Triphenyltin chloride as a new source of phenyl group for C-heteroatom and C-C bond formation

Article abstract of DOI:10.1016/j.jorganchem.2013.04.053

Ph3SnCl is introduced as a very suitable source of phenyl group for coupling with phenols, amines, and thiols in the presence of Cu(OAc)2 in Et3N at room temperature to give aryl ethers, amines, and arylthio ethers in high yields. In addition, the application of Ph3SnCl in the Stille coupling of aryl halides in the presence of Pd(0) catalyst in PEG 400 at 110C is discussed.

Full text of DOI:10.1016/j.jorganchem.2013.04.053

Accepted Manuscript
Triphenyltin Chloride as a New Source of Phenyl Group for C-Heteroatom and C-C
Bond Formation
Nasser Iranpoor, Habib Firouzabadi, Elham Etemadi Davan, Abed Rostami, Arash
Nematollahi
PII:
S0022-328X(13)00359-8
10.1016/j.jorganchem.2013.04.053
JOM 18015
DOI:
Reference:
To appear in: Journal of Organometallic Chemistry
Received Date: 17 January 2013
Revised Date: 28 April 2013
Accepted Date: 30 April 2013
Please cite this article as: N. Iranpoor, H. Firouzabadi, E.E. Davan, A. Rostami, A. Nematollahi,
Triphenyltin Chloride as a New Source of Phenyl Group for C-Heteroatom and C-C Bond Formation,
Journal of Organometallic Chemistry (2013), doi: 10.1016/j.jorganchem.2013.04.053.
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ACCEPTED MANUSCRIPT
•
•
•
Ph3SnCl is introduced as a new atom economy source of phenyl group.
Ph3SnCl is used for O-, N-, and S-arylation reactions at room temperature.
Ph3SnCl is used for Stille reaction of aryl halides catalyzed by nano and
bulk Pd(0).

ACCEPTED MANUSCRIPT
Graphical abstract
Triphenyltin Chloride as a New Source of Phenyl Group for Carbon-Heteroatom
and C-C Bond Formation
Nasser Iranpoor*, Habib Firouzabadi* , Elham Etemadi Davan, Abed Rostami, and Arash Nematollahi
Chemistry Department, College of Sciences, Shiraz University, Shiraz, Iran
Corresponding author. Tel.: +98-711-2287600; fax: +98-711-2280926;
E-mail: iranpoor@chem.susc.ac.ir (N. Iranpoor); firouzabadi@chem.susc.ac.ir (H. Firouzabadi)
Ph3SnCl is introduced as a very suitable source of phenyl group for coupling with phenols,
amines, and thiols in the presence of Cu(OAc)2. In addition, the application of Ph3SnCl in the
Stille coupling of aryl halides in the presence of PdCl2/Ph3P and PdCl2/SDPP is discussed.
Cu(OAc)2
R
RNH2
+
Ph3SnCl
N
H
Et3N, rt, 24h
60-94%
RNH2: o1 and o2 aliphatic, aromatic, and heteroaromatic
XH
X
Cu(OAc)2
+
Ph3SnCl
Et3N, r.t, 30h
X = O, S
R1
R1
Ph
X
PEG 400
110 0C
PdCl2
PPh3 or SDPP
Ph3SnCl
K2CO3
+
+
+
+
R
R
X = I, Br, Cl

