Pd-Catalyzed Decarbonylative C?H Coupling of Azoles and Aromatic Esters

Article abstract of DOI:10.1002/asia.201800478

A decarbonylative C?H coupling of azoles and aromatic esters by palladium catalysis is described. Our previously reported Ni-catalyzed C?H coupling of azoles and aromatic esters has a significant drawback regarding the substrate scope. Herein, we employ p

Full text of DOI:10.1002/asia.201800478

CHEMISTRY
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Accepted Article
Title: Pd-Catalyzed Decarbonylative C-H Coupling of Azoles and
Aromatic Esters
Authors: Kaoru Matsushita, Ryosuke Takise, Tomoya Hisada, Shin
Suzuki, Ryota Isshiki, Kenichiro Itami, Kei Muto, and Junichiro
Yamaguchi
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10.1002/asia.201800478
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Pd-Catalyzed Decarbonylative C–H Coupling of Azoles and
Aromatic Esters
Kaoru Matsushita,[a] Ryosuke Takise,[b] Tomoya Hisada,[a] Shin Suzuki,[b] Ryota Isshiki,[a] Kenichiro
Itami,[b] Kei Muto[a] and Junichiro Yamaguchi*[a]
Abstract: A decarbonylative C–H coupling of azoles and aromatic
esters by palladium catalysis is described. Our previously reported
Ni-catalyzed C–H coupling of azoles and aromatic esters has a
significant drawback regarding the substrate scope. Herein, we
employ palladium catalysis instead of nickel, resulting in a broader
substrate scope in terms of azoles and aromatic esters.
Decarbonylative transformation of aromatic esters with
nucleophiles has received significant attention from organic
chemists as
a way to achieve a unique cross-coupling
reaction.[1] Aromatic esters can be converted into functionalized
aromatics using transition-metal catalysts via decarbonylation.
Yamamoto is a pioneer of this phenomenon, as he has
discovered and developed these reactions by using nickel
complexes.[2] More than 20 years thereafter, Gooßen made a
revival of these transformations with carbon nucleophiles by
using palladium catalysts in 2002 and 2004.[3]
During our recent development of C–H functionalizations
and coupling reactions with phenol derivatives using nickel
catalysis,[4,5] we discovered the first Ni-catalyzed decarbonylative
coupling in 2012 (Scheme 1A).[6a] 1,3-Azoles reacted with phenyl
aromatic esters under a Ni/dcype catalyst to afford 2-arylazoles
by formally engaging the ester group as a leaving group. After
this reaction, our group and others reported various
decarbonylative transformations of esters,[6,7] as well as those of
amides[8] and thioesters[9] by mainly using nickel catalysts.
However, the original decarbonylative C–H coupling has a
drawback in that it has a narrow substrate scope. Benzoxazoles
and thiazoles reacted well, but lower yields were observed for
benzothiazoles, and benzimidazoles did not work at all. For the
aromatic ester component, the reaction was mainly performed
using heteroaromatic esters, and only one example employed a
simple aromatic phenyl ester. During these efforts, we noticed
that palladium catalysts were sometimes better, or at least
different, in terms of reactivity when compared with nickel
catalysts.[6d, 6e, 6g] Moreover, we discovered a new ligand, dcypt,
which was effective for these transformations.[10] In light of these
findings, we re-examined the decarbonylative C–H coupling of
1,3-azoles and identified that palladium catalytic systems are
also effective for these transformations. Herein, we report the
first Pd-catalyzed decarbonylative C–H coupling of 1,3-azoles
with aromatic esters (Scheme 1B).
Scheme 1. (A) Ni-catalyzed decarbonylative C–H coupling of azoles with
aromatic esters. (B) Pd-catalyzed decarbonylative C–H coupling of azoles with
aromatic esters. dcype = 1,2-bis(dicyclohexylphosphino)ethane, dcypt = 3,4-
bis(dicyclohexylphosphino)thiophene.
To find optimal conditions for the reaction, we selected
benzothiazole (1A) and phenyl 2-thiophenecarboxylate (2a) as
model substrates (Table 1). Firstly, we conducted the coupling in
the presence of a nickel catalyst [Ni(OAc)2] (5 mol%), dcype or
dcypt (10 mol%), and K3PO4 (2.0 equiv) in 1,4-dioxane.[6a] As a
result, desired coupling product 3Aa was obtained in 13% and
38% yields, respectively (entries 1 and 2). Changing the
transition-metal complex from Ni(OAc)2 to Pd(OAc)2 in toluene
increased the yields of 3Aa to 60% and 73% (entries 3 and 4).
