Triethanolamine as an efficient and reusable base, ligand and reaction medium for phosphane-free palladium-catalyzed heck reactions

Article abstract of DOI:10.1002/ejoc.200600561

Triethanolamine was found to be an efficient and reusable base, ligand and reaction medium for phosphane-free palladium-catalyzed Heck reactions. The olefination of iodo- and bromoarenes generated the corresponding products in good to excellent yields in the presence of catalytic amounts of palladium acetate in triethanolamine without any additive. Moderate yields of the desired products were obtained with activated chloroarenes. In addition, triethanolamine could be recovered and recycled for five consecutive trials without significant loss of its reactivity. Wiley-VCH Verlag GmbH & Co. KGaA, 2006.

Full text of DOI:10.1002/ejoc.200600561

FULL PAPER
DOI: 10.1002/ejoc.200600561
Triethanolamine as an Efficient and Reusable Base, Ligand and Reaction
Medium for Phosphane-Free Palladium-Catalyzed Heck Reactions
Hong Ji Li[a] and Lei Wang*[a,b]
Keywords: Heck reaction / Palladium / Phosphane-free catalysis / Triethanolamine / Catalysis
Triethanolamine was found to be an efficient and reusable
base, ligand and reaction medium for phosphane-free palla-
dium-catalyzed Heck reactions. The olefination of iodo- and
bromoarenes generated the corresponding products in good
to excellent yields in the presence of catalytic amounts of
palladium acetate in triethanolamine without any additive.
Moderate yields of the desired products were obtained with
activated chloroarenes. In addition, triethanolamine could be
recovered and recycled for five consecutive trials without sig-
nificant loss of its reactivity.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2006)
gands, and the use of various additives. It would still be
desirable to develop more robust, simple and cost-effective
non-phosphane ligands for use in palladium-catalyzed
Heck reactions.
Introduction
The palladium-catalyzed coupling of olefins with aryl or
vinyl halides, known as the Heck reaction, is one of the
most important, reliable and general reactions for carbon–
carbon bond formation in organic synthesis.[1] This power-
ful reaction can lead to the construction of an sp2–sp2 C–
C bond at an unfunctionalized olefinic carbon atom in a
single transformation using a wide variety of aryl and vinyl
halide substrates. It may be used for the synthesis of multi-
functional derivatives,[2] including bioactive compounds,
natural products,[3] pharmaceuticals and high-performance
materials.[4] Palladium compounds, usually complexes with
phosphane ligands, are very often used as catalyst precur-
sors in Heck reactions. Phosphanes act as stabilizers of in
situ formed soluble Pd0 complexes, which are generally con-
sidered the catalytically active forms.[5] On the other hand,
phosphane-free catalysts have received great interest re-
cently as a less complicated, environmentally friendly alter-
native to phosphane-containing systems.[6] Significant ad-
vances have been made in the past few years in developing
such catalysts. These include the use of nitrogen-[7] and sul-
fur-based palladacycles,[8] N,S-based carbenes[9] and N-het-
erocyclic carbenes (NHC) as ligands in palladium-catalyzed
Heck reactions.[10] However, all of these catalyst systems
suffer from drawbacks of one kind or another, such as the
high sensitivity of ligands towards air and moisture, a te-
dious multistep synthesis, and hence high cost of the li-
It is well known that chiral amino alcohols, such as natu-
ral amino alcohols, carbohydrate- and camphor-derived
amino alcohols and ferrocenyl amino alcohols, have been
widely used as ligands (O,N-ligands) in, for example, the
asymmetric alkynylation of aldehydes,[11] the asymmetric
addition of diethylzinc to aldehydes and imines,[12] the
asymmetric ruthenium-catalyzed transfer hydrogenation of
ketones,[13] the enantioselective trimethylsilylcyanation of
aldehydes[14] and in enantioselective Henry reactions.[15]
Furthermore, Buchwald and co-workers have disclosed that
trans-1,2-diaminocyclohexane serves as an excellent ligand
(N,N-ligand) in the copper-catalyzed amidation of aryl ha-
lides and in the N-arylation of N-heterocycles (C–N bond
coupling)[16] and ethylene glycol as a ligand (O,O-ligand) in
the copper-catalyzed amination of aryl iodides (C–N bond
coupling)[17] in 2001 and 2002, respectively. Most recently,
Gonzalez-Bobes and Fu discovered that amino alcohols
such as prolinol and trans-2-aminocyclohexanol are effec-
tive ligands (O,N-ligands) in the nickel-catalyzed Suzuki re-
actions of unactivated alkyl halides, including secondary
alkyl chlorides, with arylboronic acids (C–C bond coup-
ling).[18] However, triethanolamine exhibited lower activity
