Efficient, recoverable, copper-free Sonogashira reaction under FBS and thermomorphic mode

Article abstract of DOI:10.1016/j.jorganchem.2008.10.042

The solubility property of high fluorine content ligands allows us to report in this article the accomplishment under the fluorous biphasic system (FBS) the Pd-catalyzed Sonogashira reactions using novel recyclable Pd catalysts with fluorous-ponytails in

Full text of DOI:10.1016/j.jorganchem.2008.10.042

Journal of Organometallic Chemistry 694 (2009) 278–284
Contents lists available at ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Efficient, recoverable, copper-free Sonogashira reaction under FBS and
thermomorphic mode
a,*
a
a
a
b
Norman Lu , Yi-Chuan Chen , Wei-Shung Chen , Ter-Lin Chen , Sy-Juen Wu
a
Institute of Organic and Polymeric Materials, National Taipei University of Technology, 1, Sec. 3, Chung-Hsiao E. Rd., Taipei 106, Taiwan
Eli Lilly and Company, Indianapolis, IN 46285, United States
b
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 17 August 2008
Received in revised form 24 October 2008
Accepted 24 October 2008
Available online 31 October 2008
The solubility property of high fluorine content ligands allows us to report in this article the accomplish-
ment under the fluorous biphasic system (FBS) the Pd-catalyzed Sonogashira reactions using novel recy-
clable Pd catalysts with fluorous-ponytails in the structure of 2,2 -bpy ligands that are only soluble in
perfluorinated solvents at room temperature. Alternatively, without using any fluorous solvent but under
the thermomorphic mode, the same Pd catalysts proceed with the Cu-free Sonogashira reactions homo-
geneously in DMF at 135 ± 5 °C, whereas the product mixtures after reaction remain in solution and the
Pd catalysts precipitate from DMF at low temperature.
0
Keywords:
Sonogashira reactions
Fluorous-ponytails
Fluorous biphasic system
Thermomorphic mode
Cu-free
Ó 2008 Elsevier B.V. All rights reserved.
Homogeneous
1
. Introduction
The concept of fluorous biphasic catalysis (FBC) was first intro-
[21–23]. The reaction usually proceeds in the presence of homoge-
neous Pd catalyst and Cu salt. As the most widely employed co-cat-
alysts, the Cu salts also mediate the homocoupling of terminal
alkynes and usually may result in a high Cu contamination (of
the product) [24]. The homocoupled side product of terminal al-
kynes is problematic when terminal alkynes are difficult to obtain.
In view of all these factors, reported here are the uses of novel Pd
complexes with fluorous bipyridyl ponytails as catalysts in the
copper-free Sonogashira reaction under the fluorous biphasic sys-
tem (FBS) and separately under the thermomorphic mode.
duced by Horváth and Rábai in 1994 [1]. This field has evolved rap-
idly since then [2]. FBC has already been applied to a variety of
common organic reactions, e.g., hydroboration of alkenes [3,4],
hydroformylation of alkenes [1,5], epoxidation of alkenes [6–8],
Wacker oxidation of alkenes [9], palladium allylic alkylation [10],
and oxidation of alcohols [11]. Although FBC combines the advan-
tages of homogeneous catalysis and heterogeneous catalysis
[
12,13], the large-scale usage of perfluorocarbon solvents has suf-
fered from high cost and environmental pollutions. In response
to these limitations, new methodologies have been introduced
2. Results and discussion
[
[
14–19], one of which is based on the thermomorphic property
14,15] of catalysts in organic solvent. For example, a number of
2.1. Catalyst synthesis
fluorous bipyridine ligands have been successfully synthesized to
replace fluorinated phosphines and used in the Pd-catalyzed Heck
reaction [18,20] as well as in the Cu-catalyzed the aerobic oxida-
tion of alcohols [19]. These novel fluorous bipyridine ligands are
also useful in the Sonogashira reaction described below.
The Sonogashira coupling reaction of terminal alkynes with aryl
or vinyl halides provides a powerful tool for carbon–carbon bond
formation, which has been widely applied in areas such as natural
product synthesis, pharmaceutical industry and material science
As shown in Scheme 1, the reaction of [Pd(CH
3 2 2
CN) Cl ] or
[Pd(PhCN)
tives, 4,4 -bis(R
2
Cl
2
] with three highly fluorinated bipyridine deriva-
0
0
f
CH
2
OCH
2
)-2,2 -bpy (1a–c) [19], resulted in the Pd
0
0
complexes, [PdCl
2
(4,4 -bis-(R
f
CH
= n-C
respectively. The fluorine contents of 1a–c are 61.2%, 62.3% and
63.3%, respectively. The partition ratios of 1a–c in CH Cl /FC77 sys-
2 2
OCH )-2,2 -bpy)] (2a–c), as pale
yellow solids, where R
f
9
F19 (a), n-C10F21 (b), n-C11F23 (c),
2
2
tem are 1.04:1, 1:42 and 1:70, respectively. On the other hand, the
partition ratios of 1b–c in DMF/FC77 system are very small (ca.
