Synthesis of new alkoxy/sulfonate-substituted carbene precursors derived from [2.2]paracyclophane and their application in the asymmetric arylation of aldehydes

Article abstract of DOI:10.1016/j.tetasy.2012.09.001

A series of novel planar chiral alkoxy/sulfonate-substituted carbene precursors have been designed and synthesized. They were used as N-heterocyclic carbene ligands in the Rh-catalyzed asymmetric addition of arylboronic acids to aromatic aldehydes, affording chiral diarylmethanols with high yields and moderate enantioselectivities.

Full text of DOI:10.1016/j.tetasy.2012.09.001

Tetrahedron: Asymmetry 23 (2012) 1369–1375
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Tetrahedron: Asymmetry
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Synthesis of new alkoxy/sulfonate-substituted carbene precursors derived
from [2.2]paracyclophane and their application in the asymmetric arylation
of aldehydes
⇑
Wenzeng Duan, Yudao Ma , Bo Qu, Lei Zhao, Jianqiang Chen, 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 1 August 2012
Accepted 29 August 2012
A series of novel planar chiral alkoxy/sulfonate-substituted carbene precursors have been designed and
synthesized. They were used as N-heterocyclic carbene ligands in the Rh-catalyzed asymmetric addition
of arylboronic acids to aromatic aldehydes, affording chiral diarylmethanols with high yields and moder-
ate enantioselectivities.
Ó 2012 Elsevier Ltd. All rights reserved.
1. Introduction
nard reagents to cyclic enones (up to 96% ee). Kündig et al. de-
signed and synthesized a series of chiral alkoxy-substituted NHC
Over the last decade, much attention has been paid to the asym-
metric arylation of aldehydes because the chiral diarylmethanol
products are key intermediates for the synthesis of pharmaceuti-
cally and biologically active compounds.1 The rhodium-catalyzed
addition of arylboronic acids to aromatic aldehydes was first re-
ported by Miyaura in 1998.2 Due to the low toxicity and easy
manipulation of organoboronic acids, the asymmetric addition of
organoboronic acids to aldehydes and ketones attracted great
interest. Recently, excellent results on the enantioselective car-
bonyl addition reactions of arylboronic reagents have been re-
ported by several groups.3,4 In 2006, Hayashi reported that a
catalytic system based on the chiral methoxy-substituted phos-
phine ligand (MeO–MOP) derived from a binaphthyl backbone
afforded excellent enantioselectivity (up to 93% ee).4 It was sug-
gested that the methoxy group on the ligand backbone could play
an important role in the Rh-catalyzed asymmetric carbonyl addi-
tion of organoboronic reagents. For the investigation of novel cat-
alyst systems, the design of new chiral ligands is a key strategy
to achieve highly stereocontrolled reaction.
precursors, and applied them in Pd-catalyzed asymmetric intramo-
lecular -arylation of amides with excellent yields and enantiose-
a
lectivities.9 The importance of the alkoxy-substituted ligands led
us to investigate a series of other alkoxy-substituted NHC ligands,
such as planar chiral [2.2]paracyclophane-based NHC precursors.
Since [2.2]paracyclophane is regarded as a very good backbone
for chiral ligands,10 Bolm had already developed the methoxy-
substituted NHC precursor derived from [2.2]paracyclophane in
2005.11a However, due to the flexibility of the methylene which
linked the imidazolium salt to the [2.2]paracyclophane backbone,
the ligand did not show satisfactory efficiency in the asymmetric
arylation of aldehydes (38% ee). On the other hand, there are a
few reports concerning the carbene-metal catalyzed asymmetric
addition of arylboronic acids to aldehydes.11 Herein, we report
the synthesis of a new family of alkoxy- and sulfonate-substituted
NHC precursors based on a [2.2]paracyclophane backbone 6–8, and
10 (Fig. 1) and their application in the enantioselective rhodium-
catalyzed addition of arylboronic acids to aromatic aldehydes.
Since the end of the last century, N-heterocyclic carbenes
(NHCs) have been successfully employed in various homogeneous
metal-catalyzed reactions.5 Among them, NHC ligands have
showed good ability in asymmetric transition metal catalysis since
2. Results and discussion
We designed and synthesized five new planar chiral imidazolium
salts and one imidazolinium salt based on the [2.2]paracyclophane
skeleton. Our synthetic route to the new alkoxy- and sulfonate-
substituted planar chiral imidazolium salts is shown in Schemes 1
and 2. The synthetic pathway started with enantiomerically pure
pseudo-ortho-disubstituted [2.2]paracyclophanyl amines 1a, 1b,
1c, and 4, pseudo-gem-disubstituted [2.2]paracyclophanyl amine 5.
The planar chiral amines 1a, 1b, 1c, and 5 can be obtained following
the previous literature.12,13 (Rp)-4-Mesylate-substituted [2.2]para-
cyclophanyl amine 4 was easily prepared in high yield from (Rp)-
they are neutral,
r-donating ligands with negligible p backbond-
ing.6 Recently, Tomioka and co-workers7 and Alexakis and co-
workers8 introduced a new class of NHC precursors based on the
concept of chiral alkoxy-substituted NHC ligands. These ligands
were efficient in the enantioselective conjugate addition of Grig-
⇑
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 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetasy.2012.09.001

1370
W. Duan et al. / Tetrahedron: Asymmetry 23 (2012) 1369–1375
H3C
yield. The diimines were treated with a solution of silver triflate
and chloromethyl pivalate in dark conditions at 40 °C to form imi-
dazolium trifluoromethanesulfonates.11d,14 The mesylate-substi-
tuted imidazolium bromide 7 was obtained from its triflate
analogue by anion exchange with a saturated KBr aqueous solu-
tion. In addition, the methoxy-substituted imidazolinium tetra-
fluoroborate 10 was synthesized by converting 1a into the
corresponding dimine (Scheme 3), subsequent reduction with
NaBH4/20% H2SO4, and ring-closing with triethyl orthoformate in
the presence of a catalytic amount of formic acid.15 All the imi-
dazolium and imidazolinium salts were purified, and fully charac-
terized by NMR and mass spectrometry.
