Palladium-Catalyzed Dearomatizing Alkoxydiarylation of Furan Rings by Coupling with Arylboronic Acids: Access to Polysubstituted Oxabicyclic Compounds

Article abstract of DOI:10.1002/adsc.201601437

We report a protocol for palladium-catalyzed dearomatizing alkoxydiarylation of furan rings via aerobic oxidative coupling between arylboronic acids and 5-aryl-2-hydroxyalkylfurans. This green protocol starting from furan derivatives, which can be sustainably sourced, provides rapid access to polysubstituted 2,3,3a,6a-tetrahydrofuro[3,2-b]furans and hexahydrofuro[3,2-b]furans, oxabicyclic frameworks that are shared by various natural products and synthetic molecules with important biological activities. (Figure presented.).

Full text of DOI:10.1002/adsc.201601437

Title: Palladium-Catalyzed Dearomatizing Alkoxydiarylation of
Furan Rings by Coupling with Arylboronic Acids: Access to
Polysubstituted Oxabicyclic Compounds
Authors: Jiuyi Li, Lin Lu, Qi Pan, Bo Liu, Yanwei Ren, and Biaolin Yin
This manuscript has been accepted after peer review and appears as an
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.201601437
Link to VoR: http://dx.doi.org/10.1002/adsc.201601437

10.1002/adsc.201601437
Advanced Synthesis & Catalysis
COMMUNICATION
Palladium-Catalyzed Dearomatizing Alkoxydiarylation of
Furan Rings by Coupling with Arylboronic Acids: Access to
Polysubstituted Oxabicyclic Compounds
Jiuyi Li,[a] Lin Lu,[a] Qi Pan,[b] Yanwei Ren,[a] Bo Liu*[b] and Biaolin Yin*[a]
[a]Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of Chemistry and Chemical
Engineering, South China University of Technology, Guangzhou 510640, P. R. China, 510640, blyin@scut.edu.cn
[b]The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, P.R. China, 510006,
e-mail: doctliu@263.net
as furans, with regioselectivity and stereoselectivity
are limited.
Abstract: We report a protocol for palladium-catalyzed
dearomatizing alkoxydiarylation of furan rings via
aerobic oxidative coupling between arylboronic acids and
5-aryl-2-hydroxyalkylfurans. This green protocol starting
from furan derivatives, which can be sustainably sourced,
Previous work from other groups:
OR'
ArB(OH)
2
R'OH
+
Ar
R
Selectfluor, Au catalyst
R
provides
rapid
access
to
polysubstituted
and
OR
TEMPO
or
ClCH COOH
ArB(OH)
2
2,3,3a,6a-tetrahydrofuro[3,2-b]furans
+
Pd catalyst
hexahydrofuro[3,2-b]furans, oxabicyclic frameworks that
are shared by various natural products and synthetic
molecules with important biological activities.
Ar
X
X
2
X = O, NPG
OAc
Our previous work:
Pd
O
HO
HO
ArB(OH)
Ar
2
Keywords: aerobic oxidation, fused-ring systems, green
chemistry, regioselectivity
R
O , Pd-cat.
R
O
O
R
2
O
+
unsaturated
acetals
1
Selective introduction of two functional groups
into an alkene in a single operation is a powerful
method for the rapid construction of complex
molecules.[1] In recent years, numerous protocols for
transition-metal-catalyzed difunctionalization of
alkenes have been reported, such as dioxygenation,[2]
oxyamidation,[3] diboration,[4] and diamination.[5]
These step-economical protocols have provided a
wide range of structurally diverse functionalized
compounds that are of great importance in organic
synthesis.
