Efficient and versatile sol-gel immobilized copper catalyst for ullmann arylation of phenols

Article abstract of DOI:10.1002/adsc.200800360

A new hybrid silica with urea-based bipyridyl bridging units has been synthesized by a solgel process. The copper-complexed hybrid silica is an efficient heterogeneous catalyst for the Ullmann coupling of aryl halides with phenols. It is easily withdrawn and recovered from the reaction media by filtration. It is also a versatile catalyst for subsequent reactions with several substrates yielding products with the same efficiency even after ten reuses and with minimal leaching. This is the first example of the use of a copper-complexed bridged silsesquioxane for the preparation of a recoverable catalyst in modern Ullmann chemistry. This may represent a promising route to the reduction of waste while maintaining economic viability.

Full text of DOI:10.1002/adsc.200800360

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DOI: 10.1002/adsc.200800360
Efficient and Versatile Sol-Gel Immobilized Copper Catalyst for
Ullmann Arylation of Phenols
Sofia Benyahya,a Florian Monnier,a,* Marc Taillefer,a,* Michel Wong Chi Man,a,*
Catherine Bied,a and Fouad Ouazzanib
a
CNRS, UMR 5253, Institut Charles Gerhardt Montpellier, AM2N, ENSCM, 8, rue de l’Ecole Normale, 34296 Montpellier
Cedex 5, France
Fax : (+33)-467-144-319; e-mail: florian.monnier@enscm.fr, marc.taillefer@enscm.fr, Michel.wong-wong-chi-man@enscm.fr
LCOA, FST F›s, BP 2202. 30000 F›s, Morocco
b
Received: June 10, 2008; Published online: October 7, 2008
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.200800360.
Abstract: A new hybrid silica with urea-based bi-
pyridyl bridging units has been synthesized by a sol-
gel process. The copper-complexed hybrid silica is
an efficient heterogeneous catalyst for the Ullmann
coupling of aryl halides with phenols. It is easily
withdrawn and recovered from the reaction media
by filtration. It is also a versatile catalyst for subse-
quent reactions with several substrates yielding
products with the same efficiency even after ten re-
uses and with minimal leaching. This is the first ex-
ample of the use of a copper-complexed bridged sil-
sesquioxane for the preparation of a recoverable
catalyst in modern Ullmann chemistry. This may
represent a promising route to the reduction of
waste while maintaining economic viability.
bases) systems for the mild coupling of aryl halides
with phenols.[6] Due to the attractive cost of Cu sour-
ces for Ullmann-type reactions, very few systems have
been proposed to recover and reuse the catalytic spe-
cies.[7] The heterogenization of the Cu/L catalyst can
avoid metal residue contamination in the desired cou-
pling product and is of high importance for purity re-
quirements in pharmaceutical chemistry. Moreover,
simple filtration reduces the time-consuming process-
es and the solid catalyst which is easily separated
from the products can be recycled. In this context the
sol-gel process provides a suitable route to active het-
erogeneous catalysts.[8] Indeed metal-complexed
hybrid silsesquioxanes have already been reported as
efficient solid catalysts for asymmetric reactions,[9a,b]
metathesis[9c] and Suzuki reactions.[3b]
À
Keywords: C O coupling; copper; heterogeneous
In the present study, we report the design of a Cu/L
catalyst immobilized on silica A which was obtained
by the sol-gel hydrolysis of a silylated bispyridinyl
ligand L (Scheme 1) followed by complexation with
catalysis; N ligands; sol-gel bridged silsesquioxane
Diaryl ethers constitute an important class of structur-
al motifs for life sciences and polymer industries.[1] In
the mid 1990s Hartwigꢀs and Buchwaldꢀs groups both
À
developed Pd-catalyzed C O coupling reactions of
aryl halides and phenols.[2] Despite the high efficiency
of Pd/ligand systems in terms of TON, TOF and recy-
clability for cross-coupling reactions,[3] an alternative
and cheaper methodology to form biaryl ethers is the
classical Ullmann reaction,[4] but the harsh conditions
seriously restricted this methodology (Cu in stoichio-
metric amount at 150–2508C). Recently, several
À
groups focused on the revisited Ullmann-type C O
coupling catalyzed by copper/ligand (Cu/L) systems
to overcome the high cost of Pd sources.[5,6] Since
Scheme 1. Immobilization of ligand L leading to the hybrid
2001, our group has developed attractive Cu/L (Schiff silica A by a sol-gel process.
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Sofia Benyahya et al.
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À
Table 1. Influence of the nature of the ligands on the C O
coupling.