CH3
O
O
O
S
S
O
O
O
N
N
Br
OTf
OR
RO
N
N
6
7
a
b
c
R = : -CH3, : -CH(CH3)2, : -SO2CF3
N
N
-
BF4
N
MeO
N
HN
NH
1. (CHO)2/THF
HC(OC2H5)3
NH4BF4
OMe
MeO
OMe
1a
OTf
2. NaBH4
20% H2SO4
OMe
MeO
8
10
9
Figure 1. Novel chiral imidazolium and imidazolinium salts.
N
N
4-hydroxy-12-benzhydrylideneamino [2.2]paracyclophane 2 by
mesylation with methanesulfonyl chloride, followed by imine 3
hydrolysis under acidic conditions (Scheme 1).
-
BF4
OMe
MeO
10
OH
OSO2CH3
N=CPh2
CH3SO2Cl/Et3N
THF
Scheme 3. Synthesis of imidazolinium tetrafluoroborate.
With the novel imidazolium salts 6a, 6b, 6c, 7, 8, and imidazo-
N=CPh2
linium salts 10 in hand, we turned our attention to their applica-
tion in Rh-catalyzed asymmetric additions of arylboronic acids to
aromatic aldehydes.
2
3
We began our experiment under the identical conditions used
in our previous study on the rhodium-catalyzed asymmetric aryla-
tion of aromatic aldehydes.11d The reaction of phenylboronic acid
and 1-naphthaldehyde was performed with 3.0 mol % of catalyst
generated in situ from imidazolium salt 6a and [Rh(OAc)2]2 in
MeOH/DME (5:1) at 80 °C for 7 h. Compared to our previous work,
the enantioselectivity of the reaction was improved.11d With this
promising result, various aliphatic alcohols were screened as sol-
vents (Table 1), and it was found that in t-BuOH, ligand 6a showed
good enantioselectivity (48% ee). It was suggested that the polarity
of solvent was the crucial factor in this reaction. Thus we mixed t-
BuOH with MeOH, EtOH, and water to adjust the polarity. Among
these mixed solvents, t-BuOH/MeOH (5:1) emerged as the best
choice, affording the addition product in good enantioselectivity
(52% ee).
In t-BuOH/MeOH (5:1), we evaluated the rhodium sources and
ligands (Table 2). No enantioselectivity was observed with
[Rh(COD)Cl]2 as the rhodium source. The asymmetric reaction
employing [Rh(TFA)2]2, RhCl3, [Rh(NBD)Cl]2, Rh(CO)2(acac), and
[Rh(C2H4)2Cl]2 as rhodium sources afforded product c12 in lower
yields (40–60%) and enantioselectivities (23–46% ee) (Table 2, en-
tries 2–6). From the initial range of rhodium sources tested,
[Rh(OAc)2]2 proved to be the best. Next, we examined different
planar chiral carbene precursors shown in Figures 1 and 2. From
our predictions, imidazolium salt 6b and imidazolinium salt 10
were ineffective ligands. The carbene precursor 6c, possessing an
electron-deficient moiety, resulted in high yield (93%) and low
enantioselectivity (24% ee). Ligand 7 was found to be less efficient
in this reaction in terms of reactivity (30% yield) or enantioselectiv-
ity (31% ee). Ligand 8, bearing a methoxy substituent at the 13-po-
sition of the [2.2]paracyclophane, led to the formation of
diarylmethanol with similar enantioselectivity to ligand 6a, but a
significant decrease in reactivity was observed (Table 2, entry
13). Our former ligand 11 (Fig. 2) which showed good catalytic
OSO2CH3
THF
HCl
NH2
4
Scheme 1. Synthesis of (Rp)-4-amino-12-methanesulfonyloxy[2.2]paracyclophane.
NH2
N
N
1. (CHO)2/THF
OTf
2. AgOTf
OR
OR
RO
ClCH2OOCC(CH3)3
1
6
a
b
c
R = : -CH3, : -CH(CH3)2, : -SO2CF3
H3C
CH3
O
O
O
S
S
O
OSO2CH3
NH2
1. (CHO)2/THF
O
O
2. AgOTf
Br
ClCH2OOCC(CH3)3
N
N
3. KBr
4
7
1. (CHO)2/THF
2. AgOTf
NH2
N
MeO
N
OMe
ClCH2OOCC(CH3)3
OMe
OTf
5
8
Scheme 2. Synthesis of imidazolium triflates.
Amines 1a, 1b, 1c, 4, and 5 reacted with aqueous glyoxal in THF
to furnish the corresponding diimines in essentially quantitative

W. Duan et al. / Tetrahedron: Asymmetry 23 (2012) 1369–1375
1371
Table 1
Evaluation of the solventa
N
N
HO
*
CHO
B(OH)2
6a
(3 mol%)
Br
Br
[Rh(OAc)2]2 (3 mol%)
+
11
KOBu-t / solvent
Figure 2. Imidazolium salt 11.
