Metal-free synthesis of aryl esters by coupling aryl carboxylic acids and aryl boronic acids

Article abstract of DOI:10.1016/j.tetlet.2014.02.079

A facile synthesis of aryl esters is developed by coupling aryl carboxylic acids and aryl boronic acids in the presence of PhI(OAc)₂ and carbonyl diimidazole. A wide range of functional groups were tolerant to the metal-free reaction condition that led to the desired products in good yields.

Full text of DOI:10.1016/j.tetlet.2014.02.079

Tetrahedron Letters 55 (2014) 2345–2347
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Metal-free synthesis of aryl esters by coupling aryl carboxylic acids
and aryl boronic acids
b,
Jayaraman Sembian Ruso a, Nagappan Rajendiran a, , Rajendran Senthil Kumaran
⇑
⇑
a Department of Polymer Science, Maramalai Campus, University of Madras, Guindy, Chennai 600025, India
b Syngene International Ltd, Biocon Park #2 and 3, Bommasandra, Jigani Link Road, Bangalore 560099, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A facile synthesis of aryl esters is developed by coupling aryl carboxylic acids and aryl boronic acids in the
presence of PhI(OAc)2 and carbonyl diimidazole. A wide range of functional groups were tolerant to the
metal-free reaction condition that led to the desired products in good yields.
Ó 2014 Elsevier Ltd. All rights reserved.
Received 5 August 2013
Revised 18 February 2014
Accepted 23 February 2014
Available online 12 March 2014
Keywords:
Aryl ester
Aryl boronic acid
Phenyl iododiacetate
Carbonyl diimidazole
Esters are an omnipresent functional group in chemistry. In par-
ticular, aryl esters are the most abundant subunit found in natural
products, agrochemicals, pharmaceuticals, and polymers.1 Besides,
they serve as versatile building blocks in synthesis.2 Accordingly,
the synthetic routes to produce such systems have generated am-
ple interest among synthetic chemists.3 Conventionally, aryl esters
are prepared via the esterification process which involves coupling
of aryl carboxylic acid and phenol under acidic or basic conditions
and thus restricting the use of substrates bearing sensitive
functional groups.4 Carbodiimide based coupling agents are useful,
but separation of the by-product urea derivatives from the final
product poses difficulties. Similarly, in the Mitsunobu reaction,
multiple purifications are needed to isolate the pure esters.5
Baeyer–Villiger oxidation of ketone often displayed low regioselec-
tivity.6 Thus, the development of mild and efficient protocol to
access aryl ester is highly desirable.
aryl carboxylic acid to prepare sterically congested aryl esters by
employing a metal-free strategy.9 Concurrently, aryl boronic acid
has emerged as a valuable reagent due to its commercial availabil-
ity and easy handling. In recent years, it has been transformed to
various groups.10 Recently, Cheng and co-workers developed a
copper based Chan-Lam method to couple aryl boronic acid with
aryl carboxylic acid.11 A similar strategy was later demonstrated
by the Liu group.12 However to the best of our knowledge, a me-
tal-free approach has not been developed so far to couple the aryl
boronic acid. From the synthetic perspective, metal-free synthesis
is a beneficial approach since it involves the utilization of inexpen-
sive and environmentally benign reagents and also avoids the dis-
posal of residual metallic waste obtained during the reaction.13,14
Along these lines, we began to investigate the synthesis of aryl es-
ter and herein, we disclose the coupling of aryl carboxylic acid and
boronic acid under metal-free condition (Scheme 1).
