Ruthenium/NHC-catalyzed tandem benzylic oxidation/oxidative esterification of benzylic alcohols with phenols

Article abstract of DOI:10.1016/j.catcom.2011.12.041

An efficient methodology to access benzoate derivatives via tandem benzylic oxidation/oxidative esterification of benzylic alcohols with phenols catalyzed by ruthenium/NHC was developed. This operationally simple one-pot process uses O₂ as the clean oxidant, producing esters in good to excellent yields.

Full text of DOI:10.1016/j.catcom.2011.12.041

Catalysis Communications 20 (2012) 41–45
Contents lists available at SciVerse ScienceDirect
Catalysis Communications
journal homepage: www.elsevier.com/locate/catcom
Short Communication
Ruthenium/NHC-catalyzed tandem benzylic oxidation/oxidative esterification of
benzylic alcohols with phenols
Di Zhang a, Changduo Pan b,
⁎
a
Department of Chemical Engineering, Changzhou Institute of Engineering Technology, Changzhou 21300, P. R. China
Wenzhou Institute of Industry and Science, Wenzhou 325000, P. R. China
b
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 14 October 2011
Received in revised form 21 December 2011
Accepted 22 December 2011
Available online 11 January 2012
An efficient methodology to access benzoate derivatives via tandem benzylic oxidation/oxidative esterifica-
tion of benzylic alcohols with phenols catalyzed by ruthenium/NHC was developed. This operationally simple
one-pot process uses O2 as the clean oxidant, producing esters in good to excellent yields.
© 2012 Elsevier B.V. All rights reserved.
Keywords:
Ruthenium
Tandem
Oxidation
Oxidative esterification
Benzoate derivative
1. Introduction
Table 1
Ester groups are among the highly important and abundant func-
tional groups in organic chemistry. Thus, it is worthwhile to provide
an environmentally benign method to access esters [1,2]. The existent
traditional methodology involves the activation of the carboxylic acid
as an acyl halide, anhydride, or activated ester followed by nucleophilic
substitution [3-8]. From the atom-economic point of view, the direct ox-
idative esterification of aldehydes remains as an attractive possibility to
readily access esters [9-20]. Recently, the transition-metal-catalyzed
tandem oxidation of alcohol to aldehyde followed by an oxidative ester-
ification has received much attention [21-27]. For example, Scheidt
demonstrated a tandem oxidation of alcohols to esters using N-
heterocyclic carbenes as catalysts, which required super-stoichiometric
amounts of MnO2 as the oxidant [28]. Recently, Lei and Beller developed
palladium-catalyzed aerobic oxidative esterification of benzylic alcohols,
respectively [29,30]. However, less attention has been paid to the
synthesis of aryl benzoate derivatives, which were building blocks of
numerous active compounds and cross coupling partners [31,32]. Very
recently, Chen developed a palladium/NHC-catalyzed tandem benzylic
oxidation/oxidative esterification of benzylic alcohols with phenols to
Selected results of screening the optimal conditions.
O
O
[Ru], ligand
Ph
Ph
HO
NO2
OH
NO2
base, solvent
1a
2a
Entry
[Ru]
Ligand
Base
Solvent
Yield (%)a
1
2
3
4
5
6
7
8
[Ru(p-cymene)Cl2]2
[Ru(p-cymene)Cl2]2
[Ru(p-cymene)Cl2]2
[Ru(p-cymene)Cl2]2
[Ru(p-cymene)Cl2]2
[Ru(p-cymene)Cl2]2
[Ru(p-cymene)Cl2]2
[Ru(p-cymene)Cl2]2
[Ru(p-cymene)Cl2]2
[Ru(p-cymene)Cl2]2
[Ru(p-cymene)Cl2]2
[Ru(p-cymene)Cl2]2
[Ru(p-cymene)Cl2]2
[Ru(p-cymene)Cl2]2
[Ru(p-cymene)Cl2]2
[Ru(p-cymene)Cl2]2
[Ru(p-cymene)Cl2]2
[Ru(p-cymene)Cl2]2
Ru3(CO)12
–
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Na2CO3
K2CO3
t-BuOK
–
Xylene
Xylene
Xylene
Xylene
Xylene
Xylene
Xylene
Xylene
Xylene
Xylene
Xylene
Trace
8
20
61
L1
L2
L3
L4
L5
L5
L5
L5
L5
L5
L5
L5
L5
L5
L5
L5
L5
L5
L5
L5
80
90 (Trace)b
(76)c (b5)d
53
40
11
63
61
Trace
30
b5
85e
46f
62g
70
9
10
11
12
13
14
15
16
17
18
19
20
21
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
1,4-Dioxane
DCE
Toluene
DMF
Xylene
Xylene
Xylene
Xylene
Xylene
Xylene
access aryl benzoate derivatives [33]. Nevertheless,
a facile and
versatile procedure on such transformation still remains a highly
desired goal for organic chemists. Herein, we report a ruthenium/NHC-
catalyzed tandem oxidation/esterification of benzylic alcohols with
phenols, using O2 as the clean terminal oxidant.
