Recoverable palladium-catalyzed carbon-carbon bond forming reactions under thermomorphic mode: Stille and suzuki-miyaura reactions

Article abstract of DOI:10.3390/molecules26051414

The reaction of [PdCl₂(CH₃CN)₂] and bis-4,40-(R_fCH₂OCH₂)-2,2'-bpy (1a-d), where R_f = n- C₁₁F₂₃ (a), n-C₁₀F₂₁ (b), n-C₉F₁₉ (c) and n-C₈F₁₇ (d), respectively, in the presence of dichloromethane (CH₂C_l2) resulted in the synthesis of Pd complex, [PdCl₂[4,4'-bis-(RfCH₂OCH₂)-2,2'-bpy] (2a-d). The Pd-catalyzed Stille arylations of vinyl tributyltin with aryl halides were selected to demonstrate the feasibility of recycling usage with 2a as the catalyst using NMP (N-methyl-2-pyrrolidone) as the solvent at 120-150 °C. Additionally, recycling and electronic effect studies of 2a-c were also carried out for Suzuki-Miyaura reaction of phenylboronic acid derivatives, 4-X-C₆H₄-B(OH)₂, (X = H or Ph) with aryl halide, 4-Y-C₆H₄-Z, (Y = CN, H or OCH₃; Z = I or Br) in dimethylformamide (DMF) at 135-150 °C. At the end of each cycle, the product mixtures were cooled to lower temperature (e.g., -10 °C), and then catalysts were recovered by decantation with Pd leaching less than 1%. The products were quantified by gas chromatography/mass spectrometry (GC/MS) analysis or by the isolated yield. The complex 2a-catalyzed Stille reaction of aryl iodides with vinyl tributyltin have good recycling results for a total of 8 times, with a high yield within short period of time (1-3 h). Similarly, 2a-c-catalyzed Suzuki-Miyaura reactions also have good recycling results. The electronic effect studies from substituents in both Stille and Suzuki-Miyaura coupling reactions showed that electron withdrawing groups speed up the reaction rate. To our knowledge, this is the first example of recoverable fluorous long-chained Pd-catalyzed Stille reactions under the thermomorphic mode.

