An efficient and reusable PdCl2/TBAF system for the Heck reaction under ligand- and solvent-free conditions

Article abstract of DOI:10.3184/030823410X12706650130972

PdCl₂ combined with TBAF (n-Bu₄NF) were found to be efficient conditions for the Heck reactions. In the presence of PdCl₂ and TBAF, a variety of aryl halides were coupled with alkenes smoothly in moderate to good yields. Moreover, the PdCl₂/TBAF system could be recovered and reused several times in the reaction. Note that these reactions are conducted under solvent-free, ligand-free and reusable conditions.

Full text of DOI:10.3184/030823410X12706650130972

JOURNAL OF CHEMICAL RESEARCH 2010
RESEARCH PAPER 211
APRIL, 211–213
An efficient and reusable PdCl2/TBAF system for the Heck reaction under
ligand- and solvent-free conditions
Li-Ming Tao*, Qiang-Guo Li, Wen-Qi Liu, Yun Zhou and Ju-Feng Zhou
Department of Chemistry and Life Science, Xiangnan University, Chenzhou 423000, P. R. China
PdCl combined with TBAF (n-Bu4NF) were found to be efficient conditions for the Heck reactions. In the presence of
PdCl22 and TBAF, a variety of aryl halides were coupled with alkenes smoothly in moderate to good yields. Moreover,
the PdCl2/TBAF system could be recovered and reused several times in the reaction. Note that these reactions are
conducted under solvent-free, ligand-free and reusable conditions.
Keywords: PdCl2, TBAF, Heck coupling reaction
Table
1 Palladium-catalysed Heck reaction of 1-iodo-4-
Considerable interest in the synthesis of alkenes has been
received in the past few years because alkenes are extremely
useful intermediates in organic synthesis as well as important
units found in a tremendous range of natural products and
bioactive molecules. The palladium-catalysed Heck coupling
reaction, the coupling reactions between aryl halides and
alkenes, is one of the most commonly and straightforward
strategies to introduce new substituents into the alkene moiety
for the preparation of the new alkenes.1–29 The Heck reaction is
usually conducted under harsh reaction conditions (often at
110–150 °C). Recently, some room temperature Heck reac-
tions have been developed, but the specified ligands were
necessary to improve these reactions besides the requirement
of harmful organic solvents.1–4 Although some solvent-free
or/and ligand-free Heck procedures have been developed, the
promoters, such as phase-transfer catalysts, microwave irradi-
ation, ultrasonic irradiation, electrochemistry and others,
were still required.5–16 Wang and co-workers, for example,
have reported a ligand- and solvent-free Pd(OAc)2-catalysed
Heck reactions of aryl iodides and aryl bromides with olefins
recently, however, the reaction was conducted under the
microwave irradiation.17 Recently, we have reported that
TBAF (n-Bu4NF) was an effective basis for the solvent-free
palladium-catalysed Suzuki-Miyaura cross-coupling reactions
of aryl halides with arylboronic acids.18 During this process,
Pd nanoparticles.19–20 were generated in situ from PdCl2 with
TBAF, which displayed particular efficiency for the Suzuki–
Miyaura cross-coupling reaction. As a continuing interest in
the coupling reaction, we decided to examine the effect of the
PdCl2/TBAF system on the Heck reaction. We found that PdCl2
combined with TBAF displayed highly efficiency for the Heck
reaction without the aid of any ligands and solvents under mild
conditions (Scheme 1).21–23 Moreover, the PdCl2 immobilised
TBAF system in the Heck reaction process could be recovered
and reused several times without loss of catalytic activity.
As listed in Table 1, we initially examined the Heck reaction
between 1-iodo-4-methoxybenzene (1a) and tert-butyl acry-
late (2a) under ligand- and solvent-free conditions to optimise
the reaction conditions. A number of the Pd catalysts, such as
PdCl2, PdBr2, PdI , Pd(OAc)2, PdCl2(MeCN)2, PdCl2(PPh3)2
and PdCl2/PPh we2re tested (entries 1–7), The screening results
showed that th3e best results were obtained using PdCl2 as the
catalyst. While the commonly used Pd(OAc)2 catalyst in the
methoxybenzene (1a) with tert-butyl acrylate (2a)a
Entry [Pd]
Base
Recycle Time/h
no.
