Ligand-free copper-catalyzed arylation of olefins by the mizoroki-heck reaction

Article abstract of DOI:10.1055/s-0030-1258338

A novel ligand-free copper-catalyzed Mizoroki-Heck cross-coupling reaction of various aryl iodides with olefins has been developed. Both the solvent and the base were found to have a fundamental influence on the efficiency of the transformation in the presence of 10 mol% Cu, with DMF and tetramethylammonium bromide (TMAB) being the optimal solvent and base, respectively. As a result, a set of the corresponding E-internal olefins were obtained selectively in moderate to good yields.

Full text of DOI:10.1055/s-0030-1258338

PAPER
213
Ligand-Free Copper-Catalyzed Arylation of Olefins by the Mizoroki–Heck
Reaction
C
opper-Catalyzed
o
A
rylation of
n
O
lefins byth
g
e
Mizoroki–Hec
k
P
Reaction eng,a Jiuxi Chen,*a Jinchang Ding,a,b Miaochang Liu,a Wenxia Gao,a Huayue Wu*a
a
College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou 325035, P. R. of China
Fax +86(577)88368280; E-mail: jiuxichen@gmail.com; E-mail: huayuewu@wzu.edu.cn
b
Wenzhou Vocational and Technical College, Wenzhou 325035, P. R. of China
Received 1 September 2010; revised 19 October 2010
tolerance, and scalability in large-scale synthetic proce-
dures.11 To the best of our knowledge, a general and effi-
cient ligand-free copper-catalyzed methodology for the
arylation of olefins by the Mizoroki–Heck reaction has
Abstract: A novel ligand-free copper-catalyzed Mizoroki–Heck
cross-coupling reaction of various aryl iodides with olefins has been
developed. Both the solvent and the base were found to have a fun-
damental influence on the efficiency of the transformation in the
presence of 10 mol% Cu2O, with DMF and tetramethylammonium not been developed to date. We herein report that ligand-
bromide (TMAB) being the optimal solvent and base, respectively.
free copper-catalyzed arylation of olefins by the Mizoroki–
As a result, a set of the corresponding E-internal olefins were ob-
tained selectively in moderate to good yields.
Heck reaction selectively provide E-internal olefin deriv-
atives with yields ranging from moderate to good.
Key words: ligand-free, copper-catalyzed, Mizoroki–Heck reac-
The model coupling reaction between iodobenzene (1a)
tion, cross-coupling, E-internal olefins
and n-butyl acrylate (2a) was conducted to screen the op-
timal reaction conditions, including bases, solvents, and
catalysts and the results are listed in Table 1. Initially,
The Mizoroki–Heck cross-coupling reaction1 is an impor-
considering that the catalyst always plays important roles
tant part of the synthetic chemist’s toolbox, and has been
in metal-catalyzed chemistry, the reaction conditions us-
applied to a huge variety of different substrates.2 One of
ing CuI as the catalyst, Et3N as the base, and DMF as the
the benefits of the Mizoroki–Heck reaction is its outstand-
solvent was adopted to study the synthesis of n-butyl (E)-
ing trans-selectivity. Traditionally, palladium-catalyzed
cinnamate (3aa). It was observed that the desired product
cross-coupling reactions have been proven to be extreme-
3aa was obtained in 19% yield (Table 1, entry 1). Encour-
ly powerful synthetic tools and their scope continues to in-
aged by this promising result, the reaction conditions were
crease year after year.3 Ligand-free palladium-catalyzed
further optimized including the effect of catalysts, bases,
Mizoroki–Heck reaction has been studied for the past few
and solvents.
years.4 Later, significant efforts have been made in order
to expand the scope of Heck-type coupling reaction by
Table 1 Screening Conditions for Heck reaction Between Iodoben-
employing various transition metal catalysts.5 However, it
is a considerable drawback that an expensive metal cata-
lyst (palladium, rhodium, iridium, ruthenium, etc.) is of-
ten lost at the end of the reaction. To achieve the
recyclability of the metal catalyst, Xiao6 and Wang7 used
room temperature ionic liquid immobilized catalysts as
recyclable reaction system. Nevertheless, ionic liquids,
especially imidazolium-based systems containing BF4 an-
ion, are toxic in nature because they liberate hazardous
HF, and their high cost and disposability make their utility
limited.8 Recently, Yun and co-workers have also re-
viewed environmental fate and toxicity of ionic liquids.9
Moreover, the use of cheaper metal as a catalyst for the
Heck-type reaction has been gaining attention more and
more.10 On the other hand, the operationally and econom-
ically more advantageous ligand-free Heck reaction cata-
lyst systems remain extremely rare.
zene and n-Butyl Acrylatea
O
I
O
catalyst
On-Bu
+
solvent, base
On-Bu
1a
2a
3aa
Entry
Catalyst
CuI
Base
Solvent
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMSO
Yield (%)b
1
2
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
K2CO3
K2CO3
19
21
79
85
<5
78
53
35
85
NR
CuBr
CuCl
Cu2O
CuBr2
3
4
5
6
Cu(OTf)2
CuCl2
Recently, the use of copper salts as catalysts for the reac-
tion has gained much prominence in organic synthesis due
to their economic attractiveness, good functional group
7
8
Cu(OAc)2
Cu2O
9
SYNTHESIS 2011, No. 2, pp 0213–0216
x
x
.
x
x
.2
0
1
0
10
Cu2O
Advanced online publication: 26.11.2010
DOI: 10.1055/s-0030-1258338; Art ID: F16010SS
© Georg Thieme Verlag Stuttgart · New York