Full text of DOI:10.3390/molecules26051414

molecules
Article
Recoverable Palladium-Catalyzed Carbon-Carbon Bond
Forming Reactions under Thermomorphic Mode: Stille and
Suzuki-Miyaura Reactions
1
,†
1,†
2,3,
*, Zong-Lin Tsai , Ka Long Chan 1
,
1
Eskedar Tessema , Vijayanath Elakkat
, Chiao-Fan Chiu
Chia-Rui Shen 4 , Han-Chang Su 6 and Norman Lu
,5
1,7,
*
1
Institute of Organic and Polymeric Materials, National Taipei University of Technology, Taipei 106, Taiwan;
eskedartessema18@gmail.com (E.T.); vijayanathe123@gmail.com (V.E.); a66366268@gmail.com (Z.-L.T.);
kalongabc@gmail.com (K.L.C.)
Department of Pediatrics, Linkou Medical Center, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University,
Taoyuan 333, Taiwan
Department of Medical Biotechnology and Laboratory Sciences, College of Medicine, Chang Gung University,
Taoyuan 333, Taiwan; crshen@mail.cgu.edu.tw
Department of Ophthalmology, Linkou Medical Center, Chang Gung Memorial Hospital,
Taoyuan 333, Taiwan
2
3
4
5
6
7
Creditable Service Technology Consultants, New Taipei City 235, Taiwan; henry@mail.creditable.com.tw
Development Center for Smart Textile, National Taipei University of Technology, Taipei 106, Taiwan
Correspondence: chioufan2008@gmail.com (C.-F.C.); normanlu@mail.ntut.edu.tw (N.L.).
These authors contributed equally to this work.
*
†
ꢀ
ꢁꢂꢀꢃꢄꢅꢆꢇ
ꢀ
ꢁꢂꢃꢄꢅꢆ
Citation: Tessema, E.; Elakkat, V.;
Chiu, C.-F.; Tsai, Z.-L.; Chan, K.L.;
Shen, C.-R.; Su, H.-C.; Lu, N.
Recoverable Palladium-Catalyzed
Carbon-Carbon Bond Forming
Reactions Under Thermomorphic
Mode: Stille and Suzuki-Miyaura
Reactions. Molecules 2021, 26, 1414.
https://doi.org/10.3390/
0
0
Abstract: The reaction of [PdCl (CH CN) ] and bis-4,4 -(R CH OCH )-2,2 -bpy (1a–d), where R = n-
2
3
2
f
2
2
f
C11F23
(a), n-C10F21
(b
), n-C9F19 (c) and n-C8F17 (d), respectively, in the presence of dichloromethane
0 0
CH Cl ) resulted in the synthesis of Pd complex, [PdCl [4,4 -bis-(R CH OCH )-2,2 -bpy] (2a–d).
2 2 2 2 2
f
The Pd-catalyzed Stille arylations of vinyl tributyltin with aryl halides were selected to demonstrate
the feasibility of recycling usage with 2a as the catalyst using NMP (N-methyl-2-pyrrolidone) as the
solvent at 120–150 C. Additionally, recycling and electronic effect studies of 2a–c were also carried
out for Suzuki-Miyaura reaction of phenylboronic acid derivatives, 4-X-C H -B(OH) , (X = H or
Ph) with aryl halide, 4-Y-C H -Z, (Y = CN, H or OCH ; Z = I or Br) in dimethylformamide (DMF)
(
◦
6
4
2
6
4
3
molecules26051414
◦
at 135–150 C. At the end of each cycle, the product mixtures were cooled to lower temperature
◦
(e.g.,
−
10 C), and then catalysts were recovered by decantation with Pd leaching less than 1%. The
Academic Editor: Mark McLaughlin
products were quantified by gas chromatography/mass spectrometry (GC/MS) analysis or by the
isolated yield. The complex 2a-catalyzed Stille reaction of aryl iodides with vinyl tributyltin have
good recycling results for a total of 8 times, with a high yield within short period of time (1–3 h).
Similarly, 2a–c-catalyzed Suzuki-Miyaura reactions also have good recycling results. The electronic
effect studies from substituents in both Stille and Suzuki-Miyaura coupling reactions showed that
electron withdrawing groups speed up the reaction rate. To our knowledge, this is the first example
of recoverable fluorous long-chained Pd-catalyzed Stille reactions under the thermomorphic mode.
Received: 31 January 2021
Accepted: 1 March 2021
Published: 5 March 2021
Publisher’s Note: MDPI stays neutral
with regard to jurisdictional claims in
published maps and institutional affil-
iations.
Keywords: homogeneous; sustainable catalysis; catalyst; fluorous; thermomorphic; recovery; palla-
dium; long-chained; Stille; Suzuki-Miyaura; coupling
Copyright: © 2021 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
1. Introduction
Carbon-carbon bond forming reactions are among the most useful and most widely
studied synthetic transformations. Most importantly, the Stille, Suzuki-Miyaura, Heck,
Negishi and Sonogashira coupling reactions typically catalyzed by palladium have been
abundantly used in syntheses and widely studied in recent decades. Stille coupling, which
is the palladium-catalyzed cross-coupling of an organostannane and an organohalide, is
4
.0/).
Molecules 2021, 26, 1414. https://doi.org/10.3390/molecules26051414
https://www.mdpi.com/journal/molecules

