Axially chiral C2-symmetric N-heterocyclic carbene (NHC) palladium complexes-catalyzed asymmetric arylation of aldehydes with arylboronic acids

Article abstract of DOI:10.1016/j.tetasy.2010.06.041

Chiral C₂-symmetric N-heterocyclic carbene (NHC) palladium diaquo complexes 5ac and the chiral C₂-symmetric NHC-palladium complexes 5d and 5e prepared from (R)-BINAM or H₈-(R)-BINAM could be used as the catalysts for the e

Full text of DOI:10.1016/j.tetasy.2010.06.041

Tetrahedron: Asymmetry 21 (2010) 1928–1935
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Axially chiral C2-symmetric N-heterocyclic carbene (NHC) palladium
complexes-catalyzed asymmetric arylation of aldehydes with arylboronic acids
Rui Zhang a, Qin Xu a, Xiuchun Zhang a, Tao Zhang a, Min Shi a,b,
*
a Key Laboratory for Advanced Materials and Institute of Fine Chemicals, School of Chemistry & Molecular Engineering, East China University of Science and Technology,
130 Mei Long Lu, Shanghai 200 237, China
b State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200 032, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Chiral C2-symmetric N-heterocyclic carbene (NHC) palladium diaquo complexes 5a–c and the chiral
C2-symmetric NHC-palladium complexes 5d and 5e prepared from (R)-BINAM or H8-(R)-BINAM could
be used as the catalysts for the enantioselective arylation of arylaldehydes with arylboronic acids in
which NHC-Pd complex 5a was found to be fairly effective in this reaction to give the corresponding
adducts in moderate enantioselectivities along with moderate to good yields.
Received 14 May 2010
Accepted 11 June 2010
Available online 4 August 2010
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
ties.8 These results promoted us to explore new chiral Pd catalysts
for these asymmetric addition reactions, since we envisioned that
Chiral diarylmethanols are important intermediates in most
pharmacologically and biologically active compounds and there-
fore represent significant synthetic targets.1 With regards to the
synthesis of chiral diarylmethanols, the catalytic asymmetric ary-
lation of arylaldehydes with arylboronic acids in the presence of
chiral transition metal complexes has attracted much attention
due to its safe and mild conditions. Upon carrying out a survey
in the literature, it was found that Oi and Inoue first reported the
rhodium-catalyzed arylation of ketones and aldehydes with arylst-
annanes under mild conditions in 1997;2 then Miyaura et al.
reported the Rh complex-catalyzed 1,2-addition to aldehydes with
arylboronic acids to give diarylmethanols in high yields in 1998.3
Many synthetic methods on the transition metal-catalyzed aryla-
tion of aldehydes with arylboronic acids have since been dis-
closed.4 Among these synthetic methods, Zhou et al. developed
several novel and effective chiral Rh-spiromonophosphite com-
plexes for this reaction, achieving 62–87% ees along with good
yields for representative aromatic aldehydes.5 More recently,
Miyaura et al. have developed an interesting Me-bipam ligand
system for the enantioselective ruthenium-catalyzed arylation of
aldehydes with arylboronic acids, affording the corresponding
diarylmethanols in good yields and ees.6 Hayashi et al. also have
developed effective tbf ligands for the rhodium-catalyzed asym-
metric arylation of aldehydes, giving chiral diarylmethanols in high
yields and ees.7 However, unlike Rh and Ru catalysts, using chiral
Pd catalysts in the arylation of aldehydes has not been very
successful and usually gave the adducts in lower enantioselectivi-
with the development of novel chiral ligands, chiral Pd complexes
could work as efficient catalysts in this reaction as well. Herein, we
report several chiral C2-symmetric N-heterocyclic carbene (NHC)
palladium catalysts in the enantioselective arylation of aldehydes
with arylboronic acids under mild conditions.
2. Results and discussion
Chiral C2-symmetric N-heterocyclic carbene (NHC) palladium
diaquo complexes 5a–c in addition to chiral C2-symmetric NHC-
palladium complexes 5d and 5e were synthesized from (R)-BINAM
or (R)-H8-BINAM, respectively, according to our previous literature
(Scheme 1).9 Notably, the structure of new chiral NHC-Pd complex
5e was determined by X-ray diffraction (Fig. 1).10 In the compari-
son of the dihedral angles of the two naphthalene rings between
NHC-Pd(II) complexes 5a and 5e, we found that 5e is 84.6° and
5a is 78.2°,9 which may cause the difference in the chiral induction.
Initial examinations using 4-nitrobenzaldehyde 6a and phenyl-
boronic acid 7a as the substrates in the presence of chiral C2-sym-
metric N-heterocyclic carbene (NHC) palladium diaquo complex 5a
and 4 Å MS (20 mg) in CHCl3 were aimed at determining the
optimal conditions and the results of these experiments are sum-
marized in Table 1. It was found that no reaction occurred in the
absence of base, even when the reaction was carried out at 60 °C
(Table 1, entries 1–3). Base screening for the reaction revealed that
using KOH (1.0 equiv) as the base afforded 8aa in 48% ee and >99%
yield in CHCl3 and increasing or decreasing the employed amount
of KOH did not improve the yield of 8aa (Table 1, entries 4–6). The
other bases such as KF, K3PO4, H2O, KOtBu, Cs2CO3, Ag2CO3, and
NaOH did not give 8aa in good yields (Table 1, entries 7–13).
* Corresponding author.
E-mail address: Mshi@mail.sioc.ac.cn (M. Shi).
0957-4166/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2010.06.041

R. Zhang et al. / Tetrahedron: Asymmetry 21 (2010) 1928–1935
1929
R
N
N
N
N
N
N
Pd(OAc)2
RX (2a-c) (X = Br or I)
2X-
º
º
dioxane, 100 C, 5~24 h
THF, 70 C, 12~24 h
N
N
R
2a = MeI, 2b = BnBr,
2c = 3,5-Me2C6H3CH2Br
1
3a-c
2+
R
R
N
N
N
N
N
X
X
AgOTf
OH2
Pd
Pd
2OTf-
OH2
CH2Cl2-CH3CN (3:1), rt, 10 min
N
N
N
R
R
4a-c
R = Me, (R)-N-Me-NHC-Pd(II) 5a, 83%
R = Bn, (R)-N-Bn-NHC-Pd(II) 5b, 90%
R = 3,5-Me2C6H3CH2, (R)-N-3,5-Xyl-NHC-Pd(II) 5c, 88%
N
N
N
N
N
CF3COOAg
CH2Cl2-CH3CN (3:1), rt, 10 min
I
I
OCOCF3
OCOCF3
Pd
Pd
N
N
N
4a
R = Me, (R)-N-Me-NHC-Pd(II) 5d, 83%
N
Pd
N
N
N
N
I
I
CF3COOAg
CH2Cl2-CH3CN (3:1), rt, 10 min
OCOCF3
OCOCF3
Pd
N
N
N
4e
(R)-H8-N-Me-NHC-Pd(II) 5e, 80%
Scheme 1. General procedure for the synthesis of chiral C2-symmetric N-heterocyclic carbene cationic Pd(II) diaquo complexes 5a–c as well as chiral C2-symmetric NHC-
Pd(II) complexes 5d and 5e.