ACCEPTED MANUSCRIPT
Revised
Triphenyltin Chloride as a New Source of Phenyl Group for C-Heteroatom
and C-C Bond Formation
Nasser Iranpoor,* HabibFirouzabadi,* Elham Etemadi Davan, Abed Rostami, and Arash
Nematollahi
Chemistry Department, College of Sciences, Shiraz University, Shiraz, Iran
Corresponding author: Tel.: +98-711-2287600; fax: +98-711-2280926;
E-mail: iranpoor@chem.susc.ac.ir (N. Iranpoor); firouzabadi@chem.susc.ac.ir (H. Firouzabadi)
Abstract: Ph3SnCl is introduced as a very suitable source of phenyl group for coupling with
phenols, amines, and thiols in the presence of Cu(OAc)2 in Et3N at room temperature to give aryl
ethers, amines, and arylthio ethers in high yields. In addition, the application of Ph3SnCl in the
Stille coupling of aryl halides in the presence of Pd(0) catalyst in PEG 400 at 110 °C is discussed.
Keywords:
Triphenyltin chloride
Pd(0)
Cu(OAc)2
O-, N-, and S- nucleophile
Aryl halide
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1.
Introduction
Carbon-heteroatom and C-C cross-coupling reactions catalyzed by transition-metals are among
the most important reactions in the organic synthesis, in which the carbon bond formation
achieved with C-, O-, N-, and S- nucleophiles [1]. The corresponding reactions for carbon-
heteroatom bond formation which are catalyzed by transition metals is of great interest and are
categorized as, Ullmann-type reactions of aryl halides which is achieved by copper catalyst [2];
Buchwald–Hartwig cross-couplings of aryl halides in the presence of palladium catalytic systems
[3]; and Chan-Lam reactions catalyzed by copper in the presence of phenylboronic acids [4]. In
addition to phenylboronic acids, other copper catalytic systems in the presence of
organometalloids such as hypervalent aryl siloxanes [5], arylbismuth [6], aryllead [7],
hypervalentiodonium salts [8], and arylstannes [9] have been also developed for this
transformation. Organotins are considered as attractive reaction partners because of their
availability and stability toward air and moisture, and also variety of functional groups are
tolerated, however organotins and by-products are toxic.
The other cross-coupling reaction is C-C bond formation. Stille reaction which is the coupling of
aryl halides and organotin compounds to give biaryl derivatives is usually catalyzed by palladium
[10]. Biaryl products are an important class of compounds that are found in numerous natural
products, polymers, and pharmaceuticals [11]. The Pd-catalytic systems for the Stille reaction has
widely been studied [12]. This reaction has the high tolerance for functional groups but in most
cases it has drawbacks; first, the reactions are conducted with the use of expensive phoshphine
ligands, which lead to the limitation of their application. Second, the reactions are conducted in
toxic organic solvents. Third, equimolar amount of organotin is required for the reaction.
Different organostannes such as Me3SnPh [13], PhSnCl3 [14], and Bu3SnPh [15] have also been
used, and an equimolar amount of them is necessary for the reaction. Another tin reagent is Ph4Sn
[16] which have been used in less equimolar amount in the reaction with aryl bromides under
Stille reaction condition in 100 oC in PEG 400. However, an important drawback for this reagent
is that it is not applicable for carbon-heteroatom bond formation (Table 1, entry 18, this work).
In this paper, we wish to report the first use of triphenyltin chloride as a new source of phenyl
group for the efficient C-N, C-O, and C-S bond formation catalyzed with Cu(II) at room
temperature, and also its application in the Stille coupling reaction with aryl halides in the
presence of Pd(0) catalyst in PEG 400 at 110 °C. The use of Ph3SnCl has the advantage of atom
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economy in both carbon-carbon and carbon-hereroatom bond formation compared to Me3SnPh,
PhSnCl3 and Bu3SnPh reagents.
2.
Experimental
The activated plate silica gel type 60 (15-40 µm) was used for the preparation of phosphorylated
silica. The activation was performed by refluxing silica gel in HCl (aq. 37%) for 4 h. It was then
filtered and washed several times with distilled water to remove the produced HCl and dried in a
vacuum oven at 200 °C for 24 h before use.
2.1. Preparation of silicadiphenyl phosphinite (SDPP) [17]
SDPP was prepared as follows according to our previous report. To a flask containing activated
dried plate silica gel (0.3 g, 5 mmol), Ph2PCl (2 mL, 10 mmol) was added at room temperature
and stirred with a mechanical stirrer for 30 min under an argon atmosphere. The produced HCl
was removed by heating the mixture to 60 °C for 3 h. The reaction mixture was washed with 10
mL of diethyl ether and dried under vacuum. SDPP was obtained as a white solid (0.6 g) and
stored in a capped bottle for months without any change.
2.2. Typical procedure for N-arylation of aniline with Ph3SnCl catalyzed by Cu(OAc)2:
Copper acetate (40 mol%, 0.076 g) was added to a mixture of aniline (1.0 mmol, 0.09 mL) and
triphenyltin chloride (0.5 mmol, 0.193 g) in triethylamine (10 equiv, 1.4 mL) at room
temperature. The reaction mixture was stirred for 24 h and the progress of the reaction was
monitored by TLC. After the completion of the reaction, excess of Et3N was neutralized with
HCl (1 N, 1mL). The catalyst was then filtered and the aqueous solution was extracted with ethyl
acetate (5 × 10 mL) and dried over anhydrous Na2SO4. After evaporation of the solvent, the crude
product was purified by column chromatography on silica gel (n-hexane/EtOAc, 7/3) to afford N-
phenyl aniline in 94% yield (0.158 g). 1H-NMR (CDCl3, 250 MHz): δ 5.63 (s, 1H), 6.73-7.27 (m,
10H), 13C-NMR (CDCl3, 62.5 MHz): δ 117.7, 120.9, 128.8, 129.3, 143.0 ppm.
2.3. Typical procedure for O-arylation of phenol with Ph3SnCl catalyzed by Cu(OAc)2:
To a flask containing a stirring mixture of triphenyltin chloride (0.5 mmol, 0.193 g) and phenol
(1mmol, 0.094 g) in triethylamine (10 equiv, 1.4 mL) at room temperature, copper acetate (40
mol%, 0.076 g) was added. Monitoring the reaction with TLC showed that the reaction was
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completed within 30 h. The reaction mixture was washed with HCl (1N, 1mL) to remove the
excess of Et3N. Then, the catalyst was filtered and the aqueous solution was extracted with ethyl
acetate (5 × 10 mL) and dried over anhydrous Na2SO4. The solvent was evaporated and column
chromatography of the crude mixture on silica-gel using n-hexane/ethyl acetate (3/1) as eluent
afforded biphenyl ether in 85% yield (0.130 g). 1H-NMR (CDCl3, 250 MHz): δ 7.1-7.2 (m, 5 H),
7.42-7.49 (m, 5H). 13C-NMR (62.5 MHz, CDCl3): δ 118.0, 120.4, 129.9, 157.4 ppm.
2.4. Typical procedure for Stille coupling of aryl iodides with Ph3SnCl catalyzed PdCl2/Ph3P as
pre-catalyst:
Phenyl iodide (1.0 mmol, 0.136 mL) was added to a stirring mixture of PdCl2/Ph3P (0.15
mol%/0.62 mol%) in PEG 400. Then Ph3SnCl (0.5 mmol, 0.193 g) and KOAc (3.0 mmol, 0.294
g) were added. The reaction mixture was stirred in an oil bath at 110 °C. Monitoring of the
reaction with TLC analysis showed that the reaction was completed within 1 h. Work-up the
1
reaction mixture after completion of the reaction, afforded biphenyl in 87% yield (0.133 g). H-
13
NMR (CDCl3, 250 MHz): δ 7.63–7.31 (m, 10 H) ppm. C-NMR (CDCl3, 62.5 MHz): δ 145.5,
130.3, 127.4, 127.2 ppm.
3.
Results and discussion
To the best of our knowledge, triphenyltin chloride has not been used as a source of phenyl
nucleophile in C-heteroatom or C-C bond formation reactions. In this context, we wish to report
the first application of Ph3SnCl as a source of carbon nucleophile for these transformations.
In order to study the C-N bond formation reaction, we studied the reaction of 3-nitroaniline as a
relatively deactivated aromatic amine with Ph3SnCl in the presence of variety of solvents, bases,
and different amounts of Cu(OAc)2 as the catalyst (Table 1). Applying 0.4 molar equiv of
Cu(OAc)2 and 10 equiv of Et3N as base and also the solvent is effective for the room temperature
cross-coupling of Ph3SnCl (0.5 equiv) with 3-nitroaniline (1 equiv),which gave high yield of the
coupled product. The use of other bases such as K2CO3 and Cs2CO3, proved to be ineffective.
Solvents including CH2Cl2, EtOAc, DMF and THF were tested and the obtained results were
unsatisfactory. The presented results in Table 1 shows that the presence of various solvents retard
the reaction. Therefore, Et3N was used as the base and also solvent under the optimum
conditions. The effect of temperature on the model reaction was also investigated and it was
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observed that raising the reaction temperature to 60 °C decreases the reaction time slightly with
decrease of the product yield (Table 1). In order to compare the reactivity of Ph3SnCl with the
reported Ph4Sn, we performed a comparative study. The reaction did not produce any of the
corresponding diaryl amine, which proves the high efficiency of Ph3SnCl in comparison with
Ph4Sn. The obtained result from this study is tabulated in Table 1, entry 18.
H
NH2
N
Cu(OAc)2
+
Ph3SnCl
Solvent, Base, 24 h
NO2
NO2
Scheme 1. Optimization of different parameters for the reaction of 3-nitroaniline with Ph3SnCl.
Table 1
In continuation, we also investigated the use of different copper salts for the reaction. Among the
applied copper salts, Cu(OAc)2 was found to be the most efficient one and gave the highest yield
of the desired product in comparison with other copper sources (Table 2).
Table 2
Having the optimized conditions in hand, we used a series of aliphatic, and aromatic amines
including substituted anilines for the copper promoted N-arylation with Ph3SnCl to explore the
generality and scope of the process (Table 3).
Cu(OAc)2
R
RNH2
+
Ph3SnCl
N
H
Et3N, rt, 24h
60-94%
RNH2: o1 and o2 aliphatic, aromatic, and heteroaromatic
Scheme 2. The reaction of amines with Ph3SnCl at room temperature.
Table 3
As shown in Table 3, it was observed that this method was applicable to a broad range of
aromatic and heteroaromatic amines including substituted anilines. The results indicated that the
N-arylation with aliphatic amines occurs efficiently and gives the coupled product in good to high
yields. For example, morpholine, ethyl and n-propylamines afforded the corresponding products
in 78% and 75% yields respectively (Table 3, entries 2, 9, 10). When indole and pyrrole reacted
with Ph3SnCl, the obtained yields were moderate (Table 3, entries 1, 8). In the case of anilines
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bearing chloride- and nitro-substituents, high yields were obtained (Table 3, entries 5, 6, 12).
Steric effect was also observed in the case of 2-methylimidazol which proceeded in relatively
lower yield (Table 3, entry 7). In addition to amines, the reaction of benzamide as a model
reaction for amides was also studied. The reaction was performed successfully and its N-phenyl
derivative was obtained in good yield (Table 3, entry 3).
Our initial success on C-N bond formation turned our attention to the O- and S- nucleophiles for
this transformation. Our preliminary efforts toward such a process focused on optimizing the
reaction of Ph3SnCl and 4-methylphenol (Table 4). From the results of Table 4, we concluded
that 0.4 equiv of Cu(OAc)2 was sufficient to catalyze the reaction at room temperature. Under this
condition, the reaction afforded 80% yield of the corresponding diaryl ether. Furthermore, in
order to increase the efficiency of the coupling reaction, other bases, solvents and temperatures
were studied. According to the obtained results (Table 4), among the studied bases for the model
reaction, Et3N was the found to be the most effective one. Similar to the N-arylation reactions,
Et3N also acts as the solvent and furnished the desired product in 80% yield (Table 4, entry 9).
OH
O
Cu(OAc)2
+
Ph3SnCl
base, solvent, rt
Scheme 3. Effect of different bases, solvents and temperature on the reaction of Ph3SnCl with 4-
methylphenol.
Table 4
Similar to the N-arylation reactions, here again, among the studied copper salts, Cu(OAc)2 gave
the best results (Table 5).
Table 5
We also investigated the reaction of Ph3SnCl with a variety of electronically diverse phenols and
also with two thiols (Table 6). The reactivity of phenols under the optimal conditions is moderate
to good. It was also found that reaction conditions are also applicable for bromo and
nitrophenols, which afforded the corresponding products in good yields (Table 6, entries 5, 6, 9).
Phenols possessing electron-donating groups afforded better yields than those with electron-
withdrawing groups (Table 6, entries 2, 3, 11).
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XH
X
Cu(OAc)2
Ph3SnCl
+
Et3N, r.t, 30h
R1
R1
X = O, S
Scheme 4. The reaction of phonol and thiol derivatives in the presence of Ph3SnCl.
Table 6
Although the exact mechanism is not clear but on the basis of our observation, that Ph4Sn did not
produce any N-arylated product, it can be concluded that the presence of Sn-Cl bond in Ph3SnCl
(1a) provides a suitable site for insertion of copper to produce Ph3SnCuCl (1b). This intermediate
1b can react with Ar-X-H (X = N, O, S) to give 2b. The intermediate 2b will then react with the
base followed by phenyl migration to give Ar-X-Ph. 2b can also produces 4b which has still the
capability of transferring one more phenyl group to 6b and offer the corresponding biphenyl
derivatives (Scheme 5).
Ph3SnCl
1a
Cu(OAc)2
Ar
X Ph
Ph3Sn-CuII-Cl
1b
Ar
X
CuII Ph
3b
Ph CuII
6b
X
Ar
+
X H
Et3N
Ar
Et3N
Ar X Ph
AcO CuII
5b
Cu(OAc)
X Ar
Ph
NEt3
Ar X CuII Sn Ph
Ph Sn
Ph
4b
Ph
2b
H
Ar
X
Et3N +
X= N,O, S
Scheme 5. The proposed mechanism of Carbon-Hetero atom bond formation.
In order to find more applicability for Ph3SnCl, we examined the Stille cross-coupling reaction of
aryl halides catalyzed by PdCl2/Ph3P and also heterogeneously with the recently reported nano-
Pd(0)/silicadiphenyl phosphinite [Pd(0)/SDPP] [17]. Recently, we showed that Pd(II) is reduced
to Pd(0) in the presence of SDPP to offer nano-Pd(0)/SDPP which was then applied as a new
source of silica based nano-Pd(0) catalyst for coupling reactions. We therefore studied the Stille
7