1
:1000). The distribution results of 1a–c in two different solvent
systems are shown in Table 1. Because of good partition ratios of
*
Corresponding author. Tel.: +886 2 2771 2171x2417; fax: +886 2 2731 7174.
E-mail address: normanlu@ntut.edu.tw (N. Lu).
the ligands 1b–c in DMF/FC 77 system, the Pd complexes 2b–c
0
022-328X/$ - see front matter Ó 2008 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2008.10.042

N. Lu et al. / Journal of Organometallic Chemistry 694 (2009) 278–284
279
Rf
Rf
O
O
[
Pd(CH CN) Cl ]
N
3
2
2
N
N
Cl
Cl
or
Pd
+ by-product
+
[
Pd(PhCN) Cl ]
2 2
N
O
O
Rf
a
b
c
C9F
19
Rf
Rf
C10F21
C11F23
1
a-c
2a-c
Scheme 1.
Table 1
Distribution partition of ligands 1a–c in two biphasic systems.
Table 2
Recycling results of 2b-catalyzed Sonogashira reaction of 3b and 4a with CuI under
FBS.
Ligand (F%)
CH
2
Cl
2
:FC 77
DMF:FC 77
Cycle no.
Time (h)
Temperature (°C)
Yielda (%)
1
1
1
a: 61.2
b: 62.3
c: 63.3
1.04:1
1:42
1:70
1:6.9
1:1000
1:>1000
1
2
3
4
5
6
7
8
4
4
4
4
4
4
4
6
135
135
135
135
135
135
135
135
100 (96)
100
100 (94)
100
100 (95)
100
100
were selected as the catalysts for the C–C bond forming Sonogash-
ira reaction under FBS.
>99
2.2. Sonogashira reaction with Pd complex 2b as catalyst under FBS
Conditions: DMF/FC 77 1:1 (3 mL each); CuI 10 mol% (0.0275 mmol, 5.3 mg), iodo-4-
nitrobenzene (3b: 0.275 mmol, 68.5 mg), phenylacetylene (4a: 0.33 mmol,
3
3.7 mg), DABCO: 1.5 equivalents (0.413 mmol, 46.2 mg), 1 mol% Pd complex 2b
As shown in Scheme 2, in the presence of 2b (1 mol%) and 1,4-
(
4 mg). After each cycle, the DMF and FC 77 layers were separated at 0 °C using a
diazabicyclo[2.2.2]octane (DABCO) base, aryl iodide and phenyla-
cytelene can be smoothly coupled to afford the corresponding
arylacetylenes in moderate to excellent yields at the temperature
of 135 ± 5 °C. Tables 2 and 3 list the results of Sonogashira reaction
under FBS with and without the addition of CuI, respectively. The
Pd complex 2b is an effective catalyst in the recycling runs of Sono-
gashira reaction of iodo-4-nitrobenzene (3b) and phenylacytelene
2 2
separatory funnel. The FC 77 layer was washed with 2 mL DMF (or CH Cl ) before
proceeding to the next cycle.
a
Based on GC yield (internal standard is NMP); isolated yields are given in
parentheses.
for the 2b-catalyzed Sonogashira reaction of 4a with unactivated
iodobenzene, 3a, under FBS (see Table A in Supplementary mate-
rial). There was almost no homocoupled dimer formation under
FBS with or without CuI.
(4a), apparently.
The recycling usage of 2b-catalyst with CuI co-catalyst in Sono-
gashira reaction, shown in Table 2, gave an average yield of >99%
-nitrophenylacetylene. The similar 2b-catalyzed Sonogashira
4
2.3. Sonogashira reaction with Pd complex 2a–c as catalyst under the
reaction under a Cu-free condition gave also good results of recov-
ery and reusage. The yield slightly dropped after the 7th run as
shown in Table 3 with the average yield of 98% over 8 runs, only
a few percents lower than that in Table 2. An averaged yield of
thermomorphic mode
In addition to reactions under FBS, the same Pd-catalyzed Sono-
gashira reactions was also successfully carried out employing the
9
6% and a good recyclability up to 8 times were also demonstrated
Catalyst 2b
30 -140 C; 4-8h
o
1
Y
HI.base
R1
X
H
Y
R1
base:K CO , DABCO
2
3
FBC (DMF/FC77)
R1
R1
a H
Y
3
3
a
b
H
Y
5
5
Ph
NO
X = I
4a Ph
2
b NO Ph
2
Scheme 2.

2
80
N. Lu et al. / Journal of Organometallic Chemistry 694 (2009) 278–284
Table 3
tion during recovery of catalysts are more efficient under the ther-
momorphic mode.
Recycling results of 2b-catalyzed Sonogashira reaction of 3b and 4a without CuI
under FBS.
Shown in Fig. 1 are the pictures of the 3 stages of 2b-catalyzed
Cu-free Sonogashira reaction of 3b and 4a under the thermomor-
phic mode. Before the start of the reaction, both reactants 3b and
4a and DABCO base were soluble in DMF, yet complex 2b was
not. During the catalysis, the DMF solution became monophasic
when the temperature was raised to ca. 135 °C; the picture shown
at this stage being at the 5th run. At the end of the reaction, the
product mixtures were cooled to room temperature with concur-
rent catalyst precipitation out of DMF. By decantation the solid cat-
alyst was readily recovered by for reuse.
