Lewis Acid Mediated Electrophilic Cyanation of 2,2′-Biphenols

Article abstract of DOI:10.1021/acs.joc.0c00458

A Lewis acid mediated electrophilic cyanation of 2,2′-biphenols with a trifluoromethanesulfonyl (Tf) protecting group is reported. The cyanation reactions with less toxic, commercially available MeSCN as a cyanating reagent afforded a range of 3-cyan-2,2′-biphenols in moderate to high yields. The use of trifluoromethanesulfonyl (Tf) as a protecting group is crucial to the success of this transformation. Moreover, the cyanated products were readily transformed into various synthetically useful molecules. This protocol features high efficiency, excellent regioselectivity, and good functional group compatibility and may provide a practical tool for the synthesis and modification of biologically active compounds, catalysts, and ligands.

Full text of DOI:10.1021/acs.joc.0c00458

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Lewis Acid-Mediated Electrophilic Cyanation of 2,2'-Biphenols
Wu Zhang, Wen Yang, and Wanxiang Zhao
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 09 Jun 2020
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Page 1 of 14
The Journal of Organic Chemistry
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Lewis Acid-Mediated Electrophilic Cyanation of 2,2'-Biphenols
Wu Zhang, Wen Yang,* and Wanxiang Zhao*
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H
CN
Ar1
Ar2
Ar1
Ar2
MeSCN
i) BCl3, AlCl3,
OH
OR
OH
OH
ii) NaOH (aq.)
H,
Tf,
R =
R =
ABSTRACT: A Lewis acid-mediated electrophilic cyanation of 2,2'-biphenols with a trifloromethanesulfonyl (Tf) protecting group is
reported. The cyanation reactions with low toxic and commercially available MeSCN as a cyanating reagent afforded a range of 3-
cyan-2,2'-biphenols in moderate to high yields. The use of trifloromethanesulfonyl (Tf ) as a protecting group is crucial to the success
of this transformation. Moreover, the cyanated products were readily transformed into various synthetically useful molecules. This
protocol features high efficiency, excellent regioselectivity, and good functional group compatibility, and may provide a practical tool
for the synthesis and modification of biologically active compounds, catalysts, and ligands.
2,2'-Biphenol is a privileged structural scaffold frequently
existing in a wide range of materials, natural products,
pharmaceuticals, and agrochemicals.1 For example,
cephalochromin exhibits impressive growth-inhibitory and
apoptotic activity against human lung cancer A549 cells,1h and
schizandrin is used as an antioxidant and anti-inflammatory
agent1j (Figure 1a). In addition, 2,2'-biphenol is also present in
numerous catalysts and ligands, such as chiral BINOL-
aldehydes, phosphoric acids, bisphosphine ligands, and
phosphoramidite ligands (Figure 1b).2 Therefore, considerable
efforts have been devoted to the development of methodologies
for their synthesis, with the oxidative coupling of phenols
attracting the most attention.3 Moreover, the C−H
functionalization,4 such as halogenation, borylation, and
arylation, offers a practical tool for introducing substitutes at 3
and 3′ positions, which is extensively employed in synthesizing
catalysts and ligands with biphenol skeleton. However, to the
best of our knowledge, the cyanation of 2,2'-biphenols is yet to
be reported.
The extraordinary utility of aromatic nitriles in synthetic
chemistry is attributed to versatile functional transformations of
the cyano group, which could be converted to amine, ketone,
aldehyde, amide, and carboxylic acid.5 Additionally, aromatic
nitriles could participate in a series of transition-metal catalyzed
couplings for the formation of C−C,6b-d C−P,6e-f C−Si,6g-h and
C−B6i bonds via C−CN bond cleavage.6 In view of diverse
transformations of aromatic nitriles and the significance of 2,2'-
biphenols, we believe that the cyanation of 2,2'-biphenols
would bring great value to both synthesis and modification of
biphenol-derived catalysts, ligands, and biologically active
compounds. Although many cyanating approaches for the
synthesis of aromatic nitriles have been well established,7 the
direct C−H
a) Natural products and drugs
OH OH
O
OH
O
O
COOMe
COOMe
HO
HO
O
O
Me
Me
MeO
MeO
OH
HO
O
OH OH
cephalochromin
O
OH
O
magnolol
viriditoxin
OMe
OH
O
MeO
OMe
OH
MeO
MeO
MeO
MeO
OH
OH
HO
HO
O
MeO
OMe
OMe
OH
O
schizandrin
acerogenin E
phleichrome
b) Catalysts and ligands
CHO
R
R
O
O
R'
R'
OH
OH
O
O
Ar2P
OMe
OMe
P
P
N
O
OH
Ar2P
Ar
R
R
BINOL-aldehyde
chiral phosphoric acid
bisphosphine ligands
phosphoramidite ligands
Figure 1. 2,2'-Biphenol derivatives.
cyanation of phenols still remains underdeveloped. In this
context, Sugasawa and co-workers first reported a BCl3/AlCl3-
mediated cyanation of phenols using MeSCN as an electrophilic
cyanating reagent in 1990.8a Very recently, our group utilized N-
cyano-N-phenyl-p-toluenesulfonamide (NCTS) as a cyanating
reagent and realized an efficient cyanation of 2-naphthalenols
promoted by SnCl4 or BF3•OEt2/AlCl3.8b In continuation of our
study on cynantion, herein, we would like to demonstrate an
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efficient Lewis acid-promoted direct electrophilic cyanation of biphenol derivatives 2b-k with different substituents all
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4
5
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7
8
2,2'-biphenols.
proceeded well to afford the corresponding cyanated products
3b-k in moderate to high yields (45-82%). The electronic
property of groups on the aromatic ring had great effects on the
reaction results. The strong electron-donating group benefits
the efficiency of the electrophilic cyanation reaction. In sharp
contrast, 2,2'-biphenol derivatives 2q-s with electron-
withdrawing groups on the phenol ring were all inefficient for
this cyanation
Given the success of direct cyanation of phenols in previous
reports,8a-b we attempted to extend these methods to cyanation
of 2,2'-biphenols. Initially, we selected (1,1'-biphenyl)-2,2'-diol
1a as a substrate, and treated it with the optimal conditions
developed by Sugasawa8a and us8b (Scheme 1). Disappointingly,
we failed to get the desired dicyanated or monocyanated
products. The failure may be attributed to the reaction between
diol 1a and BX3, which generated the seven-membered
Table 1. The Effect of Protecting Groupsa
9
9
CN
cycloboron intermediate I, resulting in the deactivation of
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MeSCN
i) BCl3/AlCl3,
Lewis acid and inhibition of the cyanation process. Furthermore,
other Lewis acids, including Sn(OTf)3, In(OTf)3, Sc(OTf)3,
MgCl2, and SnCl4, were also examined, but the desired
cyanation reaction was also not achieved.
solvent, 80 oC, 24 h
ii) NaOH (aq.)
OH
OH
OH
OPG
Scheme 1. Initial Studies
2a-PG
3a
CN
entry
PG
Me
LA
3a (%)b
35
CN
'
':
1
2
3
4c
5
6
7
8
9
BCl3
BF3•OEt2
BBr3
MeSCN
Lewis acid
'CN
OH
OH
OH
OH
Me
Me
Me
Piv
Ac
N.D.
10
N.D.
23
Ph
Ts
'
N
CN
R = H or CN
BCl3
R
(NCTS)
BCl3
MeSCN
Sugasawa's conditions: BCl3/AlCl3,
Our previous conditions:
BCl3
24
NCTS
BF3OEt2/AlCl3,
Other Lewis acids
Ts
BCl3
30
O
B
X
Sn(OTf)2, In(OTf)3, Sc(OTf)3,MgCl2, SnCl4
TBS
Tf
BCl3
27
O
All failed
BCl3
75
I
aReaction conditions: i) 2a-PG (0.6 mmol), MeSCN (2.0 equiv), LA (2.0
equiv), AlCl3 (1.0 equiv), DCE (1.0 M), stirred at 80 °C for 24 h. ii) 4 M
aq. NaOH (3 mL), stirred at 80 °C for 0.5 h. bIsolated yield. cPerformed at
25 oC in the first step. LA = Lewis acid. BCl3 (1.0 M in dichloromethane).
BBr3 (1.0 M in dichloromethane). DCE = 1.2-dichloroethane. Piv =
pivaloyl. Ac
trifluoromethanesulfonyl.
Table 2. Optimization of Reaction Conditionsa
Despite the initial failures, we still aimed to realize this useful
transformation. We envisioned that the installation of a suitable
protecting group on one of the hydroxyl groups of diol 1a might
be a solution. Encouragingly, in the presence of BCl3, 2,2'-
biphenol derivative 2a-Me with a methyl protecting group
reacted with MeSCN at 80 oC to provide the desired
monocynated product 3a, albeit in only 35% yield (Table 1,
=
acetyl. TBS
=
tert-butyldimethylsilyl. Tf
=
CN
MeSCN
i) BCl3/AlCl3,
.
solvent, 80 oC, 24 h
ii) NaOH (aq.)
entry 1). The use of BF3 Et2O or BBr3 instead of BCl3, or
lowering the reaction temperature to 25 C, all gave inferior
OH
OH
OH
o
OTf
results (Table 1, entries 2−4). Subsequently, a series of
protecting groups were examined for this process (Table 1,
entries 5−9). To our delight, the trifloromethanesulfonyl (Tf)
group led to a substantial increase in yield (75%). Other
protecting groups, such as Piv, Ac, Ts, and TBS, all resulted in
diminished yields. The Tf group is crucial for this
transformation. It could prevent generating the seven-
membered cycloboron intermediate I, which deactivates the
catalyst of BCl3 and inhibits the cyanation process. Moreover,
the Tf group could be easily removed with the treatment of
NaOH aqueous solution in the second step.
Next, we used biphenol derivative 2a-Tf as the model
substrate to further optimize the reaction conditions. Reaction
parameters, including solvent, and the amount of BCl3 and
MeSCN, were examined, and the results are shown in Table 2.
Among the solvents screened, DCE proved to be the choice of
solvent (Table 2, entries 1−6). Increasing or decreasing the
amount of BCl3 and MeSCN at the same time resulted in lower
yields (Table 2, entries 7−9). Further screening of the amount
of MeSCN identified the optimal conditions (Table 2, entry 10).
The use of 3.0 equiv of MeSCN led to inferior yield (Table 2,
entry 11).
2a-Tf
3a
entry
1
MeSCN (equiv)
solvent
3a (%)b
75
2.0
2.0
2.0
2.0
2.0
2.0
1.2
1.5
2.5
2.5
3.0
DCE
toluene
MeCN
1,4-dioxane
THF
2
41
3
60
4
23
5
10
71
6
CHCl3
DCE
7c
8d
9e
10
11
63
DCE
68
DCE
70
DCE
80
DCE
75
aReaction conditions: i) 2a-Tf (0.6 mmol), MeSCN, BCl3 (2.0 equiv),
solvent (1.0 M), stirred at 80 °C, 24 h. ii) 4 M aq. NaOH (3 mL), stirred
at 80 °C for 0.5 h. bIsolated yield. BCl3 (1.2 equiv). dBCl3 (1.5 equiv).
c
eBCl3 (2.5 equiv).
process. It is worth noting that this useful transformation is well
compatible with many privileged molecules in the synthesis of
ligands and catalysts. For example, chiral H8 BINOL, BINOL,
and SPINOL substrates 2l-n worked well to deliver the desired
cyanated products 3l-n in 78%, 31%, and 75% yield, respectively,
With the optimal conditions in hand, we next examined the
substrate scope (Table 3). An array of Tf-protected 2,2'-
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The Journal of Organic Chemistry
molecules.
indicating that this protocol has great potential in the
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modification of ligands, catalysts, and biologically active
Table 3. Reaction Scopea
H
CN
Ar1
MeSCN
, AlCl3, BCl3
Ar1
Ar2
i)
DCE, 80 C, 24 h
ii) NaOH (aq.), 80 C, 0.5 h
OH
OH
OR
OTf
Ar2
7
8
9
3
, R = H or Tf
2
Me
Me
Et
CN
n-pent
CN
Ph
Ph
CN
CN
CN
Ar
Ar
CN
Me
CN
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OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
Et
n-pent
3f
(45%)
3a
3b
3c
3d
3e
3g
(75%)
(80%)
(82%)
CN
(79%)
CN
(75%)
(53%)
Ar = 3,5-Me2Ph
CN
CN
CN
CN
CN
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
Me
F
Cl
3j
(55%)
3h
3i
3k
(65%)
(72%)
(57%)
CN
3l
3m
3n
(78%, >99% ee)
F
(31%, >99% ee)
(75%, >99% ee)
I
Cl
CN
CN
OTf OH
OH
OH
OH
OH
CN
Failed
OH
OH
OH
examples
OTf
OTf
OTf
OTf
OTf
b
b
b
3p'
I
3o'
(50%)
(51%)
2s
3o
3a'
2q
(67%)
(53%)
2r
aReaction conditions: i) 2 (0.6 mmol), AlCl3 (1.0 equiv), MeSCN (2.5 equiv), BCl3 (2.0 equiv), and DCE (1.0 M). ii) 4 M NaOH (3 mL). bNaOH (4 M, 1.5
mL) for 10 min at room temperature. Isolated yield.
Scheme 2. Product Transformationsa
with NaOH at room temperature for 10 min, the products (3a',
3o', and 3p') with a Tf protecting group retained were achieved
NH2
CHO
COOH
CONH2
O
in
moderate
yields
(50-53%
yield).
The
O
Ph
OMe
OMe
OMe
OMe
OMe
OMe
trifluoromethanesulfonate moiety could serve as a convenient
handle for various coupling reactions, enhancing the practicality
of this cyanation reaction.
TfO
7
(93%)
12
5
6
(84%)
(92%)
(52%)
To show synthetic potentials of our method, we conducted
the gram-scale synthesis and various product transformations
(Scheme 2).The preparation of product 3a can be readily scaled
up to gram-scale without obvious erosion in yield (71%). The
representative products 3a and 3a' were then converted to other
useful molecules. For example, methylation of 3a with methyl
iodide led to 4, which was subsequently converted to aldehyde
5, acid 6, amide 7, ketone 8, and amine 9 via the diverse
transformations of the cyano group.10 The transetherification of
4 with (+)-fenchol using our previous method afforded the
desired chiral ether 10 with good efficiency.11 Moreover, nitrile
3a' were readily transformed to chiral oxazoline 11 and
benzofuran 12 in excellent yields.12-13
i
c
d
b
R = Tf
CN
CN
standard
conditions
a
OH
OH
OR
OMe
OMe
or
OTf 3a 3a'
(1.50 g, 71% for
R = H
3a
)
4
(87%)
2a-Tf
h
e
g
R = Tf
tBu
f
O
O
CN
O
Me
NH2
N
Me
OMe
OMe
OMe
OMe
OH
MeO
Me
TfO
H
Me
Scheme 3. Proposed Mechanism
9
8
(91%)
(84%)
10
11
(50%)
(90%, >99% ee)
aReaction conditions: (a) CH3I, K2CO3, DMF, 60 °C, overnight; (b)
DIBAL-H, Et2O, rt, overnight; (c) 34% aq. KOH, EtOH, 80°C, overnight;
(d) KOH(s), tBuOH, 60 °C, overnight; (e) i) MeMgBr, Et2O, 48 h, reflux;
ii) 10% aq. HCl,; (f) LiAlH4, Et2O, rt, overnight; (g) (+)-Fenchol, KOtBu,
1,4-dioxane, 80°C, 16 h; (h) (S)-2-Amino-3,3-dimethylbutan-1-ol, ZnCl2,
PhCl, 131 °C, 3 d; (i) 2-Bromoacetophenone, K2CO3, acetone, reflux, 8 h.
3-Hydroxynaphthalen-2-yl trifluormethanesulfonate 2o was
also a viable substrate, providing the desired product 3o in 67%
yield. Interestingly, when the cyanated products was treated
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synthesized
SMe
5,5'-diiodo-[1,1'-biphenyl]-2,2'-diol16
were
1
2
3
4
5
6
7
8
N
B
according to the known procedure. The data are all in
accordance with the literatures.
