Ionic liquid supported organotin reagents: Green tools for stille cross-coupling reactions with brominated substrates

Article abstract of DOI:10.1002/ejoc.201001195

Efficiency of ionic liquid supported organotin reagents in Stille cross-coupling reactions involving aryl bromides has been investigated. In a general manner, products were isolated with good yields by using a very simple catalytic system without the need of solvent, ligand, or additives. The organotin compounds were recycled without loss of activity and the contamination by tin was limited and controlled ([Sn] < 3 ppm). Clean tin's good! Efficiency of ionic liquid supported organotin reagents in Stille cross-coupling reactions involving aryl bromides has been investigated. Products were isolated with good yields by using a verysimple catalytic system. Organotin compounds were recycled without loss of activity and the contamination by tin was limited ([Sn] < 3 ppm).

Full text of DOI:10.1002/ejoc.201001195

FULL PAPER
DOI: 10.1002/ejoc.201001195
Ionic Liquid Supported Organotin Reagents: Green Tools for Stille Cross-
Coupling Reactions with Brominated Substrates
Nicolas Louaisil,[a] Phuoc Dien Pham,[a] Fabien Boeda,[a] Djibril Faye,[a]
Anne-Sophie Castanet,[a] and Stéphanie Legoupy*[a]
Keywords: Ionic liquids / Palladium / Cross-coupling / Tin / Sustainable chemistry
Efficiency of ionic liquid supported organotin reagents in
Stille cross-coupling reactions involving aryl bromides has
been investigated. In a general manner, products were iso-
lated with good yields by using a very simple catalytic system
without the need of solvent, ligand, or additives. The or-
ganotin compounds were recycled without loss of activity
and the contamination by tin was limited and controlled ([Sn]
Ͻ 3 ppm).
Introduction
Results and Discussion
Starting from imidazole derivative 1,[9a] new room-tem-
perature ionic liquid (RTIL) 3 (R = Et, X = Br) was easily
synthesized in a similar manner to that used for ionic liquid
2 (R = Me, X = I; Scheme 1).
Amongst the palladium-catalyzed cross-coupling meth-
ods, the Stille reaction of organostannanes with organic
electrophiles represents a versatile method for carbon–car-
bon bond formation.[1] Indeed, this transformation is one of
the most general and selective Pd-catalyzed cross-coupling
reactions for the synthesis of complex molecules because of
its broad scope and high tolerance towards many functional
groups.[2] However, the use of organotin reagents has been
avoided for the synthesis of pharmacologically active sub-
stances due to their toxicity and the difficulties of removing
residues from the products. As a result, ongoing efforts have
been devoted to solve these problems by using solid-phase
synthetic methods,[3,4] phosphonium-grafted organotins,[5]
Stille couplings catalytic in tin,[6] and other modified or-
ganotin reagents.[7]
Convenient access to biaryl compounds is receiving cur-
rently a great deal of attention due to the prominence of
this scaffold in biological and naturally occurring mole-
cules.[8] As a part of our ongoing research program dealing
with potentialities of TSILs (task-specific ionic liquids), and
particularly organotin reagents supported on ionic li-
quids,[9] we previously reported an exploration of their
scope of the Stille reaction involving aryl iodide sub-
strates.[9a,9d] High yields of biaryl products were obtained
under low-temperature, solvent-free, ligand-free conditions,
with simple purification techniques. Moreover, the products
were isolated with minimal amount of tin (Ͻ6 ppm). This
result prompted us to investigate the scope and limits of
organotin reagents supported on ionic liquid in the Stille
reaction with brominated substrates.
Scheme 1. Synthesis of ionic liquids 2 and 3.
The reactivity of compound 3 in Stille cross-coupling re-
actions has been evaluated with different palladium precat-
alysts (5 mol-%) and by using bromopyridine 4 as a bench-
mark substrate. It should be noted that this heteroaromatic
substrate was chosen to differentiate desired product 5 from
biphenyl byproduct 6.[9a] Results are summarized in
Table 1.
Table 1. Precatalyst effect on Stille cross-coupling reactions.
