Aryl bromides as inexpensive starting materials in the catalytic enantioselective arylation of aryl aldehydes: The additive TMEDA enhances the enantioselectivity

Article abstract of DOI:10.1021/jo502070r

We used aryl bromides as inexpensive starting materials to enantioselectively arylate aldehydes in one pot. Aryl bromides readily transfer aryls to aryllithiums with n-butyllithium, successively to triarylaluminums with aluminum chloride, and then to aryltitaniums with titanium isopropoxide. Finally aryltitaniums arylate aldehydes catalyzed by (S)-H₈-BINOL-Ti(Oi-Pr)₂ in excellent yields and enantioselectivities. The additive TMEDA evidently suppresses the racemic background reaction promoted by LiCl generated from salt metathesis. This procedure represents a cost-effective and operationally convenient method for enantioenriched diarylmethanols.

Full text of DOI:10.1021/jo502070r

Note
pubs.acs.org/joc
Aryl Bromides as Inexpensive Starting Materials in the Catalytic
Enantioselective Arylation of Aryl Aldehydes: The Additive TMEDA
Enhances the Enantioselectivity
Yong-Xin Yang,†,∥ Yue Liu,†,∥ Lei Zhang,† Yan-E Jia,† Pei Wang,† Fang-Fang Zhuo,† Xian-Tao An,†,‡
and Chao-Shan Da*,†,‡,§
†Institute of Biochemistry & Molecular Biology, School of Life Sciences, Lanzhou University, Lanzhou 730000, China
‡State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, China
§Key Lab of Preclinical Study for New Drugs of Gansu Province, Lanzhou University, Lanzhou 730000, China
S
* Supporting Information
ABSTRACT: We used aryl bromides as inexpensive starting
materials to enantioselectively arylate aldehydes in one pot. Aryl
bromides readily transfer aryls to aryllithiums with n-
butyllithium, successively to triarylaluminums with aluminum
chloride, and then to aryltitaniums with titanium isopropoxide.
Finally aryltitaniums arylate aldehydes catalyzed by (S)-H8-
BINOL−Ti(Oi-Pr)2 in excellent yields and enantioselectivities. The additive TMEDA evidently suppresses the racemic
background reaction promoted by LiCl generated from salt metathesis. This procedure represents a cost-effective and
operationally convenient method for enantioenriched diarylmethanols.
nantioenriched diarylmethanols are actively pursued
Yus11 transferred aryllithiums to aryltitaniums for enantiose-
Ebecause of the great importance of these compounds as lective arylation of aldehydes. However, the method only with
less reactive aryltitaniums cannot contribute to high enantio-
selectivity because the in situ-generated achiral Lewis acid
highly introduces racemic background reactions.11 Therefore,
the adverse influence of achiral Lewis acids on the
enantioselectivity is a central problem. In this regard, only the
groups of Seebach6 and Harada9 demonstrated successful
methods to address this problem. While they are very successful
in affording high enantioselectivity, the practicality of their
works suffers from the cost and inconvenience of preparing salt-
free aryltitaniums, the slow introduction of reactive aryltita-
niums to aldehydes over a long period of time with a syringe
pump, or the change of the solvent during the reaction process.
Therefore, the highly enantioselective catalytic arylation of
aldehydes with aryltitanium intermediates starting from aryl
bromides remains a challenge in its economy, practicality,
operational convenience, and method diversity. Herein we
report a different method for the catalytic enantioselective
indirect arylation of aromatic aldehydes with aryllithiums with
excellent enantioselectivity in high yield in one pot by using
readily available TMEDA as an optimal additive. Aryllithiums
are readily prepared in situ from the authentic aryl bromide
starting materials, and the reaction conditions are milder. This
method represents a conveniently performed, cost-effective,
and practicable process.
key motifs and synthetic intermediates in a considerable
number of bioactive compounds and pharmaceuticals.1 The
catalytic enantioselective arylation of aromatic aldehydes with
arylmetal reagents has emerged as a powerful and versatile
method for the synthesis of enantioenriched diarlymethanols by
C−C bond formation.2 Arylzincs and arylboronic acids have
been widely explored for enantioselective arylation of aromatic
aldehydes.3,4 While these two methods are very successful for
the preparation of enantioenriched diarylmethanols, their
practicability and economic efficiency are greatly hampered
by the high expense of arylzinc reagents, including diarylzincs
and arylethylzincs derived from the corresponding arylboronic
acids and easy-to-ignite diethylzinc,3 and the expense of
arylboronic acids themselves, which are commonly prepared
from inexpensive aryl-Grignard reagents or aryllithiums.5 The
utilization of aryltitaniums in the enantioselective arylation of
aldehydes, seminally demonstrated by Weber and Seebach,6 is
currently becoming popular because aryltitaniums can be
formed from inexpensive starting materials. The successfully
disclosed aryltitaniums have mainly been obtained from salt-
free arylaluminums,7 aryl-Grignard reagents,8 and aryl-
lithiums.6,9 Aryllithiums can be readily prepared from aryl
bromides and n-butyllithium.10 This indicates that aryl
bromides can be inexpensive starting materials for enantioen-
riched diarylmethanols, and the procedure cost can be largely
reduced.