Molecules 2021, 26, 1414
2 of 15
one of the most powerful methods for the straightforward joining together of carbon-carbon
bonds in synthetic chemistry [
for the synthesis of functional molecules and polymers, both in laboratory research and in
industry [ ]. In such kind of coupling reaction, several advantages are observed from the
1–3]. It is currently a widely used cross-coupling method
1,4
substrate groups. These include the stability and functional group tolerance of stannanes,
the broad reaction scope of aryl halides and pseudo-halides, and its chemoselectivity. On
the other hand, Suzuki-Miyaura coupling reaction has become a main method in modern
synthetic organic chemistry for the preparation of biaryl compounds [
the coupling products of both the reactions have been widely applied in natural prod-
ucts [ ], medicinal chemistry [10 11], chemical biology [12], industrial process [13] and
5,6]. Therefore,
7–9
,
materials [14,15] in a controlled and selective manner.
Homogeneous catalysis of Stille coupling reaction generally takes place in organic
solvents and, hence, it is difficult to separate the catalyst from the reaction mixture and
recover it at the end of the reaction, leading to wastage of noble metals. Concerns for the
environment and scarcity of resources is becoming a challenge, which motivates chemists to
look for greener processes that are more economical and ecofriendly. Therefore, developing
a catalyst with a better activity, excellent selectivity, easy separation and better yield is
everyone’s goal. To solve this problem, several noble strategies involving heterogeneous
and improvised homogeneous catalysts have been developed for recycling and reusing
Stille catalysts, including the use of Pd complexes supported by recombinant peptide fusion
nanoparticles [16], magnetic nanoparticles [17], stainless steel mesh-GO (graphene oxide)
nanoparticles [18], polymer [19
functionalized nanoporous silica [24
Additionally, a few reaction solvent options, including alcohols [29
ionic liquid [34 35] were also studied to ensure that successful recovery occurred. Similarly,
several recoverable Suzuki-Miyaura catalysts, including the use of Pd complexes supported
by agar [36], polymer [37], aminophosphine supported on Al O [38], perovskite-based [39],
–
21], silica [22], porous metal-organic framework (MOF) [23],
25], bulky ligands [26] and metal nanoparticles [27 28].
30], water [31 33], and
,
,
,
–
,
2
3
and magnetically recoverable ones [40,41] were used.
0
In this work, the fluorous long-chained palladium catalysts, [PdCl [4,4 -bis-(n-CF
2
3
0
(
CF ) CH OCH )-2,2 -bpy] (2a–c) had been synthesized and been applied to catalyze the
2
10
2
2
Stille and Suzuki-Miyaura reaction of aryl halides with their respective reagents. Recently
in Lu’s group, both linear and branched fluorous chains are used to diversify and enrich
the fluorous ligand selection pool, when designing the recoverable fluorous catalysis and
keeping the enough amount of fluorine content in the complex necessary for this kind of
recoverable catalysis. To the best of our knowledge, this is the first example of the appli-
cation of fluorous long-chained Pd complexes as effective, recoverable catalysts for Stille
and Suzuki-Miyaura reactions under thermomorphic condition for many times of re-usage.
The thermomorphic property of few fluorous long-chained palladium complexes was
previously demonstrated in DMF solvent in Lu’s group and published elsewhere [42,43]
.
In this study, we have a more complete thermomorphic survey of a series of the chain
length of Pd complexes and a related fluorous compound (see Figure 1 below). This type
of fluorous long-chained palladium complexes 2a–c features on homogeneously catalyzing
at high temperature in common polar organic solvent and turning to the heterogeneous
precipitation at lower temperature. Taking their good catalytic ability and good thermal
stability into consideration, these catalysts could be regarded as a very good alternative to
homogeneous complexes in sustainable catalysis.
2. Results and Discussion
2
.1. Catalyst Synthesis
0
0
The preparation of fluorous long-chained ligands bis-4,4 -(n-R CH OCH )-2,2 -bpy
f
2
2
(
1a–e), where R = n-C F
(a
), n-C10F21
respectively, followed a literature procedure [44
chained bipyridine (bpy) ligands, 1a–d, with [PdCl (CH CN) ] in CH Cl , as shown in
(
b
), n-C9F19
(c), n-C8F17 (d) and n-C7F15 (e),
f
11 23
–46]. The reaction of fluorinated long-
2
3
2
2
2

Molecules 2021, 26, 1414
3 of 15
0
0
Scheme 1, resulted in the synthesis of Pd complex [PdCl [4,4 -bis-(R CH OCH )-2,2 -bpy]
2
f
2
2
(2a–d) as pale yellow solid already published elsewhere [47,48].
Figure 1. Solubility of Pd complexes 2a–d and ligand 1e in dimethylformamide (DMF) as a function
of temperature.
Scheme 1. Synthesis of the fluorous long-chained Pd complexes.
2.2. Thermomorphic Property Study
The solubility of Pd complexes 2a–c in DMF as a function of temperature was shown on
the previously published work from Lu’s group [42,43]. As reported here, the solubility was
measured by the variable temperature nuclear magnetic resonance (NMR) spectrometer,
◦
where the temperatures were varied from
−
40 to 80 C (see Figure 1). In this study, we
0
recorded the solubility of Pd complex 2a–d and a bpy ligand, bis-4,4 -(n-C F CH OCH )-
,2 -bpy (1e), by adapting more temperature points when using a similar procedure (see
7
15
2
2
0
2
Supplementary Materials). It was shown that compounds 1e and 2a–d which showed their
solubilities increased dramatically with the increasing temperature. The complex 2d was
◦
◦
soluble in DMF at 20 C, but complexes 2a–c were not soluble at
−
10 C and below. The
Pd complexes 2a–c were then selected as good candidates for the subsequent catalytic
experiments to examine the temperature dependency of the recoverable reactions.
2.3. Recoverable Pd Complex-Catalyzed Stille Reaction of Aryl Halides
The fluorous long-chained Pd complex 2a was then examined for the following Stille
reactions where Pd-catalyzed the coupling reaction of vinyl tributyltin (
4–7) or aryl bromides (8–11).
3) with aryl iodides
(
2
.3.1. Aryl Iodides
As shown in Scheme 2, the Pd-catalyzed Stille arylation of vinyl tributyltin (
aryl iodides was selected to demonstrate the feasibility of recycling usage with 2a as the
3
) with