Entry
Pd0
Conv. [%][a]
5[a]
[%]
6[a]
[%]
1
2
3
4
5
6
7
[Pd2(dba)3·CHCl3]
[PdCl2]
[Pd(PPh3)4]
[Pd/C]
[Pd2(dba)3]
[Pd{P(tBu)3}2]
[Pd(OAc)2]
0
0
0
–
–
–
–
–
–
0
–
–
[a] Université du Maine, UCO2M, UMR CNRS 6011,
Avenue Olivier Messiaen, 72085 Le Mans cedex 9, France
Fax: +33-2-43833902
11
20
93
64
46
65
36
54
35
E-mail: stephanie.legoupy@univ-lemans.fr
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201001195.
[a] Determined by GC.
Eur. J. Org. Chem. 2011, 143–149
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N. Louaisil, P. D. Pham, F. Boeda, D. Faye, A.-S. Castanet, S. Legoupy
FULL PAPER
As an initial assay, conditions previously used for aryl temperature, formation of droplets on neck of the flask was
iodide substrates {e.g., 48 h, 35 °C, 2 (2 equiv.), and noticed. This could be the result of the condensation of
[Pd2(dba)3·CHCl3] as precatalyst} were applied. No conver- compound 4, which, as a consequence, would not remain
sion was observed with this catalytic system (Table 1, En- in the reaction mixture and would explain the decrease in
try 1). Moreover, the use of [PdCl2] (Table 1, Entry 2), the reactivity.
[Pd(PPh3)4] (Table 1, Entry 3), and [Pd/C] (Table 1, Entry 4)
did not allow the formation of the desired compound.
Table 3. Temperature effect on Stille cross-coupling reactions.
When using [Pd2(dba)3] (Table 1, Entry 5) or [Pd{P-
(tBu)3}2][10] (Table 1, Entry 6) the reaction proceeded with
only 11–20% conversion, generating a high proportion of
biphenyl product 6. The highest conversion (93%) was ob-
served when using [Pd(OAc)2] as the precatalyst with a
65:35 ratio of 3-phenylpyridine (5) and biphenyl byproduct
6 (Table 1, Entry 7).
Entry
T [°C]
Conv. [%][a]
5
6
[%][a]
[%][a]
To enhance the selectivity in favor of 3-phenylpyridine
(5), we decided to examine the influence of several ligands
with [Pd(OAc)2] as the precatalyst (Table 2). Addition of
phosphane ligands such as P(o-tolyl)3 and PPh3 (Table 2,
Entries 2 and 3), led to a loss of catalytic activity, as only
25% conversion were measured after a reaction time of
48 h. The use of ancillary ligands AsPh3 or P(tBu)3
1
2
3
35
100
150
69
100
21
68
93
79
32
7
21
[a] Determined by GC.
In summary, we showed after this optimization part that
(Table 2, Entries 4 and 5) afforded conversions of 49 and a very simple catalytic system ([Pd(OAc)2] at 100 °C) with-
82%, respectively. These results clearly highlight that our out need of solvent, ligand, or additives represented the
catalytic system does not require the addition of a ligand.
most effective conditions.
To perform a thorough evaluation of the activity of our
system, we decided to investigate the Stille cross-coupling
reaction with various brominated substrates. Results are de-
picted in Table 4.
Table 2. Ligand effect on Stille cross-coupling reactions.
Reactivity of hetreoaryl and aryl bromide substrates di-
versely substituted has been evaluated in Stille cross-cou-
pling reactions using ionic liquid 3. For instance, heteroaryl
derivatives such as 3-bromopyridine (4), 5-bromo-2-(trifluo-
romethyl)pyridine (7), and 3-bromoisoquinoline (8) turned
out to be good candidates for this transformation (Table 4,
Entries 1, 2 and 3). The coupling with 4-bromoaceto-
phenone (9) proceeded in good yield (Table 4, Entry 4),
whereas benzaldehyde 10 and benzonitrile 11 exhibited
moderate reactivities (Table 4, Entries 5 and 6). Reactions
involving naphthyl as well as styrenyl and benzothiophene
Entry
Ligand
Conv. [%][a]
5[a]
6[a]
[%]
[%]
1
2
3
4
5
none
P(o-tolyl)3
PPh3
AsPh3
P(tBu)3
93
25
25
49
82
65
21
53
58
48
35
79
47
42
52
[a] Determined by GC.
