Palladium-catalyzed oxidative olefination of phenols bearing removable directing groups under molecular oxygen

Article abstract of DOI:10.1021/jo4027403

An efficient Pd(II)-catalyzed oxidative olefination of phenols bearing removable directing groups with molecular oxygen as the sole oxidant has been developed. This reaction protocol provides an efficient and robust synthetic tool for the synthesis of o-alkenyl phenols under mild conditions.

Full text of DOI:10.1021/jo4027403

Note
pubs.acs.org/joc
Palladium-Catalyzed Oxidative Olefination of Phenols Bearing
Removable Directing Groups under Molecular Oxygen
Bin Liu,† Huai-Zhi Jiang,† and Bing-Feng Shi*,†,‡
†Department of Chemistry, Zhejiang University, Hangzhou 310027, China
‡State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of
Sciences, Shanghai 200032, China
S
* Supporting Information
ABSTRACT: An efficient Pd(II)-catalyzed oxidative olefina-
tion of phenols bearing removable directing groups with
molecular oxygen as the sole oxidant has been developed. This
reaction protocol provides an efficient and robust synthetic
tool for the synthesis of o-alkenyl phenols under mild
conditions.
ransition-metal-catalyzed oxidative cross-coupling reac-
chiometric amounts of metal oxidant [2.0 equiv of Cu(OAc)2·
Ttions have emerged as powerful tools for the construction H2O] and additive (0.25 equiv of AgSbF6) have to be used in
these reactions, which is not synthetically efficient and
beneficial from an environmental point of view. You reported
an efficient method for the olefination of arenes with 2-
pyridylmethyl as a removable directing group using oxygen as
the oxidant,10 but external additives such as 2 equiv of KHCO3
and an amino acid ligand were still needed. Herein we report a
palladium-catalyzed oxidative olefination of phenol derivatives
with molecular oxygen as the sole oxidant that does not require any
other additives. The directing group can be easily removed,
providing o-alkenylated phenols (Figure 1).
We initiated our studies with the coupling of 2-phenoxypyr-
idine (1a) and ethyl acrylate using Pd(OAc)2 (10 mol %) as a
catalyst in the presence of an oxidant under atmospheric
pressure of O2 at 100 °C. The desired product 2a was isolated
in 36% yield with a high level of selectivity when Cu(OAc)2 was
used as the oxidant (mono:di = 11:1; Table 1, entry 1).
Switching to a silver oxidant, such as AgTFA, gave a slightly
higher yield with more diolefinated product 2a′ (45%, mono:di
= 3.1:1; entry 2). Encouraged by the result that the yield
dropped when the atmosphere of O2 was replaced by N2 (entry
3), we began to use molecular oxygen as the sole oxidant. We
were delighted to find that the yield improved to 60% with the
monoolefinated product 2a produced dominantly (entry 4). A
variety of solvents such as DMAc, DMF, and MeNO2 were
screened, and the yield improved to 72% when MeNO2 was
used as the solvent. However, only moderate selectivity was
obtained (entry 7). We recently found that the use of a
coordinating solvent such as DMA or DMPU can improve the
selectivity.11 After further optimization, we were pleased to find
that the monoolefination of 1a occurred in 73% yield with high
of new C−C and C−heteroatom bonds in terms of atom and
step economy.1 A number of oxidants such as inorganic salts,
BQ, DDQ, IBX, and PhI(OAc)2 have been widely employed in
these transformations. However, in order to fulfill the
requirements of green chemistry,2 there is an increasing
demand to use oxidants that are environmentally friendly and
do not give rise to any waste products. Therefore, molecular
oxygen is recognized as the ideal oxidant because it is
environmentally friendly, inexpensive, and abundant and has a
high efficiency per unit mass of oxidant.3 However, oxidative
functionalization of C−H bonds under mild conditions using
atmospheric pressure of molecular oxygen as the sole oxidant
still remains a very challenging field.4
Fujiwara and Moritani reported the pioneering work on
alkenylation of electron-rich arenes with alkenes catalyzed by
palladium complexes.5 Recently, a large variety of oxidative
olefinations of aromatic C−H bonds have been reported.6
Alkenylation through the cleavage of two C−H bonds has
become an important transformation in organic synthesis.
