Palladium-Catalyzed Carbonylations of Arylboronic Acids: Synthesis of Arylcarboxylic Acid Ethyl Esters

Article abstract of DOI:10.1002/adsc.201500521

An approach for the palladium-catalyzed ethoxycarbonylations of arylboronic acids using diethyl pyrocarbonate as carbon monoxide/carbon dioxide (CO/CO₂) surrogate in moderate to good yields has been investigated.

Full text of DOI:10.1002/adsc.201500521

COMMUNICATIONS
DOI: 10.1002/adsc.201500521
Palladium-Catalyzed Carbonylations of Arylboronic Acids:
Synthesis of Arylcarboxylic Acid Ethyl Esters
Apeng Liang,a,b,c Shuaijun Han,a Liang Wang,a Jingya Li,b,c Dapeng Zou,a,b,c
Yangjie Wu,a,* and Yusheng Wub,d,*
a
The College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou, Peopleꢀs Republic of China
E-mail: wyj@zzu.edu.cn
b
Collaborative Innovation Center of New Drug Research and Safely Evaluation, Henan Province, Peopleꢀs Republic of
China
c
Tetranov Biopharm, LLC, No.75 Daxue Road, Zhengzhou, Peopleꢀs Republic of China
Tetranov International, Inc., 100 Jersey Avenue, Suite A340, New Brunswick, NJ 08901, USA
d
Fax: (+1)-732-253-7327; phone: (+1)-732-253-7326120; e-mail: yusheng.wu@tetranovglobal.com
Received: May 25, 2015; Revised: August 12, 2015; Published online: October 12, 2015
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201500521.
Abstract: An approach for the palladium-catalyzed
ethoxycarbonylations of arylboronic acids using di-
ethyl pyrocarbonate as carbon monoxide/carbon di-
oxide (CO/CO2) surrogate in moderate to good
yields has been investigated.
meantime Skrydstrup et al. reported a series of CO-
free carbonylation reactions using ex situ generated
carbon monoxide.[8] In the last two years, Manabe and
co-workers reported an interesting palladium-cata-
lyzed reductive carbonylation of aryl halides using N-
formylsaccharin and phenyl formate as an in situ CO
source.[9] Recently, Beller et al. have also done a lot
of excellent work in the utilization of CO surrogates
like aryl formates and paraformaldehyde in carbony-
lation reactions.[10]
Keywords: arylboronic acids; arylcarboxylic acid
ethyl esters; CO/CO2 surrogate; diethyl pyrocar-
bonate; palladium-catalyzed carbonylation
Arylboronic acids appeared to be the carbon nucle-
ophiles of choice, as they are readily available,[11] non-
toxic, air- and moisture-stable compounds that toler-
Aryl(heteroaryl)carboxylic acid derivatives are not ate the presence of many sensitive functionalities. In
only important tools and structural elements in mate- 2001, Gooßen and co-workers successfully accom-
rial sciences and chemical biology but also versatile plished the acylation reaction of arylboronic acids
building blocks in organic synthesis.[1] Ever since the using carboxylic acids or anhydrides as acylation re-
pioneering work of Heck and Schoenberg in 1974, agent.[12] A few years later, the research groups of
palladium-catalyzed carbonylations using CO and aryl Iwasawa[13] and Hou[14] reported a nucleophilic addi-
halides have enabled the synthesis of a variety of car- tion of arylboronate esters toward CO2 in the pres-
bonyl compounds.[2] Nowadays, these reactions are ence of rhodium or copper catalysts, respectively.
routinely applied for constructing carbonyl-containing Next, Lei et al. reported the oxidative carbonylation
compounds such as aldehydes, amides, esters etc, of arylboronic acid derivatives under balloon pressure
using carbon monoxide gas under high pressure and of CO with air as the oxidant.[15] In 2014, the tert-
temperature for long durations.[3] Although Beller butyl esters of (hetero)arylcarboxylic acid were syn-
and Buchwald et al. reported relatively mild reaction thesized using (Boc)2O as CO surrogate from
conditions,[4] one of the raw materials for the carbony- (hetero)arylboronic acid derivatives by our groups.[16]
lation reaction is still the toxic carbon monoxide. At the same time, Xu et al. reported the ruthenium-
À
Therefore, the search for some alternative sources of catalyzed two-fold C H tertiary alkoxycarbonylation
CO is underway to provide an effective supplement of arenes using (Boc)2O.[17] Compared to CO, CO2 or
to the carbonylation reaction.[5] For example, Liu other CO surrogates, diethyl pyrocarbonate is more
et al. successfully synthesized aromatic esters using desirable because it is a low toxic, stable, safe, widely
oxalate monoester salts as carbonylation reagent.[6] available, and inexpensive CO/CO2 surrogate. As yet
As a CO surrogate, Mo(CO)6 and Co2(CO)8 have there have been no reports of alkoxycarbonylation re-
been used extensively by Larhed and others.[7] In the actions using diethyl pyrocarbonate. Herein, we
3104
ꢁ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2015, 357, 3104 – 3108

COMMUNICATIONS
Palladium-Catalyzed Carbonylations of Arylboronic Acids
Table 1. Optimization of the reaction conditions.[a]
Entry Catalyst Ligand
Base
Solvent Yield[c]
[%]
Scheme 1. Synthesis of aryl esters by palladium-catalyzed al-
koxycarbonylation.