In recent years, carbonAoxygen bond forming reactions have
progressed rapidly with the aid of transition-metal catalyst.7 Such
a bond is present in aryl ester and thus serves as an ideal target
substrate for demonstrating new protocols. As a result, methods
are being developed to prepare aryl esters by coupling of aryl
carboxylic acids with counterparts other than phenol. In this
connection, aryl trimethoxysilane was used as a coupling partner
in the presence of a copper reagent to acquire aryl ester.8 The
olofsson group illustrated the coupling of diaryliodonium salt with
PhI(OAc)2 (1 equiv)
PhOH
4
PhB(OH)2
Et3N (2 equiv)
DCM, RT, 1 h
2a
68%
PhI(OAc)2 (0.3 equiv)
PhOH
+
PhB(OH)2
PhB(OH)2
Et3N (2 equiv)
DCM, RT, 1 h
2a
62%
2a
4
22%
PhI(OAc)2 (1 equiv)
PhOH
4
PhB(OH)2
X
DCM, RT, 1 h
2a
⇑
Corresponding authors. Tel.: +91 4422202823.
E-mail address: nrajendiar@yahoo.com (N. Rajendiran).
Scheme 1. Control experiments.
http://dx.doi.org/10.1016/j.tetlet.2014.02.079
0040-4039/Ó 2014 Elsevier Ltd. All rights reserved.

2346
J. S. Ruso et al. / Tetrahedron Letters 55 (2014) 2345–2347
Table 1
Table 3
Optimization of the reaction conditionsa
Coupling of phenyl boronic acid with various aryl carboxylic
acids
Reagent
PhI(OAc)2 (1 equiv)
PhCOOPh
+
PhCOOH
PhB(OH)2
CDI (1 equiv),
Et3N (5 equiv)
ArCOOH
+
PhB(OH)2
ArCOOPh
3aa
1a
2a
CDI (1 equiv),
Et3N (5 equiv),
DCM, rt, 3 h
3b
1
2a
Entry
Reagent
Solvent
Temp/time (h)
Yieldb (%)
O
O
O
1
2
3
4
5c
6
7
8
NaOCl
Ca(OCl)2
EtOAc
EtOAc
EtOAc
EtOAc
DCM
toluene
CH3CN
DCM
rt, 12
rt, 12
rt, 6
rt, 3
rt, 3
rt, 3
rt, 3
rt, 3
NR
NR
12
NR
22
15
12
65
Br
OPh
OPh
OPh
PhI(OAc)2
PhI(OAc)2/oxone
PhI(OAc)2
PhI(OAc)2
PhI(OAc)2
Cl
I
Br
3ba, 68%
3bc, 71%
3bb, 60%
O
O
O
PhI(OAc)2
OPh
OPh
OPh
OPh
OPh
a
Reactions were performed with benzoic acid 1a (1 mmol), phenyl boronic acid
2a (1 mmol), solvent (5 mL), carbonyl diimidazole (1 mmol), reagent (1 mmol), and
triethylamine (5 mmol).
t-Bu
NC
OMe
3bf, 65%
3be, 75%
3bd, 63%
b
Isolated yield.
O
O
CF3
O
c
30 mol % of PhI(OAc)2 was used.
OPh
O
F3C
Table 2
3bh, 63%
3bi, 72%
3bg, 67%
Coupling of benzoic acid with various aryl boronic acids
PhI(OAc)2 (1 equiv)
R1
O
OPh
Br
PhCOOAr
+
PhCOOH
ArB(OH)2
R2
O
F
O
CDI (1 equiv),
Et3N (5 equiv),
DCM, rt, 3 h
3a
1a
2
OPh
O
Br
O
O
O
O
R1 = Me; R2 = H; 3bl, 62%
R1 = H; R2 = F; 3bm, 67%
3bj, 67%
3bk, 64%
Ph
O
Ph
O
I
Ph
O
Cl
3ad, 81%
3ab, 72%
3ac, 69%
C9H19
O
O
containing phenyl boronic acid as well as nitro and cyano
substituted boronic acid smoothly delivered the desired products
(3ae–ak). Aryl esters (3al–3am) with formyl group were synthe-
sized in good yields. In general, the formyl group is susceptible
to oxidation, remained unaffected during the reaction and signifies
the mild nature of the condition. Biphenyl boronic acids also
transformed smoothly to the aryl esters (3an–3ao).
