Chromium-Catalyzed Regioselective Kumada Arylative Cross-Coupling of C(aryl)-O Bonds with a Traceless Activation Strategy

Article abstract of DOI:10.1021/acs.joc.8b02104

We report here the chromium-catalyzed regioselective Kumada arylative cross-coupling of C(aryl)-O bonds at ambient temperature. By using a simple and low-cost chromium(II) chloride salt as a precatalyst, accompanied by a 2-pyridyl ligation, the catalytic cleavage and arylative coupling of C(aryl)-O bonds were achieved with a traceless activation strategy, overcoming the regioselectivity obstacle when several C-O bonds coexist in the Kumada coupling system.

Full text of DOI:10.1021/acs.joc.8b02104

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Note
Chromium-Catalyzed Regioselective Kumada Arylative Cross-
Coupling of C(aryl)–O Bonds with a Traceless Activation Strategy
Fei Fan, Jinghua Tang, Meiming Luo, and Xiaoming Zeng
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b02104 • Publication Date (Web): 04 Oct 2018
Downloaded from http://pubs.acs.org on October 5, 2018
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The Journal of Organic Chemistry
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Chromium-Catalyzed Regioselective Kumada Arylative Cross-
Coupling of C(aryl)–O Bonds with a Traceless Activation Strategy
Fei Fan, Jinghua Tang, Meiming Luo,* and Xiaoming Zeng*
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Key Laboratory of Green Chemistry & Technology, Ministry of Education, College of Chemistry, Sichuan University,
Chengdu 610064, China
ABSTRACT: We report here the chromium-catalyzed regioselective Kumada arylative cross-coupling of C(aryl)–O bonds at am-
bient temperature. By using a simple and low-cost chromium(II) chloride salt as precatalyst, accompanied by a 2-pyridyl ligation,
the catalytic cleavage and arylative coupling of C(aryl)–O bonds was achieved with a traceless activation strategy, allowing for
overcoming the regioselectivity obstacle when several C–O bonds are coexisted in the Kumada coupling system.
Selective cleavage and transformation of unactivated
C(aryl)–O bonds by transition metal catalysis are of high syn-
thetic interest because these bonds are common in organic
chemistry.1–7 Among compounds containing C(aryl)–O bonds,
phenol and derivatives are naturally abundant and usually
non-toxic precursors compared with their halide counterparts,
which generally derived from oxygen-rich lignocellulosic
plant biomass.8 Transition metal catalysis using phenol de-
rivatives as building blocks provides an ecologically strategy
to the construction of aromatic feedstock chemicals.9–27
However, regioselectivity in the transformation of phenol
derivatives still remains a prominent issue when several
C(aryl)–O bonds are coexisted in the reaction system
(Scheme 1a).28 A pioneering work by Kakiuchi and Chatani
demonstrated that introduction of a carbonyl ligation auxilia-
ry enabled achieving the ortho-selective cleavage and trans-
formation of unactivated C(aryl)–O bonds with ruthenium
catalysis.29–32 Analogous ortho-chelation activation strategy
has been described by Snieckus33–35 and Zeng36,37 to develop
Ru or Cr-catalyzed cross-coupling reactions, which were able
to retain the related ortho-functionality in the coupling prod-
ucts after the coupling of C(aryl)–O bonds. In contrast, meth-
odology that enables the selective cleavage of a regiospecific
C(aryl)–O bond without the ligation assistance of ortho-
auxiliary has not rarely been studied for molecule construc-
tion.
Scheme 1. Transition-Metal-Catalyzed Regioselective Trans-
formation of C(aryl)–O Bonds
(a) Transition-metal-catalyzed cleavage of unactivated C–O bonds
ortho-directing strategy
traceless activation strategy
RO
Py
RO
OR
O
H
X
OR
OR OR
OR OR
cat. [Rh] or [Ni]
RO
Multiple C–O bond-
containing aryl ethers
(X = O, Nt-Bu)
Borylation, amination
(100∼130 oC)
(Chatani, Tobisu, Wang)
cat. [Ru] or [Cr]
(Kakiuchi, Snieckus...)
Regioselectivity issue
Regioselective cleavage of unactivated C–O bonds
(b) Low-valent Cr-catalyzed regioselective Kumada arylation of C–O bonds with a traceless
activation strategy
ArMgBr
RO
O
RO
Ar
CrCl2 (10 mol %)
Py
THF, 40 o
C
Cost-effective Cr catalysis
High regioselectivity
Mild conditions
RO
Cr
Ln
O
N
[M]
ligation
via
the reduction and amination of 2-pyridyl ethers can be pro-
moted by nickel catalysis.45,46 Along with our interest in prob-
ing the catalytic activity of group 6 metal chromium,47–50 we
questioned whether it’s possible to adopt 2-pyridyl as a
traceless auxiliary to assist chromium in cleavage of the phe-
nolic C(aryl)–O bonds, while keeping other C(aryl)–O bonds
in the reaction system intact to achieve the selective trans-
formation of C–O bonds. Herein, we report a regioselective
Kumada arylative cross-coupling of C(aryl)–O bonds that was
catalyzed by chromium with a traceless activation strategy,
the formation of fundamentally important biaryl motifs
(Scheme 1b).51–56 This reaction was promoted by a simple and
low-cost chromium(II) chloride salt without the need of addi-
tional ligand or ortho-ligation auxiliary.
Recently, the use of earth-abundant, inexpensive first-row
transition metals such as nickel, iron and cobalt to replace
precious metal catalysts in developing cost-effective synthet-
ic strategies has attracted much attention.38–42 To functional-
ization of C(aryl)–O bonds, nickel usually shows unique abil-
ity in catalytic cleavage of these unactivated chemical
bonds.2–5 By contrast, the reactivity of other first-row transi-
tion metals in the cleavage of C(aryl)–O bonds have not been
widely explored.39 Interestingly, by the use of aryl 2-pyridyl
ethers combined with rhodium or nickel catalysis, Chatani
and Tobisu achieved the site-selective borylation of C(aryl)–
O bonds, and the competitive transformation of ortho-C–H
bonds did not occur (Scheme 1a).43,44 While it was found that
Based on our previous studies, the formation of low-valent
chromium species by the reduction of CrCl2 with arylmagne-
sium bromide can be considered.36,56 To probe the reactivity
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of chromium in the selective cleavage of C(aryl)–O bonds, 7- such as alkoxy, phenoxy and siloxy groups into the scaffolds
1
2
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7
8
methoxy-containing naphthyl 2-pyridyl ether derivative (1a)
was choose to treat with phenyl Grignard reagent (Table 1).
We were pleased to find that the Kumada arylative coupling
occurred, giving 2-methoxy-7-phenylnaphthalene (3a) in 60%
yield by regioselective cleavage of the C(aryl)–OPy bond (en-
try 2). It was noteworthy that the C(aryl)–O bond at C7 posi-
tion and ortho-C–H bond were retained in the reaction. With-
out chromium salt, the cross-coupling did not take place (en-
try 1). Other chromium salts such as CrCl3 and Cr(acac)3 led to
inferior results in the transformation (entries 3 and 4). How-
ever, the coupling reaction did not proceed by use of Cr(CO)6
(entry 5). Interestingly, other first-row transition metal salts
of FeCl2 and NiCl2 also possess the capability to promote the
Kumada coupling of C(aryl)–O bond, albeit giving low con-
version (entries 6 and 7). However, Lewis acid of aluminium
salt (AlCl3) completely inhibited the coupling reaction (entry
8). Good result was obtained when increasing the amount of
phenyl Grignard reagent to 3 equivalent at elevated tempera-
ture (entry 11).
of aryl 2-pyridyl ether motifs did not affect the regioselectivi-
ty of Cr-catalyzed arylative cross-coupling. Only the C(aryl)–
OPy bonds were cleaved and coupled with phenylmagnesium
bromide to form the compounds 3b–3g in preparatively use-
ful yields. The coupling using 7-hydroxyl-substituted naph-
thyl 2-pyridyl ether occurred effectively, leading to the phe-
nylated naphthol compound 3h in 80% yield. Functionalities
of alkenyl and amino groups can be well compatible with the
reaction system (3k and 3l). In addition to naphthyl 2-pyridyl
ethers, the C(aryl)–O bond on the scaffold of polycyclic aro-
matic hydrocarbon coupled with phenyl Grignard smoothly,
providing access to the coupling product 3m in excellent yield.
In addition, the imino group on aryl 2-pyridyl ether derivative
can be tolerated by the reaction system, offering a method-
ology to the synthesis of terphenyl carbaldehyde compound
after work up with acid (3n). The C–O bonds on the scaffolds
of N-heterocycles were amenable to the coupling reaction,
albeit forming the phenylated quinolone and pyridine deriva-
tives in low yields (3o and 3p).
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Having the optimal reaction conditions in hand, the scope
of aryl 2-pyridyl ether derivatives was examined. As shown in
Scheme 2, the incorporation of oxygen-containing scaffolds
Scheme 2. Chromium-Catalyzed Selective Kumada Aryla-
tive Coupling of C(aryl)–N Bonds in Aryl 2-Pyridyl Ethersa
Table 1. Optimization Reaction Conditionsa
Ph
Ph
OPy
Ph
PhMgBr
2a (X equiv)
MeO
Ph
MeO
OPy
metal salt (10 mol %)
4
THF, 12 h
1a
3a
5
(not detected)
en-
try
2a
(equiv)
yield
(3a)
metal salt
T (oC)
1
–
2
2
2
2
2
2
2
2
2
2
3
rt
ndb
2
CrCl2
CrCl3
Cr(acac)3
Cr(CO)6
FeCl2
NiCl2
AlCl3
rt
60%
26%
10%
ndb
3
rt
4
rt
5
rt
6
rt
11%
5%
ndb
7
rt
8
rt
9
MgCl2
CrCl2
CrCl2
CrCl2
rt
ndb
10
11
12
40
40
40
71%
82%
80%
aConditions: 1 (0.3 mmol), 2a (0.9 mmol), CrCl2 (0.03
mmol), 40 oC, 12 h. Isolated yields were given. bPhMgBr (1.2
mmol). cIsolated as an aldehyde after aqueous workup.
4
aReactions were conducted on a 0.3 mmol scale. Isolated
b
yields are given. Not detected. The purities of metal salts: CrCl2
(99.99%), CrCl3 (99.99%), Cr(acac)3 (97%) and FeCl2 (98%).
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desired products 3v–3aa with retaining the C–OMe bond.
Scheme 3. Chromium-Catalyzed Regioselective Cleavage
of C(aryl)–O Bondsa
1
2
Moreover, this Cr-catalyzed coupling strategy can be used to
construct 2-(3-methoxyphenyl)-9-methyl-9H-carbazole motif
at ambient temperature (3ab). Interestingly, the two C(aryl)–
OPy bonds on the scaffold of naphthalene were synchro-
nously cleaved and coupled with aryl Grignard to form bis-
functionalized naphthalene derivative 3ac in 81% yield. No-
tably, phenol-derived 2-pyridyl ethers also provided the de-
sired products 3ad-3ah in relatively low yields.
