Lithium pipecolinate as a facile and efficient ligand for copper-catalyzed hydroxylation of aryl halides in water

Article abstract of DOI:10.1039/c0cc00434k

Direct hydroxylation of a wide scope of aryl halides was catalyzed by a combination of CuI and lithium pipecolinate in water with yields up to 92%.

Full text of DOI:10.1039/c0cc00434k

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Lithium pipecolinate as a facile and efficient ligand for copper-catalyzed
hydroxylation of aryl halides in waterw
Linhai Jing,ab Jiangtao Wei,a Li Zhou,a Zhiyong Huang,a
Zhengkai Lia and Xiangge Zhou*ac
Received 17th March 2010, Accepted 26th April 2010
First published as an Advance Article on the web 21st May 2010
DOI: 10.1039/c0cc00434k
Direct hydroxylation of a wide scope of aryl halides was
catalyzed by a combination of CuI and lithium pipecolinate in
water with yields up to 92%.
some asymmetric reactions,11 studies of them in coupling
reactions are less developed. To the best of our knowledge,
there were only two reported examples, in which amino acid
salts were used as the catalysts for the reaction of aryl halides
or vinyl bromides with sulfinic acid salts.12
Phenols are not only important structural motifs occurring in
numerous pharmaceuticals, polymers, and natural products,
but also serve as versatile synthetic intermediates in preparing
oxygenated heterocycles1 and aryl ethers.2 The classical non-
oxidative preparation of this class of compounds include trans-
formation of arene diazonium salts in the presence of a copper
complex, nucleophilic substitution of activated aryl halides and
the benzyne synthetic route. However, in the former case, the
presence of an amino group is necessary. In the latter case,
the nucleophilic substitution reaction is often limited by the
necessarily harsh reaction conditions or the electronic require-
ments of the substrate. 2,3 A milder method based on an iridium
phosphine catalyst for the preparation of non-ortho-substituted
phenols involved two steps: C–H activation/borylation and
oxidation.4 Recently, several palladium/phosphine-catalyzed
processes have been developed for selective formation of
phenols from different aryl halides and hydroxide salts.5 More
recently, an iron-catalyzed method has been reported for con-
version of aryl halides to phenols in water at 180 1C.6 Although
copper has led to a resurgence of interest in an Ullmann-type
coupling reaction from an economic and industrial point of
view,7 the copper-mediated direct hydroxylation of aryl halides
using hydroxide salts as nucleophiles is rare.8 On the other
hand, water has attracted much attention as reaction media
because of its low cost, availability, safety and environmentally
benign nature.9 However, two additional challenges (e.g., water
tolerance for the catalyst10 and the associated problem of
substrate solubilities and reactivities) will be resulted in. There-
fore, to explore other efficient copper-mediated and ligand-
assisted catalytic systems for direct conversion of aryl halides
into phenols in water is still in demand and challenging.
As part of our endeavours to develop environmentally
friendly protocols,13 herein we disclose direct hydroxyla-
tion of aryl halides with sodium hydroxide as a nucleophile
catalyzed by a combination of CuI and lithium pipecolinate
in water.
Initially, iodobenzene 1 was chosen as a model substrate to
optimize the reaction conditions, and the results are listed in
Table 1. In general, all of the four ligands were effective to give
moderate yields ranging from 50–66%, and lithium pipecolinate
L4 was found to be a little better than the others (Table 1,
entries 1–4). Control experiments confirmed that only 35%
Table 1 Optimization studies for the Cu-catalyzed direct hydroxyla-
tion of iodobenzene 1 in watera
Entry
[Cu] source
Ligand
Base
T/1C
Yield (%)b
1
2
3
Cu(OAc)2ÁH2O
Cu(OAc)2ÁH2O
Cu(OAc)2ÁH2O
Cu(OAc)2ÁH2O
Cu(OAc)2ÁH2O
CuSO4ÁH2O
CuCl2ÁH2O
CuO
Cu2O
CuI
CuI
CuI
L1
L2
L3
L4
L4
L4
L4
L4
L4
L4
L4
L4
L4
L4
—
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
K2CO3
KOH
120
120
120
120
120
120
120
120
120
120
120
120
110
130
130
60
63
50
66
40
60
39
43
56
76
62
76
45
92
35
4
5c
6
7
8
9
10
11
12
13
14
15
In addition, although alkali metal salts of amino acids as
efficient catalysts or ligands have been successfully applied in
a Institute of Homogeneous Catalysis, College of Chemistry,
Sichuan University, Chengdu 610064, China.
CuI
CuI
CuI
NaOH
NaOH
NaOH
E-mail: zhouxiangge@scu.edu.cn; Fax: +86-28-85412026;
Tel: +86-28-85412026
b Lab of Applied Chemistry and Pollution Control Technology,
School of Chemistry and Chemical Engineering,
a
Unless otherwise noted, the reactions were carried out using iodo-
benzene (1.0 mmol), Cu source (10 mol%), ligand (20 mol%), base
(3.0 mmol) and (n-Bu)4NF (20 mol%) in water (3 mL) for 24 h.
China West Normal University, Nanchong 637002, China
c State Key Laboratory of Coordination Chemistry, Nanjing
University, Nanjing 210093, China
w Electronic supplementary information (ESI) available: Experimental
procedure, characterisation data. See DOI: 10.1039/c0cc00434k
b
Determined by GC-MS using 1,4-dichlrobenzene as internal standard.