214
Y. Peng et al.
PAPER
Table 1 Screening Conditions for Heck reaction Between Iodoben-
zene and n-Butyl Acrylatea (continued)
ied. Increasing the amount of Cu2O in the procedure
afforded similar yield (Table 1, entry 24). The result indi-
cated that the yield was decreased to some extent when 5
mol% Cu2O was used in the system (Table 1, entry 25).
O
I
O
catalyst
On-Bu
+
With optimal conditions in hand, the scope of copper-
catalyzed coupling of various aryl iodides with different
olefins was investigated and the results are summarized in
Table 2.
solvent, base
On-Bu
1a
Entry
11
2a
3aa
Catalyst
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
Base
Solvent
toluene
xylene
EtOH
Yield (%)b
68
Table 2 Ligand-Free Copper-Catalyzed Mizoroki–Heck Reactiona
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Cs2CO3
NaOAc
LiOH
R1
R2
12
NR
Cu2O (10 mol%)
Ar
ArI
+
TMAB , DMF
NRc
R1
R2
13
1
2
3
14
MeCN
NRc
Entry Aryl iodide 1
Olefin 2
Product Yield (%)b
15
1,4-dioxane 39
Ar
R1
H
H
H
H
H
H
H
H
H
H
H
R2
16
sulfolane
HMPA
PEG-400
DMF
19
15
42
<5
60
40
37
87
87e
72f
1
2
Ph (1a)
CO2n-Bu (2a) 3aa
87
82
86
83
77
79
86
92
77
86
71
65
80
87
79
84
83
83
90
89
91
82
65
76
71
17
2-MeOC6H4 (1b)
4-MeOC6H4 (1c)
4-HOC6H4 (1d)
2-HOC6H4 (1e)
2-O2NC6H4 (1f)
3-O2NC6H4 (1g)
4-O2NC6H4 (1h)
4-BrC6H4 (1i)
4-MeC6H4 (1j)
2-H2NC6H4 (1k)
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
3ba
3ca
3da
3ea
3fa
3ga
3ha
3ia
18
3
19
4
20
DMF
5
21
DMF
6
22
LiF
DMF
7
23
TMABd
TMAB
TMAB
DMF
8
24
DMF
9
25
DMF
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
3ja
3ka
3la
a All reactions were run with iodobenzene (1a; 0.30 mmol), n-butyl
acrylate (2a; 0.45 mmol), catalyst (10 mol%), base (0.60 mmol) and
4 Å MS (100 mg) in anhyd solvent (2 mL) at 120 °C for 30 h under
N2 atmosphere.
2,4,6-Me3C6H2 (1l) H
b Isolated yield. NR = no reaction.
1b
1c
1f
Me
CO2Me (2b) 3bb
c Under reflux.
d TMAB: tetramethylammonium bromide.
e With 20 mol% Cu2O.
Me
Me
H
2b
2b
3cb
3fb
f With 5 mol% Cu2O.
1a
1c
1f
CO2Me (2c) 3ac
First, a series of copper salts such as CuBr, CuCl, Cu2O,
CuBr2, Cu(OTf)2, CuCl2, and Cu(OAc)2 were examined
(Table 1, entries 2–8). To our delight, the coupling reac-
tion proceeded smoothly and generated the desired prod-
uct n-butyl (E)-cinnamate (3aa) in 85% yield,
representing one of the best results when 10 mol% of
Cu2O was used as catalyst with ligand-free than other cop-
per salts tested in DMF under nitrogen atmosphere
(Table 1, entry 4). Next, both base and solvent were test-
ed. Among all the bases screened, TMAB was superior to
some others such as Et3N, K2CO3, Cs2CO3, NaOAc,
LiOH, LiF, and TMAB (Table 1, entries 1, 9, 19–23). The
choice of solvent was also vital to the success of the cata-
H
2c
3cc
3fc
H
2c
1h
1a
1h
1j
H
2c
3hc
3ad
3hd
3jd
3ae
3ce
3je
H
CO2Et (2d)
H
2d
H
2d
1a
1c
1j
H
Ph (2e)
2e
H
lytic reaction. DMF appeared to be the best choice among 25
the common solvents such as DMSO, toluene, xylene,
ethanol, acetonitrile, 1,4-dioxane, sulfolane, HMPA, and
PEG-400 (Table 1, entries 9–18). In addition, the influ-
H
2e
a All reactions were run with aryl iodide 1 (0.30 mmol), olefin 2 (0.45
mmol), Cu2O (10 mol%), TMAB (0.60 mmol), and 4Å MS (100 mg)
in anhyd DMF (2 mL) at 120 °C for 30 h under N2 atmosphere.
ence of the amount of catalyst on the yields was also stud- b Isolated yield.
Synthesis 2011, No. 2, 213–216 © Thieme Stuttgart · New York