With these tentatively optimized conditions in hand, we next
attempted to use catalysts 5b–e in the reaction under identical con-
ditions as shown in entry 4 of Table 1. Catalyst 5d (3 mol %) had sim-
ilar catalytic ability to that of 5a, giving the desired product 8aa in
excellent yield (>99%) and 45% ee after 36 h (Table 2, entry 3). Other
NHC-Pd complexes 5b and 5c as well as 5e having a chiral H8-
binaphthyl scaffold were not as effective as catalyst 5a (Table 2, en-
tries 1–4). Using chiral catalyst 5a, we also examined solvent effect
in this catalytic asymmetric addition reaction with toluene, tetrahy-
drofuran (THF), dichloromethane, DMSO, and DMF, but no improve-
ment could be observed in these solvents (Table 2, entries 5–9).
Using 5d as the catalyst, we also carried out the reaction in CHCl3,
THF, toluene, and CH2Cl2 combined with 0.1 mL of water in the
absence of 4 Å MS, but no improvement could be observed either
(Table 2, entries 10–13). Lowering the reaction temperature to
15 °C or 4 °C did not improve the reaction outcome if using the
NHC-Pd(II) complex 5d as the catalyst in CHCl3 (Table 2, entries 14
and 15).
Having optimized the reaction conditions, we next examined the
substrate scope with various arylaldehydes and arylboronic acids;
the results of these experiments are summarized in Table 3. The ary-
lation of either the electron-rich or the electron-deficient arylalde-
hydes with a variety of arylboronic acids proceeded smoothly to
afford the corresponding diarylmethanols in excellent yields using
5a as the catalyst (Table 3, entries 1–7, 9–14, and 16–20). In the case
of 4-nitrobenzaldehyde 6a, good enantioselectivities were achieved
using naphthalen-2-ylboronic acid 7e or biphenyl-4-ylboronic acid
7f as the arylation reagent (Table 3, entries 4 and 5). As for

1930
R. Zhang et al. / Tetrahedron: Asymmetry 21 (2010) 1928–1935
Figure 1. ORTEP drawing of Bis(NHC)-Pd(II) complex 5e with thermal ellipsoids at the 30% probability level. Selected bond distances (Å) and angles (°): Pd–C1 = 1.907 (10),
Pd–C20 = 1.944 (10), Pd–O1 = 2.802 (10), Pd–O3 = 2.096 (7), C1–Pd–C20 = 94.5 (4), C1–Pd–O1 = 90.8 (4), O1–Pd–O3 = 85.9 (3), O3–Pd–C20 = 88.8 (3), C20–Pd–O1 = 173.4 (4),
C1–Pd–O3 = 176.6 (4).
Table 1
Optimization of the reaction conditions in the asymmetric arylation of 4-nitrobenzaldehyde and phenylboronic acida
OH
(R)-N-Me-NHC-Pd(II) 5a (3 mol%)
CHO
4Å MS, Base (x equiv)
Ph
B(OH)2
+
º
CHCl3, 20 C
O2N
O2N
6a
7a (2.0 equiv)
8aa
Entry
Base
X
Time (h)
Yieldb (%)
eec (%)
1d
2
—
—
—
KOH
KOH
KOH
KF
—
—
—
24
24
24
24
24
24
24
24
24
24
24
24
24
n.r.e
n.r.
n.r.
>99
90
79
53
56
<10
<10
<10
10
n.d.
n.d.
n.d.
3f
4
1.0
2.0
0.5
1.0
1.0
1.0
1.0
1.0
1.0
1.0
48 (S)
43 (S)
39 (S)
42 (S)
37 (S)
2 (S)
13 (S)
n.d.
5
6
7
8
K3PO4ꢀ3H2O
9
KOtBu
10
11
12
13
Cs2CO3
Ag2CO3
NaOH
20 (S)
40 (S)
K2CO3
65
a
Reaction conditions: phenylboronic acid (7a, 0.5 mmol), 4-nitrobenzaldehyde (6a, 0.25 mmol), NHC-Pd(II) 5a (3 mol %, 0.0075 mmol), 4 Å MS (20 mg), CHCl3 (1.0 mL), and
the reaction was carried out at 20 °C for 24 h.
b
Isolated yields.
c
The ee value was determined by HPLC using a Chiralcel AD-H column. The absolute configuration of the products was assigned by comparison with that of the literature
compounds.
d
H2O (0.1 mL) was used as the additive in the absence of 4 Å MS.
No reaction.
This reaction was carried at 60 °C.
e
f
2,4-dichlorobenzaldehyde 6d, good enantioselectivities were
obtained using phenylboronic acid 7a and 3- or 4-methylphenylbo-
ronic acid 7c or 7d as the arylation reagents (Table 3, entries 10–14).
However, in the reactions of 6a with 7b–d, 3-nitrobenzaldehyde 6b
with 7e and 7f, and 4-cyanobenzaldehyde 6c with 7f as well as 6d
with 7b and 7f, the corresponding adducts were obtained in
10–23% ee’s (Table 3, entries 1–3, 6–7, 9, 11 and 14). Using elec-
tron-rich arylaldehydes 6e and 6f in this reaction with 7f afforded
the corresponding adducts 8ef and 8ff in 0–1% ee’s (Table 3, entries
16 and 17). In the reaction of 2- or 4-chlorobenzaldehyde with 7f or
7a and the reaction of 2-nitrobenzaldehyde with 7f, the correspond-
ing adducts 8ga, 8ha, and 8if were also obtained in low enantiomeric

R. Zhang et al. / Tetrahedron: Asymmetry 21 (2010) 1928–1935
1931
Table 2
Optimization of the reaction conditions in the asymmetric arylation of 4-nitrobenzaldehyde and phenylboronic acida
catalyst (3 mol%)
4Å MS (20 mg), KOH (1.0 equiv)
OH
O2N
B(OH)2
+
O
solvent, temperature
O2N
6a
7a (2.0 equiv)
8aa
Entry
Catalyst
Base
Solvent
Temp (°C)
Time (h)
Yieldb (%)
eec (%)
1
2
3
4
5
6
7
8
9
5b
5c
5d
5e
5a
5a
5a
5a
5a
5d
5d
5d
5d
5d
5d
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
CHCl3
CHCl3
CHCl3
CHCl3
Toluene
THF
CH2Cl2
DMSO
20
20
20
20
20
20
20
60
60
20
20
20
20
15
4
24
24
36
24
36
24
24
24
24
24
24
36
24
24
48
>99
96
>99
80
9 (S)
30 (S)
45 (S)
20 (S)
43 (S)
3 (S)
43 (S)
n.d.
3 (S)
47 (S)
3 (S)
43 (S)
47 (S)
43 (S)
n.d.
>99
>99
75
n.r.e
<10
>99
30
DMF
10d
11d
12d
13d
14
15
CHCl3/H2O
THF/H2O
Toluene/H2O
CH2Cl2/H2O
CHCl3
80
>99
75
CHCl3
n.r.
a
b
c
Reaction conditions: phenylboronic acid (7a, 0.5 mmol), 4-nitrobenzaldehyde (6a, 0.25 mmol), NHC-Pd(II) 5a (3 mol %, 0.0075 mmol), 4 Å MS (20 mg), and CHCl3 (1.0 mL).
Isolated yields.