1
2
3
4
5
6
7
8
Pd(OAc)2 PPh3
Pd(OAc)2 PPh3
–
–
–
-
–
-
–
–
–
–
–
dioxane 46[b]
dioxane 75
dioxane 36
dioxane 42
dioxane 68
dioxane 63
dioxane 33
dioxane 51
dioxane 63
dioxane 56
dioxane 20
dioxane 46
DMSO 12
toluene 64
PdCl2
PPh3
Pd2(dba)3 PPh3
Pd(TFA)2 PPh3
Pd(PPh3)4 –
Pd(OAc)2 PCy3
Pd(OAc)2 Dppf
Pd(OAc)2 S-Phos
Pd(OAc)2 Xantphos
Pd(OAc)2 Binap
report the first example of the palladium-catalyzed
carbonylation of aryl(heteroaryl)boronic acid deriva-
tives to form various aryl(heteroaryl)carboxylic acid
derivatives using diethyl pyrocarbonate as the carbon-
ylation reagent (Scheme 1).
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
The reaction of phenylboronic acid (1) with diethyl
pyrocarbonate (2) was chosen as model reaction and
the results are summarized in Table 1. Initially, this
reaction was carried out by using 2.0 equivalents of
diethyl pyrocarbonate (2) as a CO/CO2 surrogate,
with 5 mol% Pd(OAc)2 and 15 mol% PPh3 as catalyst
system in 3.0 mL of dioxane at 1008C for 15 h. To our
disappointment, only a moderate yield was observed
(Table 1, entry 1). After increasing the loading of
PPh3 to 20 mol% and the reaction temperature to
1108C, the yield of 3 increased to 75% (Table 1,
entry 2). Next, various Pd sources and ligands were
investigated (Table 1, entries 2–12). Obviously, when
palladium acetate was used as catalyst in the presence
of triphenylphosphine as ligand, the yield of the de-
sired product was better (Table 1, entry 2). The reac-
tion has also been carried out in different solvents
(Table 1, entries 13–16). Based on the results ob-
tained, we selected dioxane as the medium and 1108C
as the optimum temperature (Table 1, entry 2). Bases
are very important in transition metal-catalyzed or-
ganic reactions to promote the reaction efficiency and
increase the yields of products according to the litera-
ture.[18] Screening studies to find a suitable base for
the ethoxycarbonylation of phenylboronic acid were
carried out (Table 1, entries 17–21). The results indi-
Pd(OAc)2 DavePhos –
Pd(OAc)2 PPh3
Pd(OAc)2 PPh3
Pd(OAc)2 PPh3
Pd(OAc)2 PPh3
Pd(OAc)2 PPh3
Pd(OAc)2 PPh3
Pd(OAc)2 PPh3
Pd(OAc)2 PPh3
Pd(OAc)2 PPh3
Pd(OAc)2 PPh3
Pd(OAc)2 PPh3
–
-
–
–
DMF
21
EtOH trace[e]
dioxane 26
Et3N
DMAP dioxane 32
K2CO3 dioxane 87
Na2CO3 dioxane 92/86[d]
K3PO4 dioxane 78
Na2CO3 dioxane 23[f]
Na2CO3 dioxane 68[g]/NA[h]
[a]
Reaction conditions: 1.0 mmol 1, 2.0 mmol 2, 5 mol% cat-
alyst, 20 mol% ligand, no base or 2.0 mmol base, 3 mL
solvent, 1108C, 16 h, argon atmosphere.
15 mol% PPh3, the reaction temperature was 1008C.
The yields were determined by using GC (average of two
GC runs) using di-n-pentyl phthalate as an internal stan-
dard.
Isolated yields based on 1.