CuI. We also report the suitability of this technique to
provide an environmentally friendly solid catalyst for
the coupling of aryl halides with phenols.
Entry Ligand (10%)
Yield[a]
[%]
Bridged silsesquioxane A was synthesized from
4,4’-diamino-2,2’-bipyridine[10] and 3-isocyanatopropyl-
triethoxysilane followed by hydrolysis (Scheme 1).
During the catalytic reaction described below, we
postulated that the active species of Cu is encapsulat-
ed in the hybrid silica by chelation on the two nitro-
gen atoms of the bipyridine moiety. Besides, this syn-
thetic pathway allows a higher and controlled loading
of the organic moiety in the hybrid, compared with
the ligand grafting method on silica.[7b]
1
2
none
50
(<5)[b]
60
(<5)[b]
85
3
4
5
(<5)[b]
We chose the Ullmann-type coupling of iodoben-
zene with 3,5-dimethylphenol as the model reaction
(Scheme 2) and after several screening experiments
95
(<5)[b]
99
(99)[b]
[a]
[b]
GC yields determined with 1,3-dimethoxybenzene as in-
ternal standard.
GC Yield of product after recycling the catalytic system,
see Supporting Information for recycling procedure.
Scheme 2. Ullmann-type coupling of PhI with 3,5-dimethyl-
phenol.
with different combinations of bases and solvents, the
best conditions were determined as the following:
CuI (10 mol%), A (10 mol%) Cs2CO3 (2equiv.) in
DMF at 1108C during 20 h.[11]
Using these optimal conditions we compared the
efficiency of the Cu-complexed hybrid silica A to the
homogeneous Cu-complexed L, 2 ,2’-bipyridine and its
4,4’-diethylurea derivative and also to the reaction
performed without ligand (Table 1).
Scheme 3. Coupling of aryl iodides with phenol derivatives.
Table 2. Coupling of aryl iodides with 3,5-dimethylphenol.
Fair yields were obtained without ligand or with
bipy (entries 1 and 2), contrarily to L and A which led
to almost quantitative formation of the expected
product. A good yield was also obtained with the pro-
pylurea bipy derivative (entry 3). We then washed our
crude media with DMF for all cases and proceeded to
a second series of reactions by adding only the reac-
tants and base without further addition of Cu or
ligand sources. The high yield (99%, entry 5) ob-
served demonstrates that our Cu-complexed catalyst
A was highly efficient for this coupling without any
loss of activity while no significant coupling reactions
were observed in the other cases for the second runs
(entries 1–4). Hence besides being a good candidate
Entry R1
R2
Run Product Yield[a]
1
4-H
3,5-(Me)2
3,5-(Me)
1
2
3
4
5
6
93[b]
80
81
91
87
24-Me
1
2
3
4
5
2
3
4
5
6
4-OMe
4-NO2
4-CN
3,5-(Me)2
3,5-(Me)2
3,5-(Me)2
4-COOMe 3,5-(Me)2
91
[a]
Isolated yield in % after flash chromatography.
[b]
A copper leaching of 0.7% (185 ppm), expressed as per-
centage of the total copper charged, was obtained in the
solution phase containing the coupling product 1.
for this coupling reaction, the Cu-complexed hybrid leading to products 1 and 7. For both cases the cata-
A is also recyclable with similar activity. lytic system was recovered. On one hand the recycling
Then the substituent effect on either the aryl iodide of the heterogeneous catalyst gave the corresponding
or on the phenol was studied in the coupling reaction ethers 2–6 by successively performing and recycling
(Scheme 3, Table 2and Table 3). The reactions were
the coupling reactions of 3,5-dimethylphenol with five
performed in DMF at 1108C (22 h). 10% of catalytic differently substituted aryl iodides (entries 2–6 in
system based on CuI and A were charged only for the Table 2). On the other hand, moderate (entry 2, prod-
first experiments (entries 1 in Table 2and Table 3)
uct 8, Table 3) to excellent yields were obtained (en-
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Efficient and Versatile Sol-Gel Immobilized Copper Catalyst for Ullmann Arylation
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Table 3. Coupling of substituted phenols with iodobenzene.
“ArI” in situ formation by halogen exchange. The op-
timized reaction conditions were the following: 10%
of CuI/A system in DMF, 0.5 equiv. KI, 2equiv.