The ee value was determined by HPLC using a Chiralcel AD-H column. The absolute configuration of the products was assigned by comparison with that of the literature
compounds.
d
H2O (0.1 mL) as the additive and in the absence of 4 Å MS.
No reaction.
e
Table 3
Asymmetric arylation of arylaldehydes with various arylboronic acids under optimal conditionsa
OH
catalyst 5a or 5e (3 mol%)
4Å MS (20 mg), KOH (1.0 equiv)
∗
R'
R
B(OH)2
7 (2.0 equiv)
+
RCHO
R'
º
CHCl3, 20 C
6 (1.0 equiv)
8
Entry
RCHO
R0B(OH)2
Time (h)
Yieldb (%)
eec (%)
1
2
3
4
5
6
4-NO2–C6H4CHO, 6a
4-NO2–C6H4HO, 6a
4-NO2–C6H4CHO, 6a
4-NO2–C6H4CHO, 6a
4-NO2–C6H4CHO, 6a
3-NO2–C6H4CHO, 6b
3-NO2–C6H4CHO, 6b
3-NO2–C6H4CHO, 6b
4-CN–C6H4CHO, 6c
2,4-Dichloro-C6H3CHO, 6d
2,4-Dichloro-C6H3CHO, 6d
2,4-Dichloro-C6H3CHO, 6d
2,4-Dichloro-C6H3CHO, 6d
2,4-Dichloro-C6H3CHO, 6d
2,4-Dichloro-C6H3CHO, 6d
4-MeO–C6H4CHO, 6e
2-Me-PhB(OH)2, 7b
3-Me-PhB(OH)2, 7c
4-Me-PhB(OH)2, 7d
2-Naphthalenyl-B(OH)2, 7e
4-Biphenyl-B(OH)2, 7f
2-Naphthalenyl-B(OH)2, 7e
4-Biphenyl-B(OH)2, 7f
4-Biphenyl-B(OH)2, 7f
4-Biphenyl-B(OH)2, 7f
PhB(OH)2, 7a
24
24
24
36
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
80
90
90
70
90
60
95
70
85
85
75
80
80
90
75
70
75
95
80
85
8ab, 10 (+)
8ac, 21 (+)
8ad, 23 (+)
8ae, 48 (+)
8af, 57 (+)
8be, 20 (ꢁ)
8bf, 15 (+)
8bf, 29 (+)
8cf, 20 (+)
8da, 65 (S)
8db, 20 (ꢁ)
8dc, 50 (+)
8dd, 40 (+)
8df, 20 (ꢁ)
8df, 40 (ꢁ)
8ef, 1 (ꢁ)
7
8d
9
10e
11e
12e
13e
14e
15d
16
17
18
19
20
2-Me-PhB(OH)2, 7b
3-Me-PhB(OH)2, 7c
4-Me-PhB(OH)2, 7d
4-Biphenyl-B(OH)2, 7f
4-Biphenyl-B(OH)2, 7f
4-Biphenyl-B(OH)2, 7f
4-Biphenyl-B(OH)2, 7f
4-Biphenyl-B(OH)2, 7f
PhB(OH)2, 7a
4-Me-C6H4CHO, 6f
8ff,
0
2-Chloro-C6H4CHO, 6g
4-Chloro-C6H4CHO, 6h
2-NO2–C6H4CHO, 6i
8gf, 6 (+)
8ha, 13 (S)
8if, 5 (+)
4-Biphenyl-B(OH)2, 7f
a
b
c
Reaction conditions: arylboronic acid (7, 0.5 mmol), arylaldehyde (6, 0.25 mmol), NHC-Pd(II) 5a (3 mol %, 0.0075 mmol) and 4 Å MS (20 mg).
Isolated yields.
The ee value was determined by HPLC using a Chiralcel column. The absolute configuration of the products was assigned by comparison with that of the literature
compounds.
d
Reaction conditions: phenylboronic acid (7, 0.5 mmol), arylaldehyde (6, 0.25 mmol), NHC-Pd(II) 5e (3 mol %, 0.0075 mmol), and 4 Å MS (20 mg).
The reaction was carried out at 60 °C.
e
excesses (Table 3, entries 18–20). These results suggest that arylal-
dehydes and arylboronic acids have very subtle electronic and steric
effects on the reaction outcome and the achieved enantiomeric ex-
cesses are dependent on the substrates employed. Since chiral
NHC-Pd(II) complex 5e is a new catalyst, we also used it in the reac-
tion of 6b and 6d with biphenyl-4-ylboronic acid 7f, affording the
corresponding adducts 8bf and 8df in 29% and 40% ee’s and good
yields (Table 3, entries 8 and 15).

1932
R. Zhang et al. / Tetrahedron: Asymmetry 21 (2010) 1928–1935
4.2.2. General procedure for the synthesis of NHC-Pd(II)
3. Conclusion
complexes 4a–c
Compounds 3a–c (0.2 mmol) and Pd(OAc)2 (44.8 mg, 0.2 mmol)
were refluxed in THF (10 mL) for 16–30 h. The volatiles were then
removed under reduced pressure and the residue was purified by a
silica gel flash column chromatography (eluent: petroleum ether/
EtOAc, 2:1 to 0:1) to give 4a–c as yellow solids.
In conclusion, chiral C2-symmetric N-heterocyclic carbene (NHC)
palladium diaquo complexes 5a–c and chiral C2-symmetric NHC-
palladium complexes 5d and 5e prepared from (R)-BINAM or
H8-(R)-BINAM could be used as catalysts for the enantioselective
arylation of arylaldehydes with arylboronic acids to give the corre-
sponding adducts in moderate enantioselectivities along with
moderate to good yields. The NHC-Pd(II) complex 5a is a fairly
effective catalyst in this reaction to give the adduct in up to 65%
ee and high yield. In this catalytic asymmetric reaction, arylalde-
hydes and arylboronic acids have very subtle electronic and steric
effects on the reaction outcome. Efforts are currently underway to
elucidate the mechanistic details of this asymmetric addition reac-
tion in the presence of a chiral NHC-Pd(II) catalyst and to disclose
the exact structure of the active species in this catalytic system.
4.2.2.1. (R)-NHC-Pd(II) complex 4a. This is a known compound.9
A yellow solid; mp >300 °C (dec); ½a D20
¼ þ270:0 (c 0.086, CHCl3),
ꢂ
1H NMR (300 MHz, CDCl3, TMS): d 8.10–8.03 (m, 4H), 7.72 (d,
J = 8.4 Hz, 2H), 7.25–7.19 (m, 2H), 6.94–6.87 (m, 4H), 6.85–6.82
(m, 2H), 6.78–6.74 (m, 4H), 6.68 (d, J = 8.7 Hz, 2H), 3.82 (s, 6H).