The use of some appropriate additives to exclude the adverse
effect of achiral Lewis acids is the current method, pioneered by
Because of the high reactivity, an alternative strategy to the
use of aryllithiums is to transfer aryls from aryllithiums to less
reactive arylmetals by transmetalation. Seebach,6 Harada,9 and
Received: September 8, 2014
© XXXX American Chemical Society
A
dx.doi.org/10.1021/jo502070r | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
a
Table 1. Optimization of the Reaction Conditions for the Asymmetric Arylation of Aldehydes
b
c
d
e
f
entry mmol of PhLi
mmol of AlCl3 mmol of Ti(Oi-Pr)4 ligand (mmol) additive (mmol)
solvent
temp (time)
conv. (%)
ee (%)
1
2
1.2
1.2
1.2
1.2
1.6
2.0
1.6
1.6
1.6
1.6
1.6
1.6
1.6
1.6
1.6
1.6
1.6
1.6
1.6
1.6
1.6
1.6
1.6
1.6
2.0
3.0
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.5
0.75
0.425
0.425
0.425
0.425
0.425
0.425
0.425
0.425
0.425
0.425
0.425
0.425
0.345
0.505
0.425
0.425
0.425
0.425
0.425
0.425
0.425
0.425
0.425
0.425
0.525
0.775
L1 (0.025)
L1 (0.025)
L1 (0.025)
L1 (0.025)
L1 (0.025)
L1 (0.025)
L2 (0.025)
L2 (0.025)
L2 (0.025)
L2 (0.025)
L2 (0.0125)
L2 (0.0325)
L2 (0.025)
L2 (0.025)
L2 (0.025)
L2 (0.025)
L2 (0.025)
L2 (0.025)
L2 (0.025)
L2 (0.025)
L2 (0.025)
L2 (0.025)
L2(0.025)
L2(0.025)
L2(0.025)
L2(0.025)
none
THF/Hex
THF/Hex
THF/Hex
THF/Hex
THF/Hex
THF/Hex
THF/Hex
THF/Hex
THF/Hex
THF/Hex
THF/Hex
THF/Hex
THF/Hex
THF/Hex
THF/Hex
THF/Hex
THF/Hex
THF/Hex
THF/Hex
THF/Hex
THF
rt (24 h)
99
98
89
93
97
93
98
99
98
99
99
99
99
99
99
99
77
99
82
88
89
73
90
85
92
93
88
91
85
93
91
93
92
94
90
91
96
90
96
78
79
88
96
93
BDMAEE (1.2)
BDMAEE (1.2)
BDMAEE (1.2)
BDMAEE (1.6)
BDMAEE (2.0)
BDMAEE (1.6)
TMEDA (1.6)
TMPDA (1.6)
TEEDA (1.6)
TMEDA (1.6)
TMEDA (1.6)
TMEDA (1.6)
TMEDA (1.6)
TMEDA (0.8)
TMEDA (1.2)
TMEDA (1.2)
TMEDA (1.2)
TMEDA (1.2)
TMEDA (1.2)
TMEDA (1.2)
TMEDA (1.2)
TMEDA (1.2)
TMEDA (1.2)
TMEDA (1.5)
TMEDA (2.25)
rt (24 h)
3
rt (24 h)
4
rt (24 h)
5
rt (24 h)
6
rt (24 h)
7
rt (24 h)
8
rt (24 h)
9
rt (24 h)
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
rt (24 h)
rt (24 h)
rt (24 h)
rt (24 h)
rt (24 h)
rt (24 h)
rt (24 h)
0 °C (60 h)
30 °C (12 h)
40 °C (6 h)
50 °C (3 h)
40 °C (3 h)
40 °C (3 h)
40 °C (3 h)
40 °C (3 h)
40 °C (6 h)
40 °C (6 h)
g
99 (91 )
91
99
99
97
61
Et2O
toluene
MeCN
g
THF/Hex
THF/Hex
96
g
96
a
b
0.25 mmol of aldehyde was used. PhLi in entries 1 and 2 was prepared in situ using a PhBr:n-BuLi ratio of 1:1, in entries 3 and 5−26 using a
c
d
PhBr:n-BuLi ratio of 1:1.2, and in entry 4 using a PhBr:n-BuLi ratio of 1:1.4. L1 is (S)-BINOL; L2 is (S)-H8-BINOL. The coordinative additive.
e
TMPDA = tetramethylpropanediamine, TEEDA = N,N,N′,N′-tetraethylethylenediamine. The conversion was determined by HPLC using diphenyl
f
as an internal standard. Determined by chiral HPLC. The configurations were determined by comparison of the retention times of the major
isomers in HPLC with the reported data.8 Isolated yield.
g
the groups of Bolm,12 Chan,13 and Walsh14 in studies of
catalytic enantioselective addition of arylzinc intermediates to
aldehydes. We have also used bis[2-(N,N-dimethylamino)-
ethyl] ether (BDMAEE) to successfully suppress the back-
ground reaction in the indirect addition of Grignard reagents to
aldehydes.8c−e The introduction of additives excludes the need
to use salt-free aryltitaniums and low reaction temperatures, to
slowly add aryltitaniums to aldehydes over a long period, and to
change one solvent to another during the reaction process. We
recently explored the catalytic enantioselective arylation of
enals with aryltitanium intermediates in excellent yield and
enantioselectivity using TMEDA as the additive to exclude the
negative catalytic activity of the achiral Lewis acid.15 On the
basis of these results, we determined to explore the operation-
ally convenient and economical preparation of enantioenriched
diarylmethanols starting from aryl bromides by searching for a
proper additive to inhibit the undesired racemic background
reaction promoted by the achiral Lewis acid formed from salt
metathesis in this study.
ratio of PhLi (1.2 mmol) to AlCl3 (0.4 mmol) to Ti(Oi-Pr)4
(0.4 mmol) was 3:1:1 (Table 1, entries 1−4), and the 10
mmol % (S)-BINOL−Ti(Oi-Pr)2 complex catalyst was formed
from (S)-BINOL (0.025 mmol) and Ti(Oi-Pr)4 (0.025 mmol)
in a ratio of 1:1. The catalytic arylation was performed at room
temperature. Under the initial conditions, 82% ee was achieved
without BDMAEE (entry 1). Introducing 1 equiv of BDMAEE
raised the enantioselectivity to 88% (PhLi:BDMAEE = 1:1)
(entry 2), indicating that BDMAEE inhibited the racemic
background reaction to some extent. Modification of the
PhBr:n-BuLi ratio from 1:1 to 1:1.2 introduced a slight rise in
the enantioselectivity to 89% (entries 2 and 3). A further
change in the ratio to 1:1.4 led to a sharp decrease in the
enantioselectivity to 73% (entries 2−4). With a concurrent
increase in the amounts of PhLi and BDMAEE to 1.6 mmol
with a PhLi:BDMAEE:AlCl3 ratio of 4:4:1, the ee was slightly
enhanced to 90% (entry 5). Further increasing the amounts of
PhLi and BDMAEE decreased the enantioselectivity (entry 6).
Replacement of the chiral ligand (S)-BINOL (L1) with (S)-H8-
BINOL (L2) raised the ee to 92% (entry 7). Screening of three
other additives showed that the more easily available and cheap
TMEDA achieved the highest enantioselectivity (93% ee)
(entries 7−10). Thus, the expense of this protocol was further
reduced. Experiments on the catalyst loading showed that 10
mmol % (S)-BINOL−Ti(Oi-Pr)2 was optimal in this study
Initially, we used a model reaction (eq 1 in Table 1) to
optimize the reaction conditions with our familiar BDMAEE as
the additive. PhLi was readily prepared in situ from PhBr and n-
BuLi, initially in a ratio of 1:1. AlCl3 and Ti(Oi-Pr)4 were
successively introduced to PhLi for the production of first
Ph3Al and then PhTi(Oi-Pr)3 by salt metathesis. At first, the
B
dx.doi.org/10.1021/jo502070r | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
a
(entries 8, 11, and 12). Decreasing the amount of Ti(Oi-Pr)4
from 0.425 to 0.345 mmol induced a slight reduction in ee,
while increasing the amount of the compound did not change
the enantioselectivity (entries 8, 13, and 14). Taking
consideration of the additive loading (entries 14−16), the
slightly decreased amount of 1.2 mmol of TMEDA was ideal in
view of the enantioselectivity (94% ee). This result indicated
that the optimal proportion of PhLi to TMEDA was 4:3 (entry
16). The temperature markedly influenced the enantioselectiv-
ity (entries 16−20). At 0 °C, not only did the reaction become
very sluggish so that the reaction time was greatly prolonged to
60 h, but also the enantioselectivity dropped to 90% ee (entries
16 and 17). Raising the temperature to 40 °C not only greatly
shortened the reaction time from 24 to 6 h but also slightly
raised the enantioselectivity to 96% ee (entry 19). Using a
higher temperature depressed the enantioselectivity (entry 20).