Other ligands such as P(n-Bu)3, XPhos, dppe, and IMes shut
down the reaction (entries 5–8). 1,4-dioxane was the best
solvent to give 3Aa in 81% yield using dcypt, whereas anisole
and DMF gave lower yields (entries 9–11). Although PdCl2
slightly decreased the yield, Pd(acac)2 was superior to Pd(OAc)2,
giving 3Aa in nearly quantitative yield (entries 12–13).
Decreasing the loading of the catalyst (1 mol%) was successful,
allowing the reaction to afford 3Aa in 77% yield (entry 14).
With optimal conditions in hand, we then evaluated the
scope of other (hetero)aromatic phenyl esters
2
with
[a]
K. Matsushita, T. Hisada, R. Isshiki, Dr. K. Muto, Prof. Dr. J. Yamaguchi
Department of Applied Chemistry, Waseda University, 3-4-1 Ohkubo,
Shinjuku, Tokyo 169-8555, Japan.
benzothiazoles (1A) (Scheme 2). It turns out that the optimal
conditions in Table 1 were not always the best conditions for this
reaction, therefore we changed several parameters for each
substrate.[11] Five-membered heterocycles such as thiophene
(2a), furans (2b and 2c) and thiazole (2d) gave the
corresponding coupling products in excellent to moderate yields.
E-mail: junyamaguchi@waseda.jp (JY)
[b]
Dr. R. Takise, Dr. S. Suzuki, Prof. Dr. K. Itami
Institute of Transformative Bio-Molecules (WPI-ITbM) and Graduate
School of Science, Nagoya University, Chikusa, Nagoya 464-8602,
Japan
Supporting information for this article is given via a link at the end of the
document.
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10.1002/asia.201800478
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COMMUNICATION
Table 1. Metal-catalyzed decarbonylative C–H coupling of azoles 1A with
aromatic esters 2a.[a]
Entry
Metal
Ligand/X mol%
Solvent
Yield of 3/%[b]
1
2
Ni(OAc)2
Ni(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
PdCl2
dcype (10)
dcypt (10)
dcype (10)
dcypt (10)
P(n-Bu)3 (20)
XPhos (20)
dppe (10)
1,4-dioxane
1,4-dioxane
toluene
13
38
60
73
0
3
4
toluene
5
toluene
6
toluene
0
7
toluene
0
8[c]
9
IMes·HCl (20)
dcypt (10)
dcypt (10)
dcypt (10)
dcypt (10)
dcypt (10)
dcypt (2)
toluene
0
1,4-dioxane
anisole
81
44
43
76
<99
77
10
11
12
13
14[d]
Scheme 2. Substrate scope of benzothiazoles (1A) with various aromatic
esters 2. [a] Pd(acac)2 (5 mol%), dcypt (10 mol%) in 1,4-dioxane (1.6 mL) for
12 h; [b] Pd(OAc)2 (5 mol%), dcypt (10 mol%) for 12 h; [c] Pd(OAc)2 (10 mol%),
dcype (20 mol%); [d] Pd(OAc)2 (10 mol%), dcype (20 mol%) in 1,4-dioxane; [e]
1A (0.2 mmol); [f] 170 °C.
DMF
1,4-dioxane
1,4-dioxane
1,4-dioxane
Pd(acac)2
Pd(acac)2
[a] Conditions: 1A (0.2 mmol), 2a (0.3 mmol), metal catalyst (5 mol%), ligand
(10–20 mol%), K3PO4 (0.4 mmol), solvent (0.8 mL), 150 ºC, 12 h. [b] Yield was
determined by GC analysis using n-decane as an internal standard. [c] NaOt-
Bu (20 mol%) was added. [d] Pd(acac)2 (1 mol%), dcypt (2 mol%) were used.
In the case of phenyl picolinate (2e) and phenyl nicotinate (2f),
dcype was better than dcypt to give coupling products in 57%
and 63% yields, respectively. 4-Pyridyl (2g), 2-pyrazinyl (2h) and
other phenyl azinecarboxylates (2i and 2j) worked under basic
conditions (Table 1, entry 4) to give the corresponding coupling
products
3 in moderate to good yields. Aromatic esters
containing 1-naphthyl (2k) 2-naphthyl (2l), and phenyl (2m)
groups were also effective with dcype, providing the
corresponding 2-arylbenzothiazoles in good yields. Substrates
containing para- and meta-tolyl (2n and 2o) groups, as well as
methoxycarbonyl (2p), also afforded the coupled products.
