Synthesis of 1,3-diarylpropenes through palladium-catalyzed mizoroki-heck and allyl cross-coupling reactions using hydrazones as ligands

Article abstract of DOI:10.1002/ejoc.201101533

The palladium-catalyzed synthesis of unsymmetrical 1,3-diarylpropenes from allyl esters through a Mizoroki-Heck-type reaction with aryl iodides followed by allyl cross-coupling with a variety of arylboronic acids was developed; the products are obtained in moderate to good yields by using a hydrazone-Pd(OAc) ₂ system. The synthesis of unsymmetrical 1,3-diarylpropenes from allyl esters by a Mizoroki-Heck-type reaction followed by allyl cross-coupling with a variety of arylboronic acids was developed; the products were obtained in moderate to good yields by using a hydrazone-Pd(OAc)₂ system. Copyright

Full text of DOI:10.1002/ejoc.201101533

SHORT COMMUNICATION
DOI: 10.1002/ejoc.201101533
Synthesis of 1,3-Diarylpropenes through Palladium-Catalyzed Mizoroki–Heck
and Allyl Cross-Coupling Reactions Using Hydrazones as Ligands
Takashi Mino,*[a] Tomoko Koizumi,[a] Saori Suzuki,[a] Kiminori Hirai,[a] Kenji Kajiwara,[a]
Masami Sakamoto,[a] and Tsutomu Fujita[a]
Keywords: Palladium / Hydrazones / Cross-coupling / Arylation / Allylic compounds
The palladium-catalyzed synthesis of unsymmetrical 1,3-di-
arylpropenes from allyl esters through a Mizoroki–Heck-type
reaction with aryl iodides followed by allyl cross-coupling
with a variety of arylboronic acids was developed; the prod-
ucts are obtained in moderate to good yields by using a hy-
drazone–Pd(OAc)2 system.
Introduction
Results and Discussion
A 1,3-diarylpropene framework constitutes an important
Initially, we sought the optimal reaction conditions for
structural assembly in many molecules of biological impor- the palladium-catalyzed Mizoroki–Heck-type reaction of
tance.[1] The palladium-catalyzed allyl cross-coupling reac- allyl esters with aryl iodides by using hydrazone ligands.
tion of cinnamyl acetate with arylboronic acids provides a Allyl acetate and iodobenzene were chosen as model sub-
powerful tool for the synthesis of 1,3-diarylpropenes.[2] We strates with the Pd catalyst (5 mol-%) in toluene for 8 h un-
previously reported the use of hydrazone ligands for the der an atmosphere of air at 80 °C (Table 1). Under a modi-
palladium-catalyzed allyl cross-coupling of cinnamyl acet- fied version of Jiao’s ligand-free conditions,[4a] the Mizo-
ate with boronic acids at room temperature.[3] Previously, roki–Heck-type reaction gave a good yield of corresponding
the synthesis of cinnamyl acetate derivatives by the Mizo- product 2 with a small amount of regioisomer 3 (Table 1,
roki–Heck reaction of allyl acetate with aryl halides was Entry 1). Using 5 mol-% of hydrazone 1a as a ligand, we
studied by Jiao et al.[4] Recently, 1,3-diarylpropenes with observed that the reaction proceeded to give desired prod-
the same aryl group were synthesized through the palla- uct 2 in 56% yield (Table 1, Entry 2). We also tested hydraz-
dium-catalyzed diarylation of allylic esters with aryl iodides one 1b and found that it was an effective ligand for this
by using Pd(OAc)2 (10 mol-%) at 120 °C by Li et al.[5] To reaction (Table 1, Entry 3).
the best of our knowledge, examples of the synthesis of 1,3-
diarylpropenes with different aryl groups from allyl esters
by diarylation have not been explored. We now report the
Table 1. Optimization of the palladium-catalyzed Mizoroki–Heck-
type reaction of allyl acetate with iodobenzene.[a]
synthesis of unsymmetrical 1,3-diarylpropenes by a palla-
dium-catalyzed Mizoroki–Heck-type reaction of allyl esters
with aryl iodides followed by allyl cross-coupling with a
variety of arylboronic acids by using hydrazone 1[6] as a
ligand (Figure 1).