Ar1
Ar1
Ar1
Ar2
AlCl3
BCl3
Cl
Cl
OH
MeSCN
OBCl2
OTf
O
OTf
OTf
Synthesis of 2'-methoxy-[1,1'-biphenyl]-2-ol (2a-Me).17 To
a
- HCl
Ar2
Ar2
solution of [1,1'-biphenyl]-2,2'-diol 1a (931.0 mg, 5.0 mmol) in
acetone (20 mL) was added K2CO3 (1.04 g, 7.5 mmol). After
the reaction mixture was stirred for 15 min at room temperature,
CH3I (0.4 mL, 6.0 mmol) was added dropwise. The resulting
mixture was refluxed for 10 h. Upon completion, the reaction
mixture was concentrated, acidified with 6 M aq. HC1, and
extracted with ethyl acetate (15 mL x 3). The combined organic
layers were washed with water (15 mL) and brine (15 mL),
dried over Na2SO4, and concentrated in vacuo. The residue was
purified by column chromatography on silica gel using
petroleum ether/ethyl acetate (v/v, from 10/1 to 5/1) as an
eluent to afford the desired product 2a-Me in 62% yield (621.0
mg) as a colorless solid. m.p. 55-56 °C. Rf = 0.45 (PE/EtOAc =
2
A
B
SMe
NH
SMe
H
CN
N
B
Ar1
Ar1
H2O
NaOH
Ar1
Cl
Cl
Cl
Cl
H+
B
O
O
OH
OH
9
OTf
OTf
- TfOH
- MeSH
Ar2
Ar2
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Ar2
C
3
D
Based on previous literatures,8a-b a proposed mechanism for
this cyanation is outlined in Scheme 3. First, the intermediate A
is generated from substrate 2 and BCl3 with the help of AlCl3.
Then it reacts with MeSCN though a six-membered ring
transition state B to form the intermediate C, which undergoes
tautomerization to give the intermediate D. Finally, the
treatment of D with NaOH aqueous solution followed by
protonation leads to the cyanated product 3.
In summary, we have demonstrated an efficient Lewis acid
mediated electrophilic cyanation of 2,2'-biphenols with a
trifloromethanesulfonyl (Tf) as the protecting group that is
unable to coordinate with Lewis acid, leading to the success of
this transformation. The present cyanation reactions using low
toxic and commercially available MeSCN as the cyanating
reagent provided a range of 3-cyan-2,2'-biphenols in moderate
to high yields with excellent regioselectivity. In addition, the
gram-scale cyanation reaction performed well, and the cyanated
products were readily transformed into various synthetically
useful molecules. This protocol may provide a practical tool for
synthesis and modification of biologically active compounds,
catalysts, and ligands. Synthesis of new ligands based on this
reaction is underway in our laboratory.
1
5/1). H NMR (400 MHz, CDCl3) δ 7.47-7.29 (m, 4H), 7.16
(t, J = 7.2 Hz, 1H), 7.12-7.04 (m, 3H), 6.32 (s, 1H), 3.92 (s, 3H)
ppm. 13C{1H} NMR (100 MHz, CDCl3) δ 155.4, 153.5, 132.2,
131.1, 129.1, 129.0, 126.8, 126.1, 121.9, 120.8, 117.2, 111.4,
55.8 ppm.
Synthesis of 2'-hydroxy-[1,1'-biphenyl]-2-yl acetate (2a-Ac).18 To a
solution of [1,1'-biphenyl]-2,2'-diol 1a (931.0 mg, 5.0 mmol) in
a mixture of toluene (26 mL), CH2Cl2 (17 mL) and pyridine (5
mL) at 0 °C were added dimethyl amino pyridine (24.4 mg, 0.2
mmol) and acetic anhydride (566.0 mg, 5.5 mmol), successively.
The resulting mixture was stirred at room temperature for 6 h.
Upon completion, the solvents were removed in vacuo. The
residue was dissolved in ether (25 mL), successively washed
with 2 aq. M HCl (30 mL), saturated aqueous NaHCO3 (30
mL), and brine (30 mL), dried over Na2SO4, filtered, and
concentrated in vacuo. The residue was purified by column
chromatography on silica gel using petroleum ether/ethyl
acetate (v/v, from 8/1 to 4/1) to afford the desired product 2a-
Ac in 67% yield (764.0 mg) as a colorless solid. m.p. 61-62 °C.
1
Rf = 0.38 (PE/EtOAc = 4/1). H NMR (400 MHz, CDCl3) δ
EXPERIMENTAL SECTION
7.48-7.32 (m, 3H), 7.31-7.24 (m, 1H), 7.20 (d, J = 8.0 Hz, 1H),
7.15 (dd, J = 7.7, 1.5 Hz, 1H), 7.01-6.94 (m, 2H), 5.32 (br s,
1H), 2.04 (s, 3H) ppm. 13C{1H} NMR (100 MHz, CDCl3) δ
169.7, 152.9, 148.6, 131.8, 130.6, 130.2, 129.5, 129.4, 126.6,
123.9, 122.9, 120.4, 116.2, 20.5 ppm. HRMS (ESI) m/z: [M +
Na]+ Calcd for C14H12NaO3 251.0679; Found 251.0676. IR
(neat): 3447, 3064, 1735, 1603, 1541, 1481, 1369, 1229, 1190,
1008, 755 cm-1.
General Information. Unless otherwise noted, all reactions
were conducted in oven-dried vials with a magnetic stir bar
under nitrogen atmosphere. Solvents were purified under
nitrogen using
a solvent purification system. Column
chromatography was performed with EM Science silica gel 60
(200-300 mesh). 1H NMR and 13C NMR spectra were recorded
on Bruker 400 MHz. Chemical shifts (δ) are given in parts per
million (ppm) referenced to the appropriate solvent peak or 0.0
ppm for tetramethylsilane (1H NMR: CDCl3 at 7.26 ppm, d6-
DMSO at 2.50 ppm. 13C NMR: CDCl3 at 77.00 ppm, d6-DMSO
at 39.52 ppm). The data are reported as follows: chemical shift
(ppm), multiplicity (s = singlet, d = doublet, dd = doublet of
doublet, t = triplet, m = multiplet, br = broad), coupling
constant J (Hz) and integration. High resolution mass spectra
were recorded on a Bruker Maxis System. IR spectra were
collected on a Spectrum BX FTIR from Perkin-Elmer and
reported in unit of cm-1. Melting points were measured on an
automatic melting points instrument MP430 at ambient
pressure.
Synthesis of 2'-hydroxy-[1,1'-biphenyl]-2-yl pivalate (2a-Piv).19 To
a solution of [1,1'-biphenyl]-2,2'-diol 1a (931.0 mg, 5.0 mmol)
in acetonitrile (25 mL) was added Et3N (1.0 mL, 7.5 mmol),
then pivaloyl chloride (0.7 mL, 5.8 mmol) was added at 0 °C.
The mixture was stirred at the same temperature for 15 h. The
reaction was quenched by the addition of water (20 mL), and
then extracted with Et2O (20 mL x 3). The combined organic
layers were washed with brine (20 mL), dried over Na2SO4,
filtered, and concentrated in vacuo. The residue was purified by
column chromatography on silica gel using petroleum
ether/ethyl acetate (v/v, from 8/1 to 4/1) to afford the desired
product 2a-Piv in 71% yield (960.0 mg) as a colorless solid. m.p.
Preparation of Substrates. 2'-Hydroxy-[1,1'-biphenyl]-2-yl 4-
1
91-92 °C. Rf = 0.37 (PE/EtOAc = 4/1). H NMR (400 MHz,
methylbenzenesulfonate
2a-Ts,14
2'-((tert-
CDCl3) δ 7.48-7.42 (m, 1H), 7.39-7.32 (m, 2H), 7.28-7.23 (m,
1H), 7.15 (d, J = 8.0 Hz, 1H), 7.10 (dd, J = 7.5, 1.5 Hz, 1H),
butyldimethylsilyl)oxy)-[1,1'-biphenyl]-2-ol 2a-TBS,15 and
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The Journal of Organic Chemistry
6.99-6.91 (m, 2H), 5.06 (s, 1H), 1.06 (s, 9H) ppm. 13C{1H}
in 50% yield (1.63 g). m.p. 50-51 °C. Rf = 0.38 (PE/EtOAc =
3/1). H NMR (400 MHz, CDCl3) δ 7.14-7.06 (m, 4H), 6.93
(d, J = 8.1 Hz, 2H), 5.84 (br s, 2H), 2.63-2.54 (m, 4H), 1.68-
1.56 (m, 4H), 1.39-1.29 (m, 8H), 0.91 (t, J = 6.7 Hz, 6H) ppm.
13C{1H} NMR (100 MHz, CDCl3) δ 150.5, 136.1, 131.1, 129.5,
124.2, 116.5, 35.0, 31.5, 31.3, 22.5, 14.0 ppm.
Synthesis of [1,1':3',1'':3'',1'''-quaterphenyl]-4',6''-diol (1e).3f The
title compound 1e was synthesized from [1,1'-biphenyl]-4-ol
according to the general procedure A (eluent: petroleum
ether/ethyl acetate, from 10/1 to 6/1, v/v) and isolated as a
colorless solid in 32% yield (1.08 g). m.p. 184-185 °C. Rf = 0.35
(PE/EtOAc = 3/1). 1H NMR (400 MHz, d6-DMSO) δ 9.51 (s,
2H), 7.63 (d, J = 7.5 Hz, 4H), 7.56 (d, J = 2.3 Hz, 2H), 7.51 (d,
J = 2.3 Hz, 1H), 7.49 (d, J = 2.3 Hz, 1H), 7.40 (t, J = 7.7 Hz,
4H), 7.27 (t, J = 7.3 Hz, 2H), 7.08 (s, 1H), 7.06 (s, 1H) ppm.
13C{1H} NMR (100 MHz, d6-DMSO) δ 154.6, 140.3, 130.9,
129.9, 128.8, 126.6, 126.4, 126.2, 126.1, 116.3 ppm.
1
1
2
3
4
5
6
7
8
NMR (100 MHz, CDCl3) δ 177.4, 153.1, 149.1, 131.9, 130.7,
130.2, 129.64, 129.57, 126.6, 124.0, 122.9, 120.3, 116.2, 38.9,
26.7 ppm. HRMS (ESI) m/z: [M - H]- Calcd for C17H17O3
269.1178; Found 269.1185. IR (neat): 3453, 2973, 1738, 1584,
1479, 1442, 1281, 1191, 1125, 1008, 754 cm-1.
Synthesis of 5,5'-diiodo-2,2'-dimethoxy-1,1'-biphenyl.20 To
a
solution of 5,5'-diiodo-[1,1'-biphenyl]-2,2'-diol (4.38 g, 10.0
mmol) in acetone (40 mL) was added KOH (2.24 g, 40.0
mmol). After the mixture was stirred for 15 min, CH3I (2.49 mL,
40.0 mmol) was added. The resulting mixture was stirred for 16
h at room temperature. Upon completion, the solvent was
removed in vacuo and the residue dissolved in diethyl ether (30
mL). The organic phase was washed with water (20 mL), 1 M
aq. HCl (20 mL) and 0.2 M aq. NaHCO3 (20 mL), dried over
Na2SO4, filtered, and concentrated in vacuo. The residue was
purified by column chromatography on silica gel using
petroleum ether/ethyl acetate (v/v = 10/1) to afford the
desired product in 68% yield (3.17 g) as a colorless solid. m.p.
164-165 °C. Rf = 0.51 (PE/EtOAc = 5/1). 1H NMR (400 MHz,
CDCl3) δ 7.62 (d, J = 2.2 Hz, 1H), 7.60 (d, J = 2.3 Hz, 1H),
7.48 (d, J = 2.2 Hz, 2H), 6.74 (s, 1H), 6.71 (s, 1H), 3.75 (s, 6H)
ppm. 13C{1H} NMR (100 MHz, CDCl3) δ 156.9, 139.4, 137.7,
128.8, 113.3, 82.5, 55.8 ppm.
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
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Synthesis of 3,3''',5,5'''-tetramethyl-[1,1':3',1'':3'',1'''-quaterphenyl]-
4',6''-diol (1f). A solution of (3,5-dimethylphenyl)boronic acid
(1.88 g, 12.5 mmol) in 30 mL of ethanol was added to the
suspension of 5,5'-diiodo-2,2'-dimethoxy-1,1'-biphenyl (2.33 g,
5.0 mmol, 1 equiv), Pd(PPh3)4 (288.9 mg, 5 mol %) and K2CO3
(4.35 g, 31.5 mmol) in toluene (30 mL) and H2O (30 mL) at
room temperature under nitrogen atmosphere. The mixture was
stirred for 10 min before heated in an oil bath to 100 °C for 20
h. Upon completion, the volatile solvent was removed in vacuo,
and then extracted with ethyl acetate (30 mL x 3) for three times.
The combined organic layers were washed with water (30 mL)
and brine (30 mL), then dried over Na2SO4, filtered, and
concentrated under vacuo. The residue was purified by column
chromatography on silica gel to afford the crude product. The
crude product was then dissolved in 50 mL of CH2Cl2, and then
BBr3 (20 mL, 20.0 mmol, 1.0 M in dichloromethane) was added
Synthesis of [1,1'-biphenyl]-2,2'-diol derivatives. According to the
modified literature procedure (procedure A),21 to a stirred
suspension of AlCl3 (2.67 g, 20.0 mmol) in dry CH2Cl2 (20 mL)
was added para-substituted phenol derivative (20.0 mmol) in
dry CH2Cl2 (10 mL) under N2 atmosphere. After stirred for 30
min, anhydrous FeCl3 (3.24 g, 20.0 mmol) was added. The
resulting reaction mixture was refluxed in an oil bath for 24 h.
The reaction was quenched with 2 M aq. HCl (30 mL), and
extracted with CH2Cl2 (50 mL x 3). The combined organic
layers were washed with water and brine, dried over Na2SO4,
filtered, and concentrated in vacuo. The residue was purified by
column chromatography on silica gel to afford the desired
product 1.
o
dropwise at 0 C. The resulting mixture was stirred at room
temperature for 18 h. Upon completion, the reaction mixture
was cooled to 0 °C and quenched with water (40 mL). The
organic phase was separated and the aqueous phase was
extracted with CH2Cl2 (40 mL). The combined organic layers
were washed with brine (40 mL x 3), dried over Na2SO4, filtered,
and concentrated in vacuo. The residue was purified by column
chromatography on silica gel using petroleum ether/ethyl
acetate (v/v, 6/1) to afford the desired product 1f as a colorless
solid in 53% yield (1.05 g). m.p. 184-185 °C. Rf = 0.36
Synthesis of 5,5'-dimethyl-[1,1'-biphenyl]-2,2'-diol (1b).22 The title
compound 1b was synthesized from p-cresol according to the
general procedure A (eluent: petroleum ether/ethyl acetate,
from 10/1 to 6/1, v/v) and isolated as a colorless solid in 45%
yield (964.0 mg). m.p. 152-153 °C. Rf = 0.39 (PE/EtOAc =
3/1). 1H NMR (400 MHz, d6-DMSO) δ 8.98 (s, 2H), 7.00-6.90
(m, 4H), 6.84-6.77 (m, 2H), 2.22 (s, 6H) ppm. 13C{1H} NMR
(100 MHz, d6-DMSO) δ 152.1, 131.9, 128.5, 127.4, 125.9,
115.8, 20.2 ppm.
Synthesis of 5,5'-diethyl-[1,1'-biphenyl]-2,2'-diol (1c).23 The title
compound 1c was synthesized from 4-ethylphenol according to
the general procedure A (eluent: petroleum ether/ethyl acetate,
from 10/1 to 6/1, v/v) and isolated as a colorless solid in 47%
yield (1.14 g). m.p. 124-125 °C. Rf = 0.40 (PE/EtOAc = 3/1).