4.2.2.2. (R)-NHC-Pd(II) complex 4b. This is a known compound.9
Pale-yellow solid; mp >300 °C (dec); ½a D20
¼ þ45:0 (c 0.245, CHCl3);
ꢂ
IR (CH2Cl2)
m 3060, 2961, 2926, 2855, 1474, 1389, 1335, 1261,
1101, 1032, 804 cmꢁ1 1H NMR (300 MHz, CDCl3, TMS): d 7.84 (d,
;
4. Experimental
J = 8.4 Hz, 2H), 7.79 (d, J = 8.4 Hz, 2H), 7.63 (d, J = 8.7 Hz, 2H),
7.33 (d, J = 8.4 Hz, 2H), 7.30–7.27 (m, 6H), 6.94–6.85 (m, 10H),
6.77–6.71 (m, 8H), 5.39 (d, J = 15.9 Hz, 2H). 13C NMR (75 MHz,
CDCl3, TMS): d 170.9, 136.3, 135.3, 134.6, 133.0, 132.7, 132.1,
131.4, 130.5, 128.5, 128.1, 128.0, 127.8, 127.7, 127.4, 126.7,
124.5, 123.6, 123.1, 112.3, 111.5, 55.6.
4.1. General methods
Melting points were obtained with a Yanagimoto micro melting
point apparatus and are uncorrected. Optical rotations were deter-
mined in a solution of CHCl3, CH2Cl2, or acetone at 20 °C by using a
Perkin–Elmer-241 MC polarimeter; [a]D-values are given in units
4.2.2.3. NHC-Pd(II) complex 4c. This is a known compound.9 Pale-
of 10ꢁ1 deg cm2 gꢁ1. Infra-red spectra were measured on a spec-
trometer. 1H NMR spectra were recorded for solution in CDCl3 with
tetramethylsilane (TMS) as an internal standard; 31P NMR spectra
were recorded at 121 MHz for a solution in CDCl3 with 85%
H3PO4 as the external reference. J-Values are in hertz. Mass spectra
were recorded with an HP-5989 instrument and HRMS was mea-
sured by a Finnigan MA+ mass spectrometer. Organic solvents used
were dried by standard methods when necessary. Commercially
obtained reagents were used without further purification. All the
reactions were monitored by TLC with Huanghai 60F254 Silica Gel
coated plates. Flash column chromatography was carried out using
300–400 mesh silica gel at increased pressure. All asymmetric
addition reactions were performed under argon using standard
Schlenk techniques. The enantiomeric purities of adducts were
determined by HPLC analysis using a chiral stationary phase col-
umn (column, Daicel Co. Chiralcel AD and OD) and the absolute
configuration of the major enantiomer was assigned according to
the sign of the specific rotation.
yellow solid; mp >300 °C (dec); ½a D20
¼ þ132:0 (c 0.195, CHCl3); IR
ꢂ
(CH2Cl2)
m 3057, 2920, 2845, 1736, 1720, 1607, 1475, 1389, 1251,
1175, 1032, 853, 830, 743 cmꢁ1 1H NMR (300 MHz, CDCl3, TMS):
;
d 7.62 (d, J = 8.1 Hz, 2H), 7.48 (d, J = 8.4 Hz, 2H), 7.27–7.21 (m,
8H), 7.05–6.85 (m, 10H), 6.73 (d, J = 8.7 Hz, 2H), 6.60 (d, J = 8.1 Hz,
2H), 6.55 (d, J = 15.6 Hz, 2H), 5.29 (d, J = 15.6 Hz, 2H), 2.38 (s, 12H).
4.2.3. General procedure for the synthesis of cationic NHC-Pd(II)
diaquo complexes 5a–c
Complexes 4a–c (0.20 mmol) were suspended in a mixture of
CH2Cl2 (15 mL) and CH3CN (5 mL). Next, AgOTf (108 mg,
0.42 mmol) was added and the mixture was stirred at room tem-
perature for 10 min. The resulting suspension was filtered from
the precipitated AgX (X = Br or I) through Celite and the solvent
was removed under reduced pressure to give 5a–c as a white
powder.
4.2.3.1. Cationic NHC-Pd(II) diaquo complex 5a. This is a known
compound.9 White solid; mp 289 °C (dec); ½a 2D0
¼ þ43:0 (c 0.315,
ꢂ
4.2. General procedure for the synthesis of C2-symmetric N-
heterocarbene palladium complexes 5a–e
CHCl3); IR (CH2Cl2)
m 3223, 2925, 2847, 1580, 1511, 1395, 1290,
1168, 1029, 751 cmꢁ1 1H NMR (300 MHz, CDCl3, TMS): d 8.14 (s,
;
4H), 7.76 (d, J = 8.1 Hz, 2H), 7.30–7.27 (m, 2H), 7.05–6.91 (m,
8H), 6.84–6.77 (m, 4H), 3.93 (s, 6H), 2.16 (br s, 4H). 19F NMR
(282 MHz, CDCl3, CF3CO2H): d ꢁ83.8 (s).
4.2.1. General procedure for the synthesis of imidazolium salts
3a–c
Compounds 1 (485 mg, 0.4 mmol) and 2a–c (0.5 mmol) (2a:
MeI, 2b: BnBr, 2c: 3,5-Me2C6H3CH2Br) in dioxane (10 mL) were
stirred at reflux for 5–24 h. After cooling down to room tempera-
ture (20 °C), the volatiles were removed under reduced pressure
and the solid compound obtained was used for the next reaction
without any further purification.
4.2.3.2. Cationic NHC-Pd(II) diaquo complex 5b. This is a known
compound.9 White solid; mp 259 °C (dec); ½a 2D0
¼ þ66:0 (c 0.22,
ꢂ
CHCl3); IR (CH2Cl2)
m 2956, 2924, 2854, 1580, 1464, 1379, 1250,
1170, 1030, 745 cmꢁ1 1H NMR (300 MHz, CDCl3, TMS): d 8.03 (d,
;
J = 8.4 Hz, 2H), 7.93 (d, J = 8.4 Hz, 2H), 7.83 (d, J = 8.1 Hz, 2H),
7.35–7.32 (m, 8H), 7.03–6.89 (m, 6H), 6.84–6.72 (m, 10H), 5.84
(d, J = 16.2 Hz, 2H), 5.65 (d, J = 16.2 Hz, 2H), 4.13 (br s, >4H). 19F
NMR (282 MHz, CDCl3, CF3CO2H): d ꢁ83.6 (s).
4.2.1.1. (R)-2,20-Di (1H-benzo[d]imidazol-1-yl)-1,10-binaphthyl
1. This is a known compound.9 White solid; mp 294.5–294.8 °C;
4.2.3.3. Cationic NHC-Pd(II) diaquo complex 5c. This is a known
a 2D0
ꢂ
¼ þ516:7 (c 0.97, CHCl3); 1H NMR (400 MHz, CDCl3, TMS): d
compound.9 White solid; mp >250 °C (dec); ½a 2D0
ꢂ
¼ þ95:0 (c 0.22,
½
8.06 (d, J = 8.8 Hz, 4H), 7.67–7.63 (m, 2H), 7.55–7.48 (m, 6H),
7.43 (d, J = 8.8 Hz, 2H), 6.99 (s, 2H), 6.95 (d, J = 8.0 Hz, 2H), 6.50
(t, J = 7.6 Hz, 2H), 6.11 (d, 2H, J = 8.0 Hz).