To further optimize the reaction conditions, the Stille derivatives afforded good results in spite of difficulties con-
cross-coupling transformation was performed in the pres- cerning their isolation (Table 4, Entries 7–11). Indeed, con-
ence of copper(I)[11] (CuI, CuBr, CuCl) and a fluoride trary to Wang’s report,[14] isolation of 2-phenylnaphthalene
source[12] (CsF, NaF, KF) (classical conditions for Stille (23; Table 4, Entry 8) by flash chromatography failed be-
cross-coupling reactions often require these types of addi- cause of its similar polarity with biphenyl byproduct 6.
tives).[13] Once again, no improvement in terms of catalytic
activity was noticed.
To provide a greater versatility to our methodology, we
were concerned by the transfer of other groups than phenyl.
Temperature effect was also investigated by using 3-bro- Thus, five new organotin reagents supported on ionic liquid
mopyridine (4), ionic liquid 3, and [Pd(OAc)2] precatalyst (28–32) bearing, respectively, vinyl, allyl, anisole, fluoroben-
(Table 3). After 24 h of reaction at 35 °C, only 69% conver- zene, and thiophene moieties have been straightforwardly
sion was observed with a 5/6 ratio similar to that obtained synthesized. These compounds have been isolated with
after a reaction time of 48 h at the same temperature good yields after reaction of Grignard reagents with deriva-
(Table 3, Entry 1). It is noteworthy that an increase in tem- tive 27 (Scheme 2).
perature to 100 °C led to full conversion. More interest-
To determine the best catalytic system, new methodology
ingly, the proportion of 5 increased from 68 to 93% was employed, which required the use of vinylstannane 28
(Table 3, Entry 2). Finally, only 21% conversion were and bromoacetophenone 9 at 80 °C for 15 h (Table 5). By
reached when applying a temperature of 150 °C (Table 3, using catalysts such as [Pd(OAc)2], [Pd2(dba)3·CHCl3], and
Entry 3). Of note, under these reaction conditions, no de- [Pd2(dba)3] (Table 5, Entries 1–3), almost no coupling prod-
gradation of ionic liquid 3 was observed. However, at this ucts were detected. Interestingly, by using [Pd(PPh3)4], total
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Eur. J. Org. Chem. 2011, 143–149

Green Tools for Stille Cross-Coupling Reactions
Table 4. Stille cross-coupling reactions with phenyl stannane.
conversion was observed after 5 h of heating at 80 °C. These
reaction conditions in hand, various brominated substrates
were investigated in the Stille cross-coupling reaction.
Table 5. Precatalyst effect on Stille cross-coupling reactions.
Entry
Pd0
t [h]
Conv. [%][a]
1
2
3
4
5
[Pd(OAc)2]
[Pd2(dba)3·CHCl3]
[Pd2(dba)3]
15
15
15
15
5
4
6
3
100
100
[Pd(PPh3)4]
[Pd(PPh3)4]
[a] Determined by GC.
After optimization, it was found that the use of
[Pd(PPh3)4] in conjunction with only 1 equiv. of ionic liquid
28 or 29 constituted the best system for this application.
Both allylation and vinylation products were isolated with
good yields after 5 h of reaction. Several cross-coupling
partners bearing various functionalities were examined. The
results depicted in Table 6 clearly indicate a good tolerance
of our catalytic system towards esters, ketones, and nitro-
gen-containing heteroaromatic substrates.
Table 6. Stille cross-coupling reaction with vinyl- and allylstann-
anes.
[a] Full conversion. [b] Determined by GC. [c] 8 h. [d] Inseparable
products. [e] Conversion of 94% and 6% of R–R was formed.
[f] 80 °C.
Scheme 2. Synthesis of vinyl, allyl, aryl, and heteroaryl RTILs.
[a] Pd(PPh3)4: 2 mol-%. [b] Pd(PPh3)4: 5 mol-%.