CrCl2
(10 mol %)
3
4
5
6
7
8
OPy
Ar
+
ArMgBr
R
R
THF, 40 oC, 12 h
1
2
3
NMe2
R
MeO
9
It was found that the C(aryl)–OPy bond in the scaffold of
biologically active estrone derivative was regioselective phe-
nylated, allowing for retaining other C–O bonds in the result-
ing product (Figure 1). Notably, the two different C(aryl)–O
bonds in the motif of naphthalene were sequential function-
alized by coupling with arylmagnesium bromide with Cr and
Ni catalysis, respectively. It provides a route to the synthesis
of conjugated diaryl-bearing naphthalene derivative 6.57
Moreover, the chromium-catalyzed reaction between
C(aryl)–OPy with phenylmagnesium bromide is scalable, and
can be performed on gram-scale without loss of the efficien-
cy (Figure 1).
3q: R = 4-F (81%)
3r: R = 4-Cl (88%)
3s: R = 3-Me (83%)
MeO
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3u (85%)
3t (54%)
OMe
TMS
OMe
Ph
OMe
3x (83%)
3w (85%)
3v (87%)
Me
OMe
N
OMe
R
3y: R = H (80%)
3z: R = 4-F (92%)
3aa: R = 4-Cl (83%)
3ab (75%)
R
Having these results with chromium catalysis, the prelimi-
nary mechanistic studies were next performed. It was noted
that the Kumada coupling with naphthyl 3-pyridyl ether can-
not proceed with Cr catalysis (Scheme 4, eq 1). Meanwhile,
3ad: R = Me (35%)
3ae: R = t-Bu (45%)
MeO
OMe
3af: R = OMe (29%)
3ag: R = F (48%)
3ah: R = Cl (42%)
3ac (81%)b
the
reaction
by
the
use
of
(naphthalen-2-
yloxy)methylpyridine (8) did not give the coupling product
3ai with recovery of starting material (Scheme 4, eq 2). These
indicate that a ligation of N,O scaffolds with metal can be
considered for achieving the Cr-catalyzed coupling of
C(aryl)–O bond. To probe the possibility that the in-situ
formed reactive Cr species is responsible for the Kumada
coupling, CrCl2 was initially treated with PhMgBr, and then
naphthyl 2-pyridyl ether (1b) with another aryl Grignard of
(4-methoxyphenyl)magnesium bromide (2b) was putted into
the reaction system. When the use of 0.1 equiv of CrCl2 and
aReaction conditions: 1 (0.3 mmol), 2 (0.9 mmol), CrCl2
(0.03 mmol), 40 oC, 12 h. Isolated yields are given. b2,7-
Bis(pyridin-2-yloxy)naphthalene was used.
The Kumada coupling using phenyl Grignard reagents that
contain substituents such as alkyl, fluoride, chloride and ami-
no occurred smoothly, providing access to the arylated com-
pounds 3q–3t in moderate to good yields (Scheme 3). 2-
Naphthylmagnesium bromide can be used as partner to regi-
oselective couple with C(aryl)–O bond of aryl 2-pyridyl ether
(3u). Notably, the incorporation of methoxy group into the
motif of phenylmagnesium bromide did not affect the selec-
tivity of C(aryl)–O bond in aryl 2-pyridyl ethers, leading to the
Scheme 4. Preliminary Mechanistic Studies
Functionalization of estrone derivative
Me
OMe
OMe
Me
H
Ph
PyO
PhMgBr (3 equiv)
H
H
CrCl2 (10 mol %)
THF, 40 oC, 12 h
H
H
H
MeO
MeO
4
5 (59%)
Sequential transformation of C–O bonds
MeO
MgBr
PhMgBr (3 equiv)
MeO
2b (2 equiv)
[Ni(PCy3)2Cl2 (5 mol %)
CrCl2
(10 mol %)
MeO
Ph
Ph
1a
Toluene, 30 oC, 1 h
83% yield
THF, 40 oC, 12 h
82% yield
3a
6
Gram-Scale Reaction
OPy
Ph
CrCl2 (10 mol %)
PhMgBr
THF, 40 oC, 12 h
1b
(5 mmol, 1.11 g)
3ai
(65%, 0.66 g)
Figure 1. The application of the Cr-catalyzed regioselec-
tive cross-coupling of C(aryl)–O bonds.
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0.2 equiv of PhMgBr, the related coupling product of C(aryl)– (1.9 g, 12 mmol) were added, and then the mixture was heat-
o
1
2
3
4
5
6
7
8
O bond with phenyl Grignard reagent was not detected
(Scheme 4, eq 3). Interestingly, increasing the amount of
phenyl Grignard was able to form its coupling product with
C(aryl)–O bond. Phenyl Grignard reagent might be initially
consumed by the reduction of the CrCl2 salt in forming reac-
tive low-valent Cr species in situ, which could promote the
cross-coupling of C(aryl)–O bond.58
ed at 100 C for 24 h. EtOAc (10 mL) and H2O (10 mL) were
added and the mixture was filtered through a Celite pad. The
organic layer was separated and the aqueous layer was ex-
tracted twice with EtOAc (20 mL). The combined organic
layers were washed with H2O (20 mL), dried over anhydrous
Na2SO4, and filtered through a pad of silica gel. The filtrate
was concentrated and the residue was purified by column
chromatography using PE/EA as eluent.
In summary, we have developed a mild and regioselective
chromium catalysis for the arylative Kumada cross-coupling
of C(aryl)–O bonds. This reaction was enabled by the use of a
low-cost chromium(II) chloride as the precatalyst, regioselec-
tive providing access to fundamentally valuable biaryl motifs
at ambient temperature. A reactive Cr species that was
formed in-situ by reaction of CrCl2 with aryl Grignard is likely
to responsibility for the cleavage of C(aryl)–O bond under the
ligation assistance of 2-pyridyl. This reaction presents a Cr-
catalyzed traceless activation strategy for Kumada coupling
in tackling the regioselectivity issue, and shows that Cr pos-
sesses good reactivity in the catalytic cleavage of unactivated
C–O bonds, which is usually dominated by nickel catalysis.
Studies on the application of cost-effective chromium cataly-
sis in synthetic chemistry are under way.
9
2-((7-Methoxynaphthalen-2-yl)oxy)pyridine (1a). white solid
(2.3 g, 92%); TLC, Rf = 0.25 (PE/EtOAc = 20:1). H NMR (400
1
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MHz, CDCl3) δ 8.24–8.22 (m, 1H), 7.78 (d, J = 8.8 Hz, 1H),
7.72–7.68 (m, 2H), 7.47 (d, J = 2.4 Hz, 1H), 7.15 (dd, J = 8.8, 2.4
Hz, 1H), 7.12–7.08 (m, 2H), 7.03–6.70 (m, 1H), 6.95 (d, J = 8.4
Hz, 1H), 3.90 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 163.9, 158.1,
152.5, 147.8, 139.4, 135.6, 129.4, 129.3, 126.4, 118.8, 118.5,
118.0, 116.5, 111.6, 105.5, 55.3.
2-((7-Isopropoxynaphthalen-2-yl)oxy)pyridine (1b). white
solid (2.5 g, 90%); TLC, Rf = 0.23 (PE/EtOAc = 20:1). H NMR
1
(400 MHz, CDCl3) δ 8.24–8.22 (m, 1H), 7.79–7.67 (m, 3H), 7.44
(d, J = 2.0 Hz, 1H), 7.13 (dd, J = 8.8, 2.4 Hz, 1H), 7.09–7.07 (m,
2H), 7.01–7.00 (m, 1H), 6.94 (d, J = 8.4 Hz, 1H), 4.71–4.65 (m,
1H), 1.39 (d, J = 6.0 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ
163.9, 156.3, 152.4, 147.9, 139.4, 135.6, 129.3, 129.28, 126.3,
119.0, 118.7, 118.5, 116.4, 111.6, 69.8, 22.0.
EXPERIMENTAL SECTION
2-((7-Butoxynaphthalen-2-yl)oxy)pyridine (1c). white solid
(2.7 g, 91%); TLC, Rf = 0.20 (PE/EtOAc = 20:1). H NMR (400
General Methods. All reactions dealing with air- or mois-
ture-seneitive compounds were carried out in a flame-dried,
scaled schlenk reaction tube under an atmosphere of nitro-
gen. Analytical thin-layer chromatography was performed on
glass plates coated with 0.25 mm 230-400 mesh silica gel
containing a fluorescent indicator (Merck). Flash silica gel
chromatography was performed on silica gel 60N (spherical
and neutral, 140-325 mesh) as described by Still. NMR spec-
tra were measured on a BrukerAV-400 spectrometer and
1
MHz, CDCl3) δ 8.24–8.22 (m, 1H), 7.77 (d, J = 8.8 Hz, 1H), 7.74–
7.67 (m, 2H), 7.45 (s, 1H), 7.16–7.07 (m, 3H), 7.02–7.00 (m, 1H),
6.94 (d, J = 8.4 Hz, 1H), 4.05 (t, J = 7.2 Hz, 2H), 1.87–1.80 (m,
2H), 1.59–1.49 (m, 2H), 1.03–0.98 (m, 3H); 13C NMR (100 MHz,
CDCl3) δ 163.9, 157.7, 152.5, 147.9, 139.4, 135.7, 129.4, 129.2,
118.7, 118.5, 118.3, 116.5, 111.6, 106.3, 67.7, 31.3, 19.3, 13.9.
2-((7-(Tert-butoxy)naphthalen-2-yl)oxy)pyridine (1d). white
solid (2.6 g, 90%); TLC, Rf = 0.30 (PE/EtOAc = 20:1). H NMR
1
1
reported in parts per million. H NMR spectra were recorded
at 400 MHz in CDCl3 were referenced internally to tetrame-
thylsilane as a standard, and 13C NMR spectra were recorded
at 100 MHz and referenced to the solvent resonance. Analyti-
cal gas chromatography (GC) was carried out on a Thermo
Trace 1300 gas chromatograph, equipped with a flame ioni-
zation detector. Mass spectra (GC-MS) were taken at Thermo
Trace 1300 gas chromatograph mass spectrometer. High
resolution mass spectra (HRMS) were recorded on the Exac-
tive Mass Spectrometer (Thermo Scientific, USA) equipped
with ESI ionization source. Melting points were determined
with a Hanon MP-300. Unless otherwise noted, materials
were purchased from Tokyo Chemical Industry Co., Aldrich
Inc., Alfa Aesar, Adamas-beta and other commercial suppli-
ers and used as received. Solvents were dried over sodium
(for THF and ether) by refluxing for overnight and freshly
distilled prior to use. Metallic magnesium turnings (>99.99%)
were purchased from Adamas-beta. CrCl2 (99.99%), CrCl3
(99.99%), Cr(acac)3 (97%), AlCl3 (99.9%), MgCl2 (99.9%),
NiCl2 and FeCl2 (>98%) were purchased from Aldrich Inc. and
used as received.
(400 MHz, CDCl3) δ 8.22–8.21 (m, 1H), 7.81 (d, J = 8.8 Hz, 1H),
7.75–7.68 (m, 2H), 7.47 (d, J = 2.4 Hz, 1H), 7.34 (d, J = 2.4 Hz,
1H), 7.19 (dd, J = 8.8, 2.4 Hz, 1H), 7.13 (dd, J = 8.8, 2.4 Hz, 1H),
7.02–6.96 (m, 2H), 1.42 (s, 9H); 13C NMR (100 MHz, CDCl3) δ
163.9, 153.8, 152.1, 147.8, 139.4, 135.1, 129.2, 128.5, 127.8,
124.2, 119.9, 119.3, 118.5, 116.8, 111.6, 79.0, 28.9.