Alkene carboalkoxylation is a useful subclass of
alkene difunctionalization and has been used to
construct biologically valuable tetrahydrofurans,
dihydrobenzofurans, and other oxygen-containing
heterocycles.[6] This transformation usually involves
coupling between an exogenous carbon electrophile
or nucleophile and an alcohol that bears a pendant
alkene. However, the transformation is limited to
structurally simple alkenes, and extension to
aromatic alkenes is challenging because of the
chemical inertness of the aromatic ring. Recently,
Pd-catalyzed dearomatizing 2,3-alkoxyarylation
reactions of heteroarenes such as indoles and
benzofurans have been reported to efficiently and
This work:
Ar
Ar
H
H
OH
O
O
ArB(OH)
2
R
and
R
R
O
HO
O , Pd-cat.
2
O
O
3
Ar
1
Ar
2
Scheme 1. Alkoxydiarylation of alkenes and arenes with
boronic acids as carbon nucleophiles
Owing to its low aromaticity, the diene moiety of a
furan ring is chemically similar to a nonaromatic
alkene or diene. Therefore, furans can be readily
dearomatized. A number of reactions capitalize on
this property and have been used to synthesize other
useful compounds.[8] Recently, we reported a
protocol for Pd-catalyzed intra- and intermolecular
2,5-oxyarylation
diastereospecific synthesis of spirooxindoles
reactions
of
furans
for
.
[9] We
also reported a protocol for 2,5-oxyarylation of furan
rings via Pd-catalyzed oxidative coupling of boronic
acids with α-hydroxyalkylfurans to synthesize
spiroacetals using O2 as a green oxidant.[10] These
protocols can be viewed as a difunctionalization of
the diene segment of the furan rings and provide new
strategies for expanding the synthetic utility of furans
for the construction of polycyclic dihydrofurans. As
part of our ongoing work on dearomatizing
transformations of furans,[11] which can be
sustainably sourced, we herein report a protocol for
Pd-catalyzed dearomatizing alkoxydiarylation of
furan rings via the oxidative coupling of arylboronic
acids with 5-aryl-2-hydroxyalkylfurans 1, providing
access to two types of oxa-bicyclic skeletons 2 and 3.
stereoselectively
afford
indolines
and
2,3-dihydrobenzofurans (Scheme 1);[7] in these cases,
the chemical properties of the destroyed aromatic
alkene substrates are similar to those of simple
monoalkenes. To our knowledge, efficient methods
for
transition-metal-catalyzed
dearomatizing
difunctionalization of diene-like aromatic rings, such
1
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10.1002/adsc.201601437
Advanced Synthesis & Catalysis
To our knowledge, the tri-functionalization of the
furans via a one-pot protocol has never been
reported.
OH
OH
O
H
O
H
O
O
O
OH
OH
AcO
O
H
O
H
The success of the alkoxydiarylation of 1 to
provide 2 relies on suppression of 2,5-oxyarylation
by the choice of suitable substrates 1. We suspected
that an aryl group of R would suppress the undesired
2,5-oxyarylation. To confirm this possibility, we
O
n
n
Phytuberin
Trichodermaketones A Trichodermaketones B
Et
Et
H
O
O
O
O
O
O
O
R
O
O
O
investigated
the
reaction
of
H
H
H
Plakortones A ( R = Et)
Plakortones B ( R = Me)
Buergerinin F
2-(5-phenyl-furan-2-yl)-ethanol (1a) with PhB(OH)2
(100 mol %) by using Pd(OAc)2 (10 mol %) as the
catalyst, L1 as the ligand, O2 (balloon) as the oxidant,
70 °C as the reaction temperature, and 1:1 (v/v)
DCE/H2O as the solvent (Scheme 2). Under these
(+)-Cephalosporolide E
Figure 1. Representative furo[3,2-b]furans
To optimize the reaction condition for the
production of 2a, we began by allowing 1a to react
with PhB(OH)2 (250 mol %) in the presence of a
series of bidentate nitrogen-containing ligands (Table
1, entries 1–7). The electronic and steric properties of
the ligand played an important role in the outcome of
the reaction. Reactions with an electron-poor ligand
(L7) and with sterically hindered ligands (L2 and L3)
did not afford 2a. Among the ligands examined,
1,10-phenanthroline (L4) was found to be optimal,
giving 2a in 74% yield. Various binary solvent
systems were then screened (entries 8–11), and 1:1
(v/v) DCE/H2O proved to be optimal. Increasing the
DCE/H2O ratio to 2:1 or lowering it to 1:2 did not
improve the yield of 2a (entries 12 and 13). When
DCE was used as the sole solvent, the boronic acid
did not dissolve well, and the yield of 2a was only
17% (entry 14). Increasing the amount of 1a to 350%
mol reduced the yield (entry 15). Neither lowering
the reaction temperature to 60 °C (entry 16) nor
elevating it to 80 °C (entry 17) improved the yield.