Next, the scope of 1,3-azoles was also investigated
(Scheme 3). 4,5-Dimethylthiazole, 5-phenylthiazole, and 4-
methylthiazole were reacted with phenyl aromatic esters to give
the corresponding coupling products (3Ba, 3Bi, 3Ca, 3Da, and
3Ea) in moderate yields. Only one example of benzoxazoles
was attempted to provide 2-arylbenzoxazole (3Fa) in good yield,
since oxazoles were already investigated in a previously
reported Ni-catalyzed reaction.[6a] To our delight, benzimidazoles
also worked under palladium catalysis to give the corresponding
coupling products (3Ga and 3Gi).
Scheme 3. Substrate scope of azole 1 and phenyl ester 2. [a] 1 (0.2 mmol); [b]
Pd(OAc)2 (10 mol%), dcypt (20 mol%) in toluene (1.6 mL) for 24 h; [c]
Pd(acac)2 (10 mol%), dcype (20 mol%) for 24 h
To showcase the utility of the present C–H coupling method,
we set out to achieve a sequential decarbonylative reaction
using both palladium and nickel catalysis (Scheme 4). To this
end, diphenyl ester
4 was subjected to decarbonylative
etherification under Ni/dcypt catalysis to give ether 5 in good
yield.[6f] Subsequently, the decarbonylative C–H coupling of
ester 5 with benzothiazole (1A) under Pd/dcypt catalysis
provided 2-arylbenzothiazole 6. Instead of
a
sequential
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mol%). The vessel was evacuated in vacuo and refilled N2 gas three
times. To this vessel were added azole 1 (0.40 mmol) and dry 1,4-
dioxane (1.6 mL). The vessel was sealed with the O-ring tap and then
heated at 150 °C for 12 h in a 9-well aluminum reaction block with stirring.
After cooling the reaction mixture to room temperature, the mixture was
passed through a short silica gel pad with EtOAc as an eluent. The
filtrate was concentrated and the residue was purified by Isolera® or
PTLC to afford the corresponding C–H coupling product 3.
procedure, a one-pot procedure can also be performed to make
6: diphenyl ester 4 was reacted with 1A in the presence of both
palladium and nickel catalysts to afford the same product 6 in
38% yield.
Acknowledgements
This work was supported by JSPS KAKENHI Grant Number
JP16H01011, JP16H04148 (to J. Y.), and JP17K14453 (to K.M.),
the ERATO program from JST (to K. I.), and a JSPS research
fellowship for young scientists (to T. R. and S. S.). Materials
Characterization Central Laboratory in Waseda University is
acknowledged for HRMS measurement. ITbM is supported by
the World Premier International Research Center (WPI) Initiative,
Japan.
Scheme 4. Pd/Ni sequential decarbonylative transformations. (a) Ni(cod)2 (5
mol%), dcypt (10 mol%), K3PO4 (1.5 equiv), toluene, 150 ºC, 18 h, 83%; (b)
Pd(OAc)2 (10 mol%), dcypt (20 mol%), K3PO4 (2.0 equiv), toluene, 170 ºC, 24
h, 71%; (c) Ni(OAc)2 (5 mol%), Pd(OAc)2 (10 mol%), dcypt (30 mol%), K3PO4
(2.0 equiv), toluene, 170 ºC, 24 h, 38%.
Keywords: C–H coupling • palladium • nickel • decarbonylation •
heteroarenes
In summary, we have developed a Pd-catalyzed C–H
coupling of 1,3-azoles and aromatic esters. Adding to our
previously established Ni-catalyzed transformation, palladium
catalysts were also effective for this transformation, and
exhibited a considerably broad substrate scope. Further studies
to expand the scope of ester-based coupling by palladium
catalysis are ongoing in our group and will be reported in due
course.
References:
[1]
[2]
a) A. Correa, J. Cornella, R. Martin, Angew. Chem. Int. Ed. 2013, 52,
1878. b) R. Takise, K. Muto, J. Yamaguchi, Chem. Soc. Rev. 2017, 46,
5864.
a) J. Ishizu, T. Yamamoto, A. Yamamoto, Chem. Lett. 1976, 5, 1091; b)
T. Yamamoto, J. Ishizu, T. Kohara, S. Komiya, A. Yamamoto, J. Am.
Chem. Soc. 1980, 102, 3758.