Isolated
Yield/%b
1
2
3
4
5
6
7
8
PdCl2
PdBr2
PdI
TBAF
TBAF
TBAF
TBAF
4
10
10
24
4
96
74
83
64
93
86
81
86
81
80
95
96
98
100
100
31
14
16
0
Pd(2OAc)2
PdCl (MeCN)2 TBAF
PdCl2(PPh )2
PdCl2/PPh33
PdCl22
TBAF
TBAF
TBAF
8
8
4
1
2
4
4
9c
PdCl2
TBAF
1
1
1
1
1
2
3
10cd
11e
12
13
14
PdCl
PdCl2
PdCl2
PdCl22
0
TBAF
TBAF
KF
Cs2CO3
TBAF
12
24
8
8
24
a Under otherwise indicated, the reaction conditions were as
follows: 1a (0.5 mmol), 2a (0.75 mmol), [Pd] (3 mol %), base
(3 equiv) at 40 °C under argon atmosphere. b Isolated yield. c At
60 °C. d PdCl2 (1 mol%). e PdCl2 (0.1 mol%) at 80 °C.
Heck cross-coupling reaction gave only 64% yield of the target
product 3 after 24 h at 40 °C (entry 4), PdCl2 provided a 96%
yield of 3 in 4 h without the aid of any ligands (entry 1). Reuse
of the PdCl /TBAF system was subsequently examined at
40 °C. After2the initial experimentation, the reaction mixture
was extracted with cyclohexane, and the PdCl /TBAF system
were then solidified (evaporated and cooled)2 and subjected
to a second run of the coupling by charging with the same
substrates and base (1a, 2a and 1 equiv of TBAF). However,
the activity of the system was reduced to some extent in the
reused processes (entry 8). Gratifyingly, the reused processes
could be preformed successfully providing the identical results
in four runs when the temperature was enhanced to 60 °C
(entry 9). It was interesting to observe that quantitative yield
was still achieved from the reaction of substrate 1a with 2a and
1 mol% of Pd at 60 °C after prolonging the reaction time (entry
10). However, only a 31% yield of 3 was isolated in the pres-
ence of 0.1 mol% of PdCl2 even at 80 °C (entry 11). Finally,
two other inorganic bases, KF and Cs2CO , were evaluated,
and they both were found to be ineffectiv3e for the reaction
(entries 12 and 13). Note that no reaction is observed without
Pd catalysts (entry 14).
Scheme 1
We subsequently examined the scope and limitations of the
protocol based on both aryl halides and alkenes. As shown
* Correspondent. E-mail: taoliming2005@yahoo.com.cn

212 JOURNAL OF CHEMICAL RESEARCH 2010
Table 2 PdCl2-Catalysed Heck reaction of aryl halides (1) with
alkenes (2) in the presence of TBAFa
(vi) as medium (TBAF⋅nH2O is ropy liquid ) to improve the
reaction.
In summary, a simple and reusable PdCl2/TBAF system has
been developed for the Heck coupling reactions under solvent-
and ligand-free conditions. Based on the present results,
several interesting features are apparent: (1) PdCl2 combined
with TABF showed highly efficiency for the Heck coupling
reactions. (2) The present protocol is mild, efficient, highly
inexpensive and general. (3) The PdCl2 immobilised TBAF
system could be recovered and reused several times without
loss of any activity. (4) Importantly, these reactions were
conducted under solvent- and ligand-free conditions.
