Facile benzofuran synthesis: Palladium-catalyzed carbonylative Suzuki coupling of methyl 2-(2-iodophenoxy)acetates under CO gas-free conditions

Article abstract of DOI:10.1016/j.tetlet.2017.09.063

A palladium-catalyzed carbonylative Suzuki coupling of methyl 2-(2-iodophenoxy)acetates with arylboronic acids has been developed. The reactions were performed under CO gas-free conditions and the obtained products act as a direct precursor for the synthesis of highly functionalized benzofuran derivatives.

Full text of DOI:10.1016/j.tetlet.2017.09.063

Tetrahedron Letters 58 (2017) 4153–4155
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Facile benzofuran synthesis: Palladium-catalyzed carbonylative Suzuki
coupling of methyl 2-(2-iodophenoxy)acetates under CO gas-free
conditions
Xinxin Qi a, Chao Zhou a, Jin-Bao Peng a, Jun Ying a, Xiao-Feng Wu a,b,
⇑
a Department of Chemistry, Zhejiang Sci-Tech University, Xiasha Campus, Hangzhou 310018, People’s Republic of China
b Leibniz-Institut für Ksatalyse e.V. an der Universitat Rostock, Albert-Einstein-Strasse 29a, 18059 Rostock, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
A palladium-catalyzed carbonylative Suzuki coupling of methyl 2-(2-iodophenoxy)acetates with aryl-
boronic acids has been developed. The reactions were performed under CO gas-free conditions and the
obtained products act as a direct precursor for the synthesis of highly functionalized benzofuran
derivatives.
Received 7 September 2017
Revised 16 September 2017
Accepted 20 September 2017
Available online 21 September 2017
Ó 2017 Elsevier Ltd. All rights reserved.
Keywords:
Palladium catalyst
Carbonylation
Diarylketones
Benzofurans
CO surrogate
Domino reaction
Since the pioneering work by Heck and co-workers in the
1970s,1 palladium-catalyzed carbonylation reaction has drawn
increasing attention due to wide applications in both academic
and industrial fields.2 Carbonylation reactions represent a powerful
method for the preparation of carbonyl-containing compounds,
including ketones, aldehydes, carboxylic acids and their deriva-
tives. Although significant progress has been made, some limita-
tions still exist; for example reaction outcomes are typically
worse with ortho-substituted substrates due to steric effects and
carbon monoxide gas is usually needed which limits the applica-
tion of the corresponding methods in laboratories.
On the other hand, diarylketones frequently appear in natural
products, pharmaceuticals, and biologically active compounds.3
Many synthetic methods have been developed for diarylketone
synthesis, including the Friedel-Crafts acylation of arenes,4 Fries-
rearrangement,5 and the acylation of benzoic acid derivatives with
organometallic reagents.6 Alternatively, the palladium-catalyzed
carbonylative Suzuki coupling reaction offers another approach
to construct diarylketones. Recently, we developed a practical
and convenient synthetic method for diarylketone synthesis via
the palladium-catalyzed carbonylative Suzuki coupling reactions
of aryl halides with arylboronic acids, with formic acid as the CO
source.7 However, under these reaction conditions, dramatically
decreased yields were obtained when a functional group was
located at the ortho position of the aryl halides. Hence, this remains
a challenge which needs to be solved.
Additionally, benzofuran derivatives have been applied in many
areas and the development of new synthetic procedures is an
attractive area of research.8
Herein, we report the continuation of our work on the prepara-
tion of diarylketones via palladium-catalyzed carbonylative Suzuki
coupling reaction with formic acid as the CO source and the appli-
cation of the obtained products as a direct precursor for the syn-
thesis of highly functionalized benzofuran derivatives.