2-((7-(Benzyloxy)naphthalen-2-yl)oxy)pyridine (1e). white
solid (3.1 g, 94%); TLC, Rf = 0.33 (PE/EtOAc = 10:1). H NMR
1
(400 MHz, CDCl3) δ 8.24–8.23 (m, 1H), 7.82–7.75 (m, 2H),
7.72–7.68 (m, 1H), 7.50–7.47 (m, 3H), 7.44–7.40 (m, 2H), 7.37–
7.35 (m, 1H), 7.22–7.16 (m, 3H), 7.03–7.00 (m, 1H), 6.95 (dd, J
= 8.8, 0.8 Hz, 1H), 5.18 (s, 2H); 13C NMR (100 MHz, CDCl3) δ
163.8, 157.3, 152.5, 147.8, 139.4, 136.8, 135.5, 129.4, 129.3,
128.6, 127.5, 126.5, 118.9, 118.5, 118.3, 116.5, 111.6, 106.9,
70.0.
2-((7-Phenoxynaphthalen-2-yl)oxy)pyridine (1f). white solid
(3.0 g, 95%); TLC, Rf = 0.30 (PE/EtOAc = 10:1). H NMR (400
1
MHz, CDCl3) δ 8.22–8.20 (m, 1H), 7.82 (t, J = 8.0 Hz, 2H), 7.73–
7.68 (m, 1H), 7.43–7.35 (m, 3H), 7.24–7.21 (m, 3H), 7.16–7.13
(m, 1H), 7.09–7.07 (m, 2H), 7.03–7.00 (m, 1H), 6.96 (dd, J = 8.4,
0.8 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 163.7, 157.0, 155.8,
152.6, 147.8, 139.5, 135.4, 129.8, 129.7, 129.5, 127.6, 123.5,
120.1, 119.2, 119.1, 118.6, 116.7, 113.6, 111.8.
General Procedure for the Preparation of Aryl 2-Pyridyl
Ethers.43 An oven-dried flask was charged with phenol (10
mmol), K3PO4 (4.3 g, 20 mmol), CuI (0.19 g, 1 mmol), and
picolinic acid (0.25 g, 2 mmol). After the flask was evacuated
and back-filled with N2, DMSO (20 mL) and 2-bromopyridine
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2-((7-((Tert-butyldimethylsilyl)oxy)naphthalen-2-
139.5, 132.0, 131.8, 128.6, 128.2, 127.3, 127.1, 126.9, 126.7,
126.0, 122.9, 122.8, 122.6, 118.6, 116.2, 111.1.
1
2
yl)oxy)pyridine (1g). brown oil (3.1 g, 89%); TLC, Rf = 0.26
1
(PE/EtOAc = 20:1). H NMR (400 MHz, CDCl3) δ 8.24 (dd, J =
2-Methyl-N-((4'-(pyridin-2-yloxy)-[1,1'-biphenyl]-4-
3
4
5
6
7
8
9
5.2, 2.0 Hz, 1H), 7.79 (d, J = 8.8 Hz, 1H), 7.75–7.67 (m, 2H), 7.45
(d, J = 2.0 Hz, 1H), 7.19–7.16 (m, 2H), 7.05 (dd, J = 8.8, 2.4 Hz,
1H), 7.02–6.96 (m, 2H), 1.05 (s, 9H), 0.28 (s, 6H); 13C NMR
(100 MHz, CDCl3) δ 163.8, 154.0, 152.3, 147.8, 139.3, 135.6,
129.3, 129.2, 126.7, 121.3, 119.1, 118.4, 116.2, 114.6, 111.6,
25.7, 18.2, –4.4.
yl)methylene)propan-2-amine (1n). white solid (3.2 g, 98%);
TLC, Rf = 0.30 (PE/EtOAc = 20:1). 1H NMR (400 MHz, CDCl3) δ
8.32 (s, 1H), 8.23–8.22 (m, 1H), 7.81 (d, J = 8.4 Hz, 2H), 7.73–
7.69 (m, 1H), 7.67–7.62 (m, 4H), 7.25–7.21 (m, 2H), 7.03–6.70
(m, 1H), 6.96 (d, J = 8.8 Hz, 1H), 1.32 (s, 9H); 13C NMR (100
MHz, CDCl3) δ 163.6, 154.7, 153.8, 147.7, 142.2, 139.5, 137.0,
136.0, 128.4, 128.3, 127.1, 125.5, 118.5, 111.7, 57.3, 29.7.
7-(Pyridin-2-yloxy)naphthalen-2-ol (1h). white solid (2.0 g,
85%); TLC, Rf = 0.30 (PE/EtOAc = 5:1). 1H NMR (400 MHz,
DMSO-d6) δ 9.79 (s, 1H), 8.15 (dd, J = 4.8, 1.6 Hz, 1H), 7.87–
7.75 (m, 3H), 7.39 (d, J = 2.0 Hz, 1H), 7.13–7.02 (m, 5H); 13C
NMR (100 MHz, CDCl3) δ 163.3, 155.9, 152.1, 147.5, 140.1,
135.6, 129.3, 125.1, 119.0, 118.1, 117.9, 115.6, 111.5, 108.4.
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
2-Methyl-6-(pyridin-2-yloxy)quinolone (1o). white solid (1.9
1
g, 80%); TLC, Rf = 0.25 (PE/EtOAc = 5:1). H NMR (400 MHz,
CDCl3) δ 8.20–9.16 (m, 1H), 8.02 (d, J = 8.8 Hz, 1H), 7.96 (d, J =
8.4 Hz, 1H), 7.73–7.69 (m, 1H), 7.49–7.47 (m, 2H), 7.27–7.25 (m,
1H), 7.03–7.00 (m, 1H), 6.96 (d, J = 8.4 Hz, 1H), 2.73 (s, 3H); 13
C
2-((6-(3-Methoxyphenyl)naphthalen-2-yl)oxy)pyridine (1i).
NMR (100 MHz, CDCl3) δ 163.5, 158.2, 151.4, 147.7, 145.4,
139.6, 135.7, 130.3, 127.1, 124.7, 122.3, 118.8, 116.9, 111.8,
25.2.
2,2'-Oxydipyridine (known compounds 1, known 1p).59
slight oil (1.2 g, 70%); TLC, Rf = 0.35 (PE/EtOAc = 5:1). 1H NMR
(400 MHz, CDCl3) δ 8.28 (dd, J = 2.8, 0.8 Hz, 2H), 7.77–7.72 (m,
2H), 7.11–7.06 (m, 4H); 13C NMR (100 MHz, CDCl3) δ 161.9,
148.0, 139.5, 119.9, 113.9.
1
white solid (2.9 g, 88%); TLC, Rf = 0.35 (PE/EtOAc = 10:1). H
NMR (400 MHz, CDCl3) δ 8.24–8.23 (m, 1H), 8.06 (s, 1H), 7.93
(d, J = 8.8 Hz, 1H), 7.85 (d, J = 8.4 Hz, 1H), 7.74–7.70 (m, 2H),
7.61 (s, 1H), 7.39 (t, J = 8.0 Hz, 1H), 7.36–7.31 (m, 2H), 7.27–
7.26 (m, 1H), 7.05–6.94 (m, 3H), 3.91 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 163.8, 160.0, 152.0, 147.8, 142.5, 139.5, 137.8,
133.5, 131.1, 129.8, 127.9, 126.1, 125.7, 121.8, 119.8, 118.6,
117.2, 113.1, 112.7, 111.6, 55.3.
2-(Naphthalen-2-yloxy)pyridine (1t). white solid (2.1 g, 96%);
1
2-((6-Methoxynaphthalen-2-yl)oxy)pyridine (1j). white solid
TLC, Rf = 0.33 (PE/EtOAc = 50:1). H NMR (400 MHz, CDCl3) δ
1
(2.4 g, 96%); TLC, Rf = 0.22 (PE/EtOAc = 20:1). H NMR (400
8.25–8.22 (m, 1H), 7.91–7.85 (m, 2H), 7.81–7.79 (m, 1H), 7.73–
7.68 (m, 1H), 7.60–7.58 (m, 1H), 7.51–7.47 (m, 2H), 7.35–7.30
(m, 1H), 7.03–6.96 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 163.8,
151.8, 147.8, 139.4, 134.3, 131.0, 129.6, 127.5, 126.4, 125.2,
121.4, 118.6, 117.4, 111.6.
MHz, CDCl3) δ 8.23–8.21 (m, 1H), 7.76 (d, J = 8.8 Hz, 1H), 7.67–
7.66 (m, 2H), 7.53 (s, 1H), 7.30–7.27 (m, 1H), 7.18–7.16 (m, 2H),
7.01–6.98 (m, 1H), 6.93 (d, J = 8.4 Hz, 1H), 3.92 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 164.0, 157.2, 150.0, 147.7, 139.3,
132.0, 129.5, 128.8, 128.3, 121.8, 119.2, 118.3, 117.6, 111.3,
105.9, 55.3.
2-((6-(Trimethylsilyl)naphthalen-2-yl)oxy)pyridine
(1w).
1
white solid (2.7 g, 91%); TLC, Rf = 0.35 (PE/EtOAc = 50:1). H
NMR (400 MHz, CDCl3) δ 8.24–8.22 (m, 1H), 8.01 (d, J = 4.0
Hz, 1H), 7.89–7.87 (m, 1H), 7.82–7.76 (m, 1H), 7.72–7.67 (m,
1H), 7.62–7.59 (m, 1H), 7.55 (s, 1H), 7.33–7.30 (m, 1H), 7.03–
7.00 (m, 1H), 6.97–6.94 (m, 1H), 0.35 (s, 9H); 13C NMR (100
MHz, CDCl3) δ 163.9, 152.2, 147.9, 139.4, 137.1, 134.4, 133.6,
130.5, 130.4, 129.8, 126.5, 121.3, 118.6, 117.2, 111.6, –1.1.
2-((6-(((2-Methylallyl)oxy)methyl)naphthalen-2-
yl)oxy)pyridine (1k). white solid (2.6 g, 87%); TLC, Rf = 0.34
1
(PE/EtOAc = 20:1). H NMR (400 MHz, CDCl3) δ 8.23–8.21 (m,
1H), 7.86 (d, J = 8.8 Hz, 1H), 7.77 (t, J = 8.8 Hz, 2H), 7.70–7.68
(m, 1H), 7.57 (d, J = 2.0 Hz, 1H), 7.48 (dd, J = 8.4, 1.2 Hz, 1H),
7.30 (dd, J = 8.8, 2.4 Hz, 1H), 7.03–7.00 (m, 1H), 6.95 (d, J = 8.4
Hz, 1H), 5.05 (s, 1H), 4.96 (s, 1H), 4.66 (s, 2H), 3.98 (s, 2H),
1.80 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 163.7, 151.8, 147.7,
142.1, 139.4, 135.2, 133.7, 130.7, 129.5, 127.6, 126.3, 126.2,
121.5, 118.5, 117.3, 112.3, 111.6, 73.9, 71.8, 19.5; HRMS (ESI-
TOF) m/z: [M+H]+ Calcd for C20H20NO2 306.1489; Found
306.1483.
