LETTER
1101
Copper-Catalyzed Etherification of Aryl Iodides Using KF/Al2O3:
An Improved Protocol
C
opper-Catalyze
a
a
h
tion of ArylmIodide 2 3
s
U
sing
K
F/A
a
l
O
n Hosseinzadeh,* Mahmood Tajbakhsh,* Maryam Mohadjerani, Mohammad Alikarami
Faculty of Basic Science, Mazandaran University, Babolsar, Iran
Fax +98(11252)42002; E-mail: r.hosseinzadeh@umz.ac.ir
Received 24 September 2004
The application of KF/Al2O3 to organic synthesis has pro-
vided new methods for a wide array of organic reactions,
many of which are staples of synthetic organic chemis-
try.10 Its benefits have been achieved by taking advantage
Abstract: A simple and efficient method for the coupling of aryl
iodides with aliphatic alcohols and phenols that does not require the
use of alkoxide bases is described. This C–O bond forming proce-
dure shows that the combination of air stable CuI and 1,10-phenan-
throline in the presence of KF/Al2O3 comprises an extremely of the strongly basic nature of KF/Al2O3 which has al-
efficient and general catalyst system for the etherification of aryl
lowed it to replace organic bases in a number of reac-
tions.11 In many cases, the use of this base provides milder
iodides. Different functionalized aryl iodides were coupled with
alcohols and phenols using this method.
conditions and simpler procedures than previously report-
ed methods.
Key words: etherification, aryl iodides, copper iodide, potassium
fluoride on alumina, coupling reaction
We have explored the CuI-catalyzed O-arylation of aryl
iodides with excess of alcohol and phenol using 1,10-
phenanthroline (20 mol%) as a simple ligand and KF/
The development of mild methods for the synthesis of
Al2O3 as a suitable base in the presence of CuI (10 mol%;
C–O bonds has recently gained increased attention.1
Scheme 1).
Formation of carbon-oxygen bonds by transition metal-
The choice of 1,10-phenanthroline as ligand and KF/
Al2O3 as base in the presence of CuI (10 mol%) was made
because we have recently used this system for C–N bond
formation in N-amidation.12 To find the optimum condi-
tions, we chose the cross-coupling reaction of iodo-
benzene and n-butanol in the presence of 1,10-
phenanthroline, KF/Al2O3 and CuI in toluene, dioxane
and excess n-butanol as solvents at 100–110 °C. Under
these conditions after 15 hours, n-butyloxybenzene was
obtained in 95% yield, while in toluene or dioxane, n-bu-
tyloxybenzene was obtained in 30% and 25% yield, re-
spectively.
catalyzed cross-coupling methodology has been the sub-
ject of significant interest during recent years.2
The copper-mediated Ullmann reaction has previously
been the method of choice for the synthesis of C–O bonds.
However, these reactions often require high temperatures
(ca. 200 °C), the use of copper salts in greater than stoichi-
ometric amounts, highly polar aprotic solvents, and a
large excess of the alkoxide.3–5 The Buchwald and
Hartwig research groups have been prominent in develop-
ing palladium-based methods for C–O bond synthesis.6,7
However, although successful, these protocols have in-
herent limitations, Pd-based methods can often be rela-
tively sensitive to moisture and require expensive metal
catalysts.8 Buchwald et al. and others have reported the
copper-based protocol for the formation of aryl alky and
diaryl ethers.2b,c,9 Most of these reported methods require
Cs2CO3 as a base in a sealed tube, but Cs2CO3 has a high
sensitivity towards moisture and this problem reduces its
capability as a base in moisture-sensitive reactions.
Using the above protocol, we subjected a series of aryl
iodides to these reaction conditions (Table 1). As can be
seen in Table 1, primary, benzylic and secondary alcohols
were successfully transformed to their corresponding
ethers. The reaction between these alcohols with iodoben-
zene gives excellent yields after 5–14 hours (entries 1–3).
Substrates possessing electron-withdrawing groups such
as CF3 in the meta-position (entry 8) and bromine in the
R
R
10 mol% CuI, KF/Al2O3, 110 °C
20 mol% 1,10-phenanthroline
I
OR′
+
R′OH
excess
R′ = alkyl, aryl
Scheme 1
SYNLETT 2005, No. 7, pp 1101–1104
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Advanced online publication: 14.04.2005
DOI: 10.1055/s-2005-865198; Art ID: D28904ST
© Georg Thieme Verlag Stuttgart · New York