However, in order to control the regioselectivity, directing
groups are usually introduced; nevertheless, the practicality
might be restricted when the directing groups cannot be easily
removed from the products. Therefore, significant efforts have
been directed toward the discovery of efficient and removable
directing groups.7
Phenol derivatives are common and important structural
motifs in bioactive natural products and pharmaceuticals.8
Many phenol derivatives, such as phenol esters,9a,b phenol
carbamates,9c,d and 2-phenoxypyridines,9e,h have been widely
employed in C−H activation. Liu and Loh independently
reported Rh(III)-catalyzed olefination of phenol carbamates,9c,d
and more recently, Ackermann reported a ruthenium-catalyzed
oxidative alkenylation of phenoxypyridines.9e However, stoi-
Received: December 10, 2013
Published: January 21, 2014
© 2014 American Chemical Society
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Note
acrylate reacted efficiently with 1m under the optimized
reaction conditions to give the corresponding products 2m−o
in good to excellent yields (entries 12−14). Unfortunately,
styrene was unreactive under the present reaction conditions
(entry 15). The presence of the pyridine directing group and
the C−H bond at the ortho position were found to be essential
for the reaction, since 1n−p did not give the desired product, as
shown at the bottom of Table 2.
The 2-pyridyl group could be easily removed using a
previously reported protocol.9f As shown in Scheme 1, the
olefinated product 2c was deprotected by treating it with
methyl trifluoromethanesulfonate (MeOTf) to form the
corresponding pyridinium in toluene. Subsequently, the crude
pyridinium was added into a refluxing Na/MeOH solution to
generate 3c in 68% yield for two steps. Furthermore, the
alkenylated phenol 3c could be converted into the correspond-
ing o-alkylated phenol 4c in 93% yield by hydrogenation.
Finally, a plausible mechanism for the present palladium(II)-
catalyzed oxidative olefination of 2-phenoxypyridine (1a) is
proposed on the basis of previous studies (Scheme 2).
Coordination of 1a to palladium acetate is followed by C−H
activation to form the dimeric palladacycle A.9g,10 Subsequently,
the olefin coordinates with palladacycle A via ligand exchange.
Either the cyclized intermediate C or the uncyclized
intermediate D is formed via olefin insertion, followed by β-
hydride elimination to give the desired product 2a and liberate
Pd(0). The Pd(II) is regenerated from the oxidation of Pd(0)
by molecular oxygen. DMPU can possibly act as a ligand to
improve the monoselectivity and prevent the aggregation of
Pd(0).11
Figure 1. Trasition-metal-catalyzed oxidative olefination of phenol
derivatives.
selectivity (mono:di = 13.6:1) when MeNO2 and DMPU were
used together (20:1 v/v) as cosolvents (entry 8). An attempt to
conduct the reaction under ambient air led to a reduced yield
(48%; entry 9).
With the optimized conditions in hand, we further explored
the scope of this oxidative olefination reaction. As shown in
Table 2, a wide range of phenol derivatives were compatible
with the optimized conditions and reacted efficiently with ethyl
acrylate to give the corresponding olefinated products in
moderate to high yields. Various methyl- and methoxy-
substituted phenols could be olefinated to give the desired
products in good yields (entries 1−3 and 5−6). However, the
o-methoxyphenol derivative gave a reduced yield (2e, 8%; entry
4), which might be due to weak coordination of the o-methoxy
group with palladium. Chloro- and trifluoromethoxy-substi-
tuted phenols were also compatible with the optimized
conditions, albeit affording the products in reduced yields
(entries 7−9). Reasonably, 3,5-dimethylphenol derivative 1j
reacted slowly to give the desired product in only 38% yield
because of the steric congestion at the ortho position (entry
10). The present reaction protocol was successfully extended to
other acrylates. Ethyl acrylate, methyl acrylate, and tert-butyl
In conclusion, we have developed a simple and efficient
palladium-catalyzed direct C−H olefination of phenol deriva-
tives with a readily removable directing group. This protocol
can proceed well with oxygen at atmospheric pressure as the
sole oxidant without the need of any other additives, providing
an expeditious strategy for the synthesis of o-alkenyl or o-alkyl
phenols.