2-([1,1'-Biphenyl]-4-yloxy)pyridine (1x). white solid (2.3 g,
1
94%); TLC, Rf = 0.23 (PE/EtOAc = 50:1). H NMR (400 MHz,
CDCl3) δ 8.25–8.24 (m, 1H), 7.73–7.69 (m, 1H), 7.65–7.60 (m,
4H), 7.47–7.43 (m, 2H), 7.37–7.34 (m, 1H), 7.27–7.22 (m, 2H),
7.03–7.00 (m, 1H), 6.96 (d, J = 8.8 Hz, 1H); 13C NMR (100 MHz,
CDCl3) δ 163.7, 153.6, 147.7, 140.6, 139.4, 137.7, 128.7, 128.4,
127.1, 127.0, 121.4, 118.5, 111.7.
N,N-Dimethyl-7-(pyridin-2-yloxy)naphthalen-1-amine (1l).
white solid (2.3 g, 88%); TLC, Rf = 0.27 (PE/EtOAc = 5:1). H
1
2-((6-Phenylnaphthalen-2-yl)oxy)pyridine (1y). white solid
(2.7 g, 92%); TLC, Rf = 0.40 (PE/EtOAc = 50:1). H NMR (400
NMR (400 MHz, CDCl3) δ 8.23–8.21 (m, 1H), 7.98 (d, J = 2.0 Hz,
1H), 7.85 (d, J = 8.8 Hz, 1H), 7.69–7.66 (m, 1H), 7.52 (d, J = 8.0
Hz, 1H), 7.35 (t, J = 8.0 Hz, 1H), 7.32–7.29 (m, 1H), 7.08 (d, J =
7.2 Hz, 1H), 7.01–6.93 (m, 2H), 2.87 (s, 6H); 13C NMR (100 MHz,
CDCl3) δ 164.1, 151.4, 150.6, 147.8, 139.3, 132.3, 130.0, 129.9,
125.1, 122.7, 121.1, 118.4, 114.5, 111.4, 45.1.
1
MHz, CDCl3) δ 8.26–8.25 (m, 1H), 8.07 (s, 1H), 7.94 (d, J = 8.8
Hz, 1H), 7.86 (d, J = 8.4 Hz, 1H), 7.79–7.70 (m, 4H), 7.62 (s, 1H),
7.53–7.49 (m, 2H), 7.42–7.35 (m, 2H), 7.05–6.99 (m, 2H); 13C
NMR (100 MHz, CDCl3) δ 163.8, 152.0, 147.8, 141.0, 139.4,
137.9, 133.4, 131.2, 129.9, 128.8, 127.3, 126.1, 125.6, 121.8,
118.6, 117.2, 111.6.
2-(Phenanthren-9-yloxy)pyridine (1m). white solid (2.4 g,
90%); TLC, Rf = 0.30 (PE/EtOAc = 50:1). H NMR (400 MHz,
1
2-((6-(4-Fluorophenyl)naphthalen-2-yl)oxy)pyridine
(1z).
CDCl3) δ 8.73 (d, J = 8.4 Hz, 1H), 8.68 (d, J = 8.0 Hz, 1H), 8.24–
8.22 (m, 1H), 8.12 (d, J = 8.0 Hz, 1H), 7.82 (d, J = 8.0 Hz, 1H),
7.72–7.68 (m, 2H), 7.66–7.58 (m, 3H), 7.51 (s, 1H), 7.03–7.00
(m, 2H); 13C NMR (100 MHz, CDCl3) δ 164.2, 148.5, 148.0,
1
white solid (2.8 g, 89%); TLC, Rf = 0.36 (PE/EtOAc = 50:1). H
NMR (400 MHz, CDCl3) δ 8.23 (d, J = 4.0 Hz, 1H), 8.00 (s, 1H),
7.91 (d, J = 8.8 Hz, 1H), 7.84 (d, J = 8.8 Hz, 1H), 7.74–7.65 (m,
4H), 7.60 (s, 1H), 7.34 (d, J = 8.8 Hz, 1H), 7.16 (t, J = 8.4 Hz, 2H),
7.05–6.98 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 163.8, 161.3 (d,
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J = 245.0 Hz), 152.0, 147.8, 139.5, 137.1 (d, J = 3.0 Hz), 136.9,
133.3, 131.1, 129.8, 128.8 (d, J = 8.0 Hz), 128.0, 125.9, 125.5,
122.0, 118.6, 117.2, 115.6 (d, J = 21.0 Hz), 111.7.
cyclopenta[a]phenanthren-2-yl)phenoxy)pyridine (4). White
solid (1.48 g, 80%); TLC, Rf = 0.34 (PE/EtOAc = 20:1). H NMR
1
1
2
3
4
5
6
7
8
(400 MHz, CDCl3) δ 8.24 (d, J = 4.4 Hz 1H), 7.71–7.67 (m, 1H),
7.57–7.54 (m, 2H), 7.28 (s, 1H), 7.16 (m, 2H), 6.99 (t, J = 6.0 Hz,
1H), 6.94 (d, J = 8.0 Hz, 1H), 6.71 (s, 1H), 3.80 (s, 3H), 3.40 (s,
3H), 3.32 (t, J = 8.0 Hz, 1H), 2.91 (d, J = 5.2 Hz, 2H), 2.35–2.23
(m, 2H), 2.06 (d, J = 10.8 Hz, 2H), 1.92 (d, J = 9.6 Hz, 1H), 1.71
(d, J = 9.6 Hz, 1H), 1.57–1.48 (m, 3H), 1.46–1.36 (m, 3H), 1.28–
1.21 (m, 1H), 0.82 (d, J = 1.2 Hz, 3H); 13C NMR (100 MHz, CDCl3)
δ 163.8, 154.3, 152.9, 147.8, 139.3, 137.1, 135.2, 132.6, 130.8,
128.1, 127.4, 120.5, 118.4, 111.5, 90.7, 57.9, 55.5, 50.2, 43.9,
43.2, 38.6, 38.0, 29.8, 27.8, 27.3, 26.5, 23.0, 11.5; HRMS (ESI-
TOF) m/z: [M+H]+ Calcd for C31H36NO3 470.2690; Found
470.2683.
2-((6-(4-Chlorophenyl)naphthalen-2-yl)oxy)pyridine (1aa).
1
white solid (3.0 g, 90%); TLC, Rf = 0.35 (PE/EtOAc = 20:1). H
NMR (400 MHz, CDCl3) δ 8.24–8.23 (m, 1H), 8.01 (s, 1H), 7.91
(d, J = 8.8 Hz, 1H), 7.84 (d, J = 8.8 Hz, 1H), 7.74–7.68 (m, 2H),
7.65–7.60 (m, 3H), 7.47–7.44 (m, 2H), 7.37–7.34 (m, 1H), 7.05–
6.98 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 163.7, 152.1, 147.8,
139.4, 136.6, 133.5, 133.4, 131.1, 129.0, 128.5, 128.1, 125.7,
125.6, 122.0, 118.7, 117.2, 111.7.
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
9-Methyl-2-(pyridin-2-yloxy)-9H-carbazole (1ab). white solid
1
(2.2 g, 82%); TLC, Rf = 0.30 (PE/EtOAc = 5:1). H NMR (400
MHz, CDCl3) δ 8.26–8.25 (m, 1H), 8.11–8.03 (m, 2H), 7.72–7.68
(m, 1H), 7.47–7.45 (m, 1H), 7.38 (d, J = 8.0 Hz, 1H), 7.28–7.24
(m, 1H), 7.21–7.16 (m, 1H), 7.06–7.00 (m, 2H), 6.95 (dd, J = 8.4,
0.8 Hz, 1H), 3.90 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 164.4,
152.8, 147.9, 141.4, 139.3, 125.2, 122.6, 121.1, 119.9, 119.89,
119.1, 118.2, 112.8, 111.3, 108.3, 101.4, 29.1.
General Procedure for Cr-Catalyzed Regioselective Ary-
lative Kumada Cross-Couplings of Aryl 2-Pyridyl Ethers. In
a dried Schlenk tube were placed aryl 2-pyridyl ether (0.3
mmol) and CrCl2 (3.7 mg, 0.03 mmol), then a freshly distilled
THF (0.5 ml) was added by a syringe under atmosphere of
nitrogen. After stirring at room temperature for 5 min, aro-
matic Grignard reagent (0.9 ml, 1.0 M in THF, 0.9 mmol) was
dropwise added, and the mixture was stirred at 40 oC for 12 h.
After quenched with saturated aqueous solution of NH4Cl (1
mL), the mixture was extracted three times with ethyl ace-
tate. The organic phases were collected, dried over anhy-
drous Na2SO4 and concentrated under reduced pressure. The
residue was purified by column chromatography to afford
the desired coupling product.
2,7-Bis(pyridin-2-yloxy)naphthalene (1ac). white solid (2.5 g,
1
80%); TLC, Rf = 0.33 (PE/EtOAc = 10:1). H NMR (400 MHz,
CDCl3) δ 8.22–8.21 (m, 2H), 7.86 (d, J = 8.8 Hz, 2H), 7.70–7.67
(m, 2H), 7.51 (s, 2H), 7.28–7.25 (m, 2H), 7.02–6.99 (m, 2H),
6.94 (d, J = 8.0 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 163.7,
152.5, 147.8, 139.5, 135.3, 129.6, 128.5, 120.7, 118.7, 117.1,
111.6.
2-(p-tolyloxy)pyridine (1ad). colorless oil (1.7 g, 91%); TLC,
1
Rf = 0.32 (PE/EtOAc = 50:1). H NMR (400 MHz, CDCl3) δ 8.20
2-Methoxy-7-phenylnaphthalene (known compounds 2,
known 3a).60 white solid (58 mg, 82%); TLC, Rf = 0.40
(dd, J = 4.8, 2.0 Hz, 1H), 7.68–7.64 (m, 1H), 7.20 (d, J = 8.0 Hz,
2H), 7.03 (d, J = 8.4 Hz, 2H), 6.98–6.95 (m, 1H), 6.88 (d, J = 8.4
Hz, 1H), 2.37 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 164.0, 151.7,
147.7, 139.2, 134.2, 130.1, 121.0, 118.1, 111.2, 20.8.
1
(PE/EtOAc = 50:1). H NMR (400 MHz, CDCl3) δ 7.96 (s, 1H),
7.84 (d, J = 8.4 Hz, 1H), 7.78–7.72 (m, 3H), 7.61 (dd, J = 8.4, 1.6
Hz, 1H), 7.48 (t, J = 7.6 Hz, 2H), 7.37 (t, J = 7.2 Hz, 1H), 7.21 (d, J
= 2.4 Hz, 1H) 7.16 (dd, J = 8.8, 2.4 Hz, 1H), 3.95 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 157.9, 141.3, 138.9, 134.9, 129.1,
128.1, 127.4, 127.3, 124.6, 123.4, 118.6, 105.8, 55.3; GC-MS
(EI): [M+] Calcd for C17H14O 234.10; Found 234.11.