Thus, the optimal reaction conditions involved the
use of Pd(OAc)2 as the catalyst, O2 as the oxidant,
1:1 DCE/H2O as the solvent, and 70 °C as the
reaction temperature.
conditions,
reaction
for
21
h
provided
alkoxydiarylated product of furo[3,2-b]furan 2a in
16% yield, along with a 19% yield of alkoxyarylated
furo[3,2-b]furan 3a. The 2,5-oxyarylation product
was not observed.
To gain insight into this transformation, we
conducted three control experiments (Scheme 3).
When we carried out the reaction of 1a under
identical conditions except that we used less
PhB(OH)2 (50 mol %) and added it in portions, the
yield of 3a dropped to 6% (Scheme 3a). Carrying out
the reaction of 1a with more PhB(OH)2 (250 mol %)
elevated the yield of 2a (35%) and reduced the yield
of 3a (14%) (Scheme 3b), relative to the yield under
the standard conditions. These results suggested that
increasing the amount of PhB(OH)2 and tuning the
reaction conditions would afford efficient access to
2a. In the presence of 100 mol % PhB(OH)2 but
otherwise identical conditions, reaction of 3a
provided 2a in 76% yield (Scheme 3c), indicating
that 2a may be formed by direct phenylation of 3a.[12]
The furo[3,2-b]furan is shared by various natural
products and synthetic compounds with important
biological activities (Figure 1),[13] so we directed our
efforts at developing a route to this skeleton by
means of 2,3-oxydiarylation of furans.
Table 1. Optimization of reaction conditions for formation of
2a[a]
PhB(OH) (100 mol %)
2
Pd(OAc) (10 mol %)
2
H
H
Ph
H
O
O
Ph
O
PhB(OH)2 (250 mol %)
Ph
Ph
H
1
O
L
(12 mol %)
H
O
O
Ph
Ph
(balloon), 70 C, 21 h
Ph
Pd(OAc)2 (10 mol %), L
O
O
O
O
o
O
O
2
Ph
N
Ph
3a (19%)
1a
Ph
2,5-oxyarylation
O2 (balloon), T, 21 h
O
DCE/H O (1:1, v/v)
Ph
2
O
2a (16%)
2a
product (not observed)
Ph
N
1a
MeO
OMe
L1
O
N
N
N
N
Ph
N
N
N
N
N
N
N
N
L2
L4
L3
L5
L6
L7
Scheme 2. Reaction of 1a with PhB(OH)2
entry
1
L
solvent
yield (%)[b]
PhB(OH)2
(50 mol %)
L1
L2
L3
L4
L5
L6
L7
L4
L4
L4
L4
DCE/H2O (1:1)
DCE/H2O (1:1)
DCE/H2O (1:1)
DCE/H2O (1:1)
DCE/H2O (1:1)
DCE/H2O (1:1)
DCE/H2O (1:1)
MeCN/H2O (1:1)
THF/H2O (1:1)
DMF/H2O (1:1)
MeOH/H2O (1:1)
35
0
(a)
1a
2a (trace) + 3a (6%)
2
PhB(OH)2
(250 mol %)
3
0
2a (35%) + 3a (14%) (b)
1a
3a
4
74
19
45
0
5
PhB(OH)2
(100 mol %)
6
2a (76%)
(c)
Scheme 3. Control experiments
7
8
9
9
18
trace
58
10
11
2
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10.1002/adsc.201601437
Advanced Synthesis & Catalysis
L4
L4
L4
L4
L4
L4
L4
DCE/H2O (2:1)
DCE/H2O (1:2)
DCE
49
25
17
21
49
55
35
2 (yield
12
13
entry
R
Ar
R1
n