RuCl2(PPh3)3
RuCl·3H2O
85
12
aAll reactions were run with phenylmethanol 1a (0.3 mmol), 4-nitrophenol 2a
(0.2 mmol), [Ru] (5 mol %), ligand (10 mol %) and base (10 mol %), in dry solvent
(2 mL) under O2 at 130 °C for 24 h. Isolated yields: bin the absence of Ru, cunder air,
dunder N2, eCs2CO3 (20 mol %), fCs2CO3 (50 mol %), and gat 110 °C.
⁎
Corresponding author.
E-mail address: changduo@yahoo.cn (C. Pan).
1566-7367/$ – see front matter © 2012 Elsevier B.V. All rights reserved.
doi:10.1016/j.catcom.2011.12.041

42
D. Zhang, C. Pan / Catalysis Communications 20 (2012) 41–45
N
N
N
N
N
N
Cl
Cl
Cl
L1
L2
L3
N
N
N
N
BF4
C
L4
L5
Fig. 1. Selected imidazolium salts screened.
2. Results and discussion
phenylmethanol with 4-nitrophenol as the model reaction employ-
ing [RuCl2(p-cymene)]2 the catalyst under oxygen (Table 1). Only a
trace of the product was formed in the absence of ligand as deter-
mined by GC–MS (Table 1, entry 1). Various precursors of N-
heterocyclic carbene (NHC) (Fig. 1) were investigated for this
From the economical and environmental point of view, the use
of molecular oxygen as the terminal oxidant has attracted consider-
able attention. With this in mind, we began our investigation using
Table 2
Ruthenium/NHC-catalyzed tandem benzylic oxidation/oxidative esterification of phenylmethanol with phenols.
R2
O
O
[RuCl2(p-cymene)]2, L5
CH2OH
+
OH
.
Cs2CO3, xylene, O2
R2
1a
2
3
Entry
1
Phenol 2
Product 3
Yield (%)a
88
O
NO2
2a
OH
O2N
F
3aa
3ab
3ac
O
O
2
3
4
5
83
95
82
80
2b
OH
F
O
O
Cl
2c
OH
Cl
O
O
OH
2d
3ad
3ae
3af
3ag
3ah
3ai
Cl
O Cl
O
OH
2e
Br
O
O
Br
6
85
79
90
81
84
90
CN
2f
NC
OH
O
O
7
2g
OH
O
O
8
2h
OH
O
O
9
OMe
2i
OH
MeO
MeO
O
O
10
11
2j
3aj
OH
OH
O
O
OMe
2k
3ak
O
aReaction conditions: 1a (0.3 mmol), 2 (0.2 mmol), [RuCl2(p-cymene)]2 (5 mol %), L5 (10 mol %) and Cs2CO3 (10 mol %) in dry xylene (2 mL) under O2 at 130 °C for 24 h.
Isolated yield.

D. Zhang, C. Pan / Catalysis Communications 20 (2012) 41–45
43
reaction and an excellent yield was obtained with L5 (Table 1, entry
6). No product was detected by GC–MS when the reaction was car-
ried out under nitrogen and 76% yield was provided under air con-
dition (Table 1, entry 7). These results suggested that the oxygen
played a significant role in the reaction. Meanwhile, the base used
also had an important effect in the reaction and Cs2CO3 proved to
be the best. In addition, the amount of Cs2CO3 had dramatic effect
on the reaction (Table 1, entries 6, 16 and 17). For example, the
yield was sharply decreased to 46% when using 50 mol % of
Cs2CO3. Moreover, reaction in dioxane, DCE, DMF and toluene
resulted in low efficiencies or no reaction (Table 1, entries 12–15).