2-(4-(Tert-butyl)phenoxy)pyridine (1ae). white solid (2.0 g,
1
90%); TLC, Rf = 0.36 (PE/EtOAc = 50:1). H NMR (400 MHz,
CDCl3) δ 8.22–8.20 (m, 1H), 7.69–7.64 (m, 1H), 7.42–7.39 (m,
2H), 7.09–7.05 (m, 2H), 6.99–6.96 (m, 1H), 6.88 (d, J = 8.4 Hz,
1H); 13C NMR (100 MHz, CDCl3) δ 163.9, 151.7, 147.8, 147.3,
139.3, 126.6, 120.5, 118.2, 111.4, 34.4, 31.5.
2-Isopropoxy-7-phenylnaphthalene (3b). slight yellow oil (64
mg, 81%); TLC, Rf = 0.36 (PE/EtOAc = 50:1). 1H NMR (400
MHz, CDCl3) δ 7.95 (d, J = 0.8 Hz, 1H), 7.84 (d, J = 8.4 Hz, 1H),
7.80–7.74 (m, 3H), 7.61 (dd, J = 8.4, 1.6 Hz, 1H), 7.53–7.49 (m,
2H), 7.43–7.39 (m, 1H), 7.24 (d, J = 2.4 Hz, 1H), 7.16 (dd, J = 8.8,
2.4 Hz, 1H), 4.78–4.72 (m, 1H), 1.45 (d, J = 6.0 Hz, 6H); 13C
NMR (100 MHz, CDCl3) δ 156.1, 141.1, 138.9, 134.9, 129.0,
128.8, 128.0, 127.4, 127.2, 124.5, 123.2, 119.8, 108.6, 69.3,
21.9; IR(neat) 2974, 2927, 1625, 1606, 1458, 1363, 1207, 1116,
977, 841, 746, 693 cm-1; HRMS (ESI-TOF) m/z: [M+H]+ Calcd
for C19H19O 263.1430; Found 263.1436.
2-(4-Methoxyphenoxy)pyridine (1af). colorless oil (1.8 g,
1
92%); TLC, Rf = 0.32 (PE/EtOAc = 20:1). H NMR (400 MHz,
CDCl3) δ 8.19–8.18 (m, 1H), 7.67–7.63 (m, 1H), 7.10–7.06 (m,
2H), 6.97–6.91 (m, 3H), 6.86 (d, J = 8.0 Hz, 1H), 3.81 (s, 3H);
13C NMR (100 MHz, CDCl3) δ 164.2, 156.5, 147.7, 147.4, 139.2,
122.3, 118.0, 114.7, 111.0, 55.5.
2-(4-Fluorophenoxy)pyridine (1ag). colorless oil (1.7 g, 93%);
TLC, Rf = 0.36 (PE/EtOAc = 50:1). 1H NMR (400 MHz, CDCl3) δ
8.19–8.17 (m, 1H), 7.71–7.66 (m, 1H), 7.12–7.06 (m, 4H), 7.00–
6.97 (m, 1H), 6.90 (d, J = 8.4 Hz, 1H); 13C NMR (100 MHz,
CDCl3) δ 163.9, 158.3 (d, J = 242.5 Hz), 149.8 (d, J = 2.9 Hz),
147.6, 139.4, 122.7 (d, J = 8.6 Hz), 118.5, 116.1 (d, J = 24.0 Hz),
111.4.
2-Butoxy-7-phenylnaphthalene (3c). slight yellow oil (62 mg,
74%); TLC, Rf = 0.38 (PE/EtOAc = 50:1). H NMR (400 MHz,
1
CDCl3) δ 7.96 (d, J = 1.2 Hz, 1H), 7.84 (d, J = 8.4 Hz, 1H), 7.79–
7.74 (m, 3H), 7.61 (dd, J = 8.4, 2.0 Hz, 1H), 7.53–7.49 (m, 2H),
7.43–7.38 (m, 1H), 7.22–7.18 (m, 2H), 4.11 (t, J = 6.4 Hz, 2H),
1.92–1.83 (m, 2H), 1.64–1.53 (m, 2H), 1.03 (t, J = 8.0 Hz, 3H);
13C NMR (100 MHz, CDCl3) δ 157.5, 141.3, 139.0, 134.9, 129.0,
128.8, 128.1, 128.0, 127.4, 127.2, 124.7, 123.2, 119.1, 106.8,
67.7, 31.3, 19.3, 13.9; IR(neat) 2955, 2870, 1626, 1459, 1211,
1175, 1123, 1004, 896, 840, 753, 698 cm-1; HRMS (ESI-TOF)
m/z: [M+H]+ Calcd for C20H21O 277.1587; Found 277.1586.
2-(4-chlorophenoxy)pyridine (1ah). colorless oil (1.9 g, 92%);
TLC, Rf = 0.36 (PE/EtOAc = 50:1). 1H NMR (400 MHz, CDCl3) δ
8.18 (dd, J = 4.8, 1.6 Hz, 1H), 7.72–7.67 (m, 1H), 7.36 (dd, J =
6.8, 2.0 Hz, 2H), 7.11-7.08 (m, 2H), 7.02-6.99 (m, 1H), 6.92 (d,
J = 8.4 Hz, 1H), 2.37 (s, 3H); 13C NMR (100 MHz, CDCl3): δ =
163.3, 152.6, 147.6, 139.5, 129.8, 129.6, 122.5, 118.7, 111.6.
2-(4-((8R,9S,13S,14S,17S)-3,17-Dimethoxy-13-methyl-
7,8,9,11,12,13,14,15,16,17-decahydro-6H-
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2-(Tert-butoxy)-7-phenylnaphthalene (3d). slight yellow oil
(63 mg, 76%); TLC, Rf = 0.36 (PE/EtOAc = 50:1). H NMR (400
113.1, 112.8, 55.3; IR(neat) 2955, 2835, 1576, 1485, 1433, 1296,
1
1205, 1029, 871, 789, 755,695 cm-1; HRMS (ESI-TOF) m/z:
[M+H]+ Calcd for C23H19O 311.1430; Found 311.1435.
1
2
3
4
5
6
7
8
MHz, CDCl3) δ 7.99 (d, J = 1.2 Hz, 1H), 7.89 (d, J = 8.4 Hz, 1H),
7.79 (d, J = 8.8 Hz, 1H), 7.77–7.75 (m, 2H), 7.68 (dd, J = 8.4, 2.0
Hz, 1H), 7.53–7.50 (m, 3H), 7.43–7.39 (m, 1H), 7.22 (dd, J = 8.8,
2.0 Hz, 1H), 1.48 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 153.6,
141.1, 138.7, 134.4, 129.4, 128.8, 128.3, 128.0, 127.4, 127.3,
125.1, 125.05, 124.3, 120.0, 79.0, 28.9; IR(neat) 2981, 1627,
1457, 1363, 1158, 1142, 963, 906, 843, 752, 695 cm-1; HRMS
(ESI-TOF) m/z: [M+H]+ Calcd for C20H21O 277.1587; Found
277.1583.
2-Methoxy-6-phenylnaphthalene (known compounds 4,
known 3j).62 white solid (46 mg, 65%); TLC, Rf = 0.36
(PE/EtOAc = 50:1). 1H NMR (400 MHz, CDCl3) δ 7.99 (d, J = 1.6
Hz, 1H), 7.84–7.80 (m, 2H), 7.75–7.72 (m, 3H), 7.51–7.48 (m,
2H), 7.40–7.36 (m, 1H), 7.21–7.18 (m, 2H), 3.96 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 157.7, 141.2, 136.3, 133.7, 129.6,
129.1, 128.8, 127.2, 127.19, 127.0, 126.0, 125.6, 119.1, 105.5,
54.8; GC-MS (EI): [M+] Calcd for C17H14O 234.10; Found 234.12.
9
10
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12
13
14
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16
17
18
19
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22
23
24
25
26
27
28
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33
34
35
36
37
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39
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46
47
48
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50
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60
2-(Benzyloxy)-7-phenylnaphthalene (3e). white solid (66 mg,
2-(((2-Methylallyl)oxy)methyl)-6-phenylnaphthalene
(3k).
o
1
71%); m.p. = 125–127 C; TLC, Rf = 0.30 (PE/EtOAc = 50:1). H
NMR (400 MHz, CDCl3) δ 7.92 (s, 1H), 7.81 (d, J = 8.8 Hz, 1H),
7.75 (d, J = 8.8 Hz, 1H), 7.72–7.69 (m, 2H), 7.61–7.58 (m, 1H),
7.50–7.42 (m, 4H), 7.41–7.34 (m, 4H), 7.27–7.21 (m, 2H), 5.18
(s, 2H); 13C NMR (100 MHz, CDCl3) δ 157.1, 141.2, 139.1, 136.8,
134.7, 129.2, 128.8, 128.6, 128.2, 128.1, 128.0, 127.5, 127.4,
127.3, 124.8, 123.5, 119.1, 107.5, 70.0; IR(neat) 2924, 1625,
1454, 1373, 1207, 1173, 1127, 1007, 885, 755, 697 cm-1; HRMS
(ESI-TOF) m/z: [M+H]+ Calcd for C23H19O 311.1430; Found
311.1426.
slight yellow oil (63 mg, 72%); TLC, Rf = 0.34 (PE/EtOAc =
1
50:1). H NMR (400 MHz, CDCl3) δ 8.05 (s, 1H), 7.93–7.90 (m,
2H), 7.84 (s, 1H), 7.81–7.73 (m, 3H), 7.54–7.49 (m, 3H), 7.38 (t, J
= 7.2 Hz, 1H), 5.07 (s, 1H), 4.98 (s, 1H), 4.68 (d, J = 5.2 Hz, 2H),
4.01 (s, 2H), 1.82 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 142.2,
141.0, 138.5, 136.0, 133.2, 132.4, 128.8, 128.4, 128.36, 127.4,
127.3, 126.2, 126.1, 125.8, 125.6, 112.4, 74.1, 71.9, 19.6;
IR(neat) 2697, 2913, 2849, 1657, 1446, 1353, 1138, 1123, 889,
825, 752, 691 cm-1; HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for
C21H20ONa 311.1406; Found 311.1404.
2-Phenoxy-7-phenylnaphthalene (3f). white solid (62 mg,
N,N-Dimethyl-7-phenylnaphthalen-1-amine (3l). white solid
(56 mg, 75%). m.p. = 77–79 oC; TLC, Rf = 0.28 (PE/EtOAc =
10:1). 1H NMR (400 MHz, CDCl3) δ 8.54 (t, J = 0.8 Hz, 1H), 7.94
(d, J = 8.4 Hz, 1H), 7.82–7.76 (m, 3H), 7.64–7.53 (m, 3H), 7.48–
7.40 (m, 2H), 7.17–7.15 (m, 1H), 2.99 (s, 6H); 13C NMR (100
MHz, CDCl3) δ 151.1, 141.6, 137.8, 133.9, 128.9, 128.86, 128.8,
127.5, 127.1, 125.9, 125.3, 122.5, 122.2, 114.3, 45.2; IR(neat)
2942, 2823, 1596, 1493, 1449, 1373, 1179, 1037, 932, 838, 751,
694 cm-1; HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C18H18N
248.1434; Found 248.1432.
9-Phenylphenanthrene (known compounds 5, known 3m).63
white solid (69 mg, 90%); TLC, Rf = 0.36 (PE/EtOAc = 100:1).