[3]
[4]
a) L. J. Gooßen, J. Paetzold, Angew. Chem. Int. Ed. 2002, 41, 1237; b)
L. J. Gooßen, J. Paetzold, Angew. Chem. Int. Ed. 2004, 43, 1095.
Experimental Section
For
a review of Ni-catalyzed C–H functionalizations, see: a) J.
Yamaguchi, K. Muto, K. Itami, Eur. J. Org. Chem. 2013, 19; b) S. Z.
Tasker, E. A. Standley, T. F. Jamison, Nature 2014, 509, 299; c) L. C.
M. Castro, N. Chatani, Chem. Lett. 2015, 44, 410; d) G. Pototschnig, N.
Maulide, M. Schnürch, Chem. Eur. J. 2017, 23, 9206. e) J. Yamaguchi,
K. Muto, K. Itami, Top Curr. Chem, 2016, 374, 55.
General Information
Unless otherwise noted, all reactants or reagents including dry solvents
were obtained from commercial suppliers and used as received.
Pd(OAc)2, K3PO4 and thiazole (1E) were obtained from Wako Chemicals.
Ni(OAc)2·4H2O and 3,4-bis(dicyclohexylphosphino)thiophene (dcypt)
[5]
[6]
a) K. Muto, J. Yamaguchi, K. Itami, J. Am. Chem. Soc. 2012, 134, 169;
b) L. Meng, Y. Kamada, K. Muto, J. Yamaguchi, K. Itami, Angew. Chem.
Int. Ed. 2013, 52, 10048; c) K. Muto, J. Yamaguchi, A. Lei, K. Itami, J.
Am. Chem. Soc. 2013, 135, 16384; d) H. Xu, K. Muto, J. Yamaguchi, C.
Zhao, K. Itami, D. G. Musaev, J. Am. Chem. Soc. 2014, 136, 14834; e)
K. Muto, T. Hatakeyama, J. Yamaguchi, K. Itami, Chem. Sci. 2015, 6,
6792; f) R. Takise, K. Itami, J. Yamaguchi, Org. Lett. 2016, 18, 4428.
a) K. Amaike, K. Muto, J. Yamaguchi, K. Itami, J. Am. Chem. Soc. 2012,
134, 13573; b) K. Muto, J. Yamaguchi, D. G. Musaev, K. Itami, Nat.
Commun. 2015, 6, 7508; c) K. Amaike, K. Itami, J. Yamaguchi, Chem.
Eur. J. 2016, 22, 4384; d) K. Muto, T. Hatakeyama, K. Itami, J.
Yamaguchi, Org. Lett. 2016, 18, 5106; e) T. Okita, K. Kumazawa, R.
Takise, K. Muto, K. Itami, J. Yamaguchi, Chem. Lett. 2017. 46, 218; f)
R. Takise, R. Isshiki, K. Muto, K. Itami, J. Yamaguchi, J. Am. Chem.
Soc. 2017, 139, 3340; g) R. Isshiki, R. Takise, K. Itami, K. Muto, J.
Yamaguchi, Synlett 2017, 28, 2599; h) R. Isshiki, K. Muto, J.
Yamaguchi, Org. Lett. 2018, 20, 1150.
were
obtained
from
KANTO
Chemical.
1,2-
Bis(dicyclohexylphosphino)ethane (dcype) was obtained from Sigma-
Aldrich. Pd(acac)2, benzothiazole (1A), 4,5-dimethylthiazole (1B), 4-
methylthiazole (1D), benzoxazole (1F), 1-methylbenzimidazole (1G) and
phenyl benzoate (2m) were obtained from TCI Chemical. Other
substrates were synthesized according to procedures and the spectra
matched with those of compounds reported in the literature.[11] Unless
otherwise noted, all reactions were performed with dry solvents under an
atmosphere of N2 in dried glassware using standard vacuum-line
techniques. All C–H coupling reactions were performed in 20-mL glass
vessel tubes equipped with a J. Young® O-ring tap and heated (YMC EX-
Thermo Stirring, AR-HSC) in a 9-well aluminum reaction block (IKA H
135.103 Block 9 x 16 ml) unless otherwise noted. All work-up and
purification procedures were carried out with reagent-grade solvents in
air.
[7]
a) N. A. LaBerge, J. A. Love, Eur. J. Org. Chem. 2015, 5546. b) L. Guo,
A. Chatupheeraphat, M. Rueping, Angew. Chem. Int. Ed. 2016, 55,
11810. c) X. Pu, J. Hu, Y. Zhao, Z. Shi, ACS Catal. 2016, 6, 6692. d) H.