[%])[b]
2a (71)
2b (78)
2c (46)
2d (61)
2e (65)
2f (57)
2g (84)
2h (70)
2i (71)
1
2
3
4
5
6
7
8
9
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
H
H
H
H
H
H
H
H
H
1
1
1
1
1
1
1
1
1
14
15[c]
16[d]
17[e]
18[f]
DCE/H2O (1:1)
DCE/H2O (1:1)
DCE/H2O (1:1)
DCE/H2O (1:1)
4-Me-C6H4
4-MeO-C6H4
4-F-C6H4
4-Cl-C6H4
4-Br-C6H4
3-Me-C6H4
3-F-C6H4
[a]
Reaction conditions, unless otherwise noted: 1a (0.2 mmol),
PhB(OH)2 (0.5 mmol) (added in three equal portions at 4-h
intervals), Pd(OAc)2 (10 mol %), L (12 mol %), T = 70 °C, 21 h.
3-MeO-C6H4
[b]
1
Yields were determined by H NMR spectroscopy of the crude
3,5-di-Me-
C6H3
3-Me-4-F-
C6H3
products with dibromomethane as an internal standard.
[c] PhB(OH)2 (0.7 mmol).
[d] T = 60 °C.
[e] T = 80 °C.
[f] T = 80 °C, Pd(OAc)2 (5 mol %), L4 (6 mol %).
10
11
Ph
Ph
H
H
1
1
2j (81)
2k (30)
12
13
14
Ph
Ph
Ph
4-NO2-C6H4
1-Np
H
H
H
1
1
1
2l (ND)
2m (trace)
2n (ND)
To investigate the scope of the reaction, we carried
out reactions between various aryl boronic acids and
α-hydroxyalkylfurans 1 with different n values and
substitution patterns under the optimized conditions
to synthesize 2,3,3a,6a-tetrahydrofuro[3,2-b]furans 2
(Table 2). When R was phenyl (entries 1–14), R2
could be a phenyl group, either unsubstituted or with
an electron-donating or electron-withdrawing
substituent, and the corresponding products were
obtained in good to excellent yields, except in the
cases of 2c, 2k, and 2l. The strongly
electron-donating para MeO group and the strongly
electron-withdrawing para NO2 group may have
been responsible for the very low yields of 2c and 2l,
respectively (entries 3 and 12). The low yield of 2k
(entry 11) may have been due to the poor solubility
of the corresponding boronic acid in the reaction
solvent. Notably, the use of a bulky naphthyl boronic
acid resulted in only a trace amount of product 2m
(entry 13). When R2 was a vinyl group, none of the
corresponding product (2n) was obtained. The R
substituent could also be a phenyl group with an
CH2=CH
4-Me-
C6H4
2-Me-
C6H4
3,5-di-
Me-C6
H3
15
16
3-Me-C6H4
3-Me-C6H4
H
H
1
1
2o (86)
2p (47)
17
3-Me-C6H4
H
1
2q (72)
4-Cl-
C6H4
18
3-Me-C6H4
H
1
2r (40)[c]
19
20
21
22
23
24
Ph
Me
Et
3-Me-C6H4
3-Me-C6H4
3-Me-C6H4
3-Me-C6H4
3-Me-C6H4
3-Me-C6H4
Me
H
1
1
1
1
2
3
2s (65)[d]
2t (39)
H
2u (ND)
2v (ND)
2w (64)[e]
2x (21)[f]
i-Pr
Ph
H
H
Ph
H
[a]
Reaction conditions: 1 (0.4 mmol), ArB(OH)2 (1.0
mmol, added in three equal portions at 4-h intervals),
Pd(OAc)2 (0.04 mmol), L4 (0.048 mmol), DCE (2
mL), H2O (2 mL), 70 °C, under O2 (balloon), 21 h.