Entry Aryl halide
Alkene
Recycle Time/
Yield/
b
no.
h
%
1
R1=4-CH O
X=I (1a) 3
(1a)
R2=COOnBu
(2b)
6
88 (4)
2
3
R2=Ph (2c)
R2=COOtBu
(2a)
6
3
63 (5)
100 (6)
R1=4-NO2
X=I (1b)
(1b)
4
5
(2c)
(2a)
12
3
100 (7)
100 (8)
R1=4-CH CO
X=I (1c) 3
R1=H
Experimental
NMR spectroscopy was performed on an INOVA-400 (Varian) or a
Bruck-300 (Bruck) spectrometer operating at 400 MHz (1H NMR)
and 100 MHz (13C NMR) or 300 MHz (1H NMR) and 75 MHz
(13C NMR). TMS (tetramethylsilane) was used an internal standard
and CDCl3 was used as the solvent.
6
(2a)
1
2
3
3
4
3
86 (9)
84 (9)c
90 (9)c
100 (10)
X=I (1d)
7
8
R1=4-Me
X=I (1e)
R1=2-Me
X=I (1f)
(1f)
(2a)
(2a)
3
90 (11)
Typical experimental procedure for the palladium-catalysed Heck
coupling reaction
9
10
(2b)
(2a)
12
18
80 (12)
trace (3)
A mixture of aryl halide 1 (0.5 mmol), alkene 2 (0.75 mmol), PdCl
(3 mol %), and TBAF⋅nH2O (3 equiv) was stirred in a Schlenk tube a2t
the indicated temperature (40 to 110 °C) for the indicated time until
complete consumption of starting material as monitored by TLC.
After the reaction was finished, ethyl acetate was poured into the
mixture, then washed with brine, extracted with diethyl ether, dried
by anhydrous Na2SO4 and evaporated under vacuum. The residue
was purified by flash column chromatography (hexane/ethyl acetate)
to afford the desired coupled product 3–13.
R1=4-CH3O
X=Br (1g)
(1g)
11c
12c
(2a)
(2a)
18
9
40 (3)
81 (6)
R1=4-NO2
X=Br (1h)
R1=4-CH3CO
X=Br (1i)
R1=H
13c
14c
(2a)
(2a)
6
98 (8)
77 (9)
18
X=Br (1j)
(1j)
15c
16c
(2c)
(2a)
18
14
77 (13)
80 (10)
R1=4-Me
X=Br(1k)
R1=2-Me
X=Br(1L)
R1=4-NO2
X=Cl (1m)
R1=H
Typical experimental procedure for the reusable palladium-catalysed
Heck cross-coupling reaction
17c
18c
19c
(2a)
(2a)
(2a)
15
15
24
65 (11)
70 (6)
25 (9)
A mixture of aryl halide 1 (0.5 mmol), alkene 2 (0.75 mmol), PdCl
(3 mol %), and TBAF⋅nH O (3 equiv) was stirred in a Schlenk tube a2t
the indicated temperature2(40–60 °C) for the indicated time until com-
plete consumption of starting material as monitored by TLC. After the
reaction was finished, the product was extracted by cyclhexane (1m ×
8). The extraction was then evaporated under vacuum to give the resi-
due, which was purified by flash column chromatography (hexane–
ethyl acetate) to afford the desired coupled product. After initial
experimentation, the residue (the PdCl2/TBAF system) was then
solidified (evaporated in vacuo and cooled) and subjected to a second
run of the Heck reaction by charging with the same substrates
(aryl halide, alkene and 1 equiv of TBAF).
X=Cl (1n)
a Reaction conditions: 1 (0.5 mmol), 2 (0.75 mmol), PdCl (3 mol
%) and TBAF⋅nH2O (3 equiv) at 40 °C under argon atmo2sphere.
b Isolated yield. c At 110 °C.