PAPER
Copper-Catalyzed Arylation of Olefins by the Mizoroki–Heck Reaction
215
As shown in Table 2, aryl iodides bearing either electron- Next, the Heck reaction of aryl bromides with n-butyl
donating or electron-withdrawing groups on the aromatic acrylate was also examined (Scheme 1). Unfortunately,
ring were investigated under the optimal conditions. In the present catalytic system was less effective when aryl
general, the substitution groups on the aromatic ring have bromides were used. The treatment of activated aryl bro-
no obvious effect on the yields. It is worth mentioning that mides 1n–p with n-butyl acrylate afforded the corre-
4-nitroiodobenzene (1h) reacted smoothly with 2a, 2c, 2d sponding products in lower yields. Attempt to couple 1-
to afford 3ha, 3hc and 3hd in 92%, 90%, and 91% yield, bromo-4-methylbenzene with n-butyl acrylate failed.
respectively (Table 2, entries 8, 19 and 21). Next, the
chemoselective reaction in the presence of unprotected re-
active functional groups, such as OH, NH2 also proved to
be successful. The corresponding products of 3da, 3ea,
Finally, the Heck reaction in a 2.2:1:0.01 molar ratio of n-
butyl acrylate to 4,4¢-diiodobiphenyl (1m) to Cu2O in
DMF was investigated (Scheme 2). As expected, the reac-
tion proceeded using the present protocol and the desired
and 3ka were obtained in good yields (Table 2, entries 4,
product 3ma was obtained in moderate yield.
5, and 11). Furthermore, the bromo group was left un-
In summary, a ligand-free copper-catalyzed Mizoroki–
Heck reaction has been developed for the selective syn-
thesis of E-internal olefins in moderate to good yields in
the presence of TMAB in DMF under nitrogen atmo-
touched in the coupling reaction of the substrate 1-bromo-
4-iodobenzene (1i) with 2a to give the product 3ia
(Table 2, entry 9).
This method was also successful with various olefins to
sphere. Although the reactivity of Cu2O under these con-
afford the corresponding E-internal olefins 3 in moderate
ditions is limited only to the coupling of aryl iodides and
to good yields under standard conditions. Compared to
olefins, this limitation is more than offset by the benefit of
acrylate 2a–d, styrene (2e) reacted with 1a, 1c, and 1j
using a ligand-free as well as inexpensive catalyst. Work
sluggishly compared to the olefins containing electron-
to probe the detailed mechanism and apply the reaction in
withdrawing groups and gave comparatively lower yields
organic synthesis is currently underway.
(Table 2, entries 23–25).
The steric effect in our system was then examined. A
All chemicals were either purchased or purified by standard tech-
monosubstitution on the ortho-, meta- and para-position
of aryl iodides (Table 2, entries 2–8) had some effects on
the yields of the reaction. For example, 2a reacted with
aryl iodides, such as 2-nitroiodobenzene (1f), 3-nitroiodo-
benzene (1g), and 4-nitroiodobenzene (1h) efficiently and
afforded 3fa, 3ga, and 3ha in 79%, 86%, and 92% yield,
respectively (Table 2, entries 6–8). Interestingly, using
the present protocol, the larger sterically hindered aryl io-
dide such as 2,4,6-trimethyliodobenzene (1l) also reacted
with 2a, providing 3la in 65% yield (Table 2, entry 12).
niques without special mention. The molecular sieve (4Å) powder
has to be activated before using. IR spectra were recorded on a
Bruker EQUINOX55 spectrometer. 1H NMR and 13C NMR spectra
were recorded on a Bruker 300 spectrometer or Bruker 500 spec-
trometer using CDCl3 as the solvent with TMS as an internal stan-
dard at r.t. Mass spectrometric analysis was performed by GC/MS
analysis (Shimadzu GC/MS-QP2010). Elemental analyses were
determined on a Carlo-Erba 1108 instrument. All reactions were
conducted using standard Schlenk techniques. Column chromato-
graphy was performed using EM Silica gel 60 (300–400 mesh).
O
O
Br
Cu2O (10 mol%)
R
+
Ar
On-Bu
On-Bu
TMAB , DMF, 120 °C
1
2a
3
1n R = 4-NO2
1o R = 4-Ac
1p R = 4-CHO
O
O
O
On-Bu
On-Bu
On-Bu
H
O2N
O
O
3na (3ha, 42%)
3oa (18%)
3pa (36%)
Scheme 1 Heck reaction of aryl bromides with n-butyl acrylate
I
I
1m
Cu2O (10 mmol%)
+
O
O
TMAB, DMF, 120 °C
64%
On-Bu
n-BuO
On-Bu
O
3ma
2a
Scheme 2 Heck reaction of 4,4¢-diiodobiphenyl with n-butyl acrylate
Synthesis 2011, No. 2, 213–216 © Thieme Stuttgart · New York

