5 ꢁ 10ꢀ3 mmol, 3 mol %) phenylbo-
ronic acid (61.0 mg, 0.50 mmol), KOBu-t (28.0 mg, 0.25 mmol), and
1-naphthaldehyde (34.0 mg, 0.25 mmol) were added successively.
The resulting mixture was stirred at 80 °C for 2 h. The reaction
mixture was concentrated under reduced pressure and the residue
was purified by chromatography (ethyl acetate/hexane), yielding
the desired secondary alcohol as a slightly yellow oil which crystal-
lized upon standing at low temperature (fridge).
4.4.6. N,N0-Bis[(4Rp,13Sp)-13-bromo-4-[2.2]paracyclophanyl]-
imidazolium trifluoromethanesulfonate 5a
Compound 5a was obtained as a white solid (78% yield). Mp
>260 °C; Rf 0.4 (CH2Cl2/ethanol = 20:1); ½a D20
¼ þ151:0 (c 0.4,
ꢂ
CHCl3); 1H NMR (300 MHz, CDCl3, rt): d 10.08–10.01 (s, 1H), 7.64
(s, 2H), 7.10 (s, 2H), 6.99 (s, 2H), 6.70 (s, 6H), 6.47 (d, J = 7.8 Hz,
2H), 3.69–3.59 (m, 2H), 3.47–3.24 (m, 8H), 3.13–3.05 (m, 2H),
2.94–2.86 (m, 4H); 13C NMR (75 MHz, CDCl3, rt): d 142.6, 142.4,
137.7, 136.6, 135.9, 135.8, 135.1, 133.8, 135.1, 133.8, 131.3,
130.5, 125.6, 123.8, 123.1, 37.10, 34.5, 34.1, 29.0. HRMS (ESI): calcd
for C35H31Br2N2 (MꢀOTf)+ 639.0834, found 639.0908.
4.6. General procedure for the ligand evaluation (Table 2)
4.4.7. N,N0-Bis[(4Rp,13Sp)-13-phenyl-4-[2.2]paracyclophanyl]-
imidazolium Trifluoromethanesulfonate 5c
At first, Rh2(OAc)4 (3.3 mg, 7.5 ꢁ 10ꢀ3 mmol, 3 mol %) was
weighed into a flamed dried tube equipped with a condenser and
under an argon atmosphere. Next, MeOH/DME (5:1) (0.50 mL)
Compound 5c was obtained as a white solid (58% yield). Mp
178–180 °C; Rf 0.4 (CH2Cl2/ethanol = 20:1); ½a D20
¼ þ172:8 (c 0.4,
ꢂ

Q. Ma et al. / Tetrahedron: Asymmetry 21 (2010) 292–298
297
was added and the suspension was stirred at room temperature for
5 min. Then, NHC ligand (7.5 ꢁ 10ꢀ3 mmol, 3 mol %) phenylboronic
acid (61.0 mg, 0.50 mmol), KOBu-t (28.0 mg, 0.25 mmol), and 1-
naphthaldehyde (34.0 mg, 0.25 mmol) were added successively.
The resulting mixture was stirred at reflux for 2 h. The reaction
mixture was concentrated under reduced pressure and the residue
was purified by chromatography (ethyl acetate/hexane), yielding
the desired secondary alcohol as a slightly yellow oil which crystal-
lized upon standing at low temperature (fridge).
(Chiralpak IA column, n-hexane/chloroform = 3:1, flow 1.0 ml/
min, detection at 254 nm), retention times 24.9 min (minor) and
27.0 min (major). 1H NMR (300 MHz, CDCl3, rt): d 8.06–8.03 (m,
1H), 7.86–7.78 (m, 2H), 7.60 (d, J = 7.2 Hz, 1H), 7.48–7.40 (m,
3H), 7.25–7.20 (m, 1H), 6.98–6.98 (m, 1H), 6.80 (d, J = 8.1 Hz,
1H), 6.49 (s, 1H), 3.75 (s, 3H), 2.36 (s, 1H). 13C NMR (75 MHz, CDCl3,
rt): d 159.8, 144.8, 138.7, 133.9, 130.7, 129.5, 128.8, 128.5, 126.2,
125.6, 125.3, 124.7, 123.9, 119.4, 113.0, 112.7, 73.5, 55.2. HRMS
(ESI): calcd for C18H15O (MꢀOH)+ 247.1123, found 247.1118.