The reaction temperature was 808C.
Oxygen atmosphere.
Reaction performed in the presence of H2O (1.0 mmol,
1.0 equiv.).
[b]
[c]
[d]
[e]
[f]
[g]
[h]
Reaction performed in the presence of H2O (1.0 mL).
cated that Na2CO3 (Table 1, entry 20) to be a relatively tion of 5 mol% Pd(OAc)2, 20 mol% PPh3, 2.0 equiv.
good base. We also tested an oxygen atmosphere[15,19] Na2CO3, in anhydrous dioxane at 1108C.
in the reaction (Table 1, entry 22), and found that the
This transformation was next applied to a variety of
yield was less than the result under an argon atmos- different arylboronic acid derivatives. The representa-
phere (Table 1, entry 20). It was also found that the tive examples shown in Table 2 were selected to high-
yield was lower in the presence of a certain amount light not only the broad scope but also the limitations
of water[12] (Table 1, entry 23). Finally, the optimum of this method. Aromatic boronic acids bearing either
reaction conditions were determined as the combina- electron-donating (methyl, methoxy) or electron-with-
Adv. Synth. Catal. 2015, 357, 3104 – 3108
ꢁ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
3105

COMMUNICATIONS
Apeng Liang et al.
Table 2. Palladium-catalyzed ethoxycarbonylation of arylboronic aicds with diethylpyrocarbonate.[a,b]
[a]
Reaction conditions: 1.0 mmol 1, 2.0 mmol 2, 5 mol% Pd(OAc)2, 20 mol% PPh3, 2.0 mmol
Na2CO3, 3 mL dioxane, 1108C, 16 h, argon atmosphere.
Isolated yields base on 1.
Using boronic acid pinacol ester as substrate.
[b]
[c]
drawing (cyano, trifluoromethyl, fluoro, methyl ester) ethoxycarbonylation of 1z with 2 provided 3z in 76%
substituents underwent ethoxycarbonylation in mod- yield. So, we have developed a new method for the
erate to high yields. While the conversion rates of 1i, synthesis of substituted estratriene analogues as 17ß-
1j, 1m, 1n and 1o were very good as detected by GC, HSD inhibitors.[20] This result demonstrates that this
the isolated yields of 3i, 3j, 3m, 3n and 3o were rela-
tively lower because the fluorinated organic com-
pounds have high volatility. A variety of different po-
tentially reactive functional groups which can be fur-
ther functionalized (aromatic chloride, alcohol,
ketone, aldehyde) were quite well-tolerated. Mean-
while, boronic acids derived from pyridine, furan, and
thiophene all underwent the ethoxycarbonylation in
middle yields.
To demonstrate the scalability of the reaction, we
chose the ethoxycarbonylation of 1b with 2 on a 1.0 g
scale. The desired ethoxycarbonylated product 3b was
isolated in 83% yield (0.98 g) (Scheme 2).
Subsequently, the method was investigated in the
synthesis of an estrone derivative (Scheme 3). The Scheme 2. Scalability of the ethoxycarbonylation of 1b.
3106
asc.wiley-vch.de
ꢁ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2015, 357, 3104 – 3108

COMMUNICATIONS
Palladium-Catalyzed Carbonylations of Arylboronic Acids
(122300413203), and Technology Research and Development
Funds of Zhengzhou (141PRCYY516) for financial support.
References
[1] a) B. S. Furniss; A. J. Hannaford; P. W. G. Smith; A. R.
Tatchell, Vogelꢀs Textbook of Practical Organic Chemis-
try, 5th edn.; Wiley, New York, 1989; p 1266; b) R. C.
Larock, Comprehensive Organic Transformations, 2nd
edn., VCH: New York, 1989, p 881; c) A. C. Carmo,
L. K. C. de Souza, C. E. F. de Costa, E. Longo, J. R.
Zamian, G. N. da Rocha Filha, Fuel 2009, 88, 461; d) T.
Nishikubo, A. Kameyama, Y. Yamada, Y. J. Yoshida,
Polym. Sci. Part A: Polym. Chem. 1996, 34, 3531;
e) H. R. Ansari, A. J. Curtis, J. Soc. Cosmet. Chem.
1974, 25, 203.
Scheme 3. The ethoxycarbonylation of an estrone derivative.
method is extendable to other pharmaceutically rele-
vant molecules.
[2] a) A. Schoenberg, I. Bartoletti, R. F. Heck, J. Org.
Chem. 1974, 39, 3318; b) A. Schoenberg, R. F. Heck, J.