CHCl3); IR (CH2Cl2)
m 2958, 2925, 2852, 1581, 1487, 1339, 1258,
1172, 1030, 745 cmꢁ1
;
1H NMR (300 MHz, CDCl3, TMS): d 7.78 (d,
J = 7.8 Hz, 2H), 7.44–7.34 (m, 4H), 6.97–6.73 (m, 18H), 6.66–6.63

R. Zhang et al. / Tetrahedron: Asymmetry 21 (2010) 1928–1935
1933
(m, 4H), 5.72 (d, J = 9.9 Hz, 2H), 5.37 (br s, 4H), 2.27 (s, 12H). 19F
NMR (282 MHz, CDCl3, CF3CO2H): d ꢁ83.6 (s).
tminor = 12.52 min and tmajor = 15.47 min]. 1H NMR (400 MHz,
CDCl3, TMS) d 8.18 (d, J = 8.8 Hz, 2H), 7.57 (d, J = 8.8 Hz, 2H),
7.36–7.31 (m, 5H), 5.91 (s, 1H), 2.49 (br s, 1H).
4.2.3.4. NHC-Pd(II) complex 5d. At first, NHC-Pd(II) complex 5d
was prepared by a similar procedure using (R)-2,20-di (1H-benzo-
[d]imidazol-1-yl)-1,10-binaphthyl as the starting material. This is
4.2.4.2. (+)-(4-Nitrophenyl)(o-tolyl)methanol 8ab. A known
compound,12 80% yield, a yellow oil, ½a 2D0
¼ þ6:8 (c 1.06, CHCl3),
ꢂ
a known compound.9 White solid; mp >250 °C (dec); ½a 2D0
ꢂ
¼
10% ee [HPLC conditions: Chiracel AD-H column, hexane/2-propa-
ꢁ33:0 (c 0.395, CHCl3); IR (CH2Cl2)
m
2957, 2925, 2854, 1735,
nol = 90:10, flow rate = 1.0 mL/min, wavelength = 254 nm, tminor =
1466, 1379, 1260, 1174, 1031, 747 cmꢁ1; 1H NMR (300 MHz, CDCl3,
TMS) d 8.09 (s, 4H), 7.73 (d, J = 7.8 Hz, 2H), 7.28–7.23 (m, 2H),
6.98–6.83 (m, 10H), 6.78–6.76 (m, 2H), 3.88 (s, 6H). 19F NMR
(282 MHz, CDCl3, CF3CO2H) d ꢁ74.9 (s).
10.39 min and tmajor = 13.13 min]. 1H NMR (300 MHz, CDCl3,
TMS) d 8.14 (d, J = 7.8 Hz, 2H), 7.49 (d, J = 10.2 Hz, 2H), 7.32–7.29
(m, 1H), 7.25–7.15 (m, 3H). 6.05 (s, 1H), 2.70 (br s, 1H), 2.28
(s, 3H).
4.2.3.5. NHC-Pd(II) complex 4e. This is a known compound.9 Pale-
4.2.4.3. (+)-(4-Nitrophenyl)(m-tolyl)methanol 8ac. A known com-
yellow solid; mp >300 °C (dec); ½a D20
ꢂ
¼ þ53 (c 0.24, CHCl3); IR
pound,13 90% yield, yellow oil. ½a 2D0
¼ þ13:5 (c 0.24, CHCl3), 21% ee
ꢂ
(CH2Cl2):
m
3054, 2930, 2306, 1480, 1436, 1340, 1132, 897, 740,
[HPLC conditions: Chiracel AD-H column, hexane/2-propa-
705, 557 cmꢁ1
;
1H NMR (300 MHz, CDCl3, TMS):
d
7.60 (d,
nol = 90:10, flow rate = 1.0 mL/min, wavelength = 254 nm, tminor =
J = 8.1 Hz, 2H), 7.24–7.22 (m, 3H), 7.20–7.18 (m, 1H), 7.15–7.11
(m, 4H), 6.89 (d, J = 8.1 Hz, 2H), 3.92 (s, 6H), 2.66–2.56 (m, 2H),
2.31–2.20 (m, 2H), 1.91–1.81 (m, 2H), 1.64–1.55 (m, 4H), 1.41–
1.17 (m, 6H).
10.51 min and tmajor = 14.09 min]. 1H NMR (400 MHz, CDCl3, TMS) d
8.16 (d, J = 8.8 Hz, 2H), 7.55 (d, J = 8.8 Hz, 2H), 7.25–7.22 (m, 1H),
7.13–7.11 (m, 3H), 5.85 (s, 1H), 2.56 (br s, 1H), 2.33 (s, 3H).
4.2.4.4. (+)-(4-Nitrophenyl)(p-tolyl)methanol 8ad. A known com-
4.2.3.6. NHC-Pd(II) complex 5e. NHC-Pd(II) complex 5e was pre-
pared by a similar procedure using (R)-1,10-(4a,5,50,6,60,7,70,8,8a,80-
decahydro-1,10-binaphthyl-2,20-diyl)bis(1H-benzo[d]imidazole) as
pound,12 90% yield, yellow oil. ½a 2D0
¼ þ11:1 (c 1.03, CHCl3), 23% ee
ꢂ
[HPLC conditions: Chiracel AD-H column, hexane/2-propanol =
90:10, flow rate = 1.0 mL/min, wavelength = 254 nm, tminor
=
the starting materials. White solid; mp >290 °C (dec); ½a D20
ꢂ
¼
12.94 min and tmajor = 15.89 min]. 1H NMR (400 MHz, CDCl3, TMS)
d 8.16 (d, J = 8.8 Hz, 2H), 7.55 (d, J = 8.4 Hz, 2H), 7.21 (d, J = 8.0 Hz,
2H), 7.16 (d, J = 8.0 Hz, 2H), 5.86 (s, 1H), 2.53 (br s, 1H), 2.33 (s, 3H).
þ54:0 (c 0.162, CHCl3); IR (CH2Cl2)
m
3450, 3016, 2970, 1738,
1439, 1366, 1228, 1217, 1130, 1085, 897, 838, 747, 724 cmꢁ1
;
1H
NMR (400 MHz, CDCl3, TMS): d 7.68 (d, J = 8.0 Hz, 2H), 7.30–7.24
(m, 4H), 7.20–7.13 (m, 4H), 6.90 (d, J = 8.0 Hz, 2H), 3.96 (s, 6H),
2.65–2.60 (m, 2H), 2.32–2.26 (m, 2H), 2.01–1.93 (m, 2H), 1.77–
1.72 (m, 2H), 1.44–1.40 (m, 2H), 1.29–1.22 (m, 4H), 0.44–0.41
(m, 2H). 13C NMR (100 MHz, CDCl3, TMS): d 166.7, 161.7 (q,
J = 35.3 Hz), 139.9, 137.6, 135.4, 134.5, 133.8, 133.7, 129.7, 124.9,
124.1, 123.8, 116.0 (q, J = 289.6 Hz), 112.6, 109.8, 34.9, 29.2, 27.2,
21.9, 21.5. 19F NMR (282 MHz, CDCl3, CF3CO2H): d ꢁ74.6 (s). MS
(ESI) m/z: 741.2 (M+ꢁCF3COO, 100). HRMS (ESI) calcd for
4.2.4.5. (+)-Naphthalen-2-yl(4-nitrophenyl)methanol 8ae. A known
compound,8b 70% yield, yellow oil, ½a 2D0
¼ þ2:0 (c 0.58 CHCl3), 48% ee
ꢂ
[HPLC conditions: Chiracel AD-H column, hexane/2-propanol = 90:10,
flow rate = 1.0 mL/min, wavelength = 254 nm, tminor = 20.72 min and
tmajor = 24.95 min].1H NMR (400 MHz, CDCl3, TMS)
d 8.20 (d,
J = 8.8 Hz, 2H), 7.85 (d, J = 8.0 Hz, 2H), 7.83 (d, J = 8.0 Hz, 2H), 7.63
(d, J = 8.4 Hz, 2H), 7.51 (t, J = 3.6 Hz, 2H), 7.39 (dd, J = 1.6, 8.4 Hz,
1H), 6.09 (s, 1H), 2.50 (br s, 1H).