Cycle no.
Time (h)
Temperature (°C)
Yielda (%)
1
2
3
4
5
6
7
8
4
4
4
4
4
4
8
8
135
135
135
135
135
135
135
135
100
100 (96)
100
100 (96)
97
97
98 (95)
92
Reaction conditions: 1 mol% Pd complex 2b (4 mg); DMF/FC 77 (3 mL each); CuI-
free; 3b (0.275 mmol, 68.5 mg); 4a (0.33 mmol, 33.7 mg); DABCO (0.413 mmol,
Both 2a and 2c were also good catalysts for Pd-catalyzed Sono-
gashira reactions. The catalytic abilities in the decreasing order are
4
6.2 mg).
a
Based on GC yield; isolated yields are given in parentheses.
2
a > 2b > 2c (see Table B in Supplementary material) parallel to the
fluorous chain length [19]. Although 2a was the best catalyst
among the three used in Sonogashira reaction under the thermo-
morphic mode, its operating temperature range [18] between
ꢀ10 and 140 °C was less convenient. Thus, 2b whose operating
temperature range was between 25 and 140 °C was chosen to dem-
onstrate most reactions. A variety of bases including DABCO,
thermomorphic mode. Shown in Scheme 3, the Pd-catalyzed Sono-
gashira reactions of aryl halide (3a–f) with alkyne (4a–b) demon-
strated the recycling usage with 2a–c as the catalysts in DMF
under the thermomorphic mode, at 135 ± 5 °C varying between 2
and 8 h in each run. At the end of each cycle, the product mixtures
were cooled to ꢀ10 °C then centrifuged, followed by decantation
for recovery of catalysts. The collected 2a–c was added again with
fresh DMF, substrates, and base to proceed to the next cycle. The
products were quantified by GC analysis with an internal standard
K
2
CO
mentary material), and it was found that K
ally worked better than remaining organic bases used.
Furthermore, because K CO was not totally soluble in DMF, it
may also precipitate out along with the recovered catalyst. The
slight insolubility of K CO could occasionally result in the separa-
3
, NEt
3
, and piperidine had been used (see Table C in Supple-
2
CO and DABCO gener-
3
2
3
(
NMP) or alternatively by isolated weights. The results showed that
the Sonogashira coupling at this setting is clean and efficient. One
example is shown in Table 4, in which the 2b-catalyzed Sonogash-
ira reaction of 3b and 4a with 10% CuI gave rise to excellent yields
and a good recycling capability for 14 times under the thermomor-
phic mode.
Both 2a and 2b-catalyzed Sonogashira reactions of 3a with 1-
hexyne, 4b, was tested under the thermomorphic mode with the
results shown in Table 5. Almost quantitative yields were obtained
for the first 3 runs each with time between 4 and 6 h. Afterwards,
the yield dropped greatly as expected because of the lower reactiv-
ity of 4b relative to that of 4a.
2
3
tion and recovery problems. DABCO, on the other hand, was chosen
as a better base because of high b.p. and good solubility in DMF.
The expected substituent electronic influence was also observed
[25], with electron-withdrawing group speeding up and the
electron-releasing group slowing down the reaction, respectively.
Consistently, the rate of the catalyzed Sonogashira reaction with
R
1
-C
6
H -I [R
4
1
2 3
= H (3a), NO (3b), and CH (3c)] decreased with sub-
stituent NO
2
> H > CH (see Table D in Supplementary material).
3
Low Pd catalyst loadings had also been tested. Instead of
1 mol%, reactions with 0.1, 0.02 and 0.001 mol% of Pd catalyst 2b
were also successfully carried out. The results were shown in Table
7.
The Cu-free condition was successful in 2b-catalyzed Sonogash-
ira reaction of 3b with 4a under the thermomorphic mode. As
shown in Table 6, very high yields have been easily achieved for
In a polymer supported, heterogeneous, Pd-catalyzed Sonogash-
ira reaction, the turnover number (TON) is usually around 1000 at
the high end in a single batch mode [26]. Interestingly, the effec-
tive Pd-catalyzed Sonogashira reaction of aryl iodide and phenyl-
acetylene by 2b shows a very high TON. The TON of 82000
(entry 3 in Table 7) from the Cu-free Sonogashira reaction of this
type was easily achieved at 140 °C under the thermomorphic con-
ditions. It seems that the present Sonogashira reaction under the
thermomorphic mode may have overcome the difficult separation
and low efficiency problems at the same time.
