Atom-efficient, palladium-catalyzed stille coupling reactions of tetraphenylstannane with aryl iodides or aryl bromides in polyethylene glycol 400 (PEG-400)

Article abstract of DOI:10.1002/adsc.200800754

The Stille coupling of tetraphenylstannane with aryl iodides or aryl bromides using the bis(triphenylphosphine)palladium dichloride/sodium acetate/polyethylene glycol 400 [PdCl₂(PPh₃) ₂/NaOAc/ PEG-400] catalytic system at

Full text of DOI:10.1002/adsc.200800754

FULL PAPERS
DOI: 10.1002/adsc.200800754
Atom-Efficient, Palladium-Catalyzed Stille Coupling Reactions
of Tetraphenylstannane with Aryl Iodides or Aryl Bromides in
Polyethylene Glycol 400 (PEG-400)
Wen-Jun Zhou,a Ke-Hu Wang,a and Jin-Xian Wanga,b,*
a
Institute of Chemistry, Department of Chemistry, Northwest Normal University, 967 An Ning Road (E.), Lanzhou
730070, Peopleꢀs Republic of China
Fax : (+86)-931-776-8159; e-mail: Wangjx@nwnu.edu.cn
State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, Peopleꢀs Republic of China
b
Received: December 4, 2008; Revised: April 2, 2009; Published online: June 3, 2009
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.200800754.
Abstract: The Stille coupling of tetraphenylstannane mides coupled effectively with 1 equivalent of tetra-
with aryl iodides or aryl bromides using the bis(tri- phenylstannane to furnish 4 equivalents of the corre-
phenylphosphine)palladium dichloride/sodium ace- sponding functionalized biaryls in high yields.
tate/polyethylene glycol 400 [PdCl2ACHTUNTRGENUNG(PPh3)2/NaOAc/
PEG-400] catalytic system at 1008C has been devel- Keywords: aryl bromides; aryl iodides; atom efficien-
oped. The reactions were carried out in an atom-effi- cy; polyethylene glycol 400 (PEG-400); Stille cou-
cient way, as 4 equivalents of aryl iodides or aryl bro- pling; tetraphenylstannane
Introduction
opment of atom-efficient organometallic reagents to
react with more than 1 equivalent of the electrophilic
The palladium-catalyzed cross-coupling of organo- coupling reagents in order to reduce the organometal-
stannanes with organic halides and triflates, known as lic loadings for industrial scale preparations is
Stille reaction, is an important, powerful, and versa- needed.[7] In the course of our continuing investiga-
tile tool for the formation of carbon-carbon bonds.[1] tions, we found that tetraphenylstannane, unlike with
This coupling reaction has been widely applied in or- other organotin reagents, can react with 4 equivalents
ganic synthesis[2] since a variety of functionalities can of electrophilic reagents, which has attracted our at-
be tolerated in either partner. The yields of coupled tention as a viable atom-efficient organometallic cou-
À
products are often high, and the organotin reagents pling partner for C C bond formation. Hence, to
can be readily synthesized, purified, and stored. The expand the scope and reactivity of tetraphenylstan-
importance of this method led to the development of nane, the development of new and efficient catalytic
numerous new catalytic protocols.[3] However, most protocols is in demand.
of these reactions are carried out in organic solvents
Recently, polyethylene glycol (PEG) was found to
associated with the protection of a nitrogen atmos- be an interesting solvent system.[8] PEG as an envi-
phere to improve the yields. In addition, the lack of ronmentally benign protocol proved to have many
atom efficiency is another drawback of these meth- particular applications, such as in coupling,[9] substitu-
ods.
tion,[10] oxidation,[11] addition,[12] and reduction reac-
Since tetraphenylstannane is known to be an impor- tions.[13] To the best of our knowledge, the palladium-
tant organometallic reagent, it is a potentially useful catalyzed atom-efficienct Stille cross-coupling reac-
candidate for Stille cross-coupling reactions. Up to tion of tetraphenylstannane in PEG-400 has not so far
the present, a few reactions involving tetraphenylstan- been reported. In our search for developing new pro-
[4–6]
nane for C C bond formation have been reported.
cesses for cross-coupling reactions,[14] in this paper, we
À
Furthermore, the known reactions of tetraphenylstan- wish to report a highly efficient palladium-catalyzed
nane with electrophilic reagents always suffer from protocol for an atom-efficient coupling of tetraphe-
disadvantages such as atom inefficiency, long reaction nylstannane with aryl iodides or aryl bromides in
times, and harsh reaction conditions. Thus, the devel- PEG-400. The methodology reported here has the fol-
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Adv. Synth. Catal. 2009, 351, 1378 – 1382