In the above investigations, a mixed solvent of THF and hexane
was used. THF was used to dissolve PhBr and AlCl3, while
hexane was the solvent for n-BuLi. Therefore, the effect of using
a single solvent on the enantioselectivity was investigated
(entries 21−24). The THF/hexane mixed solvent was
completely removed in vacuo and then another dried solvent
was introduced into the reaction mixture in the experimental
process. Both THF and the THF/hexane mixed solvent gave
the same highest enantioselectivity (96% ee; entries 19 and 21).
On the basis of operational convenience, procedure cost, and
reduction of waste solvents, the THF/hexane mixture was
selected as the preferred solvent. Finally, we investigated the
PhLi loading in terms of the enantioselectivity and yield
(entries 19, 25, and 26). The results clearly indicated that
increasing the amount of PhLi to 2.0 mmol was ideal, as it gave
a raised 96% yield (entry 25) while maintaining the high 96%
ee.
With the finely optimized reaction conditions in hand, we
explored the substrate scope of this protocol. We first examined
the phenylation of aldehydes with PhBr as the starting material
(Table 2, entries 1−15). Remarkable yields and enantioselec-
tivities were obtained with these aldehydes. Electron-with-
drawing and electron-donating groups in the benzene ring were
both well-tolerated. The highest enantioselectivity was up to
96% ee (entries 1, 10, and 12). Heteroaryl aldehydes also
afforded high yields and ee (entries 10 and 11). Aliphatic
aldehydes gave lower yields because of their low reactivities. An
α-branched aldehyde obtained high ee (92%) (entry 14). For
the linear aldehyde, the enantioselectivity was depressed to 80%
ee (entry 15). Next, we explored arylation of different aromatic
aldehydes with various available aryl bromides as starting
materials (entries 16−36). The results indicated that this
process could be well-compatible with these aryl sources. Aryl
aldehydes with either electron-withdrawing or electron-
donating groups gave high enantioselectivities and yields. The
highest enantioselectivity was up to 96% ee (entry 21).
Heteroaryl aldehydes also resulted in ≥90% ee (entries 23, 27,
and 31). Even aliphatic aldehydes achieved a high ee of 86%
(entries 28 and 35).
Table 2. Catalytic Asymmetric Arylation of Aldehydes
b
c
entry
Ar1
Ar2
yield (%)
ee (%)
1
2
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
3-MeOC6H4
4-MeOC6H4
3-MeC6H4
4-MeC6H4
2-ClC6H4
4-ClC6H4
4-BrC6H4
4-FC6H4
4-F3CC6H4
2-thienyl
2-furyl
92
94
96
95
95
95
92
89
94
94
90
91
90
72
71
98
85
92
90
83
81
87
87
94
96
93
86
75
95
99
93
84
98
89
79
94
96
92
92
94
89
92
91
92
90
96
92
96
90
92
80
93
91
94
91
88
96
90
90
86
88
87
91
86
92
90
93
86
86
93
86
83
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
1-naphthyl
2-naphthyl
c-Hex
n-nonyl
4-FC6H4
Ph
4-FC6H4
2-naphthyl
1-naphthyl
Ph
4-FC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
3-MeOC6H4
3-MeOC6H4
3-MeOC6H4
3-MeOC6H4
3-MeOC6H4
4-MeC6H4
4-MeC6H4
4-MeC6H4
2-naphthyl
2-naphthyl
2-naphthyl
2-naphthyl
2-naphthyl
4-MeOC6H4
1-naphthyl
4-FC6H4
2-thienyl
Ph
4-ClC6H4
4-MeC6H4
2-thienyl
c-Hex
Ph
1-naphthyl
2-thienyl
4-ClC6H4
4-MeOC6H4
1-naphthyl
c-Hex
2-thienyl
a
2.0 mmol of Ar1Li from Ar1Br:n-BuLi = 1:1.2 at −78 °C, 0.25 mmol
of Ar2CHO, 0.5 mmol of AlCl3, 0.525 mmol of Ti(Oi-Pr)4, and 1.5
mmol of TMEDA were used. Isolated yields. Determined with chiral
HPLC. The configurations were determined by comparison of the
retention times of major isomers in HPLC with the reported data.8
b
c
We suppose that the LiCl side product generated in situ
during the salt metathesis is chelated by TMEDA (Figure 1).16
The chelation strongly suppresses the racemic background
reaction catalyzed by LiCl, just as in Walsh’s report with
TEEDA14 and our work with BDMAEE.8c−e The phenyl group
is finally transferred to Ti by continuous transmetalation. The
resulting PhTi(Oi-Pr)3 delivers the phenyl group to the
Figure 1. Proposed reaction mechanism.
aldehyde catalyzed by (S)-H8-BINOL−Ti(Oi-Pr)2 in a highly
enantioselective mode.
In summary, we have successfully developed a highly
enantioselective catalytic arylation of aldehydes using cheap
C
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The Journal of Organic Chemistry
Note
hexane/i-PrOH = 90:10, flow rate 1.0 mL/min, λ = 234.5 nm) tr
(major) = 40.6 min, tr (minor) = 35.8 min, ee = 92%; H NMR (400
aryl bromides as starting aryl sources under the catalysis of the
(S)-H8-BINOL−Ti(Oi-Pr)2 complex under mild reaction
conditions in one pot. Aryl bromides readily transfer aryls to
aryllithiums following the conventional method. Addition of
AlCl3 allows aryl transfer to triarylaluminums and generates the
achiral Lewis acid LiCl as well. Later introduction of Ti(Oi-Pr)4
produces aryltitaniums, which finally enantioselectively transfer
aryls to aldehydes. LiCl promotes the racemic background
reaction and reduces the enantioselectivity of the trans-
formation. TMEDA strongly chelates LiCl and suppresses its
catalytic activity, guaranteeing the excellent enantioselectivity in
this study. This efficient protocol does not need salt-free
aryltitanium intermediates, slow addition of reactive aryltita-
nium intermediates over a long period, or a change of one
solvent to another during the reaction process. Therefore, this
work demonstrates a cost-effective, operationally convenient,
and thus a very practical method for the synthesis of
enantiopure diarylmethanols.