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cross-coupling reaction of aryl halides catalyzed with nano-Pd(0)/SDPP and compared its
reactivity with the conventional Pd(0)/PPh3 system.
Our preliminary investigation was to screen the solvent and base effect for the reaction of
iodobenzene with Ph3SnCl catalyzed with Pd(0)/Ph3P (Table 7).
The model reaction was performed in EtOH in the presence of different bases and the best results
were obtained with K2CO3 and Cs2CO3. In the presence of organic bases, the reaction did not go
to completion. Therefore, we chose K2CO3 instead of Cs2CO3 as the appropriate base because of
its cheapness (Table 7, entry 1). Due to the long reaction times in ethanol, the model reaction was
also performed with other solvents at 90 °C using K2CO3 as the optimized base. The obtained
results showed that the shorter reaction time and the highest yield of biphenyl can be obtained in
PEG400 among other solvents (Table 7, entry 8). Next, we studied the effect of temperature on
the model reaction in PEG400 as the optimized solvent. At 110 °C, the reaction afforded the
corresponding biaryl in the highest yield with the shortest reaction time (Table 7, entry 13).
Following these findings, we continued our optimization to determine the effective amount of
Ph3SnCl. It was observed that the reaction proceeded in the presence of 0.5 equimolar of Ph3SnCl
and high yield of the product was obtained (Table 7, entry 13). To evaluate the effective amount
of PdCl2, various amounts of PdCl2 were also tested and among them, 0.15 mol% of PdCl2 was
found to be ideal in the presence of Ph3P. Finally, the obtained optimized conditions were applied
for the reaction of iodobenzene replacing Ph3P with the SDPP. In the presence of SDPP, Pd(II) is
reduced to Pd(0) and the nano-Pd(0)/SDPP is produced [17]. This reaction was performed
successfully with the in situ generated Pd(0) catalyst using the pre-catalyst PdCl2/SDPP (Table 7,
entry 19). For comparison, we also used per-prepared nano-Pd(0)/SDPP catalyst [17], however,
the reaction time and the isolated yield was observed to be almost identical in both cases (Table
7, entry 20). Therefore, it was concluded that the reaction can be performed either in the presence
of the pre-prepared nano-Pd(0)/SDDP or the in situ generated catalyst.
PdCl2/Ph3P
I
+
Ph3SnCl
base, solvent, temperature
Scheme 6. Coupling of iodobenzene with Ph3SnCl catalyzed by PdCl2/PPh3 in the presence of different
solvents, temperatures, and bases.
Table 7
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In the case of iodobenzene, the desired biphenyl is from the coupling of iodobenzene with
Ph3SnCl, but not from the homo-coupling of either iodobenzene or Ph3SnCl. The reason to accept
this concept is that in the case of other aryl halides there is no side-product formed from homo-
coupling of aryl halide. Formation of biphenyl from Ph3SnCl in the reactions of aryl halides is
only in the range of 5-8% which is similar with the reactions of phenylboronic acid (Table 8,
entries 3, 9).
With these results in hand, we performed the reaction under the optimized conditions employing
variety of aryl iodides in the presence of Ph3SnCl for synthesizing biphenyl derivatives (Table 8).
To perform this transformation for aryl bromides, it was found that the reaction proceeded well in
the presence of 0.31 mol% of PdCl2 in the presence of Ph3P. Applying this condition to other aryl
bromides, the desired biaryls were obtained in high yields. Next, we turned our attention to the
reaction of aryl chlorides and moderate yields of the target products were obtained applying 1.25
mol% of PdCl2 (Table 8).
Ph
X
PEG 400
110 0C
PdCl2
PPh3 or SDPP
Ph3SnCl
K2CO3
+
+
+
+
R
R
X = I, Br, Cl
Scheme 7. Coupling of aryl halides with Ph3SnCl catalyzed by PdCl2 as pre-catalyst in the presence of
Ph3P or SDDP in PEG 400 at 110 °C.
Table 8
The results of Table 8 demonstrate that different aryl halides produce their corresponding biaryl
derivatives in good to excellent yields under relatively short reaction times.
In the case of the Stille reaction, the probable mechanism for conversion of alkyl halides to
biphenyl derivatives is shown in Scheme 8.
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PdCl2
SDPP or Ph3P
Ar
X
[Pd]0
Ar
Ph
Ar
Pd
X
Ph3SnCl
Ar
Pd Ph
Ph2SnXCl
Scheme 8. The proposed mechanism for Stille reaction.
4.
Conclusion
In summary, we have introduced Ph3SnCl as a new source of atom economy phenyl nucleophile
and developed an effective method for room temperature N-, O-, and S- arylation and also C-C
bond formation through coupling with aryl iodides, bromides and chlorides at 110 °C. These
transformations worked well under the optimal conditions and afford moderate to high yields of
the target products under mild conditions for diverse reactants. The atom economy, stability and
relatively cheapness of Ph3SnCl together with the mild reactions condition make this method
useful for both carbon-heteroatom and carbon-carbon bond formation reactions.
Acknowledgments
We gratefully acknowledge the partial financial support of this study by the Shiraz University
Research Council.
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Commun.(1998) 2095-2096; (d) D. A. Alonso, C. Na´ jera, M. C. Pacheco,Oximepalladacycles: Stable and efficient
catalysts for carbon-carbon coupling reactions,Org. Lett. 2 (2000) 1823-1826; (e) N. Kim, M. S. Kwon, C. M. Park,
J. Park, One-pot synthesis of recyclable palladium catalysts for hydrogenations and carbon–carbon coupling
reactions, Tetrahedron Lett. 45 (2004) 7057-7059; (f) H. Zhao, Y. Wang, J. Sha, S. Sheng, M. Cai, MCM-41-
supported bidentate phosphine Palladium(0) complex as an efficient catalyst for the heterogeneous Stille reaction,
Tetrahedron 64 (2008) 7517-7523; (g) M. M. Dell’ Anna, A. Lufo, P. Mastrorilli, V. Mucciante, C. F. Nobile, Stille
coupling reactions catalyzed by a polymer supported Palladium complex, J. Organomet. Chem. 691 (2006) 1331-
137.
[13] C. E. Domini, G. F. Silbestri, B. F. Band, A. B. Chopa, Ultrasound-assisted synthesis of unsymmetrical biaryls
by Stille cross-coupling reactions, Ultrason. Sonochem. 19 (2012) 410-414.
[14] (a) B. P. Dennis, M. Sethi, S. E. Jones, R. R. Naik, M. R. Knecht, Biomimetic synthesis of Pdnano catalysts for
the Stille coupling reaction, ACS Nano 3 (2009) 1288-1296; (b) R. Rai, K. B. Aubrecht, D. B. Collum, Palladium-
catalyzed Stille Couplings of aryl-, vinyl-, and alkyltrichlorostannanes in aqueous solution, Tetrahedron Lett. 36
(1995) 3111-3114.
[15] (a) W. Su, S. Urgaonkar, J. G. Verkade, Pd2(dba)3/P(i-BuNCH2CH2)3N-catalyzed Stille cross-coupling of aryl
chlorides, Org. Lett. 6 (2004) 1421-1424; (b) J.-H.Li, Y. Liang, D.-P.Wang, W.-J.Liu,Y.-X.Xie, D.-L. Yin, Efficient
Stille cross-coupling reaction catalyzed by Pd(OAc)2/Dabco catalytic system,J. Org. Chem. 70 (2005) 2832-2834; (c)
W. Su, S.Urgaonkar, P. A. McLaughlin, J. G. Verkade, Highly active Palladium catalysts supported by bulky
proazaphosphatrane ligands for Stille cross-coupling:ꢀ coupling of aryl and vinyl chlorides, room temperature
coupling of aryl bromides, coupling of aryl triflates, and synthesis of sterically hindered biaryls, J. Am. Chem. Soc.
126 (2004) 16433-16439; (d) W. Hao, Z. Xi; M. Cai, A practical synthesis of biaryls and aromatic acetylenes by
Stille coupling in room-temperature ionic liquids, Synth. Commun. 42 (2012), 2396-2406; (e) A. V. Coelho, A. L. F.
de Souza, P. G. de Lima, J. L. Wardell, O. A. C. Antunes, Ligand-free Stille cross-coupling reaction using Pd/CaCO3
as reservoir, Tetrahedron Lett. 48 (2007) 7671-7674; (f) T. Z. Nichele, A. L. Monteiro, Synthesis of diarylmethane
derivatives from Stille cross-coupling reactions of benzylic halides, Tetrahedron Lett. 48 (2007) 7472-7475; (g)
12