8
cycles. Judged between the results in Table 3 and in Table 6,
one can conclude that in the same Sonogashira reaction catalyzed
by 2b, the recycling results with the thermomorphic mode were
better than with FBS. With the thermomorphic mode, the depen-
dence of the solubility of fluorous catalysts in organic solvent on
temperature only is important for recovery of catalysts. However,
with FBS the solubility of fluorous catalysts in organic solvent
and in fluorous solvent are both important. Apparently in this case,
the single phase formation during catalysis and the phase separa-
Catalyst 2a-c
30 -140 C; 2-8 h
o
1
R1
X
H
Y
R1
Y
HX.base
base:K CO , DABCO, etc.
2
3
FBC (DMF/FC77)
R1
X
R1
5a H
X
Y
I
Y
Ph
Ph
Ph
3
3
3
3
3
3
a
H
I
I
I
b NO
I
4a Ph
4b C H
5b NO
2
2
2
2
c
Me
I
4
9
5c
Me
d NO
Br
Br
Br
5d NO
5e CN
Br Ph
e
f
CN
CH CO
Br
Br
I
Ph
Ph
5f
CH CO
3
3
6
a
H
C H
4
9
Scheme 3.

N. Lu et al. / Journal of Organometallic Chemistry 694 (2009) 278–284
281
Table 4
Recycling results of 2b-catalyzed Sonogashira reaction of 3b and 4a under the thermomorphic mode.
Cycle no.
Yield (%)
1
2
3
4
5
6
7
8
9
10
11
12
74
13
82
14
91
100
100
100
100
100
100
100
100
100
100
100
Conditions: reaction time = 4 h; 1 mol% Pd complex 2b (4 mg); DMF (5 mL); CuI 10 mol% (0.0275 mmol, 5.3 mg); 3b (0.275 mmol, 68.5 mg); 4a (0.33 mmol, 33.7 mg); DABCO:
.5 equivalents (0.413 mmol, 46.2 mg).
1
Table 5
Table 7
Recycling results of 2a- and 2b-catalyzed Sonogashira reactions of 3a and 4b under
Different loadings of catalyst in 2b-catalyzed Cu-free Sonogashira reaction under the
the thermomorphic mode.
thermomorphic mode.
Catalyst
Loading (%)
Temperature (°C)
Base
Yielda
2b loading (%)
Reactant
Time (h)
3
Yielda (%)
100 (100)
TON
2
a
1
1
135
135
K
K
2
CO
CO
3
99, 99, 99, 30
99, 99, 99, 28
1
0.1
3b, 4a
1000
990
990
5000
4950
82000
b
2
b
2
3
99
b
99
Conditions: 1 mol% Pd complex [2a (3.7 mg), 2b (4 mg)]; DMF (5 mL); CuI 10 mol%
0.0275 mmol, 5.3 mg); 3a (0.275 mmol, 56.1 mg); 4b (0.33 mmol, 33.7 mg);
CO : 1.5 equivalents (0.413 mmol, 57.1 mg).
Based on GC yield.
2
3
0.02
3b, 4a
3b, 4a
6
7
100
(
b
99
K
2
a
3
0.001
82 (82)
a
Based on GC yield (internal standard is NMP); isolated yields are given in
parentheses.
In order to show the recoverability, 2b in entry 1 and entry 2 was recycled and
reused for twice and once, respectively.
b
Table 6
Recycling results of 2b-catalyzed CuI-free Sonogashira reaction of 3b and 4a under
the thermomorphic mode.
Cycle no.
Time (h)
Temperature (°C)
Yielda (%)
Table 8
Recycling results of 2b-catalyzed Sonogashira reaction of activated bromobenzenes,
1
2
3
4
5
6
7
8
2
2
4
4
4
4
4
4
135
135
135
135
135
135
135
135
100 (98)
100
100
100 (97)
100
100 (97)
100
3d–f, and 4a under the thermomorphic mode.
Yielda
Substrate Loading (%) Temperature
°C)
Base
(
3d
1
1
1
135
135
135
DABCO 98, 97 (96), 92, 90 (88), 89
CO 98, 98 (97), 93, 92 (91), 90
DABCO 96, 96 (94), 82, 66 (65)
CO 97, 96 (95), 89, 56 (56)
DABCO 50, trace
CO 51, trace
K
2
3
100 (96)
3e
K
2
3
Reaction condition: 1 mol% Pd catalyst 2b (4.0 mg); DMF (5 ml); CuI-free; 3b
3f
(
0.275 mmol, 68.5 mg), 4a (0.33 mmol, 33.7 mg), DABCO (0.412 mmol, 46.2 mg).
K
2
3
a
Based on GC yield; isolated yields are given in parentheses.
Reaction condition: 1 mol% Pd catalyst 2b (4.0 mg); DMF (5 ml); 10% CuI; 3d–f
0.275 mmol), 4a (0.33 mmol, 33.7 mg), DABCO: 1.5 equivalents (0.412 mmol,
(
4
6.2 mg); reaction time = 14 h.
Based on GC yield (internal standard is NMP); isolated yields are given in
a
parentheses.
3
d better than 3e better than 3f, parallel to the substituent elec-
tronic effects for bromobenzenes. Because the acetyl group was
not electron-withdrawing enough, the relevant second cycle data
gave already a poor yield. The strong electron-withdrawing nitro
group gave the best results. The results of Sonogashira reaction
using three different activated bromobenzens were shown in Table
2 3
8, using either DABCO or K CO as a base.