Further studies showed that the [RuCl2(p-cymene)]2 was the best
ruthenium source (Table 1, entries 3 and 19–21). The yield was
sharply decreased to 62% when the procedure ran at 110 °C. In
Table 3
Ruthenium/NHC-catalyzed tandem benzylic oxidation/oxidative esterification of phenylmethanol with phenols.
O
[RuCl2(p-cymene)]2, L5
ArCH2OH
OH
+
Ar
.
O
Cs2CO3, xylene, O2
R
R
1
3
2a or 2g
Entry
1
Substrate 1
Product 3
Yield (%)a
86
CH2OH
O
O
NO2
3ba
1b
2
60
CH2OH
O
O
NO2
3ca
1c
3
4
84
79
Et
CH2OH
O
O
NO2
3da
Et
1d
MeO
CH2OH
1e
O
O
NO2
3ea
MeO
5
77
CH2OH
O
O
NO2
1f
3fa
6
7
8
86
88
60
F
CH2OH
O
NO2
F
1g
3ga
O
O
NO2
Cl
CH2OH
Cl
3ha
1h
O
1e
O
O
MeO
O2N
3eg
3ig
9
83
86
O
O2N
CH2OH
1i
O
10
CH2OH
O
O
1j
3jg
O2N
F3C
O2N
F3C
11
12
13
76
90
65
CH2OH
O
O
1k
3kg
MeOOC
NC
CH2OH
O
O
MeOOC
1l
3lg
O
CH2OH
NC
1m
O
3mg
14
15
52
50
O
O
CH2OH
1n
NO2 3na
O
CH2OH
1o
3oa
O
NO2
aReaction conditions: 1 (0.3 mmol), 2 (0.2 mmol), [RuCl2(p-cymene)]2 (5 mol %), L5 (10 mol %) and Cs2CO3 (10 mol %) in dry xylene (2 mL) under O2 at 130 °C for 24 h.
Isolated yield.

44
D. Zhang, C. Pan / Catalysis Communications 20 (2012) 41–45
O
CH2OH
O
[RuCl2(p-cymene)]2 (5 mol%)
1a
trace
3ag
3ig
L5 (10 mol %)
0.15 mmol
O
Cs2CO3(10 mol%)
HO
2g
xylene
O
CHO
0.2 mmol
NO2
O2N
1i'
0.15 mmol
63%
Scheme 1. Competitive reaction of phenol with phenylmethanol and 4-nitrobenzaldehyde.
addition, only a trace of the product was detected by GC–MS in the
absence of [RuCl2(p-cymene)]2.
aldehydes as the key rate-determining step in the course of the
reaction.
With the optimized conditions in hand, the scope of the reaction
with respect to phenols was investigated (Table 2). The reaction pro-
ceeded smoothly and tolerated various functional groups such as
methoxy, nitro, cyano, chloro, acetamido, fluoro and bromo groups
and provided the products in good to excellent yields. The substituent
on different positions on the aromatic ring of phenols affected the re-
action yield slightly. Importantly, the reaction tolerates halogens
groups (Table 2, entries 4–6) and the surviving halogen atom
(X=Cl, Br) could be valuable for further manipulation.
Next, the scope of the esterification of various primary alcohols
was examined (Table 3). The strong electron-withdrawing groups
such as ―CF3, ―COOMe and ―NO2 could also be tolerated under
the standard conditions. In case of allyl alcohol and 1-butanol as allylic
alcohol substrates, the desired ester was isolated in 52% and 50% yield,
respectively (Table 3, entries 14–15).
To understand the mechanism more clearly, more experiments
were carried out. Conversion of benzylic alcohol to the aromatic alde-
hyde was observed under the standard procedure by GC–MS. More-
over, under the standard procedure without L5, naphthalene-1-
methanol produced 1-naphthaldehyde in 93% yield (Scheme 1).
Next, when 1-naphthaldehyde and benzaldehyde were subjected to
the standard procedure, the desired products were isolated in 75%
and 85% yield, respectively (Scheme 2). These results could disclose
the possibility of a tandem oxidation of benzylic alcohol to aromatic
aldehyde followed by an esterification pathway.