C38H34N4O2F3Pd requires: 741.1669. Found: 741.1653. Anal. Cald
for 4[C40H34F6N4O4Pd]ꢀCH2Cl2: C, 55.16; H, 3.97; N, 6.39. Found:
C, 55.08; H, 4.22; N, 6.39. Crystals that were suitable for X-ray dif-
fraction analysis were grown from solutions in CH2Cl2/hexane
(2:1).
4.2.4.6. (+)-Biphenyl-4-yl(4-nitrophenyl)methanol 8af. 90% yield,
white solid; mp 138.7.2–140.1 °C; ½a D20
¼ þ65:0 (c 0.35 CHCl3), 57%
ꢂ
ee [HPLC conditions: Chiracel OD-H column, hexane/2-propa-
nol = 90:10, flow rate = 1.0 mL/min, wavelength = 254 nm, tminor
=
35.59 min and tmajor = 40.19 min]. IR (CH2Cl2) 3534, 3106, 3074,
m
4.2.4. General procedure for the asymmetric arylation of
arylaldehydes and arylboronic acids
3029, 2920, 2876, 2844, 1731, 1715, 1602, 1511, 1486, 1346,
1286, 1189, 1170, 1106, 1042, 1007, 962, 878, 866, 825, 803, 763,
At first, NHC-PdII catalyst 5a (3 mol %, 7.5
l
mol), KOH
755, 731, 697 cmꢁ1 1H NMR (400 MHz, CDCl3, TMS) d 8.19 (d,
;
(1.0 equiv, 0.25 mmol, 14 mg), and 20 mg activated 4 Å molecule
sieves were dissolved in CHCl3 (1.0 mL) in a flame-dried Schlenk
tube equipped with a septum and stirring bar and the mixture
was stirred under argon at room temperature (20 °C) for 10 min.
Arylboronic acid 7 (2.0 equiv, 0.5 mmol) was added followed by
the addition of the corresponding arylaldehyde 6 (0.25 mmol).
After that, the reaction mixture was stirred at 20 °C for 24 h, and
then saturated aqueous solution of NaHCO3 (5 mL) was added into
the reaction mixture. The organic phase was separated and the
resulting aqueous layer was extracted with EtOAc (3 ꢃ 10 mL).
The combined organic phases were filtered through a thin-layer
of Celite. The filtrate was washed with brine (5 mL), dried over
anhydrous Na2SO4, concentrated under reduced pressure, and
purified by flash chromatography on silica gel (eluent: EtOAc/
petroleum ether = 1:8) to yield the corresponding pure product 8.
J = 8.8 Hz, 2H), 7.61–7.54 (m, 6H), 7.45–7.39 (m, 4H), 7.37–7.33
(m, 1H), 5.95 (s, 1H), 2.49 (br s, 1H). 13C NMR (100 MHz, CDCl3,
TMS) d 150.6, 147.2, 141.6, 141.4, 140.3, 128.8, 127.64, 127.56,
127.13, 127.06, 123.7, 75.3. MS (%) m/z 305.1 (M+, 100), 241.1 (9),
181.1 (29), 155.1 (97), 77.0 (8). HRMS (EI) calcd for C19H15NO3 re-
quires: 305.1052. Found: 305.1051.
4.2.4.7. (ꢁ)-Naphthalen-2-yl(3-nitrophenyl)methanol 8be. 60%
yield, yellow oil; ½a D20
¼ ꢁ87 (c 0.215, CHCl3), 20% ee [HPLC condi-
ꢂ
tions: Chiracel OD-H column, hexane/2-propanol = 90:10, flow
rate = 1.0 mL/min, wavelength = 254 nm, tminor = 44.04 min and
tmajor = 50.66 min]. IR (CH2Cl2)
1601, 1528, 1349, 1267, 1164, 1122, 1093, 1036, 966, 901, 860,
812, 777, 746, 727, 697 cmꢁ1 1H NMR (400 MHz, CDCl3, TMS) d
m 3419, 3056, 2922, 2853, 1731,
;
8.35 (s, 1H), 8.11 (d, J = 8.0 Hz, 1H), 7.86–7.81 (m, 4H), 7.73 (d,
J = 8.0 Hz, 1H), 7.52–7.46 (m, 3H), 7.40 (dd, J = 1.6, 8.8 Hz, 1H),
6.07 (s, 1H), 2.56 (br s, 1H); 13C NMR (100 MHz, CDCl3, TMS) d
148.4, 145.6, 140.0, 133.19, 133.13, 132.5, 129.4, 129.0, 128.1,
127.7, 126.6, 126.5, 125.6, 124.2, 122.5, 121.4, 75.5. MS (%) m/z
279.1 (M+, 79), 215.1 (14), 202.1 (10), 155.0 (16), 150.0 (17),
4.2.4.1. (S)-(4-Nitrophenyl)(phenyl)methanol 8aa. A known
compound,11,12 99% yield, a yellow oil. ½a 2D0
¼ þ14:0 (c 1.715,
ꢂ
CHCl3), 48% ee [HPLC conditions: Chiracel AD-H column, hexane/
2-propanol = 90:10, flow rate = 1.0 mL/min, wavelength = 254 nm,

1934
R. Zhang et al. / Tetrahedron: Asymmetry 21 (2010) 1928–1935
129.1 (100), 104.0 (5), 77.0 (4). HRMS (EI) calcd for C17H13NO3 re-
quires: 279.0895. Found: 279.0897.
4.2.4.13. (+)-(2,4-Dichlorophenyl)(p-tolyl)methanol 8dd. A known
compound,16 80% yield, colorless oil, ½a 2D0
¼ þ1:0 (c 0.50, CHCl3), 40%
ꢂ
ee [HPLC conditions: Chiracel OD-H column, hexane/2-propanol =
95:5, flow rate = 0.7 mL/min, wavelength = 254 nm, tminor = 14.28
min and tmajor = 15.08 min]. 1H NMR (400 MHz, CDCl3, TMS) d 7.58
(d, J = 8.4 Hz, 1H), 7.33 (d, J = 2.0 Hz, 1H), 7.28–7.21 (m, 3H), 7.13
(d, J = 8.0 Hz, 2H), 6.08 (s, 1H), 2.43 (br s, 1H), 2.32 (s, 3H).
4.2.4.8. (+)-Biphenyl-4-yl(3-nitrophenyl)methanol 8bf. 70%
yield, yellow solid; mp 89.6–91.1 °C, ½a D20
¼ þ8:0 (c 0.35, CHCl3),
ꢂ
29% ee [HPLC conditions: Chiracel OD-H column, hexane/2-propa-
nol = 90:10, flow rate = 1.0 mL/min, wavelength = 254 nm, tminor
47.21 min and tmajor = 83.52 min]. IR (CH2Cl2) 3416, 3125, 1617,
1525, 1485, 1401, 1350, 1030, 1007, 846, 802, 764, 749, 724,
697, 477 cmꢁ1 1H NMR (400 MHz, CDCl3, TMS) d 8.32 (s, 1H),
=
m
4.2.4.14. (ꢁ)-Biphenyl-4-yl(2,4-dichlorophenyl)methanol 8df.