1H NMR (400 MHz, CDCl3) δ 8.87 (d, J = 8.4 Hz, 1H), 8.81 (d, J
= 8.0 Hz, 1H), 8.09 (d, J = 7.6 Hz, 1H), 8.01–7.99 (m, 1H), 7.83–
7.82 (m, 1H), 7.79–7.58 (m, 9H); 13C NMR (100 MHz, CDCl3) δ
140.8, 138.7, 131.5, 131.1, 130.5, 130.0, 129.9, 128.6, 128.3,
127.5, 127.3, 126.9, 126.8, 126.5, 126.4, 126.39, 122.9, 122.5;
GC-MS (EI): [M+] Calcd for C20H14 254.11; Found 254.10.
o
1
70%); m.p. = 105–108 C; TLC, Rf = 0.33 (PE/EtOAc = 50:1). H
NMR (400 MHz, CDCl3) δ 7.92–7.87 (m, 3H), 7.74–7.69 (m, 3H),
7.52–7.48 (m, 2H), 7.43–7.39 (m, 4H), 7.30 (dd, J = 8.8, 2.4 Hz,
1H), 7.20–7.12 (m, 3H); 13C NMR (100 MHz, CDCl3) δ 157.1,
155.6, 140.9, 139.2, 134.5, 129.8, 129.6, 129.3, 128.8, 128.2,
127.4, 127.38, 125.0, 124.4, 123.5, 120.0, 119.2, 114.2; IR(neat)
2923, 2852, 1585, 1486, 1218, 1166, 964, 910, 848, 757, 696,
689 cm-1; HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C22H17O
297.1274; Found 297.1279.
Tert-butyldimethyl((7-phenylnaphthalen-2-yl)oxy)silane (3g).
slight yellow oil (76 mg, 76%); TLC, Rf = 0.33 (PE/EtOAc =
1
100:1). H NMR (400 MHz, CDCl3) δ 7.94 (d, J = 1.2 Hz, 1H),
7.86 (d, J = 8.4 Hz, 1H), 7.79–7.74 (m, 3H), 7.63 (dd, J = 8.4, 1.6
Hz, 1H), 7.53–7.49 (m, 2H), 7.43–7.39 (m, 1H), 7.30 (d, J = 2.4
Hz, 1H), 7.12 (dd, J = 8.8, 1.6 Hz, 1H), 1.09 (s, 9H), 0.30 (s, 6H);
13C NMR (100 MHz, CDCl3) δ 153.9, 141.2, 138.8, 134.9, 129.1,
128.8, 128.4, 128.1, 127.4, 127.3, 124.6, 123.4, 122.2, 115.0,
25.4, 18.3, –4.3; IR(neat): 2928, 2857, 1629, 1459, 1368, 1240,
1169, 971, 836, 763, 752, 696 cm-1; HRMS(ESI-TOF) m/z:
[M+H]+ Calcd for C22H27OSi 335.1826; Found 335.1828.
[1,1':4',1''-Terphenyl]-4-carbaldehyde (3n). white solid (36
mg, 46%); m.p. = 201–203 oC; TLC, Rf = 0.25 (PE/EtOAc =
100:1). H NMR (400 MHz, CDCl3) δ 10.07 (s, 1H), 7.97 (d, J =
1
7-Phenylnaphthalen-2-ol (known compounds 3, known
3h).61 white solid (53 mg, 80%); TLC, Rf = 0.30 (PE/EtOAc =
10:1). H NMR (400 MHz, CDCl3) δ 7.83 (t, J = 8.4 Hz, 2H), 7.77
8.4 Hz, 2H), 7.80 (d, J = 8.4 Hz, 2H), 7.73 (s, 4H), 7.65 (d, J = 8.0
Hz, 2H), 7.47 (t, J = 8.0 Hz, 2H), 7.38 (t, J = 7.2 Hz, 1H); 13C
NMR (100 MHz, CDCl3) δ 191.9, 146.6, 141.3, 140.3, 138.5,
135.2, 130.3, 128.9, 127.7, 127.69, 127.6, 127.5, 127.0; IR(neat)
2833, 2741, 1700, 1600, 1482, 1204, 1172, 1003, 818, 724, 686
cm-1; HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C19H14ONa
281.0937; Found 281.0937.
1
(d, J = 8.8 Hz, 1H), 7.70 (d, J = 7.2 Hz, 2H), 7.59 (dd, J = 8.4, 1.6
Hz, 1H), 7.47 (t, J = 8.0 Hz, 2H), 7.37 (t, J = 8.0 Hz, 1H), 7.20 (d,
J = 2.0 Hz, 1H), 7.10 (dd, J = 8.8, 2.4 Hz, 1H), 5.05 (s, 1H); 13C
NMR (100 MHz, CDCl3) δ 153.6, 141.2, 139.2, 134.9, 129.7,
128.8, 128.1, 127.4, 127.36, 124.3, 123.4, 117.7, 109.8; GC-MS
(EI): [M+] Calcd for C16H12O 220.09; Found 220.08.
2-Methyl-6-phenylquinoline (known compounds 6, known
3o).64 yellow solid (17 mg, 26%); TLC, Rf = 0.34 (PE/EtOAc =
10:1). H NMR (400 MHz, CDCl3) δ 8.10–8.08 (m, 2H), 7.96–
1
2-(3-Methoxyphenyl)-6-phenylnaphthalene (3i). white solid
(66 mg, 71%); m.p. = 113–115 C; TLC, Rf = 0.34 (PE/EtOAc =
o
7.94 (m, 2H), 7.73–7.71 (m, 2H), 7.51–7.47 (m, 2H), 7.41–7.37
(m, 1H), 7.30 (d, J = 8.4 Hz, 1H), 2.77 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 159.0, 147.3, 140.5, 138.4, 136.3, 129.1, 129.0,
128.9, 127.5, 127.4, 126.6, 125.2, 122.4, 25.5; GC-MS (EI): [M+]
Calcd for C16H13N 219.10; Found 219.11.
1
50:1). H NMR (400 MHz, CDCl3) δ 8.08 (s, 2H), 7.97 (dd, J =
8.4, 1.6 Hz, 2H), 7.81–7.75 (m, 4H), 7.50 (t, J = 8.0 Hz, 2H),
7.45–7.39 (m, 2H), 7.34 (d, J = 8.0 Hz, 1H), 7.30 (d, J = 1.6 Hz,
1H), 6.95 (dd, J = 8.4, 1.6 Hz, 1H), 3.92 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 160.0, 142.4, 141.0, 138.6, 138.4, 132.9, 132.8,
129.9, 128.9, 128.7, 128.67, 127.4, 126.0, 125.6, 125.5, 119.9,
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2-Phenylpyridine (known compounds 7, known 3p).65 slight
yellow oil (18 mg, 39%); TLC, Rf = 0.30 (PE/EtOAc = 20:1). H
7.95–7.89 (m, 3H), 7.78–7.76 (m, 1H), 7.53–7.51 (m, 2H), 7.45–
7.42 (m, 1H), 7.34 (d, J = 8.0 Hz, 1H), 7.30–7.27 (m, 1H), 6.98–
1
1
2
3
4
5
6
7
8
NMR (400 MHz, CDCl3) δ 8.71–8.69 (m, 1H), 8.01–7.98 (m, 2H),
7.75–7.72 (m, 2H), 7.50–7.46 (m, 2H), 7.44–7.40 (m, 1H), 7.24–
7.21 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 157.5, 149.7, 139.3,
136.7, 128.9, 128.7, 126.9, 122.1, 120.5; GC-MS (EI): [M+]
Calcd for C11H9N 155.07; Found 155.10.
6.96 (m, 1H), 3.92 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 160.0,
142.6, 138.4, 133.6, 132.7, 129.9, 128.4, 128.2, 127.6, 126.3,
126.0, 125.9, 125.6, 119.9, 113.1, 112.7, 55.3; GC-MS (EI): [M+]
Calcd for C17H14O 234.10; Found 234.09.
(6-(3-Methoxyphenyl)naphthalen-2-yl)trimethylsilane (3w).
1
2-(4-Fluorophenyl)-7-methoxynaphthalene (3q). slight yel-
low solid (61 mg, 81%); m.p. = 97–98 oC; TLC, Rf = 0.28
(PE/EtOAc = 50:1). 1H NMR (400 MHz, CDCl3) δ 7.91 (d, J = 1.2
Hz, 1H), 7.83 (d, J = 8.4 Hz, 1H), 7.77 (d, J = 8.4 Hz, 1H), 7.70–
7.65 (m, 2H), 7.55 (dd, J = 8.4, 1.6 Hz, 1H), 7.21–7.16 (m, 4H),
3.96 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 161.2 (d, J = 245.0
Hz), 157.9, 138.0, 137.3 (d, J = 3.0 Hz), 134.8, 129.1, 128.8 (d, J
= 8.0 Hz), 128.2, 128.0, 124.5, 123.1, 118.8, 115.5 (d, J = 21.0
Hz), 105.9, 55.2; 19F NMR (377 MHz, CDCl3) δ –115.6; IR(neat)
2966, 2933, 1629, 1572, 1504, 1423, 1263, 1172, 1030, 897, 815,
734 cm-1; HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for
C17H13FONa 275.0843; Found 275.0847.
slight oil (78 mg, 85%); TLC, Rf = 0.33 (PE/EtOAc = 50:1). H
NMR (400 MHz, CDCl3) δ 8.06 (s, 2H), 7.95–7.90 (m, 2H), 7.77
(dd, J = 8.4, 1.6 Hz, 1H), 7.66 (d, J = 8.0 Hz, 1H), 7.41 (t, J = 8.0
Hz, 1H), 7.34 (d, J = 7.6 Hz, 1H), 7.30 (t, J = 2.0 Hz, 1H), 6.96
(dd, J = 8.0, 2.4 Hz, 1H), 3.92 (s, 3H), 0.40 (s, 9H); 13C NMR
(100 MHz, CDCl3) δ 160.0, 142.6, 138.7, 138.1, 133.8, 133.4,
132.1, 130.3, 129.8, 128.5, 127.2, 125.6, 125.57, 119.9, 113.1,
112.7, 55.4, -1.1; IR(neat) 2954, 1607, 1465, 1436, 1251, 1212,
1084, 1053, 819, 776, 751, 693 cm-1; HRMS (ESI-TOF) m/z:
[M+Na]+ Calcd for C20H22OSiNa 329.1332; Found 329.1329.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
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37
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48
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60
3-Methoxy-1,1':4',1''-terphenyl (known compounds 10,
known 3x).68 white solid (65 mg, 83%); TLC, Rf = 0.35
(PE/EtOAc = 50:1). H NMR (400 MHz, CDCl3) δ 7.70–7.66 (m,
1
2-(4-Chlorophenyl)-7-methoxynaphthalene (3r). slight yel-
low solid (71 mg, 88%); m.p. = 69–71 oC; TLC, Rf = 0.28
6H), 7.50–7.46 (m, 2H), 7.42–7.36 (m, 2H), 7.27–7.25 (m, 1H),
7.21–7.20 (m, 1H), 6.95–6.93 (m, 1H), 3.90 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 160.0, 142.2, 140.7, 140.3, 140.0, 129.8,
128.8, 127.5, 127.46, 127.4, 127.0, 119.5, 112.7, 55.2; GC-MS
(EI): [M+] Calcd for C19H16O 260.12; Found 260.11.