ACCEPTED MANUSCRIPT
Pyrazole-tetheredphosphine ligands for Pd(0): useful catalysts for Stille, Kumada, Hiyama cross-coupling reactions,
Tetrahedron 66 (2010) 5451-5458.
[16](a) V. Calo, A. Nacci, A. Monopoli, F. Montingelli, Pdnano particles as efficient catalysts for Suzuki and Stille
coupling reactions of aryl halides in ionic liquids, J. Org. Chem. 70 (2005) 6040-6044; (b) Y. Yabe, T. Maegawa, Y.
Monguchi, H. Sajiki, Palladium on charcoal-catalyzed ligand-free Stille coupling, Tetrahedron 66 (2010) 8654-8660.
[17] (a) N. Iranpoor, H. Firouzabadi, S. Motevalli, M. Talebi, Palladium nanparticles supported on silicadiphenyl
phosphinite (SDPP) as efficient catalyst for Mizoroki-Heck and Suzuki-Miyaura coupling reactions, J. Organomet.
Chem. 708-709 (2012) 118-124; (b) N. Iranpoor, H. Firouzabadi, S. Motevalli, Silicadiphenyl phosphinite
(SDPP)/Pd(0) nanocatalyst for efficient aminocarbonylation of aryl halides with POCl3 and DMF, J. Mol. Catal. A:
Chem. 335 (2012) 69-74.
13