[b] Isolated yields; ND, not detected.
electron-donating
or
electron-withdrawing
substituent (entries 15–18). However, when R was a
4-ClC6H4 group, the yield dropped to 40% (entry 18).
When R1 was a methyl group, the product 2s was
[c]
1
Yield was determined by H NMR spectroscopy of
the crude products with dibromomethane as an
internal standard.
formed in
a
good yield (65%) with
a
diasteroselectivity of 1.3/1 (entry 19). A substrate
with a methyl group as R gave a low yield (2t, 39%),
owing to the formation of a significant amount of
unverified by-product (entry 20). When R was ethyl
or i-propyl group, none of the desired products were
afforded (entries 21 and 22). Notably, when n was 2,
product 2w was obtained in 64% yield (entry 23).
When n was 3, product 2x was obtained but in a very
low yield (21%, entry 24).
[d]
Ratio trans/cis = 1.3/1. Diastereomer ratios were
1
determined by H NMR spectroscopy of the crude
products.
[e]
[f]
1
Ratio trans/cis = 6/1, as determined by H NMR
spectroscopy.
1
Ratio trans/cis = 5/1, as determined by H NMR
spectroscopy.
Table 2. Synthesis of tetrahydrofuro[3,2-b]furans 2[a]
ArB(OH)2 (2.5 equiv)
Ar
L4 (12 mol %)
H
HO
O
Pd(OAc)2 (10 mol %)
R
R1
R1
R
O
O
DCE/H2O (1/1, v/v)
21 h, 70 oC, O2 (balloon)
n
n
Ar
1
2
n = 1, 2
3
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10.1002/adsc.201601437
produces complex 5. 5 then undergoes O-allylation
to produce 6, which is transformed into 3 via
transmetalation followed by reduction elimination.
The Pd(0) is oxidized into Pd(II) by O2 to complete
the catalytic recycle. Similarly, the electrophilic
palladation of 3 with Pd(OAc)2 produces complex 8.
8 is deprotonated to form 9 which is transformed into
Advanced Synthesis & Catalysis
2
via transmetalation followed by reductive
elimination.
To explain the stereochemistry of 4, we propose
the pathway outlined in Scheme 5. Coordination of
the palladium atom to the double bond of 2 from the
same face of the Ar group provides complex 11.
Nucleophilic attack of a hydroxyl ion from the face
opposite the palladium atom gives intermediate 12,
which then undergoes protonation to yield semiacetal
13. Compound 13 can be isomerized into 14 and 15.
The cyclization of 15 provides the thermodynamic
stable product 4 exclusively.
Figure 2. ORTEP diagram of 4a with 30% ellipsoid
probability.