in Table 2, the Heck reaction of substrate 1a with the other
alkenes 2b or 2c, PdCl2 and TBAF were also conducted
smoothly at 40 °C in good yields (entries 1 and 2). Under the
same conditions, the other aryl iodides 1b–f underwent the
reaction with alkenes efficiently in good to excellent yields
(entries 3–9). We next evaluated the reactions of aryl bromides
with alkenes (entries 10–17). Unfortunately, a trace amount
of the target product 3 was observed from the reaction of
the deactivated bromide 1g with 2a at 40 °C (entry 10). Thus,
we decided to perform the reaction at a higher reaction tem-
perature, the yield of 3 was enhanced to 40% when the reaction
was conducted at 110 °C (entry 11). Subsequently, the Heck
reactions of the other bromides 1h–l were then carried out at
110 °C, and moderate to good yields were obtained (entries
12–17). The activated chloride 1m also underwent the reaction
with 2a smoothly to give the desired product 6 in a 70% yield
under the same conditions (entry 18), but a rather low yield
was isolated from the coupling of the less active chloride 1n
(entry 19).
tert-Butyl (E)-3-(4-methoxyphenyl)acrylate (3)24–27
: Colourless
liquid. 1H NMR (300 MHz, CDCl3): δ: 7.55 (d, J = 15.9 Hz, 1H), 7.44
(d, J = 8.7 Hz, 2H), 6.89 (d, J = 9.0, 2H), 6.24 (d, J=15.9, 1H), 3.83 (s,
3H), 1.53 (s, 9H). 13C NMR (75 MHz, CDCl3) δ: 161.1, 143.2, 129.5,
127.4, 118.2, 117.7, 114.2, 80.2, 55.3, 28.2.
Butyl (E)-3-(4-methoxyphenyl)acrylate (4)24,26–27: Colourless liquid.
1H NMR (300 MHz, CDCl3) δ: 7.64 (d, J = 16.0 Hz, 1H), 7.47 (d, J =
8.8 Hz, 2H), 6.89 (d, J = 8.8 Hz, 2H), 6.31 (d, J = 16.0 Hz, 1H), 4.20
(d, J = 6.6 Hz, 2H), 3.83 (s, 3H), 1.73–1.64 (m, 2H), 1.50–1.37 (m,
2H), 0.96 (t, J = 7.2 Hz, 3H). 13C NMR (75 MHz, CDCl ): δ 167.4,
161.3, 144.2, 129.6, 127.2, 115.7, 114.2, 64.2, 55.3, 30.8, 319.2, 13.7.
(E)-1-(4-Methoxystyryl)benzene (5)24–25: White solid. m.p. 131–
134 °C (Lit..[24] 132 °C). 1H NMR (400 MHz, CDCl ) δ: 7.49–7.44 (m,
4H), 7.34 (t, J = 8.0 Hz, 2H), 7.24-7.23 (m, 1H), 7.032 (dd, J = 16.8 Hz,
16.4 Hz, 2H), 6.89 (d, J = 8.8 Hz, 2H), 3.82 (s, 3H). 13C NMR
(75 MHz, CDCl3) δ: 160.0, 137.7, 130.2, 128.6, 128.2, 127.7, 127.2,
126.6, 126.2, 114.1, 55.3.
1
tert-Butyl (E)-3-(4-nitrophenyl)acrylate (6)27: Pale-yellow oil. H
NMR (300 MHz, CDCl3) δ: 8.23 (d, J = 8.8 Hz, 2H), 7.67–7.58 (m,
3H), 6.49 (d, J = 16.0 Hz, 1H), 1.55 (s, 9H). 13C NMR (75 MHz,
CDCl3) δ: 165.2, 148.3, 140.9, 140.6, 128.5, 124.5, 124.1, 81.3, 28.1.
(E)-2-(4-Nitrophenyl)styrene (7)24,28–29: Pale-yellow solid, m.p.
86–88 °C (lit.[24] 88 °C). 1H NMR (300 MHz, CDCl3) δ: 8.22 (d,
J = 8.8 Hz, 2H), 7.63 (d, J = 8.8 Hz, 2H), 7.55 (d, J = 8.4 Hz, 2H),
7.43–7.11 (m, 5H); 13C NMR (75 MHz, CDCl3) δ: 146.8, 143.8, 136.2,
133.3, 128.9, 128.8, 127.0, 126.8, 126.3, 124.1.