ACCEPTED MANUSCRIPT
Table 1
Optimization of different parameters for the reaction of 3-nitroaniline withPh3SnCl.a
H
NH2
N
Cu(OAc)2
+
Ph3SnCl
Solvent, Base, 24 h
NO2
Entry
NO2
Solvent
Cu(OAc)2 mol%
Base (equiv)
Et3N (5)
Temperature °C
Yield %
40
65
65
65
15
0
1
2
40
70
CH2Cl2
rt
rt
Et3N (5)
CH2Cl2
3
100
100
100
100
100
100
100
100
50
Et3N (5)
CH2Cl2
rt
4
Et3N (5)
EtOAc
60
80
80
80
80
rt
5
Et3N (5)
DMF
6
Cs2CO3 (2)
K2CO3 (2)
Et3N (5)
DMF
7
DMF
0
8
THF
30
65
80
80
70
55
80
65
65
70b
9
Et3N (10)
Et3N (10)
Et3N (10)
Et3N (10)
Et3N (5)
EtOAc
10
11
12
13
14
15
16
17
18
-
-
-
-
-
-
-
-
-
rt
rt
50
rt
40
rt
40
Et3N (10)
Et3N (10)
nPr3N (10)
Et3N (10)
Et3N (10)
rt
rt
30
50
rt
40
60
rt
40
0c
a
b
c
Reaction conditions: 1.0 mmol of 3-nitroaniline, 0.5 mmol of Ph3SnCl. The reaction was finished after 18h. The
reaction was performed with 0.4 equiv of Ph4Sn.
14