Furthermore, a competitive experiment using phenol with alcohol
and aldehyde was conducted (Scheme 3). A mixture with 1:1 ration
of 1a and 4-nitrobenzaldehyde 1i′ with 2g was carried out under
the same conditions as for entry 6, Table 1. A trace of 3ag was
detected, while 3ig was isolated in 63% yield after 6 h. This result
suggests that this reaction involves the oxidation of alcohols to
A plausible mechanism for this tandem oxidation/esterification is
outlined in Scheme 4. First, aromatic aldehyde was produced from
benzylic alcohols via ruthenium-catalyzed aerobic oxidation reaction
[34]. In step (ii), the deprotonation of the heteroazolium salt generates
the N-heterocyclic carbene A that adds to the carbonyl of the acyl group,
after which, the Breslow's intermediate undergoes an oxidation step to
afford B [16,28,35]. In step (iii), the reaction of B with phenol produces
intermediate C. Ultimately, in step (iv), intermediate C produces ester D
and regenerates NHC catalyst to complete the catalytic cycle in the pres-
ence of base [16,28,35].
Ar
O
N
O
Ar1
OAr2
D
N
Ar1
H
A
(iv)
(ii)
Ar
[Ru], O2, base
(i)
base
Ar1CH2OH
H
O
Ar2O
Ar1
Ar
N
N
HO
Ar1
Ar
N
Ar
N
Ar
(iii)
B
C
Ar2OH
Scheme 4. Plausible mechanism.
CHO
CH2OH
[RuCl2(p-cymene)]2 (5 mol%)
Cs2CO3 (10 mol%), xylene,O2
In summary, we have developed an efficient methodology to ac-
cess benzoate derivatives via tandem benzylic oxidation/oxidative es-
terification of benzylic alcohols with phenols catalyzed by ruthenium/
NHC. Notably, the amount of base in the procedure is only 10 mol %.
This operationally simple one-pot process uses O2 as the clean oxi-
dant, producing esters in good to excellent yields.
1f
1f' 93%
Scheme 2. Oxidation of naphthalene-1-methanol to 1-naphthaldehyde.
[RuCl2(p-cymene)]2, L5
O
O
NO2
NO2
O2N
O2N
OH
CHO
CHO
Cs2CO3, xylene, O2
3. Experimental
75%
3fa
1f'
2a
2a
Chemicals were either purchased or purified by standard tech-
niques without special instructions. 1H NMR and 13C NMR spectra
were measured on a 500 MHz spectrometer (1H 500 MHz, 13C
125 MHz), using CDCl3 as the solvent with tetramethylsilane
(TMS) as the internal standard at room temperature. Chemical shifts
O
[RuCl2(p-cymene)]2, L5
OH
Cs2CO3, xylene, O2
O
1a'
85%
3aa
Scheme 3. Oxidative esterification of aryl aldehydes with phenols.

D. Zhang, C. Pan / Catalysis Communications 20 (2012) 41–45
45
[8] M. Hatano, Y. Furuya, T. Shimmura, K. Moriyama, S. Kamiya, T. Maki, K. Ishihara,
Org. Lett. 13 (2011) 426–429.
[9] S.D. Sarkar, S. Grimme, A. Studer, J. Am. Chem. Soc. 132 (2010) 1190–1191.
[10] K. Zeitler, Angew. Chem., Int. Ed. 44 (2005) 7506–7510.
[11] S.-I. Kiyooka, Y. Wada, M. Ueno, T. Yokoyama, R. Yokoyama, Tetrahedron 63
(2007) 12695–12701.
[12] S. De Sarkar, A. Biswas, C.H. Song, A. Studer, Synthesis (2011) 1974–1983.
[13] B. Maji, S. Vedachalan, X. Ge, S. Cai, X.-W. Liu, J. Org. Chem. 76 (2011) 3016–3023.
[14] H. Jiang, B. Gschwend, Ł. Albrecht, K.A. Jørgensen, Org. Lett. 12 (2010) 5052–5055.
[15] M. Zhang, S. Zhang, G. Zhang, F. Chen, J. Cheng, Tetrahedron Lett. 52 (2011)
2480–2483.
[16] R.S. Reddy, J.N. Rosa, L.F. Veiros, S. Caddick, P.M.P. Gois, Org. Biomol. Chem. 9
(2011) 3126–3129.
[17] J.N. Rosa, R.S. Reddy, N.R. Candeias, P.M.S.D. Cal, P.M.P. Gois, Org. Lett. 12 (2010)
2686–2689.
