Palladium-catalyzed Mizoroki-Heck type reaction with aryliodine diacetates using hydrazone ligand

Article abstract of DOI:10.3987/COM-13-12786

We developed a palladium-catalyzed Mizoroki-Heck type reaction of olefins with such hypervalent iodine reagents as iodobenzene diacetate in good to high yields using 2 mol% of a heterocyclic hydrazone (1b)-Pd(OAc)₂ system in NMP under air at 90 °C. The Japan Institute of Heterocyclic Chemistry.

Full text of DOI:10.3987/COM-13-12786

HETEROCYCLES, Vol. 87, No. 10, 2013
2015
HETEROCYCLES, Vol. 87, No. 10, 2013, pp. 2015 - 2021. © The Japan Institute of Heterocyclic Chemistry
Received, 22nd July, 2013, Accepted, 26th August, 2013, Published online, 29th August, 2013
DOI: 10.3987/COM-13-12786
PALLADIUM-CATALYZED MIZOROKI-HECK TYPE REACTION
WITH ARYLIODINE DIACETATES USING HYDRAZONE LIGAND
Takashi Mino,* Kohei Watanabe, Taichi Abe, Taketo Kogure, and Masami
Sakamoto
Department of Applied Chemistry and Biotechnology, Graduate School of
Engineering, Chiba University, 1-33, Yayoi-cho, Inage-ku, Chiba 263-8522,
Japan
tmino@faculty.chiba-u.jp
Abstract – We developed a palladium-catalyzed Mizoroki-Heck type reaction of
olefins with such hypervalent iodine reagents as iodobenzene diacetate in good to
high yields using 2 mol% of a heterocyclic hydrazone (1b)-Pd(OAc)2 system in
NMP under air at 90 °C.
INTRODUCTION
The arylation of olefins, also known as the Mizoroki-Heck reaction, is one of the most widely used
palladium-catalyzed methodologies in organic synthesis. The efficiency of several catalysts for the
reaction of aryl halides with acrylates or styrene derivatives has been studied.1 Recently,
palladium-catalyzed Mizoroki-Heck type reactions of olefins with aryliodine diacetates as hypervalent
iodine reagents instead of aryl halides were reported.2 For example, Mao and co-workers reported a
palladium-catalyzed Mizoroki-Heck type reaction with aryliodine diacetates with 4 mol% of Pd(OAc)2.3
But PEG-400 had to be used as a solvent because such commonly used organic solvents as DMF and
THF were not effective under these conditions. Magedov and co-workers also reported a reaction with
aryliodine diacetates.4 In this case, binary catalysts such as Pd(OAc)2 (3-5 mol%)-Ag2CO3 (50 mol%)
systems with TEMPO (50 mol%) as an additive in MeCN are needed to efficiently obtain the products.
On the other hand, we recently demonstrated hydrazone as an effective ligand for such
palladium-catalyzed C-C bond formation as the Suzuki-Miyaura reaction,5 the Mizoroki-Heck reaction,6

2016
HETEROCYCLES, Vol. 87, No. 10, 2013
the Sonogashira cross-coupling reaction,7 the Hiyama cross-coupling reaction,7a and the allyl
cross-coupling reaction of allylic acetate8 and ether9 with boronic acid. We also reported a
palladium-catalyzed Mizoroki-Heck type reaction with aryl trimethoxysilanes.10 We now report the use of
hydrazone ligands (1a-e) and (2) (Figure 1) for a palladium-catalyzed Mizoroki-Heck type reaction of
olefins with iodobenzene diacetates instead of aryl halides.