EXPERIMENTAL SECTION
■
General Information. Dioxane was dried by sodium and freshly
distilled. The other materials and solvents were purchased from
commercial suppliers and used without additional purification. NMR
spectra were recorded at 400 MHz (1H) and 100 MHz (13C) using
a
Table 1. Optimization of the Reaction Conditions
d
Entry
Oxidant
T (°C)
Solvent
1,4-dioxane
Yield (%)
b
1
Cu(OAc)2
AgTFA
100
100
100
100
100
100
100
100
100
36 (11:1)
45 (3.1:1)
36 (3.5:1)
60 (9:1)
b
2
1,4-dioxane
c
3
AgTFA
1,4-dioxane
4
5
6
7
8
9
O2 (1 atm)
O2 (1 atm)
O2 (1 atm)
O2 (1 atm)
O2 (1 atm)
air (1 atm)
1,4-dioxane
DMAc
65 (3.3:1)
61 (7.7:1)
72 (5.5:1)
73 (13.6:1)
48 (16:1)
DMF
MeNO2
MeNO2:DMPU = 20:1
MeNO2:DMPU = 20:1
a
b
Reaction conditions: 1a (0.2 mmol), Pd(OAc)2 (10 mol %), ethyl acrylate (0.4 mmol), and oxidant in 2 mL of solvent at 100 °C for 24 h. Under
c
d
O2. Under N2. Yields of isolated products after chromatography. Values in parentheses are mono:di ratios.
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a
Table 2. Pd-Catalyzed Olefination of Phenol Derivatives
a
Reaction conditions: 1 (0.2 mmol), Pd(OAc)2 (10 mol %), ethyl acrylate (0.4 mmol), and O2 (1 atm) in MeNO2/DMPU (20:1 v/v) at 100 °C.
Yields of isolated products after chromatography. Values in parentheses are mono:di ratios. When no ratio is given, a less than 5% yield of
b
diolefinated product was observed.
TMS as an internal standard. Chemical shifts are given relative to
Scheme 1. Removal of the Directing Group
1
CDCl3 (7.26 ppm for H NMR, 77.16 ppm for 13C NMR). Data are
represented as follows: chemical shift (multiplicity, coupling
constant(s) in Hz, integration). Multiplicities are denoted as follows:
br = broad, s = singlet, d = doublet, t = triplet, q = quartet, m =
multiplet. Mass spectroscopy data of the products were collected on an
HRMS-TOF instrument using EI ionization.
General Procedure for the Olefination of 2-Phenoxypyridine
Derivatives 1 with Acrylates. A mixture of substrate (0.2 mmol),
Pd(OAc)2 (10 mol %), ethyl acrylate (0.4 mmol), CH3NO2 (2.0 mL),
and DMPU (0.1 mL) in a 50 mL Schlenk tube (purged with O2) was
heated at 100 °C for 24 h. The reaction mixture was cooled to room
temperature, and concentrated in vacuo. Purification of the residue by
chromatography with petroleum ether and EtOAc as the eluent
provided the desired products.
(E)-Ethyl 3-(2-(Pyridin-2-yloxy)phenyl)acrylate (2a). 2a was
obtained as a yellow oil (74 mg, 68% yield) according to the general
procedure. 1H NMR (400 MHz, CDCl3): δ 8.16 (dd, J1 = 4.8 Hz, J2 =
2.0 Hz, 1H), 7.89 (d, J = 16.0 Hz, 1H), 7.74−7.66 (m, 2H), 7.4 (dt, J1
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Note
1
mg, 5% yield) according to the general procedure. H NMR (400
MHz, CDCl3): δ 8.05 (d, J = 4.0 Hz, 1H), 7.74 (d, J = 8.8 Hz, 1H),
7.68 (d, J = 16.0 Hz, 2H), 7.51 (s, 2H), 7.06 (d, J = 8.4 Hz, 1H), 6.95
(t, J = 6.0 Hz, 1H), 6.40 (d, J = 16.0 Hz, 2H), 4.17 (q, J = 7.2 Hz, 4H),
2.40 (s, 3H), 1.26 (t, J = 7.0 Hz, 6H).
Scheme 2. Proposed Mechanism of Pd(II)-Catalyzed
Oxidative Olefination Reaction
(E)-Ethyl 3-(3-Methoxy-2-(pyridin-2-yloxy)phenyl)acrylate
(2e). 2e was obtained as a yellow solid (10 mg, 8% yield) according
1
to the general procedure. Mp: 113−115 °C. H NMR (400 MHz,
CDCl3): δ 8.09 (d, J = 4.0 Hz, 1H), 7.84 (d, J = 16.4 Hz, 1H), 7.67 (m,
1H), 7.28 (d, J = 8.0 Hz, 1H), 7.22 (t, J = 7.8 Hz, 1H), 7.01 (t, J = 8.2
Hz, 1H), 6.95 (t, J = 6.0 Hz, 1H), 6.45 (d, J = 16.0 Hz, 1H), 4.19 (q, J
= 7.0 Hz, 2H), 3.72 (s, 3H), 1.28 (t, J = 7.0 Hz, 1H). 13C NMR (100
MHz, CDCl3): 167.0, 163.5, 152.6, 147.6, 141.7, 139.5, 138.9, 129.3,
126.0, 120.4, 119.3, 118.4, 114.2, 110.6, 60.6, 56.2, 14.4. HRMS (EI-
TOF) m/z: calcd for C17H17NO4 (M+) 299.1158, found 299.1161.