Entry
Ligand
Yield of 2 [%][b]
Yield of 3 [%][b]
1
2
3
none
1a
1b
76
56
80
6
5
6
[a] Reaction conditions: Iodobenzene (0.5 mmol), allyl acetate
(1.0 mmol), Pd(OAc)2 (5 mol-%), ligand 1 (5 mol-%), Ag2CO3
(0.3 mmol), PhMe (3 mL) at 80 °C for 8 h in air. [b] Determined
by 1H NMR spectroscopy by using 2-methoxynaphthalene as an
internal standard; E/Z ratio of 2 was Ͼ20:1.
Figure 1. Hydrazone ligands 1.
[a] Department of Applied Chemistry and Biotechnology,
Graduate School of Engineering, Chiba University,
1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
Fax: +81-43-290-3401
We next tried to synthesize 1,3-diarylpropenes from allyl
acetate through the Mizoroki–Heck-type reaction with
iodobenzene in toluene at 80 °C for 8 h (Table 2, Reac-
tion 1) followed by allyl cross-coupling with a phenylbor-
onic acid in DMF/H2O (3:1) at room temperature for 15 h
E-mail: tmino@faculty.chiba-u.jp
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201101533.
678
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2012, 678–680

Palladium-Catalyzed Synthesis of 1,3-Diarylpropenes
under an atmosphere of air (Table 2, Reaction 2). Although Table 3. Palladium-catalyzed Mizoroki–Heck reaction and allyl
cross-coupling reaction.[a]
the reaction under ligand-free conditions gave intermediate
product 2 without desired product 4a (Table 2, Entry 1),
with the use of ligand 1b the reaction gave desired product
4a in 37% yield, as determined by NMR spectroscopy
(Table 2, Entry 2). When the reaction temperature of reac-
tion 2 was increased to 50 °C, corresponding product 4a
was obtained in good yield (Table 2, Entry 3). After optimi-
zation of the reaction temperature, a Mizoroki–Heck-type
reaction at 90 °C (reaction 1) followed by allyl cross-cou-
pling at 50 °C led to 71% yield of corresponding product
4a (Table 2, Entry 5). When allyl benzoate was used instead
of allyl acetate, the corresponding product was obtained in
high yield (85%, as determined by NMR spectroscopy;
Table 2, Entry 7).
Entry
Ar
R
ArЈ
Yield 4 + 5
Ratio
[%][b]
4/5[c]
1
2
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Me
Ph
Ph
Ph
92
67
58
67
69
67
68
70
64
51
85
15 (4a):1
13 (4b):1
9 (4c):1
10 (4d):1
10 (4e):1
10 (4f):1
17 (4g):1
14 (4h):1
7 (4i):1
4-MeC6H4
4-MeOC6H4
4-ClC6H4
3[d]
4
5[e]
6
Ph 3,5-Me2C6H3
Ph
Ph
2-MeC6H4
1-naph
Ph
7[f]
8
4-MeC6H4 Me
4-MeOC6H4 Ph
4-ClC6H4
Table 2. Optimization of the palladium-catalyzed Mizoroki–Heck
reaction and allyl cross-coupling reaction with iodobenzene.[a]
9[g]
10
11
Ph
Ph
Ph
Ph
12 (4j):1
13 (4k):1
3-MeC6H4 Me
[a] Reaction conditions: Reaction 1: Aryl iodide (0.5 mmol), allyl
ester (1.0 mmol), Pd(OAc)2 (5 mol-%), ligand 1b (5 mol-%),
Ag2CO3 (0.3 mmol), PhMe (3 mL) at 90 °C for 8 h in air; Reac-
tion 2: Arylboronic acid (1.2 mmol), K2CO3 (2 mmol), DMF
(1.5 mL), H2O (0.5 mL) at 50 °C for 15 h in air. [b] Isolated yield.
[c] Determined by 1H NMR spectroscopy; E/Z ratio of 4 was
Ͼ40:1. [d] Reaction 1 was carried out for 6 h. [e] Reaction 1 was
carried out for 6 h and Reaction 2 was carried out for 24 h at 70 °C.
[f] Reaction 2 was carried out at 70 °C. [g] Reaction 1 was carried
out for 6 h and reaction 2 was carried out for 24 h.