Based on the above results and the previously proposed
mechanism, we deduced that several roles of TBAF may play
in the reaction:3–4,18 (i) conversion of PdCl to Pd nanoparticles;
(ii) activation of the active Pd(0) nanop2articles species; (iii)
stabilisation of the low coordination Pd(0) nanoparticles spe-
cies; (iv) as a basis to improve the reaction; (v) phase-transfer
catalyst for the substrate/catalysis/base/product phases; and
tert-Butyl (E)-3-(4-acetylphenyl)acrylate (8)24: Colourless liquid.
1H NMR (300 MHz, CDCl3) δ: 7.95 (d, J = 8.4 Hz, 2H), 7.63–7.58

JOURNAL OF CHEMICAL RESEARCH 2010 213
References
(m, 3H), 6.46 (d, J = 15.8 Hz, 1H), 2.61 (s, 3H), 1.54 (s, 9H). 13C
NMR (75 MHz, CDCl3) δ: 197.3, 165.7, 141.9, 139.0, 137.8, 128.8,
128.0, 122.8, 80.9, 28.1, 26.6.
1
S.S. Pawar, D.V. Dekhane, M.S. Shingare and S.N. Thore, Tetrahedron
Lett., 2008, 49, 4252.
M. Cypryk, P. Pospiech, K. Strzelec, K.Wąsikowska and J.W. Sobczak,
J. Mol. Catal. A: Chem., 2010, 319, 30.
1
tert-Butyl (E)-cinnamate (9)26: Colourless liquid. H NMR (400
2
MHz, CDCl3) δ: 7.59 (d, J = 16.4 Hz, 1H), 7.52–7.50 (m, 2H),
7.38–7.36 (m, 3H), 6.37 (d, J = 16.0 Hz, 1H), 1.54 (s, 9H). 13C NMR
(100 MHz, CDCl3) δ: 166.4, 143.6, 134.6, 130.0, 128.8, 127.9, 120.1,
80.5, 28.2.
3
4
5
6
7
K. Koehler, S.S. Proeckl and W. Kleist, Curr. Org. Chem., 2006, 10, 1585.
Y.X. Xie, J.H. Li and D.L. Yin, Chin. J. Org. Chem., 2006, 26, 1155.
V. Polshettiwar and R.S. Varma, Acc. Chem. Res., 2008, 41, 629.
D. Bogdal and A. Loupy, Org. Process Res. Dev., 2008, 12, 710.
Y. Wan, H. Wang, Q. Zhao, M. Klingstedt, O. Terasaki and D. Zhao, J. Am.
Chem. Soc., 2009, 131, 4541.
tert-Butyl (E)-3-(4-methylphenyl)acrylate (10)24–27
: Colourless
liquid. 1H NMR (400 MHz, CDCl3) δ: 7.57 (d, J = 16.0 Hz, 1H), 7.41
(d, J = 7.6 Hz, 2H), 7.18 (t, J = 8.0, 2H), 6.33 (d, J = 16.0 Hz, 1H),
2.37 (s, 3H), 1.53 (s, 9H). 13C NMR (100 MHz, CDCl3) δ: 166.4,
143.4, 140.1, 131.6, 129.4, 127.8, 118.8, 80.2 28.0, 21.3.
8
9
V. Polshettiwar and A. Molnar, Tetrahedron, 2007, 63, 6949.
F. Chen, K. Toh, S. Shen and G.J. Gan, Catal. Commun., 2007, 8, 405.
10 D.D. Pathak, H. Maheswaran, K.L. Prasanth and M.L. Kantam, Synlett,
2007, 5, 757.
11 S. Haneda, C. Ueba, K. Eda and M. Hayashi, Adv. Synth. Catal., 2007, 349,
tert-Butyl (E)-3-(2-methylphenyl)acrylate (11)24–27
: Colourless
liquid. 1H NMR (400 MHz, CDCl3) δ: 7.89 (d, J = 16.0 Hz, 1H), 7.55
(d, J = 9.2 Hz, 1H), 7.26 (t, J = 8.4, 1H), 7.20 (t, J = 7.6, 2H), 6.30 (d,
J = 16.0 Hz, 1H), 2.43 (s, 3H), 1.54 (s, 9H). 13C NMR (100 MHz,
CDCl3) δ: 166.3, 141.0, 137.3, 133.3, 130.5, 129.6, 126.1 (2C), 120.8,
80.3, 28.0, 19.6.