1
MHz, CDCl3) δ 2.70 (s, 1H), 3.72 (s, 3H), 5.68 (s, 1H), 6.79−6.82 (d,
J = 12 Hz, 2H), 7.20−7.32 (m, 7H); 13C NMR (100 MHz, CDCl3) δ
55.2, 75.7, 113.8, 126.3, 127.3, 127.8, 128.3, 130.9, 136.1, 143.9, 158.9.
(S)-Phenyl(m-tolyl)methanol (3).8c Yield 47.6 mg, 96%; light-
yellow solid, mp 52−53 °C; [α]2D5 = −1 (c 1.0, CHCl3); HPLC (OB-
H, hexane/i-PrOH = 80:20, flow rate 1.0 mL/min, λ = 226.0 nm) tr
1
(major) = 15.0 min, tr (minor) = 9.6 min, ee = 92%; H NMR (400
MHz, CDCl3) δ 2.31 (s, 3H), 2.34 (s, 1H), 5.75 (s, 1H), 7.05−7.07 (d,
J = 8.0 Hz, 1H), 7.13−7.36 (m, 8H); 13C NMR (100 MHz, CDCl3) δ
21.4, 76.2, 123.5, 126.4, 127.1, 127.4, 128.3, 128.4, 138.1, 143.7.
(S)-Phenyl(p-tolyl)methanol (4).8c Yield 47.1 mg, 95%; white solid,
mp 57−58 °C; [α]2D5 = −5 (c 1.0, CHCl3); HPLC (OB-H, hexane/i-
PrOH = 90:10, flow rate 1.0 mL/min, λ = 221.0 nm) tr (major) = 12.9
min, tr (minor) = 11.6 min, ee = 94%; 1H NMR (400 MHz, CDCl3) δ
2.22 (s, 1H), 2.28 (s, 3H), 5.74 (s, 1H), 7.08−7.33 (m, 9H); 13C NMR
(100 MHz, CDCl3) δ 21.0, 76.0, 126.4, 126.5, 127.4, 128.4, 129.1,
137.2, 140.9, 143.9.
(S)-(2-Chlorophenyl)(phenyl)methanol (5).8c Yield 51.9 mg, 95%;
light-yellow oil; [α]2D5 = −16 (c 1.0, CHCl3); HPLC (OJ-H, hexane/i-
PrOH = 70:30, flow rate 1.0 mL/min, λ = 222.2 nm) tr (major) = 12.9
min, tr (minor) = 10.2 min, ee = 89%; 1H NMR (400 MHz, CDCl3) δ
2.54 (s, 1H), 6.17 (s, 1H), 7.13−7.57 (m, 8H), 7.59−7.60 (d, J = 4 Hz,
1H); 13C NMR (100 MHz, CDCl3) δ 72.6, 126.9, 127.0, 127.7, 127.9,
128.4, 128.7, 129.5, 132.4, 140.9, 142.1.
EXPERIMENTAL SECTION
■
General. All of the reactions were performed under an argon
atmosphere, and solvents were dried according to established
procedures prior to use. All of the reagents were commercial.
Reactions were monitored by thin-layer chromatography (TLC);
column and preparative TLC purification were carried out using silica
gel. Melting points were recorded on an X-4 melting point apparatus
and are uncorrected. Optical rotations were recorded on a polarimeter.
1H NMR and 13C NMR spectra were measured on 400 and 100 MHz
(S)-(4-Chlorophenyl)(phenyl)methanol (6).8c Yield 51.9 mg, 95%;
light-yellow solid, mp 51−52 °C; [α]2D5 = +19 (c 1.0, CHCl3); HPLC
(OD-H, hexane/i-PrOH = 85:15, flow rate 1.0 mL/min, λ = 225.0
nm) tr (major) = 12.0 min, tr (minor) = 9.0 min, ee = 92%; 1H NMR
(400 MHz, CDCl3) δ 2.59 (s, 1H), 5.70 (s, 1H), 7.21−7.40 (m, 9H);
13C NMR (100 MHz, CDCl3) δ 75.5, 126.4, 127.8, 128.6, 133.2, 142.1,
143.3.
spectrometers, respectively, in CDCl3 with TMS as an internal
standard; chemical shifts are reported in parts per million. The
determination of ee values was carried out using chiral HPLC with an
OD-H, OB-H, AS-H, or AD-H column.
(S)-(4-Bromophenyl)(phenyl)methanol (7).8c Yield 60.5 mg, 92%;
light-yellow solid, mp 73−75 °C; [α]2D5 = +19 (c 1.0, CHCl3); HPLC
(OB-H, hexane/i-PrOH = 80:20, flow rate 1.0 mL/min, λ = 230.0 nm)
tr (major) = 11.4 min, tr (minor) = 9.1 min, ee = 91%; 1H NMR (400
MHz, CDCl3) δ 2.32 (s, 1H), 5.77 (s, 1H), 7.23−7.32 (m, 2H), 7.33−
7.40 (m, 4H), 7.42−7.45 (m, 3H); 13C NMR (100 MHz, CDCl3) δ
75.5, 121.3, 126.4, 127.8, 128.1, 128.6, 131.4, 142.6, 143.3.
General Procedure for the Catalytic Asymmetric Arylation
of Aldehydes. Freshly distilled bromobenzene (2.0 mmol, 0.21 mL)
and 2.0 mL of dry THF were introduced into a dry 10 mL round-
bottom flask equipped with a clean stir bar under an argon
atmosphere. The flask was placed into a cold bath at −78 °C, and
n-BuLi (1.8 M, 2.4 mmol, 1.33 mL) was added dropwise. After 1 h, the
mixture was warmed to 0 °C, and a solution of AlCl3 (67 mg, 0.5
mmol) in 1.0 mL of dry THF was added dropwise into the flask. After
the flask was warmed to room temperature and kept stirring for about
12 h, TMEDA (1.5 mmol, 223.5 μL) was added. After 30 min of
stirring, a mixture of (S)-H8-BINOL (7.4 mg, 0.025 mmol) and Ti(Oi-
Pr)4 (0.525 mmol, 155.4 μL), which had previously been stirred for
about 15 min in 1.0 mL of dry THF, was introduced, and the resulting
mixture was stirred for further 60 min. Then the aldehyde (0.25
mmol) was added to the flask at room temperature, and the flask was
placed into an oil bath at 40 °C and kept stirring for about 6 h
(checking with TLC until the reaction was complete). Two drops of
icy water was added to the mixture to quench the reaction with a pipet,
and then 3.0 mL of 5% HCl was further added into the mixture. The
resulting mixture was extracted with ethyl acetate (8.0 mL × 3), and
the organic layers were combined, washed with 2.0 mL of brine, dried
with anhydrous Na2SO4, and condensed under reduced pressure to
give an oily residue. The residue was then purified by column
chromatography on silica gel (petroleum ether/ethyl acetate = 8:1) to
furnish the pure diarylmethanol.
