Palladium-catalyzed Mizoroki-Heck reaction of allyl aryl ethers with aryl iodides using phosphine-free hydrazone ligands

Article abstract of DOI:10.1016/j.tetlet.2009.07.046

Palladium-catalyzed Mizoroki-Heck reaction of allyl aryl ethers with aryl iodides gave aryl cinnamyl ethers using a catalytic amount of Pd(OAc)₂ in DMF at 50 °C with phosphine-free hydrazone as a ligand in good yields.

Full text of DOI:10.1016/j.tetlet.2009.07.046

Tetrahedron Letters 50 (2009) 5358–5360
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Tetrahedron Letters
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Palladium-catalyzed Mizoroki–Heck reaction of allyl aryl ethers with aryl
iodides using phosphine-free hydrazone ligands
*
Takashi Mino , Hiroaki Shindo, Tomoko Kaneda, Tomoko Koizumi, Yoshio Kasashima, Masami Sakamoto,
Tsutomu Fujita
Department of Applied Chemistry and Biotechnology, Graduate School of Engineering, Chiba University, 1-33, Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Palladium-catalyzed Mizoroki–Heck reaction of allyl aryl ethers with aryl iodides gave aryl cinnamyl
ethers using a catalytic amount of Pd(OAc)2 in DMF at 50 °C with phosphine-free hydrazone as a ligand
in good yields.
Received 8 June 2009
Revised 2 July 2009
Accepted 3 July 2009
Available online 15 July 2009
Ó 2009 Elsevier Ltd. All rights reserved.
The Mizoroki–Heck reaction is one of the most widely used pal-
ladium-catalyzed methodologies in organic synthesis. The effi-
ciency of several catalysts for the reaction of aryl halides with
acrylates or styrene derivatives has been studied.1 Although the
synthesis of alkyl cinnamyl ethers using the Mizoroki–Heck-type
reaction of allyl ethers has been reported by several groups,2 the
synthesis of aryl cinnamyl ethers using the Mizoroki–Heck-type
reaction of allyl aryl ethers has attracted less attention.3,4 However
an aryl cinnamyl ether framework constitutes an important struc-
tural assembly in many molecules of biological importance.4,5 The
synthesis of aryl cinnamyl ethers using palladium-catalyzed ether-
ification of cinnamyl alcohol,6 cinnamyl acetate,7 or cinnamyl car-
the presence of Pd(OAc)2 with K3PO4 as a base in DMF as a solvent
proceeded to give (E)-cinnamyl phenyl ether (2a) in 83% yield with
a small amount of 313 and 43a as by-products (Table 1, entry 1). We
also tested other bishydrazones 1b–d, and found that hydrazone
1b was a very effective ligand for this reaction (entry 2 vs entries
1, 3 and 4). The effect of various palladium sources was investi-
gated (entries 2, and 5–7). The use of Pd(OAc)2 led to high yield
for this reaction (entry 2). Several commonly used bases were
tested (entries 2, and 8–11); K3PO4 was preferred this reaction (en-
try 2). The effect of various solvents was also investigated (entries
2, and 12–15). The use of DMF as a solvent led to high yield for this
reaction (entry 2). We found the following optimized conditions;
using the Pd(OAc)2/hydrazone 1b system, the reaction proceeded
with 83% in DMF at 50 °C (entry 2).
bonate8 by phenols via
p-allylpalladium intermediate with
phosphine ligands has been also reported. In these cases, it is nec-
essary to prepare the corresponding cinnamyl alcohol derivatives.
We recently demonstrated an air-stable phosphine-free hydra-
zone as an effective ligand for palladium-catalyzed C–C bond for-
mations such as the Suzuki–Miyaura reaction,9 the Mizoroki–
Heck reaction of acrylates and styrene,10 the Sonogashira cross-
coupling reaction,11 the Hiyama cross-coupling reaction,11 and
the allyl cross-coupling reaction of allylic acetate with boronic
acid.12 We now report the use of phosphine-free hydrazone ligands
1a–d (Fig. 1) for a palladium-catalyzed Mizoroki–Heck reaction of
allyl aryl ethers with aryl halides for the synthesis of aryl cinnamyl
ethers.
Under optimized reaction conditions,14 the effect of various aryl
iodides in the Mizoroki–Heck reaction was investigated using ally
phenyl ether (Table 2, entries 1–13). Using iodobenzene and
4-substituted aryl iodides led to good yields of the corresponding
(E)-cinnamyl phenyl ether derivatives (entries 1–7). Moreover,
3-substituted, 2-substituted and multi-substituted aryl iodides
also led to good yields (entries 8–12). Using 3-iodothiophene led
to moderate yield of the corresponding product (entry 13). Based
on the results of the Mizoroki–Heck reaction using allyl phenyl
ether, we tested the reaction of various allyl aryl ethers (entries
Initially, we tried to seek the optimal reaction conditions for the
palladium-catalyzed Mizoroki–Heck reaction of allyl aryl ethers
with aryl halides. Iodobenzene and ally phenyl ether were chosen
as model substrates with 3 mol % of Pd catalyst for 24 h under an
argon atmosphere at 50 °C (Table 1). Using 3 mol % of hydrazone
1a as a ligand, we observed that the Mizoroki–Heck reaction in
R1
N N
R2
R1
R2
N N
1
a: R1 = Ph, R2 = Me
b: R1, R2 = -(CH2)6-
c: R1, R2 = -(CH2)5-
d: R1, R2 = -(CH2)2O(CH2)2-
* Corresponding author. Tel.: +81 43 290 3385; fax: +81 43 290 3401.
E-mail address: tmino@faculty.chiba-u.jp (T. Mino).
Figure 1. Hydrazone ligands 1a–d.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.07.046