(E)-Ethyl 3-(4-Methoxy-2-(pyridin-2-yloxy)phenyl)acrylate
(2f). 2f was obtained as a yellow oil (85 mg, 71%) according to the
1
general procedure. H NMR (400 MHz, CDCl3): δ 8.18 (d, J = 3.6
Hz, 1H), 7.81 (d, J = 16.0 Hz, 1H), 7.72 (dt, J1 = 7.8 Hz, J2 = 1.2 Hz,
1H), 7.61 (d, J = 8.8 Hz, 1H), 7.03−6.97 (m, 2H), 6.79 (dd, J1 = 8.8
Hz, J2 = 2.0 Hz, 1H), 6.61 (d, J = 2.0 Hz, 1H), 6.35 (d, J = 16.0 Hz,
1H), 4.19 (q, J = 7.1 Hz, 2H), 3.79 (s, 3H), 1.27 (t, J = 7.2 Hz, 3H).
13C NMR (100 MHz, CDCl3): δ 167.4, 163.4, 162.2, 154.3, 148.0,
139.8, 138.8, 129.2, 120.2, 119.0, 117.3, 111.9, 111.8, 107.7, 60.4, 55.7,
14.4. HRMS (EI-TOF) m/z: calcd for C17H17NO4 (M+) 299.1158,
found 299.1155.
= 8.4 Hz, J2 = 1.6 Hz, 1H), 7.23 (t, J = 7.4 Hz, 1H), 7.10 (d, J = 8.0
Hz, 1H), 7.02−6.97 (m, 2H), 6.47 (d, J = 16.4 Hz, 1H), 4.21 (q, J =
6.6 Hz, 2H), 1.29 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ
167.1, 163.6, 153.1, 147.9, 139.8, 139.0, 131.3, 128.2, 127.6, 125.3,
122.5, 120.0, 119.0, 111.9, 60.6, 14.4. HRMS (EI-TOF) m/z: calcd for
C16H15NO3 (M+) 269.1052, found 269.1050.
(2E,2′E)-Diethyl 3,3′-(2-(Pyridin-2-yloxy)-1,3-phenylene)-
diacrylate (2a′). 2a′ was obtained as a white solid (6 mg, 5%
yield) according to the general procedure. 1H NMR (400 MHz,
CDCl3): δ 8.04 (ddd, J1 = 5.0 Hz, J2 = 2.0 Hz, J3 = 0.8 Hz, 1H), 7.75−
7.69, (m, 3H), 7.72 (d, 16.0 Hz, 2H), 7.31 (t, J = 7.8 Hz, 1H), 7.06 (d,
J = 8.4 Hz, 1H), 6.98−6.94 (m, 1H), 6.42 (d, J = 16.4 Hz, 1H), 4.17
(q, J = 7.0 Hz, 4H), 1.26 (t, J = 7.0 Hz, 6H).
(E)-Ethyl 3-(5-Methoxy-2-(pyridin-2-yloxy)phenyl)acrylate
(2g). 2g was obtained as a yellow oil (57 mg, 56% yield) according
to the general procedure. 1H NMR (400 MHz, CDCl3): δ 8.14 (d, J =
4.0 Hz, 1H), 7.81 (d, J = 16.4 Hz, 1H), 7.68 (dt, J1 = 7.6 Hz, J2 = 1.2
Hz, 1H), 7.14 (d, J = 2.4 Hz, 1H), 7.05 (d, J = 9.2 Hz, 1H), 6.98−6.94
(m, 3H), 6.44 (d, J = 16.0 Hz, 1H), 4.20 (q, J = 7.1 Hz, 2H), 3.83 (s,
3H), 1.28 (t, J = 7.1 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 166.9,
164.0, 156.7, 147.8, 146.5, 139.7, 138.9, 128.3, 124.0, 120.0, 118.6,
117.7, 111.7, 111.4, 60.6, 55.7, 14.4. HRMS (EI-TOF) m/z: calcd for
C17H17NO4 (M+) 299.1158, found 299.1157.