3
. Conclusions
To our knowledge, this is the first example of Pd-catalyzed
Sonogashira reaction of aryl halide with alkynes, with the same
Pd catalysts running under either FBS or the thermomorphic mode.
If taking advantage of the thermomorphic property, the use of
expensive fluorinated solvents can be avoided. We have also dem-
onstrated that the good TON of Cu-free Sonogashira catalysis is
achieved, with both aryl iodides and aryl bromides as the sub-
strate, and the Pd catalysts easily recovered and reused (up to 14
cycles in one of the examples).
Fig. 1. Photographs of 2b-catalyzed Sonogashira reaction (I) reactant mixture
3b + 4a) plus DABCO in DMF and the insoluble Pd catalyst, (II) homogeneous DMF
solution at 135 °C from 5th run, and (III) product mixture in DMF and the
precipitation of catalyst 2b at 25 °C.
(
2
.4. The 2b-catalyzed Sonogashira reaction of activated bromobenzene
under thermomorphic mode
4. Experimental
The activated bromobenzenes, R
1
-C
6
H -Br [R
4
1
= NO
2
(3d), CN
4.1. General procedures
(
3
3e), and CH CO (3f)], were also tested in the Sonogashira reactions
under the thermomorphic mode. A much longer time, ca. 14 h, was
needed for the reaction to complete; and the recycling results were
Gas chromatographic/mass spectrometric data were obtained
using an Agilent 6890 Series gas chromatograph with a series

2
82
N. Lu et al. / Journal of Organometallic Chemistry 694 (2009) 278–284
5
973 mass selective detector. The reaction was monitored with a
HP 6890 GC using a 30 m ꢁ 0.250 mm HP-1 capillary column with
a 0.25 m stationary phase film thickness. The flow rate was 1 mL/
min and splitless. Samples analyzed by fast atom bombardment
FAB) mass spectroscopy were done by the staff of the National
–CF
ꢀ125.7 (4F); C NMR (126 MHz, DMF-d
trum was not obtained due to the extremely weak signal at
3
), ꢀ119.3 (4F), ꢀ121.3 (24F), ꢀ122.2 (4F), ꢀ122.9 (4F),
1
3
1
3
6
, d ppm): C NMR spec-
l
ꢀ1
90 °C; FT-IR (KBr pellets, vmax/cm ): 1602, 1558 (m, mbpy), 1207,
+
35
(
1152 (vs,
m
CF
2
); HR-MS (FAB): (M ; m/z=) C36
N
2
H
F
14
F
46
O
2
Pd Cl
2
Pd Cl35Cl
3
7
Central University (Taiwan) mass spectrometry laboratory. Infra-
red spectra were obtained on a Perkin–Elmer RX I FT-IR Spectrom-
eter. NMR spectra were recorded on Bruker AM 500 and Joel AM
calcd. 1555.8732, found 1555.8721;
calcd. 1557.8679, found 1557.8656; C36
1559.8674, found 1559.8662.
C
36
N
2
H
14
46
O
2
3
7
N
H
2 14
F
46
O
2
Pd Cl
2
calcd.
2
00 using 5 mm sample tubes. CD
3 2 2 3
OD, CD Cl , CDCl , deuterated
1
DMF and deuterated Me SO were the references for both H and
2
1
3
Ò
19
4.2.4. Recycling studies
C NMR spectra; and Freon 11 (CFCl
NMR spectra.
3
) was the reference for
F
All the Pd-catalyzed Sonogashira reaction products are known
products. The products (5a–f and 6a) have been checked by GC/
MS, NMR spectrometer and m.p. if the product is a solid. These data
are listed below.
4
.1.1. Starting materials
Chemicals, reagents, and solvents employed were commercially
available and used as received. C OH, C10 OH and
OH were purchased from Aldrich and SynQuest.
9
F
19CH
2
F21CH
2
1
(
5a) PhC„CPh: white solid, m.p.: 60–61 °C. H NMR (500 MHz,
10 2
C F23CH
CDCl
H).GC/MS (m/z; EI): 178 (M ), 89 (M ꢀC
5b = 5d) 4-O NC CCPh: yellow solid, m.p.: 119–120 °C. H
NMR (500 MHz, CDCl , d ppm, J Hz): 8.20 (d, J = 8.6, 2H), 7.65
d, J = 8.6, 2H), 7.57–7.52 (m, 2H), 7.38–7.36 (m, 3H).GC/MS
3
, d ppm, J Hz): d 7.56–7.51 (m, 4H), 7.38–7.31 (m,
+
+
+
6
7 7 6 4
H ), 76 (C H ).
4.2. Preparation of Pd complexes 2a–c where R
f 9 21
= n-C F19 (a), n-C10F
1
(
2
6 4
H
(
b), and n-C11 23 (c)
F
3
(
(
(
(
(
Equal molar [PdCl
respective ligands 1a–c (0.52 mmol) [19] in different reactions
were charged into a round bottomed flask, and CH Cl (3 mL)
added as solvent. The solution color changed from red to yellow
after the mixing for several min. The solution was further stirred
at 60 °C for 24 h before the solvents and volatiles were removed
under vacuum. The resulting yellow solids were collected as spec-
troscopically pure products.