Cs2CO3 at 1208C (22 h). All the expected products (1,
3, 5, 13–15) were isolated in almost quantitative
yields. As above (Table 2and Table 3), the Cu and
the hybrid A sources were only introduced in the first
experiment yielding 1. The catalyst was recovered and
reused successively for nine coupling experiments. In-
terestingly, even the coupling of heteroaryl bromides
with 3,5-dimethylphenol gave the corresponding
cross-coupling product in high yield (cycle No. 4,
Entry
R1
R2
Run
Product
Yield[a]
1
2H
3
4
5
H
4-Cl
H
H
H
4-H
7
8
9
10
11
12
90
50
91
95
95
94
1
4-t-Bu
4-OMe
4-Me
2-Me
2
3
4
5
6
H
[a]
Isolated yield in % after flash chromatography.
tries 3–6, products 9–12, Table 3) for the coupling of product 13). Besides, similarly to the previous results
substituted phenols with PhI. These results clearly on ArI, the supported catalytic system was still highly
show the versatility of this heterogeneous catalyst efficient for the subsequent nine runs (cycles No. 2–
which can be reused with the same efficiency which- 10). Optimizing the stirring of the media has been en-
ever the substituent on the substrate.[11] Interestingly, gaged after the cycle No. 7 by washing the heterogen-
a very low amount of copper leaching was observed ized catalytic system with degassed water under nitro-
with our catalytic system. For example a leaching of gen to eliminate accumulated salt residues during the
0.7% of copper (expressed as percentage of the total seven first cycles. Coupling products in cycles No. 7 to
copper charged) was measured in the solution phase 10 were observed in a quantitative manner by MS-GC
containing the 3,5-dimethylphenol
entry 1).
Finally, this methodology was applied to the C O silica A with urea-based bipyridyl bridging units by
coupling of various aryl bromides with different phe- the sol-gel process. The Cu-complexed A turned out
nols (Scheme 4) in the presence of KI which allows as an efficient heterogeneous catalyst for the Ull-
1
(Table 2, in the presence of internal standard.
In summary, we have synthesized a new hybrid
À
Scheme 4. Coupling of aryl bromides with phenol derivatives with the same catalytic system supported on hybrid silica. Con-
ditions for cycle No. 1: 10% CuI, 10% A, 2mmol of ArBr, 3 mmol of ArOH, 0.5 equiv KI, 2equiv Cs 2CO3, 3 mL DMF,
1208C, 22 h. Conditions for cycles No. 2–10: 2mmol of ArBr, 3 mmol of ArOH, 0.5 equiv KI, 2equiv Cs 2CO3, 3 mL DMF,
1208C, 22 h. For cycles 7 to 10: Product obtained in quantitative yield by GC-MS with an internal standard.
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References
mann-type coupling of aryl halides with phenols. This
hybrid is easily withdrawn and recovered from the re-
action media by filtration. It proved to be a versatile
catalyst for subsequent reactions with several sub-
strates yielding products with the same efficiency
even after ten re-uses. To date, this is the first exam-
ple in modern Ullmann chemistry of the use of a Cu-
complexed bridged silsesquioxane for the preparation
of recoverable catalyst. This represents a promising
route that may contribute to the reduction of the gen-
eration of waste while maintaining economic viability.
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General Procedure for Coupling Reaction of Phenols
with Aryl Halides (Entries 1 of Table 2, Table 3 and
Scheme 4)
After standard cycles of evacuation and back-filling with dry
and pure nitrogen, an oven-dried Schlenk tube was charged
with CuI (0.2mmol), ligand A (0.2mmol), Cs 2CO3 (4 mmol)
phenol (3 mmol) and aryl halides (2mmol) if solids. In the
case of ArBr, 0.5 equivalents of dry KI were added. The
tube was then evacuated, back-filled with nitrogen and
capped with a rubber septum. If liquids, phenols and aryl
halides were added under a nitrogen atmosphere by syringe
at room temperature. Then 3 mL of anhydrous and degassed
DMF were added under a nitrogen atmosphere. The septum
was removed and the Schlenk tube sealed under a positive
nitrogen atmosphere and the reaction mixture stirred in an
oil bath (1108C for ArI, 1208C for ArBr) for the required
time period. After complete consumption of aryl halides,
the reaction mixture was then allowed to cool to room tem-
perature. The crude mixture was then filtered under nitro-
gen with a canula and washed two times with 5 mL of dry
DMF. The extracted solution was then filtered on a celite
plug, then concentrated under vacuum, and chromatograph-
ed on silica gel.
Supporting Information
Detailed experiments on general procedure for coupling re-
action and recycling procedure are available as Supporting
Information. All the products were isolated by flash chro-
1
matography on silica gel and were fully characterized by H
and 13C NMR and MS-GC. Data are available in the Sup-
porting Information.
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Acknowledgements
The authors thank CNRS for financial support and CNRST
of Morocco for a PhD grant for S. B.
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[11] See Supporting Information.
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