(S)-(4-Fluorophenyl)(phenyl)methanol (8).8c Yield 45.0 mg, 89%;
light-yellow oil; [α]2D5 = +8 (c 1.0, CHCl3); HPLC (OB-H, hexane/i-
PrOH = 80:20, flow rate 1.0 mL/min, λ = 224.0 nm) tr (major) = 18.4
min, tr (minor) = 15.6 min, ee = 92%; 1H NMR (400 MHz, CDCl3) δ
2.77 (s, 1H), 5.68 (s, 1H), 6.93−6.99 (m, 2H), 7.22−7.53 (m, 7H);
13C NMR (100 MHz, CDCl3) δ 75.5, 115.1, 115.3, 126.4, 127.7, 128.1,
128.2, 128.5, 139.5, 143.6, 160.9, 163.3.
(S)-Phenyl(4-(trifluoromethyl)phenyl)methanol (9).8c Yield 59.3
mg, 94%; light-yellow solid, mp 79−81 °C; [α]2D5 = +27 (c 1.0,
CHCl3); HPLC (OB-H, hexane/i-PrOH = 90:10, flow rate 1.0 mL/
min, λ = 225.0 nm) tr (major) = 10.2 min, tr (minor) = 7.6 min, ee =
90%; 1H NMR (400 MHz, CDCl3) δ 2.63 (s, 1H), 5.80 (s, 1H), 7.27−
7.35 (m, 5H), 7.45−7.47 (m, 2H), 7.55−7.57 (m, 2H); 13C NMR
(100 MHz, CDCl3) δ 75.7, 125.3, 126.6, 128.0, 128.7, 143.1, 147.4.
(S)-Phenyl(thiophen-2-yl)methanol (10).8c Yield 44.7 mg, 94%;
light-yellow solid, mp 49−52 °C; [α]2D5 = +27 (c 1.0, CHCl3); HPLC
(OD-H, hexane/i-PrOH = 95:5, flow rate 1.0 mL/min, λ = 237.8 nm)
tr (major) = 16.9 min, tr (minor) = 19.1 min, ee = 96%; 1H NMR (400
MHz, CDCl3) δ 2.72 (s, 1H), 5.96 (s, 1H), 6.83−6.91 (m, 2H), 7.21−
7.41 (m, 6H); 13C NMR (100 MHz, CDCl3) δ 72.3, 124.8, 125.4,
126.2, 126.6, 127.9, 128.5, 130.0, 130.9, 143.0, 148.1.
(S)-(3-Methoxyphenyl)(phenyl)methanol (1).8c Yield 49.3 mg,
92%; light-yellow oil; [α]2D5 = +7 (c 1.0, CHCl3); HPLC (OD-H,
hexane/i-PrOH = 75:25, flow rate 1.0 mL/min, λ = 222.9 nm) tr
(S)-Furan-2-yl(phenyl)methanol (11).8f Yield 39.2 mg, 90%; light-
yellow oil; [α]2D5 = −6 (c 1.0, CHCl3); HPLC (OD-H, hexane/i-PrOH
= 95:5, flow rate 1.0 mL/min, λ = 218.9 nm) tr (major) = 15.1 min, tr
(minor) = 20.9 min, ee = 92%; 1H NMR (400 MHz, CDCl3) δ 2.87 (s,
1H), 5.74 (s, 1H), 6.06−6.07 (d, J = 4.0 Hz, 1H), 6.28 (s, 1H), 7.27−
7.40 (m, 6H); 13C NMR (100 MHz, CDCl3) δ 70.0, 107.4, 110.1,
126.5, 128.0, 128.4, 140.7, 142.5, 155.9.
1
(major) = 7.8 min, tr (minor) = 11.1 min, ee = 96%; H NMR (400
MHz, CDCl3) δ 2.64 (s, 1H), 3.73 (s, 3H), 5.71 (s, 1H), 6.75−6.76 (d,
J = 4.0 Hz, 1H), 6.78−6.90 (d, 2H), 6.91−7.34 (m, 6H); 13C NMR
(100 MHz, CDCl3) δ 55.2, 76.1, 112.0, 112.9, 118.8, 126.5, 127.6,
128.5, 129.5, 131.0, 143.6, 145.4, 159.7.
(S)-(4-Methoxyphenyl)(phenyl)methanol (2).8c Yield 50.4 mg,
94%; light-yellow oil; [α]2D5 = −19 (c 1.0, CHCl3); HPLC (OJ-H,
(S)-Naphthalen-1-yl(phenyl)methanol (12).8c Yield 53.3 mg, 91%;
colorless oil; [α]2D5 = −42 (c 1.0, CHCl3); HPLC (OD-H, hexane/i-
D
dx.doi.org/10.1021/jo502070r | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
PrOH = 75:25, flow rate 1.0 mL/min, λ = 225.8 nm) tr (major) = 7.8
min, tr (minor) = 17.1 min, ee = 96%; 1H NMR (400 MHz, CDCl3) δ
2.68 (s, 1H), 6.37 (s, 1H), 7.16−7.42 (m, 8H), 7.52−7.54 (d, J = 8.0
Hz, 1H), 7.74−7.82 (m, 2H), 7.92−7.94 (d, J = 8.0 Hz, 1H); 13C
NMR (100 MHz, CDCl3) δ 73.5, 123.9, 124.5, 125.2, 125.5, 126.1,
127.0, 127.6, 128.4, 128.7, 130.6, 133.8, 138.7, 143.0.
(S)-(4-Chlorophenyl)(naphthalen-1-yl)methanol (21).8c Yield 54.1
mg, 81%; light-yellow oil; [α]2D5 = −64 (c 1.0, CHCl3); HPLC (OD-H,
hexane/i-PrOH = 85:15, flow rate 1.0 mL/min, λ = 233.6 nm) tr
1
(major) = 10.8 min, tr (minor) = 25.3 min, ee = 96%; H NMR (400
MHz, CDCl3) δ 2.45 (s, 1H), 6.45 (s, 1H), 7.24−7.32 (m, 4H), 7.41−
7.48 (m, 3H), 7.55−7.57 (d, J = 8.0 Hz, 1H), 7.81−7.87 (m, 2H),
7.96−7.98 (d, J = 8.0 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 73.2,
123.8, 124.8, 125.3, 125.7, 126.3, 128.3, 128.6, 128.8, 130.5, 134.0,
138.4, 141.6.