a1
b2
c12
Entry
Solvent
Yieldb (%)
eec (%)
Table 3
1
2
3
4
5
6
7
8
9
10
11
12
13
14
MeOH/DME
MeOH
EtOH
n-PrOH
i-PrOH
t-BuOH
t-Amyl alcohol
t-BuOH/MeOH (10:1)
t-BuOH/MeOH (5:1)
t-BuOH/EtOH (10:1)
t-BuOH/H2O (10:1)
t-BuOH/EtOH (3:1)
t-BuOH/EtOH (1:1)
t-BuOH/EtOH (1:3)
90
72
80
48
88
64
0
76
76
88
36
88
88
76
46 (S)
38 (S)
32 (S)
18 (S)
33 (S)
48 (S)
—
49 (S)
52 (S)
47 (S)
47 (S)
42 (S)
41 (S)
30 (S)
Scope of the methodologya
6a 3 mol%
OH
O
[Rh(OAc)2]2 3 mol%
+
Ar2 B(OH)2
Ar1
Ar2
Ar1
H
KOBu-t
t-BuOH / MeOH
c
a
b
Entry
Ar1
Ar2
Yieldb (%)
eec (%)
1
2
3
4
5
6
7
8
1-Naphthyl a1
1-Naphthyl a1
1-Naphthyl a1
Phenyl a2
Phenyl a2
Phenyl a2
Phenyl b2
76 c12
52 c13
95 c14
99 c21
94 c23
99 c24
99 c31
93 c32
93 c33
99 c34
99 c41
99 c42
93 c43
81 c44
52 (S)
44 (+)
42 (ꢀ)
46 (R)
36 (R)
48 (S)
54 (S)
52 (S)
22 (+)
54 (S)
54 (+)
53 (R)
48 (ꢀ)
54 (+)
2-MeOC6H4 b3
3-MeOC6H4 b4
1-Naphthyl b1
2-MeOC6H4 b3
3-MeOC6H4 b4
1-Naphthyl b1
Phenyl b2
2-MeOC6H4 b3
3-MeOC6H4 b4
1-Naphthyl b1
Phenyl b2
a
Reaction conditions: [Rh(OAc)2]2 (3 mol %), 6a (3 mol %), KOBu-t (1 equiv),
arylboronic acids (2 equiv), N2, 80 °C, 7 h.
b
Isolated yield.
4-ClC6H4 a3
4-ClC6H4 a3
c
Determined by chiral HPLC (CHIRALPAK IA Columns) analysis.
9
4-ClC6H4 a3
10
11
12
13
14
4-ClC6H4 a3
Table 2
4-MeOOCC6H4 a4
4-MeOOCC6H4 a4
4-MeOOCC6H4 a4
4-MeOOCC6H4 a4
Evaluation of rhodium source and liganda
2-MeOC6H4 b3
3-MeOC6H4 b4
HO
CHO
B(OH)2
*
ligand (3 mol%)
a
Reaction conditions: metal source (3 mol %), ligand (3 mol %), KOBu-t (1 equiv),
arylboronic acids (2 equiv), N2, 80 °C, 7 h.
metal source (3 mol%)
+
b
Isolated yield.
KOBu-t
t-BuOH/MeOH
c
Determined by chiral HPLC (CHIRALPAK IA Columns) analysis.
a1
b2
c12
Yieldb (%)
eec (%)
of aromatic aldehydes under our optimized conditions. In most
cases, the asymmetric reactions gave the desired products in excel-
lent yields (up to 99%). With the electron-deficient arylaldehydes,
the catalyst was more enantioselective (Table 3, entries 7, 10, 11
and 14). However, the ortho-methoxy substituent on the arylbo-
ronic acid b3 reacted with aromatic aldehydes to produce the chi-
ral diarylmethanols with lower enantiomeric excess (Table 3,
entries 2, 5, 9 and 13).
Entry
Metal source
Ligand
1d
2
[Rh(COD)Cl]2
[Rh(TFA)2]2
RhCl3
6a
6a
6a
6a
6a
6a
6a
6a
6a
6b
6c
7
78
52
33
60
52
40
73
71
67
0
0
37 (S)
46 (R)
46 (S)
23 (S)
42 (S)
40 (S)
38 (S)
37 (S)
—
24 (S)
31 (R)
48 (S)
—
3
4d
5
[Rh(NBD)Cl]2
Rh(CO)2(acac)
[Rh(C2H4)2Cl]2
[Rh(OAc)2]2
[Rh(OAc)2]2
[Rh(OAc)2]2
[Rh(OAc)2]2
[Rh(OAc)2]2
[Rh(OAc)2]2
[Rh(OAc)2]2
[Rh(OAc)2]2
[Rh(OAc)2]2
6d
7e
8f
9g
10
11
12
13
14
15
3. Conclusion
93
30
40
0
8
10
11
In conclusion, a series of alkoxy- and sulfonate-substituted pla-
nar chiral carbene precursors based on the [2.2]paracyclophane
skeleton have been prepared and applied in asymmetric additions
of arylboronic acids to aromatic aldehydes. Among the new ligands
screened, the methoxy-substituted ligand 6a gave the best enanti-
oselectivity. This shows that the methoxy substituent on the ligand
backbone plays an important role in the catalytic process. Studies
on further modifications of [2.2]paracyclophane-based carbene
precursors as well as applications in asymmetric catalysis are cur-
rently in progress.
36
23 (R)
a
Reaction conditions: metal source (3 mol %), ligand (3 mol %), KOBu-t (1 equiv),
arylboronic acids (2 equiv), N2, 80 °C, 7 h.
b
Isolated yield.
c
Determined by chiral HPLC (CHIRALPAK IA Columns) analysis.
Metal source: 1.5 mol %.
[Rh(OAc)2]2 (4.5 mol %).
[Rh(OAc)2]2 (2.25 mol %).
d
e
f
g
[Rh(OAc)2]2 (1.5 mol %).
abilities in the MeOH/DME system11d was also used in t-BuOH/
MeOH, and exhibited low activity (36% yield) and enantioselectiv-
ity (23% ee). So these results indicate that the methoxy group on
the [2.2]paracyclophanyl ligand backbone plays an important role
in the catalytic process.