1
(PE/EtOAc = 50:1). H NMR (400 MHz, CDCl3) δ 7.91 (s, 1H),
7.83 (d, J = 8.4 Hz, 1H), 7.75 (d, J = 8.8 Hz, 1H), 7.63 (d, J = 8.4
Hz, 2H), 7.54 (dd, J = 8.4, 2.0 Hz, 1H), 7.44 (d, J = 8.4 Hz, 2H),
7.19–7.15 (m, 2H), 3.95 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
158.1, 139.7, 137.8, 134.8, 133.4, 129.1, 128.9, 128.6, 128.3,
128.2, 124.7, 123.0, 119.0, 106.0, 55.3; IR(neat) 2966, 1627,
1515, 1492, 1420, 1241, 1171, 1094, 1027, 834, 778, 758 cm-1;
HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C17H14ClO 269.0728;
Found 269.0728.
2-(3-Methoxyphenyl)-6-phenylnaphthalene (3y). white solid
o
(75 mg, 80%); m.p. = 113–115 C; TLC, Rf = 0.31 (PE/EtOAc =
1
50:1). H NMR (400 MHz, CDCl3) δ 8.08 (s, 2H), 7.97 (dd, J =
8.4, 1.6 Hz, 2H), 7.81–7.75 (m, 4H), 7.50 (t, J = 8.0 Hz, 2H),
7.45–7.39 (m, 2H), 7.34 (d, J = 8.0 Hz, 1H), 7.30 (d, J = 1.6 Hz,
1H), 6.95 (dd, J = 8.4, 1.6 Hz, 1H), 3.92 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 160.0, 142.4, 141.0, 138.6, 138.4, 132.9, 132.8,
129.9, 128.9, 128.7, 128.67, 127.4, 126.0, 125.6, 125.5, 119.9,
113.1, 112.8, 55.3; IR(neat) 2955, 2835, 1576, 1485, 1433, 1296,
1205, 1029, 871, 789, 755,695 cm-1; HRMS (ESI-TOF) m/z:
[M+H]+ Calcd for C23H19O 311.1430; Found 311.1435.
2-Methoxy-7-(m-tolyl)naphthalene (3s). slight oil (62 mg,
1
83% yield); TLC, Rf = 0.26 (PE/EtOAc = 50:1). H NMR (400
MHz, CDCl3) δ 8.07 (d, J = 4.4 Hz, 1H), 7.93–7.90 (m, 1H), 7.87–
7.83 (m, 1H), 7.72–7.65 (m, 3H), 7.50–7.46 (m, 1H), 7.33–7.27
(m, 3H), 4.01 (s, 3H), 2.58 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
157.9, 141.2, 139.1, 138.3, 134.8, 129.1, 128.7, 128.1, 128.0,
124.6, 124.5, 123.3, 118.6, 105.9, 55.1, 21.5; HRMS (ESI-TOF)
m/z: [M+Na]+ Calcd for C18H16ONa 271.1093; Found 271.1089.
2-(4-Fluorophenyl)-6-(3-methoxyphenyl)naphthalene (3z).
white solid (91 mg, 92%); m.p. = 153–155 oC; TLC, Rf = 0.31
1
N,N-Dimethyl-4-(naphthalen-2-yl)aniline (known com-
pounds 8, known 3t).66 white solid (40 mg, 54%); TLC, Rf =
(PE/EtOAc = 50:1). H NMR (400 MHz, CDCl3) δ 8.07 (s, 1H),
8.01 (s, 1H), 7.97 (d, J = 3.6 Hz, 1H), 7.94 (d, J = 4.0 Hz, 1H),
7.78 (dd, J = 8.4, 1.6 Hz, 1H), 7.74–7.67 (m, 3H), 7.41 (t, J = 8.0
Hz, 1H), 7.33 (d, J = 7.6 Hz, 1H), 7.30–7.29 (m, 1H), 7.22–7.16
(m, 2H), 6.97–6.95 (m, 1H), 3.92 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 161.3 (d, J = 245.0 Hz), 160.1, 142.5, 138.5, 137.6,
137.1 (d, J = 3.0 Hz), 132.9, 132.7, 129.9, 128.9, 128.8 (d, J = 3.0
Hz), 128.6, 126.1, 125.8, 125.6, 125.3, 119.9, 115.6 (d, J = 21.0
Hz), 113.1, 112.8, 55.3; 19F NMR (377 MHz, CDCl3) δ = -115.4;
IR(neat) 2932, 2837, 1578, 1488, 1436, 1292, 1207, 1056, 839,
808, 791, 688 cm-1; HRMS (ESI-TOF) m/z: [M+H]+ Calcd for
C23H18FO 329.1336; Found 329.1334.
1
0.31 (PE/EtOAc = 10:1). H NMR (400 MHz, CDCl3) δ 8.01 (d, J
= 1.2 Hz, 1H), 7.90–7.84 (m, 3H), 7.75 (dd, J = 8.4, 1.6 Hz, 1H),
7.69–7.65 (m, 2H), 7.51–7.43 (m, 2H), 6.88–6.86 (m, 2H), 3.03
(s, 6H); 13C NMR (100 MHz, CDCl3) δ 150.0, 138.5, 133.9, 132.0,
128.9, 128.2, 127.93, 127.9, 127.6, 126.0, 125.3, 125.2, 124.2,
112.8, 40.3; GC-MS (EI): [M+] Calcd for C18H17N 247.14; Found
247.13.
7-Methoxy-2,2'-binaphthalene (3u). white solid (73 mg,
85%); TLC, Rf = 0.32 (PE/EtOAc = 50:1). H NMR (400 MHz,
1
CDCl3) δ 8.14 (s, 1H), 8.05 (s, 1H), 7.94–7.84 (m, 5H), 7.77–7.70
(m, 2H), 7.52–7.46 (m, 2H), 7.21 (s, 1H), 7.15 (dd, J = 8.8, 2.4
Hz, 1H), 3.92 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 150.8, 138.9,
138.6, 134.9, 133.7, 132.6, 129.1, 128.4, 128.23, 128.20, 128.18,
127.6, 126.3, 126.1, 125.9, 125.7, 125.1, 123.5, 118.8, 106.1,
55.2; HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C21H17O
285.1274; Found: 285.1272.
2-(4-Chlorophenyl)-6-(3-methoxyphenyl)naphthalene (3aa).
white solid (86 mg, 83%); m.p. = 158–160 oC; TLC, Rf = 0.32
(PE/EtOAc = 50:1). H NMR (400 MHz, CDCl3) δ 8.07 (s, 1H),
1
8.03 (s, 1H), 7.98–7.94 (m, 2H), 7.80–7.65 (m, 4H), 7.53–7.45
(m, 2H), 7.41 (d, J = 8.0 Hz, 1H), 7.33 (d, J = 7.6 Hz, 1H), 7.28 (t,
J = 2.0 Hz, 1H), 6.97–6.95 (m, 1H), 3.92 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 160.1, 142.4, 139.4, 138.7, 137.4, 133.5, 132.9,
132.86, 129.9, 129.0, 128.9, 128.7, 128.6, 127.4, 126.2, 125.6,
125.56, 125.4, 119.9, 113.1, 112.8, 55.3; IR(neat) 3027, 2927,
1600, 1485, 1432, 1294, 1229, 1171, 1091, 1033, 1010, 875, 776,
2-(3-Methoxyphenyl)naphthalene (known compounds 9,
known 3v).67 white solid (61 mg, 87%); TLC, Rf = 0.29
(PE/EtOAc = 50:1). H NMR (400 MHz, CDCl3) δ 8.08 (s, 1H),
1
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7.94–7.88 (m, 3H), 7.72-7.65 (m, 3H), 7.54-7.46 (m, 4H); 13C
670 cm-1; HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C23H18ClO
1
2
3
4
5
6
7
8
345.1041; Found 345.1035.
NMR (100 MHz, CDCl3) δ 139.5, 137.2, 133.6, 133.4, 132.7,
129.0, 128.6, 128.2, 127.6, 126.4, 126.1, 125.7, 125.2; GC-MS
(EI): [M+] Calcd for C16H11Cl 238.05; Found 238.02.
2-(3-Methoxyphenyl)-9-methyl-9H-carbazole (3ab). white
solid (65 mg, 75%); m.p. = 85–86 oC; TLC, Rf = 0.25 (PE/EtOAc
1
= 20:1). H NMR (400 MHz, CDCl3) δ 8.31 (t, J = 8.0 Hz, 2H),
Application of the Cr-Catalyzed Arylative Kumada Cou-
pling. (1) Functionalization of Estrone Derivative: The gen-
eral procedure was applied to 2-(4-((8R,9S,13S,14S,17S)-3,17-
dimethoxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-
7.61 (s, 1H), 7.54–7.50 (m, 2H), 7.42 (t, J = 8.0 Hz, 2H), 7.35 (dd,
J = 7.6, 1.2 Hz, 1H), 7.32–7.28 (m, 2H), 6.97–6.95 (m, 1H), 3.93
(s, 3H), 3.89 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 159.9, 143.7,
141.5, 141.4, 138.9, 129.7, 125.7, 122.5, 122.1, 120.4, 120.3,
120.1, 119.0, 118.6, 113.4, 112.3, 108.4, 107.0, 55.3, 29.0;
IR(neat) 2923, 1604, 1561, 1419, 1316, 1205, 1174, 1050, 1032,
889, 724, 696 cm-1; HRMS (ESI-TOF) m/z: [M+H]+ Calcd for
C20H18NO 288.1383; Found 288.1378.
6H-cyclopenta[a]phenanthren-2-yl)phenoxy)pyridine
(141
9
mg, 0.3 mmol) and phenylmagnesium bromide (0.9 mL, 1.0
M in THF, 0.9 mmol). The crude product was purified by col-
umn chromatography on silica gel (EtOAc/PE = 1/10) to af-
ford the title compound. (8R,9S,13S,14S,17S)-2-([1,1'-
Biphenyl]-4-yl)-3,17-dimethoxy-13-methyl-
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
2,7-Bis(3-methoxyphenyl)naphthalene (3ac). white solid (83
o
7,8,9,11,12,13,14,15,16,17-decahydro-6H-
mg, 81%); m.p. = 90–91 C; TLC, Rf = 0.34 (PE/EtOAc = 20:1).