Org. chem. 1974, 39, 3327; c) A. Schoenberg, R. F.
Heck, J. Am. Chem. Soc. 1974, 96, 7761.
In summary, we have developed a mild and general
CO/CO2-free carbonylation protocol for the palladi-
um-catalyzed ethoxycarbonylation of arylboronic acid
derivatives. Notably, the advantage of this method is
that diethyl pyrocarbonate is a readily available and
an inexpensive carbonylation reagent. What is more,
this method offers a convenient alternative for
ethoxycarbonylation compared to conventional car-
bonylations using syngas or CO/CO2 directly. Avoid-
ing the use of high-pressure equipment is another
merit of this method.
[3] a) A. Brennführer, H. Neumann, M. Beller, Angew.
Chem. 2009, 121, 4176; Angew. Chem. Int. Ed. 2009, 48,
4114; b) X. F. Wu, H. Neumann, M. Beller, Chem. Soc.
Rev. 2011, 40, 4986; c) X. F. Wu, H. Neumann, M.
Beller, Chem. Rev. 2013, 113, 1; d) X. F. Wu, H. Neu-
mann, M. Beller, ChemSusChem 2013, 6, 229; e) Q.
Liu, H. Zhang, A. Lei, Angew. Chem. 2011, 123, 10978;
Angew. Chem. Int. Ed. 2011, 50, 10788; f) C. F. J. Bar-
nard, Organometallics 2008, 27, 5402; g) B. Gabriele, R.
Mancuso, G. Salerno, Eur. J. Org. Chem. 2012, 6825.
[4] a) W. Mägerlein, A. F. Indolese, M. Beller, Angew.
Chem. 2001, 113, 2940; Angew. Chem. Int. Ed. 2001, 40,
2856; b) R. H. Munday, J. R. Martinelli, S. L. Buchwald,
J. Am. Chem. Soc. 2008, 130, 2754; c) D. A. Watson, X.
Fan, S. L. Buchwald, J. Org. Chem. 2008, 73, 7096.
[5] a) T. Morimoto, K. Kakiuchi, Angew. Chem. 2004, 116,
5698; Angew. Chem. Int. Ed. 2004, 43, 5580; b) L. Wu,
Q. Liu, R. Jackstell, M. Beller, Angew. Chem. 2014,
126, 6426; Angew. Chem. Int. Ed. 2014, 53, 6310.
Experimental Section
Palladium-Catalyzed Carbonylations of Arylboronic
acids with Diethyl Pyrocarbonate; Typical Reaction
Procedure
Pd(OAc)2 ( 11.2 mg, 0.05 mmol, 5 mol%), PPh3 (52.4 mg,
0.20 mmol, 20 mol%), Na2CO3 (212 mg, 2.0 mmol,
2.0 equiv.), arylboronic acid (1.0 mmol, 1.0 equiv.), diethyl
pyrocarbonate ( 324.0 mg, 2.0 mmol, 2.0 equiv.) and dioxane
(3 mL) were placed in a dried glass reaction tube and the
air was replaced three times with argon. The reaction mix-
ture was stirred at 1108C for 16 h. After the mixture had
been cooled to room temperature it was extracted with
EtOAc and H2O. The combined organic layer was washed
with brine, and then dried over anhydrous Na2SO4. The sol-
vent was evaporated under vacuum to afford the crude reac-
tion mixture, which was then purified on silica gel plates to
produce the desired product. The products were character-
ized by 1H NMR, 13C NMR and LC-MS.
[6] R. Shang, Y. Fu, J. B. Li, S. L. Zhang, Q. X. Guo, L.
Liu, J. Am. Chem. Soc. 2009, 131, 5738.
[7] a) A. Wieckowska, R. Fransson, L. R. Odell, M.
Larhed, J. Org. Chem. 2011, 76, 978; b) R. L. Odell, F.
Russo, M. Larhed, Synlett 2012, 685; c) X. F. Wu, M.
Sharif, K. Shoaib, H. Neumann, A. Pews-Davtyan, P.
Langer, M. Beller, Chem. Eur. J. 2013, 19, 6230; d) P.
Baburajan, R. Senthilkumaran, K. P. Elango, New J.
Chem. 2013, 37, 3050.
[8] a) S. D. Friis, R. H. Taaning, A. T. Lindhardt, T.
Skrydstrup, J. Am. Chem. Soc. 2011, 133, 18114; b) P.
Hermange, T. M. Gøgsig, A. T. Lindhardt, R. H. Taan-
ing, T. Skrydstrup, Org. Lett. 2011, 13, 2444; c) T. M.