4. Experimental
4.1. General
Commercially available reagents were used without further
purification unless otherwise noted. Solvents were reagent grade
and purified by standard techniques. (Sp)-4-amino-12-
As shown in Table 3, various substrates with different steric and
electronic properties were examined in the asymmetric arylation

1372
W. Duan et al. / Tetrahedron: Asymmetry 23 (2012) 1369–1375
methoxy[2.2]paracyclophane
1a,
(Sp)-4-amino-12-i-propoxy
4.3.1. N,N0-Bis[(Sp)-(+)-12-methoxy-4-[2.2]paracyclophanyl]-
[2.2]paracyclophane 1b, (Sp)-4-amino-12-trifluoromethanesulfo-
nyloxy[2.2]paracyclophane 1c, (Rp)-4-benzhydrylideneamino-12-
hydroxy[2.2]paracyclophane 2, (Sp)-4-amino-13-methoxy[2.2]
paracyclophane 5, and N,N0-bis[(Sp)-12-bromo-4-[2.2]paracyclo-
phanyl]imidazolium triflate 11 were prepared according to pub-
imidazolium triflate 6a
Compound 6a was obtained as a white solid (68% yield). Mp
>260 °C; Rf 0.6 (CH2Cl2/ethanol = 20:1);
½
a 2D0
ꢂ
¼ þ20:9 (c 0.36,
CH2Cl2); 1H NMR (300 MHz, CDCl3, rt): d 8.97 (s, 1H), 8.10 (s,
2H), 7.02 (s, 2H), 6.80 (d, J = 7.9 Hz, 2H), 6.69–6.64 (m, 4H), 6.48
(d, J = 7.8 Hz, 2H), 6.01 (s, 2H), 3.83 (s, 6H), 3.45–3.41 (m, 2H),
3.30–2.68 (m, 14H). 13C NMR (75 MHz, CDCl3, rt): d 158.4, 143.0,
142.0, 136.6, 136.2, 135.3, 133.9, 133.7, 132.0, 130.0, 128.1,
124.6, 123.5, 119.6, 59.9, 34.4, 33.6, 31.1, 30.3. HRMS (ESI): calcd
for C37H37O2N2 (M-OTf)+ 541.2855. Found: 541.2860.
lished procedures.11d,13 Melting points were recorded on
a
melting point apparatus and are uncorrected. 1H and 13C NMR
spectra were recorded on Bruker Avance 400 and 300 MHz spec-
trometers. HRMS spectra were recorded on an Agilent 100 ABI-
API4000 spectrometer. Enantiomeric excess was determined using
HPLC on a Chiralpak IA chiral column 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.
4.3.2. N,N0-Bis[(Sp)-(ꢀ)-12-isopropoxy-4-[2.2]paracyclophanyl]-
imidazolium triflate 6b
Compound 6b was obtained as a yellow solid (45% yield). Mp
4.2. Synthesis of (Rp)-4-amino-12-methanesulfonyloxy[2.2]para-
cyclophane 4
115–118 °C; Rf 0.6 (CH2Cl2/ethanol = 20:1); ½a D20
¼ ꢀ74:4 (c 0.68,
ꢂ
CH2Cl2); 1H NMR (300 MHz, CDCl3, rt): d 9.10 (s, 1H), 8.21 (s,
2H), 6.99 (s, 2H), 6.82 (d, J = 7.8 Hz, 2H), 6.71–6.65 (m, 4H),
6.51(d, J = 7.5 Hz, 2H), 6.10 (s, 2H), 4.20–4.11 (m, 2H), 3.41–3.32
(m, 2H), 3.18–2.77 (m, 14H), 1.30–1.23 (m, 12H); 13C NMR
(75 MHz, CDCl3, rt): d 155.7, 143.0, 141.6, 136.3, 135.3, 134.9,
133.9, 132.5, 129.1, 124.5, 124.3, 123.3, 34.4, 33.7, 31.1, 30.5,
29.7, 22.7, 22.5. HRMS (ESI): Calcd for C41H45O2N2 (M-OTf)+
597.3476. Found: 597.3481.
In an oven-dried Schlenk flask, (Rp)-4-benzhydrylideneamino-
12-hydroxy[2.2]paracyclophane (320 mg, 0.8 mmol) and anhy-
drous Et3N (0.222 mL, 1.6 mmol) were dissolved in anhydrous
THF (4.0 mL). Under 0 °C, methanesulfonyl chloride (0.0624 mL,
0.8 mmol) in anhydrous THF (2.0 mL) was added dropwise to the
stirred mixture over 20 min. The mixture was then stirred at room
temperature for 6 h. After the reaction was complete, hydrochloric
acid (12.0 M, 0.4 mL) was added to the mixture. Stirring was con-
tinued for 4 h. After the yellow mixture faded, the white precipi-
tate formed was filtered, washed with ether (3 ꢁ 5.0 mL), and
dried in vacuo. The remaining solid was dissolved in ethanol
(4.0 mL), and saturated NaOH was added dropwise until the stirred
mixture tested basic (pH 9). The solvent was removed, and the res-
idue was purified by chromatography on silica gel (petroleum
ether/ethyl acetate = 10:1). Target compound 4 was obtained as a
white solid (221 mg, 88% yield). Mp 220–222 °C; Rf 0.4 (CH2Cl2/
4.3.3. N,N0-Bis[(Sp)-(+)-12-trifluoromethanesulfonyloxy-4-[2.2]-
paracyclophanyl]-imidazolium triflate 6c
Compound 6c was obtained as a white solid (82% yield). Mp
>260 °C; Rf 0.6 (CH2Cl2/ethanol = 20:1); ½a D20
¼ þ146:3 (c 0.36,
ꢂ
CH2Cl2); 1H NMR (300 MHz, CDCl3, rt): d 9.35 (s, 1H), 7.91 (s,
2H), 7.11 (d, J = 7.8 Hz, 2H), 6.91–6.80 (m, 6H), 6.70–6.72 (d, 2H),
6.29 (s, 2H), 3.55–3.45 (m, 2H), 3.36–3.10 (m, 8H), 3.03–2.95 (m,
6H); 13C NMR (75 MHz, CDCl3, rt): d 147.3, 143.1, 141.4, 137.0,
136.1, 135.5, 134.7, 133.2, 132.5, 131.1, 123.3, 122.9, 122.6,
120.4(d, J = 319.5 Hz), 116.1, 33.6, 32.6, 30.6, 30.1. HRMS (ESI):
Calcd for C37H31F6N2O6S2 (M-OTf)+ 777.1522. Found: 777.1567.