[18] Z. Ye, G. Lv, W. Wang, M. Zhang, J. Cheng, Angew. Chem., Int. Ed. 49 (2010)
3671–3674.
(δ) are given in ppm relative to TMS; the coupling constants J are given
in Hz.
3.1. General procedure of ruthenium/NHC-catalyzed tandem benzylic ox-
idation/oxidative esterification of benzylic alcohols with phenols
Under oxygen, a reaction tube was charged with phenols (0.2 mmol),
benzylic alcohols (0.3 mmol), [RuCl2(p-cymene)]2 (6.1 mg, 5 mol %), L5
(8.5 mg, 10 mol %), Cs2CO3 (6.5 mg, 10 mol %) in dry xylene (2 mL).
After the mixture was stirred for 24 h at 130 °C, the solvent was evapo-
rated under reduced pressure and the residue was purified by flash col-
umn chromatography on silica gel to give the product.
[19] F. Luo, S. Pan, C. Pan, P. Qian, J. Cheng, Adv. Synth. Catal. 353 (2011) 320–324.
[20] G. Lv, G. Huang, G. Zhang, C. Pan, F. Chen, J. Cheng, Tetrahedron 67 (2011)
4879–4886.
Acknowledgment
[21] T. Zweifel, J.-V. Naubron, T. Büttner, T. Ott, H. Grützmacher, Angew. Chem., Int. Ed.
47 (2008) 3245–3248.
[22] H. Miyamura, T. Yasukawa, S. Kobayashi, Green Chem. 12 (2010) 776–778.
[23] M.G. Coleman, A.N. Brown, B.A. Bolton, H. Guana, Adv. Synth. Catal. 352 (2010)
967–970.
[24] N. Yamamoto, Y. Obora, Y. Ishii, J. Org. Chem. 76 (2011) 2937–2941.
[25] M. Ito, A. Osaku, A. Shiibashi, T. Ikariya, Org. Lett. 9 (2007) 1821–1824.
[26] Y. Obora, Y. Ishii, Synlett (2011) 30–51.
[27] C. Gunanathan, L.J.W. Shimon, D. Milstein, J. Am. Chem. Soc. 131 (2009)
3146–3147.
We thank the Natural Science Foundation of Zhejiang Province
(No. Y4110109) for financial support.
Appendix A. Supplementary data
Supplementary data to this article can be found online at doi:10.
1016/j.catcom.2011.12.041.
[28] B.E. Maki, A. Chan, E.M. Phillips, K.A. Scheidt, Org. Lett. 7 (2007) 371–374.
[29] C. Liu, J. Wang, L. Meng, Y. Deng, Y. Li, A. Lei, Angew. Chem., Int. Ed. 50 (2011)
5144–5148.
References
[1] J. Otera, Esterification: Methods, Reactions, and Applications, Wiley-VCH, Wein-
heim, 2003.
[30] S. Gowrisankar, H. Neumann, M. Beller, Angew. Chem., Int. Ed. 50 (2011)
5139–5143.
[2] A. Parenty, X. Moreau, J.-M. Campagne, Chem. Rev. 106 (2006) 911–939.
[3] K. Ishihara, Tetrahedron 65 (2009) 1085–1109.
[4] J. Otera, Acc. Chem. Res. 37 (2004) 288–296.
[5] N. Nowrouzi, A.M. Mehranpour, J.A. Rad, Tetrahedron 66 (2010) 9596–9601.
[6] G.A. Grasa, R. Singh, S.P. Nolan, Synthesis (2004) 971–985.
[7] T. Shinada, M. Hamada, K. Miyoshi, M. Higashino, T. Umezawa, Y. Ohfune, Synlett
(2010) 2141–2145.
[31] A. Moretto, A. Nicolli, M. Lotti, Toxicol. Appl. Pharm. 219 (2007) 196–201.
[32] M.D. Barratt, D.A. Basketter, D.W. Roberts, Toxicol. in Vitro 8 (1994) 823–826.
[33] F. Luo, C. Pan, J. Cheng, F. Chen, Tetrahedron 67 (2011) 5878–5882.
[34] M. Lee, S. Chang, Tetrahedron Lett. 41 (2000) 7507–7510.
[35] P. Arde, B.T. Ramanjaneyulu, V. Reddy, A. Saxena, R. Vijaya Anand, Org. Biomol.
Chem. 10 (2012) 848.