Yue, L. Guo, H.-H. Liao, Y. Cai, C. Zhu, M. Rueping, Angew. Chem. Int.
Ed. 2017, 56, 4282. e) X. Liu, J. Jia, M. Rueping, ACS Catal. 2017, 7,
4491. f) H. Tatamidani, F. Kakiuchi, N. Chatani, Org. Lett. 2004, 6,
3597. g) A. Chatupheeraphat, H. H. Liao, W. Srimontree, L. Guo, Y.
Minenkov, A. Poater, L. Cavallo, M. Rueping, J. Am. Chem. Soc. 2018,
140, 3724. For related nondecarbonylative couplings of aromatic esters,
General Procedure for Pd-catalyzed Decarbonylative C–H coupling
A 20-mL glass vessel equipped with a J. Young® O-ring tap containing a
magnetic stirring bar and K3PO4 (169.8 mg, 0.80 mmol, 2.0 equiv) was
dried with a heat gun in vacuo and filled with N2 after cooling to room
temperature. To this vessel were added aromatic ester 2 (0.60 mmol, 1.5
equiv), Pd(acac)2 (6.09 mg, 0.02 mmol, 5.0 mol%) and 3,4-
bis(dicyclohexylphosphino)thiophene (dcypt: 19.1 mg, 0.04 mmol, 10
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see: h) L. Hie, N. F. Fine Nathel, X. Hong, Y.-F. Yang, K. N. Houk, N. K.
Garg, Angew. Chem. Int. Ed. 2016, 55, 2810. i) T. Ben Halima, W.
Zhang, I. Yalaoui, X. Hong, Y.-F. Yang, K. N. Houk, S. G. Newman, J.
Am. Chem. Soc. 2017, 139, 1311.
[8]
For a review, see: a) G. Meng, S. Shi, M. Szostak, Synlett 2016, 27,
2530. For selected examples, see: b) Y. Kajita, S. Matsubara, T.
Kurahashi, J. Am. Chem. Soc. 2008, 130, 6058. c) G. Meng, M.
Szostak, Angew. Chem. Int. Ed. 2015, 54, 14518. d) S. Shi, G. Meng,
M. Szostak, Angew. Chem. Int. Ed. 2016, 55, 6959. e) J. Hu, Y. Zhao, J.
Liu, Y. Zhang, Z. Shi, Angew. Chem. Int. Ed. 2016, 55, 8718. f) X. Liu,
H. Yue, J. Jia, L. Guo, M. Rueping, Chem. Eur. J. 2017, 23, 11771. g)
C. Liu, M. Szostak, Angew. Chem. Int. Ed. 2017, 57, 3939. h) W.
Srimontree, A. Chatupheeraphat, H. H. Liao, M. Rueping, Org. Lett.
2017, 19, 3091. For related nondecarbonylative couplings of aromatic
amides, see: i) L. Hie, N. F. Fine Nathel, T. K. Shah, E. L. Baker, X.
Hong, Y.-F. Yang, P. Liu, K. N. Houk, N. K. Garg, Nature 2015, 524, 79.
j) N. A. Weires, E. L. Baker, N. K. Garg, Nat. Chem. 2016, 8, 75. k) J. E.
Dander, N. K. Garg, ACS Catal. 2017, 7, 1413.
[9]
a) H. Ochiai, Y. Uetake, T. Niwa, T. Hosoya, Angew. Chem. Int. Ed.
2017, 56, 2482; b) T. Niwa, H. Ochiai, M. Isoda, T. Hosoya, Chem. Lett.
2017, 46, 1315; c) N. Ichiishi, C. A. Malapit, Ł. Woźniak, M. S. Sanford,
Org. Lett. 2018, 20, 44; d) S.-C. Lee, H.-H. Liao, A. Chatupheeraphat,
M. Rueping, Chem. Eur. J. 2018, 24, 3608; e) C. Liu, M. Szostak,
Chem. Commun. 2018, 54, 2130.
[10] a) R. Takise, K. Muto, J. Yamaguchi, K. Itami, Angew. Chem. Int. Ed.
2014, 53, 6791; b) E. Koch, R. Takise, A. Studer, J. Yamaguchi, K.
Itami, Chem. Commun. 2014, 51, 855.
[11] See supporting information for detail.
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Entry for the Table of Contents
Changing from Ni to Pd in the decarbonylative C–H coupling of azoles and aromatic esters.
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