216
Y. Peng et al.
PAPER
E-Internal Olefins 3; General Procedure
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Me4NBr (0.6 mmol), Cu2O (10 mol%), and activated 4 Å MS pow-
der (100 mg) in anhyd DMF (2 mL) was placed in a Schlenk tube.
After stirring for 0.5 h at r.t., the solution was heated to 120 °C for
30 h under N2 atmosphere. After completion of the reaction (moni-
tored by TLC), the reaction mixture was then allowed to cool to r.t.
and added to H2O (20 mL) and extracted with CH2Cl2 (3 × 20 mL).
The combined organic layers were dried (MgSO4) and concentrated
in vacuo. The residue was purified by flash chromatography on sil-
ica gel with EtOAc–petroleum ether (bp 60–90 °C) to give the de-
sired product 3 (Table 2).
Methyl (E)-2-Methyl-3-(2-nitrophenyl)acrylate (3fb)
Yield: 79%; yellow oil.
IR (KBr): 2984, 1737, 1528, 1373, 1237, 1118, 1045, 939, 846, 789,
712 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.12–8.15 (m, 1 H, ArH), 7.90 (s,
1 H, C=CH), 7.63–7.68 (m, 1 H, ArH), 7.48–7.53 (m, 1 H, ArH),
7.35–7.37 (m, 1 H, ArH), 3.84 (s, 3 H, OCH3), 1.90 (s, 3 H, CH3).
13C NMR (125 MHz, CDCl3): d = 168.1 (C=O), 147.8 (ArNO2),
135.6 (C=CH), 133.2, 131.8, 131.3, 130.2, 129.0, 124.9, 52.2
(OCH3), 14.0.
MS (EI, 70 eV): m/z (%) = 221 (0.19, [M+]), 144 (25), 120 (100),
115 (32), 92 (52), 77 (28), 65 (21).
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Anal. Calcd for C20H21NO2: C, 59.73; H, 5.01. Found: C, 59.79; H,
4.96.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.
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Acknowledgment
We are grateful for financial support from the National Key Tech-
nology R & D Program (No. 2007BAI34B00), the National Natural
Science Foundation of China (No. 21072153), the Natural Science
Foundation of Zhejiang Province (No. Y4080107), and the Wen-
zhou Science & Technology Bureau Program (No. G20090076).
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Synthesis 2011, No. 2, 213–216 © Thieme Stuttgart · New York