(2E,2′E)-Diethyl 3,3′-(5-Methoxy-2-(pyridin-2-yloxy)-1,3-
phenylene)diacrylate (2g′). 2g′ was obtained as a yellow solid
(10 mg, 6%) according to the general procedure. 1H NMR (400 MHz,
CDCl3): δ 8.05 (d, J = 4.0 Hz, 1H), 7.72 (d, J = 7.2 Hz, 1H), 7.68 (d, J
= 16.0 Hz, 2H), 7.21 (s, 2H), 7.05 (d, J = 8.4 Hz, 1H), 6.95 (t, J = 6.0
Hz, 1H), 6.41 (d, J = 16.0 Hz, 2H), 4.17 (q, J = 7.2 Hz, 4H), 3.87 (s,
3H), 1.26 (t, J = 7.2 Hz, 6H).
(E)-Ethyl 3-(4-Chloro-2-(pyridin-2-yloxy)phenyl)acrylate
(2h). 2h was obtained as a yellow solid (50 mg, 41% yield) according
to the general procedure. Mp: 75−77 °C. 1H NMR (400 MHz,
CDCl3): δ 8.18 (d, J = 3.6 Hz, 1H), 7.82 (d, J = 16.0 Hz, 1H), 7.75
(dt, J1 = 7.8 Hz, J2 = 1.8 Hz, 1H), 7.59 (d, J = 8.4 Hz, 1H), 7.19 (dd, J1
= 8.4 Hz, J2 = 1.6 Hz, 1H), 7.11 (d, J = 2.0 Hz, 1H), 7.07−7.01 (m,
2H), 6.45 (d, J = 16.0 Hz, 1H), 4.21 (q, J = 7.2 Hz, 2H), 1.29 (t, J =
7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 166.9, 162.9, 153.4,
147.9, 140.0, 137.9, 136.5, 128.9, 126.0, 122.7, 120.2, 119.5, 112.1,
60.7, 14.4. HRMS (EI-TOF) m/z: calcd for C16H14ClNO3 (M+)
303.0662, found 303.0661.
(E)-Ethyl 3-(3-Methyl-2-(pyridin-2-yloxy)phenyl)acrylate
(2b). 2b was obtained as a white solid (70 mg, 62% yield) according
1
to the general procedure. Mp: 106−107 °C. H NMR (400 MHz,
CDCl3): δ 8.10 (dd, J1 = 5.0 Hz, J2 =1.8 Hz, 1H), 7.79 (d, J = 16.0 Hz,
1H), 7.69 (dt, J1 = 7.8 Hz, J2 = 1.8 Hz, 1H), 7.53 (d, J = 7.6 Hz, 1H),
7.30 (d, J = 7.2 Hz, 1H), 7.19 (t, J = 7.2 Hz, 1H), 6.95−6.93 (m, 2H),
6.42 (d, J = 16.0 Hz, 1H), 4.18 (q, J = 7.1 Hz, 2H), 2.10 (s, 3H), 1.26
(t, J = 7.0 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 167.0, 163.3,
150.9, 147.9, 139.7, 139.3, 133.2, 132.5, 128.4, 125.8, 125.5, 119.9,
118.3, 110.4, 60.5, 16.8, 14.4. HRMS (EI-TOF) m/z: calcd for
C17H17NO3 (M+) 283.1208, found 283.1205.
(E)-Ethyl 3-(4-Methyl-2-(pyridin-2-yloxy)phenyl)acrylate
(2c). 2c was obtained as a white solid (100 mg, 88% yield) according
1
to the general procedure. Mp: 101−103 °C. H NMR (400 MHz,
CDCl3): δ 8.17 (d, J = 4.0 Hz, 1H), 7.84 (d, J = 16.0 Hz, 1H), 7.70
(dt, J1 = 7.8 Hz, J2 = 1.8 Hz, 1H), 7.56 (d, J = 8.0 Hz, 1H), 7.04−6.95
(m, 3H), 6.90 (s, 1H), 6.43 (d, J = 16.0 Hz, 1H), 4.19 (q, J = 7.1 Hz,
2H), 2.35 (s, 3H), 1.28 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz,
CDCl3): 167.7, 163.6, 152.9, 147.9, 142.2, 139.7, 139.0, 128.0, 126.3,
124.6, 122.9, 118.8, 60.4, 21.6, 14.4. HRMS (EI-TOF) m/z: calcd for
C17H17NO3 (M+) 283.1208, found 283.1200.