75% yield, white solid; mp 67.6–69.7 °C, ½a D20
¼ ꢁ5:6 (c 1.19,
ꢂ
;
CHCl3), 40% ee [HPLC conditions: Chiracel AD-H column, hexane/
2-propanol = 90:10, flow rate = 1.0 mL/min, wavelength = 254 nm,
8.10 (d, J = 8.0 Hz, 1H), 7.73 (d, J = 7.6 Hz, 1H), 7.57 (d, J = 8.4 Hz,
2H), 7.55 (d, J = 7.6 Hz, 2H), 7.49 (t, J = 8.0 Hz 1H), 7.43 (d,
J = 7.6 Hz, 2H), 7.41 (d, J = 8.0 Hz, 2H), 7.34 (t, J = 7.2, 1H), 5.93 (s,
1H), 2.65 (br s, 1H); 13C NMR (100 MHz, CDCl3, TMS) d 148.4,
144.9, 140.9, 140.6, 138.5, 133.5, 129.4, 128.8, 128.5, 127.41,
127.37, 127.3, 127.1, 124.8, 71.3. MS (%) m/z 305.1 (M+, 100),
241.1 (8), 228.1 (7), 183.1 (18), 155.1 (89), 134.0 (3), 104.0 (3),
77.0 (8). HRMS (EI) calcd for C19H15NO3 requires: 305.1052. Found:
305.1054.
tminor = 11.63 min and tmajor = 12.97 min]. IR (CH2Cl2):
m 3468,
2956, 2924, 2854, 1737, 1590, 1562, 1486, 1468, 1376, 1270,
1229, 1217, 1178, 1095, 1057, 1030, 1008, 866, 828, 810, 753,
697 cmꢁ1 1H NMR (400 MHz, CDCl3, TMS) d 7.64 (d, J = 8.8 Hz,
;
1H), 7.58 (d, J = 8.0 Hz, 4H), 7.46–7.43 (m, 4H), 7.39–7.31 (m,
3H), 6.22 (s, 1H), 2.44 (br s, 1H); 13C NMR (100 MHz, CDCl3, TMS)
d 140.9, 140.8, 140.6, 139.6, 133.9, 133.1, 129.3, 128.9, 128.8,
127.5, 127.4, 127.33, 127.30, 127.1, 72.1; MS (%) m/z 328 (M+,
86), 311 (6), 275 (11), 239 (11), 228 (4), 183 (16), 173 (31), 155
(100), 110 (6) 77 (5). HRMS (EI) calcd for C19H14Cl2O requires:
328.0422. Found: 328.0421.
4.2.4.9. (+)-4-(Biphenyl-4-yl(hydroxy)methyl)benzonitrile 8cf.
85% yield, white solid; mp 158.4–161.1 °C, ½a D20
¼ þ7:8 (c 0.50,
ꢂ
CHCl3), 20% ee [HPLC conditions: Chiracel OD-H column, hexane/
2-propanol = 90:10, flow rate = 1.0 mL/min, wavelength = 254 nm,
4.2.4.15. (ꢁ)-Biphenyl-4-yl(4-methoxyphenyl)methanol 8ef. A
known compound,17 70% yield, white solid; mp 107.3–109.2 °C.
tmajor = 37.00 min and tminor = 42.34 min]. IR (CH2Cl2)
m 3467,
½
a 2D0
ꢂ
¼ ꢁ1:0 (c 0.24, CHCl3), 1% ee [HPLC conditions: Chiracel AD-
3029, 2927, 2852, 2232, 1731, 1606, 1485, 1406, 1275, 1228,
1191, 1122, 1060, 1017, 871, 828, 803, 770, 749, 733, 695,
H
column, hexane/2-propanol = 90:10, flow rate = 1.0 mL/min,
624 cmꢁ1 1H NMR (400 MHz, CDCl3, TMS) d 7.61 (d, J = 8.0 Hz,
;
wavelength = 254 nm, tmajor = 17.38 min and tminor = 18.91 min].
1H NMR (400 MHz, CDCl3, TMS) d 7.59–7.56 (m, 4H), 7.46–7.41
(m, 4H), 7.35–7.32 (m, 3H), 6.89 (d, J = 8.8 Hz, 2H), 5.87 (s, 1H),
3.80 (s, 3H).
2H), 7.57–7.52 (m, 6H), 7.44–7.32 (m, 5H), 5.88 (s, 1H), 2.46 (br
s, 1H); 13C NMR (100 MHz, CDCl3, TMS) d 148.8, 141.7, 141.2,
140.4, 132.3, 128.8, 127.53, 127.50, 127.1, 127.02, 127.00, 118.8,
111.2, 75.3. MS (%) m/z 285.1 (M+, 100), 268.1 (9), 181.1 (21),
155.1 (94), 130.0 (25), 102.0 (14), 77.0 (16). HRMS (EI) calcd for
4.2.4.16. Biphenyl-4-yl(p-tolyl)methanol 8ff. A known com-
pound,18 75% yield, white solid; mp 108.5–110.2 °C. ½a 2D0
ꢂ
¼ 0 (c
C20H15NO requires: 285.1154. Found: 285.1147.
0.24, CHCl3), 0% ee [HPLC conditions: Chiracel OD-H column,
hexane/2-propanol = 90:10, flow rate = 1.0 mL/min, wavelength =
254 nm, tminor = 12.18 min and tmajor = 13.68 min]. 1H NMR
(400 MHz, CDCl3, TMS) d 7.66 (d, J = 7.6 Hz, 1H), 7.57–7.55 (m,
4H), 7.47–7.40 (m, 4H), 7.36–7.30 (m, 3H), 7.25–7.21 (m, 1H),
6.27 (s, 1H), 2.50 (br s, 1H), 2.16 (s, 3H).
4.2.4.10. (S)-(2,4-Dichlorophenyl)(phenyl)methanol 8da. A known
compound,8c,14 85% yield, colorless oil, ½a 2D0
¼ ꢁ4:6 (c 0.91, acetone),
ꢂ
65% ee [HPLC conditions: Chiracel OD-H column, hexane/2-propa-
nol = 95:5, flow rate = 1.0 mL/min, wavelength = 230 nm, tmajor
=
16.27 min and tminor = 18.13 min]. 1H NMR (400 MHz, CDCl3, TMS)
d 7.58 (d, J = 8.4 Hz, 1H), 7.37–7.25 (m, 7H), 6.16 (s, 1H), 2.33 (s, 1H).