After the synthesis of various aryl benzoates 3a, it was planned
to couple the phenyl boronic acid 2a with benzoic acids bearing
different functional groups (Table 3). As expected, halo substituted
benzoic acids underwent a smooth coupling reaction. Benzoic acids
embedded with electron donating as well as withdrawing groups
led to the aryl esters in good yields. Also, cinnamic acid afforded
the unsaturated ester. Monofluoro and difluoro substituted phenyl
boronic acids provided the corresponding aryl esters.
To understand the mechanism of the transformation, phenyl
boronic acid 2a was stirred with 1 equiv of phenyl iododiacetate
and 2 equiv of triethyl amine in DCM at RT for 1 h, phenol 4 was
obtained in 65% yield whereas the same reaction with only
0.3 equiv of phenyl iododiacetate gave only 22% of 4 and 62% unre-
acted phenyl boronic acid (Scheme 1). Thus it is clear that phenol is
the intermediate of this reaction. Further, in the absence of trieth-
ylamine, no phenol formation was observed. This shows that tri-
ethylamine is essential for the conversion of aryl boronic acid to
phenol and also used for the mixed anhydride formation from aryl
carboxylic acid.
Based on the result, a possible mechanism is proposed as shown
in Scheme 2. Aryl boronic acid 2 and phenyl iodoacetate give a
Lewis adduct A. Triethylamine is expected to abstract a proton
from the boronic acid A to form B which on intramolecular acetyl
transfer followed by protonation led to D. This species undergoes
an aryl migration to generate E which on exchange with in situ
generated AcOH afforded phenol 4. Finally, phenol and mixed
anhydride F generated from aryl carboxylic acid and carbodiimi-
dazole produced aryl ester 3.
O
Ph
O
Ph
O
Ph
O
3ae, 66%
3ag, 83%
3af, 62%
OMe
NO2
OBn
O
O
O
Ph
O
Ph
Ph
O
Ph
Ph
O
3ai, 78%
3ah, 63%
3aj, 65%
CHO
O
O
O
O
Ph
O
O
CN
CHO
3am, 73%
3al, 70%
3ak, 62%
O
O
Ph
O
Ph
Ph
O
3ao, 68%
3an, 78%
To initiate this study, the model substrates, benzoic acid 1a and
phenyl boronic acid 2a with carbonyl diimidazole (1 equiv) and tri-
ethyl amine (5 equiv) were subjected to various conditions as
shown in Table 1. Under sodium hypochlorite and calcium hypo-
chlorite conditions, no product was obtained whereas phenyl iod-
odiacetate (30 mol %) alone gave 3aa albeit in low yield (entry 3).
Conversely, the addition of oxone with phenyl iododiacetate was
found unsuccessful (entry 4). However, aryl ester 3aa was obtained
in 65% yield with one equivalent of phenyl iododiacetate.15 A quick
screening of various solvents such as toluene, acetonitrile, and
DCM revealed that the latter is found to be the best solvent for this
transformation (65%).
Having the optimized condition in hand, benzoic acid 1a was
subjected to coupling with various aryl boronic acids 2 as depicted
in Table 2. Phenyl boronic acid substituted with halo units such as
chloro, bromo, and iodo16 furnished the corresponding aryl esters
in good yields. Methyl, ethyl, nonyl, benzyloxy, and methoxy

J. S. Ruso et al. / Tetrahedron Letters 55 (2014) 2345–2347
2347
3. (a) Montalbetti, C. A. G. N.; Falque, V. Tetrahedron 2005, 61, 10827; (b) Valeur,
E.; Bradley, M. Chem. Soc. Rev. 2009, 38, 606.
HO
O
HO
OH
OH
NEt3
O
Ar
B
O
Ar
B
Ar
B
4. (a) Lowrance, W. W., Jr. Tetrahedron Lett. 1971, 12, 3453; (b) Keshavamurthy, K.
S.; Vankar, Y. D.; Dhar, D. N. Synthesis 1982, 506; (c) Ueda, M.; Oikawa, H. J. Org.
Chem. 1985, 50, 760; (d) Ueda, M.; Mori, H. Bull. Chem. Soc. Jpn. 1992, 65, 1636;
(e) Eshghi, H.; Rafei, M.; Karimi, M. H. Synth. Commun. 2001, 31, 771; (f) Lee, C.