ACCEPTED MANUSCRIPT
Table 2
Effect of different copper salts (40mol%) on the reaction of
3-nitroaniline with Ph3SnCl at room temperature.a
Entry
Copper salt
Cu(OAc)2
Cu(OAc)2.H2O
CuSO4
Time (h)
Isolated Yield %
1
2
3
4
5
24
24
24
24
24
80
70
65
65
35
CuCl2
CuI
aReaction conditions: 1.0 mmol of 3-nitroaniline, 0.5 mmol of Ph3SnCl, 10 equiv of Et3N.
15

ACCEPTED MANUSCRIPT
Table 3
The reaction of amines with Ph3SnCl at room temperature.a
Cu(OAc)2
R
RNH2
+
Ph3SnCl
N
H
Et3N, rt, 24h
60-94%
RNH2: o1 and o2 aliphatic, aromatic, and heteroaromatic
Entry
1
Amine
Product
Isolated Yield %
60
N
N
H
Ph
O
N
2
3
4
O
N H
78
75
94
O
O
NH2
N Ph
H
H
N Ph
NH2
Cl
NH2
5
6
80
84
Cl
NH
H
Cl
Cl
NH2
N Ph
Cl
Cl
N
N
N
CH3
7
8
70
65
75
75
N
H
H3C
N
N H
9
NH2
N
H
H
NH2
10
N
17

ACCEPTED MANUSCRIPT
H
N
11
12
N
N
85
80
N
H
N
NH2
NO2
NO2
H
N
NH2
13
92
H3C
H3C
a Reaction condition: 1.0 mmol of 3-nitroaniline, 0.5 mmol of Ph3SnCl, 10 equiv of Et3N, 40 mol% of Cu(OAc)2.
18