Atom-Efficient, Palladium-Catalyzed Stille Coupling Reactions of Tetraphenylstannane
FULL PAPERS
lowing advantages: atom economy, short reaction entries 7 and 8). As shown in Table 1, the reactions
time, and broad substrate scope.
carried out in the presence of different bases in PEG-
400 revealed NaOAc as a suitable base giving a 94%
cross-coupling yield (Table 1, entry 9) and 3.5 equiva-
lents of base are necessary to obtain a high yield of
the cross-coupling product (Table 1, entries 11–14).
Results and Discussion
As a starting point for the development of the atom- Furthermore, lowering or elevating the reaction tem-
economic reaction in PEG-400, we initially studied perature had no positive effect, and 1008C is the best
the Stille coupling of bromobenzene with tetraphenyl- temperature for the Stille cross-coupling reaction
stannane for optimizing the reaction conditions, and (Table 1, entries 15–21). Control reactions carried out
the effects of base, reaction time, temperature on the without base delivered only 38% cross-coupling con-
yield of the coupling reaction are summarized in version indicating that the role of the base is to acti-
Table 1.
vate tetraphenylstannane for the cross-coupling reac-
It was found that bases such as K2CO3, Na2CO3, tion (Table 1, entry 22). From this study, it was clear
NaOH, and KOH were ineffective in providing the that NaOAc (3.5 equiv.) in PEG-400 with PdCl2
corresponding cross-coupling product (Table 1, en-
ACHTUNGTREN(UNNG PPh3)2 (0.01 equiv.) at 1008C are the optimized con-
tries 1–4). However, an increase in the cross-coupling ditions for high cross-coupling conversion.
reactivity was observed with NaHCO3 or KF/Al2O3
In previous reports on the coupling reaction of aryl
(mol ratio of 1:1) under similar conditions (Table 1, halides with tetraphenylstannane,[4–6] usually only one
entries 5 and 6). A comparative reactivity study of or two phenyl groups could be transferred. In order
bases in the reaction showed that KF or K3PO4 to explore the possibility for further efficient transfer
proved to be more effective for this coupling (Table 1, of the phenyl groups in tetraphenylstannane, we ex-
amined the reaction of bromobenzene with 0.25, 0.28
or 0.33 equiv. of tetraphenylstannane again under the
optimized conditions. As summarized in Table 2,
Table 1. Optimized conditions for the coupling of bromo-
benzene with Ph4Sn.[a]
either increasing the reaction temperature or prolong-
ing the reaction time could not promote the reaction
when 0.25 equiv. of tetraphenylstannane was used,
and we only detected a trace of bromobenzene by
TLC (Table 2, entries 1 and 2). A satisfactory result
could be achieved when the reaction was performed
at 1008C for 1 h with 0.28 equiv. of tetraphenylstan-
nane (Table 2, entries 3 and 4). There is no significant
difference in yield when 0.33 equiv. of tetraphenyl-
stannane were reacted with bromobenzene (Table 2,
entry 5). These results indicate that all four phenyl
groups of tetraphenylstannane could be efficiently uti-
lized in the Stille cross-coupling reactions.
Entry
Base (mmol)
T [oC]
t [h]
Yield [%][b]
1
2
3
4
5
6
7
8
K2CO3 (3.5)
Na2CO3 (3.5)
KOH (3.5)
NaOH (3.5)
NaHCO3 (3.5)
KF/Al2O3 (3.5)
KF (3.5)
K3PO4 (3.5)
NaOAc (3.5)
Et3N (3.5)
NaOAc (4.0)
NaOAc (3.0)
NaOAc (2.5)
NaOAc (2.0)
NaOAc (3.5)
NaOAc (3.5)
NaOAc (3.5)
NaOAc (3.5)
NaOAc (3.5)
NaOAc (3.5)
NaOAc (3.5)
none
100
100
100
100
100
100
100
100
100
100
100
100
100
100
80
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
24
45
36
40
32
63
56
72
79
94
10
90
91
90
83
85
90
92
92
88
89
89
38[c]
Subsequently, we investigated the cross-coupling re-
action of various aryl bromides with tetraphenylstan-
nane, and the results are given in Table 3.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
Table 2. Reaction of bromobenzene with Ph4Sn.[a]
Entry Amount of Ph4Sn [equiv. T [oC] t [h] Yield [%][b]
to bromobenzene]
90
95
1
2
3
4
5
0.25
0.25
0.28
0.28
0.33
120
100
100
100
100
1
6
87
88
105
110
115
120
100
0.5 86
1
1
94
94
[a]
Reactions were carried out using bromobenzene
(1.0 mmol), Ph4Sn as indicated in the table, NaOAc
[a]
Reaction conditions: bromobenzene (1.0 mmol), Ph4Sn
(0.28 mmol), PEG-400 (3 mL), base, PdCl2A(PPh3)2
C
(3.5 mmol), and PdACHTUNGTERNNU(G PPh3)2Cl2 (0.01 mmol) in PEG-400
(0.01 mmol), stirring for the appropriate temperature.
Isolated yield based on bromobenzene.
Homocoupling product was obtained.
(3 mL), stirring at the appropriate temperature for the
indicated time.
Isolated yield based on bromobenzene.
[b]
[c]
[b]