Initially, methyl 2-(2-iodophenoxy)acetate and phenyl boronic
acid were used as model substrates, with formic acid as the CO
source, Pd(OAc)2 as the catalyst, PPh3 as the ligand and K2CO3 as
the base, in toluene at 100 °C for 16 h. Gratifyingly, the desired pro-
duct was obtained in 43% yield (Table 1, entry 1). We then exam-
ined the efficiency of various ligands. Monodentate ligands PCy3
and BuPAd2 gave higher yields, while Xphos resulted in a lower
yield (Entries 2–4). Bidentate ligands DPPF and DPPE also provided
the desired product in decreased yields (Entries 5–6). Next, various
bases including Cs2CO3, Ag2CO3, Et3N, DIPEA, and DBU were inves-
tigated (Entries 7–11), where Cs2CO3 provided the best results. Sol-
vent screening showed that toluene was the optimal solvent for
⇑
Corresponding author at: Department of Chemistry, Zhejiang Sci-Tech Univer-
sity, Xiasha Campus, Hangzhou 310018, People’s Republic of China.
E-mail address: xiao-feng.wu@catalysis.de (X.-F. Wu).
https://doi.org/10.1016/j.tetlet.2017.09.063
0040-4039/Ó 2017 Elsevier Ltd. All rights reserved.

4154
X. Qi et al. / Tetrahedron Letters 58 (2017) 4153–4155
Table 1
O
Pd(OAc)2 (5.0 mol%)
BuPAd2 (10.0 mol%)
Cs2CO3 (3.0 equiv.)
Screening of the reaction conditions.a
O
O
O
B(OH)2
R'
O
R
O
HCOOH
O
O
Ac2O (4.0 equiv.)
toluene, 100 °C, 16 h
R
O
I
O
B(OH)2
O
R'
O
I
[Pd], Ligand
Base, solvent
O
O
HCOOH
1
2
3
O
O
O
O
O
O
O
O
O
O
O
O
Entry
Catalyst
Ligand
Base
Solvent
Yield (%)b
O
O
O
O
1
2
3
4
5
6
7
8
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd2(dba)2
PdCl2(PPh3)4
PdCl2
PPh3
PCy3
BuPAd2
XPhos
DPPF
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Cs2CO3
Ag2CO3
Et3N
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
DMSO
43
47
55
13
37
34
67
23
61
52
47
0
Trace
63
55
53
0
3ad, 66%
3ac , 61%
3ab, 56%
3aa , 67%
DPPE
O
O
O
BuPAd2
BuPAd2
BuPAd2
BuPAd2
BuPAd2
BuPAd2
BuPAd2
BuPAd2
BuPAd2
BuPAd2
BuPAd2
BuPAd2
BuPAd2
O
O
O
O
O
O
O
O
O
O
O
9
O
O
10
11
12
13
14
15
16
17
18
19
DIPEA
DBU
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
CH3CN
DCE
O
Cl
OCF3
3ah, 40%
3ag, 30%
3ae , 52%
3af, 37%
1,4-Dioxane
Toluene
Toluene
Toluene
Toluene
O
O
O
O
O
O
O
O
O
O
O
O
O
51
62
O
O
Cl
O
Pd(TFA)2
a
Reagents and conditions: methyl 2-(2-iodophenoxy)acetate (0.5 mmol), phenyl
S
boronic acid (1.0 mmol), catalyst (5.0 mol%), ligand (10.0 mol% for monodentate
ligand; 5.0 mol% for bidentate ligand), base (1.5 mmol), formic acid (2.0 mmol),
acetic anhydride (2.0 mmol), solvent (4.0 mL), 100 °C, 16 h.
3ba
, 40%
3ai
, 62%
3aj
3ak
, 50%
, 72%
b
GC yield, with dodecane as an internal standard.
O
O
O
this transformation (Entries 12–15). Other palladium pre-catalysts,
including Pd2(dba)3, PdCl2(PPh3)4, PdCl2, and Pd(TFA)2 were also
studied, however, no further improvement of the reaction outcome
could be obtained (Entries 16–19).