1H NMR (400 MHz, CDCl3) δ 7.15-7.10 (m, 4H), 6.95-6.91 (m,
2H), 6.07 (s, 2H), 2.65 (q, J = 7.6 Hz, 4H), 1.26 (t, J = 7.6 Hz,
6H) ppm. 13C{1H} NMR (100 MHz, CDCl3) δ 150.5, 137.4,
130.5, 129.0, 124.2, 116.5, 28.0, 15.8 ppm.
1
(PE/EtOAc = 3/1). H NMR (400 MHz, CDCl3) δ 7.61-7.57
(m, 3H), 7.56 (d, J = 2.2 Hz, 1H), 7.22 (s, 4H), 7.11 (s, 1H),
7.09 (s, 1H), 7.00 (s, 2H), 6.21 (br s, 2H), 2.39 (s, 12H) ppm.
13C{1H} NMR (100 MHz, CDCl3) δ 152.0, 140.3, 138.3, 135.2,
130.2, 128.6, 128.4, 124.9, 124.7, 117.1, 21.3 ppm. HRMS (ESI)
m/z: [M - H]- Calcd for C28H25O2 393.1855; Found 393.1862.
IR (neat): 3385, 2919, 1601, 1501, 1462, 1377, 1234, 1117,
1043, 850, 823 cm-1.
Synthesis of 2'-hydroxy-1,1'-biphenyl triflates. According to the
literature procedure (procedure B),24 to a solution of [1,1'-
biphenyl]-2,2'-diol derivative 1 (3.0 mmol, 1.0 equiv) and N-
ethyldiisopropylamine (0.5 mL, 387.9 mg, 3.0 mmol) in
dichloromethane (9 mL) under N2 atmosphere was added
trifluoromethanesulfonic anhydride (0.55 mL, 930.6 mg, 3.3
mmol) dropwise at 0 °C. The resulting mixture was stirred
overnight at room temperature. Upon completion, the reaction
was quenched with 2 M HCl aqueous solution, and then
Synthesis of 5,5'-dipentyl-[1,1'-biphenyl]-2,2'-diol (1d).23 The title
compound 1d was synthesized from 4-pentylphenol according
to the general procedure A (eluent: petroleum ether/ethyl
acetate, from 10/1 to 6/1, v/v) and isolated as a colorless solid
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extracted with dichloromethane (15 mL x 3). The combined as yellow oil in 80% yield (898.6 mg). Rf = 0.44 (PE/EtOAc =
5/1). 1H NMR (400 MHz, CDCl3) δ 7.34-7.27 (m, 3H), 7.17-
7.11 (m, 1H), 7.04 (s, 1H), 6.89 (d, J = 8.3 Hz, 1H), 4.81 (br s,
1H), 2.72 (q, J = 7.6 Hz, 2H), 2.62 (q, J = 7.6 Hz, 2H), 1.28 (t,
J = 7.6 Hz, 3H), 1.23 (t, J = 7.6 Hz, 3H) ppm. 13C{1H} NMR
(100 MHz, CDCl3) δ 150.7, 145.6, 144.9, 136.5, 131.8, 131.2,
130.4, 129.5, 128.9, 122.2, 121.7, 118.4 (q, J = 320.0 Hz), 116.0,
28.2, 27.9, 15.7, 15.1 ppm. HRMS (ESI) m/z: [M - H]- Calcd
for C17H16F3O4S 373.0721; Found 373.0729. IR (neat): 3554,
2968, 2875, 1617, 1508, 1483, 1421, 1211, 1141, 911, 876 cm-1.
1
2
3
4
5
6
7
8
organic layers were washed with brine (15 mL), dried over
Na2SO4, filtered, and concentrated in vacuo. The residue was
purified by column chromatography on silica gel to give the
desired product 2.
General procedure C. A solution of arylboronic acid (5.0 mmol,
1.0 equiv) in 15 mL of ethanol was added to the suspension of
aryl bromide (5.0 mmol, 1.0 equiv), Pd(PPh3)4 (288.9 mg, 5
mol %), and K2CO3 (4.35 g, 31.5 mmol) in toluene (30 mL) at
room temperature under nitrogen atmosphere.25 The mixture
was stirred for 10 min before heated in an oil bath to 100 °C for
20 h. Upon completion, the volatile solvent was removed in
vacuo, and then extracted with ethyl acetate (30 mL x 3) for
three times. The organic layers were washed with water (30 mL)
and brine (30 mL), then dried over Na2SO4, filtered, and
concentrated under vacuo. The residue was purified by column
chromatography on silica gel to afford the crude product. The
crude product was added Tf2O (1.7 mL, 2.82 g, 10.0 mmol) and
iPr2NEt (0.83 mL, 646.5 mg, 5.0 mmol). Upon completion, the
solvent was concentrated in vacuo, and then dissolved in 100
mL of dry CH2Cl2. BBr3 (1.0 M in dichloromethane, 10.0 mL,
10.0 mmol) was added dropwise at 0 oC.8 The resulting mixture
was stirred at room temperature for 18 h. Upon completion, the
reaction mixture was cooled to 0 °C and quenched with water
(40 mL). The organic phase was separated and the aqueous
phase was extracted with CH2Cl2 (40 mL). The combined
organic layers were washed with brine (40 mL x 3), dried over
Na2SO4, filtered, and concentrated in vacuo. The residue was
purified by column chromatography on silica gel to afford the
desired product 2.
9
Synthesis
of
2'-hydroxy-5,5'-dipentyl-[1,1'-biphenyl]-2-yl
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
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
trifluoromethane-sulfonate (2d). The title compound 2d was
synthesized from 1d according to the general procedure B
(eluent: petroleum ether/ethyl acetate, 10/1, v/v) and isolated
as yellow oil in 82% yield (1.13 g). Rf = 0.47 (PE/EtOAc = 5/1).
1H NMR (400 MHz, CDCl3) δ 7.32-7.24 (m, 3H), 7.14-7.09 (m,
1H), 7.01 (d, J = 2.0 Hz, 1H), 6.88 (d, J = 8.3 Hz, 1H), 4.74 (s,
1H), 2.70-2.63 (m, 2H), 2.60-2.53 (m, 2H), 1.69-1.56 (m, 4H),
1.39-1.27 (m, 8H), 0.94-0.86 (m, 6H) ppm. 13C{1H} NMR
(100 MHz, CDCl3) δ 150.7, 145.6, 143.8, 135.3, 132.3, 131.0,
130.9, 130.1, 129.5, 122.1, 121.8, 118.4 (q, J = 320.5 Hz), 115.9,
35.3, 34.9, 31.5, 31.30, 31.26, 30.9, 22.5, 22.4, 13.97, 13.95 ppm.
HRMS (ESI) m/z: [M - H]- Calcd for C23H28F3O4S 457.1660;
Found 457.1669. IR (neat): 3568, 2931, 2859, 1617, 1508,
1483, 1422, 1211, 1142, 1038, 881 cm-1.
Synthesis
of
6''-hydroxy-[1,1':3',1'':3'',1'''-quaterphenyl]-4'-yl
trifluoromethane-sulfonate (2e). The title compound 2e was
synthesized from 1e according to the general procedure B
(eluent: petroleum ether/ethyl acetate, 10/1, v/v) and isolated
as yellow oil in 77% yield (1.09 g). Rf = 0.43 (PE/EtOAc = 5/1).
1H NMR (400 MHz, CDCl3) δ 7.74 (d, J = 2.3 Hz, 1H), 7.73-
7.68 (m, 1H), 7.64-7.56 (m, 5H), 7.53 (d, J = 2.2 Hz, 1H), 7.52-
7.42 (m, 5H), 7.41 (d, J = 2.4 Hz, 1H), 7.36-7.30 (m, 1H), 7.06
(d, J = 8.4 Hz, 1H), 5.14 (br s, 1H) ppm. 13C{1H} NMR (100
MHz, CDCl3) δ 152.4, 146.9, 141.9, 140.3, 138.9, 134.2, 131.6,
131.1, 130.0, 129.0, 128.96, 128.7, 128.3, 128.2, 127.2, 126.9,
126.8, 122.6, 122.3, 118.4 (q, J = 320.7 Hz), 116.5 ppm. HRMS
(ESI) m/z: [M - H]- Calcd for C25H16F3O4S 469.0721; Found
469.0730. IR (neat): 3539, 1702, 1605, 1514, 1478, 1421, 1213,
1046, 1139, 896, 764 cm-1.
Synthesis
of
2'-hydroxy-[1,1'-biphenyl]-2-yl
trifluoromethanesulfonate (2a). The title compound 2a was
synthesized from 1a according to the general procedure B
(eluent: petroleum ether/ethyl acetate, 10/1, v/v) and isolated
as colorless oil in 80% yield (763.0 mg). Rf = 0.41 (PE/EtOAc
= 5/1). 1H NMR (400 MHz, CDCl3) δ 7.52-7.46 (m, 3H), 7.45-
7.39 (m, 1H), 7.36-7.30 (m, 1H), 7.26-7.22 (m, 1H), 7.04 (t, J
= 7.5 Hz, 1H), 6.94 (d, J = 8.2 Hz, 1H), 5.21 (s, 1H) ppm.
13C{1H} NMR (100 MHz, CDCl3) δ 152.8, 147.6, 132.6, 131.4,
131.3, 130.3, 129.7, 128.6, 122.2, 121.9, 120.8, 118.3 (q, J =
320.4 Hz), 116.1 ppm. HRMS (ESI) m/z: [M - H]- Calcd for
C13H8F3O4S 317.0095; Found 317.0103. IR (neat): 3553, 1606,
1592, 1509, 1481, 1420, 1213, 1140, 1046, 893, 759 cm-1.
Synthesis of 6''-hydroxy-3,3''',5,5'''-tetramethyl-[1,1':3',1'':3'',1'''-
quaterphenyl]-4'-yl trifluoromethanesulfonate (2f). The title
compound 2f was synthesized from 1f according to the general
procedure B (eluent: petroleum ether/ethyl acetate, 10/1, v/v)
and isolated as colorless oil in 79% yield (1.25 g). Rf = 0.45
(PE/EtOAc = 5/1). 1H NMR (400 MHz, CDCl3) δ 7.72 (s, 1H),
7.68 (d, J = 8.6 Hz, 1H), 7.59-7.54 (m, 1H), 7.51-7.45 (m, 2H),
7.22 (s, 2H), 7.20 (s, 2H), 7.07-7.02 (m, 2H), 6.98 (s, 1H), 5.14
(s, 1H), 2.39 (s, 6H), 2.38 (s, 6H). 13C{1H} NMR (100 MHz,
CDCl3) δ 152.2, 146.8, 142.1, 140.3, 138.9, 138.5, 138.2, 134.4,
131.5, 131.2, 130.0, 129.8, 128.9, 128.6, 128.2, 125.1, 124.7,
122.6, 122.1, 118.4 (q, J = 320.6 Hz), 116.4, 21.3, 21.2 ppm.
HRMS (ESI) m/z: [M - H]- Calcd for C29H24F3O4S 525.1347;
Found 525.1356. IR (neat): 3540, 2922, 1710, 1604, 1512,
1472, 1422, 1210, 1140, 1040, 885 cm-1.
Synthesis
of
2'-hydroxy-5,5'-dimethyl-[1,1'-biphenyl]-2-yl
trifluoromethane-sulfonate (2b). The title compound 2b was
synthesized from 1b according to the general procedure B
(eluent: petroleum ether/ethyl acetate, 10/1, v/v) and isolated
as yellow oil in 85% yield (883.0 mg). Rf = 0.45 (PE/EtOAc =
5/1). 1H NMR (400 MHz, CDCl3) δ 7.32-7.25 (m, 3H), 7.15-
7.10 (m, 1H), 7.04 (s, 1H), 6.86 (d, J = 8.2 Hz, 1H), 5.08 (br s,
1H), 2.43 (s, 3H), 2.34 (s, 3H) ppm. 13C{1H} NMR (100 MHz,
CDCl3) δ 150.5, 145.5, 138.7, 133.0, 131.4, 131.1, 130.6, 130.1,
130.0, 122.1, 121.5, 118.4 (q, J = 320.2 Hz), 115.9, 20.7, 20.3
ppm. HRMS (ESI) m/z: [M - H]- Calcd for C15H12F3O4S:
345.0408; Found 345.0416. IR (neat): 3554, 2926, 1617, 1509,
1490, 1420, 1213, 1141, 1042, 878, 816 cm-1.
Synthesis
of
2'-hydroxy-5'-methyl-[1,1'-biphenyl]-2-yl
Synthesis
of
5,5'-diethyl-2'-hydroxy-[1,1'-biphenyl]-2-yl
trifluoromethanesulfonate (2g). The title compound 2g was
synthesized using (2-hydroxyphenyl)boronic acid and 2-
bromo-1-methoxy-4-methylbenzene as the starting material
according to the general procedure C (eluent: petroleum
trifluoromethane-sulfonate (2c). The title compound 2c was
synthesized from 1c according to the general procedure B
(eluent: petroleum ether/ethyl acetate, 10/1, v/v) and isolated
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The Journal of Organic Chemistry
1
ether/ethyl acetate, 10/1, v/v) and isolated as yellow oil in 42%
Rf = 0.46 (PE/EtOAc = 5/1). H NMR (400 MHz, CDCl3) δ
8.02 (d, J = 9.1 Hz, 1H), 7.97 (d, J = 8.1 Hz, 1H), 7.65-7.57 (m,
2H), 7.56-7.49 (m, 2H), 7.47-7.41 (m, 1H), 7.25 (d, J = 8.8 Hz,
1H), 7.15- 7.06 (m, 2H), 4.76 (s, 1H) ppm. 13C{1H} NMR (100
MHz, CDCl3) δ 153.5, 145.1, 132.9, 132.6, 131.9, 130.8, 130.7,
128.3, 127.9, 127.7, 127.2, 126.4, 120.9, 119.5, 119.4, 118.4 (q,
J = 318.3 Hz), 116.3 ppm. HRMS (ESI) m/z: [M - H]- Calcd
for C17H10F3O4S 367.0252; Found 367.0257. IR (neat): 3540,
1613, 1584, 1511, 1450, 1422, 1216, 1173, 1140, 974, 836 cm-1.
yield (697.8 mg). Rf = 0.44 (PE/EtOAc = 5/1). 1H NMR (400
MHz, CDCl3) δ 7.50-7.44 (m, 3H), 7.43-7.38 (m, 1H), 7.15-
7.09 (m, 1H), 7.03 (s, 1H), 6.85 (d, J = 8.2 Hz, 1H), 4.99 (br s,
1H), 2.33 (s, 3H) ppm. 13C{1H} NMR (100 MHz, CDCl3) δ
150.5, 147.6, 132.6, 131.6, 131.5, 130.7, 130.1, 129.6, 128.5,
122.0, 121.8, 118.4 (q, J = 320.4 Hz), 116.0, 20.3 ppm. HRMS
(ESI) m/z: [M - H]- Calcd for C14H10F3O4S 331.0252; Found
331.0257. IR (neat): 3555, 2926, 1618, 1510, 1487, 1421, 1213,
1140, 1094, 905, 871 cm-1.
1
2
3
4
5
6
7
8
Synthesis of (S)-2'-hydroxy-5,5',6,6',7,7',8,8'-octahydro-[1,1'-
binaphthalen]-2-yl trifluoromethanesulfonate (2l). The title
compound 2l was synthesized from (S)-5,5',6,6',7,7',8,8'-
octahydro-[1,1'-binaphthalene]-2,2'-diol 1l according to the
general procedure B (eluent: petroleum ether/ethyl acetate,
10/1, v/v) and isolated as yellow oil in 85% yield (1.09 g). Rf =
9
Synthesis
of
2'-hydroxy-5-methyl-[1,1'-biphenyl]-2-yl
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trifluoromethanesulfonate (2h). The title compound 2h was
synthesized using (2-methoxyphenyl) boronic acid and 2-
bromo-4-methylphenol as the starting material according to the
general procedure C (eluent: petroleum ether/ethyl acetate,
10/1, v/v) and isolated as yellow oil in 43% yield (714.4 mg).