T. Mino et al. / Tetrahedron Letters 50 (2009) 5358–5360
5359
Table 1
PhI
Optimization of reaction conditions on the palladium-catalyzed Mizoroki–Heck
reaction of allyl phenyl ether with iodobenzenea
Pd source
ligand, base
Ph
OPh
2a
I
+
PhI
Ph
N
OPh
+
Pd0
solvent, 50 °C
24 h, Ar
PdII
R
N
R
Ph
R
N
R
R
R
R
OPh
N
N
N
N
N
R
3
+
Base·HI
Base
OPh
Ph
OPh
4
insertion
Entry
Ligand
Pd source
Base
Solvent
Yieldb (%) 2a(E:Z)/3/4
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
1a
1b
1c
1d
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
PdCl2
Pd(OCOCF3)2
Pd2(dba)3
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K2CO3
Cs2CO3
KOAc
Na2CO3
K3PO4
K3PO4
K3PO4
K3PO4
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
NMP
DMAc
DMSO
PhMe
76(34:1)/3/5
83(31:1)/4/5
79(32:1)/3/6
75(35:1)/3/5
55(45:1)/2/5
66(39:1)/3/6
53(45:1)/3/5
67(28:1)/3/6
2(À)/trace/trace
45(22:1)/2/5
37(34:1)/2/3
80(31:1)/3/5
78(42:1)/3/6
19(14:1)/1/1
4(72:1)/trace /1
OPh
Ph
HA HB
H
Ph
OPh
PdIII
PdIII
R
N
R
R
N
R
R
R
N
R
or
N
N
N
N
N
R
I
II
β-HA elimination
β-HB elimination β-H elimination
Ph
Ph
OPh
Ph
OPh
OPh
a
Reaction conditions: PhI (0.5 mmol), allyl phenyl ether (0.7 mmol), ligand
(3 mol %), Pd source (3 mol %), base (0.7 mmol), solvent (1 mL) at 50 °C for 24 h
under Ar.
4
2a
3
Scheme 1. A plausible mechanism for Mizoroki–Heck reaction of allyl phenyl ether
b
Determined by 1H NMR using diphenylmethane as an internal standard.
with iodobenzene.
14–16). Using allyl 4-methylphenyl ether and allyl 4-methoxy-
phenyl ether led to good yields of the Mizoroki–Heck reaction
products (entries 14 and 15). The reaction of allyl 4-chlorophenyl
ether with iodobenzene was necessary to extend the reaction
times, such as to 48 h (entry 16). We also investigated the reaction
of bromobenzene instead of that of iodobenzene. Unfortunately,
the reaction using bromobenzene with ally phenyl ether gave
(E)-cinnamyl phenyl ether with low yield (entry 17).
Table 2
Palladium-catalyzed Mizoroki–Heck reaction of allyl aryl ethers with aryl halidesa
R
+
ArX
O
Pd(OAc)2
ligand 1b, K3PO4
R
A plausible mechanism for Mizoroki–Heck reaction of allyl phe-
nyl ether with iodobenzene is illustrated in Scheme 1. The first step
is the oxidative addition of iodobenzene to Pd(0)–hydrazone com-