CH3COOC2H5 = 10:1);
½
a 2D0
ꢂ
¼ þ15:5 (c 0.1, CH2Cl2); 1H NMR
(300 MHz, CDCl3, rt): d 7.08 (d, J = 1.7 Hz, 1H), 6.64 (d, J = 7.9 Hz,
1H), 6.44 (dd, J = 7.9, 1.5 Hz, 1H), 6.33 (d, J = 7.7 Hz, 1H), 6.10 (dd,
J = 7.7, 1.6 Hz, 1H), 5.86 (s, 1H), 3.75 (s, 2H), 3.45–3.30 (m, 1H),
3.20–3.07 (m, 2H), 3.02 (d, J = 5.2 Hz, 4H), 2.93 (t, J = 7.2 Hz, 2H),
2.67 (d, J = 13.3 Hz, 2H); 13C NMR (75 MHz, CDCl3, rt) d 147.2,
144.1, 141.8, 140.8, 134.9, 134.7, 131.5, 131.0, 123.9, 122.5,
121.8, 118.2, 36.3, 33.1, 31.7, 31.5, 30.9. HRMS (ESI) Calcd for
4.3.4. N,N0-Bis[(Rp)-(+)-12-methanesulfonyloxy-4-[2.2]para-
cyclophanyl] -imidazolium bromide 716
The pure product N,N0-bis[(Rp)-(+)-12-methanesulfonyloxy-4-
[2.2]paracyclophanyl]-imidazolium triflate (240 mg, 0.29 mmol)
was dissolved in CH2Cl2 (10.0 mL), saturated KBr aqueous solution
(10.0 mL) was added and the mixture was stirred. After 12 h, satu-
rated KBr aqueous solution was removed. The products were col-
lected by filtration. Compound 7 was obtained as a white solid
(42% yield). Mp >240 °C (decomposition); Rf 0.4 (CH2Cl2/etha-
C
17H19NO3S (M+H)+ 318.1158. Found: 318.1187.
4.3. General procedures for the synthesis of imidazolium
triflates 6, 7 and 8
nol = 20:1); ½a 2D0
ꢂ
¼ þ82:6 (c 0.2, CH3CN); 1H NMR (300 MHz,
Compound 1, 4 or 5 (1.0 mmol), and 40% glyoxal (145 mg,
1.0 mmol) in 0.5 mL of THF was stirred at room temperature for
5–8 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, to the mixture was added water
(2.0 mL) and then extracted with CH2Cl2 (3 ꢁ 5.0 ml). The solvent
was removed on a rotary evaporator, and the desired diimine
was obtained as a yellow solid.
DMSO-d6, rt): d 9.35 (s, 1H), 8.17 (s, 2H), 7.27 (s, 2H), 6.93 (t,
J = 8.0 Hz, 4H), 6.82 (t, J = 6.8 Hz, 4H), 6.42 (s, 2H), 3.31 (s, 8H),
3.25–3.06 (m, 8H), 2.97 (d, J = 6.3 Hz, 6H); 13C NMR (75 MHz,
DMSO-d6) d 147.8, 143.5, 142.9, 137.7, 136.8, 136.6, 134.8, 133.5,
133.2, 125.9, 124.6, 124.4, 56.9, 38.5, 34.3, 33.5, 31.8, 31.1, 19.5.
HRMS (ESI): Calcd for C37H37BrN2O6S2 (M-Br)+ 669.2099. Found:
669.2148.
A solution of AgOTf (0.66 mg, 0.26 mmol) and chloromethyl
pivalate (0.035 ml, 0.24 mmol) in THF was stirred in a sealed
tube in the dark at room temperature for 10 min, until a white
4.3.5. N,N0-Bis[(Sp)-(+)-13-methoxy-4-[2.2]paracyclophanyl]-
imidazolium triflate 8
Compound 8 was obtained as a white solid (45% yield). Mp
precipitate appeared. Next,
a solution of diimine (104.8 mg,
>245 °C (decomposition); Rf 0.6 (CH2Cl2/ethanol = 20:1);
0.2 mmol) in CH2Cl2 (2.0 ml) was added to the above suspension,
and the mixture was sequentially stirred at 40 °C for 24 h. After
the solvent was removed in vacuo, the resulting oil was chro-
matographed on silica gel (CH2Cl2/EtOH = 100:1–20:1) to give
the crude product. After recrystallization in THF, the pure prod-
uct was obtained.
½
a 2D0
ꢂ
¼ þ81:7 (c 0.17, CH2Cl2); 1H NMR (300 MHz, CDCl3, rt): d
9.32 (s, 1H), 7.86 (d, J = 1.5 Hz, 2H), 7.16 (s, 2H), 6.66 (dd, J = 7.8,
1.2 Hz, 2H), 6.58 (dd, J = 7.8, 2.9 Hz, 4H), 6.45 (dd, J = 7.7, 1.5 Hz,
2H), 6.29 (d, J = 1.5 Hz, 2H), 3.60 (s, 6H), 3.42–3.00 (m, 14H),
2.79–2.70 (m, 2H). 13C NMR (75 MHz, CDCl3, rt): d 159.3, 142.9,
142.4, 137.2, 135.2, 134.6, 133.3, 131.3, 126.9, 125.6, 125.2,

W. Duan et al. / Tetrahedron: Asymmetry 23 (2012) 1369–1375
1373
123.7, 120.7, 57.5, 34.5, 34.4, 31.8 29.8. HRMS (ESI): Calcd for
37H37O2N2 (M-OTf)+ 541.285. Found: 541.2853.