1H NMR (400 MHz, CDCl3) δ 8.11 (s, 2H), 7.93 (d, J = 8.4 Hz,
2H), 7.75 (d, J = 8.4 Hz, 2H), 7.45–7.41 (m, 2H), 7.34 (d, J = 6.8
Hz, 2H), 7.29 (s, 2H), 6.97–6.95 (m, 2H), 3.92 (s, 6H); 13C NMR
(100 MHz, CDCl3) δ 159.9, 142.2, 138.7, 133.6, 131.7, 129.6,
128.3, 126.1, 125.7, 119.8, 113.1, 112.8, 55.2; IR(neat) 2929,
1603, 1578, 1487, 1423, 1289, 1204, 1169, 1029, 841, 778, 966
cm-1; HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C24H20O2Na
363.1356; Found 363.1360.
cyclopenta[a]phenanthrene (5). white solid (80 mg, 59%);
o
1
m.p. = 172–174 C; TLC, Rf = 0.26 (PE/EtOAc = 50:1). H NMR
(400 MHz, CDCl3) δ 7.67–7.46 (m, 6H), 7.50–7.46 (m, 2H),
7.40–7.32 (m, 2H), 6.75 (d, J = 1.2 Hz, 1H), 3.84 (d, J = 2.8 Hz,
3H), 3.41 (d, J = 3.6 Hz, 3H), 3.38–3.33 (m, 1H), 2.96–2.94 (m,
2H), 2.39–2.26 (m, 2H), 2.10–2.07 (m, 2H), 1.97–1.94 (m, 1H),
1.78–1.71 (m, 1H), 1.64–1.43 (m, 6H), 1.30–1.23 (m, 1H), 0.84
(d, J = 4.0 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 154.3, 141.1,
139.5, 137.8, 137.3, 132.6, 129.9, 128.7, 128.0, 127.6, 127.1,
126.7, 111.5, 90.7, 57.9, 55.6, 50.2, 43.9, 43.2, 38.6, 38.0, 29.8,
27.7, 27.2, 26.5, 23.0, 11.5; IR(neat) 2921, 2850, 1498, 1483,
1448, 1390, 1225, 1130, 1101, 1047, 837, 771,698 cm-1; HRMS
(ESI-TOF) m/z: [M+Na]+ Calcd for C32H36O2Na 475.2608;
Found 475.2614. (2) Sequential Transformation of C–O Bonds:
In a dried Schlenk tube were placed 3a (47 mg, 0.2 mmol) and
[Ni(PCy3)2Cl2] (7 mg, 0.01 mmol), then a freshly distilled tolu-
ene (0.5 mL) was added by a syringe under atmosphere of
nitrogen. After stirring at room temperature for 5 min, (4-
methoxyphenyl)magnesium bromide (0.4 mL, 1.0 M in THF,
0.4 mmol) was dropwise added, and the mixture was stirred
2-(p-tolyl)naphthalene (known compounds 11, known
3ad).69 white solid (23 mg, 35%); TLC, Rf = 0.40 (PE/EtOAc =
100:1). 1H NMR (400 MHz, CDCl3) δ 8.06 (s, 1H), 7.94–7.88 (m,
3H), 7.76 (d, J = 8.4 Hz, 1H), 7.65 (d, J = 6.4 Hz, 2H), 7.54-7.48
(m, 2H), 7.32 (d, J = 7.2 Hz, 2H), 2.45 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 138.5, 138.2, 137.1, 133.7, 132.5, 129.6, 128.3,
128.1, 127.6, 127.2, 126.2, 125.7, 125.5, 125.4, 21.1; GC-MS
(EI): [M+] Calcd for C17H14 218.11; Found 218.08.
2-(4-(Tert-butyl)phenyl)naphthalene (known compounds 12,
known 3ae).69 white solid (35 mg, 45%); TLC, Rf = 0.26
1
(PE/EtOAc = 100:1). H NMR (400 MHz, CDCl3) δ 8.06 (s, 1H),
o
7.93–7.87 (m, 3H), 7.76 (dd, J = 8.4, 1.6 Hz, 1H), 7.71–7.68 (m,
2H), 7.55–7.46 (m, 4H), 1.04 (s, 9H); 13C NMR (100 MHz, CDCl3)
δ 150.4, 138.4, 138.2, 133.7, 132.5, 128.3, 128.1, 127.6, 127.0,
126.2, 125.8, 125.75, 125.6, 125.5, 34.6, 31.4; GC-MS (EI): [M+]
Calcd for C20H20 260.16; Found 260.15.
at 30 C for 1 h. After quenched with saturated aqueous solu-
tion of NH4Cl (1 mL), the mixture was extracted three times
with ethyl acetate. The organic phases were collected, dried
over anhydrous Na2SO4 and concentrated under reduced
pressure. The residue was purified by column chromatog-
raphy (EtOAc/PE = 1/50) to afford the desired coupling prod-
uct. 2-(4-Methoxyphenyl)-7-phenylnaphthalene (6). slight oil
2-(4-Methoxyphenyl)naphthalene (known compounds 13,
known 3af).69 white solid (20 mg, 29%); TLC, Rf = 0.33
(PE/EtOAc = 50:1). H NMR (400 MHz, CDCl3) δ 8.01 (s, 1H),
1
1
(63 mg, 83%); TLC, Rf = 0.36 (PE/EtOAc = 50:1). H NMR (400
MHz, CDCl3) δ 8.10 (s, 1H), 8.07 (s, 1H), 7.95–7.91 (m, 2H),
7.78–7.72 (m, 4H), 7.717–7.69 (m, 2H), 7.54–7.50 (m, 2H), 7.43–
7.41 (m, 1H), 7.07–7.04 (m, 2H), 3.89 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 159.3, 141.1, 138.9, 138.6, 134.0, 133.6, 131.5,
128.8, 128.4, 128.1, 128.08, 127.4, 127.36, 125.9, 125.5, 125.4,
125.3, 114.3, 55.4; IR(neat) 2956, 1604, 1506, 1463, 1292, 1246,
1182, 1038, 902, 833, 760, 699 cm-1; HRMS (ESI-TOF) m/z:
[M+H]+ Calcd for C23H19O 311.1430; Found 311.1425.
7.92–7.86 (m, 3H), 7.73 (dd, J = 8.4, 1.6 Hz, 1H), 7.67 (d, J = 8.8
Hz, 2H), 7.53–7.46 (m, 2H), 7.03 (d, J = 8.8 Hz, 2H), 3.89 (s, 3H);
13C NMR (100 MHz, CDCl3) δ 159.2, 138.1, 133.7, 133.6, 132.3,
128.4, 128.3, 128.0, 127.6, 126.2, 125.6, 125.4, 125.0, 114.3,
55.4; GC-MS (EI): [M+] Calcd for C17H14O 234.10; Found 234.12.
2-(4-Fluorophenyl)naphthalene (known compounds 14,
known 3ag).70 white solid (32 mg, 48%); TLC, Rf = 0.38
1
(PE/EtOAc = 100:1). H NMR (400 MHz, CDCl3) δ 8.01 (s, 1H),
Preliminary Mechanistic Studies. Probing the Catalytic
Activity of Low-Valent Cr Species that was Formed in-Situ in
the Cleavage of C(aryl)–O Bond: In a dried Schlenk tube were
placed CrCl2 (4–18 mg, 0.03–0.15 mmol), a freshly distilled
THF (0.5 mL) was added by a syringe under atmosphere of
nitrogen. After stirring at room temperature for 5 min, phe-
nylmagnesium bromide (0.06–0.3 mL, 1.0 M in THF, 0.06–0.3
7.94–7.88 (m, 3H), 7.72–7.67 (m, 3H), 7.54–7.51 (m, 2H), 7.21–
7.17 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 161.3 (d, J = 245.0
Hz), 137.5, 137.2 (d, J = 3.0 Hz), 133.6, 132.4, 128.9 (d, J = 8.0
Hz), 128.5, 128.1, 127.6, 126.4, 126.0, 125.6, 125.4, 115.6 (d, J
= 21.0 Hz); 19F NMR (377 MHz, CDCl3) δ –115.4; GC-MS (EI):
[M+] Calcd for C16H11F 222.08; Found 222.10.
2-(4-chlorophenyl)naphthalene (known compounds 15,
known 3ah).69 white solid (30 mg, 42%); TLC, Rf = 0.29
(PE/EtOAc = 100:1). H NMR (400 MHz, CDCl3) δ 8.02 (s, 1H),
o
mmol) was dropwise added, after stirring at 40 C for 30 min,
1
the mixture was added 2-(naphthalen-2-yloxy)pyridine (67
mg, 0.3 mmol) and (4-methoxyphenyl)magnesium bromide
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Supporting Information. 1H, 13C and 19F NMR spectra and kinet-
ic data. This material is available free of charge via the Internet
at http://pubs.acs.org.
(0.9 mL, 1.0 M in THF, 0.9 mmol) stirred at 40 oC for 12 h.
After quenched with saturated aqueous solution of NH4Cl (1
mL), the mixture was extracted three times with ethyl ace-
tate. The organic phases were collected, dried over anhy-
drous Na2SO4 and concentrated under reduced pressure. The
residue was purified by column chromatography to afford
the desired coupling product. 2-Phenylnaphthalene (known
compounds 16, known 3ai).70 1H NMR (400 MHz, CDCl3) δ
8.09 (s, 1H), 7.97–7.89 (m, 3H), 7.81–7.76 (m, 3H), 7.57–7.52 (m,
4H), 7.45–7.41 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 141.1,
138.5, 133.7, 132.6, 128.8, 128.4, 128.2, 127.6, 127.4, 127.3,
126.3, 125.9, 125.8, 125.6; GC-MS (EI): [M+] Calcd for C16H12
204.09; Found 204.10.
1
2
3
4
5
6
7
8
AUTHOR INFORMATION
Corresponding Author
*E-mails: zengxiaoming@scu.edu.cn (X.Z)
luomm@scu.edu.cn (M.L.)
Notes
The authors declare no competing financial interests.
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ACKNOWLEDGMENT
We thank the National Natural Science Foundation of China
(Nos. 21202128 , 21572175 and 21871186 ), SCU and BNLMS for
financial support of this research.
Kinetic Studies. (1) Procedure for determining the order in
CrCl2: Aryl 2-Pyridyl ether 1a (0.500 mmol) and different
amounts of CrCl2 (0.0125, 0.025, 0.0375, 0.05, 0.075 mmol)
were placed in a Schlenk tube, followed by addition of n-
tridecane (0.25 mmol, an internal standard for GC analysis)
and freshly distilled THF (0.5 mL). After stirring the mixture
for 5 min, phenylmagnesium bromide 2a (1.5 mmol, 1 M in
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THF) was dropwise added by syringe in one minute at 40 C.
Periodic aliquots (30 μL) were removed by a syringe and
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(0.05 mmol) were placed in a Schlenk tube, followed by addi-
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concentration of 1a at 0.25 M ). After stirring the mixture for
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2.0 mmol, 1 M in THF) was dropwise added by syringe in one
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o
minute at 40 C. Periodic aliquots (30 μL) were removed by a
syringe and quenched by an aqueous solution of NH4Cl (3 N,
0.5 mL) for another 5 min. The resulting mixture was extract-
ed with ethyl acetate (1.0 mL) and the organic phase was
analyzed by GC using n-tridecane as internal standard. The
concentrations of the products were plotted to yield the ini-
tial rates for the formation of 3a. (3) Procedure for determin-
ing the order in Aryl 2-Pyridyl ether 1a: Different amounts of
Aryl 2-Pyridyl ether 1a (0.25, 0.50, 0.75, 1.00, 1.25, 1.50 mmol)
and different amounts of CrCl2 (0.05 mmol) were placed in a
Schlenk tube, followed by addition of n-tridecane (0.25 mmol,
an internal standard for GC analysis) and freshly distilled THF
(0.5 mL). After stirring the mixture for 5 min, phenylmagne-
sium bromide 2a (1.5 mmol, 1 M in THF) was dropwise added
by syringe in one minute at 40 oC. Periodic aliquots (30 μL)
were removed by a syringe and quenched by an aqueous
solution of NH4Cl (3 N, 0.5 mL) for another 5 min. The result-
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organic phase was analyzed by GC using n-tridecane as in-
ternal standard. The concentrations of the products were
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ArMgBr
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O
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RO
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