Eur. J. Org. Chem. 2011, 143–149
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N. Louaisil, P. D. Pham, F. Boeda, D. Faye, A.-S. Castanet, S. Legoupy
FULL PAPER
Aryl–aryl or aryl–heteroaryl cross-coupling reactions (Table 8, Entry 4); the heteroaryl product was obtained with
using arylstannanes 30 and 31 were investigated. The results a yield of 80%.
are summarized in Table 7. Reactions between anisol-con-
taining stannane 30 bearing an electron-donating substitu-
Table 8. Stille cross-coupling reaction with thiophenstannane.
ent (MeOC6H4; Table 7, Entries 1–3) and heteroaryl or aryl
bromides were carried out in the presence of [Pd(OAc)2] at
100 °C for 15 h. As a general trend, coupling products were
isolated in good yields (63–82%). Fluorine-containing com-
pounds represent versatile building blocks in medicinal
chemistry.[15] Indeed, cross-coupling reactions between fluo-
rinated tin reagent 31 and various aryl and heteroaryl bro-
mides were examined (Table 7, Entries 4–6) and the ex-
pected products were isolated with good yields in the range
of 70%.
Table 7. Stille cross-coupling reaction with aryl stannanes 30 and
31.
Table 9. Recycling of the tin compound.
The reactivity of thiophene-containing organotin reagent
32 was tested in the Stille reaction with various brominated
substrates (Table 8). Products were obtained in very good
yields (75–80%). Interestingly, the coupling reaction was
successfully performed in the presence of bromoquinoline 8 2 steps. [c] ICP-MS: 2.4 ppm.
[a] Recovered tin reagent 29 from the previous cycle. [b] Yield over
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Green Tools for Stille Cross-Coupling Reactions
H, 8-H), 1.80–1.65 (m, 6 H, 10-H and 15-H), 1.62 (t, J = 7.6 Hz,
3 H, 6-H), 1.50–1.30 (m, 14 H, 9-H, 11-H, 12-H, 13-H, and 14-H),
0.90 (t, J = 7.2 Hz, 6 H, 16-H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 135.9 (2-C), 122.4 (3-C or 4-C), 121.8 (3-C or 4-C), 49.8 (7-C),
45.2 (5-C), 32.0 (J = 34 Hz, 11-C), 29.6 (8-C), 28.2 (J = 12 Hz, 15-
C), 26.8 (J = 37 Hz, 14-C), 25.2 (J = 13 Hz, 10-C), 24.9 (9-C), 21.9
(J = 194 Hz, 13-C), 21.4 (J = 190 Hz, 12-C), 15.5 (6-C), 13.7 (16-
C) ppm. 119Sn NMR (149 MHz, CDCl3): δ = +54.8 ppm. HRMS
(ESI): calcd. for C19H38ClN2Sn [M – Br]+ 449.1740; found
449.1739.
Benefiting from the intrinsic properties of ILs, we pro-
posed to recycle our organotin-supported reagent. Indeed,
halogenotin-supported ionic liquid 50, obtained after Stille
reaction, could be easily separated from product 37 or 38
by extraction with ethyl ether. After addition of allylmagne-
sium bromide in THF, ionic liquid 29 can be regenerated in
two steps with good yield. Thus, organotin compound 29
could be recycled five times with different bromide sub-
strates 9 and 34 without loss of reactivity (Table 9).
It is noteworthy that ICP-MS analysis confirmed that
contamination by tin in the coupling product was avoided
([Sn] Ͻ 3 ppm).
General Procedure for the Synthesis of Ionic Liquids 28–32: To a
solution of ionic liquid 27 (3.76 g, 7.11 mmol) in THF (100 mL) at
room temperature was added a solution of the Grignard reagent
(30.5 mL, 21.33 mmol). After 2 h at room temperature, the solution
was quenched with H2O. The organic layer was then extracted with
CH2Cl2, dried with MgSO4, filtered, and concentrated under re-
duced pressure. The residue was purified by silica gel flash column
chromatography to afford ionic liquids 28–32.
Conclusions
In conclusion, new diversely substituted organotin rea-
gents supported on ionic liquid turned out to be useful
tools for Stille cross-coupling reactions involving bromi-
nated substrates. We have shown that these transformations
could be performed without solvents or additives by using
commercially available precatalysts. Organotin compound
was recycled five times with good yield and reused in Stille
cross-coupling reactions without loss of reactivity. More-
over, it is noteworthy that contamination by tin was limited.