2 3 2
(CH CN) ] (134.9 mg, 0.52 mmol) and
+
+
+
m/z; EI): 223 (M ), 193 (M ꢀNO), 177 (M ꢀNO
2
), 165
+
+
M ꢀCNO
2
), 151 (M ꢀC
2 2 2
H NO ).
2
2
1
3 6 4
5c) 4-CH C H C„CPh: white solid, m.p.: 73–74 °C. H NMR
3
500 MHz, CDCl , d ppm, J Hz): d 7.54–7.50 (m, 2H), 7.42 (d,
J = 8.0, 2H), 7.37–7.26 (m, 3H), 7.14 (d, J = 8.0, 2H), 2.36 (s,
+
+
3
H).GC/MS (m/z; EI): 192 (M ), 165 (M ꢀC
2
H
3
), 115
+
6 5
H
), 96 (M2+).
(
(
(
(
M ꢀC
5e) 4-NCC
500 MHz, CDCl
m, 2H), 7.40 (d, J = 2.1, 2H), 7.39 (d, J = 1.65, 1H).GC/MS (m/z;
1
H
6 4
C„CPh: yellow solid, mp.: 91–92. H NMR
3
, d ppm, J Hz): 7.63 (q, J = 8.5, 4H), 7.55–7.56
4.2.1. Analytical data of 2a
(
NMR data collected in d-DMF at 90 °C because of poor solubil-
+
+
+
1
EI): 203 (M ), 176 (M ꢀCHN), 150 (M ꢀC H N), 101
3
3
6
ity): yield 96%; H NMR (500 MHz, DMF-d , d ppm, J Hz) 9.29 (d,
2
5
NMR (470.5 MHz, DMF-d
–
+ + +
3
3
(M ꢀC H N), 88 (M ꢀC H N), 75 (M ꢀC H N).
7
4
8
5
9
6
H,
J
HH = 5.8, H
6
), 8.47 (s, 2H, H
3 5
), 7.81 (d, 2H, JHH = 5.8, H ),
3
19
3 6 4
(5f) 4-CH COC H C„CPh: white solid, m.p.: 98–99 °C.
.08 (s, 4H, bpy-CH
2
), 4.47 (t, 4H,
J
HF = 14.6, C10
, d ppm, J Hz) ꢀ80.9 (t, 6F,
F
21-CH
2
);
F
1
3
3
H NMR (500 MHz, CDCl , d ppm, J Hz): d 7.95 (d, J = 8.0, 2H),
6
JFF = 7.52,
7
.61 (d, J = 8.0, 2H), 7.55 (d, J = 2.4, 2H), 7.39–7.35 (m, 3H), 2.62
CF
3
), ꢀ119.3 (4F), ꢀ121.2 (16F), ꢀ122.2 (4F), ꢀ122.8 (4F),
13
(s, 3H).
GC/MS (m/z; EI): 220 (M ), 205 (M ꢀCH
ꢀ
125.6 (4F); C NMR (126 MHz, DMF-d
CF ), 121.5, 125.0, 150.5, 153.0, 157.0 (bpy), 105.0–
21); FT-IR (KBr pellets, vmax/cm ): 1624, 1561 (m,
6 2
, d ppm) 72.4 (bpy-CH ),
+
+
+
3
), 176 (M ꢀC
2 4
H O),
6
1
1
C
C
C
8.2 (CH
16.0 (C10
2
2
+
+
ꢀ1
151 (M ꢀC H O), 88 (M ꢀC H O).
4
5
9
8
F
m
bpy)
m/z=)
calcd. 1355.8860, found 1355.8823;
1
+
2 3 3
(6a) PhC„C(CH ) CH : colorless liquid. H NMR (500 MHz,
207, 1148
(vs,
m
CF
2
);
HR-MS
(FAB):
(M ;
3
5
CDCl , d ppm, J Hz): d 7.41–7.37 (m, 2H), 7.29–7.25 (m, 3H),
3
32
32
32
N
2
N
2
N
2
H
H
H
14
14
14
F
38
F
38
F
38
O
2
O
2
O
2
Pd Cl
2
35
3
7
2.41 (t, J = 7.2, 2H), 1.63–1.56 (m, 2H), 1.54–1.47 (m, 2H), 0.95
Pd Cl Cl calcd. 1357.8864, found 1357.8848;
Pd Cl calcd. 1359.8835, found 1359.8792.
2
+
+
3
7
(t, J = 7.2, 3H).GC/MS (m/z; EI): 158 (M ), 143 (M ꢀCH ), 129
3
+
+
+
(
M ꢀCH
CH
3 2
), 115 (M ꢀCH
3 2
CH CH
2
), 102 (M ꢀC
4 8
H ), 89
+
+
(
M ꢀC
H
5 9
), 77 (C H
6 5
).