R1
N N
R2
R1
R2
Ph
N N
N
N N
Me
1
2
a: R1, R2 = -(CH2)5-
b: R1, R2 = -(CH2)6-
c: R1 = Ph, R2 = Me
d: R1 = 2-pyridyl, R2 = Me
e: R1, R2 =
Figure 1. Hydrazones 1 and 2
RESULTS AND DISCUSSION
Initially, we examined the reaction of iodobenzene diacetate and n-butyl acrylate as model substrates with
2 mol% of Pd catalyst for 4 h under an air atmosphere at 90 °C (Table 1). Using 2 mol% of
PdCl2(MeCN)2 and hydrazone (1a) as a ligand, we observed that the reaction in the presence of Cs2CO3 as
a base in NMP as a solvent gave corresponding product (3a) in a 62% yield (Table 1, Entry 1). We tested
other hydrazones (1b-e) and (2) (Entries 2-6) and found that heterocyclic hydrazone (1b) was an effective
ligand for this reaction (Entry 2). Several palladium sources were also tested (Entries 2, and 7–12).
Palladium acetate was the most effective palladium source in this reaction (Entry 7). Next, the effects of
various bases and solvents were investigated (Entries 7, and 13-22). Using Cs2CO3 in NMP led to a 96%
yield for this reaction (Entry 7). Although the Mizoroki-Heck type reaction proceeded in MeCN under
Magedov’s conditions,4 MeCN was not an effective solvent in the hydrazone (1b)-Pd(OAc)2 system
(Entry 22).

HETEROCYCLES, Vol. 87, No. 10, 2013
2017
Table 1. Optimization of Palladium-Catalyzed Mizoroki-Heck Type Reaction with Iodobenzene
Diacetate Using Hydrazone Liganda
Pd source (Pd = 2 mol%)
O
Ligand (2 mol%)
Base (2.8 equiv.)
I(OAc)2
O
OnBu
+
OnBu
Solvent (0.25 M)
90 °C, air, 4 h
3a
Entry
1
Pd source
Ligand
Base
Solvent
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
DMA
DMSO
DMF
PhMe
MeCN
Yield of 3a (%)b
PdCl2(MeCN)2 1a
PdCl2(MeCN)2 1b
PdCl2(MeCN)2 1c
PdCl2(MeCN)2 1d
PdCl2(MeCN)2 1e
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
K2CO3
K3PO4
62
78
69
21
74
42
96
87
87
83
79
87
36
54
11
16
49
76
66
43
42
4
2
3
4
5
6
PdCl2(MeCN)2
Pd(OAc)2
2
7
1b
8
Pd(acac)2
[Pd(!3-allyl)Cl]2 1b
1b
9
10
11
12
13
14
15
16
17
18
19
20
21
22
PdCl2
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
Pd(tfa)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
Pd(OAc)2
Pd(OAc)2
Ca(OH)2
NaOAc
Et3N
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
a Reaction conditions: Iodobenzene diacetate (0.5 mmol), n-butyl acrylate (3.0 mmol), Pd source (Pd = 2
mol%), ligand (2 mol%), base (1.4 mmol), solvent (2 mL) at 90 °C for 4 h under air.
b Isolated yields.
Under optimized reaction conditions (Table 1, Entry 7), we explored the scope and limitation of both
aryliodine diacetates and olefins (Table 2). The reaction of iodobenzene diacetate with n-butyl acrylate
for 2 h also gave product (3a) with high yield instead of 4 h (Table 2, Entry 1 vs. Table 1, Entry 7). When
the reaction was carried out without using ligand (1b), the yield of 3a was decreased (Entry 1 vs. Entry 2).
Using iodobenzene diacetate with tert-butyl acrylate and ethyl acrylate for 4 h led to good yields of

2018
HETEROCYCLES, Vol. 87, No. 10, 2013
corresponding products (3b) and (3c) (Entries 3 and 4). The reaction of methyl acrylate also gave
corresponding product (3d) in 81% for 18 h (Entry 5). Moreover, methyl vinyl ketone and styrene led to
good yields of products (3e) and (3f) (Entries 6 and 7). We also found that the reaction of iodomesitylene
diacetate and m-(diacetoxyiodo)anisole with various acrylates gave corresponding products (3g-l) with
moderate to good yields (Entries 8-13). Although true mechanism was not revealed, we thought the
aryliodine was generated in situ from aryliodine diacetate and then the related Mizoroki-Heck type
reaction occurred.3,4
Table 2. Scope and Limitations of Palladium-Catalyzed Mizoroki-Heck Type Reaction of Olefins with
Aryliodine Diacetatesa
Pd(OAc)2 (2 mol%)
1b (2 mol%)
I(OAc)2
R'
Cs2CO3 (2.8 equiv.)