833.
12 D. Dallinger and C.O. Kappe, Chem. Rev., 2007, 107, 2563.
13 L. Huang, Z. Wang, T.P. Ang, J. Tan and P.K. Wong, Catal. Lett., 2006, 112,
219.
14 C. Amatore, B. Godin, A. Jutand and F. Lemaitre, Chem. Eur. J., 2007, 13,
2002.
n-Butyl (E)-3-(2-methylphenyl)acrylate (12)24–27: Colourless liquid.
1H NMR (400 MHz, CDCl3) δ: 7.97 (d, J = 15.6 Hz, 1H), 7.54
(d, J = 7.6 Hz, 1H), 7.28–7.24 (m, 1H0, 7.19 (t, J = 7.6, 1H), 6.36 (d,
J = 16.4, 1H), 4.21 (t, J = 6.8 Hz, 2H), 2.43 (s, 3H), 1.71–1.67 (m,
2H), 1.47–1.41 (m, 2H), 0.97 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz,
CDCl3) δ: 167.1, 142.2, 137.5, 133.4, 130.7, 129.9, 126.3 (2C), 119.2,
64.4, 30.7, 19.7, 19.2, 13.7.
15 B. Karimi and D. Enders, Org. Lett., 2006, 8, 1237.
16 N. Iranpoor, H. Firouzabadi and R. Azadi, Eur. J. Org. Chem., 2007, 13,
2197.
17 L.H. Du and Y.G. Wang, Synth. Commun., 2007, 37, 217.
18 L.M. Tao, Y.X. Xie, C.L. Deng and J.H. Li, Chin. J. Chem., 2009, 27,
1365.
19 J.J. Davis, C.B. Bagshaw, B.K.L. usuttil, Y. Hanyu and K.S. Coleman,
J. Am. Chem. Soc., 2006, 128, 14135.
20 D. Astruc, Inorg. Chem., 2007, 46, 1884.
(E)-1,2-Diphenylethene (13)27–28: White solid. m.p. 122–125 °C
(lit.27 124 °C). 1H NMR (300 MHz, CDCl3) δ: 7.51 (d, J = 8.4 Hz, 4H),
7.35 (t, J = 7.2 Hz, 4H), 7.27 (t, J = 6.3 Hz, 2H), 7.11 (s, 2H). 13C
NMR (75 MHz, CDCl3) δ: 137.3, 128.7, 127.6, 126.5.
21 H.J. Li and L. Wang, Eur. J. Org. Chem., 2006, 22, 5099.
22 M.L. Kantam, M. Roy, S. Roy, M.S. Subhas, B. Sreedhar and B.M.
Choudary, Synlett., 2006, 14, 2266.
23 H.X. Zhang, C.C. Luo, T. Jin and X.P. Luo, Synth. Commun., 2007, 37,
191.
We thank the National Natural Science Foundation of China
(No 20973145) for financial support.
24 R. Wang, B. Twamley and J.M. Shreeve, J. Org. Chem., 2006, 71, 426.
25 Cahiez, O. Gager and F. Lecomte, Org. Lett., 2008, 10, 5255.
26 D. Yang, Y.C. Chen and N.Y. Zhu, Org. Lett., 2004, 6, 1577.
27 D. Das, G.K. Rao and A.K. Singh, Organometallics, 2009, 28, 6054.
28 F. Luo, C. Pan, W. Wang, Z. Ye and J. Cheng, Tetrahedron, 2010, 66,
1399.
Received 28 December 2009; accepted 16 March 2010
Paper 090931 doi: 10.3184/030823410X12706650130972
Published online: 28 April 2010
29 K. Selvakumar, A. Zapf and M. Beller, Org. Lett., 2002, 4, 3031.

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