(S)-Naphthalen-2-yl(phenyl)methanol (13).7b Yield 52.7 mg, 90%;
white solid, mp 44−46 °C; [α]2D5 = +6 (c 1.0, CHCl3); HPLC (OD-H,
hexane/i-PrOH = 92:8, flow rate 1.0 mL/min, λ = 235.7 nm) tr
1
(R)-(4-Chlorophenyl)(4-fluorophenyl)methanol (22).4c Yield 51.5
mg, 87%; light-yellow oil; [α]2D5 = −7 (c 1.0, CHCl3); HPLC (OB-H,
hexane/i-PrOH = 80:20, flow rate 1.0 mL/min, λ = 223.4 nm) tr
(major) = 18.9 min, tr (minor) = 22.9 min, ee = 90%; H NMR (400
MHz, CDCl3) δ 2.95 (s, 1H), 5.77 (s, 1H), 7.19−7.10 (m, 6H), 7.39−
7.42 (m, 2H), 7.66−7.73 (m, 4H); 13C NMR (100 MHz, CDCl3) δ
76.3, 112.9, 124.7, 125.0, 125.9, 126.1, 126.6, 127.6, 128.0, 128.3,
128.5, 130.1, 131.0, 132.8, 133.2, 137.1, 141.0, 143.6, 151.4.
1
(major) = 13.1 min, tr (minor) = 17.4 min, ee = 90%; H NMR (400
MHz, CDCl3) δ 2.40 (s, 1H), 5.76 (s, 1H), 6.99−7.03 (t, J = 8.8 Hz,
2H), 7.25−7.31 (m, 6H); 13C NMR (100 MHz, CDCl3) δ 74.9, 115.3,
115.5, 127.7, 128.1, 128.2, 128.6, 133.4, 139.1, 142.0, 161.0, 163.5.
(S)-(4-Chlorophenyl)(thiophen-2-yl)methanol (23).8c Yield 48.9
mg, 87%; light-yellow solid, mp 49−51 °C; [α]2D5 = +2 (c 1.0, CHCl3);
HPLC (AD-H, hexane/i-PrOH = 98:2, flow rate 1.0 mL/min, λ =
240.1 nm) tr (major) = 23.4 min, tr (minor) = 27.9 min, ee = 90%; 1H
NMR (400 MHz, CDCl3) δ 2.54 (s, 1H), 6.01 (s, 1H), 6.87−6.95 (m,
2H), 7.25−7.38 (m, 5H); 13C NMR (100 MHz, CDCl3) δ 71.7, 125.0,
125.7, 126.7, 127.6, 128.7, 133.7, 141.5, 147.6.
(R)-Cyclohexyl(phenyl)methanol (14).8c Yield 34.3 mg, 72%; white
solid, mp 64−65 °C; [α]D25 = +26 (c 1.0, CHCl3); HPLC (OD-H,
hexane/i-PrOH = 98:2, flow rate 1.0 mL/min, λ = 213.8 nm) tr
1
(major) = 12.9 min, tr (minor) = 11.6 min, ee = 92%; H NMR (400
MHz, CDCl3) δ 0.86−1.59 (m, 12H), 4.33−4.34 (d, J = 4 Hz, 1H),
7.23−7.34 (m, 5H); 13C NMR (100 MHz, CDCl3) δ 25.9, 26.0, 26.4,
28.7, 29.3, 44.8, 79.2, 126.8, 128.3, 129.1, 145.3.
(R)-1-Phenyldecan-1-ol (15).8c Yield 41.6 mg, 71%; colorless oil;
[α]2D5 = +24 (c 1.0, CHCl3); HPLC (OD-H, hexane/i-PrOH = 98:2,
flow rate 1.0 mL/min, λ = 209.7 nm) tr (major) = 9.5 min, tr (minor)
= 10.3 min, ee = 80%; 1H NMR (400 MHz, CDCl3) δ 0.86−0.89 (m,
3H), 1.18−1.24 (m, 14H), 1.68−1.82 (m, 2H), 2.02 (s, 1H), 4.61−
4.65 (t, J = 8.0 Hz, 1H), 7.25−7.33 (m, 5H); 13C NMR (100 MHz,
CDCl3) δ 14.0, 22.6, 25.7, 29.2, 29.5, 31.8, 39.0, 74.5, 125.8, 127.3,
128.2, 144.9.
(R)-(3-Methoxyphenyl)(phenyl)methanol (24).8c Yield 50.4 mg,
94%; light-yellow oil; [α]2D5 = −10 (c 1.0, CHCl3); HPLC (OD-H,
hexane/i-PrOH = 75:25, flow rate 1.0 mL/min, λ = 225.8 nm) tr
1
(major) = 10.4 min, tr (minor) = 7.5 min, ee = 86%; H NMR (400
MHz, CDCl3) δ 2.32 (s, 1H), 3.77 (s, 1H), 5.78 (s, 1H), 6.78−6.80
(m, 1H), 6.92−6.94 (m, 2H), 7.22−7.37 (m, 6H); 13C NMR (100
MHz, CDCl3) δ 55.2, 76.1, 112.0, 112.9, 118.8, 126.5, 127.6, 128.5,
129.5, 131.0, 143.6, 145.4, 151.3, 159.7.
(R)-(4-Fluorophenyl)(phenyl)methanol (16).3d Yield 49.5 mg, 98%;
light-yellow oil; [α]2D5 = −11 (c 1.0, CHCl3); HPLC (OB-H, hexane/i-
PrOH = 80:20, flow rate 1.0 mL/min, λ = 210.0 nm) tr (major) = 14.8
min, tr (minor) = 20.0 min, ee = 93%; 1H NMR (400 MHz, CDCl3) δ
2.29 (s, 1H), 5.79 (s, 1H), 6.98−7.03 (m, 2H), 7.24−7.34 (m, 7H);
13C NMR (100 MHz, CDCl3) δ 75.5, 121.3, 126.4, 127.8, 128.1, 128.6,
131.4, 142.6, 143.3.