4.2.2. Analytical data of 2b
(
NMR data collected in d-DMF at 90 °C because of poor solubil-
1
ity): yield 96%; H NMR (500 MHz, DMF-d
H,
.08 (s, 4H, bpy-CH
NMR (470.5 MHz, DMF-d
6
, d ppm, J Hz) 9.29 (d,
), 7.81 (d, 2H, JHH = 5.8, H ),
3 5
4.3. Recycling studies of the Sonogashira reaction with Pd complex 2b
as catalyst under FBS
3
3
2
5
J
HH = 5.8, H
6
), 8.47 (s, 2H, H
3
19
2
), 4.47 (t, 4H,
J
HF = 14.6, C10
, d ppm, J Hz) ꢀ80.9 (t, 6F,
F
21-CH
2
);
F
3
4.3.1. With the addition of 10% CuI
4.3.1.1. Sonogashira reaction with C H I, 3a, as the substrate. Under
6 5
6
J
FF = 7.52,
–
CF
3
), ꢀ121.0 (4F), ꢀ121.3 (20F), ꢀ122.1 (4F), ꢀ122.7 (4F),
1
3
ꢀ
125.5 (4F); C NMR (126 MHz, DMF-d
CF ), 120.3, 124.5, 140.9, 151.8, 157.3 (bpy), 105.0–
21); FT-IR (KBr pellets, vmax/cm ): 1623, 1558 (m,
6
, d ppm) 74.2 (bpy-CH
2
),
the fluorous biphasic system, the vessel was charged with DMF
(3 mL), FC77 (3 mL), 3a (0.275 mmol, 56.1 mg), phenylacetylene
(4a: 0.33 mmol, 33.7 mg), DABCO (0.825 mmol, 92.4 mg), the
1 mol% Pd complex 2b (4 mg), and 10 mol% CuI (0.0275 mmol,
5.3 mg). The reaction mixture was refluxed at 135 °C for 4–6 h be-
fore the reaction was stopped and the 2 layers separated using a
separatory funnel at 0 °C. The FC77 fraction was retained for recy-
cling experiments.
6
1
1
C
C
C
8.2 (CH
2
2
ꢀ
1
16.0 (C10
F
m
bpy)
m/z=)
calcd. 1455.8869, found 1455.8842;
+
208, 1151
(vs,
m
CF
2
);
HR-MS
(FAB):
(M ;
3
5
34
34
34
N
N
N
2
2
2
H
14
H
14
H
14
F
F
F
42
42
42
O
O
O
2
2
2
Pd Cl
2
37
3
5
Pd Cl Cl calcd. 1457.8767, found 1457.8741;
Pd Cl calcd. 1459.8737, found 1459.8734.
2
3
7
4.2.3. Analytical data of 2c
(
NMR data collected in d-DMF at 90 °C because of very poor sol-
6 4 2
4.3.1.2. Sonogashira reaction with p-IC H NO , 3b, as the sub-
1
ubility): yield 90.4%; H NMR (500 MHz, DMF-d
6
, d ppm, J Hz) 9.29
strate. Under the fluorous biphasic system, the vessel was charged
with DMF (3 mL), FC77 (3 mL), 3b (0.275 mmol, 68.5 mg), 4a
(0.33 mmol, 33.7 mg), DABCO (0.825 mmol, 92.4 mg), the 1 mol%
Pd complex 2b (4 mg), and 10 mol% CuI (0.0275 mmol, 5.3 mg).
3
3
(
5
d, 2H, JHH = 5.8, H
.09 (4H, s, bpy-CH
NMR (470.5 MHz, DMF-d
6 3 5
), 8.47 (s, 2H, H ), 7.81 (d, 2H, JHH = 6.0, H ),
3
19
2
), 4.48 (t, 4H,
J
HF = 14.29, C10
F
23-CH
2
);
F
3
6
, d ppm, J Hz) ꢀ81.0 (t, 6F,
JFF = 7.5,

N. Lu et al. / Journal of Organometallic Chemistry 694 (2009) 278–284
283
The reaction mixture was refluxed at 135 °C for several hours be-
fore the reaction was stopped and the 2 layers separated using a
separatory funnel at 0 °C. The FC77 fraction was retained for recy-
cling experiments.
685 mg), 4a (3.3 mmol, 337.1 mg), DABCO (4.13 mmol, 462 mg)],
[0.02%: 2b (4 mg), 3b (13.75 mmol, 3426.5 mg), 4a (16.5 mmol,
1685.5 mg), DABCO (20.65 mmol, 2310 mg)] and [0.001%: 2b
(1 mg), 3b (69 mmol, 14.2 g), 4a (82.5 mmol, 8.57 g), DABCO
(
100 mmol, 11.5 g)]}. Then the reaction mixture was set to react
4
4
.3.2. Without CuI addition
.3.2.1. Sonogashira reaction with p-IC H NO , 3b, as the sub-
6 4 2
in DMF, at 140 °C for a period of time before GC analysis. After
the reaction, the product mixtures were centrifuged and the pre-
cipitated 2b was recovered by decantation at room temperature.