+
R'
NMP (0.25 M)
90 °C, air, 4 h
R
R
3
Entry
1c
2c,d
R
H
H
H
H
H
H
H
R’
yield of 3 (%)b
96(3a)
85(3a)
71(3b)
88(3c)
81(3d)
58(3e)
79(3f)
CO2nBu
CO2nBu
CO2tBu
CO2Et
CO2Me
COMe
Ph
3
4
5e
6f
7e
8
9g
10e
11
12g
2,4,6-triMe
2,4,6-triMe
2,4,6-triMe
3-MeO
CO2nBu
CO2tBu
CO2Et
CO2nBu
CO2tBu
CO2Et
79(3g)
39(3h)
58(3i)
93(3j)
3-MeO
59(3k)
91(3l)
13e
3-MeO
a
Reaction conditions: Aryliodine diacetate (0.5 mmol), olefin (3.0 mmol), Pd(OAc)2 (2 mol%), 1b (2
mol%), Cs2CO3 (1.4 mmol), NMP (2 mL) at 90 °C for 4 h under air.
b Isolated yields.
c This reaction was carried out for 2 h.
d This reaction was carried out without using ligand 1b.
e This reaction was carried out for 18 h.
f This reaction was carried out for 8 h.
g This reaction was carried out for 24 h.

HETEROCYCLES, Vol. 87, No. 10, 2013
2019
In summary, we found that a palladium-catalyzed Mizoroki-Heck type reaction of olefins with aryliodine
diacetates in NMP gave corresponding products in good to high yields using 2 mol% of heterocyclic
hydrazone (1b)-Pd(OAc)2 system under air at 90 °C for 2-24 h.
EXPERIMENTAL
General
Melting points were measured on a Asone micromelting point apparatus and are uncorrected. 1H and C
13
NMR spectra were recorded on a Bruker DPX-300 spectrometer. Chemical shifts are reported in ! ppm
referenced to an internal SiMe4 standard. Infrared (IR) spectra were obtained using a JASCO FT/IR 230
spectrophotometer. Mass spectra were recorded on a GCMS-QP5050. HRMS was recorded on a Thermo
Fisher Scientific Exactive using ESI.
General Procedure for Palladium-Catalyzed Mizoroki-Heck Type Reaction with Aryliodine Diacetates.
To a mixture of aryliodine diacetate (0.5 mmol), Cs2CO3 (1.4 mmol), Pd(OAc)2 (10 µmol), and 1b (10
µmol) in NMP (2 mL) was added olefin (3.0 mmol) at room temperature under an air atmosphere. The
mixture was stirred at 90 °C. After 2-24 h, the mixture was diluted with EtOAc 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:EtOAc = 20-10:1 or CHCl3:EtOAc = 10:1).
(E)-n-Butyl cinnamate (3a):10 96% as a colorless oil; IR (neat, cm-1): 1713 (C=O); 1H NMR (CDCl3) !:
0.97 (t, J = 7.3 Hz, 3H), 1.38-1.50 (m, 2H), 1.65-1.72 (m, 2H), 4.21 (t, J = 6.7 Hz, 2H), 6.45 (d, J = 16.0
Hz, 1H), 7.38-7.40 (m, 3H), 7.52-7.55 (m, 2H), 7.69 (d, J = 16.1 Hz, 1H); 13C NMR (CDCl3) !: 13.7, 19.2,
30.7, 64.4, 118.2, 128.0, 128.9, 130.2, 134.4, 144.5, 167.1; EI-MS m/z (rel intensity) 204 (M+, 23).