5 min. Next, NHC ligand 6a (2.6 mg, 3.8 ꢁ 10ꢀ3 mmol, 3 mol %)
phenylboronic acid (30.5 mg, 0.25 mmol), KOBu-t (14.0 mg,
0.125 mmol), and 1-naphthaldehyde (19.5 mg, 0.125 mmol) were
added successively. The resulting mixture was stirred at 80 °C for
7 h. The reaction mixture was concentrated in vacuo and the resi-
due was purified by chromatography (hexanes/ethyl ace-
tate = 10:1), to give the desired diarylmethanols as a slightly
yellow oil at room temperature.
C
4.4. Synthesis of N,N0-bis[(Sp)-(ꢀ)-12-methoxy-4-[2.2]para-
cyclophanyl]- imidazolinium tetrafluoroborate 10
To a suspension of the diimine obtained from 1a (326 mg,
0.6 mmol) in THF (9.0 mL) at 0 °C was added NaBH4 (331.2 mg,
8.4 mmol) in 20 mg portions. H2SO4 (20%, 1.2 mL) in THF (5.0 mL)
was added dropwise for 1 h. After being stirred at room tempera-
ture for another 2 h, to the mixture were added 5.0 ml of water
and then 3.0 ml of 3.0 M hydrochloric acid. A colorless solid precip-
itated and saturated NaOH was added dropwise until the stirred
mixture tested basic (pH 9). The solution was extracted with
dichloromethane (3 ꢁ 10.0 mL). The solvent was removed on a ro-
tary evaporator and the crude product was subjected to chroma-
tography on silica gel with hexanes/ethyl acetate (5:1) to give
the desired glyoxal diamine 9 as a white solid (272 mg, 83%). Mp
4.7. General procedure for the ligand evaluation (Table 2)
At first, Rh2(OAc)4 (1.7 mg, 3.8 ꢁ 10ꢀ3 mmol, 3 mol %) was
weighed into a dried tube equipped with a condenser under a
nitrogen atmosphere. Next, t-BuOH/MeOH (5:1) (1.2 mL) was
added and the suspension was stirred at room temperature for
5 min. Then, the NHC ligand (3.8 ꢁ 10ꢀ3 mmol, 3 mol %) phenylbo-
ronic acid (30.5 mg, 0.25 mmol), KOBu-t (14.0 mg, 0.125 mmol),
and 1-naphthaldehyde (19.5 mg, 0.125 mmol) were added succes-
sively. The resulting mixture was stirred at 80 °C for 7 h. The reac-
tion mixture was concentrated in vacuo and the residue was
purified by chromatography (hexanes/ethyl acetate = 10:1), giving
the desired diarylmethanols as a slightly yellow oil at room
temperature.
185–190 °C; Rf 0.4 (CH2Cl2/ethanol = 20:1); ½a D20
¼ þ21:6 (c 0.81,
ꢂ
CH2Cl2) 1H NMR (300 MHz, CDCl3, rt): d 6.40 (d, J = 7.5 Hz, 2H)
6.23(d, J = 7.8 Hz, 2H), 6.19 (s, 2H), 6.08 (d, J = 7.5 Hz, 2H), 5.94
(d, J = 7.5 Hz, 2H), 5.23 (s, 4H), 3.69–3.60(m, 2H), 3.56 (d,
J = 4.5 Hz, 2H), 3.49 (s, 4H), 3.3–3.16 (m, 4H), 2.98–2.78 (m, 8H),
2.62–2.45 (m, 4H); 13C NMR (75 MHz, CDCl3, rt): d 157.7, 146.1,
142.4, 141.7, 135.2, 134.9, 126.9, 124.5, 123.7, 122.0, 113.6,
112.5, 58.5, 43.1, 33.9, 33.2, 32.2, 31.3. HRMS (ESI): Calcd for
4.8. General procedure for the evaluation of the methodology
C
37H38O2N2 (M+H)+ 533.3168. Found: 533.3196.
At first, Rh2(OAc)4 (1.7 mg, 3.8 ꢁ 10ꢀ3 mmol, 3 mol %) was
weighed into a dried tube equipped with a condenser under a
nitrogen atmosphere. Next, t-BuOH/MeOH (5:1) (1.2 mL) was
added and the suspension was stirred at room temperature for
5 min. Then, NHC ligand 6a (2.6 mg, 3.8 ꢁ 10ꢀ3 mmol, 3 mol %)
arylboronic acid (0.25 mmol), KOBu-t (14.0 mg, 0.125 mmol), and
aryl aldehyde (0.125 mmol) were added successively. The resulting
mixture was stirred at 80 °C for 7 h. The reaction mixture was con-
centrated in vacuo and the residue was purified by chromatogra-
phy (hexanes/ethyl acetate = 10:1), giving the desired
diarylmethanols as a slightly yellow oil at room temperature.
A mixture of diamine 9 (105.2 mg, 0.2 mmol), triethylorthofor-
mate (1.0 mL), one drop of formic acid, and ammonium tetrafluo-
roborate (31.4 mg, 0.3 mmol) was stirred at 120 °C for 8 h. After
completion of the reaction as indicated by TLC, the solvent was re-
moved on a rotary evaporator. The crude product was subjected to
chromatography on silica gel (dichloromethane/ethanol = 50:1),
and the target compoud 10 was obtained as a green solid
(102 mg, 82% yield). Mp >180 °C (decomposition); Rf 0.6 (CH2Cl2/
ethanol = 20:1); ½a D20
ꢂ
¼ ꢀ58:8 (c 0.4, CH2Cl2); 1H NMR (300 MHz,
CDCl3, rt): d 8.44 (s, 1H), 6.69 (d, J = 8.1 Hz, 2H), 6.80 (s, 2H),
6.59 (d, J = 7.8 Hz, 2H), 6.52 (d, J = 7.8 Hz, 2H), 6.45 (d, J = 7.8
Hz, 2H), 6.33 (s, 2H), 4.99 (m, 2H), 4.51 (m, 2H), 3.75 (s, 6H),
3.12–2.94 (m, 13H), 2.80–2.76 (m, 3H); 13C NMR (75 MHz, CDCl3,
rt): d 157.2, 141.8, 141.3, 135.5, 134.1, 133.8, 133.6, 131.4, 128.0,
126.6, 120.1, 118.8, 58.1, 50.3, 33.7, 32.7, 30.4, 29.2, 28.7. HRMS
(ESI): Calcd for C37H39O2N2 (M-BF4)+ 543.3006. Found: 543.3001.