plex. Subsequently, the insertion reaction of Pd complex with allyl
phenyl ether followed by b-hydride elimination of HA gives cin-
namyl phenyl ether 2a. On the other hand, enol ether 4 is obtained
from Pd complex I by b-hydride elimination of HB instead of HA.
When Pd complex II is formed instead of Pd complex I, branched
allyl ether 3 is obtained. After reductive elimination of HI by base,
the Pd(0) complex is regenerated and the catalytic cycle is
completed.
Ar
O
DMF, 50 °C
24 h, Ar
2
Entry
ArX
R
Product
Yieldb (%)
1
2
3
PhI
H
H
H
H
H
H
H
H
H
H
H
H
H
2a
2b
2c
2d
2e
2f
2g
2h
2i
2j
2k
2l
2m
2n
2o
2p
2a
76
74
64
70
64
43
77
68
74
74
73
60
51
71
71
62
17
4-MeC6H4I
4-iPrC6H4I
4-CF3C6H4I
4-MeOC6H4I
4-AcC6H4I
4-BrC6H4I
3-MeC6H4I
3-CF3C6H4I
3,5-Me2C6H3I
3,4-Me2C6H3I
2-MeC6H4I
3-Iodothiophene
4-MeC6H4I
4-MeC6H4I
PhI
4
5
6c
7
8
9
In summary, we found that the palladium-catalyzed Mizoroki–
Heck reaction of allyl aryl ethers with various aryl iodides gave aryl
cinnamyl ethers using a catalytic amount of Pd(OAc)2 in DMF at
50 °C with phosphine-free hydrazone as a ligand in good yields.
10
11
12
13
14
15
16d
17
4-Me
4-MeO
4-Cl
H
Supplementary data
PhBr
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2009.07.046.
a
Reaction conditions: Aryl halide (0.5 mmol), allyl aryl ether (0.7 mmol), ligand
(3 mol %), Pd(OAc)2 (3 mol %), K3PO4 (0.7 mmol), DMF (1 mL) at 50 °C for 24 h under
Ar.
b
Yields refer to isolated yields with >98% purity as determined by GC–MS or 1H
References and notes
NMR.
c
This reaction was carried out for 3 h.
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This reaction was carried out for 48 h.

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ethers with aryl halides: To a mixture of aryl halide (0.5 mmol), K3PO4
(148.5 mg, 0.7 mmol), Pd(OAc)2 (3.37 mg, 15 mmol) and ligand 1b (3.75 mg,
15 mmol) in DMF (1.0 mL) was added allyl aryl ether (0.7 mmol) at room
temperature under an atmosphere of argon. The mixture was stirred at 50 °C.
After 24 h, the mixture was diluted with ethyl acetate and water. The organic
layer was washed with brine, dried over MgSO4 and concentrated under
reduced pressure. The residue was purified by silica gel chromatography
(hexane/CHCl3 = 80–6/1).