ACCEPTED MANUSCRIPT
Table 4
Effect of different bases, solvents and temperature on the reaction of Ph3SnCl with 4-
methylphenol.a
OH
O
Cu(OAc)2
+
Ph3SnCl
base, solvent, rt
Entry
1
Base (equiv)
t-BuOK (2)
K2CO3 (2)
Et3N (3)
Temperature
Solvent
t-BuOH
DMF
DMF
THF
CH2Cl2
CH2Cl2
CH2Cl2
EtOAc
-
Time (h)
Isolated Yield (%)
rt
90
90
60
rt
12
12
12
24
30
30
30
30
30
30
30
30
0
2
0
3
15
35
50
45b
65
62
80c
65d
0e
4
Et3N (3)
5
Et3N (3)
6
Et3N (5)
rt
7
Et3N (10)
Et3N (5)
rt
8
60
rt
60
rt
9
Et3N (10)
Et3N (10)
Et3N (10)
nPr3N (10)
10
12
11
-
-
60
-
70
a Reaction conditions: Ph3SnCl (0.5 mmol), 4-methylphenol (1mmol). b1 equiv of Cu(OAc)2 was used. c,d 40 mol% of
Cu(OAc)2 was used. e The reaction was performed with 0.4 equiv of Ph4Sn.
19

ACCEPTED MANUSCRIPT
Table 5
Effect of different copper salts (40 mol%) on the reaction
of 4-metylphenol with Ph3SnCl at room temperature.a
Entry
Copper salt
Cu(OAc)2
Cu(OAc)2.H2O
CuSO4
Time (h)
Isolated Yield (%)
1
2
3
4
5
30
30
30
30
30
80
75
75
70
20
CuCl2
CuI
a Reaction conditions: Ph3SnCl (0.5 mmol), 4-methyl phenol (1mmol), Et3N (10 equiv).
20

ACCEPTED MANUSCRIPT
Table 6
The reaction of phonol and thiol derivatives in the presence of Ph3SnCl.a
XH
X
Cu(OAc)2
+
Ph3SnCl
Et3N, r.t, 30h
R1
R1
X = O, S
Entry
1
R-XH
Product
Isolated Yield %
85
OH
O
OH
O
2
3
80
78
Me
Me
OH
O
Me
Me
Me
OH
O
O
4
5
6
70
65
60
Me
OH
Br
Br
Br
Br
OH
O
OH
O
7
8
9
60
65
57
Cl
I
Cl
I
OH
O
OH
O
O2N
O2N
21

ACCEPTED MANUSCRIPT
OH
OPh
10
75
OH
O
11
12
85
MeO
MeO
SH
S
75
78
SH
13
S
a Reaction conditions: Ph3SnCl (0.5 mmol), phenol or thiophenol (1.0 mmol), Et3N (10 equiv),
40 mol% of Cu(OAc)2.
22

ACCEPTED MANUSCRIPT
Table 7
Coupling of iodobenzene with Ph3SnCl catalyzed by PdCl2/PPh3 in the presence of different
solvents, temperatures, and bases.a
PdCl2/Ph3P
I
+
Ph3SnCl
base, solvent, temperature
PdCl2
Entry
Base
Ph3SnCl
Solvent
Temp
Time (h)
Yield %
(mol%)
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
-
1
2
K2CO3
Cs2CO3
NaOH
Et3N
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
1.0
EtOH
EtOH
70
70
9.0
6.0
7.0
7.0
7.0
7.0
7.0
1.5
7.0
7.0
0.5
2.2
1.5
3.0
4.0
1.0
0.7
80
80
50
40
70
20
20
85
40
40
90
90
90
75
-
3
EtOH
70
4
EtOH
70
5
KOAc
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
EtOH
70
6
H2O
90
7
Dioxane
PEG400
DMF
90
8
90
9
90
10
13
14
11
12
15
16
17
Et3N
90
PEG400
PEG400
PEG400
PEG400
PEG400
PEG400
PEG 400
110
70
110
110
110
110
110
0.33
0.5
0.5
-
0.15
0.15
87
90b
23

ACCEPTED MANUSCRIPT
18
19
20
K2CO3
K2CO3
K2CO3
0.5
0.5
0.5
0.15
0.62
-
PEG 400
PEG 400
PEG 400
110
110
110
18
1.0
0.9
65c
87d
83e
a
Reaction conditions: PhI (1.0mmol), Base (1.5 mmol), 4.0 equimolars of Ph3P was used respect to the amounts of
PdCl2. b The reaction was performed with 1.5 mmol of PhB(OH)2.c,d The reaction was performed in the presence of
e
SDPP instead of Ph3P. The reaction was performed in the presence of per-prepared nano-Pd(0)/SDPP catalyst (4.0
mgr).
24

ACCEPTED MANUSCRIPT
Table 8
Coupling of aryl halides with Ph3SnCl catalyzed by PdCl2 as pre-catalyst in the presence of Ph3P
or SDDP in PEG 400 at 110 °C.a
Ph
X
PEG 400
110 0C
PdCl2
PPh3 or SDPP
Ph3SnCl
K2CO3
+
+
+
+
R
R
X = I, Br, Cl
Time (h)
Pd(0)/PPh3
Time (h)
Pd(0)/SDPP
Entry
1
Aryl Halide
Yield
88
Yieldb
1
1
1.2
1
83
87
I
2
3
87
I
OMe
0.7
82
87
1.5
84
88
0.4c
1.4d
I
I
OMe
I
4
5
84
82
2
83
80
2.6
1
NO2
0.8
Me
I
6
1
87
0.8
84
NO2
NO2
Cl
7
8
0.5
0.5
85
83
0.5
1.4
88
87
I
Br
0.8
82
85
0.5
85
88
9
0.8e
0.3f
Br
10
11
1.5
0.5
85
84
0.4
0.7
80
82
Br
Br
25