(E)-Ethyl 3-(5-Chloro-2-(pyridin-2-yloxy)phenyl)acrylate (2i).
2i was obtained as a yellow oil (60 mg, 49% yield) according to the
1
general procedure. H NMR (400 MHz, CDCl3): δ 8.14 (d, J = 4.4
Hz, 1H), 7.79 (d, J = 16.0 Hz, 1H), 7.71 (dt, J1 = 7.8 Hz, J2 = 1.4 Hz,
1H), 7.63 (d, J = 2.0 Hz, 1H), 7.35 (dd, J1 = 8.8 Hz, J2 = 2.4 Hz, 1H),
7.06 (d, J = 8.8 Hz, 1H), 7.02 (t, J = 6.8 Hz, 2H), 6.46 (d, J = 16.0 Hz,
1H), 4.21 (q, J = 7.1 Hz, 2H), 1.28 (t, J = 7.2 Hz, 3H). 13C NMR (100
MHz, CDCl3): δ 166.6, 163.2, 151.3, 147.8, 139.9, 137.6, 131.3, 130.6,
129.1, 127.7, 124.1, 121.0, 119.2, 111.9, 60.7, 14.3. HRMS (EI-TOF)
m/z: calcd for C16H14ClNO3 (M+) 303.0662, found 303.0661.
(2E,2′E)-Diethyl 3,3′-(5-Chloro-2-(pyridin-2-yloxy)-1,3-
phenylene)diacrylate (2i′). 2i′ was obtained as a white solid (11
(E)-Ethyl 3-(5-Methyl-2-(pyridin-2-yloxy)phenyl)acrylate
(2d). 2d was obtained as a yellow oil (62 mg, 55% yield) according
to the general procedure. 1H NMR (400 MHz, CDCl3): δ 8.15 (d, J =
3.6 Hz, 1H), 7.84 (d, J = 16.4 Hz, 1H), 7.69 (dt, J1 = 7.8 Hz, J2 = 1.6
Hz, 1H), 7.47 (s, 1H), 7.21 (d, J = 8.0 Hz, 1H), 7.01−6.96 (m, 3H),
6.46 (d, J = 16.0 Hz, 1H), 4.20 (q, J = 7.1 Hz, 2H), 2.37 (s, 3H), 1.28
(t, J = 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 167.1, 163.8,
150.7, 147.9, 139.7, 139.1, 134.9, 132.2, 127.2, 122.6, 119.6, 118.7,
111.6, 60.5, 21.0, 14.4. HRMS (EI-TOF) m/z: calcd for C17H17NO3
(M+) 283.1208, found 283.1211.
1
mg, 7% yield) according to the general procedure. H NMR (400
MHz, CDCl3): δ 8.03 (d, J = 4.0 Hz, 1H), 7.74 (t, J = 7.8 Hz, 1H),
7.65 (s, 2H), 7.63 (d, J = 16.8 Hz, 2H), 7.10 (d, J = 8.4 Hz, 1H), 6.99
(2E,2′E)-Diethyl 3,3′-(5-Methyl-2-(pyridin-2-yloxy)-1,3-
phenylene)diacrylate (2d′). 2d′ was obtained as a white solid (8
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Note
(t, J = 5.8 Hz, 1H), 6.40 (d, J = 16.0 Hz, 2H), 4.18 (q, J = 7.2 Hz, 4H),
1.26 (t, J = 7.0 Hz, 6H).