1
0.42 (PE/EtOAc = 5/1). H NMR (400 MHz, CDCl3) δ 7.23
1
Rf = 0.44 (PE/EtOAc = 5/1). H NMR (400 MHz, CDCl3) δ
(d, J = 8.5 Hz, 1H), 7.17 (d, J = 8.5 Hz, 1H), 7.07 (d, J = 8.3
Hz, 1H), 6.80 (d, J = 8.3 Hz, 1H), 4.65 (s, 1H), 2.91-2.84 (m,
2H), 2.82-2.74 (m, 2H), 2.57-2.47 (m, 1H), 2.41-2.22 (m, 2H),
2.11-2.01 (m, 1H), 1.84-1.64 (m, 8H) ppm. 13C{1H} NMR
(100 MHz, CDCl3) δ 150.4, 145.6, 139.8, 138.6, 135.8, 130.6,
130.57, 129.8, 129.0, 120.1, 118.4, 118.3 (q, J = 318.4 Hz),
113.5, 29.6, 29.1, 27.3, 27.1, 22.94, 22.88, 22.5, 22.3 ppm.
HRMS (ESI) m/z: [M - H]- Calcd for C21H20F3O4S 425.1034;
Found 425.1042. IR (neat): 3562, 2933, 1594, 1480, 1466,
1418, 1211, 1141, 1053, 932, 852 cm-1.
7.34-7.27 (m, 4H), 7.23-7.19 (m, 1H), 7.05-6.99 (m, 1H), 6.96
(d, J = 8.2 Hz, 1H), 5.05 (s, 1H), 2.42 (s, 3H) ppm. 13C{1H}
NMR (100 MHz, CDCl3) δ 152.8, 145.5, 138.8, 133.0, 131.2,
130.9, 130.21, 130.15, 122.3, 121.6, 120.7, 118.3 (q, J = 320.3
Hz), 116.0, 20.7 ppm. HRMS (ESI) m/z: [M - H]- Calcd for
C14H10F3O4S 331.0252; Found 331.0257. IR (neat): 3572, 2927,
1589, 1474, 1422, 1265, 1216, 1141, 1097, 896 cm-1.
Synthesis
of
5-fluoro-2'-hydroxy-[1,1'-biphenyl]-2-yl
trifluoromethanesulfonate (2i). The title compound 2i was
synthesized using (5-fluoro-2-hydroxyphenyl) boronic acid and
1-bromo-2-methoxybenzene as the starting material according
to the general procedure C (eluent: petroleum ether/ethyl
acetate, 10/1, v/v) and isolated as yellow oil in 41% yield (689.4
mg). Rf = 0.47 (PE/EtOAc = 5/1). 1H NMR (400 MHz, CDCl3)
δ 7.40-7.30 (m, 2H), 7.24-7.12 (m, 3H), 7.04 (t, J = 7.5 Hz, 1H),
6.92 (d, J = 8.1 Hz, 1H), 5.07 (s, 1H) ppm. 13C{1H} NMR (100
MHz, CDCl3) δ 161.3 (d, J = 249.9 Hz), 152.6, 143.3 (d, J = 3.1
Hz), 133.7 (d, J = 8.9 Hz), 131.2, 130.7, 123.5 (d, J = 9.3 Hz),
121.5, 121.1, 119.3 (d, J = 23.8 Hz), 118.3 (q, J = 318.5 Hz),
116.3 (d, J = 23.7 Hz), 116.2 ppm. HRMS (ESI) m/z: [M - H]-
Calcd for C13H7F4O4S 335.0001; Found 335.0006. IR (neat):
3554, 1624, 1590, 1509, 1480, 1420, 1334, 1214, 1141, 1025,
879 cm-1.
Synthesis
of
(R)-2'-hydroxy-[1,1'-binaphthalen]-2-yl
trifluoromethanesulfonate (2m). The title compound 2m was
synthesized from [1,1'-binaphthalene]-2,2'-diol 1m according
to the general procedure B (eluent: petroleum ether/ethyl
acetate, 10/1, v/v) and isolated as a colorless solid in 86% yield
1
(1.08 g). m.p. 110-111 °C. Rf = 0.47 (PE/EtOAc = 5/1). H
NMR (400 MHz, d6-DMSO) δ 9.99 (s, 1H), 8.24 (d, J = 9.1 Hz,
1H), 8.13 (d, J = 8.2 Hz, 1H), 7.99 (d, J = 8.9 Hz, 1H), 7.90 (d,
J = 7.9 Hz, 1H), 7.68 (d, J = 9.1 Hz, 1H), 7.64-7.57 (m, 1H),
7.47-7.38 (m, 2H), 7.30-7.18 (m, 3H), 6.84 (d, J = 8.3 Hz, 1H)
ppm. 13C{1H} NMR (100 MHz, d6-DMSO) δ 153.6, 145.5,
133.5, 133.0, 132.4, 130.64, 130.60, 128.4, 128.1, 127.8, 127.6,
127.08, 127.06, 126.6, 126.4, 123.7, 122.7, 119.5, 118.2, 117.8
(q, J = 318.1 Hz), 111.2 ppm. HRMS (ESI) m/z: [M - H]- Calcd
for C21H12F3O4S 417.0408; Found 417.0413. IR (neat): 3539,
1706, 1622, 1598, 1508, 1471, 1420, 1347, 1216, 1068, 863 cm-1.
Synthesis
of
4-chloro-2'-hydroxy-[1,1'-biphenyl]-2-yl
trifluoromethanesulfonate (2j). The title compound 2j was
synthesized using (2-methoxyphenyl) boronic acid and 2-
bromo-5-chlorophenol as the starting material according to the
general procedure C (eluent: petroleum ether/ethyl acetate,
10/1, v/v) and isolated as colorless oil in 36% yield (634.9 mg).
Synthesis
of
(S)-7'-hydroxy-2,2',3,3'-tetrahydro-1,1'-
spirobi[inden]-7-yl trifluoro-methanesulfonate (2n). The title
compound 2n was synthesized from 2,2',3,3'-tetrahydro-1,1'-
spirobi[indene]-7,7'-diol 1n according to the general procedure
B (eluent: petroleum ether/ethyl acetate, 10/1, v/v) and
isolated as a colorless solid in 92% yield (1.06 g). m.p. 89-90 °C.
1
Rf = 0.40 (PE/EtOAc = 5/1). H NMR (400 MHz, CDCl3) δ
7.48-7.40 (m, 3H), 7.36-7.30 (m, 1H), 7.22-7.17 (m, 1H),
7.06-7.00 (m, 1H), 6.95-6.90 (m, 1H), 5.09 (s, 1H) ppm.
13C{1H} NMR (100 MHz, CDCl3) δ 152.7, 147.4, 134.8, 133.3,
131.3, 130.6, 130.2, 128.9, 122.4, 121.4, 121.0, 118.3 (q, J =
320.4 Hz), 116.2 ppm. HRMS (ESI) m/z: [M - H]- Calcd for
C13H7ClF3O4S 350.9706; Found 350.9711. IR (neat): 3555,
1602, 1561, 1481, 1424, 1333, 1216, 1139, 1084, 917, 826 cm-1.
1
Rf = 0.42 (PE/EtOAc = 5/1). H NMR (400 MHz, CDCl3) δ
7.32-7.27 (m, 2H), 7.18-7.08 (m, 2H), 6.88 (d, J = 7.4 Hz, 1H),
6.56 (d, J = 7.9 Hz, 1H), 4.34 (s, 1H), 3.16-2.97 (m, 4H), 2.41-
2.21 (m, 4H) ppm. 13C{1H} NMR (100 MHz, CDCl3) δ 152.0,
148.0, 146.1, 145.6, 139.6, 132.1, 129.1, 128.9, 124.6, 118.6,
118.0 (q, J = 318.0 Hz), 117.3, 113.8, 58.9, 38.23, 38.17, 31.3,
31.1 ppm. HRMS (ESI) m/z: [M - H]- Calcd for C18H14F3O4S
383.0565; Found 383.0572. IR (neat): 3556, 2950, 1759, 1592,
1467, 1415, 1279, 1213, 1140, 991, 857 cm-1.
Synthesis
of
1-(2-hydroxyphenyl)
naphthalen-2-yl
trifluoromethanesulfonate (2k). The title compound 2k was
synthesized using (2-methoxyphenyl) boronic acid and 1-
bromonaphthalen-2-ol as the starting material according to the
general procedure C (eluent: petroleum ether/ethyl acetate,
10/1, v/v) and isolated as yellow oil in 45% yield (828.7 mg).
Synthesis of 3-hydroxynaphthalen-2-yl trifluoromethanesulfonate
(2o). The title compound 2o was synthesized from naphthalene-
2, 3-diol 1o according to the general procedure B (eluent:
ACS Paragon Plus Environment

The Journal of Organic Chemistry
petroleum ether/ethyl acetate, 10/1, v/v) and isolated as a
Page 8 of 14
123.3, 117.5, 115.7, 100.6, 20.1, 19.6 ppm. HRMS (ESI) m/z:
[M - H]- Calcd for C15H12NO2 238.0868; Found 238.0873. IR
(neat): 3224, 2924, 2231, 1595, 1502, 1477, 1408, 1246, 1134,
1045, 817 cm-1.
1
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colorless solid in 86% yield (753.9 mg). m.p. 72-73 °C. Rf = 0.37
(PE/EtOAc = 5/1). 1H NMR (400 MHz, CDCl3) δ 7.77 (d, J =
8.1 Hz, 1H), 7.73 (s, 1H), 7.68 (d, J = 8.2 Hz, 1H), 7.49 (t, J =
7.5 Hz, 1H), 7.42 (t, J = 7.5 Hz, 1H), 7.33 (s, 1H), 5.62 (s, 1H)
ppm. 13C{1H} NMR (100 MHz, CDCl3) δ 145.2, 138.0, 133.3,
128.2, 127.8, 127.6, 126.3, 125.2, 120.8, 18.7 (q, J = 320.6 Hz),
113.1 ppm. HRMS (ESI) m/z: [M - H]- Calcd for C11H6F3O4S
290.9939; Found 290.9944. IR (neat): 3531, 1769, 1605, 1530,
1478, 1420, 1364, 1226, 1139, 1070, 889 cm-1.
Synthesis
carbonitrile (3c). The title compound 3c was synthesized from 2c
according to the general procedure (eluent:
of
5,5'-diethyl-2,2'-dihydroxy-[1,1'-biphenyl]-3-
dichloromethane/ethyl acetate, from 20/1 to 10/1, v/v) and
isolated as a colorless solid in 79% yield (126.7 mg). m.p. 148-
149 °C. Rf = 0.33 (CH2Cl2/EtOAc = 10/1). 1H NMR (400 MHz,
d6-DMSO) δ 9.53 (br s, 1H), 7.43 (d, J = 2.0 Hz, 1H), 7.29 (d,
J = 2.1 Hz, 1H), 7.07 (dd, J = 8.2, 2.0 Hz, 1H), 7.00 (d, J = 2.0
Hz, 1H), 6.88 (d, J = 8.2 Hz, 1H), 2.61-2.51 (m, 4H), 1.16 (t, J
= 7.6 Hz, 6H) ppm. 13C{1H} NMR (100 MHz, d6-DMSO) δ
155.0, 152.2, 136.2, 135.7, 134.6, 130.7, 130.6, 128.54, 128.46,
123.4, 117.6, 115.8, 100.7, 27.4, 26.9, 15.9, 15.5 ppm. HRMS
(ESI) m/z: [M - H]- Calcd for C17H16NO2 266.1181; Found
266.1186. IR (neat): 3240, 2931, 2872, 2234, 1594, 1503, 1476,
1416, 1234, 1135, 824 cm-1.
9
Synthesis of 8-hydroxynaphthalen-1-yl trifluoromethanesulfonate
(2p). The title compound 2p was synthesized from naphthalene-
1,8-diol 1p according to the general procedure B (eluent:
petroleum ether/ethyl acetate, 10/1, v/v) and isolated as a
colorless solid in 74% yield (1.08 g). m.p. 142-143 °C. Rf = 0.46
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1
(PE/EtOAc = 5/1). H NMR (400 MHz, d6-DMSO) δ 10.87
(s, 1H), 7.93 (d, J = 8.2 Hz, 1H), 7.54-7.40 (m, 3H), 7.36 (d, J
= 7.6 Hz, 1H), 7.05-6.99 (m, 1H) ppm. 13C{1H} NMR (100
MHz, d6-DMSO) δ 152.3, 145.3, 137.0, 129.0, 128.1, 125.6,
118.8, 118.5 (q, J = 319.0 Hz), 118.3, 117.4, 111.4 ppm. HRMS
(ESI) m/z: [M - H]- Calcd for C11H6F3O4S 290.9939; Found
290.9944. IR (neat): 3492, 1759, 1605, 1473, 1409, 1368, 1218,
1138, 1057, 870, 821 cm-1.
Synthesis
of
2,2'-dihydroxy-5,5'-dipentyl-[1,1'-biphenyl]-3-
carbonitrile (3d). The title compound 3d was synthesized from
2d according to the general procedure (eluent:
dichloromethane/ethyl acetate, from 20/1 to 10/1, v/v) and
isolated as a colorless solid in 75% yield (158.2 mg). m.p. 109-
110 °C. Rf = 0.34 (CH2Cl2/EtOAc = 10/1). 1H NMR (400 MHz,
CDCl3) δ 7.37 (d, J = 2.1 Hz, 1H), 7.32 (d, J = 2.1 Hz, 1H),
7.14 (dd, J = 8.2, 2.1 Hz, 1H), 7.05 (d, J = 2.0 Hz, 1H), 6.93 (d,
J = 8.2 Hz, 1H), 2.64-2.54 (m, 4H), 1.67-1.55 (m, 4H), 1.38-
1.29 (m, 8H), 0.94-0.86 (m, 6H) ppm. 13C{1H} NMR (100
MHz, CDCl3) δ 154.7, 149.8, 136.5, 136.3, 136.0, 131.8, 131.4,
129.9, 127.8, 123.0, 117.4, 116.1, 101.3, 35.0, 34.6, 31.4, 31.3,
31.2, 30.9, 22.44, 22.39, 14.0, 13.9 ppm. HRMS (ESI) m/z: [M
- H]- Calcd for C23H28NO2 350.2120; Found 350.2125. IR
(neat): 3236, 2928, 2856, 2236, 1593, 1503, 1468, 1415, 1217,
1135, 883 cm-1.
General Procedure for Lewis Acid-Mediated Cyanation Reaction.
To a solution of 2'-hydroxy-1,1'-biphenyl triflate 2 (0.6 mmol,
1.0 equiv), CH3SCN (0.1 mL, 1.5 mmol, 2.5 equiv) and AlCl3
(80.0 mg, 0.6 mmol) in DCE (0.6 mL) was added BCl3 (1.0 M
in dichloromethane, 1.2 mL, 1.2 mmol). The resulting reaction
o
mixture was stirred at 80 C for 24 h in an oil bath. Upon
completion, 4 M aq. NaOH (3.0 mL) was added and refluxed
for 0.5 h. After cooling, the reaction mixture was acidified with
6 M HC1 (4 mL), and then extracted with ethyl acetate (15 mL
x 3) for 3 times. The combined organic layers were washed with
water, dried over Na2SO4, filtered, and concentrated in vacuo.
The residue was purified by column chromatography on silica
gel to afford the desired product 3.