4.2.4.17. (+)-Biphenyl-4-yl(2-chlorophenyl)methanol 8gf. A known
compound,19 95% yield, colorless oil. ½a 2D0
¼ þ1:8 (c 0.78, CHCl3), 6%
ꢂ
4.2.4.11. (ꢁ)-(2,4-Dichlorophenyl)(o-tolyl)methanol 8db. A known
ee [HPLC conditions: Chiracel OD-H column, hexane/2-propanol =
90:10, flow rate = 1.0 mL/min, wavelength = 254 nm, tminor = 13.15
min and tmajor = 20.77 min]. 1H NMR (400 MHz, CDCl3, TMS) d 7.66–
7.63 (m, 1H), 7.57–7.54 (m, 4H), 7.46–7.40 (m, 4H), 7.36–7.29 (m,
3H), 7.24–7.20 (m, 1H), 6.26 (s, 1H), 2.44 (br s, 1H).
compound,15 75% yield, colorless oil. ½a 2D0
¼ ꢁ4:6 (c 0.75, CHCl3), 20%
ꢂ
ee [HPLC conditions: Chiracel OD-H column, hexane/2-propa-
nol = 95:5, flow rate = 0.7 mL/min, wavelength = 230 nm, tminor
=
14.04 min and tmajor = 25.37 min]. 1H NMR (400 MHz, CDCl3, TMS) d
7.39 (d, J = 2.0 Hz, 1H), 7.34 (d, J = 8.8 Hz, 1H), 7.27–7.18 (m, 5H),
6.24 (s, 1H), 2.64 (br s, 1H), 2.31 (s, 3H).
4.2.4.18. (S)-(4-Chlorophenyl)(phenyl)methanol 8ha. A known
compound,6 80% yield, colorless oil. ½a 2D0
¼ þ3:0 (c 0.15, CHCl3),
ꢂ
4.2.4.12. (+)-(2,4-Dichlorophenyl)(m-tolyl)methanol 8dc. 80%
13% ee [HPLC conditions: Chiracel AD-H column, hexane/2-propa-
yield, colorless oil, ½a D20
¼ þ3:6 (c 1.95, CHCl3), 50% ee [HPLC condi-
ꢂ
nol = 95:5, flow rate = 0.70 mL/min, wavelength = 254 nm, tminor
=
21.16 min and tmajor = 18.82 min]. 1H NMR (400 MHz, CDCl3,
TMS) d 7.35–7.34 (m, 4H), 7.31–7.27 (m, 5H), 5.82 (s, 1H), 2.24
(br s, 1H).
tions: Chiracel OD-H column, hexane/2-propanol = 95:5, flow
rate = 0.7 mL/min, wavelength = 230 nm, tminor = 13.27 min and
tmajor = 14.29 min]. IR (CH2Cl2):
1561, 1469, 1400, 1385, 1188, 1149, 1102, 1056, 1030, 846, 824,
794, 754, 696, 583, 455 cmꢁ1 1H NMR (400 MHz, CDCl3, TMS) d
m 3390, 3134, 2923, 1607, 1590,
;
4.2.4.19. (+)-Biphenyl-4-yl(2-nitrophenyl)methanol 8if. 85%
yield, yellow oil, ½a D20
¼ þ2:4 (c 0.545, CHCl3), 5% ee [HPLC condi-
ꢂ
7.56 (d, J = 8.4 Hz, 1H), 7.34 (d, J = 2.0 Hz, 1H), 7.28–7.20 (m, 2H),
7.15–7.08 (m, 3H), 6.10 (s, 1H), 2.41 (br s, 1H), 2.32 (s, 3H); 13C
NMR (100 MHz, CDCl3, TMS) d 141.7, 139.6, 138.3, 133.7, 133.0,
129.2, 128.9, 128.8, 128.5, 127.5, 127.4, 123.9, 72.3, 21.4. MS (%)
m/z 266.0 (M+, 100), 251.0 (72), 213.0 (14), 173.0 (67), 119.0
(43), 93.1 (53), 77.0 (9). HRMS (EI) calcd for C14H12Cl2O requires:
266.0625. Found: 266.0624.
tions: Chiracel OD-H column, hexane/2-propanol = 90:10, flow
rate = 1.0 mL/min, wavelength = 254 nm, tminor = 23.42 min and
tmajor = 19.51 min]. IR (CH2Cl2):
2926, 1606, 1525, 1484, 1350, 1265, 1176, 1024, 855, 761,
736 cmꢁ1 1H NMR (400 MHz, CDCl3, TMS) d 7.95 (d, J = 8.0 Hz,
1H), 7.80 (d, J = 7.6 Hz, 1H), 7.65 (t, J = 7.6 Hz, 1H), 7.57–7.55 (m,
m 3640, 3556, 3320, 3151, 3123,
;

R. Zhang et al. / Tetrahedron: Asymmetry 21 (2010) 1928–1935
1935
Feringa, B. L.; Minnaard, A. J. J. Comb. Chem. 2007, 9, 407–414; (k) Toullec, P. Y.;
Jagt, R. B. C.; de Vries, J. G.; Feringa, B. L.; Minnaard, A. J. Org. Lett. 2006, 8, 2715–
2718; (l) Yamamoto, K.; Tsyrymi, K.; Sakurai, F.; Kondo, K.; Aoyama, T. Synthesis
2008, 3585–3590; (m) Focken, T.; Rudolph, J.; Bolm, C. Synthesis 2005, 429–
436; (n) Suzuki, K.; Ishii, S.; Kondo, K.; Aoyama, T. Synlett 2006, 648–650; (o)
Arao, T.; Suzuki, K.; Ishii, S.; Kondo, K.; Aoyama, T. Synthesis 2006, 3809–3814;
(p) Duan, H.-F.; Xie, J.-H.; Shi, W.-J.; Zhang, Q.; Zhou, Q.-L. Org. Lett. 2006, 8,
1479–1481; (q) Ma, Q.; Ma, Y.; Liu, X.; Duan, W.; Qu, B.; Song, C. Tetrahedron:
Asymmetry 2010, 21, 292–298.
4H), 7.48–7.39 (m, 5H), 7.35 (d, J = 7.6 Hz, 1H), 6.48 (s, 1H), 2.63 (br
s, 1H); 13C NMR (100 MHz, CDCl3, TMS) d 148.3, 140.9, 140.5, 138.5,
133.5, 129.4, 129.0, 128.8, 128.5, 127.40, 127.37, 127.3, 127.1,
124.8, 71.3. MS (ESI) m/z: 344.1 (M++K, 24). HRMS (ESI) calcd for
C19H15NO3K requires: 344.0689. Found: 344.0687.
Acknowledgments
5. Duan, H.-F.; Xie, J.-H.; Qiao, X.-C.; Wang, L.-X.; Zhou, Q.-L. Angew. Chem., Int. Ed.
2008, 47, 4351–4353.
Financial support from the Shanghai Municipal Committee of
Science and Technology (06XD14005 and 08dj1400100-2), the
National Basic Research Program of China (973)-2010CB833302,
and the National Natural Science Foundation of China (20902019,
20872162, 20672127, 20821002, 20732008 and 20702059) is greatly
acknowledged.
6. Yamamoto, Y.; Kurihara, K.; Miyaura, N. Angew. Chem., Int. Ed. 2009, 48, 4414–
4416.
7. Nishimura, T.; Kumamoto, H.; Nagaosa, M.; Hayashi, T. Chem. Commun. 2009,
5713–5715.
8. (a) Yamaoto, T.; Ohta, T.; Ito, Y. Org. Lett. 2005, 7, 4153–4155; (b) Lin, S.; Lu, X. J.
Org. Chem. 2007, 72, 9757–9760; (c) Yu, A.; Cheng, B.; Wu, Y.; Li, J.; Wei, K.
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