temperature. A white solid was obtained when the solvent was
evaporated. The solid was dissolved in dry ethanol (5.0 mL) and was
added under N2 to a solution of Na (294 mg, 12 mmol) in dry ethanol
(15 mL). The reaction mixture was heated at 80 °C for 15 min. The
reaction mixture was allowed to cool to ambient temperature, and the
solvent was evaporated in vacuo. The residue was purified by column
chromatography on silica gel (petroleum ether/EtOAc 8:1) to yield 3c
(E)-Ethyl 3-(2-(Pyridin-2-yloxy)-5-(trifluoromethoxy)phenyl)-
acrylate (2j). 2j was obtained as a white solid (37 mg, 25% yield)
1
according to the general procedure. Mp: 42−44 °C. H NMR (400
MHz, CDCl3): δ 8.15 (d, J = 3.6 Hz, 1H), 7.82 (d, J = 16.0 Hz, 1H),
7.75 (dt, J1 = 7.6 Hz, J2 = 1.8 Hz, 1H), 7.50 (d, J = 1.6 Hz, 1H), 7.26−
7.23 (m, 1H), 7.14 (d, J = 9.2 Hz, 1H), 7.06−7.02 (m, 2H), 6.46 (d, J
= 16.0 Hz, 1H), 4.21 (q, J = 7.2 Hz, 2H), 1.29 (t, J = 7.1 Hz, 3H). 13C
NMR (100 MHz, CDCl3): δ 166.6, 163.1, 151.1, 147.8, 145.9, 140.0,
137.6, 128.9, 123.9, 123.8, 121.3, 120.6 (q, JC−F = 256.0 Hz), 120.3,
119.4, 112.0, 60.8, 14.4. HRMS (EI-TOF) m/z: calcd for
C17H14F3NO4 (M+) 353.0875, found 353.0868.
1
(70 mg, 68%) as a white solid. Mp: 88−90 °C. H NMR (400 MHz,
CDCl3): δ 7.96 (d, J = 16.4 Hz, 1H), 7.35 (d, J = 8.0 Hz, 1H), 6.73 (d,
J = 6.8 Hz, 1H), 6.65 (s, 1H), 6.56 (d, J = 16.4 Hz, 1H), 6.07 (s, 1H),
4.27 (q, J = 7.2 Hz, 2H), 2.31 (s, 3H), 1.34 (t, J = 7.2 Hz, 3H). 13C
NMR (100 MHz, CDCl3): δ 168.3, 155.2, 142.4, 140.3, 129.3, 122.1,
119.2, 117.8, 117.1, 60.6, 21.5, 14.5. HRMS (EI-TOF) m/z: calcd for
C12H14O3 (M+) 206.0943, found 206.0943.
(E)-Ethyl 3-(2,4-Dimethyl-6-(pyridin-2-yloxy)phenyl)acrylate
(2k). 2k was obtained as a yellow oil (45 mg, 38% yield) according to
the general procedure. 1H NMR (400 MHz, CDCl3): δ 8.18 (d, J = 4.8
Hz, 1H), 7.76 (d, J = 16.4 Hz, 1H), 7.68 (t, J = 5.0 Hz, 1H), 6.98 (t, J
= 6.0 Hz, 1H), 6.91 (d, J = 8.4 Hz, 1H), 6.90 (s, 1H), 6.74 (s, 1H),
6.42 (d, J = 16.4 Hz, 1H), 4.18 (q, J = 7.1 Hz, 2H), 2.43 (s, 3H), 2,29
(s, 3H), 1.27 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ
167.6, 163.4, 153.2, 148.0, 140.5, 139.6, 139.5, 138.4, 128.6, 124.0,
122.6, 120.8, 118.6, 111.8, 60.4, 21.4, 21.1, 14.4. HRMS (EI-TOF) m/
z: calcd for C18H19NO3 (M+) 297.1365, found 297.1359.
(E)-Ethyl 3-(4-Chloro-1-(pyridin-2-yloxy)naphthalen-2-yl)-
acrylate (2l). 2l was obtained as a white solid (115 mg, 84% yield)
according to the general procedure. Mp: 161−163 °C. 1H NMR (400
MHz, CDCl3): δ 8.25 (d, J = 8.4 Hz, 1H), 8.02 (d, J = 5.2 Hz, 1H),
7.90 (d, J = 16.4 Hz, 1H), 7.86 (d, J = 8.0 Hz, 1H), 7.85 (s, 1H), 7.74
(dt, J1 = 7.8 Hz, J2 = 1.8 Hz, 1H), 7.62 (t, J = 7.6 Hz, 1H), 7.48 (d, J =
7.6 Hz, 1H), 7.10 (d, J = 8.0 Hz, 1H), 6.98 (t, J = 6.0 Hz, 1H), 6.51 (d,
J = 16.0 Hz, 1H), 4.21 (q, J = 7.1 Hz, 2H), 1.29 (t, J = 7.2 Hz, 3H).