And the products were analyzed by GC/MS and NMR spectrometer.
strate. Except for no CuI addition, the procedures of this section
are almost the same as those of Section 4.3.1.2.
4.4. Recycling studies of the Sonogashira reaction with Pd complex 2a–
4.6. Aryl bromides as substrates
c as catalyst under thermomorphic mode (aryl iodides as substrates)
The procedures of Sections 4.6.1–4.6.3 are almost the same as
those of Section 4.4.1 except that the reaction time was 14 h and
the bromobenzene derivatives were used instead of aryl iodides.
Below, only the amounts of chemicals used were given.
4
.4.1. Sonogashira reaction of 1-hexyne and C
In a typical run, the reaction vessel was charged with DMF
5 mL), 3a (0.275 mmol, 56.1 mg), 4b (0.412 mmol, 33.2 mg),
DABCO (0.825 mmol, 92.4 mg), the 1 mol% Pd complex 2a–c
about 4 mg), and 10 mol% CuI (0.0275 mmol, 5.3 mg). Then the
6 5
H I
(
(
4.6.1. Sonogashira reaction with p-BrC
DMF (5 mL), 4-NO Br (3d: 0.275 mmol, 55.6 mg), 4a
(0.33 mmol, 33.7 mg), DABCO or CO (0.825 mmol), the
6 4 2
H NO , 3d, as the substrate
reaction mixture was set to react at ca. 135 °C for 4h before
GC analysis. After the reaction, the product mixtures were cen-
trifuged and the precipitated catalyst was recovered by decanta-
tion at room temperature after each run. The recovered Pd
2 6 4
C H
K
2
3
1 mol% Pd complex 2b (4 mg), and 10 mol% CuI (0.0275 mmol,
5.3 mg).
2 2
catalyst was washed with 2 mL DMF (or CH Cl ) before proceed-
ing to the next cycle.
4.6.2. Sonogashira reaction with p-BrC
DMF (5 mL), p-BrC CN (3e: 0.275 mmol, 50.1 mg), 4a
(0.33 mmol, 33.7 mg), DABCO or K CO (0.825 mmol), the 1 mol%
2b (4 mg), and 10 mol% CuI (0.0275 mmol, 5.3 mg).
6 4
H CN, 3e, as the substrate
6 4
H
4.4.2. Sonogashira reaction with C
6
H
5
I as the substrate
2
3
In a typical run, the reaction vessel was charged with DMF
(
(
1
5 mL), 3a (0.275 mmol, 56.1 mg), 4a (0.33 mmol, 33.7 mg), DABCO
0.825 mmol, 92.4 mg), the 1 mol% Pd complex (about 4 mg), and
0 mol% CuI (0.0275 mmol, 5.3 mg). Then the reaction mixture
4.6.3. Sonogashira reaction with p-BrC
DMF (5 mL), 4-CH C(O)C Br (3f: 0.275 mmol, 54.7 mg), 4a
(0.33 mmol, 33.7 mg), DABCO or K CO (0.825 mmol), the 1 mol%
6 4 3
H C(O)CH , 3f, as the substrate
3
6 4
H
was set to react at ca. 135 °C for a period of time before GC analysis.
After the reaction, the product mixtures were centrifuged and the
precipitated Pd catalyst was recovered by decantation at room
temperature after each run. The recovered Pd catalyst was washed
2
3
2b (4 mg), and 10 mol% CuI (0.0275 mmol, 5.3 mg).
Acknowledgment
2 2
with 2 mL DMF (or CH Cl ) before proceeding to the next cycle.
Authors thank the National Science Council (NSC 96-2113-M-
027-004-MY2), Taiwan, for the funding.
4
.4.3. Sonogashira reaction with p-IC
In a typical run, the reaction vessel was charged with DMF
5 mL), 3b (0.275 mmol, 68.5 mg), 4a (0.33 mmol, 33.7 mg), DAB-
CO (0.825 mmol, 92.4 mg), the 1 mol% Pd complex (4 mg), and
0 mol% CuI (0.0275 mmol, 5.3 mg). Then the reaction mixture
6 4 2
H NO as the substrate
(
Appendix A. Supplementary material
1
The data for other Tables (A–D) as supplementary materials can
be found in the online version. Supplementary data associated with
this article can be found, in the online version, at doi:10.1016/
j.jorganchem.2008.10.042.
was set to react at ca. 135 °C for a period of time before GC anal-
ysis. After the reaction, the product mixtures were centrifuged
and the precipitated Pd catalyst was recovered by decantation
at room temperature after each run. The recovered Pd catalyst
was washed with 2 mL DMF (or CH
the next cycle.
2 2
Cl ) before proceeding to
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.4.4. Sonogashira reaction with p-IC
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DABCO (0.825 mmol, 92.4 mg), the 1 mol% Pd complex 2b
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6 4
H Me as the substrate
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[
[
[
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2 2
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to the next cycle.
4
[
[
[
[
[
[
[
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.5. Recycling studies of the Sonogashira reaction with Pd complex 2b
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4
.5.1. General procedures
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