1
(E)-t-Butyl cinnamate (3b):10 71% as a colorless oil; IR (neat, cm-1): 1708 (C=O); H NMR (CDCl3) !:
1.54 (s, 9H), 6.37 (d, J = 16.0 Hz, 1H), 7.36-7.38 (m, 3H), 7.50-7.53 (m, 2H), 7.59 (d, J = 16.0 Hz, 1H);
13C NMR (CDCl3) !: 28.2, 80.5, 120.1, 127.9, 128.8, 129.9, 134.6, 143.5, 166.3; EI-MS m/z (rel intensity)
204 (M+, 10).
1
(E)-Ethyl cinnamate (3c):10 88% as a colorless oil; IR (neat, cm-1): 1708 (C=O); H NMR (CDCl3) !:
1.34 (t, J = 7.1 Hz, 3H), 4.27 (q, J = 7.1 Hz, 2H), 6.44 (d, J = 16.0 Hz, 1H), 7.38-7.40 (m, 3H), 7.52-7.55
13
(m, 2H), 7.69 (d, J = 16.0 Hz, 1H); C NMR (CDCl3) !: 14.3, 60.5, 118.2, 128.0, 128.8, 130.2, 134.4,
144.5, 167.0; EI-MS m/z (rel intensity) 176 (M+, 40).
(E)-Methyl cinnamate (3d):10 81% as a white solid; mp 33-34 ºC; IR (KBr, cm-1): 1718 (C=O); 1H NMR
(CDCl3) !: 3.81 (s, 3H), 6.45 (d, J = 16.0 Hz, 1H), 7.37-7.40 (m, 3H), 7.51-7.55 (m, 2H), 7.70 (d, J = 16.0
13
Hz, 1H); C NMR (CDCl3) !: 51.7, 117.7, 128.0, 128.9, 130.3, 134.3, 144.9, 167.4; EI-MS m/z (rel
intensity) 162 (M+, 53).

2020
HETEROCYCLES, Vol. 87, No. 10, 2013
(E)-4-Phenylbut-3-en-2-one (3e):10 58% as a yellow oil; IR (neat, cm-1): 1668 (C=O); 1H NMR (CDCl3)
13
!: 2.39 (s, 3H), 6.72 (d, J = 16.3 Hz, 1H), 7.39-7.41 (m, 3H), 7.49-7.57 (m, 3H); C NMR (CDCl3) !:
27.5, 127.1, 128.2 128.9, 130.5, 134.4, 143.4, 198.4; EI-MS m/z (rel intensity) 146 (M+, 65).
1
trans-Stilben (3f):10 79% as a white solid; mp 124-125 ºC; H NMR (CDCl3) !: 7.11 (s, 2H), 7.24-7.28
(m, 2H), 7.36 (t, J = 7.5 Hz, 4H), 7.52 (d, J = 7.3 Hz, 4H); 13C NMR (CDCl3) !: 126.5, 127.6, 128.7,
137.3; EI-MS m/z (rel intensity) 180 (M+, 100).
(E)-n-Butyl 3-mesitylacrylate (3g).11 79% as a white solid; mp 30-31 ºC; IR (KBr, cm-1): 1709 (C=O);
1H NMR (CDCl3) !: 0.97 (t, J = 7.4 Hz, 3H), 1.38-1.50 (m, 2H), 1.65-1.74 (m, 2H), 2.28 (s, 3H), 2.33 (s,
6H), 4.21 (t, J = 6.7 Hz, 2H), 6.06 (d, J = 16.4 Hz, 2H), 6.89 (s, 2H), 7.84 (d, J = 16.4 Hz, 1H); 13C NMR
(CDCl3) !: 13.8, 19.2, 21.0, 21.1, 30.7, 64.4, 123.1, 129.1, 130.1, 136.8, 138.3, 143.1, 167.1; EI-MS m/z
(rel intensity) 246 (M+, 24).