Entry
Temperature [°C]
Yield of 4a [%][b]
Reaction 1
Reaction 2
1[c]
2
3
4
5
80
80
80
80
90
r.t.
r.t.
50
70
50
50
50
0(71)
37(34)
68(0)
64(0)
71(0)
34(22)
85(0)
Conclusions
6
100
90
7[d]
In conclusion, we found that a hydrazone–Pd(OAc)2-cat-
alyzed Mizoroki–Heck-type reaction of allyl esters with aryl
iodides in toluene followed by allyl cross-coupling with a
variety of arylboronic acids in DMF/H2O (3:1), all in air,
provides unsymmetrical 1,3-diarylpropenes in moderate to
good yields.
[a] Reaction conditions: Reaction 1: Iodobenzene (0.5 mmol), allyl
acetate (1.0 mmol), Pd(OAc)2 (5 mol-%), ligand 1b (5 mol-%),
Ag2CO3 (0.3 mmol), PhMe (3 mL) for 8 h in air; Reaction 2: Phen-
ylboronic acid (1.2 mmol), K2CO3 (2 mmol), DMF (1.5 mL), H2O
1
(0.5 mL) for 15 h in air. [b] Determined by H NMR spectroscopy
by using 2-methoxynaphthalene as an internal standard. NMR
yield of 2 is shown in parentheses. [c] This reaction was carried out
without the use of a ligand. [d] Allyl benzoate was used instead of
allyl acetate.
Experimental Section
General Procedure for the Palladium-Catalyzed Mizoroki–Heck and
Allyl Cross-Coupling Reactions: To a mixture of aryl iodide
(0.5 mmol), Ag2CO3 (0.3 mmol), Pd(OAc)2 (25 μmol), and ligand
1b (25 μmol) in PhMe (3.0 mL) was added allyl ester (1.0 mmol) at
room temperature under an atmosphere of air. The mixture was
stirred at 90 °C. After 8 h, the reaction mixture was filtered though
Celite. The filtrate was concentrated under reduced pressure. To a
mixture of arylboronic acid (1.2 mmol) and K2CO3 (2.0 mmol) in
DMF (1.5 mL) and H2O (0.5 mL) was added the residue at room
temperature under an atmosphere of air. The mixture was stirred
at 50 °C. After 15 h, the mixture was diluted with ethyl acetate and
water. The organic layer was washed with brine, dried with MgSO4,
and concentrated under reduced pressure. The residue was purified
by silica gel chromatography (hexane or hexane/ethyl acetate, 20:1).
Consequently, the scope of the aryl iodides and aryl-
boronic acids was explored for 1,3-diarylpropenes under the
optimized reaction conditions by using allyl benzoate or
acetate. The use of iodobenzene with phenylboronic acid
led to good yields of product 4a with regioisomer 5a[7] from
intermediate 3 (4a/5a = 15:1; Table 3, Entry 1). The use of
iodobenzene with 4-substituted arylboronic acids led to
good yields of the corresponding unsymmetrical 1,3-diaryl-
propenes (Table 3, Entries 2–4). Moreover, 3,5-dimethyl-
phenylboronic acid, 2-tolylboronic acid, and 1-naphthylbor-
onic acid led to good yields (Table 3, Entries 5–7). We also
tested the reaction of various aryl iodides with phenylbor-
onic acid (Table 3, Entries 8–11). The corresponding un-
symmetrical 1,3-diarylpropenes gave moderate to good
Supporting Information (see footnote on the first page of this arti-
cle): Characterization data and copies of the NMR spectra of the
yields by using 4-substituted and 3-substituted aryl iodides. products.
Eur. J. Org. Chem. 2012, 678–680
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
679

T. Mino et al.
SHORT COMMUNICATION
[2]
a) Y. Uozumi, H. Danjo, T. Hayashi, J. Org. Chem. 1999, 64,
3384–3388; b) D. Bouyssi, V. Gerusz, G. Balme, Eur. J. Org.
Chem. 2002, 2445–2448; c) L. Botella, C. Nájera, J. Organomet.
Chem. 2002, 663, 46; d) G. Ortar, Tetrahedron Lett. 2003, 44,
4311–4314; e) C. Nájera, J. Gil-Moltó, S. Karlström, Adv.