Further applications of organotin reagents on ionic liquids
are currently under investigation in our laboratory.
1-{6-[Dibutyl(vinyl)stannyl]hexyl}-3-ethyl-1H-imidazol-3-ium Bro-
1
mide (28): Yield: 90%. H NMR (400 MHz, CDCl3): δ = 10.32 (s,
1 H, 2-H), 7.50 (s, 1 H, 3-H or 4-H), 7.34 (s, 1 H, 3-H or 4-H),
6.42 (dd, J = 20.8, 14.0 Hz, 1 H, 17-H), 6.12 (dd, J = 3.6, 14.0 Hz,
1 H, 18-Hcis), 5.63 (dd, J = 3.6, 20.8 Hz, 1 H, 18-Htrans), 4.39 (q, J
= 7.6 Hz, 2 H, 5-H), 4.28 (t, J = 7.2 Hz, 2 H, 7-H), 1.88–1.75 (m,
2 H, 8-H), 1.58 (t, J = 7.6 Hz, 3 H, 6-H), 1.50–1.40 (m, 6 H, 10-H
and 15-H), 1.35–1.20 (m, 10 H, 9-H, 11-H, 12-H and 14-H), 1.00–
0.75 (m, 4 H, 13-H), 0.87 (t, J = 7.2 Hz, 6 H, 16-H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 139.0 (J = 188 Hz, 17-C), 137.3 (2-
C), 133.9 (18-C), 121.9 (3-C or 4-C), 121.9 (3-C or 4-C), 50.2 (7-
C), 45.4 (5-C), 33.7 (J = 28 Hz, 11-C), 30.4 (8-C), 29.1 (J = 10 Hz,
15-C), 27.3 (J = 26 Hz, 14-C), 26.7 (J = 10 Hz, 10-C), 25.9 (9-C),
15.7 (6-C), 13.8 (16-C), 9.3 (J = 170 Hz, 12-C), 9.3 (J = 170 Hz,
13-C) ppm. 119Sn NMR (149 MHz, CDCl3): δ = –51.4 ppm.
HRMS (ESI): calcd. for C21H41N2Sn [M – Br]+ 441.2286; found
441.2304.
Experimental Section
1-{6-[Dibutyl(phenyl)stannyl]hexyl}-3-ethyl-1H-imidazol-3-ium Bro-
mide (3): To imidazole derivative 1[9d] (5.35 g, 11.60 mmol) in a se-
aled tube was added bromoethane (9 mL, 110.60 mmol). The mix-
ture was stirred for 17 h at 45 °C then concentrated under reduced
pressure to give ionic liquid 3 (6.61 g, quant.). 1H NMR (400 MHz,
CDCl3): δ = 10.34 (s, 1 H, 2-H), 7.68 (s, 1 H, 3-H or 4-H), 7.47–
7.43 (m, 2 H, Harom.), 7.42 (s, 1 H, 3-H or 4-H), 7.35–7.25 (m, 3
1-{6-[Dibutyl(allyl)stannyl]hexyl}-3-ethyl-1H-imidazol-3-ium Bro-
1
mide (29): Yield: 84%. H NMR (400 MHz, CDCl3): δ = 10.42 (s,
1 H, 2-H), 7.78 (s, 1 H, 3-H or 4-H), 7.54 (s, 1 H, 3-H or 4-H),
5.92 (ddt, J = 8.4, 10.0, 16.8 Hz, 1 H, 18-H), 4.77 (dd, J = 2.0,
H, Harom.), 4.43 (q, J = 7.2 Hz, 2 H, 5-H), 4.28 (t, J = 7.6 Hz, 2 16.8 Hz, 1 H, 19-Htrans), 4.63 (dd, J = 2.0, 10.0 Hz, 1 H, 19-Hcis),
H, 7-H), 2.00–1.80 (m, 2 H, 8-H), 1.60 (t, J = 7.2 Hz, 3 H, 6-H), 4.47 (q, J = 7.2 Hz, 2 H, 5-H), 4.35 (t, J = 7.2 Hz, 2 H, 7-H), 1.97–
1.57–1.47 (m, 6 H, 10-H and 15-H), 1.38–1.27 (m, 8 H, 9-H, 11-H
1.86 (m, 2 H, 8-H), 1.76 (d, J = 8.4 Hz, 2 H, 17-H), 1.62 (t, J =