Gøgsig, D. U. Nielsen, A. T. Lindhardt, T. Skrydstrup,
Org. Lett. 2012, 14, 2536; d) D. U. Nielsen, K. Neu-
mann, R. H. Taaning, A. T. Lindhardt, A. Modvig, T.
Skrydstrup, J. Org. Chem. 2012, 77, 6155; e) C. Bran-
cour, T. Fukuyama, Y. Mukai, T. Skrydstrup, I. Ryu,
Org. Lett. 2013, 15, 2794; f) M. N. Burhardt, R. H.
Taaning, T. Skrydstrup, Org. Lett. 2013, 15, 948; g) S.
Korsager, R. H. Taaning, A. T. Lindhardt, T. Skrydstr-
up, J. Org. Chem. 2013, 78, 6112.
Acknowledgements
We are grateful to the Natural Science Foundation of China
(20772114, 21172200), Research Program of Fundamental
and
Advanced
Technology
of
Henan
Province
Adv. Synth. Catal. 2015, 357, 3104 – 3108
ꢁ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
3107

COMMUNICATIONS
Apeng Liang et al.
[9] a) T. Ueda, H. Konishi, K. Manabe, Angew. Chem.
2013, 125, 8773; Angew. Chem. Int. Ed. 2013, 52, 8611;
b) T. Ueda, H. Konishi, K. Manabe, Org. Lett. 2013, 15,
5370; c) T. Ueda, H. Konishi, K. Manabe, Tetrahedron
Lett. 2012, 53, 5171; d) T. Ueda, H. Konishi, K.
Manabe, Org. Lett. 2012, 14, 3100.
[14] T. Ohishi, M. Nishiura, Z. Hou, Angew. Chem. 2008,
120, 5876; Angew. Chem. Int. Ed. 2008, 47, 5792.
[15] Q. Liu, G. Li, J. He, J. Liu, P. Li, A. W. Lei, Angew.
Chem. 2010, 122, 3443; Angew. Chem. Int. Ed. 2010, 49,
3371.
[16] X. J. Li, D. P. Zou, H. L. Zhu, Y. P. Wang, J. Y. Li, Y. J.
[10] a) H. Li, H. Neumann, M. Beller, X. F. Wu, Angew.
Chem. 2014, 126, 3247; Angew. Chem. Int. Ed. 2014, 53,
3183; b) K. Natte, A. Dumrath, H. Neumann, M.
Beller, Angew. Chem. 2014, 126, 10254; Angew. Chem.
Int. Ed. 2014, 53, 10090.
[11] a) T. Ishiyama, M. Murata, N. Miyaura, J. Org. Chem.
1995, 60, 7508; b) T. Ishiyama, Y. Itoh, T. Kitano, N.
Miyaura, Tetrahedron Lett. 1997, 38, 3447; c) M.
Murata, T. Oyama, S. Watanabe, Y. Masuda, J. Org.
Chem. 1997, 62, 6458; d) M. Murata, T. Oyama, S. Wa-
tanabe, Y. Masuda, J. Org. Chem. 2000, 65, 164.
[12] L. J. Gooßen, K. Ghosh, Angew. Chem. 2001, 113,
3566; Angew. Chem. Int. Ed. 2001, 40, 3458.
Wu, Y. S. Wu, Org. Lett. 2014, 16, 1836.
[17] X. H. Hou, H. Wang, B. X. Liu, B. Xu, Chem.
Commun. 2014, 50, 14129.
[18] a) K. Ouyang, Z. Xi, Acta Chim. Sin. 2013, 71, 13;
b) J. R. Martinelli, T. P. Clark, D. A. Watson, R. H.
Munday, S. L. Buchwald, Angew. Chem. 2007, 119,
8612; Angew. Chem. Int. Ed. 2007, 46, 8460.
[19] K. S. Yoo, C. H. Yoon, K. W. Jung, J. Am. Chem. Soc.
2006, 128, 16384.
[20] Substituted estratriene derivatives were reported as
17ß-HSD inhibitors, see: M. Josef, H. Bettina, S. Uwe,
T. Heinrich-Hubert, K. Pasi, U. Mikko, PCT Int. Appl.
2008065100, 2008 (WO 2008065100A1).
[13] K. Ukai, M. Aoki, J. Takaya, N. Iwasawa, J. Am. Chem.
Soc. 2006, 128, 8706.
3108
asc.wiley-vch.de
ꢁ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2015, 357, 3104 – 3108