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Table 3. Pd(II)-catalyzed cross coupling of aryl bromides (1) with Ph4Sn (2).[a]
Entry
Ar-Br
Products[b]
t [h]
1
Yield [%][c]
1
2
3
4
5
6
7
8
94
95
85
93
93
94
95
75
1
1
1
1
1
1
3
9
1
1
90
93
10
11
12
1
1
1
88
75
92
13
[a]
Reaction conditions: 1 (1.0 mmol), 2 (0.28 mmol), PEG-400 (3 mL), NaOAc (3.5 mmol), PdACHTUNGTERN(UNGN PPh3)2Cl2 (0.01 mmol), stirring
at 1008C for the appropriate time.
All products were characterized by melting point, IR, H NMR and MS.
The yields are based on 1.
[b]
[c]
1
The reactivity and substrate scope provided by the sponding coupling products in excellent yields
aryl bromides under the present conditions are excel- (Table 2, entries 1, 9 and 10). Similarly, the reactivity
lent giving good to high yields of the cross-coupled of heterocyclic bromides also provided the cross cou-
products. As shown in Table 3, the cross-coupling re- pling products in high yields (Table 2, entries 11–13).
action of various functionalized aryl bromides oc- Further study revealed that cross-coupling reactions
curred efficiently with tetraphenylstannane. For ex- of electron-rich functional groups such as methyl, me-
ample, the reaction of a variety of functionalized elec- thoxyl, ethoxyl, amino, and acetamido groups in aryl
tron-poor aryl bromides reacted very well with tetra- bromides at the para-position furnished moderate
phenylstannane leading to good to high yields of the yields of cross-coupled biphenyls: 48%, 45%, 41%,
functionalized biaryls (Table 2, entries 2–8). Further, 45% and 39%, respectively. Notably, the aryl bro-
bromobenzene, 1-bromonaphthalene and 2-bromo- mides with electron-withdrawing groups studied
naphthalene were remarkable, furnishing the corre- showed good to high cross-coupling reactivity with
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Atom-Efficient, Palladium-Catalyzed Stille Coupling Reactions of Tetraphenylstannane
FULL PAPERS
tetraphenylstannane. On the other hand, electron-rich mides using a catalytic system that employs PdCl2
substrates, which are otherwise known to show poor (PPh3)2 along with NaOAc as base in PEG-400. The
reactivity in this type of reaction showed moderate re- high atom-efficiency of tetraphenylstannane as dem-
activity. onstrated by reacting with 4 equivalents of electro-
AHCTUNGTRENNUNG
The reactions of substituted aryl iodides with tetra- philic coupling partners further defines its breadth
phenylstannane were found to be faster and efficient and versatility, which is not known with similar re-
in furnishing good to high yields of the cross-coupled agents. Thus, the present study and the established
biphenyls in a short period of 0.5 h. The cross-cou- new palladium protocol is expected to exploit the ad-
pling reactivity with aryl iodides was found to be effi- vantages associated with tetraphenylstannane as an
cient even with a lower temperature when compared atom-efficient reagent for application in organic syn-
to the corresponding reactivity with aryl bromides. As thesis.
shown in Table 4, the reactions of electron-deficient
aryl iodides afforded high yields of cross-coupling
products (Table 4, entries 1–4). The reaction of 1-io- Experimental Section
donaphthalene gave 93% of the corresponding cou-
pled product (Table 4, entry 5). The reactions of elec- General Procedure
tron-rich substituted phenyl iodides, such as p-me-
thoxy- and m-methylphenyl iodides, furnished 49% or
50% yields of the products.
A hot, oven-dried Schlenk tube was charged with aryl bro-
mides (1.0 mmol) followed by tetraphenylstannane
(0.28 mmol), NaOAc (3.5 mmol), PdCl2ACHTUNRGTNEUNG(PPh3)2 (0.01 mmol),
and PEG-400 (3 mL). Then the mixture was stirred at
1008C for 1 h. After cooling to room temperature, the mix-
ture was directly extracted four times with diethyl ether.
The upper layers were decanted, combined, washed with
water and brine, dried over anhydrous MgSO4 and concen-
trated under vacuum. Silica gel column chromatography
using ethyl acetate in petroleum ether as eleunt afforded the
pure products.
Table 4. Pd(II)-catalyzed cross coupling of aryl iodides (1)
with Ph4Sn (2).[a]
Entry Ar-I
Products[b]
t
Yield
[h] [%][c]
Acknowledgements
1
2
0.5 98
The work was supported by the Natural Science Foundation
of China (Grant 20272047, 20572086), the Gansu Natural
Science Foundation of China (0308RJZA-100) and Key Lab-
oratory of Eco-Environment-Related Polymer Material
(Northwest Normal University), Ministry of the Education of
China.
0.5 96
3
4
0.5 95
1
90
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