Synth. Catal. 2004, 346, 1798–1811; f) V. Polackova, S. Toma,
C. O. Kappe, Tetrahedron 2007, 63, 8742–8745; g) H. Tsukam-
oto, T. Uchiyama, T. Suzuki, Y. Kondo, Org. Biomol. Chem.
2008, 6, 3005–3013.
T. Mino, K. Kajiwara, Y. Shirae, M. Sakamoto, T. Fujita, Syn-
lett 2008, 2711–2715.
a) D. Pan, A. Chen, Y. Su, W. Zhou, S. Li, W. Jia, J. Xiao, Q.
Liu, L. Zhang, N. Jiao, Angew. Chem. 2008, 120, 4807; Angew.
Chem. Int. Ed. 2008, 47, 4729–4732; b) D. Pan, N. Jiao, Synlett
2010, 1577–1588.
Acknowledgments
This work was partially supported by the Iodine Research Project,
Chiba University.
[1] a) B. Kramer, S. R. Waldvogel, Angew. Chem. 2004, 116, 2501;
Angew. Chem. Int. Ed. 2004, 43, 2446–2449; b) J. C. Anderson,
C. Headly, P. D. Stapleton, P. W. Taylor, Tetrahedron 2005, 61,
7703–7711; c) M. Belley, C. C. Chan, Y. Gareau, M. Gallant,
H. Juteau, K. Houde, N. Lachance, M. Labelle, N. Sawyer, N.
Tremblay, S. Limontage, M.-C. Carrière, D. Denis, G. M.
Greig, D. Slipez, R. Gordon, N. Chauret, C. Lo, R. J. Zam-
boni, K. M. Metters, Bioorg. Med. Chem. Lett. 2006, 16, 5639–
5642; d) C.-R. Su, Y.-C. Shen, P.-C. Kuo, Y.-L. Leu, A. G.
Damu, Y.-H. Wang, T.-S. Wu, Bioorg. Med. Chem. Lett. 2006,
16, 6155–6160; e) C. Ito, M. Itoigawa, T. Kanematsu, Y. Im-
amura, H. Tokuda, H. Nishino, H. Furukawa, Eur. J. Med.
Chem. 2007, 42, 902–909; f) S. Cheenpracha, C. Karalai, C.
Ponglimanont, A. Kanjana-Opas, J. Nat. Prod. 2009, 72, 1395–
1398; g) K. N. Mewett, S. P. Fernandez, A. K. Pasricha, A.
Pong, S. O. Devenish, D. E. Hibbs, M. Chebib, G. A. R. John-
ston, J. R. Hanrahan, Bioorg. Med. Chem. 2009, 17, 7156–7173;
h) K. Umehara, K. Nemoto, A. Matsushita, E. Terada, O.
Monthakantirat, W. De-Eknamkul, T. Miyase, T. Warashina,
M. Degawa, H. Noguchi, J. Nat. Prod. 2009, 72, 2163–2168; i)
F. M. Abdel Bar, M. A. Khanfar, A. Y. Elnagar, F. A. Badria,
A. M. Zaghloul, K. F. Ahmad, P. W. Sylverster, K. A. El Sayed,
Bioorg. Med. Chem. 2010, 18, 496–507.
[3]
[4]
[5] Y. Liu, B. Yao, C.-L. Deng, R.-Y. Tang, X.-G. Zhang, J.-H. Li,
Org. Lett. 2011, 13, 1126–1129.
[6] a) T. Mino, Y. Shirae, M. Sakamoto, T. Fujita, Synlett 2003,
882–884; b) T. Mino, Y. Shirae, M. Sakamoto, T. Fujita, J. Org.
Chem. 2005, 70, 2191–2194; c) T. Mino, Y. Shirae, Y. Sasai, M.
Sakamoto, T. Fujita, J. Org. Chem. 2006, 71, 6834–6839; d) T.
Mino, H. Shindo, T. Kaneda, T. Koizumi, Y. Kasashima, M.
Sakamoto, T. Fujita, Tetrahedron Lett. 2009, 50, 5358–5360.
[7] D. V. Moiseev, A. V. Gushchin, A. S. Shavirin, Y. A. Kursky,
V. A. Dodonov, J. Organomet. Chem. 2003, 667, 176–184.
Received: October 20, 2011
Published Online: December 20, 2011
680
www.eurjoc.org
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2012, 678–680