in the Heck reaction of chlorobenzene with styrene in water
using catalytic palladium on carbon.[19]
Herein we report on triethanolamine, a cheap and com-
mercially available organic compound, as an efficient and
recyclable base, ligand (O,N-ligand) and reaction medium
in palladium-catalyzed Heck reactions (C–C bond coup-
ling). The olefination reactions of iodo- and bromoarenes
with olefins generated the corresponding cross-coupling
products in good to excellent yields under phosphane-free
reaction conditions. For activated chloroarenes, moderate
[a] Department of Chemistry, Huaibei Coal Teachers College,
Huaibei, Anhui 235000, P. R. China
Fax: +86-561-3090-518
E-mail: leiwang@hbcnc.edu.cn
[b] State Key Laboratory of Organometallic Chemistry, Shanghai
Institute of Organic Chemistry, Chinese Academy of Sciences,
Shanghai 200032, P. R. China
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
Eur. J. Org. Chem. 2006, 5099–5102
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H. J. Li, L. Wang
FULL PAPER
Scheme 1.
yields of the desired products were obtained. Moreover, tri- Table 1. Effect of solvent, ligand and base on the Heck reaction.[a]
ethanolamine could be recovered and recycled for five con-
secutive trials without significant loss of its reactivity
(Scheme 1).
Results and Discussion
Although phosphorus ligands stabilize palladium and in-
fluence its reactivity, the simplest and cheapest palladium
catalysts are of course phosphane-free systems, specifically
when used in low loading. Such an experimental protocol
would constitute a significant advancement, especially if
generally applicable. In our initial screening experiments,
our goal was to perform palladium-catalyzed Heck reac-
tions in the absence of phosphorus ligands. When we se-
arched for a cross-coupling protocol for the reaction be-
tween bromobenzene and styrene, we observed that no
cross-coupling products were isolated when the reactions
were carried out in n-butylamine, piperidine, morpholine,
triethylamine, pyridine or ethylenediamine (Table 1, En-
[a] Styrene (104 mg, 1.00 mmol), bromobenzene (157 mg,
1.00 mmol) and [Pd(OAc)2] (2.3 mg, 0.01 mmol) in the solvent
(2.0 mL) and at the temperature indicated in Table 1 for 10 h. [b]
Isolated yields. [c] n.r. = no reaction.
tries 1–6) in the absence of any phosphorus ligand. To our
delight, 58 and 64% yields of products were obtained when
the reactions were conducted in a triethylamine/ethylene
glycol (1:1, v/v) or triethylamine/glycerol mixture (1:1, v/v),
respectively (Table 1, Entries 10 and 11), which indicates
that hydroxy groups in polyhydric alcohols can promote
phosphane-free palladium-catalyzed Heck reactions. En-
The effect of the palladium source on the Heck reaction
couraged by these results, we continued to improve the yield was also examined. Among the palladium sources tested,
by optimizing the reaction conditions. When monoethanol- [Pd(OAc)2] and PdCl2 proved to be the best choice.
amine, diethanolamine or triethanolamine, which contain [Pd(CH3CN)2]Cl2 and palladium on activated carbon were
hydroxy and amine groups within a molecular unit, was inferior and led to slower reactions. Palladium powder (mi-
used instead of a triethylamine/ethylene glycol or triethyl- cron), [Pd2(dba)3] and [Pd(PPh3)2]Cl2 were found to be in-
amine/glycerol mixture as reaction medium, excellent yields active towards the Heck reaction in triethanolamine.
of products were isolated for the Heck olefination of bro- [Pd(OAc)2] was chosen as the palladium source in further
mobenzene and styrene (Table 1, Entries 12–14). Among investigations because of its high efficiency (Table 2).
them, triethanolamine was found to be superior to monoe-
During the course of our further optimization of the re-
thanolamine and diethanolamine. However, no reaction oc- action conditions, when using 1 mol-% of palladium acetate
curred when the reaction was performed in a triethylamine/ in triethanolamine, the reactions were generally completed
methanol (1:1, v/v), triethylamine/ethanol (1:1, v/v) or n- in a matter of hours, but the time, as expected, was inversely
propanol/triethylamine mixture (1:1, v/v) (Table 1, En- proportional to the temperature. A reaction temperature of
tries 7–9). In addition, no Heck olefination product was iso- 100 °C was found to be optimal. Thus, the optimal reaction
lated when the reaction was carried out in ethylene glycol or conditions for this Heck reaction are [Pd(OAc)2] (1 mol-%)
glycerol without triethylamine being added to the reaction in triethanolamine at 100 °C for 10 h in the absence of any
system (Table 1, Entries 15 and 16).
additive.
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Eur. J. Org. Chem. 2006, 5099–5102