ACCEPTED MANUSCRIPT
CN
12
13
14
3
2.5
1
80
80
85
0.5
2.2
0.8
83
84
88
Br
Br
N
N
Br
N
Br
15
8
88
8
85
16
17
25
20
82
80
25
20
85
85
Cl
NO2
Cl
PdCl2/Ph3P (0.15 mol%/0.6 mol%) or PdCl2/SDPP (0.62 mol%/5.0 mg) for aryl iodides; PdCl2/Ph3P (0.31
a
mol%/1.24 mol%) or PdCl2/SDPP (1.25 mol%/10.0 mg) for aryl bromides; PdCl2/Ph3P (1.25 mol%/5 mol%) or
PdCl2/SDPP (1.25 mol%/10.0 mg) for aryl chlorides. The reaction of aryl chlorides was performed in a sealed tube. b
This is the isolated yield% of the pure product. In addition, 5-8% of biphenyl is also obtained. c-f For comparison,
phenylboronic acid was used instead of Ph3SnCl and g.c analysis showed the formation of 4-10% of biphenyl.
26

ACCEPTED MANUSCRIPT
Supplementary section:
Spectral data of the Stille coupling reaction:
1H-NMR (250 MHz, CDCl3) δ (ppm): 7.36-7.61(m, 10 H); 13C-NMR (CDCl3, 62.9
MHz): δ (ppm): 127.16, 127.24, 128.74, 141.23.
1H-NMR (CDCl3, 250 MHz): δ (ppm): 2.51(s, 3H), 7.37-7.64 (m, 7H), 7.69-7.73 (m,
2H); 13C-NMR (CDCl3, 62.9 MHz): δ (ppm): 21.20, 126.92, 127.08, 127.10, 129.56, 129.60, 137.09,
138.47, 141.27.
1H-NMR (CDCl3, 250 MHz): δ (ppm):2.25 (s, 3H), 7.20-7.32 (m, 7H), 7.35-7.36 (m,
2H); 13C-NMR (CDCl3, 62.9 MHz): δ (ppm): 20.44, 125.74, 126.73, 127.15, 128.04, 128.73, 129.17,
129.77, 130.28, 135.31, 141.92.
NO2
1H-NMR (CDCl3, 250 MHz): δ (ppm): 2.36 (s, 3H), 7.28-7.46 (m, 5H), 8.06-8.14
13
(m, 3H); C-NMR (CDCl3, 62.9 MHz): δ (ppm): 20.63, 120.89, 125.14, 127.99, 128.69, 129.14, 131.91,
137.86, 139.75, 146.9, 148.55.
NO2
1H-NMR (CDCl3, 250 MHz): δ (ppm):7.23-7.50 (m, 3H),7.60 (d, 2H, J=9.0 Hz),
7.70 (d, 2H, J= 9.0 Hz), 8.25 (d, 2H, J=9.0 Hz); 13C-NMR (CDCl3, 62.9 MHz): δ (ppm): 124.07, 127.36,
127.75, 128.92, 129.15, 138.70, 147.03, 147.57.
27

ACCEPTED MANUSCRIPT
Ph
1H-NMR (CDCl3, 250 MHz): δ (ppm): 7.36-7.47 (m, 9H), 7.87-7.90 (m, 3H); 13C-NMR
(CDCl3, 62.9 MHz): δ (ppm): 124.3, 125.3, 125.7, 127.17, 127.3, 127.5, 127.8, 128.7, 130.0, 131.5, 133.7,
140.2, 140.7.
N
Ph
1H-NMR (CDCl3, 250 MHz): δ (ppm): 7.47-7.57 (m, 5H), 8.93 (s, 2H), 9.19 (s, 1H); 13C-
N
NMR (CDCl3, 62.9 MHz): δ (ppm): 126.96, 129.14, 129.22, 134.24, 134,27, 154.87, 157.46.
Cl
1H-NMR (CDCl3, 250 MHz): δ (ppm): 7.33-7.57 (m, 9H);13C-NMR (CDCl3, 62.9
MHz): δ (ppm): 126.90, 127.58, 128.36, 128.75, 129.00, 133.73, 138.41, 139.11.
CN
1H-NMR (CDCl3, 250 MHz): δ (ppm):7.39-7.66 (m, 9H); 13C-NMR (CDCl3, 62.9
MHz): δ (ppm): 110.50, 119.00, 126.90, 127.33, 128.63, 129.02, 132.40, 136.24, 141.80.
1H-NMR (CDCl3, 250 MHz): δ (ppm):7.33-7.57 (m, 6H), 7.84 (d, 1H, J= 8.0 Hz), 8.57
N
(s, 1H), 8.85 (s, 1H), 8.85 (s, 1H); 13C-NMR (CDCl3, 62.9 MHz): δ (ppm): 122.21, 127.43, 128.32,
129.04, 136.59, 136.59, 137.76, 148.25, 148.40.
OMe
1H-NMR (CDCl3, 250 MHz): δ (ppm): 3.81 (s, 3H), 6.95 (d, 2H, J= 7.5 Hz), 7.29
(t, 1H, J= 7.3 Hz), 7.39 (t, 1H, J= 7.3 Hz), 7.49-7.55 (m, 4H); 13C-NMR (CDCl3, 62.9 MHz): δ (ppm):
55.30, 114.23, 126.15, 126.37, 128.18, 128.76, 133.80, 140.85, 159.18.
28