4.8.1. (1-Naphthyl) phenylmethanols c12 and c21
(S)-(ꢀ)-c12: 76% yield; ½a D20
¼ ꢀ23:6 (c 0.16, CH2Cl2) with 52%
ꢂ
ee; the 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 17.3 min (major)
and 18.4 min (minor).
4.5. General procedure for the optimization of the solvent over
the arylation of aldehyde (Table 1)
(R)-(+)-c21: 76% yield; ½a D20
¼ þ15:7 (c 0.11, CH2Cl2) with 46%
ꢂ
ee; the 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 21.5 min (minor)
and 23.0 min (major).
At first, Rh2(OAc)4 (1.7 mg, 3.8 ꢁ 10ꢀ3 mmol, 3 mol %) was
weighed into a dried tube equipped with a condenser under a
nitrogen atmosphere. The solvent (1.0 mL) was added and the sus-
pension was stirred at room temperature for 5 min. Next, ligand 3a
(2.6 mg, 3.8 ꢁ 10ꢀ3 mmol, 3 mol %), phenylboronic acid (30.5 mg,
0.25 mmol), KOBu-t (14.0 mg, 0.125 mmol), and 1-naphthaldehyde
(19.5 mg, 0.125 mmol) were added successively. The resulting
mixture was stirred at 80 °C for 7 h. The reaction mixture was con-
centrated in vacuo and the residue was purified by chromatogra-
phy (hexanes/ethyl acetate = 10:1), giving the desired
diarylmethanols as a slightly yellow oil at room temperature.
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
C
17H13 (MꢀOH)+ 217.1017. Found: 217.1022.
4.8.2. (1-Naphthyl) (2-methoxyphenyl) methanol c13
(+)-c13: 52% yield; ½a D20
¼ þ27:1 (c 0.14, CH2Cl2) with 44% 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 21.2 min (major)
and 25.4 min (minor). 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,
4.6. General procedure for the rhodium source evaluation
(Table 2)
At first, the metal source (3.8 ꢁ 10ꢀ3 mmol, 3 mol %) was
weighed into a dried tube equipped with a condenser under a
nitrogen atmosphere. Next, t-BuOH/MeOH (5:1) (1.2 mL) was
added and the suspension was stirred at room temperature for

1374
W. Duan et al. / Tetrahedron: Asymmetry 23 (2012) 1369–1375
124.2, 120.8, 110.5, 101.1, 72.6, 68.4, 55.5. HRMS (ESI): Calcd for
C
(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.
18H15O (MꢀOH)+ 247.1123. Found: 247.1116.
4.8.3. (1-Naphthyl) (3-methoxyphenyl)methanol c14
(ꢀ)-c14: 95% yield; ½a D20
¼ ꢀ34:5 (c 0.12, CH2Cl2) with 42% ee;
ꢂ
the 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 34.2 min (major) and
37.4 min (minor). 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.
4.8.9. (4-Chlorophenyl)(3-methoxyphenyl)methanol c34
(S)-(+)-c34: 99% yield; ½a D20
¼ þ25:0 (c 0.12, CH2Cl2) with 54%
ꢂ
ee; the 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 39.0 min (minor)
and 42.8 min (major) 1H NMR (300 MHz, CDCl3, rt): d 7.33–7.21 (m,
5H), 6.9–6.79 (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
C
14H12ClO (MꢀOH)+ 231.0577. Found: 231.0579.
4.8.4. (2-Methoxyphenyl)phenylmethanol c23
4.8.10. (1-Naphthyl) [4-(methoxycarbonyl)phenyl] methanol
c41
(R)-(+)-c23: 94% yield; ½a D20
¼ þ10:9 (c 0.10, CH2Cl2) with 36%
ꢂ
ee; the ee value was determined by HPLC analysis using a chiral
column (Chiralpak IA column, n-hexane/i-propanol = 10:1, flow
1.0 ml/min, detection at 254 nm), retention times 16.4 min (minor)
and 17.3 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 128.7, 128.1, 127.8,
127.1, 126.6, 120.8, 110.8, 72.1, 55.4. HRMS (ESI): Calcd for
(+)-c41: 99% yield; ½a D20
¼ þ34:8 (c 0.23, CH2Cl2) with 54% ee;
ꢂ
the ee value was determined by HPLC analysis using a chiral col-
umn (Chiralpak IA column, n-hexane/i-propanol = 4:1, flow
1.0 ml/min, detection at 254 nm), retention times 17.7 min (major)
and 21.3 min (minor). 1H NMR (300 MHz, CDCl3, rt): 8.01 (d, J = 6.0
Hz, 1H), 7.99 (t, J =8.4 Hz, 2H), 7.87–7.80 (m, 2H), 7.53–7.40 (m,
6H), 6.53 (s, 1H), 3.87 (s, 3H), 2.55 (s, 1H); 13C NMR (75 MHz,
CDCl3, rt): d 166.9, 148.2, 138.3, 134.1, 130.6, 129.8, 129.3, 128.9,
128.8, 126.8, 126.3, 125.8, 125.3, 125.2, 123.9, 73.5, 52.1. HRMS
(ESI): Calcd for C19H15O2 (MꢀOH)+ 275.1072. Found: 275.1079.
C
14H13O (MꢀOH)+ 197.0966. Found: 197.0960.