Encouraged by the above-described results, we
attempted
the
synthesis
of
hexahydrofuro[3,2-b]furans 4, which have four chiral
carbon centers, from 1. As shown in Table 3, after
completion of the reaction of 1 with boronic acids
under the conditions described above for the
formation of 2, we added 200 mol % Na2CO3
without work-up and continued the reaction for an
o
additional 8 h at 70 C. As a result, products 4 were
obtained diastereospecifically by means of a one-pot
protocol in moderate to good yields. The
stereochemistry of 4 was unambiguously determined
by X-ray crystallographic analysis (4a, Figure 2).[14]
Table 3. One-pot formation of hexahydrofuro[3,2-b]furans
4[a]
ArB(OH) (2.5 equiv)
2
L
(12 mol %)
Ar
HO
Ph
4
Na CO
(200 mol %)
H
2
3
HO
Pd(OAc) (10 mol %)
O
2
Ph
O
8 h
DCE/H O (1/1, v/v)
2
O
1
o
Ar
21 h, 70 C, O (Balloon)
2
4
entry
1
Ar
4 (yield [%])[b]
4a (78)
4b (62)
4c (55)
4d (56)
4e (72)
4f (71)
Ph
2
4-Me-C6H4
4-Cl-C6H4
4-Br-C6H4
4-Et-C6H4
4-t-Bu-C6H4
3-Me-C6H4
3-MeO-C6H4
3-F-C6H4
3
4
Scheme 4. Proposed pathway for formation of 2 from 1
5
OAc
6
Ar
Pd
AcO
AcO
Ar
H
H
Pd
H
Ar
O
O
O
protonation
Pd(OAc)2
7
4g (60)
4h (66)
4i (44)
R
HO
R
R
O
O
O
Ar
Ar
HO-
Ar
8
11
2
12
9
Ar
Ar
Ar
H
H
H
H
H
O
H
O
O
O
R
R
10
11
3,5-di-Cl-C6H4
3,5-di-Me-C6H4
4j (21)
HO
HO
O
R
O
HO
Ar
Ar
Ar
4k (70)
13
4
15
[a]Reaction conditions: 1 (0.4 mmol), ArB(OH)2 (1.0 mmol), Pd(OAc)2
(0.04 mmol), L4 (0.048 mmol), DCE (2 ml), H2O (2 ml), 70 °C, under
O2 (balloon), 21 h. Then Na2CO3 (0.8 mmol) was added to the
same pot, and the reaction was continued for 8 h.
[b] Isolated yields.
Ar
H
H
O
O
R
HO
Ar
14
Scheme 5. Proposed pathway for formation of 4 from 2
On the basis of our previous studies and control
experiments outcome, we propose the pathway for
the formation of 2. As outlined in Scheme 4, the
In summary, we have developed a protocol for
palladium-catalyzed alkoxydiarylation of furan rings
via aerobic oxidative coupling of boronic acids with
electrophilic palladation of
1 with Pd(OAc)2
4
This article is protected by copyright. All rights reserved.

10.1002/adsc.201601437
(film): 3618, 3078, 2986, 2925, 2858, 1649, 1595,
1509, 1426, 1384, 1328, 1260, 1212, 1128, 1067,
Advanced Synthesis & Catalysis
5-aryl-2-hydroxyalkylfurans,
sustainably sourced. This protocol constitutes a green,
which
can
be
1
856, 799, 703 cm-1; H NMR (400 MHz, CDCl3) δ
diastereoselective
2,3,3a,6a-tetrahydrofuro[3,2-b]furans
hexahydrofuro[3,2-b]furans),
oxabicyclic compounds that may be biologically
interesting and synthetically useful. This study can
be expected to serve as a foundation for the design of
new difunctionalization reactions of diene-like
five-membered aromatic rings.
route
to
and
7.67–7.62 (m, 2H), 7.46–7.40 (m, 4H), 7.38–7.34 (m,
3H), 7.30 (m, 1H), 7.26–7.23 (m, 3H), 7.13 (m, 2H),
5.45 (d, J = 6.4 Hz, 1H), 4.31–4.21 (m, 2H), 3.47 (d,
J = 6.4 Hz, 1H), 2.71–2.64 (m, 1H), 2.35 (d, J = 1.6
Hz, 1H), 2.27–2.16 (m, 1H); 13C NMR (100 MHz,
CDCl3) δ 146.9, 142.2, 135.7, 129.8, 128.5, 128.3,
128.2, 127.9, 127.1, 126.8, 125.6, 124.6, 106.9, 96.0,
92.9, 67.4, 62.5, 45.9; HRMS (ESI) m/z calculated
for C24H22NaO3 [M+Na]+: 381.1461, found: 381.1466.