O
O
3ca
, 42%
O
With the best reaction condition in hand, we then turned our
attention to examining the substrate scope.9 As shown in Scheme 1,
aryl boronic acids with a single electron-donating group gave the
corresponding products in good yields (3ab–ae), while the 3,5-
dimethyl groups resulted in a lower yield (3af). Trifluoromethoxy
substituted iodides gave the corresponding product in moderate
yield (3ag). A moderate yield was also obtained with para-chloro
substitution (3ah). Furthermore, 1-naphthyl and 2-naphthyl boro-
nic acids were also studied; the corresponding products were iso-
lated in 62% and 72% yield, respectively (3ai–aj). 3-Thiophenyl
boronic acid was also tolerated and afforded the corresponding
product in 50% yield (3ak). For aryl iodides, substitution at the
meta-position to the iodo group with chloro and ester groups pro-
vided the corresponding products in 45% and 42% yields, respec-
tively (3ba–ca).
Scheme 1. Substrate scope for the carbonylative Suzuki coupling reaction.
Reagents and conditions: aryl iodides (0.5 mmol), aryl boronic acid (1.0 mmol),
Pd(OAc)2 (5.0 mol%), BuPAd2 (10.0 mol%), Cs2CO3 (1.5 mmol), formic acid
(2.0 mmol), acetic anhydride (2.0 mmol), toluene (4.0 mL), 100 °C, 16 h, isolated
yields.
Acknowledgments
The authors thank the financial support from NSFC (21472174,
21602201) and Zhejiang Natural Science Fund for Distinguished
Young Scholars (LR16B020002). X.-F Wu appreciates the general
support from Professor Matthias Beller in LIKAT.
A. Supplementary data
Under our standard reaction conditions, we then explored a
one-pot benzofuran synthesis reaction. After completion of the car-
bonylative Suzuki coupling reaction, sodium methoxide and
methanol were added to the reaction mixture, affording benzofu-
ran (4) in 40% yield after heating at 130 °C for 6 h.
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2017.09.
063.
References
1) Pd(OAc)2 (5.0 mol%)
BuPAd2 (10.0 mol%)
Cs2CO3 (3.0 equiv.)
Ac2O (4.0 equiv.)
1. (a) Heck RF. J Am Chem Soc. 1968;90:5546–5548;
O
CO2CH3
(b) Schoenberg A, Bartoletti I, Heck RF. J Org Chem. 1974;39:3318–3326;
(c) Schoenberg A, Heck RF. J Org Chem. 1974;39:3327–3331.
2. (a) For selected reviews, see: Sumino S, Fusano A, Fukuyama T, Ryu I. Acc Chem
Res. 2014;47:1563–1574;
(b) Friis SD, Lindhardt AT, Skrydstrup T. Acc Chem Res. 2016;49:594–605;
(c) Wu X-F. RSC Adv. 2016;6:83831–83837;
O
B(OH)2
O
I
toluene, 100 °C, 16 h
HCOOH
O
2) NaOMe, MeOH
130 °C, 6 h
4
, 40% yield
(d) Peng J-B, Qi X, Wu X-F. ChemSusChem. 2016;9:2279–2283;
(e) Peng J-B, Qi X, Wu X-F. Synlett. 2017;28:175–194;
(f) Gabriele B, Mancuso R, Salerno G. Eur J Org Chem. 2012;6825–6839.
3. (a) Jiang Y, Tu P. Chem Pharm Bull. 2005;53:1164–1166;
(b) Nilar L-HD, Nguyen G, Venkatraman K-Y, Sim L, Harrison J. Phytochemistry.
In summary, we have disclosed a carbonylative Suzuki coupling
of methyl 2-(2-iodophenoxy)acetates under gaseous CO-free con-
ditions. Additionally, the one-pot reaction for benzofuran synthesis
was also developed.

X. Qi et al. / Tetrahedron Letters 58 (2017) 4153–4155
(h) Zhang Y, Rovis T. J Am Chem Soc. 2004;126:15964–15965;
4155
2005;66:1718–1723;
(c) Rancon S, Chaboud A, Darbour N, et al. Phytochemistry. 2001;57:553–557;
(d) Ito H, Nishitani E, Konoshima T, Takasaki M, Kozuka M, Yoshida T.
Phytochemistry. 2000;54:695–700;
(e) Li J-C, Nohara T. Chem Pharm Bull. 2000;48:1354–1355.