(R)-(4-Chlorophenyl)(3-methoxyphenyl)methanol (25).4c Yield
59.7 mg, 96%; white solid, mp 66−67 °C; [α]2D5 = −2 (c 1.0,
CHCl3); HPLC (OD-H, hexane/i-PrOH = 85:15, flow rate 1.0 mL/
min, λ = 237.7 nm) tr (major) = 16.8 min, tr (minor) = 10.4 min, ee =
1
88%; H NMR (400 MHz, CDCl3) δ 2.38 (s, 1H), 3.75−3.77 (m,
(S)-(4-Fluorophenyl)(naphthalen-2-yl)methanol (17).8c Yield 53.6
mg, 85%; light-yellow oil; [α]2D5 = −43 (c 1.0, CHCl3); HPLC (OD-H,
hexane/i-PrOH = 80:20, flow rate 1.0 mL/min, λ = 268.9 nm) tr
3H), 5.75 (s, 1H), 6.80−6.82 (d, J = 8.0 Hz, 1H), 6.90−6.91 (m, 2H),
7.22−7.35 (m, 5H); 13C NMR (100 MHz, CDCl3) δ 55.2, 75.4, 112.0,
113.1, 118.8, 127.8, 128.6, 129.7, 130.1, 131.0, 133.3, 142.0, 145.0,
159.8.
1
(major) = 9.1 min, tr (minor) = 10.4 min, ee = 91%; H NMR (400
MHz, CDCl3) δ 2.38 (s, 1H), 6.50 (s, 1H), 6.98−7.02 (m, 2H), 7.34−
7.51 (m, 5H), 7.60−7.62 (d, J = 8.0 Hz, 1H), 7.81−7.88 (m, 2H),
7.97−7.98 (d, J = 8.0 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 75.6,
115.2, 115.4, 124.5, 125.0, 126.1, 126.3, 127.7, 128.0, 128.4, 132.9,
133.2, 139.3, 140.9.
(R)-(3-Methoxyphenyl)(p-tolyl)methanol (26).3k Yield 53.1 mg,
93%; light-yellow oil; [α]2D5 = −22 (c 1.0, CHCl3); HPLC (OD-H,
hexane/i-PrOH = 90:10, flow rate 1.0 mL/min, λ = 224.8 nm) tr
1
(major) = 17.5 min, tr (minor) = 12.6 min, ee = 87%; H NMR (400
(S)-(4-Fluorophenyl)(naphthalen-1-yl)methanol (18).8c Yield 58.0
mg, 92%; white solid, mp 54−56 °C; [α]2D5 = +4 (c 1.0, CHCl3);
HPLC (OD-H, hexane/i-PrOH = 80:20, flow rate 1.0 mL/min, λ =
MHz, CDCl3) δ 2.32 (s, 4H), 3.77 (s, 3H), 5.75 (s, 1H), 6.77−7.26
(m, 8H); 13C NMR (100 MHz, CDCl3) δ 55.1, 75.9, 111.9, 112.8,
118.7, 126.4, 129.1, 129.4, 137.2, 140.8, 145.6, 159.6.
1
(S)-(3-Methoxyphenyl)(thiophen-2-yl)methanol (27).17 Yield 47.4
mg, 86%; light-yellow solid, mp 66−67 °C; [α]2D5 = −7 (c 1.0, CHCl3);
HPLC (OD-H, hexane/i-PrOH = 90:10, flow rate 1.0 mL/min, λ =
226.8 nm) tr (major) = 18.0 min, tr (minor) = 15.3 min, ee = 91%; 1H
NMR (400 MHz, CDCl3) δ 2.59 (s, 1H), 3.78 (s, 3H), 6.00 (s, 1H),
6.82−7.01 (m, 5H), 7.24−7.29 (m, 2H); 13C NMR (100 MHz,
CDCl3) δ 55.2, 72.2, 111.6, 113.5, 118.6, 124.9, 125.4, 126.6, 129.5,
144.7, 147.8, 159.7.
222.5 nm) tr (major) = 8.6 min, tr (minor) = 21.5 min, ee = 94%; H
NMR (400 MHz, CDCl3) δ 2.38 (s, 1H), 5.97 (s, 1H), 6.99−7.04 (t, J
= 8.0 Hz, 2H), 7.36−7.51 (m, 5H), 7.78−7.86 (m, 4H); 13C NMR
(100 MHz, CDCl3) δ 73.0, 115.2, 115.4, 123.8, 124.5, 125.3, 125.6,
126.2, 128.6, 128.7, 130.5, 133.9, 138.5, 138.8, 160.9, 163.4.
(R)-(4-Chlorophenyl)(phenyl)methanol (19).4c Yield 49.2 mg,
90%; white solid, mp 52−53 °C; [α]2D5 = −16 (c 1.0, CHCl3);
HPLC (OB-H, hexane/i-PrOH = 80:20, flow rate 1.0 mL/min, λ =
(R)-Cyclohexyl(3-methoxyphenyl)methanol (28).17 Yield 41.3 mg,
75%; light-yellow oil; [α]2D5 = +16 (c 1.0, CHCl3); HPLC (OD-H,
hexane/i-PrOH = 95:5, flow rate 1.0 mL/min, λ = 215.4 nm) tr
1
223.2 nm) tr (major) = 9.0 min, tr (minor) = 12.9 min, ee = 91%; H
NMR (400 MHz, CDCl3) δ 2.59 (s, 1H), 5.70 (s, 1H), 7.21−7.40 (m,
9H); 13C NMR (100 MHz, CDCl3) δ 75.5, 126.4, 127.8, 128.6, 133.2,
142.1, 143.3.
1
(major) = 19.7 min, tr (minor) = 11.3 min, ee = 86%; H NMR (400
(R)-(4-Chlorophenyl)(4-methoxyphenyl)methanol (20).4c Yield
51.6 mg, 83%; light-yellow oil; [α]2D5 = −21 (c 1.0, CHCl3); HPLC
(OD-H, hexane/i-PrOH = 90:10, flow rate 1.0 mL/min, λ = 228.4
nm) tr (major) = 15.1 min, tr (minor) = 14.4 min, ee = 88%; 1H NMR
(400 MHz, CDCl3) δ 2.33 (s, 1H), 3.78 (s, 3H), 5.74 (s, 1H), 6.84−
MHz, CDCl3) δ 0.92−1.25 (m, 5H), 1.37−1.40 (d, J = 12.0 Hz, 1H),
1.56−1.78 (m, 4H), 1.85 (s, 1H), 1.96−1.99 (d, J = 12.0 Hz, 1H), 3.81
(s, 3H), 4.33−4.34 (d, J = 4.0 Hz, 1H), 6.80−6.88 (m, 3H), 7.22−7.26
(t, J = 8.0 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 25.9, 26.0, 26.4,
28.7, 29.3, 44.8, 55.1, 79.2, 112.1, 112.7, 119.0, 129.1, 145.3, 159.5.