4.7. General procedure for the evaluation of the in situ
methodology (Table 3)
4.7.4. (2-Methoxyphenyl)phenylmethanol (8bc and 8cb)
(S)-(ꢀ)-8bc: 97% yield; ½a D20
¼ ꢀ17:8 (c 0.4, CHCl3) with 46% ee;
ꢂ
The ee value was determined by HPLC analysis using a chiral col-
umn (Chiralpak IA column, n-hexane/chloroform = 3:1, flow
1.0 ml/min, detection at 254 nm), retention times 13.7 min (major)
and 14.7 min (minor).
At first, Rh2(OAc)4 (1.7 mg, 2.5 ꢁ 10ꢀ3 mmol, 0.3 mol %) was
weighted into a flamed dried tube equipped with a condenser and
under argon atmosphere. MeOH/DME (5:1) (0.5 mL) was added
and the suspension was stirred at room temperature for 5 min.
Then, NHC ligand 4a (3.0 mg, 2.5 ꢁ 10ꢀ3 mmol, 0.3 mol %) arylbo-
ronic acid (305.0 mg, 2.5 mmol), KOBu-t (140.0 mg, 1.25 mmol),
and aryl aldehyde (170.0 mg, 1.25 mmol) were added successively.
The resulting mixture was stirred at reflux for 6 h. The reaction mix-
ture was concentrated under reduced pressure and the residue was
purified by preparative thin layer chromatography (ethyl acetate/
hexane), yielding the desired secondary alcohol as a slightly yellow
oil which crystallized upon standing at low temperature (fridge).
(R)-(+)-8cb: 95% yield; ½a D20
¼ þ17:8 (c 0.4, CHCl3) with 46% ee;
ꢂ
The ee value was determined by HPLC analysis using a chiral col-
umn (Chiralpak IA column, n-hexane/chloroform = 3:1, flow
1.0 ml/min, detection at 254 nm), retention times 13.6 min (minor)
and 14.5 min (major). 1H NMR (300 MHz, CDCl3, rt): d 7.39–7.26
(m, 7H), 6.95–6.85 (m, 2H), 6.04 (d, J = 4.5 Hz, 1H), 3.78 (s, 3H),
3.05 (s, 1H). 13C NMR (75 MHz, CDCl3, rt): d 156.7, 143.3, 132.0,
128.7, 128.1, 127.8, 127.1, 126.6, 120.8, 110.8, 72.1, 55.4. HRMS
(ESI): calcd for C14H13O (MꢀOH)+ 197.0966, found 197.0960.
4.7.1. (1-Naphthyl)phenylmethanols 8ab and 8ba
4.7.5. (3-Methoxyphenyl)phenylmethanol 8bd
(R)-(+)-8ab: 94% yield; ½a D20
ꢂ
¼ þ10:5 (c 0.4, CHCl3) with 41% ee;
(S)-(ꢀ)-8bd: 97% yield; ½a D20
¼ ꢀ7:8 (c 0.4, CHCl3) with 28% ee;
ꢂ
The ee value was determined by HPLC analysis using a chiral col-
umn (Chiralpak IA column, n-hexane/chloroform = 3:1, flow
1.0 ml/min, detection at 254 nm), retention times 18.0 min (minor)
and 19.1 min (major).
The ee value was determined by HPLC analysis using a chiral col-
umn (Chiralpak IA column, n-hexane/chloroform = 3:1, flow
1.0 ml/min, detection at 254 nm), retention times 19.9 min (major)
and 20.9 min (minor). 1H NMR (300 MHz, CDCl3, rt): d 7.36–7.19
(m, 6H), 6.93–6.90 (m, 2H), 6.79–6.76 (m, 1H), 5.74 (s, 1H), 3.75
(s, 3H), 2.4 (s, 1H). 13C NMR (75 MHz, CDCl3, rt): d 159.7, 145.5,
143.7, 129.5, 128.5, 127.6, 126.5, 118.9, 113.0, 112.1, 72.1, 55.2.
HRMS (ESI): calcd for C14H13O (MꢀOH)+ 197.0966, found 197.0962.
(S)-(ꢀ)-8ba: 94% yield; ½a D20
¼ ꢀ10:5 (c 0.4, CHCl3) with 41% ee;
ꢂ
The ee value was determined by HPLC analysis using a chiral col-
umn (Chiralpak IA column, n-hexane/chloroform = 3:1, flow
1.0 ml/min, detection at 254 nm), retention times 17.8 min (major)
and 19.0 min (minor).