K.; Yu, J. S.; Lee, H.-J. J. Heterocycl. Chem. 2002, 39, 1207; (g) Vijayakumar, B.;
Iyengar, P.; Nagendrappa, G.; Prakash, B. S. J. J. Indian Chem. Soc. 2005, 82, 922;
(h) Won, J.; Kim, H.; Kim, J.; Yim, H.; Kim, M.; Kang, S.; Chung, H.; Lee, S.; Yoon,
Y. Tetrahedron 2007, 63, 12720; (i) Konwar, D.; Gogoi, P. K.; Gogoi, P.; Borah, G.;
Baruah, R.; Hazarika, N.; Borgohain, R. Indian J. Chem. Technol. 2008, 15, 75.
5. (a) Fitzjarrald, V. P.; Pongdee, R. Tetrahedron Lett. 2007, 48, 3553; (b) Iranpoor,
N.; Firouzabadi, H.; Khalili, D.; Motevalli, S. J. Org. Chem. 2008, 73, 4882.
6. (a) Toda, F.; Yagi, M.; Kiyoshige, K. J. Chem. Soc., Chem. Commun. 1988, 958; (b)
Olah, G. A.; Wang, Q.; Trivedi, N. J.; Prakash, G. K. S. Synthesis 1991, 739; (c)
Kotsuki, H.; Arimura, K.; Araki, T.; Shinohara, T. Synlett 1999, 462; (d) Yadav, J.
S.; Reddy, B. V. S.; Basak, A. K.; Narsaiah, A. V. Chem. Lett. 2004, 33, 248; (e)
Gaikwad, D. D.; Dake, S. A.; Kulkarni, R. S.; Jadhav, W. N.; Kakde, S. B.; Pawar, R.
P. Synth. Commun. 2007, 37, 4093; (f) Ghazanfari, D.; Hashemi, M. M.; Shahidi-
Zandi, M. Synth. Commun. 2008, 38, 2037.
O
O
-HNEt3
OH
O
2
Ph
I
I
Ph
OAc
OAc
B
O
A
Ph
I
OAc
HO
Ar
OAc
HO
Ar B
OAc
HNEt3
-NEt3
B
OAc
O
B
O
HO
I
-AcOH
-PhI
Ph
O
I
Ph
OAc
OAc
Ar
E
C
D
H
ArCOOH
1
AcOH
-HOB(OAc)2
NEt3 CDI
NEt3
O
O
7. (a) Palucki, M.; Wolfe, J. P.; Buchwald, S. L. J. Am. Chem. Soc. 1996, 118, 10333;
(b) Palucki, M.; Wolfe, J. P.; Buchwald, S. L. J. Am. Chem. Soc. 1997, 119, 3395; (c)
Widenhoefer, R. A.; Zhong, H. A.; Buchwald, S. L. J. Am. Chem. Soc. 1997, 119,
6787; (d) Mann, G.; Hartwig, J. F. J. Org. Chem. 1997, 62, 5413.
ArOH
ArCOOAr
+
-imidazole
-CO2
3
4
N
Ar
O
N
F
8. (a) Luo, F.; Pan, C.; Qian, P.; Cheng, J. Synthesis 2010, 2005; (b) Luo, F.; Pan, C.;
Qian, P.; Cheng, J. J. Org. Chem. 2010, 75, 5379.
Scheme 2. Possible mechanism for the metal-free aryl ester synthesis.
9. Petersen, T. B.; Khan, R.; Olofsson, B. Org. Lett. 2011, 13, 3462.
In conclusion, a convenient and metal-free synthesis of aryl
esters by employing the coupling of aryl boronic acid with aryl car-
boxylic acid is demonstrated. A wide range of functional groups
were found to be tolerant under the reaction condition. The condi-
tion is mild and provided the desired products in good yields. A
possible mechanism is proposed for this metal-free synthesis.