(R)-Phenyl(p-tolyl)methanol (29).8c Yield 47.1 mg, 95%; white
solid, mp 55−57 °C; [α]D25 = +20 (c 1.0, CHCl3); HPLC (OB-H,
hexane/i-PrOH = 90:10, flow rate 1.0 mL/min, λ = 217.9 nm) tr
1
6.86 (d, J = 8.0 Hz, 2H), 7.22−7.29 (m, 6H); H NMR (400 MHz,
CDCl3) δ 2.33 (s, 1H), 3.78 (s, 3H), 5.74 (s, 1H), 6.84−6.86 (d, J =
8.0 Hz, 2H), 7.22−7.29 (m, 6H); 13C NMR (100 MHz, CDCl3) δ
55.2, 74.9, 115.3, 115.5, 126.9, 127.7, 128.1, 128.2, 128.6, 133.4, 139.1,
142.0, 158.9.
1
(major) = 7.3 min, tr (minor) = 8.3 min, ee = 92%; H NMR (400
MHz, CDCl3) δ 2.22 (s, 1H), 2.28 (s, 3H), 5.74 (s, 1H), 7.08−7.33
E
dx.doi.org/10.1021/jo502070r | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
(m, 9H); 13C NMR (100 MHz, CDCl3) δ 21.0, 76.0, 126.4, 126.5,
127.4, 128.4, 129.1, 137.2, 140.9, 143.9.
white solid. The solid was recrystallized with n-heptane to furnish (S)-
H8-BINOL as white crystals. Yield 1.40 g, 95%; mp 160−161 °C; [α]D25
= −72 (c 1.0, CHCl3); 1H NMR (400 MHz, CDCl3) δ 1.65−1.77 (m,
10H), 2.12−2.33 (m, 5H), 2.73−2.76 (m, 5H), 4.57 (s, 2H), 6.82−
6.84 (d, J = 8.0 Hz, 2H), 7.06−7.08 (d, J = 8.0 Hz, 2H).
(S)-Naphthalen-1-yl(p-tolyl)methanol (30).8c Yield 61.5 mg, 99%;
light-yellow oil; [α]2D5 = −33 (c 1.0, CHCl3); HPLC (OD-H, hexane/i-
PrOH = 80:20, flow rate 1.0 mL/min, λ = 281.6 nm) tr (major) = 7.9
min, tr (minor) = 16.6 min, ee = 90%; 1H NMR (400 MHz, CDCl3) δ
2.30 (s, 3H), 2.37 (s, 1H), 6.47 (s, 1H), 7.10−7.12 (d, J = 8.0 Hz, 2H),
7.25−7.27 (d, J = 8.0 Hz, 2H), 7.38−7.49 (m, 3H), 7.63−7.65 (d, J =
8.0 Hz, 1H), 7.78−7.85 (m, 2H), 7.98−8.00 (m, 1H); 13C NMR (100
MHz, CDCl3) δ 21.1, 73.4, 123.9, 124.3, 125.3, 125.5, 125.5, 126.0,
127.0, 128.3, 128.7, 129.2, 130.6, 133.8, 137.3, 138.8, 140.2.
(S)-Thiophen-2-yl(p-tolyl)methanol (31).17 Yield 47.5 mg, 93%;
light-yellow solid, mp 64−65 °C; [α]2D5 = +12 (c 1.0, CHCl3); HPLC
(AD-H, hexane/i-PrOH = 95:5, flow rate 1.0 mL/min, λ = 232.2 nm)
tr (major) = 13.0 min, tr (minor) = 15.1 min, ee = 93%; 1H NMR (400
MHz, CDCl3) δ 2.26 (s, 3H), 2.50 (s, 1H), 5.99 (s, 1H), 6.74−6.93
(m, 2H), 7.15−7.17 (d, J = 8.0 Hz, 2H), 7.23−7.24 (d, J = 4.0 Hz,
1H), 7.30−7.32 (d, J = 8.0 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ
21.1, 72.2, 124.7, 125.2, 126.2, 126.6, 129.1, 137.7, 140.2, 148.3.
(R)-(4-Chlorophenyl)(naphthalen-2-yl)methanol (32).14b Yield
56.4 mg, 84%; light-yellow solid, mp 85−86 °C; [α]2D5 = +11 (c 1.0,
CHCl3); HPLC (OD-H, hexane/i-PrOH = 90:10, flow rate 1.0 mL/
min, λ = 229.1 nm) tr (major) = 16.8 min, tr (minor) = 18.7 min, ee =
86%; 1H NMR (400 MHz, CDCl3) δ 2.42 (s, 1H), 5.94 (s, 1H), 7.26−
7.53 (m, 7H), 7.78−7.95 (m, 5H); 13C NMR (100 MHz, CDCl3) δ
75.7, 124.5, 125.1, 126.1, 126.3, 127.7, 128.0, 128.6, 132.9, 133.2,
133.3, 140.6, 141.9.
ASSOCIATED CONTENT
* Supporting Information
NMR spectra and HPLC chromatograms. This material is
available free of charge via the Internet at http://pubs.acs.org.
■
S
AUTHOR INFORMATION
Corresponding Author
*E-mail: dachaoshan@lzu.edu.cn.
■
Author Contributions
∥Y.-X.Y. and Y.L. contributed equally.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We are grateful to the National Natural Science Foundation of
China (21072087 and 20672051) and the Program for
Changjiang Scholars and Innovative Research Team in
University (IRT1137) for financial support.
(R)-(4-Methoxyphenyl)(naphthalen-2-yl)methanol (33).14b Yield
64.8 mg, 98%; light-yellow solid, mp 71−73 °C; [α]2D5 = −21 (c 1.0,
CHCl3); HPLC (OD-H, hexane/i-PrOH = 90:10, flow rate 1.0 mL/
min, λ = 226.1 nm) tr (major) = 22.8 min, tr (minor) = 19.0 min, ee =
86%; 1H NMR (400 MHz, CDCl3) δ 2.34 (s, 1H), 3.78 (s, 3H), 5.95
(s, 1H), 6.85−6.87 (d, J = 8.0 Hz, 2H), 7.30−7.32 (d, J = 8.0 Hz, 2H),
7.39−7.41 (d, J = 8.0 Hz, 1H), 7.44−7.49 (m, 2H), 7.77−7.84 (m,
3H), 7.89 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 55.2, 75.8, 113.8,
124.7, 125.8, 126.1, 127.6, 128.0, 128.2, 132.7, 133.2, 135.9, 141.3,
159.0.
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