polysubstituted
Experimental Section
General procedure for synthesis of 2 (2a)
Acknowledgements
To a stirred solution of 1a (0.4 mmol) in 1:1 (v/v)
DCE/H2O (4 mL) in a Schlenk flask under a balloon
of O2 were added Pd(OAc)2 (9.0 mg, 0.04 mmol, 10
mol %), 1,10-phenanthroline (8.6 mg, 0.048 mmol,
12 mol %), and ArB(OH)2 (1.0 mmol, 250 mol %)
(added in three equal portions at 4-h intervals). The
reaction mixture was heated at 70 °C until TLC
indicated the disappearance of the starting material.
Then H2O (5 mL) was added, and the resulting
mixture was extracted with ethyl acetate (3 × 5 mL).
The combined organic extracts were washed with
brine, dried over Na2SO4, and filtered, and the filtrate
was concentrated. The residue was purified by flash
chromatography on silica gel (with 30:1 petroleum
ether/ethyl acetate as the eluent) to give 2a.
This work was supported by grants from the National
Program on Key Research Project (2016YFA0602900), the
National Natural Science Foundation of China (nos. 21272078
and 21572068), and the Science and Technology Planning
Project of Guangdong Province, China (no. 2014A020221035).
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[M+H]+: 341.1536, found: 341.1534.
General procedure for the synthesis of 4 (4a)
To a stirred solution of 1a (0.4 mmol) in 1:1
DCE/H2O (4 mL) in a Schlenk flask under a balloon
of O2 atmosphere were added Pd(OAc)2 (9.0 mg,
0.04 mmol, 10 mol %), 1,10-phenanthroline (8.6 mg,
0.048 mmol, 12 mol %), and ArB(OH)2 (1.0 mmol,
added in three equal portions at 4-h intervals). The
reaction mixture was heated at 70 °C until TLC
indicated the disappearance of the starting material
(~21 h). Then Na2CO3 (84.8 mg, 0.8 mmol) was
added to the reaction mixture at 70 °C, and the
reaction was continued for an additional 8 h. H2O (5
mL) was then added, and the resulting mixture was
extracted with ethyl acetate (3 × 5 mL). The
combined organic extracts were washed with brine,
dried over Na2SO4, and filtered, and the filtrate was
concentrated. The residue was purified by flash
chromatography on silica gel (with 30:1 petroleum
ether/ethyl acetate as the eluent) to give 4a.
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10.1002/adsc.201601437
Advanced Synthesis & Catalysis
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6
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10.1002/adsc.201601437
Advanced Synthesis & Catalysis
COMMUNICATION
Palladium-Catalyzed
Dearomatizing
Alkoxydiarylation of Furan Rings by
Coupling with Arylboronic Acids: Access
ArB(OH)2 (2.5 equiv)
Pd(OAc)2 (10 mol %)
1,10-Phenanthroline (12 mol %)
Ar
H
O
HO
R
R1
R1
R
to
Polysubstituted
Oxabicyclic
O
DCE/H2O (1/1, v/v)
21 h, 70 0C, O2 (balloon)
n
O
n
Ar
n = 1, 2
Compounds
22 examples
up to 86% yield
ArB(OH)2 (2.5 equiv)
Pd(OAc)2 (10 mol %)
1,10-Phenanthroline (12 mol %)
Ar
H
Na2CO3
(200 mol %)
HO
O
HO
Adv. Synth. Catal. Year, Volume, Page –
Ph
O
Ph
8 h
DCE/H2O (1/1, v/v)
21 h, 70 0C, O2 (balloon)
O
Page
Ar
11 examples
yield: 21% ~ 78%
Jiuyi Li,[a] Lin Lu,[a] Qi Pan,[b] Yanwei Ren,[a]
Bo Liu*[b] and Biaolin Yin*[a]
This article is protected by copyright. All rights reserved.