and 14-H), 1.10–0.97 (m, 6 H, 12-H and 13-H), 0.88 (t, J = 7.2 Hz,
7.6 Hz, 3 H, 6-H), 1.55–1.42 (m, 6 H, 10-H and 15-H), 1.40–1.22
6 H, 16-H) ppm. 13C NMR (100 MHz, CDCl3): δ = 141.6 (17-C), (m, 8 H, 9-H, 11-H, and 14-H), 0.89 (t, J = 7.2 Hz, 6 H, 16-H),
136.4 (2-C), 136.3 (J = 15 Hz, 18-C), 127.9 (J = 20 Hz, 19-C), 127.9
(J = 6 Hz, 20-C), 122.1 (3-C or 4-C), 121.9 (3-C or 4-C), 49.9 (7-
0.92–0.77 (m, 6 H, 12-H and 13-H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 137.8 (J = 22 Hz, 18-C), 136.3 (2-C), 122.1 (3-C or 4-
C), 45.1 (5-C), 33.6 (J = 28 Hz, 11-C), 30.2 (8-C), 28.9 (J = 10 Hz, C), 121.9 (3-C or 4-C), 109.1 (J = 22 Hz, 19-C), 49.9 (7-C), 45.0
15-C), 27.2 (J = 28 Hz, 14-C), 26.5 (J = 10 Hz, 10-C), 25.6 (9-C), (5-C), 33.6 (J = 27 Hz, 11-C), 30.2 (8-C), 28.9 (J = 10 Hz, 15-C),
15.6 (6-C), 13.6 (16-C), 9.5 (J = 170 Hz, 12-C), 9.4 (J = 170 Hz, 27.0 (J = 26 Hz, 14-C), 26.5 (J = 10 Hz, 10-C), 25.7 (9-C), 15.9 (J
13-C) ppm. 119Sn NMR (149 MHz, CDCl3): δ = –43.8 ppm.
HRMS (ESI): calcd. for C25H43N2Sn [M – Br]+ 491.2443; found
491.2456.
= 123 Hz, 17-C), 15.6 (6-C), 13.5 (16-C), 8.9 (J = 156 Hz, 12-C),
8.8 (J = 153 Hz, 13-C) ppm. 119Sn NMR (149 MHz, CDCl3): δ =
–18.9 ppm. HRMS (ESI): calcd. for C22H43N2Sn [M – Br]+
455.2443; found 455.2453.
1-[6-(Dibutylchlorostannyl)hexyl]-3-ethyl-1H-imidazol-3-ium Bro-
mide (27): To a solution of ionic liquid 3 (1.092 g, 1.916 mmol) in
CH2Cl2 (10 mL) at 0 °C was added a solution of HCl (2 m in Et2O,
1.05 mL, 2.107 mmol). The mixture was stirred for 4 h at room
temperature, then treated with H2O. The organic layer was ex-
tracted with CH2Cl2, dried with MgSO4, filtered, and concentrated
under reduced pressure to yield ionic liquid 27 (1.006 g, quant.) as
a yellow oil. 1H NMR (400 MHz, CDCl3): δ = 10.05 (s, 1 H, 2-H),
7.59 (s, 1 H, 3-H or 4-H), 7.59 (s, 1 H, 3-H or 4-H), 4.41 (q, J =
1-{6-[Dibutyl(4-methoxyphenyl)stannyl]hexyl}-3-ethyl-1H-imid-
azol-3-ium Bromide (30): Yield: 85%. 1H NMR (200 MHz, CDCl3):
δ = 10.51 (s, 1 H, 2-H), 7.45 (s, 1 H, 3-H or 4-H), 7.36 (d, J =
8.6 Hz, 2 H, Harom.), 7.28 (s, 1 H, 3-H or 4-H), 6.90 (d, J = 8.6 Hz,
2 H, Harom.), 4.44 (q, J = 7.5 Hz, 2 H, 5-H), 4.29 (t, J = 7.5 Hz, 2
H, 7-H), 3.80 (s, 3 H, 21-H), 1.70–1.95 (m, 2 H, 8-H), 1.60 (t, J =