Synthesis of 4',6''-dihydroxy-[1,1':3',1'':3'',1'''-quaterphenyl]-5'-
Synthesis of 2,2'-dihydroxy-[1,1'-biphenyl]-3-carbonitrile (3a). The
title compound 3a was synthesized from 2a according to the
general procedure (eluent: dichloromethane/ethyl acetate,
from 20/1 to 10/1, v/v) and isolated as a colorless solid in 80%
yield (101.4 mg). m.p. 162-163 °C. Rf = 0.37 (CH2Cl2/EtOAc
= 10/1). 1H NMR (400 MHz, d6-DMSO) δ 9.77 (br s, 2H), 7.60
(dd, J = 7.7, 1.6 Hz, 1H), 7.43 (dd, J = 7.6, 1.7 Hz, 1H), 7.27-
7.20 (m, 1H), 7.16 (dd, J = 7.6, 1.6 Hz, 1H), 7.05 – 6.94 (m,
2H), 6.92-6.86 (m, 1H) ppm. 13C{1H} NMR (100 MHz, d6-
DMSO) δ 157.0, 154.6, 136.6, 132.2, 131.4, 129.4, 128.3, 123.4,
120.2, 119.4, 117.4, 115.8, 100.8 ppm. HRMS (ESI) m/z: [M -
H]- Calcd for C13H8NO2 210.0555; Found 210.0560. IR (neat):
3239, 2234, 1600, 1581, 1502, 1462, 1441, 1375, 1247, 1060,
750 cm-1.
carbonitrile (3e). The title compound 3e was synthesized from 2e
according
to
the
general
procedure
(eluent:
dichloromethane/ethyl acetate, from 20/1 to 10/1, v/v) and
isolated as a colorless solid in 53% yield (115.6 mg). m.p. 255-
256 °C. Rf = 0.36 (CH2Cl2/EtOAc = 10/1). 1H NMR (400 MHz,
d6-DMSO) δ 10.02 (br s, 2H), 7.96 (d, J = 2.3 Hz, 1H), 7.80 (d,
J = 2.3 Hz, 1H), 7.71 (d, J = 7.4 Hz, 2H), 7.66 (d, J = 7.4 Hz,
2H), 7.61-7.56 (m, 2H), 7.46-7.38 (m, 4H), 7.33 (t, J = 7.3 Hz,
1H), 7.28 (t, J = 7.3 Hz, 1H), 7.10 (d, J = 8.2 Hz, 1H) ppm.
13C{1H} NMR (100 MHz, d6-DMSO) δ 156.8, 154.7, 140.0,
138.2, 134.9, 132.2, 131.4, 130.1, 129.8, 129.0, 128.8, 128.7,
127.7, 127.4, 126.6, 126.5, 126.2, 123.9, 117.4, 116.5, 101.5
ppm. HRMS (ESI) m/z: [M - H]- Calcd for C25H16NO2
362.1181; Found 362.1185. IR (neat): 3436, 2217, 1601, 1509,
1483, 1448, 1392, 1264, 1133, 965, 761 cm-1.
Synthesis
of
2,2'-dihydroxy-5,5'-dimethyl-[1,1'-biphenyl]-3-
carbonitrile (3b). The title compound 3b was synthesized from
2b according to the general procedure (eluent:
dichloromethane/ethyl acetate, from 20/1 to 10/1, v/v) and
isolated as a colorless solid in 82% yield (117.7 mg). m.p. 184-
185 °C. Rf = 0.35 (CH2Cl2/EtOAc = 10/1). 1H NMR (400 MHz,
d6-DMSO) δ 9.53 (br s, 1H), 7.39 (s, 1H), 7.25 (s, 1H), 7.03
(d, J = 8.1 Hz, 1H), 6.96 (s, 1H), 6.85 (d, J = 8.2 Hz, 1H), 2.25
(s, 3H), 2.23 (s, 3H) ppm. 13C{1H} NMR (100 MHz, d6-DMSO)
δ 154.9, 152.1, 137.2, 131.74, 131.68, 129.7, 129.2, 128.3, 127.9,
Synthesis
of
4',6''-dihydroxy-3,3''',5,5'''-tetramethyl-
[1,1':3',1'':3'',1'''-quaterphenyl]-5'-carbonitrile (3f). The title
compound 3f was synthesized from 2f according to the general
procedure (eluent: dichloromethane/ethyl acetate, from 20/1
to 10/1, v/v) and isolated as a colorless solid in 45% yield
(113.3 mg). m.p. 230-231 °C. Rf = 0.34 (CH2Cl2/EtOAc =
1
10/1). H NMR (400 MHz, d6-DMSO) δ 7.76 (d, J = 2.3 Hz,
1H), 7.71 (d, J = 2.3 Hz, 1H), 7.52-7.45 (m, 2H), 7.26 (s, 2H),
7.23 (s, 2H), 6.96-6.88 (m, 3H), 2.30 (s, 12H) ppm. 13C{1H}
ACS Paragon Plus Environment

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The Journal of Organic Chemistry
NMR (100 MHz, d6-DMSO) δ 161.9, 156.4, 140.3, 138.8, 137.9,
C13H7ClNO2 244.0165; Found 244.0171. IR (neat): 3224, 2231,
1584, 1501, 1473, 1460, 1363, 1268, 1097, 907, 791 cm-1.
1
2
3
4
5
6
7
8
137.7, 134.0, 130.9, 129.9, 129.8, 129.1, 128.9, 128.2, 127.8,
127.1, 126.0, 124.0, 123.9, 118.9, 117.4, 101.4, 21.1, 21.0 ppm.
HRMS (ESI) m/z: [M - H]- Calcd for C29H24NO2 418.1807;
Found 418.1811. IR (neat): 3436, 2921, 2220, 1602, 1494,
1462, 1443, 1378, 1275, 1027, 846 cm-1.
Synthesis of 2-hydroxy-3-(2-hydroxynaphthalen-1-yl)benzonitrile
(3k). The title compound 3k was synthesized from 2k according
to the general procedure (eluent: dichloromethane/ethyl
acetate, from 20/1 to 10/1, v/v) and isolated as a colorless solid
in 65% yield (101.9 mg). m.p. 119-120 °C. Rf = 0.35
Synthesis of 2,2'-dihydroxy-5-methyl-[1,1'-biphenyl]-3-carbonitrile
(3g). The title compound 3g was synthesized from 2g according
to the general procedure (eluent: dichloromethane/ethyl
acetate, from 20/1 to 10/1, v/v) and isolated as a colorless solid
in 75% yield (101.3 mg). m.p. 99-100 °C. Rf = 0.35
1
(CH2Cl2/EtOAc = 10/1). H NMR (400 MHz, d6-DMSO) δ
9.70 (br s, 2H), 7.85 (d, J = 8.7 Hz, 2H), 7.70 (dd, J = 7.7, 1.3
Hz, 1H), 7.40-7.26 (m, 4H), 7.16 (d, J = 8.2 Hz, 1H), 7.08 (t, J
= 7.6 Hz, 1H) ppm. 13C{1H} NMR (100 MHz, d6-DMSO) δ
158.0, 153.1, 137.8, 133.6, 132.6, 129.6, 128.1, 128.1, 126.4,
125.3, 123.6, 122.6, 120.0, 118.6, 117.5, 115.0, 100.4 ppm.
HRMS (ESI) m/z: [M - H]- Calcd for C17H10NO2 260.0712;
Found 260.0717. IR (neat): 3408, 2228, 1621, 1583, 1511,
1458, 1343, 1262, 1043, 818, 747 cm-1.
9
10
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1
(CH2Cl2/EtOAc = 10/1). H NMR (400 MHz, d6-DMSO) δ
9.64 (br s, 2H), 7.39 (s, 1H), 7.28-7.20 (m, 2H), 7.16 (d, J =
7.3 Hz, 1H), 6.99 (d, J = 8.0 Hz, 1H), 6.89 (t, J = 7.4 Hz, 1H),
2.25 (s, 3H) ppm. 13C{1H} NMR (100 MHz, d6-DMSO) δ
154.9, 154.5, 137.3, 131.9, 131.4, 129.33, 129.30, 128.3, 123.7,
119.5, 117.6, 115.9, 100.7, 19.6 ppm. HRMS (ESI) m/z: [M -
H]- Calcd for C14H10NO2 224.0712; Found 224.0718. IR (neat):
3423, 2924, 2220, 1607, 1474, 1439, 1297, 1266, 1118, 1043,
867 cm-1.
Synthesis of (S)-2,2'-dihydroxy-5,5',6,6',7,7',8,8'-octahydro-[1,1'-
binaphthalene]-3-carbonitrile (3l). The title compound 3l was
synthesized from 2l according to the general procedure (eluent:
dichloromethane/ethyl acetate, from 20/1 to 10/1, v/v) and
isolated as a colorless solid in 78% yield (149.5 mg). m.p. 185-
186 °C. Rf = 0.33 (CH2Cl2/EtOAc = 10/1). The ee was
determined by HPLC (>99% ee, Chiralpak IA-H, n-hexane/i-
Synthesis of 2,2'-dihydroxy-5'-methyl-[1,1'-biphenyl]-3-carbonitrile
(3h). The title compound 3h was synthesized from 2h according
to the general procedure (eluent: dichloromethane/ethyl
acetate, from 20/1 to 10/1, v/v) and isolated as a colorless solid
in 72% yield (97.3 mg). m.p. 164-165 °C. Rf = 0.34
(CH2Cl2/EtOAc = 10/1). 1H NMR (400 MHz, d6-DMSO) δ
7.59 (dd, J = 7.7, 1.6 Hz, 1H), 7.42 (dd, J = 7.6, 1.6 Hz, 1H),
7.06-6.95 (m, 3H), 6.85 (d, J = 8.2 Hz, 1H), 2.23 (s, 3H) ppm.
13C{1H} NMR (100 MHz, d6-DMSO) δ 157.2, 152.2, 136.5,
132.1, 131.7, 129.8, 128.5, 127.9, 123.2, 120.1, 117.5, 115.8,
100.9, 20.1 ppm. HRMS (ESI) m/z: [M - H]- Calcd for
C14H10NO2 224.0712; Found 224.0718. IR (neat): 3200, 2923,
2231, 1599, 1511, 1462, 1408, 1274, 1197, 1138, 817 cm-1.
1
PrOH = 90/10, 1.0 mL/min, n = 220 nm, tr = 12.0 min). H
NMR (400 MHz, CDCl3) δ 7.30 (s, 1H), 7.02 (d, J = 8.2 Hz,
1H), 6.77 (d, J = 8.3 Hz, 1H), 5.53 (br s, 1H), 5.03 (br s, 1H),
2.81-2.67 (m, 4H), 2.41-2.00 (m, 4H), 1.77-1.62 (m, 8H) ppm.
13C{1H} NMR (100 MHz, CDCl3) δ 153.4, 151.3, 144.0, 137.0,
133.3, 131.4, 130.9, 130.5, 121.7, 117.3, 116.4, 113.6, 96.9, 29.0,
28.8, 27.5, 26.9, 22.8, 22.7, 22.3, 22.3 ppm. HRMS (ESI) m/z:
[M - H]- Calcd for C21H20NO2 318.1494; Found 318.1499. IR
(neat): 3492, 2931, 2226, 1599, 1477, 1423, 1374, 1280, 1155,
1041, 940 cm-1.
Synthesis of (R)-2,2'-dihydroxy-[1,1'-binaphthalene]-3-carbonitrile
(3m). The title compound 3m was synthesized from 2m
Synthesis of 5'-fluoro-2,2'-dihydroxy-[1,1'-biphenyl]-3-carbonitrile
(3i). The title compound 3i was synthesized from 2i according
to the general procedure (eluent: dichloromethane/ethyl
acetate, from 20/1 to 10/1, v/v) and isolated as a colorless solid
in 57% yield (78.4 mg). m.p. 187-188 °C. Rf = 0.31
according
to
the
general
procedure
(eluent:
dichloromethane/ethyl acetate, from 20/1 to 10/1, v/v) and
isolated as a yellow solid in 31% yield (57.9 mg). m.p. 235-
236 °C. Rf = 0.37 (CH2Cl2/EtOAc = 10/1). The ee was
determined by HPLC (>99% ee, Chiralpak IA-H, n-hexane/i-
1
(CH2Cl2/EtOAc = 10/1). H NMR (400 MHz, d6-DMSO) δ
9.76 (br s, 2H), 7.61 (dd, J = 7.7, 1.7 Hz, 1H), 7.44 (dd, J = 7.6,
1.7 Hz, 1H), 7.10-6.98 (m, 3H), 6.97-6.91 (m, 1H) ppm.
13C{1H} NMR (100 MHz, DMSO-d6) δ 157.0, 155.4 (d, J =
234.3 Hz), 151.1 (d, J = 1.6 Hz), 136.6, 132.6, 127.2, 124.4 (d,
J = 8.0 Hz), 120.1, 117.4 (d, J = 22.9 Hz), 117.35, 116.7 (d, J =
8.2 Hz), 115.6 (d, J = 22.5 Hz), 101.0 ppm. 19F{1H} NMR (376
MHz, d6-DMSO) δ -125.83 (td, J = 8.7, 5.0 Hz) ppm. HRMS
(ESI) m/z: [M - H]- Calcd for C13H7FNO2 228.0461; Found
228.0467. IR (neat): 3202, 2232, 1602, 1512, 1463, 1422, 1360,
1268, 1184, 974, 762 cm-1.
1
PrOH = 90/10, 1.0 mL/min, n = 220 nm, tr = 33.8 min). H
NMR (400 MHz, d6-DMSO) δ 9.65-9.50 (br s, 2H), 8.57 (s,
1H), 8.07-7.84 (m, 3H), 7.45-7.18 (m, 5H), 6.91 (t, J = 9.4 Hz,
2H) ppm. 13C{1H} NMR (100 MHz, d6-DMSO) δ 154.1, 152.1,
135.9, 135.5, 134.0, 130.0, 129.2, 128.8, 128.3, 128.2, 127.3,
126.5, 124.6, 124.1, 123.7, 122.6, 118.8, 117.8, 117.4, 112.0,
102.8 ppm. HRMS (ESI) m/z: [M - H]- Calcd for C21H12NO2
310.0868; Found 310.0874. IR (neat): 3357, 2233, 1622, 1596,
1505, 1453, 1434, 1378, 1274, 1045, 818 cm-1.
Synthesis
of
(S)-7,7'-dihydroxy-2,2',3,3'-tetrahydro-1,1'-
Synthesis of 4'-chloro-2,2'-dihydroxy-[1,1'-biphenyl]-3-carbonitrile
(3j). The title compound 3j was synthesized from 2j according
to the general procedure (eluent: dichloromethane/ethyl
acetate, from 20/1 to 10/1, v/v) and isolated as a colorless solid
in 55% yield (81.1 mg). m.p. 171-172 °C. Rf = 0.31
spirobi[indene]-6-carbonitrile (3n). The title compound 3n was
synthesized from 2n according to the general procedure (eluent:
dichloromethane/ethyl acetate, from 20/1 to 10/1, v/v) and
isolated as a colorless solid in 75% yield (124.8 mg). m.p. 214-
215 °C. Rf = 0.35 (CH2Cl2/EtOAc = 10/1). The ee was
determined by HPLC (>99% ee, Chiralpak IA-H, n-hexane/i-
1
(CH2Cl2/EtOAc = 10/1). H NMR (400 MHz, d6-DMSO) δ
10.00 (br s, 1H), 7.60 (dd, J = 7.7, 1.6 Hz, 1H), 7.38 (dd, J =
7.6, 1.6 Hz, 1H), 7.14 (d, J = 8.1 Hz, 1H), 7.04-6.90 (m, 3H)
ppm. 13C{1H} NMR (100 MHz, d6-DMSO) δ 157.1, 156.0,
136.5, 133.1, 132.6, 132.5, 127.1, 122.6, 120.0, 119.0, 117.3,
115.5, 100.7 ppm. HRMS (ESI) m/z: [M - H]- Calcd for
1
PrOH = 90/10, 1.0 mL/min, n = 220 nm, tr = 10.2 min). H
NMR (400 MHz, d6-DMSO) δ 9.52 (s, 1H), 8.89 (s, 1H), 7.35
(d, J = 7.8 Hz, 1H), 6.95 (t, J = 7.6 Hz, 1H), 6.87 (d, J = 7.8 Hz,
1H), 6.67 (d, J = 7.3 Hz, 1H), 6.51 (d, J = 7.8 Hz, 1H), 3.03-
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 14
2.85 (m, 4H), 2.26-2.05 (m, 4H) ppm. 13C{1H} NMR (100
Found 315.9897.IR (neat): 3205, 2236, 1568, 1508, 1457, 1425,
1242, 1141, 1019, 866, 785 cm-1.