13C NMR (100 MHz, CDCl3): 166.7, 164.2, 148.0, 147.9, 140.1, 137.6,
Ethyl 3-(2-Hydroxy-4-methylphenyl)propanoate (4c). To a
solution of 3c (41.3 mg, 0.2 mmol) in EtOAc was added 10% Pd/C
(4.1 mg), and the reaction mixture was stirred under a hydrogen
atmosphere for 6 h. The palladium catalyst was removed by filtration,
and the solvent was evaporated in vacuo. The residue was purified by
column chromatography on silica gel (petroleum ether/EtOAc 10:1)
to yield 4c (39 mg, 95%) as a yellow oil. 1H NMR (400 MHz,
CDCl3): δ 7.14 (s, 1H), 6.96 (d, J = 7.6 Hz, 1H), 6.71 (s, 1H), 6.98 (d,
J = 7.6 Hz, 1H), 4.14 (q, J = 7.2 Hz, 2H), 2.86 (t, J = 6.4 Hz, 2H), 2.68
(d, J = 6.4 Hz, 2H), 2.27 (s, 1H), 1.23 (t, J = 7.2 Hz, 3H). 13C NMR
(100 MHz, CDCl3): δ 174.9, 153.3, 137.1, 129.5, 123.4, 120.7, 117.0,
60.4, 34.6, 23.4, 20.1, 13.2. HRMS (EI-TOF) m/z: calcd for C12H16O3
(M+) 208.1099, found 208.1097.
ASSOCIATED CONTENT
■
S
* Supporting Information
Experimental details and spectral data for all new compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
132.7, 129.8, 129.3, 128.5, 127.8, 125.2, 124.8, 123.8, 123.4, 120.7,
118.8, 110.5, 60.7, 14.4. HRMS (EI-TOF) m/z: calcd for
C20H16ClNO3 (M+) 353.0819, found 353.0817.
(E)-Ethyl 3-(1-(Pyridin-2-yloxy)naphthalen-2-yl)acrylate
(2m). 2m was obtained as a white solid (119 mg, 93% yield)
according to the general procedure. Mp: 143−145 °C. 1H NMR (400
MHz, CDCl3): δ 8.06 (d, J = 4.0 Hz, 1H), 8.00 (d, J = 16.0 Hz, 1H),
7.85 (t, J = 7.6 Hz, 2H), 7.75 (s, 2H), 7.72 (dt, J1 = 7.8 Hz, J2 = 1.6 Hz,
1H), 7.50 (t, J = 7.4 Hz, 1H), 7.42 (t, J = 7.8 Hz, 1H), 7.03 (d, J = 8.4
Hz, 1H), 6.96 (t, J = 5.4 Hz, 1H), 6.54 (d, J = 16.0 Hz, 1H), 4.21 (q, J
= 7.1 Hz, 2H), 1.29 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3):
δ 167.0, 164.4, 148.9, 148.0, 139.9, 138.7, 135.8, 128.2, 128.1, 127.6,
127.0, 126.1, 124.3, 123.3, 119.9, 118.6, 110.3, 60.6, 14.4. HRMS (EI-
TOF) m/z: calcd for C20H17NO3 (M+) 319.1208, found 319.1201.
(E)-Methyl 3-(1-(Pyridin-2-yloxy)naphthalen-2-yl)acrylate
(2n). 2n was obtained as a white solid (85 mg, 69% yield) according
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: bfshi@zju.edu.cn.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Financial support from the National Natural Science
Foundation of China (21002087, 21272206), the Fundamental
Research Funds for the Central Universities (2010QNA3033),
the Zhejiang Provincial NSFC (Z12B02000), the Qianjiang
Project (2013R10033), and the Specialized Research Fund for
the Doctoral Program of Higher Education (20110101110005)
is gratefully acknowledged.
1
to the general procedure. Mp: 154−155 °C. H NMR (400 MHz,
CDCl3): δ 8.05 (d, J = 4.8 Hz, 1H), 8.01 (d, J = 16.4 Hz, 1H), 7.84 (t,
J = 7.8 Hz, 2H), 7.75−7.69 (m, 3H), 7.50 (t, J = 7.4 Hz, 1H), 7.42 (t, J
= 7.8 Hz, 1H), 7.03 (d, J = 8.0 Hz, 1H), 6.96 (t, J = 6.0 Hz, 1H), 6.55
(d, J = 16.4 Hz, 1H), 3.75 (s, 3H). 13C NMR (100 MHz, CDCl3): δ
167.4, 164.4, 149.0, 148.0, 139.9, 138.9, 135.8, 128.2, 128.1, 127.6,
127.0, 126.2, 124.2, 123.3, 119.4, 118.6, 110.3, 51.8. HRMS (EI-TOF)
m/z: calcd for C19H15NO3 (M+) 305.1052, found 305.1055.
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