7.5 Hz, 3 H, 6-H), 1.40–1.60 (m, 6 H, 10-H and 15-H), 1.20–1.40
(m, 8 H, 9-H, 11-H, and 14-H), 0.95–1.10 (m, 6 H, 12-H and 13-
7.6 Hz, 2 H, 5-H), 4.34 (t, J = 7.2 Hz, 2 H, 7-H), 2.05–1.85 (m, 2 H), 0.88 (t, J = 7.1 Hz, 6 H, 16-H) ppm. 13C NMR (100 MHz,
Eur. J. Org. Chem. 2011, 143–149
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FULL PAPER
CDCl3): δ = 159.5 (20-C), 137.3 (J = 20 Hz, 19-C), 136.2 (2-C),
131.5 (J = 203 Hz, 17-C), 122.0 (3-C or 4-C), 121.9 (3-C or 4-C),
113.7 (J = 22 Hz, 18-C), 57.8 (21-C), 49.8 (7-C), 45.0 (5-C), 33.5
(J = 28 Hz, 11-C), 30.1 (8-C), 28.9 (J = 10 Hz, 15-C), 27.2 (J =
28 Hz, 14-C), 26.5 (J = 10 Hz, 10-C), 25.6 (9-C), 15.5 (6-C), 13.5
(16-C), 9.4 (J = 165 Hz, 12-C), 9.3 (J = 165 Hz, 13-C) ppm. 119Sn
NMR (149 MHz, CDCl3): δ = –41.9 ppm. HRMS (ESI): calcd. for
C26H45N2OSn [M – Br]+ 521.2548; found 521.2582.
Acknowledgments
We thank CNRS (Centre National de la Recherche Scientifique),
the Université du Maine, the Agence Nationale de la Recherche
(Grant N°: ANR-07-JCJC-0026-01), and the French MENRT
(Ministère de l’Education Nationale de la Recherche et de Technol-
ogie) for a fellowship to P.D.P. We also thank Amélie Durand for
technical support.
1-{6-[Dibutyl(4-fluorophenyl)stannyl]hexyl}-3-ethyl-1H-imidazol-3-
1
ium Bromide (31): Yield: 88%. H NMR (400 MHz, CDCl3): δ =
10.32 (s, 1 H, 2-H), 7.72 (s, 1 H, 3-H or 4-H), 7.46 (s, 1 H, 3-H or
4-H), 7.32 (dd, J = 8.5 Hz, JH,F = 8.5 Hz, 2 H, Harom.), 6.9 (dd, J
= 8.5 Hz, JH,F = 8.5 Hz, 2 H, Harom.), 4.38 (q, J = 7.1 Hz, 2 H, 5-
H), 4.24 (t, J = 7.7 Hz, 2 H, 7-H), 1.70–1.90 (m, 2 H, 8-H), 1.52
(t, J = 7.1 Hz, 3 H, 6-H), 1.35–1.50 (m, 6 H, 10-H and 15-H), 1.15–
1.35 (m, 8 H, 9-H, 11-H, and 14-H), 0.85–1.10 (m, 6 H, 12-H and
13-H), 0.80 (t, J = 7.1 Hz, 6 H, 16-H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 162.9 (d, JC,F = 250 Hz, 20-C), 137.6 (d, JC,F = 6 Hz,
J = 18 Hz, Carom.), 136.3 (17-C), 136.2 (2-C), 122.1 (3-C or 4-C),
121.9 (3-C or 4-C), 114.9 (d, JC,F = 19 Hz, J = 22 Hz, Carom.), 49.8
(5-C), 45.0 (7-C), 33.5 (J = 28 Hz, 11-C), 30.1 (8-C), 28.8 (J =
10 Hz, 15-C), 27.1 (J = 28 Hz, 14-C), 26.4 (J = 10 Hz, 10-C), 25.6
(9-C), 15.5 (6-C), 13.5 (16-C), 9.5 (J = 165 Hz, 12-C), 9.4 (J =
165 Hz, 13-C) ppm. 19F NMR (376 MHz, CDCl3): δ = –114.7 ppm.
119Sn NMR (149 MHz, CDCl3): = δ–40.5 (d, JSn,F = 8.1 Hz) ppm.