1H NMR (300 MHz, CDCl3, rt): d 8.03 (d, J = 3.3 Hz, 1H), 8.01–
7.80 (m, 2H), 7.64 (d, J = 6.9 Hz, 1H), 7.50–7.35 (m, 5H) 7.34–7.24
(m, 3H), 6.53 (s, 1H), 2.35 (s, 1H). 13C NMR (75 MHz, CDCl3, rt): d
143.1, 138.7, 133.9, 130.7, 128.8, 128.6, 128.5, 127.7, 127.06,
126.1, 125.6, 125.3, 124.6, 123.9, 73.6. HRMS (ESI): calcd for
C17H13 (MꢀOH)+ 217.1017, found 217.1022.
4.7.6. (2-Methoxyphenyl) (3-methoxyphenyl)methanol 8cd
(+)-8cd: 99% yield; ½a D20
¼ þ26:7 (c 0.4, CHCl3) with 40% ee; The
ꢂ
ee value was determined by HPLC analysis using a chiral column
(Chiralpak IA column, n-hexane/chloroform = 3:1, flow 1.0 ml/
min, detection at 254 nm), retention times 15.7 min (minor) and
17.1 min (major). 1H NMR (300 MHz, CDCl3, rt): d 7.27–7.18 (m,
3H), 6.97–6.75 (m, 5H), 6.02 (d, J = 3.6 Hz, 1H), 3.79 (s, 3H), 3.76
(s, 3H), 3.07–3.06 (d, 1H). 13C NMR (75 MHz, CDCl3, rt): d 159.5,
156.7, 145.0, 131.9, 129.1, 128.7, 127.9, 120.8, 118.9, 112.6,
112.1, 110.8, 72.0, 55.4, 55.1. HRMS (ESI): calcd for C15H15O2
(MꢀOH)+ 227.1072, found 227.1065.
4.7.2. (1-Naphthyl) (2-methoxyphenyl)methanols 8ac and 8ca
(ꢀ)-8ac: 97% yield; ½a D20
¼ ꢀ28:3 (c 0.4, CHCl3) with 52% ee; The
ꢂ
ee value was determined by HPLC analysis using a chiral column
(Chiralpak IA column, n-hexane/chloroform = 3:1, flow 1.0 ml/
min, detection at 254 nm), retention times 13.6 min (minor) and
14.5 min (major).
4.7.7. (4-Chlorophenyl) (1-naphthyl)methanol 8da
(+)-8ca: 96% yield; ½a D20
¼ þ28:3 (c 0.4, CHCl3) with 52% ee; The
ꢂ
(R)-(ꢀ)-8da: 92% yield; ½a D20
¼ ꢀ35:2 (c 0.4, CHCl3) with 45% ee;
ꢂ
ee value was determined by HPLC analysis using a chiral column
(Chiralpak IA column, n-hexane/chloroform = 3:1, flow 1.0 ml/
min, detection at 254 nm), retention times 13.7 min (major) and
14.7 min (minor).
The ee value was determined by HPLC analysis using a chiral col-
umn (Chiralpak IA column, n-hexane/chloroform = 3:1, flow
1.0 ml/min, detection at 254 nm); retention times 25.3 min (major)
and 26.6 min (minor). 1H NMR (300 MHz, CDCl3, rt): d 7.85–7.76
(m, 3H), 7.51–7.20 (m, 8H), 6.37 (s, 1H), 2.56 (s, 1H). 13C NMR
(75 MHz, CDCl3, rt): d 141.6, 138.4, 134.0, 133.3, 130.6, 128.8,
128.7, 128.6, 128.3, 126.3, 125.7, 125.3, 124.8, 123.8, 73.0. HRMS
(ESI): calcd for C17H12Cl (MꢀOH)+ 2251.0628, found 251.0622.