4. (a) Song CE, Shim WH, Roh EJ, Choi JH. Chem Commun. 2000;1695–1696;
(b) Fürstner A, Voigtländer D, Schrader W, Giebel D, Reetz MT. Org Lett.
2001;3:417–420;
(i) Silbestri GF, Bogel-Masson R, Lockhart MT, Chopa AB. J Organomet Chem.
2006;691:1520–1524;
(j) Jafarpour F, Rashidi-Ranjbar P, Kashani AO. Eur J Org Chem. 2011;2128–2132;
(k) Sharma P, Rohilla S, Jain N. J Org Chem. 2017;82:1105–1113.
7. Qi X, Jiang L-B, Li H-P, Wu X-F. Chem Eur J. 2015;21:17650–17656.
8. (a) For selected examples, see: Mandali PK, Chand DK. Synthesis.
2015;1661–1668;
(c) Nara SJ, Harjani JR, Salunkhe MM. J Org Chem. 2001;66:8616–8620;
(d) Ross J, Xiao JL. Green Chem. 2002;4:129–133;
(b) Varela-Fernández A, González-Rodríguez C, Varela JA, Castedo L, Saá C. Org
Lett. 2009;11:5350–5353;
(e) Gmouh S, Yang H, Vaultier M. Org Lett. 2003;5:2219–2222;
(f) Fillion E, Fishlock D, Wilsily A, Goll JM. J Org Chem. 2005;70:1316–1327;
(g) Jang DO, Moon KS, Cho DH, Kim JG. Tetrahedron Lett. 2006;47:6063–6066;
(h) Sartori G, Maggi R. Chem Rev. 2006;106:1077–1104;
(i) Dzudza A, Marks TJ. J Org Chem. 2008;73:4004–4016.
5. (a) Bellus D, Hrdlovic P. Chem Rev. 1967;67:599–609;
(b) Sibi MP, Snieckus V. J Org Chem. 1983;48:1935–1937.
6. (a) Labadie JW, Stille JK. J Am Chem Soc. 1983;105:6129–6137;
(b) Hatanaka Y, Fukushima S, Hiyama T. Tetrahedron. 1992;48:2113–2126;
(c) Goossen LJ, Ghosh K. Angew Chem Int Ed. 2001;40:3458–3460;
(d) Huang YC, Majumdar KK, Cheng C-H. J Org Chem. 2002;67:1682–1684;
(e) Zapf A. Angew Chem Int Ed. 2003;42:5394–5399;
(c) Wang S, Li P, Yu L, Wang L. Org Lett. 2011;13:5968–5971;
(d) Wang J-R, Manabe K. J Org Chem. 2010;75:5340–5342;
(e) Eidamshaus C, Burch JD. Org Lett. 2008;10:4211–4214;
(f) Carril M, SanMartin R, Tellitu I, Dominguez E. Org Lett. 2006;8:1467–1470;
(g) Anxionnat B, Pardo DG, Ricci G, Rossen K, Cossy J. Org Lett.
2013;15:3876–3879.
9. General procedure: Pd(OAc)2 (5 mol%), BuPAd2 (10 mol%), phenylboronic acid
(1.0 mmol, 2 equiv) and Cs2CO3 (1.5 mmol) were transferred into an oven-dried
tube filled with nitrogen. Toluene (4.0 mL), acetic acid-2 (2-iodophenoxy)-
methyl ester (0.5 mmol, 1 equiv) and Et3N (4 mmol) were added into the
reaction tube. Then a cooled mixture of formic acid (2.0 mmol) and acetic
anhydride (2.0 mmol), which was stirred for 1.0 h at 60 °C, was rapidly added to
the reaction tube and the reaction mixture stirred for 14–16 h at 100 °C. Upon
completion, the reaction mixture was concentrated and purified by silica gel
column chromatography.
(f) Wang D, Zhang Z. Org Lett. 2003;5:4645–4648;
(g) Tatamidani H, Yokota K, Kakiuchi F, Chatani N.
2004;69:5615–5621;
J
Org Chem.