10. (a) Xu, J.; Wang, X.; Shao, C.; Su, D.; Cheng, G.; Hu, Y. Org. Lett. 1964, 2010, 12;
(b) Anbarasan, P.; Neumann, H.; Beller, M. Angew. Chem., Int. Ed. 2011, 50, 539;
(c) Prakash, G. K. S.; Chiradeep, P.; Thomas, M.; Vijayalakshmi, S.; Petasis, N. A.;
Olah, G. A. Org. Lett. 2004, 6, 2205; (d) Srimanta, M.; Soham, M.; Suja, R.;
Soumitra, A.; Debabrata, M. Org. Lett. 2012, 14, 1736.
11. Zhang, L.; Zhang, G.; Zhang, M.; Cheng, J. J. Org. Chem. 2010, 75, 7472.
12. Dai, J.-J.; Liu, J.-H.; Luo, D.-F.; Liu, L. Chem. Commun. 2011, 677.
13. For review, see: (a) Merritt, E. A.; Olofsson, B. Synthesis 2011, 517; (b) Merritt,
E. A.; Olofsson, B. Angew. Chem., Int. Ed. 2009, 48, 9052.
14. (a) Kita, Y.; Morimoto, K.; Ito, M.; Ogawa, C.; Goto, A.; Dohi, T. J. Am. Chem. Soc.
2009, 131, 1668; (b) Dohi, T.; Ito, M.; Yamaoka, N.; Morimoto, K.; Fujioka, H.;
Kita, Y. Angew. Chem., Int. Ed. 2010, 49, 3334; (c) Morimoto, K.; Yamaoka, N.;
Ogawa, C.; Nakae, T.; Fujioka, H.; Dohi, T.; Kita, Y. Org. Lett. 2010, 12, 3804; (d)
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2014.02.
079.
ˇ
Ackermann, L.; DellAcqua, M.; Fenner, S.; Vicente, R.; Sandmann, R. Org. Lett.
2011, 13, 2358.
15. Typical procedure for aryl ester synthesis: To a mixture of benzoic acid 1a
(1 mmol), carbonyl diimidazole (1 mmol), triethylamine (5 mmol), and
PhI(OAc)2 (0.32 g, 1 mmol) in DCM (5 mL) was added phenyl boronic acid 2a
(1 mmol) at rt. The reaction mixture was stirred for 3 h. The mixture was
evaporated under reduced pressure to obtain a residue which was purified by a
silica gel (60–120) column chromatography with petroleum ether–ethyl
acetate (8:2) as an eluent to obtain aryl ester 3a in 65% yield.
References and notes
1. (a) Humphrey, M. J.; Chamberlin, R. A. Chem. Rev. 1997, 97, 2243; (b) Allen, C. L.;
Williams, J. M. J. Chem. Soc. Rev. 2011, 40, 3405.
2. (a) Barratt, M. D.; Basketter, D. A.; Roberts, D. W. Toxicol. In Vitro 1994, 8, 823;
(b) Berndt, M. C.; Bowles, M. R.; King, G. J.; Zerner, B. Biochim. Biophys. Acta
1996, 1298, 159; (c) Beginn, U.; Zipp, G.; Moller, M. Chem.-Eur. J. 2000, 6, 2016;
(d) Moretto, A.; Nicolli, A.; Lotti, M. Toxicol. Appl. Pharmacol. 2007, 219, 196; (e)
James, C.; Snieckus, V. J. Org. Chem. 2009, 74, 4080.
16. 3-Iodophenyl benzoate (3ad): white solid; yield 81%; mp 78–79 °C, 1H NMR
(400 MHz CDCl3) d: 7.16–7.20 (m, 1H), 7.24–7.27(m, 1H), 7.56–7.52 (m, 2H),
7.69–7.63 (m, 2H) 8.23 (d, 1H, J = 5.7 Hz). 13C NMR (100 MHz CDCl3) d: 93.7,
121.4, 128.7, 129.1, 130.2, 130.8, 130.9, 133.9, 135.0, 151.2, 164.7. GCMS: 324.