1H NMR (300 MHz, CDCl3, rt): d 8.00 (d, J = 7.8 Hz 1H), 7.86–7.78
(m, 2H), 7.65 (d, J = 7.2 Hz, 1H), 7.50–7.38 (m, 3H) 7.28–7.23 (m,
1H), 6.96–6.78 (m, 4H), 3.89 (s, 3H), 3.05 (s, 1H). 13C NMR
(75 MHz, CDCl3, rt): d 156.9, 138.0, 133.7, 131.3, 131.0, 129.0,
128.6, 128.4, 125.9, 125.5, 125.4, 124.3, 124.2, 120.8, 110.5,
101.1, 72.6, 68.4, 55.5. HRMS (ESI): calcd for C18H15O (MꢀOH)+
247.1123, found 247.1116.
4.7.8. (4-Chlorophenyl)(2-methoxyphenyl)methanol 8db
(ꢀ)-8db: 95% yield; ½a D20
¼ ꢀ15:6 (c 0.7, CHCl3) with 42% ee;
ꢂ
The ee value was determined by HPLC analysis using a chiral col-
umn (Chiralpak IA column, n-hexane/chloroform = 3:1, flow
1.0 ml/min, detection at 254 nm), retention times 13.0 min (major)
4.7.3. (1-Naphthyl) (3-Methoxyphenyl)methanol 8ad
(+)-8ad: 97% yield; ½a D20
¼ þ20:5 (c 0.4, CHCl3) with 34% ee; The
ꢂ
ee value was determined by HPLC analysis using a chiral column

298
Q. Ma et al. / Tetrahedron: Asymmetry 21 (2010) 292–298
and 13.9 min (minor). 1H NMR (300 MHz, CDCl3, rt): d 7.32–7.19
(m, 6H), 6.96–6.85 (m, 2H), 6.00 (s, 1H), 3.79 (s, 3H), 3.03 (s, 1H).
13C NMR (75 MHz, CDCl3, rt): d 156.6, 141.9, 132.8, 131.5, 128.9,
128.2, 127.9, 127.7, 120.9, 110.8, 71.6, 55.4. HRMS (ESI): calcd for
C14H12ClO (MꢀOH)+ 231.0577, found 231.0573.
Xing, C. H.; Liu, T. P.; Zheng, J. R.; Ng, J.; Esposito, M. J. Tetrahedron Lett. 2009, 50,
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4.7.9. (4-Chlorophenyl)(3-methoxyphenyl)methanol 8dd
(R)-(ꢀ)-8dd: 93% yield; ½a D20
¼ ꢀ2:7 (c 1.2, CHCl3) with 38% ee;
ꢂ
5. (a) Arduengo, A. J.; Harlow, R. L.; Kline, M. J. Am. Chem. Soc. 1991, 113, 361–363;
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The ee value was determined by HPLC analysis using a chiral col-
umn (Chiralpak IA column, n-hexane/chloroform = 3:1, flow
1.0 ml/min, detection at 254 nm), retention times 28.2 min (major)
and 29.7 min (minor). 1H NMR (300 MHz, CDCl3, rt): d 7.33–7.21
(m, 5H), 6.91–6.79 (m, 3H), 5.76 (s, 1H), 3.77 (s, 3H), 2.27 (s, 1H).
13C NMR (75 MHz, CDCl3, rt): d 159.8, 145.0, 142.1, 133.3, 129.6,
127.8, 118.8, 113.1, 112.1, 75.5, 55.2. HRMS (ESI): calcd for
C14H12ClO (MꢀOH)+ 231.0577, found 231.0579.
4.8. Crystallographic analysis of 4a
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Colorless, needle-like crystals were grown from hexane–CH2Cl2
(10:1), C36H31Br2F3N2O3S, M = 788.50, a = 9.7672(9) Å, b =
16.2570(15) Å, c = 20.1385(18) Å,
v
= 3197.7(5) Å3, T = 273(2) K,
Z = 35, Dcalcd = 3.922 Mg/m3. Final R indices [I > 2
r(I)], R1 = 0.0459,
wR2 = 0.0769; R indices (all data), R1 = 0.1023, wR2 = 0.0932.
Crystallographic data (excluding structure factors) for 4a have
been deposited with the CambridgeCrystallographic Data Centre
as supplementary publication number CCDC 753625. Copies of
the data can be obtained, free of charge, on application to CCDC,
12Union Road, Cambridge, CB2 1EZ, UK [fax: +44(0) 1223 336033
or e-mail: deposit@ccdc.cam.ac.uk].
Acknowledgments
Financial support from the National Natural Science Foundation
of China (Grant Nos. 20441004, 20671059) and Department of Sci-
ence and Technology of Shandong Province is gratefully
acknowledged.
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