Without addition of (n-Bu)4NF.
c
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yield of the desired product 2a was detected without the aid of
a ligand (Table 1, entry 15). Meanwhile, only 40% yield was
obtained in the absence of (n-Bu)4NF (Table 1, entry 5). The
catalytic activities of different copper sources were com-
pared, and CuI was found to be superior to others (Table 1,
entries 4 and 6–10). After screening a set of bases (e.g., K2CO3,
NaOH and KOH), we found that both NaOH and KOH gave
the best result of 76% yield (Table 1, entries 10 and 12).
Meanwhile, weak bases such as K2CO3 provided an inferior
result (Table 1, entry 11). Taking into consideration the cost,
NaOH was chosen as the base for the further experiments.
Reaction temperature was another important factor to affect
the results. As shown in Table 1, higher temperature had a
beneficial effect on product yield (entries 10, 13 and 14).
Taking into consideration the base-sensitivity of some func-
tional groups at high temperature, 130 1C was chosen as the
appropriate temperature for this reaction. In summary, the
optimal conditions for the direct hydroxylation of aryl halides
in water consist of the combination of CuI (10 mol%), L4
(20 mol%), (n-Bu)4NF (20 mol%) and NaOH (3 equiv.) at
130 1C for 24 h.
With the optimized reaction conditions in hand, the scope of
aryl halides was then explored. As shown in Table 2, different
aryl iodides, aryl bromides and even aryl chlorides were
transformed into the corresponding phenols with moderate
to excellent isolated yields ranging from 45% to 91%. The
yields for reactions of aryl iodides were slightly superior to aryl
bromides (Table 2, entries 1–8). Moreover, the good yields
obtained in the reactions of p-chloroiodobenzene, p-bromo-
iodobenzene or p-chlorobromobenzene implied that there was
good chemoselectivity between iodide, bromide or chloride
(Table 2, entries 7–9). It was observed that steric hindrance of
the substituent of the substrate had a significant effect on the
reactions. For example, p-bromotoluene gave the desired
product in 69% yield, o-bromotoluene afforded the corres-
ponding product in 60% yield, while 2-bromo-m-xylene gave
only 45% product under the same conditions (Table 2, entries
6 and 15–16). Similar phenomenons have been observed in
recently reported iron-catalyzed hydroxylation of aryl halides.6
Meanwhile, the catalytic system could well tolerate a variety of
functional groups, including nitro, hydroxy, carboxyl acid,
aldehyde, methoxy, cyano and ketone groups (Table 2, entries
3–4, 10–13, 17–19, 22–23 and 26). Heterocyclic compounds,
such as 2-bromopyridine and 3-bromopyridine could also
afford the corresponding products in 75% and 74% yields,
respectively (Table 2, entries 24 and 25). In addition, in most
cases, aryl halides with electron-withdrawing groups could
afford the corresponding products in good to excellent
yields. It is noteworthy that aryl chloride with two strong
electron-withdrawing groups, such as 2,4-dinitrochloro-
benzene, could also give 2,4-dinitrophenol in 70% yield,
though this class of reaction has not yet been investigated in
detail (Table 2, entry 26).
Table 2 Direct hydroxylation of aryl halides catalyzed by CuI/L4 in
watera
Entry
ArX
Product
Yield (%)b
1
2
3
4
5
6
7
8
9
2a
2a
2b
2b
2c
2c
2d
2d
2e
85
72
91
81
79
69
72
67
80
10
11
2f
85
76
2g
12
13
2h
2i
72
70
14
15
2j
74
60
2k
16
2l
45
17
18
2m
2n
62
60
19
20
2o
2p
50
65
21
2q
62
22
23
24
2r
2s
2t
80
75
75
25
2u
2v
74
70
In summary, we have developed a simple, efficient, economical
and environmentally friendly protocol for copper-mediated
and ligand-assisted direct hydroxylation of aryl halides in
water. This method avoids the use of toxic organic solvents
as well as inert reaction conditions. Moreover, the catalyst can
be easily generated using a mixture of CuI and lithium
26
a
Reactions were carried out using aryl halide (1.0 mmol), CuI (10 mol%),
L4 (20 mol%), NaOH (3.0 mmol) and (n-Bu)4NF (20 mol%) in water
b
(3 mL) at 130 1C for 24 h. Isolated yield after column chromatography.
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pipecolinate. In addition, the catalytic system can work well
with a variety of aryl iodides, bromides and even aryl chloride.
Further investigations of this protocol for other reactions are
currently ongoing in this laboratory.
6 Y. L. Ren, L. Cheng, X. Z. Tian, S. Zhao, J. J. Wang and
C. D. Hou, Tetrahedron Lett., 2010, 51, 43.
7 For recent reviews of copper-catalyzed cross-coupling reactions,
see: (a) F. Monnier and M. Taillefer, Angew. Chem., Int. Ed., 2009,
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J. B. Lan and J. S. You, Angew. Chem., Int. Ed., 2009, 48, 8729.
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We thank the financial support from the Natural Science
Foundation of China (Nos. 20672075, 20771076), Sichuan
Provincial Foundation (08ZQ026-041) and Ministry of
Education (NCET-10-0581). We also thank Analytic and
Testing Centre of Sichuan University for the NMR spectral
measurement.
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ꢀc
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Chem. Commun., 2010, 46, 4767–4769 | 4769