4.8.5. (3-Methoxyphenyl)phenylmethanol c24
(S)-(+)-c24: 99% yield; ½a D20
¼ þ13:8 (c 0.22, CH2Cl2) with 48%
ꢂ
ee; the 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 30.2 min (major)
and 34.7 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.
4.8.11. [4-(Methoxycarbonyl)phenyl]phenylmethanol c42
(R)-(ꢀ)-c42: 99% yield; ½a D20
¼ ꢀ14:4 (c 0.21, CH2Cl2) with 53%
ꢂ
ee; the ee value was determined by HPLC analysis using a chiral
column (Chiralpak IA column, n-hexane/chloroform = 2:1, flow
1.0 ml/min, detection at 254 nm), retention times 23.7 min (major)
and 29.2 min (minor). 1H NMR (300 MHz, CDCl3, rt): d 8.05–7.97
(m, 3H), 7.54–7.40 (m, 6H), 6.55 (s, 1H), 3.88 (s, 3H), 2.50 (d, J
=3.0 Hz, 1H); 13C NMR (75 MHz, CDCl3, rt): d 166.9, 148.1, 138.3,
129.8, 128.9, 126.8, 126.4, 125.8, 125.2, 73.6, 52.1. HRMS (ESI):
Calcd for C15H13O2 (MꢀOH)+ 225.0916. Found: 225.0910.
HRMS (ESI): Calcd for
197.0962.
C
14H13
O
(MꢀOH)+ 197.0966. Found:
4.8.6. (4-Chlorophenyl) (1-naphthyl)methanol c31
(S)-(ꢀ)-c31: 99% yield; ½a D20
ꢂ
¼ ꢀ48:4 (c 0.10, CH2Cl2) with 54%
4.8.12. (2-Methoxyphenyl)[4-
ee; the ee value was determined by HPLC analysis using a chiral
column (Chiralpak IA column, n-hexane/i-propanol = 10:1, flow
1.0 ml/min, detection at 254 nm), retention times 8.5 min (major)
and 9.1 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.
(methoxycarbonyl)phenyl]methanol c43
(ꢀ)-c43: 93% yield; ½a D20
¼ ꢀ20:0 (c 0.25, CH2Cl2) with 48% ee;
ꢂ
the ee value was determined by HPLC analysis using a chiral col-
umn (Chiralpak IA column, n-hexane/chloroform = 2:1, flow
1.0 ml/min, detection at 254 nm), retention times 14.7 min (major)
and 16.7 min (minor). 1H NMR (300 MHz, CDCl3, rt): d 8.00–7.97 (d,
J =8.1 Hz, 2H), 7.47 (d, J = 9.0 Hz, 2H), 7.31–7.20 (m, 2H), 6.97-6.88
(m, 2H), 6.08 (s, 1H), 3.90 (s, 3H), 3.80 (s, 3H); 13C NMR (75 MHz,
CDCl3, rt): d 156.7, 148.5, 131.4, 129.5, 129.1, 128.9, 127.9, 126.4,
120.9, 110.9, 72.1, 55.4, 52.0. HRMS (ESI): Calcd for C16H15O3
(MꢀOH)+ 255.1021. Found: 255.1010.
4.8.7. (4-Chlorophenyl) phenylmethanol c32
(S)-(+)-c32: 93% yield; ½a D20
¼ þ25:0 (c 0.1, CH2Cl2) with 52% ee;
ꢂ
the ee value was determined by HPLC analysis using a chiral col-
umn (Chiralpak IA column, n-hexane/i-propanol = 10:1, flow
1.0 ml/min, detection at 254 nm), retention times 18.0 min (major)
and 19.1 min (minor). 1H NMR (300 MHz, CDCl3, rt): d 7.35–7.25
(m, 9H), 5.81 (s, 1H), 2.23 (s, 1H); 13C NMR (75 MHz, CDCl3, rt): d
143.4, 142.2, 133.3, 128.7, 128.6, 127.9, 127.86, 126.5, 75.6. HRMS
(ESI): Calcd for C13H10Cl (MꢀOH)+ 219.0285. Found: 219.0249.
4.8.13. (3-Methoxyphenyl)[4-(methoxycarbonyl)phenyl]-
methanol c44
(+)-c44: 81% yield; ½a D20
¼ þ36:9 (c 0.23, CH2Cl2) with 54% ee;
ꢂ
the ee value was determined by HPLC analysis using a chiral col-
umn (Chiralpak IA column, n-hexane/i-propanol = 4:1, flow
1.0 ml/min, detection at 254 nm), retention times 16.4 min (major)
and 20.0 min (minor). 1H NMR (300 MHz, CDCl3, rt): d 7.99 (d,
J = 6.0 Hz, 2H), 7.46 (d, J = 6.0 Hz, 2H), 7.28–7.22 (m, 1H), 6.92 (d,
J = 6.0 Hz, 2H), 6.83–6.79 (m, 1H), 5.84 (s, 1H), 3.89 (s, 3H), 3.77
(s, 3H), 2.38 (s, 1H); 13C NMR (75 MHz, CDCl3, rt): d 166.9, 159.9,
148.5, 144.9, 129.8, 129.7, 129.3, 126.3, 118.9, 113.3, 112.2, 75.8,
55.2, 52.1. HRMS (ESI): Calcd for C16H15O3 (MꢀOH)+ 255.1021.
Found: 255.1031.
4.8.8. (4-Chlorophenyl)(2-methoxyphenyl)methanol c33
(+)-c33: 93% yield; ½a D20
¼ þ26:8 (c 0.11, CH2Cl2) with 22% 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 (major)
and 19.1 min (minor). 1H NMR (300 MHz, CDCl3, rt): d 7.32–7.19

W. Duan et al. / Tetrahedron: Asymmetry 23 (2012) 1369–1375
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Acknowledgments
Financial support from the National Natural Science Foundation
of China (Grant No. 20671059) and the Department of Science and
Technology of the Shandong Province is gratefully acknowledged.
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