Triethanolamine for Phosphane-Free Palladium-Catalyzed Heck Reactions
Table 2. Effect of palladium source on the Heck reaction.[a]
FULL PAPER
moarenes, such as p-, m-, and o-bromotoluene as well as
p-bromoanisole, also reacted with styrene to generate the
corresponding cross-coupling products in good yields
(Table 3, Entries 8–11). Olefination of the haloarene was
also tolerant of ortho substitution in the aryl bromide and
led to a good yield (Table 3, Entry 10). The scope of this
catalytic system with other vinyl substrates, such as ethyl
acrylate, butyl acrylate and acrylonitrile, was also examined
and good to excellent results were obtained for iodo- and
bromoarenes including deactivated ones under identical
conditions (Table 3, Entries 12–17). As expected, moderate
yields of the desired products were obtained with activated
chloroarenes (Table 3, Entries 18 and 19).
Entry
Palladium source (amount)
Yield [%][b]
1
2
3
4
5
6
7
palladium powder (micron, 1mol-%)
[Pd2(dba)3] (1mol-%)
[Pd(PPh3)2]Cl2 (1mol-%)
[Pd(CH3CN)2]Cl2 (1mol-%)
Pd on activated carbon (1mol-%)
PdCl2 (1mol-%)
n.r.[c]
n.r.[c]
trace
75
50
98
[Pd(OAc)2] (1mol-%)
99
[a] Styrene (104 mg, 1.00 mmol), bromobenzene (157 mg,
1.00 mmol), palladium source (0.01 mmol) and triethanolamine
(2.0 mL) at 100 °C for 10 h. [b] Isolated yields. [c] n.r. = no reac-
tion.
To investigate the recyclability of triethanolamine, a
more practical method was applied to the reaction between
bromobenzene and styrene under the present reaction con-
ditions. When bromobenzene was treated with styrene with
a catalyst loading of 1 mol-% of palladium acetate in trie-
thanolamine at 100 °C for 10 h, the desired coupling prod-
uct was obtained in 99% isolated yield. After extraction of
the product from the reaction mixture using diethyl ether,
the triethanolamine was recovered and fresh starting mate-
rials and palladium catalyst were added to the reaction mix-
ture. The reactions still proceeded well and no unreacted
substrates were detected at the end of the reaction. Trie-
thanolamine was recycled five times with no loss of its ac-
tivity (Table 4).
To examine the versatility of this procedure, the Heck
reactions of styrene with iodoarenes containing electron-
rich, electron-poor or electron-neutral substituents were in-
vestigated. The results are listed in Table 3. It shows that
the conversions, regioselectivities [Ͼ99% (E) products] and
yields were satisfactory under the present reaction condi-
tions (Table 3, Entries 1–3). For bromobenzene and acti-
vated bromoarenes, excellent yields of cross-coupling prod-
ucts were isolated under the standard reaction conditions
(Table 3, Entries 4–7). On the other hand, unactivated bro-
Table 4. Successive trials of the Heck reaction using recovered trie-
thanolamine.[a]
Table 3. Palladium-catalyzed Heck reactions in triethanolamine.[a]
Trial
Yield [%][b]
Trial
Yield [%][b]
1
2
3
99
96
95
4
5
6
94
93
90
[a] Styrene (104 mg, 1.00 mmol), bromobenzene (157 mg,
1.00 mmol), [Pd(OAc)2] (2.3 mg, 0.01 mmol) and triethanolamine
(2.0 mL) at 100 °C for 10 h. [b] Isolated yield.
Conclusions
We have presented herein an efficient and economic cata-
lyst system for Heck reactions using triethanolamine as the
solvent, ligand and base and palladium acetate as the cata-
lyst under phosphane-free reaction conditions. The ole-
fination reactions of iodo- and bromoarenes with olefins
generated the corresponding coupling products in good to
excellent yields under these reaction conditions. Moreover,
triethanolamine could be recovered and recycled for five
consecutive trials without significant loss in activity.
[a] Olefin (1.00 mmol), organic halide (1.00 mmol) and [Pd(OAc)2]
(2.3 mg, 0.01 mmol), in triethanolamine (2.0 mL) at 100 °C for
10 h. [b] Isolated yields. [c] [Pd(OAc)2] (1.1 mg, 0.005 mmol) was
used.
Experimental Section
General Remarks: Melting points were recorded with a WRS-2
melting point apparatus and are uncorrected. All 1H NMR spectra
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H. J. Li, L. Wang
FULL PAPER
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General Heck Olefination Procedure: Under nitrogen, an oven-
dried, two-necked round-bottom flask containing a stirring bar was
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Recyclability of Triethanolamine: After carrying out the reaction,
the mixture was extracted with diethyl ether [note: the solubility of
triethanolamine in diethyl ether is 1.6% at 25 °C]. After neutraliza-
tion of the ammonium salt formed during the reaction with potas-
sium carbonate, triethanolamine was separated and washed suc-
cessively with Et2O (3.0 mL) and hexane (3.0 mL) in order to re-
move adsorbed organic substrates. After drying in an oven, it can
be reused directly without further purification.
Supporting Information (see footnote on the first page of this arti-
cle): Selected characterization data for Heck reaction products.
Acknowledgments
We gratefully acknowledge financial support from the National
Natural Science Foundation of China (No. 20372024), the Excel-
lent Scientist Foundation of Anhui Province, China (No.
04046080), the Scientific Research Foundation for Returned Over-
seas Chinese Scholars, State Education Ministry, China (No.
2002247), the Excellent Young Teachers Program of MOE, China
(No. 2024) and the Key Project of Science and Technology of the
State Education Ministry, China (No. 0204069).
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Received: June 30, 2006
Published Online: September 11, 2006
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