Gram-Scale Synthesis. To solution of 2'-hydroxy-[1,1'-
1
2
3
4
5
6
7
8
MHz, d6-DMSO) δ 155.7, 153.7, 151.4, 145.0, 137.6, 133.5,
131.7, 127.7, 117.8, 117.1, 115.1, 113.0, 98.1, 58.4, 37.5, 37.3,
31.4, 31.0 ppm. HRMS (ESI) m/z: [M - H]- Calcd for
C18H14NO2: 276.1025; Found 276.1031. IR (neat): 3478, 2942,
2228, 1612, 1591, 1465, 1444, 1285, 1204, 1000, 782 cm-1.
a
biphenyl]-2-yl trifluoromethanesulfonate 2a (3.18 g, 10.0
mmol), CH3SCN (1.69 mL, 1.83 g, 25.0 mmol) and AlCl3 (1.33
g, 10.0 mmol) in DCE (10 mL) was added BCl3 (20 mL, 20.0
mmol, 1.0 M in dichloromethane). The resulting mixture was
stirred at 80 o C for 24 h. Upon completion, 4 M aq. NaOH (50
mL) was added and refluxed for 0.5 h. After cooling, the
reaction was acidified with 6 M aq. HC1 (66 mL), and then
extracted with ethyl acetate (50 mL x 3) for 3 times. The
combined organic layers were washed with water, dried over
Na2SO4, filtered, and concentrated in vacuo. The residue was
purified by column chromatography on silica gel to afford the
desired product 3a in 71% yield (1.50 g).
Synthesis of 2,3-dihydroxy-1-naphthonitrile (3o). The title
compound 3o was synthesized from 2o according to the general
procedure (eluent: dichloromethane/ethyl acetate, from 5/1 to
3/1, v/v) and isolated as a colorless solid in 67% yield (74.5 mg).
9
1
m.p. 242-243 °C. Rf = 0.31 (CH2Cl2/EtOAc = 3/1). H NMR
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
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(400 MHz, d6-DMSO) δ 10.93 (br s, 2H), 7.75 (d, J = 8.2 Hz,
2H), 7.49-7.33 (m, 3H) ppm. 13C{1H} NMR (100 MHz, d6-
DMSO) δ 153.7, 145.7, 128.0, 127.2, 126.7, 125.6, 124.6, 122.4,
115.9, 114.2, 92.1 ppm. HRMS (ESI) m/z: [M - H]- Calcd for
C11H6NO2 184.0399; Found 184.0405. IR (neat): 3251, 2924,
2226, 1607, 1526, 1495, 1458, 1355, 1283, 1211, 927 cm-1.
Synthesis of 2,2'-dimethoxy-[1,1'-biphenyl]-3-carbonitrile (4) To a
solution of 3a (1.06 g, 5.0 mmol) in DMF (20 mL) was added
potassium carbonate (2.76 g, 20.0 mmol). After stirring for 30
min at room temperature, CH3I (1.24 mL, 20.0 mmol) was
added. The resulting mixture was stirred at 60 oC in an oil bath
overnight. Upon completion, the mixture was washed with
saturated aqueous ammonium chloride (60 mL) and water (60
mL), and extracted with ethyl acetate (30 mL x 3). The
combined organic layers were dried over Na2SO4, filtered, and
concentrated under vacuo. The residue was purified by column
chromatography on silica gel (petroleum ether/ethyl acetate =
10/1) to give the desired product 4 as a colorless solid in 87%
yield (1.04 g). m.p. 73-74 °C. Rf = 0.48 (PE/EtOAc = 5/1). 1H
NMR (400 MHz, CDCl3) δ 7.57 (dd, J = 7.7, 1.6 Hz, 1H), 7.48
(dd, J = 7.7, 1.6 Hz, 1H), 7.42-7.36 (m, 1H), 7.23 (dd, J = 7.4,
1.5 Hz, 1H), 7.18 (t, J = 7.7 Hz, 1H), 7.06-6.97 (m, 2H), 3.79
(s, 3H), 3.68 (s, 3H) ppm. 13C{1H} NMR (100 MHz, CDCl3)
δ 160.4, 156.6, 136.9, 132.8, 132.6, 131.0, 129.7, 125.7, 123.3,
120.6, 116.9, 111.0, 106.2, 61.5, 55.6 ppm. HRMS (ESI) m/z:
[M + Na]+ Calcd for C15H13NNaO2 262.0838; Found 262.0840.
IR (neat): 2936, 2227, 1581, 1495, 1462, 1413, 1242, 1180,
1124, 998, 753 cm-1.
Synthesis
of
3'-cyano-2'-hydroxy-[1,1'-biphenyl]-2-yl
trifluoromethanesulfonate (3a’). Following the general procedure,
4 M aq. NaOH (1.5 mL) was added and stirred for 10 min at
room temperature. 3a’ was obtained as a colorless solid in 53%
yield (109.2 mg) with 2a as the substrate using
dichloromethane/ethyl acetate (v/v, from 10/0 to 20/1) as an
1
eluent. m.p. 122-123 °C. Rf = 0.41 (CH2Cl2). H NMR (400
MHz, CDCl3) δ 7.61 (dd, J = 7.8, 1.5 Hz, 1H), 7.59-7.50 (m,
2H), 7.48-7.43 (m, 3H), 7.11 (t, J = 7.7 Hz, 1H), 5.97 (s, 1H)
ppm. 13C{1H} NMR (100 MHz, CDCl3) δ 155.7, 147.2, 136.3,
133.6, 132.3, 130.7, 129.4, 128.9, 124.0, 122.3, 121.0, 118.3 (q,
J = 320.4 Hz), 115.9, 100.6 ppm. 19F{1H} NMR (376 MHz,
CDCl3) δ -74.04 (s) ppm. HRMS (ESI) m/z: [M - H]- Calcd
for C14H7F3NO4S 342.0048; Found 342.0054. IR (neat): 3287,
2236, 1587, 1493, 1460, 1422, 1319, 1213, 1138, 1055, 895 cm-1.
Synthesis
trifluoromethanesulfonate (3o’).
of
4-cyano-3-hydroxynaphthalen-2-yl
Following the general
procedure, 4 M aq. NaOH (1.5 mL) was added and stirred for
10 min at room temperature. 3o’ was obtained as a yellow solid
in 51% yield (97.1 mg) with 2o as the substrate using
dichloromethane/ethyl acetate (v/v, from 6/1 to 3/1) as an
eluent. m.p. 189-190 °C. Rf = 0.37 (CH2Cl2/EtOAc = 3/1). 1H
NMR (400 MHz, d6-DMSO) δ 7.69 (s, 1H), 7.63 (d, J = 8.0 Hz,
1H), 7.47 (d, J = 8.3 Hz, 1H), 7.37 (t, J = 7.6 Hz, 1H), 7.01 (t,
J = 7.4 Hz, 1H) ppm. 13C{1H} NMR (100 MHz, d6-DMSO) δ
165.3, 145.7, 135.8, 128.6, 128.0, 122.3, 120.6, 120.4, 120.3,
119.9, 118.5 (q, J = 318.2 Hz), 89.6 ppm. 19F{1H} NMR (376
MHz, d6-DMSO) δ -75.04 (s) ppm. HRMS (ESI) m/z: [M - H]-
Calcd for C12H5F3NO4S: 315.9891; Found 315.9897. IR (neat):
3398, 2208, 1621, 1500, 1476, 1423, 1364, 1208, 1140, 933, 813
cm-1.
Synthesis of 2,2'-dimethoxy-[1,1'-biphenyl]-3-carbaldehyde (5).10b
To a stirred solution of 4 (71.8 mg, 0.3 mmol) in Et2O (1 mL)
at 0 ºC under nitrogen atmosphere was added dropwise
diisopropylaluminum hydride (1.0 M in hexane, 0.75 mL, 0.75
mmol). The solution was allowed to warm to room temperature
and stirred overnight. Upon completion, the reaction was
quenched with 10% aq. HCl, and stirred for 30 min at room
temperature. The reaction was extracted with ethyl acetate (10
mL x 3). The combined organic layers were washed with
saturated aqueous NaHCO3 (10 mL) and brine (10 mL), dried
over MgSO4, filtered, and concentrated in vacuo. The residue
was purified by column chromatography on silica gel
(petroleum ether/ethyl acetate = 10/1) to afford the desired
product 5 as a colorless solid in 52% yield (37.8 mg). m.p. 95-
Synthesis
of
7-cyano-8-hydroxynaphthalen-1-yl
trifluoromethanesulfonate (3p’) Following the general procedure
D, 4 M aq. NaOH (1.5 mL) was added and stirred for 10 min at
room temperature. 3p’ was obtained as a yellow solid in 50%
yield (95.2 mg) with 2p as the substrate. m.p. 160-161 °C. Rf =
0.43 (CH2Cl2/EtOAc = 10/1).1H NMR (400 MHz, d6-DMSO)
δ 12.27 (br s, 1H), 8.06 (d, J = 8.2 Hz, 1H), 7.74 (t, J = 8.0 Hz,
1H), 7.69-7.62 (m, 2H), 7.56 (d, J = 7.7 Hz, 1H) ppm. 13C{1H}
NMR (100 MHz, d6-DMSO) δ 156.8, 145.2, 138.3, 129.5, 129.3,
128.8, 120.9, 120.7, 118.7, 118.4 (q, J = 319.2 Hz), 117.1, 97.4
ppm. 19F{1H} NMR (376 MHz, d6-DMSO) δ -73.12 (s) ppm.
HRMS (ESI) m/z: [M - H]- Calcd for C12H5F3NO4S 315.9891;
1
96 °C. Rf = 0.48 (PE/EtOAc = 5/1). H NMR (400 MHz,
CDCl3) δ 10.46 (s, 1H), 7.85 (dd, J = 7.7, 1.5 Hz, 1H), 7.53
(dd, J = 7.5, 1.6 Hz, 1H), 7.43-7.36 (m, 1H), 7.30 (dd, J = 7.4,
1.4 Hz, 1H), 7.24 (t, J = 7.5 Hz, 1H), 7.07-6.99 (m, 2H), 3.80
(s, 3H), 3.52 (s, 3H) ppm. 13C{1H} NMR (100 MHz, CDCl3)
δ 190.4, 161.4, 156.7, 138.5, 132.8, 131.1, 129.4, 129.2, 127.5,
126.2, 123.6, 120.6, 111.1, 62.5, 55.6 ppm. HRMS (ESI) m/z:
[M + Na]+ Calcd for C15H14NaO3 265.0835; Found 265.0836.
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The Journal of Organic Chemistry
IR (neat): 2929, 1685, 1578, 1496, 1467, 1420, 1381, 1240,
128.9, 126.8, 123.3, 120.5, 111.1, 61.4, 55.6, 30.9 ppm. HRMS
1072, 999, 752 cm-1.
(ESI) m/z: [M + H]+ Calcd for C16H17O3 257.1172; Found
257.1173. IR (neat): 2931, 1677, 1578, 1497, 1464, 1412, 1355,
1239, 1117, 1004, 754 cm-1.
1
2
3
4
5
6
7
8
Synthesis of 2,2'-dimethoxy-[1,1'-biphenyl]-3-carboxylic acid (6).26
To a Schlenk tube equipped with a magnetic stir bar was
charged with 5 (71.8 mg, 0.3 mmol). The tube was added EtOH
(2.4 mL) and KOH (2.4 mL, 34% aqueous solution) via syringe.
Synthesis of (2,2'-dimethoxy-[1,1'-biphenyl]-3-yl)methanamine
(9).10b An oven-dried Schlenk tube equipped with a magnetic
stir bar was charged with LiAlH4 (34.2 mg, 0.9 mmol, 3.0 equiv)
and Et2O (1.2 mL) under N2 atmosphere. The resulting
mixture was cooled to -35 °C, and a solution of 5 (71.8 mg, 0.3
mmol) in 1.2 mL of Et2O (-35 °C) was then added dropwise.
The grey suspension was stirred overnight. The reaction was
cooled to 0 °C, and H2O (0.12 mL) was added, followed by aq.
NaOH (0.12 mL, 2 M) and H2O (0.2 mL). The suspension was
filtered and washed with ethyl acetate (30 mL). The filtrate was
washed with brine, dried over MgSO4, filtered, and
concentrated in vacuo. The residue was purified by column
o
The resulting reaction mixture was allowed to heat to 80 C in
an oil bath and stirred overnight. After cooling, the reaction
mixture was acidified with 2 M aq. HCl (2 M), then extracted
with ethyl acetate (10 mL x 3). The combined organic layers
were washed with brine, dried over MgSO4, filtered, and
concentrated in vacuo. The residue was purified by column
chromatography on silica gel (petroleum ether/ethyl acetate
=4/1) to afford 6 as a colorless solid in 84% yield (65.1 mg).
m.p. 114-115 °C. Rf = 0.30 (PE/EtOAc = 2/1). 1H NMR (400
MHz, CDCl3) δ 8.14 (dd, J = 7.8, 1.8 Hz, 1H), 7.51 (dd, J = 7.6,
1.8 Hz, 1H), 7.43-7.38 (m, 1H), 7.31-7.25 (m, 2H), 7.07-7.00
(m, 2H), 3.80 (s, 3H), 3.52 (s, 3H) ppm. 13C{1H} NMR (100
MHz, CDCl3) δ 166.0, 157.2, 156.5, 137.9, 132.0, 131.9, 131.0,
129.8, 125.6, 124.4, 121.6, 120.7, 111.2, 61.9, 55.6 ppm.
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
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
chromatography
on
silica
gel
(methanol/triethylamine/dichloromethane
=
1/1/100) to
afford 9 as colorless oil in 84% yield (61.3 mg). Rf = 0.39
(MeOH/Et3N/CH2Cl2 = 0.1/ 0.1/5). 1H NMR (400 MHz,
CDCl3) δ 7.35 (t, J = 7.9 Hz, 1H), 7.32-7.27 (m, 2H), 7.19 (d,
J = 7.3 Hz, 1H), 7.12 (t, J = 7.5 Hz, 1H), 7.05-6.97 (m, 2H),
3.90 (s, 2H), 3.78 (s, 3H), 3.39 (s, 3H) ppm. 13C{1H} NMR
(100 MHz, CDCl3) δ 156.7, 156.1, 136.1, 131.6, 131.3, 130.9,
128.8, 127.9, 127.6, 123.4, 120.4, 111.0, 60.5, 55.6, 42.3 ppm.
HRMS (ESI) m/z: [M + H]+ Calcd for C15H18NO2 244.1332;
Found 244.1333. IR (neat): 3368, 2927, 2853, 1580, 1499,
1462, 1421, 1239, 1123, 1009, 754 cm-1.
Synthesis of 2,2'-dimethoxy-[1,1'-biphenyl]-3-carboxamide (7).10b
t
To a solution of 5 (71.8 mg, 0.3 mmol) in BuOH (6 mL) was
added solid KOH (253.0 mg, 4.5 mmol) in a N2-filled glovebox.
The reaction was heated to 60 ºC in an oil bath and stirred
overnight. Upon completion, the reaction was extracted with
ethyl acetate (10 mL x 3). The combined organic layers were
washed with brine, dried over Na2SO4, filtered, and
concentrated in vacuo. The product was purified by column
chromatography on silica gel (petroleum ether/ethyl acetate =
2/1) to yield 7 as a colorless solid in 93% yield (71.8 mg). m.p.
138-139 °C. Rf = 0.31 (PE/EtOAc = 1/1). 1H NMR (400 MHz,
d6-DMSO) δ 7.75 (br s, 1H), 7.61 (dd, J = 7.5, 1.4 Hz, 1H),
7.53 (br s, 1H), 7.41-7.35 (m, 1H), 7.27 (dd, J = 7.5, 1.8 Hz,
1H), 7.22-7.15 (m, 2H), 7.11 (d, J = 8.2 Hz, 1H), 7.01 (t, J =
7.4 Hz, 1H), 3.72 (s, 3H), 3.42 (s, 3H) ppm. 13C{1H} NMR
(100 MHz, d6-DMSO) δ 167.7, 156.5, 155.5, 133.8, 132.4,
130.9, 129.22, 129.16, 129.0, 126.6, 123.1, 120.2, 111.3, 61.0,
55.4 ppm. HRMS (ESI) m/z: [M + H]+ Calcd for C15H16NO3
258.1125; Found 258.1126. IR (neat): 3448, 2935, 1665, 1572,
1497, 1466, 1383, 1240, 1123, 1024, 756 cm-1.