(E)-t-Butyl 3-mesitylacrylate (3h): 39% as a white solid; mp 62-63 ºC; IR (KBr, cm-1): 1711 (C=O); 1H
NMR (CDCl3) !: 1.54 (s, 9H), 2.28 (s, 3H), 2.33 (s, 6H), 5.98 (d, J = 16.3 Hz, 1H), 6.88 (s, 2H), 7.75 (d,
13
J = 16.3 Hz, 1H); C NMR (CDCl3) !: 21.0, 21.1, 28.2, 80.4, 124.8, 129.1, 131.1, 136.8, 138.0, 138.1,
142.0; EI-MS m/z (rel intensity) 246 (M+, 28); HRMS (ESI-MS) m/z calcd for C16H22O2+Na 269.1512,
found 269.1510.
1
(E)-Ethyl 3-mesitylacrylate (3i):12 58% as a white solid; mp 36-37 ºC; IR (KBr, cm-1): 1701 (C=O); H
NMR (CDCl3) !: 1.35 (t, J = 7.1 Hz, 3H), 2.28 (s, 3H), 2.33 (s, 6H), 4.27 (q, J = 7.1 Hz, 2H), 6.06 (d, J =
16.3 Hz, 1H), 6.90 (s, 2H), 7.84 (d, J = 16.3 Hz, 1H); 13C NMR (CDCl3) !: 14.3, 21.0, 21.1, 60.5, 123.1,
129.1, 130.9, 136.8, 138.3, 143.1, 167.0; EI-MS m/z (rel intensity) 218 (M+, 40).
(E)-n-Butyl 3-(3-methoxyphenyl)acrylate (3j):13 93% as a colorless oil; IR (neat, cm-1): 1713 (C=O); 1H
NMR (CDCl3) !: 0.97 (t, J = 7.3 Hz, 3H), 1.38-1.50 (m, 2H), 1.65-1.74 (m, 2H), 3.84 (s, 3H), 4.21 (t, J =
6.7 Hz, 2H), 6.43 (d, J =15.9 Hz, 1H), 6.93 (dd, J = 8.2 and 1.8 Hz, 1H), 7.05 (t, J = 2.0 Hz, 1H), 7.12 (d,
J = 7.7 Hz, 1H), 7.30 (t, J = 7.9 Hz, 1H), 7.65 (d, J = 16.0 Hz, 1H); 13C NMR (CDCl3) !: 13.7, 19.2, 30.7,
55.2, 64.4, 112.8, 116.1, 118.5, 120.7, 129.8, 135.8, 144.4, 159.8, 167.0; EI-MS m/z (rel intensity) 234
(M+, 40).
1
(E)-t-Butyl 3-(3-methoxyphenyl)acrylate (3k):14 59% as a yellow oil; IR (neat, cm-1): 1706 (C=O); H
NMR (CDCl3) !: 1.54 (s, 9H), 3.83 (s, 3H), 6.36 (d, J = 16.0, 1H), 6.91 (dd, J = 8.2 and 2.5 Hz, 1H), 7.03
(t, J = 1.9 Hz, 1H), 7.10 (d, J = 7.8 Hz, 1H), 7.29 (t, J = 7.7 Hz, 1H), 7.55 (d, J = 16.0 Hz, 1H); 13C NMR
(CDCl3) !: 28.2, 55.2, 80.5, 112.7, 115.8, 120.4, 120.7, 129.8, 136.0, 143.4, 159.8, 166.3; EI-MS m/z (rel
intensity) 234 (M+, 28).
1
(E)-Ethyl 3-(3-methoxyphenyl)acrylate (3l):15 91% as a colorless oil; IR (neat, cm-1): 1712 (C=O); H
NMR (CDCl3) !: 1.34 (t, J = 7.1 Hz, 3H), 3.83 (s, 3H), 4.27 (q, J = 7.1 Hz, 2H), 6.43 (d, J = 16.0 Hz, 1H),
6.93 (dd, J = 8.2 and 1.9 Hz, 1H), 7.04 (t, J = 1.9 Hz, 1H), 7.12 (d, J = 7.6 Hz, 1H), 7.30 (t, J = 7.9 Hz,

HETEROCYCLES, Vol. 87, No. 10, 2013
2021
13
1H) 7.65 (d, J = 16.0 Hz, 1H); C NMR (CDCl3) !: 14.3, 55.3, 60.5, 112.8, 116.1, 118.5, 120.7, 129.8,
135.8, 144.5, 159.8, 166.9; EI-MS m/z (rel intensity) 206 (M+, 67).
