6
680
T. Kylmälä et al. / Tetrahedron Letters 49 (2008) 6679–6681
Table 2
2+
Suzuki reactions with aryl bromides using iron–pyridine catalysts 1 or 2 in aqueous
a
media under air
N
Fe N
N
Entry
Solvent
Product
R
Yield % using catalyst
-
N
2Cl
1
2
1
2
3
4
5
6
7
8
9
Ethanol/water 1:1
Ethanol/water 1:1
Ethanol/water 1:1
Ethanol/water 1:1 + TBAB
Ethanol/water 1:1 + TBAB
Ethanol/water 1:1 + TBAB
Water
NO
COMe
OMe
2
57
66
5
100
100
12
nr
75
43
96
99
48
98
80
49
28
94
7
NO
2
1
COMe
OMe
Figure 1. The isolated iron–pyridine complex 1.
NO
2
Water
Water
COMe
OMe
1
1
1
0
1
2
Water + TBAB
Water + TBAB
Water + TBAB
NO
COMe
OMe
2
81
100
63
100
100
59
Reaction in air (Table 1, entries 4–6) compared to reactions per-
formed under argon (Table 1, entries 1–3) led us to store both com-
plexes under air, although we noticed some loss of catalytic
Nr: no reaction. No remarkable difference in yields was observed when reactions
were performed under argon instead.
2 4
activity. Although some iron(III)–pyridine complexes and FeCl py
13
are reported to need an inert atmosphere, compounds 1 and 2
seem to be reasonably stable in air. The difference in stabilities
might arise due to different dissociation processes of the pyridine
ligands. In our case, the initial iron species might be converted to
a
The reaction was carried out using 1.0 equiv of aryl bromide, 1.3 equiv of
phenylboronic acid, and 1 mol % of catalyst in the presence of 3.0 equiv of K
and 1.3 equiv of TBAB.
2 3
CO
2 3
-Fe O
as reported previously.25 This would be the case, especially
c
when reactions are performed under air. We noticed, however, that
the yields were not significantly different although all the reactions
presented in Table 2 were performed under argon. Therefore, at
present, we do not speculate about the conversions of iron species
before additional experiments have been performed.
Due to the fact that reactions proceeded with moderate to
excellent yields when performed under argon, and that good yields
could also be obtained if the reactions were performed under air,
especially when the para substituent was nitro or acetyl (Table 1,
entries 4–5), we concluded that it would perhaps also be possible
to use complexes 1 and 2 in aqueous solvent systems (Table 2). We
observed that when using a mixture of ethanol/water 1:1 (Table 2,
entries 1–3), the yields were similar to those in neat ethanol under
air (Table 1, entries 4–6). The catalyst activity did not vary greatly
when ethanol was replaced by water as solvent (Table 2, entries
In conclusion, we have shown that an iron–pyridine complex
can serve as an excellent catalyst for Suzuki–Miyaura coupling
reactions performed under air in ethanol, aqueous ethanol, or
water as solvent. Our result offers a less expensive preparation of
biphenyls. This phosphine and palladium-free method is simple
and can be used to generate products with low catalyst loading.
The protocol not only represents the first example of an iron–pyr-
idine catalyst suitable for biaryl coupling, but also demonstrates
the versatility of iron catalysts and broadens the prospects of their
applications in organic synthesis.
Preparation of trans-tetrakis(pyridine) dichloroiron(II) (1):
FeCl
3
ꢀ6H
2
O (1 equiv) was dissolved in pyridine (18 equiv) and re-
fluxed for 2 h under argon and filtered. Light yellow crystals (mp
242–245 °C) were obtained in 75% isolated yield, and used for X-
ray analysis. The crystal structure was the same as that reported
by Long and Clarke. Tetrakis(pyridine)dichloroiron(II) can be pre-
2
pared starting from FeCl and pyridine. However, in this refer-
7
–9).
Addition of tetrabutylammonium bromide (TBAB) accelerated
1
4
2
3
the cross-coupling reaction in the aqueous environment. We be-
lieve that the addition of TBAB increased the organic substrate sol-
ubility and also activated the boronic acids by forming a boronate
complex, as previously described.26 We, therefore decided to use
TBAB as the phase-transfer catalyst in aqueous reaction mixtures.
Addition of 1.3 equiv of TBAB improved the yields in ethanol/water
ence the exact structure of the complex was not reported.
Preparation of trans-tetrakis(2,6-dichloropyridine) dichloroiron(II)
(2): FeCl
3
ꢀ6H
2
O (1 equiv) was dissolved in acetonitrile, and 2,6-
dichloropyridine (6.1 equiv) was added in one portion to the boil-
ing reaction mixture. After addition, the reaction vessel was
flushed with argon, and the reaction mixture was refluxed for 2 h
under argon. Filtration and evaporation of the solvent yielded yel-
low micro crystals in 83% isolated yield. Reliable data for the melt-
ing point could not be obtained.
1
:1 (Table 2, entries 4–6) and in water (Table 2, entries 10–12).
Table 1
General Suzuki reaction procedure: The aryl bromide (0.56 mmol,
Suzuki reactions of phenylboronic acid with three aryl bromides using iron–pyridine
catalysts 1 and 2 in ethanol
1 equiv), phenylboronic acid (0.728 mmol, 1.3 equiv),
2 3
K CO
(
232 mg, 1.68 mmol, 3 equiv), and catalyst (1 mol %) were dis-
1
mol% 1 or 2
B(OH)2
+
Br
R
solved in the appropriate solvent (3 ml), and thereafter the mixture
was stirred for 24 h at 80 °C. The mixture was cooled to room tem-
perature, EtOAc (ꢁ20 ml) was added and the reaction mixture was
filtered through a 3G glass sinter. The organic layer was washed
with distilled water (2 ꢂ 15 ml) and brine (2 ꢂ 15 ml) and then
R
8
0 °C, 20 h,
Solvent, 3 eq K CO
2
3
1
.3 eq
1 eq
3: R = NO2
4
5
: R = COMe
: R = OMe
4
dried over MgSO . Evaporation and purification by column chro-
1
13
Entry
Atmosphere
Product
R
Yield % using catalyst
matography yielded the products 3–5. H and C NMR data for
the products were in accordance with literature values.5
1
2
1
2
3
4
5
6
Argon
Argon
Argon
Air
Air
Air
NO
COMe
OMe
2
99
99
19
62
50
38
99
99
48
82
86
48
Acknowledgments
NO
2
We acknowledge the Academy of Finland for financial support
COMe
OMe
[
110043 (R.F.) and 122350 (K.R.)], and thank Noora Kuuloja and
Tommi Aronen for helpful discussions during the work.