Synthesis of 1-(2,2'-dimethoxy-[1,1'-biphenyl]-3-yl) ethan-1-one
(8).10b To a Schlenk tube equipped with a magnetic stir bar was
charged with 4 (71.8 mg, 0.3 mmol) and dry Et2O (1.8 mL).The
tube was sealed and purged with N2. MeMgBr (0.3 mL, 0.9
mmol, 3 M in ether) was added dropwise. The resulting mixture
was refluxed in an oil bath for 48 h. After cooling to room
temperature, the reaction was added to a mixture of Et2O (3.6
mL), ice water (3 mL), and HCl (10% aq., 3 mL) and stirred at
room temperature for 0.5 h. The reaction mixture was then
extracted with ethyl acetate (10 mL x 3). The combined organic
layers were washed with saturated aqueous NaHCO3 and brine,
dried over MgSO4, filtered, and concentrated in vacuo. The
residue was purified by column chromatography on silica gel
(petroleum ether/ethyl acetate = 10/1) to afford 8 as a yellow
solid in 91% yield (70.0 mg). m.p. 92-93 °C. Rf = 0.46
(PE/EtOAc = 5/1). 1H NMR (400 MHz, CDCl3) δ 7.63 (dd, J
= 7.7, 1.8 Hz, 1H), 7.43-7.34 (m, 2H), 7.29 (dd, J = 7.4, 1.7 Hz,
1H), 7.18 (t, J = 7.6 Hz, 1H), 7.06-6.99 (m, 2H), 3.79 (s, 3H),
3.43 (s, 3H), 2.66 (s, 3H) ppm. 13C{1H} NMR (100 MHz,
CDCl3) δ 200.8, 157.4, 156.7, 135.9, 133.3, 132.6, 131.2, 129.1,
Synthesis of 2'-methoxy-2-(((1R, 2S, 4S)-1,3,3-trimethylbicyclo
[2.2.1] heptan-2-yl) peroxy)-[1,1'-biphenyl]-3-carbonitrile (10).11
An oven-dried vial equipped with a magnetic stir bar was
charged with 5 (119.7 mg, 0.5 mmol). The vial was then moved
into a N2 filled glovebox. KOtBu (112.2 mg, 1.0 mmol), (+)-
fenchol (1.0 mmol), and 1, 4-dioxane (0.5 mL) were added to
the vial. After stirring 80 °C in an oil bath for 16 h, the reaction
mixture was diluted with Et2O (3 mL), filtered through a plug
of silica gel, washed with THF. The filtrate was concentrated in
vacuo and purified by column chromatography on silica gel
(petroleum ether/ethyl acetate = 10/1) to provide 10 as
colorless oil in 50% yield (90.4 mg). Rf = 0.43 (PE/EtOAc =
5/1). 1H NMR (400 MHz, CDCl3) δ 7.51 (dd, J = 7.6, 1.4 Hz,
1H), 7.41-7.33 (m, 2H), 7.21-7.13 (m, 1H), 7.10-6.93 (m, 3H),
3.77 (s, 3H), 1.69-1.58 (m, 1H), 1.51 (s, 1H), 1.38-1.18 (m,
4H), 0.98-0.86 (m, 2H), 0.83 (s, 3H), 0.79 (s, 3H), 0.68-0.47
(m, 3H) ppm. 13C{1H} NMR (100 MHz, CDCl3) δ 160.0, 156.5,
137.4, 133.0, 131.4, 129.6, 126.8, 124.4, 123.9, 121.8, 120.5,
118.0, 110.8, 105.8, 55.2, 50.1, 48.2, 41.6, 39.8, 29.2, 26.1, 25.6,
20.7, 19.9 ppm. HRMS (ESI) m/z: [M + H]+ Calcd for
C24H28NO2 362.2115; Found 362.2116. IR (neat): 2956, 2872,
2227, 1735, 1581, 1497, 1464, 1367, 1242, 1030, 753 cm-1.
Synthesis of (S)-3'-(4-(tert-butyl)-4,5-dihydrooxazol-2-yl)-2'-
hydroxy-[1,1'-biphenyl]-2-yl trifluoromethanesulfonate (11).12 An
oven-dried vial equipped with a magnetic stir bar was charged
with 3a’ (103.0 mg, 0.3 mmol). The vial was then moved into a
N2 filled glovebox. (S)-2-Amino-3, 3-dimethylbutan-1-ol (70.3
mg, 0.6 mmol), ZnCl2 (41.0 mg, 0.3 mmol), and PhCl (1.2 mL)
were added to the vial. After stirring at 131 °C in an oil bath for
3 days, the reaction was quenched with water (1 mL) and
extracted with CH2Cl2 (10 mL x 3). The combined organic layer
was washed with water (10 mL) and brine (10 mL), dried over
Na2SO4, filtered, and concentrated under vacuo. The residue
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 14
Wu Zhang − College of Chemistry and Chemical Engineering,
Hunan University, Changsha 410082, People’s Republic of China
was purified by column chromatography on silica gel
(petroleum ether-ethyl acetate = 6/1) to afford 11 as a colorless
solid in 90% yield (119.7 mg). m.p. 104-105 °C. Rf = 0.53
(PE/EtOAc = 3/1). The ee was determined by HPLC (>99%
ee, Chiralpak IA-H, n-hexane/i-PrOH = 95/5, 0.5 mL/min, n =
1
2
3
4
5
6
7
8
Notes
The authors declare no competing financial interest.
1
220 nm, tmin = 7.9 min, tmax = 8.7 min). H NMR (400 MHz,
ACKNOWLEDGMENT
CDCl3) δ 13.02 (s, 1H), 7.77 (d, J = 7.7 Hz, 1H), 7.57-7.37 (m,
5H), 6.99 (t, J = 7.6 Hz, 1H), 4.40 (t, J = 9.3 Hz, 1H), 4.26 (t,
J = 8.2 Hz, 1H), 4.15 (t, J = 8.9 Hz, 1H), 0.95 (s, 9H) ppm.
13C{1H} NMR (100 MHz, CDCl3) δ 165.1, 157.5, 147.5, 134.8,
132.5, 131.8, 129.2, 128.6, 128.1, 123.6, 121.5, 118.4 (q, J =
318.4 Hz), 118.2, 110.8, 74.9, 68.2, 33.7, 25.6 ppm. HRMS
(ESI) m/z: [M + H]+ Calcd for C20H21F3NO5S 444.1087;
Found 444.1088. IR (neat): 2960, 2871, 1641, 1576, 1453,
1422, 1370, 1209, 1143, 890, 755 cm-1.
This work was supported by financial support from the National
Natural Science Foundation of China (Grant No. 21702056,
21971059, and 21702055), the National Program for Thousand
Young Talents of China and the Fundamental Research Funds for
the Central Universities.
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REFERENCES
(1) (a) Kozlowski, M. C.; Morgan, B. J.; Linton, E. C. Total
synthesis of chiral biaryl natural products by asymmetric biaryl
coupling. Chem. Soc. Rev. 2009, 38, 3193−3207. (b)
Bringmann, G.; Gulder, T.; Gulder, T. A. M.; Breuning, M.
Atroposelective total synthesis of axially chiral biaryl natural
products. Chem. Rev. 2011, 111, 563−639. (c) Zask, A.;
Murphy, J. E.; Ellestad, G. A. Biological stereoselectivity of
atropisomeric natural products and drugs. Chirality 2013, 25,
265−274. (d) Cui, Y.; Lee, S. J.; Lin, W. Interlocked chiral
nanotubes assembled from quintuple helices. J. Am. Chem. Soc.
2003, 125, 6014−6015. (e) Li, Q.; Green, L.; Venkataraman,
N.; Shiyanovskaya, I.; Khan, A. Reversible photoswitchable
axially chiral dopants with high helical twisting power. J. Am.
Chem. Soc. 2007, 129, 12908−12909. (f) Pu, L.
Enantioselective fluorescent sensors: a tale of BINOL. Acc.
Chem. Res. 2012, 45, 150−163. (g) Ogura, T.; Usuki, T. Total
synthesis of acerogenins E, G and K, and centrolobol.
Tetrahedron 2013, 69, 2807−2815. (h) Hsiao, C.; Hsiao, G.;
Chen, W.; Wang, S.; Chiang, C.; Liu, L.; Guh, J.; Lee, T.;
Chung, C. Cephalochromin induces G0/G1 cell cycle arrest
and apoptosis in A549 human non-small-cell lung cancer cells
by inflicting mitochondrial disruption. J. Nat. Prod. 2014, 77,
758−765. (i) Schmidt, B.; Riemer, M. Suzuki−Miyaura
coupling of halophenols and phenol boronic acids: systematic
investigation of positional isomer effects and conclusions for
the synthesis of phytoalexins from pyrinae. J. Org. Chem. 2014,
79, 4104−4118. (j) Zhang, X.; Zhao, Y.; Bai, D.; Yuan, X.;
Cong, S. Schizandrin protects H9c2 cells against
lipopolysaccharide-induced injury by downregulating Smad3.
J. Biochem. Mol. Toxicol. 2019, 33, e22301−e22309. (k) Fayez,
S.; Li, J.; Feineis, D.; Assi, L. A.; Kaiser, M.; Brun, R.; Anany,
M. A.; Wajant, H.; Bringmann, G. A near-complete series of
four atropisomeric jozimine A2 type naphthylisoquinoline
dimers with antiplasmodial and cytotoxic activities and related
alkaloids from ancistrocladus abbreviatus. J. Nat. Prod. 2019,
82, 3033−3046. (l) Qi, L.; Li, S.; Xiang, S.; Wang, J.; Tan, B.
Asymmetric construction of atropisomeric biaryls via a redox
neutral cross-coupling strategy. Nat. Catal. 2019, 2, 314−323.
Synthesis of 2-(3-amino-2-benzoylbenzofuran-7-yl) phenyl
trifluoromethane-sulfonate (12).13 To a suspension of 3a’ (103.0
mg, 0.3 mmol) and potassium carbonate (83.0 mg, 0.6 mmol)
in acetone (0.6 mL) was added 2-bromoacetophenone (59.7
mg, 0.3 mmol). The resulting reaction mixture was refluxed in
an oil bath for 8 h. After cooling, the reaction mixture was
diluted with ethyl acetate (10 mL), and washed with water and
brine. The organic layer was dried over Na2SO4, filtered, and
concentrated in vacuo. The residue was purified by column
chromatography on silica gel (petroleum ether/ethyl acetate =
10/1) to afford 12 as a yellow solid in 92% yield (127.3 mg).
m.p. 132-133 °C. Rf = 0.43 (PE/EtOAc = 5/1). 1H NMR (400
MHz, CDCl3) δ 8.20 (d, J = 5.6 Hz, 2H), 7.75-7.33 (m, 10H),
6.16 (br s, 2H) ppm. 13C{1H} NMR (100 MHz, CDCl3) δ 183.0,
151.5, 147.0, 141.9, 137.4, 135.3, 132.4, 131.8, 130.9, 131.0,
129.6, 129.2, 128.4, 128.0, 122.5, 121.9, 121.3, 120.9, 120.7,
118.2 (q, J = 320.7 Hz) ppm. HRMS (ESI) m/z: [M + H]+
Calcd for C22H15F3NO5S 462.0618; Found 462.0619. IR (neat):
3325, 1629, 1576, 1493, 1422, 1351, 1215, 1140, 1069, 902, 749
cm-1.
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the ACS
Publications website.
Copies of 1H and 13C{1H} NMR data (PDF)
AUTHOR INFORMATION
Corresponding Authors
Wanxiang Zhao − State Key Laboratory of Chemo/Biosensing and
Chemometrics, College of Chemistry and Chemical Engineering,
Hunan University, Changsha 410082, People’s Republic of China;
orcid.org/0000-0002-6313-399X;
(2) (a) Feringa, B. L. Phosphoramidites: marvellous ligands in
catalytic asymmetric conjugate addition. Acc. Chem. Res. 2000,
33, 346−353. (b) Chen, Y.; Yekta, S.; Yudin, A. K. Modified
BINOL ligands in asymmetric catalysis. Chem. Rev. 2003, 103,
3155−3211. (c) Brunel, J. M. BINOL: a versatile chiral reagent.
Chem. Rev. 2005, 105, 857−897. (d) Shimizu, H.; Nagasaki, I.;
Saito. T. Recent advances in biaryl-type bisphosphine ligands.
Tetrahedron 2005, 61, 5405−5432. (e) Parmar, D.; Sugiono, E.;
Raja, S.; Rueping, M. Complete field guide to asymmetric
BINOL-phosphate derived Brønsted acid and metal catalysis:
history and classification by mode of activation; Brønsted
E-mail: zhaowanxiang@hnu.edu.cn
Wen Yang − College of Chemistry and Chemical Engineering,
Hunan University, Changsha 410082, People’s Republic of China;
orcid.org/0000-0002-3166-4171;
E-mail: yangwen@hnu.edu.cn
Authors
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acidity, hydrogen bonding, ion pairing, and metal phosphates.
from benzonitriles. Tetrahedron Lett. 2001, 42, 6991−6993. (c)
Miller, J. A.; Dankwardt, J. W. Nickel catalyzed cross-coupling
of modified alkyl and alkenyl Grignard reagents with aryl- and
heteroaryl nitriles: activtion of the C-CN bond. Tetrahedron
Lett. 2003, 44, 1907−1910. (d) Yu, D. G.; Yu, M.; Guan, B. T.;
Li, B. J.; Zheng, Y.; Wu, Z. H.; Shi, Z. J. Carbon-carbon
formation via Ni-catalyzed suzuki-miyaura coupling through C-
CN bond cleavage of aryl nitrile. Org. Lett.2009, 11, 3374−3377.
(e) Sun, M.; Zhang, H. Y.; Han, Q.; Yang, K.; Yang, S. D.
Nickel-catalyzed C−P cross-coupling by C−CN bond cleavage.
Chem. Eur. J. 2011, 17, 9566−9570. (f) Zhang, J. S.; Chen, T.;
Zhou, Y.; Yin, S. F.; Han, L. B. Catalytic sp3 C-CN bond
cleavage: Ni-mediated phosphorylation of alkylnitriles. Org.
Lett. 2018, 20, 6746−6749. (g) Tobisu, M.; Kita, Y.; Chatani, N.
Rh(I)-catalyzed silylation of aryl and alkenyl cyanides involving
the cleavage of C−C and Si−Si bonds. J. Am. Chem. Soc. 2006,
128, 8152−8153. (h) Tobisu, M.; Kita, Y.; Ano, Y.; Chatani, N.
Rhodium-catalyzed silylation and intramolecular arylation of
nitriles via the silicon-assisted cleavage of carbon-cyano bonds.
J. Am. Chem. Soc. 2008, 130, 15982−15989. (i) Tobisu, M.;
Kinuta, H.; Kita, Y.; Rémond, E.; Chatani, N. Rhodium(I)-
catalyzed borylation of nitriles through the cleavage of
carbon−cyano bonds. J. Am. Chem. Soc. 2012, 134, 115−118.
(7) (a) Sundermeier, M.; Zapf, A.; Beller, M. Palladium-catalyzed
cyanation of aryl halides: recent developments and perspectives.
Eur. J. Inorg. Chem. 2003, 3513−3526. (b) Kim, J.; Kim, H. J.;
Chang S. Synthesis of aromatic nitriles using nonmetallic
cyano-group sources. Angew. Chem., Int. Ed. 2012, 51,
11948−11959. (c) Anbarasan, P.; Schareina T.; Beller, M.
Recent developments and perspectives in palladium-catalyzed
cyanation of aryl halides: synthesis of benzonitriles. Chem. Soc.
Rev. 2011, 40, 5049−5067. (d) Schörgenhumer, J.; Waser, M.
New strategies and applications using electrophilic cyanide-
transfer reagents under transition metal-free conditions. Org.
Chem. Front. 2016, 3, 1535−1540. (e) Jia, X.; Yang, D.; Zhang,
S.; Cheng, J. Chelation-assisted palladium-catalyzed direct
cyanation of 2-arylpyridine C−H bonds. Org. Lett. 2009, 11,
4716−4719. (f) Yan, G.; Kuang, C.; Zhang, Y.; Wang, J.