HRMS (ESI): calcd. for C25H42N2FSn [M – Br]+ 509.2349; found
509.2386.
[1]
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1-{6-[Dibutyl(thiophen-2-yl)stannyl]hexyl}-3-ethyl-1H-imidazol-3-
1
ium Bromide (32): Yield: 79%. H NMR (400 MHz, CDCl3): δ =
10.47 (s, 1 H, 2-H), 7.64 (d, J = 4.7 Hz, 1 H, 20-H), 7.63 (s, 1 H,
3-H or 4-H), 7.40 (s, 1 H, 3-H or 4-H), 7.26 (dd, J = 3.0, 4.7 Hz,
1 H, 19-H), 7.18 (d, J = 3.0 Hz, 1 H, 18-H), 4.44 (q, J = 7.5 Hz, 2
H, 5-H), 4.30 (t, J = 7.5 Hz, 2 H, 7-H), 1.80–1.95 (m, 2 H, 8-H),
1.60 (t, J = 7.5 Hz, 3 H, 6-H), 1.50–1.60 (m, 6 H, 10-H and 15-H),
1.25–1.40 (m, 8 H, 9-H, 11-H, and 14-H), 1.00–1.15 (m, 6 H, 12-
H and 13-H), 0.89 (t, J = 7.1 Hz, 6 H, 16-H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 136.1 (2-C), 135.5 (17-C), 134.9 (J = 13 Hz,
19-C), 130.3 (20-C), 127.6 (J = 20 Hz, 18-C), 122.1 (3-C or 4-C),
121.8 (3-C or 4-C), 49.6 (7-C), 44.8 (5-C), 33.2 (J = 28 Hz, 11-C),
29.9 (8-C), 28.6 (J = 10 Hz, 15-C), 26.9 (J = 28 Hz, 14-C), 26.1 (J
= 10 Hz, 10-C), 25.4 (9-C), 15.4 (6-C), 13.3 (16-C), 10.5 (J =
165 Hz, 12-C), 10.5 (J = 165 Hz, 13-C) ppm. 119Sn NMR
(149 MHz, CDCl3): δ = –40.0 ppm. HRMS (ESI): calcd. for
C23H41N2SSn [M – Br]+ 497.2007; found 497.2021.
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[7]
General Procedure for Recycling Tin Compound 29: To a solution
of ionic liquid 29 (950 mg, 1.780 mmol) was added Pd(PPh3)4
(102 mg, 5 mol-%) and aryl bromide 9 or 34 (290 μL, 1.780 mmol).
The mixture was stirred for 5 h at 80 °C. Ionic liquid 50 (1.076 g)
was separated from product 37 or 38 by extraction with ether. The
organic layer was concentrated, and the crude product was purified
by silica gel flash column chromatography to afford allyl com-
pound 37 or 38 (290 mg, 86%). Ionic liquid 29 was heated (70 °C)
under high vacuum. After cooling to room temperature, allylmag-
nesium bromide (1 m in Et2O, 5.6 mL, 3.228 mmol) was added in
THF (30 mL) at room temperature. The mixture was stirred for 2 h
at room temperature, then treated with H2O. The organic layer was
extracted with CH2Cl2, dried with MgSO4, filtered, and concen-
trated under reduced pressure. The crude product was purified by
silica gel flash column chromatography to afford ionic liquid 29
(710 mg, 75% in two steps) as a yellow oil.
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Supporting Information (see footnote on the first page of this arti-
cle): Experimental details and copies of the 1H and 13C NMR spec-
tra.
148
www.eurjoc.org
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 143–149

Green Tools for Stille Cross-Coupling Reactions
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Received: August 24, 2010
Published Online: November 24, 2010
Eur. J. Org. Chem. 2011, 143–149
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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