ACKNOWLEDGEMENTS
This work was partially supported by Iodine Research Project in Chiba University and the Society of
Iodine Science.
REFERENCES
1. For reviews, see the following: (a) A. de Meijere and F. E. Meyer, Angew. Chem., Int. Ed. Engl.,
1995, 33, 2379; (b) W. A. Herrmann, V. P. W. Böhm, and C.-P. Reisinger, J. Organomet. Chem.,
1999, 576, 23; (c) I. P. Beletskaya and A. V. Cheprakov, Chem. Rev., 2000, 100, 3009; (d) N. J.
Whitcombe, K. K. (Mimi) Hii, and S. E. Gibson, Tetrahedron, 2001, 57, 7449; (e) F. Alonso, I. P.
Beletskaya, and M. Yus, Tetrahedron, 2005, 61, 11771.
2. (a) N. R. Deprez and M. S. Sanford, Inorg. Chem., 2007, 46, 1924; (b) J. Aydin, J. M. Larsson, N.
Selander, and K. J. Szabó, Org. Lett., 2009, 11, 2852.
3. X. Qu, P. Sun, T. Li, and J. Mao, Adv. Synth. Catal., 2011, 353, 1061.
4. N. M. Evdokimov, A. Kornienko, and I. V. Magedov, Tetrahedron Lett., 2011, 52, 4327.
5. (a) T. Mino, Y. Shirae, M. Sakamoto, and T. Fujita, Synlett, 2003, 882; (b) T. Mino, Y. Shirae, M.
Sakamoto, and T. Fujita, J. Org. Chem., 2005, 70, 2191.
6. (a) T. Mino, Y. Shirae, Y. Sasai, M. Sakamoto, and T. Fujita, J. Org. Chem., 2006, 71, 6834; (b) T.
Mino, H. Shindo, T. Kaneda, T. Koizumi, Y. Kasashima, M. Sakamoto, and T. Fujita, Tetrahedron
Lett., 2009, 50, 5358.
7. (a) T. Mino, Y. Shirae, T. Saito, M. Sakamoto, and T. Fujita, J. Org. Chem., 2006, 71, 9499; (b) T.
Mino, S. Suzuki, K. Hirai, M. Sakamoto, and T. Fujita, Synlett, 2011, 1277.
8. (a) T. Mino, K. Kajiwara, Y. Shirae, M. Sakamoto, and T. Fujita, Synlett, 2008, 2711; (b) T. Mino, T.
Koizumi, S. Suzuki, K. Hirai, K. Kajiwara, M. Sakamoto, and T. Fujita, Eur. J. Org. Chem., 2012,
678.
9. T. Mino, T. Kogure, T. Abe, T. Koizumi, T. Fujita, and M. Sakamoto, Eur. J. Org. Chem., 2013,
1501.
10. T. Mino, M. Shibuya, S. Suzuki, K. Hirai, M. Sakamoto, and T. Fujita, Tetrahedron, 2012, 68, 429.
11. G.-W. Wang and T. Miao, Chem. Eur. J., 2011, 17, 5787.
12. P. R. Blakemore, D. K. H. Ho, and W. M. Nap, Org. Biomol. Chem., 2005, 3, 1365.
13. R. Martinez, F. Voica, J.-P. Genet, and S. Darses, Org. Lett., 2007, 9, 3213.
14. B. H. Lipshutz, S. Ghorai, W. W. Y. Leong, and B. R. Taft, J. Org. Chem., 2011, 76, 5061.
15. D.-H. Lee, A. Taher, S. Hossain, and M.-J. Jin, Org. Lett., 2011, 13, 5540.