Palladium-catalyzed direct cyanation of indoles with
K4[Fe(CN)6]. Org. Lett. 2010, 12, 1052−1055. (g) Anbarasan,
P.; Neumann, H.; Beller, M. A general rhodium-catalyzed
cyanation of aryl and alkenyl boronic acids. Angew. Chem., Int.
Ed. 2011, 50, 519−522. (h) Yang, Y.; Zhang, Y.; Wang, J. Lewis
acid catalyzed direct cyanation of indoles and pyrroles with N-
cyano-N-phenyl-p-toluenesulfonamide (NCTS). Org. Lett.
2011, 13, 5608−5611; (i) Jin, J.; Wen, Q.; Lu, P.; Wang Y.
Copper-catalyzed cyanation of arenes using benzyl nitrile as a
cyanide anion surrogate. Chem. Commun. 2012, 48, 9933−9935.
(j) Kou, X.; Zhao, M.; Qiao, X.; Zhu, Y.; Tong, X.; Shen, Z.
Copper-catalyzed aromatic C−H bond cyanation by C−CN
bond cleavage of inert acetonitrile. Chem. Eur. J. 2013, 19,
16880−16886. (k) Shu, Z.; Ji, W.; Wang, X.; Zhou, Y.; Zhang,
Y.; Wang, J. Iron(II)-catalyzed direct cyanation of arenes with
aryl(cyano)-iodonium triflates. Angew. Chem., Int. Ed. 2014, 53,
2186−2189. (l) Zhu, Y.; Li, L.; Shen, Z. Cu-catalyzed cyanation
of arylboronic acids with acetonitrile: a dual role of TEMPO.
Chem. Eur. J. 2015, 21, 13246−13252. (m) Zhu, Y.; Zhao, M.;
Lu, W.; Li, L.; Shen, Z. Acetonitrile as a cyanating reagent: Cu-
catalyzed cyanation of arenes. Org. Lett. 2015, 17, 2602−2605.
(n) Zhang, X.; Xia, A.; Chen, H.; Liu, Y. General and mild
nickel-catalyzed cyanation of aryl/heteroaryl chlorides with
Zn(CN)2: key roles of DMAP. Org. Lett. 2017, 19, 2118−2121.
(o) McManus, J. B.; Nicewicz, D. A. Direct C−H cyanation of
arenes via organic photoredox catalysis. J. Am. Chem. Soc. 2017,
1
2
3
4
5
6
7
8
Chem. Rev. 2014, 114, 9047−9153. (f) Xu, B.; Shi, L.; Zhang,
Y.; Wu, Z.; Fu, L.; Luo, C.; Zhang, L.; Peng Y.; Guo, Q.
Catalytic asymmetric direct α-alkylation of amino esters by
aldehydes via imine activation. Chem. Sci. 2014, 5, 1988−1991.
(g) Akiyama, T.; Mori, K. Stronger Brønsted acids: recent
progress. Chem. Rev. 2015, 115, 9277−9306. (h)Wen, W.; Chen,
L.; Luo, M.; Zhang, Y.; Chen, Y.; Ouyang, Q.; Guo, Q. Chiral
aldehyde catalysis for the catalytic asymmetric activation of
glycine esters. J. Am. Chem. Soc. 2018, 140, 9774−9780. (i)
Chen, J.; Gong, X.; Li, J.; Li, Y.; Ma, J.; Hou, C.; Zhao, G.; Yuan,
9
10
11
W.; Zhao, B. Carbonyl catalysis enables
a biomimetic
asymmetric mannich reaction. Science 2018, 360, 1438−1442.
(3) (a) Gaster, E.; Vainer, Y.; Regev, A.; Narute, S.; Sudheendran,
K.; Werbeloff, A.; Shalit, H.; Pappo, D. Significant
enhancement in the efficiency and selectivity of iron-catalyzed
oxidative cross-coupling of phenols by fluoroacohols. Angew.
Chem., Int. Ed. 2015, 54, 4198−4202. (b) Lee, Y. E.; Cao, T.;
Torruellas, C.; Kozlowski, M. C. Selective oxidative homo- and
cross-coupling of phenols with aerobic catalysts. J. Am. Chem.
Soc. 2014, 136, 6782−6785. (c) Chen, Y.; Cheng, D.; Zhang, J.;
Wang, Y.; Liu, X.; Tan, B. Atroposelective synthesis of axially
chiral biaryldiols via organocatalytic arylation of 2‑naphthols. J.
Am. Chem. Soc. 2015, 137, 15062−15065. (d) Li, S.; Zhang, J.;
Li, X.; Cheng, D.; Tan, B. Phosphoric acid-catalyzed
asymmetric synthesis of SPINOL derivatives. J. Am. Chem. Soc.
2016, 138, 16561−16566. (e) Wang, J.; Zhou, J.; Xu, C.; Sun,
H.; Kurti, L.; Xu, Q. Symmetry in cascade chirality-transfer
processes: a catalytic atroposelective direct arylation approach
to BINOL derivatives. J. Am. Chem. Soc. 2016, 138, 5202−5205.
(f) More, N. Y.; Jeganmohan, M. Solvent-controlled selective
synthesis of biphenols and quinones via oxidative coupling of
phenols. Chem. Commun. 2017, 53, 9616−9619. (g) Kang, H.;
Lee, Y. E.; Reddy, P. V. G.; Dey, S.; Allen, S. E.; Niederer, K.
A.; Sung, P.; Hewitt, K.; Torruellas, C.; Herling, M. R.;
Kozlowski, M. C. Asymmetric oxidative coupling of phenols
and hydroxycarbazoles. Org. Lett. 2017, 19, 5505−5508. (h)
Shalit, H.; Dyadyuk, A.; Pappo, D. Selective oxidative phenol
coupling by iron catalysis. J. Org. Chem. 2019, 84, 1677−1686.
(i) Reiss, H.; Shalit, H.; Vershinin, V.; More, N. Y.; Forckosh,
H.; Pappo, D. Cobalt(II)[salen]-catalyzed selective aerobic
oxidative cross-coupling between electron-rich phenols and
2‑naphthols. J. Org. Chem. 2019, 84, 7950−7960.
(4) (a) Alexakis, A.; Polet, D.;´Rosset, S.; March, S. Biphenol-
based phosphoramidite ligands for the enantioselective copper-
catalyzed conjugate addition of diethylzinc. J. Org. Chem. 2004,
69, 5660−5667. (b) Yang, J.; Wang, R.; Wang, Y.; Yao, W.; Liu,
Q.; Ye, M. Ligand-accelerated direct C-H arylation of BINOL:
a rapid one-step synthesis of racemic 3,3’-diaryl BINOLs.
Angew. Chem., Int. Ed. 2016, 55, 14116−14120. (c) Xiong X.;
Yeung, Y. Ammonium salt-catalyzed highly practical ortho-
selective monohalogenation and phenylselenation of phenols:
scope and applications. ACS Catal. 2018, 8, 4033−4043. (d)
Bisht, R.; Chaturvedi, J.; Pandey, G.; Chattopadhyay, B.
Double-fold ortho and remote C−H bond activation/borylation
of BINOL: a unified strategy for arylation of BINOL. Org. Lett.
2019, 21, 6476−6480.
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
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(5) Larcok, R. C. Comprehensive Organic Transformations: A Guide
to Functional Group Preparations, 2nd ed.; VCH: New York,
U.S.A, 1999.
(6) (a) Wen, Q.; Lu, P.; Wang, Y. Recent advances in transition-
metal-catalyzed C–CN bond activations. RSC Adv. 2014, 4,
47806−47826. (b) Miller, J. A. C-C Bond activation with
selective functionalization: reparation of unsymmetrical biaryls
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 14 of 14
139, 2880−2883. (p) Yu, L.; Chen, X.; Song, Z.; Liu, D.; Hu,
(16) Bentley, K. W.; Joyce, L. A.; Sherer, E. C.; Sheng, H.; Wolf,
1
2
3
4
5
6
7
8
L.; Yu, Y.; Tan, Z.; Gui, Q. Selective synthesis of aryl nitriles
and 3‑imino-1-oxoisoindolines via nickel-promoted C(sp2)−H
cyanations. Org. Lett. 2018, 20, 3206−3210. (q) Hayrapetyan,
D.; Rit, R. K.; Kratz, M.; Tschulik, K.; Goosen, L. J.
C.; Welch, C. J. Antenna biphenols: development of extended
wavelength chiroptical reporters. J. Org. Chem. 2016, 81,
1185−1191.
(17) Berkessel, A.; Gnther, T.; Wang, Q.; Neudorfl, J. M. Titanium
salalen catalysts based on cis-1,2-diaminocyclohexane:
enantioselective epoxidation of terminal non-conjugated
olefins with H2O2. Angew. Chem., Int. Ed. 2013, 52,
8467−8471.
(18) Gupta, P.; Rouf, A.; Shah, B. A.; Mahajan, N.; Chaubey, A.;
Taneja, S. C. Arthrobacter sp. lipase catalyzed kinetic
resolution of BINOL: the effect of substrate immobilization. J.
Mol. Catal., B Enzym. 2014, 101, 35−39.
(19) Aoyama, H.; Tokunaga, M.; Kiyosu, J.; Iwasawa, T.; Obora,
Y.; Tsuji, Y. Kinetic resolution of axially chiral 2,2’-dihydroxy-
1,1’-biaryls by palladium-catalyzed alcoholysis. J. Am. Chem.
Soc. 2005, 127, 10474−10475.
(20) Ishii, Y.; Onda, Y.; Kubo, Y. 2,2’-Biphenyldiol-bridged
bis(free base porphyrin): synthesis and chiroptical probing of
asymmetric amino alcohols. Tetrahedron Lett. 2006, 47,
8221−8225.
Electrochemical
C−H
cyanation
of
electron-rich
(hetero)arenes. Chem. Eur. J. 2018, 24, 11288−11291. (r) Gan,
Y.; Wang, G.; Xie, X.; Liu, Y. Nickel-catalyzed cyanation of
phenol derivatives with Zn(CN)2 involving C−O bond
cleavage. J. Org. Chem. 2018, 83, 14036−14048. (s) Holmberg-
Douglas, N.; Nicewicz, D. A. Arene cyanation via cation-radical
accelerated-nucleophilic aromatic substitution. Org. Lett. 2019,
21, 7114−7118. (t) Liu, L.; Yeung, K.; Yu J. Ligand-promoted
non-directed C−H cyanation of arenes. Chem. Eur. J. 2019, 25,
2199−2202.
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
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(8) (a) Adachi, M.; Sugasawa, T. Exclusive ortho cyanation and
alkylthiocarbonylation of anilines and phenols using boron
trichloride. Synth. Commun. 1990, 20, 71−84. (b) Zhang, W.;
Li, T.; Wang, Q.; Zhao, W. Lewis acid-mediated cyanation of
phenols using N-cyano-N-phenyl-p-toluenesulfonamide. Adv.
Synth. Catal. 2019, 361, 4914−4918. (c) Sardarian, A. R.;
Inaloo, I. D.; Modarresi-Alam, A. R.; Kleinpeter, E.; Schilde, U.
Metal-free regioselective monocyanation of hydroxy‑, alkoxy‑,
and benzyloxyarenes by potassium thiocyanate and silica
sulfuric acid as a cyanating agent. J. Org. Chem. 2019, 84,
1748−1756. (d) Yeung, P. Y.; So, C. M.; Lau, C. P.; Kwong, F.
Y. A mild and efficient palladium-catalyzed cyanation of aryl
(21) Sartori, G.; Maggi, R.; Bigi, F.; Arienti, A.; Casnati, G.
Oxidative coupling of dichloroaluminium phenolates: highly
selective synthesis of hydroxylated bi- and tetraaryls.
Tetrahedron 1992, 48, 9483−9494.
(22) Jiang, J.; Chen, C.; Huang, J.; Liu, H.; Cao, S.; Ji, Y.
Cu(OAc)2-catalyzed
remote
benzylic
C(sp3)–H
t
mesylates in water or BuOH/water. Angew. Chem., Int. Ed.
oxyfunctionalization for C=O formation directed by the
hindered para-hydroxyl group with ambient air as the terminal
oxidant under ligand- and additive-free conditions. Green
Chem. 2014, 16, 1248−1254.
2010, 49, 8918−8922. (e) Zhao, C.; Fang, W.; Rakesh K. P.;
Qin, H. Pd-catalyzed one-pot dehydroxylative coupling of
phenols with K4[Fe(CN)6] mediated by SO2F2 ：a practical
method for direct converting phenols to aryl nitriles. Org. Chem.
Front. 2018, 5, 1835−1839. (f) Mills, L. R.; Graham, J. M.; Patel,
P.; Rousseaux, S. A. L. Ni-catalyzed reductive cyanation of aryl
halides and phenol derivatives via transnitrilation. J. Am. Chem.
Soc. 2019, 141, 19257−19262.
(23) Fuchs, A.; Rempel, V.; Muller, C. E. The natural product
magnolol as a lead structure for the development of potent
cannabinoid receptor agonists. PLoS One 2013, 8,
e77739−e77751.
(24) Visco, M. D.; Wieting, J. M.; Mattson, A. E. Carbon−silicon
bond formation in the synthesis of benzylic silanes. Org. Lett.
2016, 18, 2883−2885.
(25) He, Z.; Shrives, H. J.; Fernandez-Salas, J. A.; Abengozar, A.;
Neufeld, J.; Yang, K.; Pulis, A. P.; Procter, D. J. Synthesis of
C2 substituted benzothiophenes via an interrupted
pummerer/[3,3]-sigmatropic/1,2-migration cascade of
benzothiophene S-oxides. Angew. Chem., Int. Ed. 2018, 57,
5759−5764.
(26) Baret, P.; Bkguin, C.; Gaude, D.; Gellon, G.; Mourral, C.;
Pierre, J.; Serratrice, G.; Favier, A. Tripodal ligands possessing
six convergent hydroxyl groups a novel family of iron
sequestering agents based on o,o’-dihydroxybiphenyl subunits.
Tetrahedron 1994, 50, 2077−2094.
(9) Thormeier, S.; Carboni, B.; Kaufmann, D. E. Chiral boronates-
versatile reagents in asymmetric synthesis. J. Organomet. Chem.
2002, 657, 136−145.
(10) (a) Danheiser, R. L.; Casebier, D. S.; Huboux, A. H. Total
synthesis of aegyptinones A and B. J. Org. Chem. 1994, 59,
4844−4848. (b) Liskey, C. W.; Liao, X.; Hartwig. J. F.
Cyanation of arenes via iridium-catalyzed borylation. J. Am.
Chem. Soc. 2010, 132, 11389−11391.
(11) Wang, X.; Li, C.; Wang, X.; Wang, Q.; Dong, X.; Duan, A.;
Zhao, W. Metal-free etherification of aryl methyl ether
derivatives by C−OMe bond cleavage. Org. Lett. 2018, 20,
4267−4272.
(12) Aspinall, H. C.; Beckingham, O.; Farrar, M. D.; Greeves, N.;
Thomas, C. D. A general and convenient route to oxazolyl
ligands. Tetrahedron Lett. 2011, 52, 5120−5123.
(13) Kumaraswamy, M. N.; Prathima Mathias, D. A.;
Chandrashekhar, C.; Vaidya, V. P. Synthesis and
pharmacological evaluation of 2-mercapto-4-substituted-
naphtho[2,1-b]furo[3,2-d]pyrimidines. Indian J. Pharm. Sci.
2006, 68, 731−736.
(14) Solinas, M.; Meadows, R. E.; Wilson, C.; Blake, A. J.;
Woodward, S. Efficient synthesis of 2-methyl derivatives of
1,1-bi(2-naphthol) and 1,1-bi(2-phenols). Eur. J. Org. Chem.
2007, 1613−1623.
(15) Schmidt, B.; Riemer, M. Microwave-promoted Pd-catalyzed
synthesis of dibenzofurans from ortho-arylphenols. J.
Heterocyclic Chem. 2017, 54, 1287−1297.
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