Molecules 2021, 26, 1414
4 of 15
catalyst using NMP (N-methyl-2-pyrrolidone) as the solvent under thermomorphic mode,
◦
at ca 120 C for 1–8 h varying in each run for different substituents. At the end of each
◦
cycle, the product mixtures were cooled to below
−
10 C and centrifuged, and the catalyst
was recovered by decantation. The recovered 2a was added with NMP and substrates
to proceed to the next cycle. The products were quantified with GC/MS analysis by
comparison to internal standard (anisole). As one example shown in Table 1, 2a-catalyzed
Stille reaction of C H I (4) with vinyl tributyltin (3) could give rise to the good recycling
6
5
results for a total of 8 times. To our knowledge, this is the first example of recoverable
fluorous Pd-catalyzed Stille reaction under a thermomorphic mode with such a high yield
and recyclability.
Scheme 2. The Pd catalyst (2a)-catalyzed Stille reaction of aryl iodides (4–7) with vinyl tributyltin (
under the thermomorphic condition.
3
)
)
Table 1. Recycling results of 2a-catalyzed Stille reaction of iodobenzene (4) and vinyl tributyltin (
3
under the thermomorphic mode.
◦
Yield (%) a
TON c
Cycle No.
Time (h)
Temp ( C)
100 (99) b
100 (91)
100 (95)
100
1
2
3
4
5
6
7
8
3
3
3
3
4
4
6
6
120
120
120
120
130
130
130
130
20
20
20
20
20
20
20
20
100
100
100
100
◦
Reaction conditions: Temp (T) = 120–130 C, cat. 2a (5 mol%),
mL. : measured by GC/MS (see Supplementary Materials); : isolated yield in parenthesis; : turnover number.
4
(204 mg, 1 mmol),
3
(333 mg, 1.05 mmol), solvent:
a
b
c
5
With electron-withdrawing groups (EWGs) CN and NO substituents on iodobenzene,
2
the 2a-catalyzed Stille reactions also gave rise to respective 5a and 6a with the excellent
yield and recyclability under the thermomorphic mode (see Tables 2 and 3).
Table 2. Recycling results of 2a-catalyzed Stille reaction of 4-cyanoiodobenzene (
utyltin (3) under the thermomorphic mode.
5) and vinyl trib-
◦
Yield (%) a
Cycle No.
Time (h)
Temp ( C)
TON
100 (98) b
100
100 (95)
100
100 (99)
100
1
2
3
4
5
6
7
8
1
1
1
1
1
1
1
120
120
120
120
120
120
120
120
100
100
100
100
100
100
99
99
98
1
98
◦
Reaction conditions: T = 120 C, cat. 2a (1 mol%),
measured by GC/MS; : isolated yield in parenthesis.
5 (229 mg, 1 mmol), 3 (320.3 mg, 1.01 mmol), solvent: 5 mL
a
b
:

Molecules 2021, 26, 1414
5 of 15
Table 3. Recycling results of 2a-catalyzed Stille reaction of 4-nitroiodobenzene (
3) under the thermomorphic mode.
6) and vinyl tributyltin
(
◦
Yield (%) a
Cycle No.
Time (h)
Temp ( C)
TON
100 (98) b
100 (95)
100 (97)
100
1
2
3
4
5
6
7
8
1
1
1
1
1
1
1
120
120
120
120
120
120
120
120
100
100
100
100
100
100
99
100
100
99
97
1
97
◦
a
Reaction conditions: T = 120 C, cat. 2a (1 mol%),
measured by GC/MS; : isolated yield in parenthesis.
6
(249 mg, 1 mmol),
3
(320.3 mg, 1.01 mmol), solvent: 5 mL :
b
Similar to the recycling observed in the reaction of parent aryl compound (4), here
complex 2a could be easily recovered and reused in the Pd-catalyzed Stille arylation of vinyl
tributyltin under the thermomorphic mode. The aryl compounds with EWGs exhibited a
greater rate (only 1 h as shown in Tables 2 and 3) than the parent aryl compound, which
needed 3–6 h to complete the reaction.
When an electron-releasing group (ERG) CH substituted on iodobenzene (7) was
3
used as a substrate in 2a-catalyzed Stille reaction, the electron-releasing Me group slowed
down the reactions (Table 4), although 8 mol% of catalytic loading was used. Nonetheless,
the recyclability could be demonstrated, only with both a longer time and at higher
◦
temperature. The yields were 100% throughout, but the temperature was 130 C for the
◦
first five cycles in 8 h and raised to 140 C time to 9 h in the sixth cycle; it then continued to
◦
rise to 150 C in the seventh and eighth cycles in 10 and 15 h, respectively.
Table 4. Recycling results of 2a-catalyzed Stille reaction of 4-iodotoluene (7) and vinyl tributyltin (3)
under thermomorphic mode.
◦
Yield (%) a
Cycle No.
Time (h)
Temp ( C)
TON
100 (98) b
100 (95)
100 (99)
100
1
2
3
4
5
6
7
8
8
8
8
8
8
9
10
15
◦
130
130
130
130
130
140
150
150
12.5
12.5
12.5
12.5
12.5
12.5
12.5
12.5
100
100
100
100
Reaction conditions: T = 130–150 C, cat. 2a (8 mol%),
measured by GC/MS; : isolated yield in parenthesis.
7 (218 mg, 1 mmol), 3 (323.4 mg, 1.02 mmol), solvent: 5 mL
a
b
:
Sajiki and his co-workers [49] have reported palladium on charcoal-catalyzed ligand-
free Stille coupling aryl iodides as shown on Scheme 2. They have used 5 mol% of catalytic
loading for 4-cyanoiodobenzne to obtain a yield of 88% in 24 h at an elevated temperature
−
1
with turnover number (TON) and turnover frequency (TOF) values of 17.6 and 0.73 h
,
respectively. For same catalytic loading and duration of time, they have obtained 63%
◦
−1
,
yield at 50 C by using 4-nitroiodobenzene with TON and TOF values of 12.6 and 0.52 h
respectively. However, for a similar reaction only 1 mol% of catalytic loading was needed
◦
for our catalyst 2a to have a 100% yield at 120 C in 1 h with TON and TOF values of 100
and 100, respectively. Thus, the activity of catalyst 2a reported here is robust with better
recovery of 8 cycles.
Thus, the iodobenzene bearing an electron-withdrawing group (CN and NO ) smoothly
2
underwent the cross-coupling reaction compared to the non-substituted (R = H) case or the
case bearing an electron-releasing group (R = CH ) to give the desired vinyl derivatives in
3
excellent yields.

Molecules 2021, 26, 1414
6 of 15
2
.3.2. Aryl Bromides
The Pd complex 2a was also found to be effective in the Pd-catalyzed Stille vinylation
of less reactive aryl bromide under thermomorphic mode, as shown in Scheme 3. Table 5
shows the results of Stille reaction of the unsubstituted aryl bromides (8) with vinyl
tributyltin (3) using NMP as a solvent.
Scheme 3. The Pd catalyst (2a)-catalyzed Stille reaction of aryl bromides (8–10) with vinyl tributyltin (
thermomorphic condition.
3) under the
Table 5. Recycling result of 2a-catalyzed Stille reaction of bromobenzene (
8) and vinyl tributyltin (3)
under the thermomorphic mode.
◦
Yield (%) a
Cycle No.
Time (h)
Temp ( C)
TON
1
2
3
4
5
6
7
8
12
12
12
14
14
20
24
140
140
140
150
150
150
150
150
100
100 (99) b
100
100
100
100 (97)
95
10
10
10
10
10
10
9.5
8.6
30
◦
86
Reaction conditions: T = 140–150 C, cat. 2a (10 mol%),
measured by GC/MS; : isolated yield in parenthesis.
8 (157 mg, 1 mmol), 3 (475.6 mg, 1.5 mmol), solvent: 5 mL
a
b
:
Tables 6 and 7 show the good results of reactivities and recycling of 2a-catalyzed Stille
reaction of the EWGs CN and NO -containing aryl bromides ( and 10, respectively) with
) using NMP as a solvent. The same reaction had been performed by
9
2
vinyl tributyltin (
3
using an aryl bromide containing the ERG CH in the same conditions expressed above.
3
Although the reaction proceeded forming the products, it took a very long time to finish
the reaction. Thus, those data have not been presented here.
Table 6. Recycling results of 2a-catalyzed Stille reaction of 4-cyanobromobenzene (
9) and vinyl
tributyltin (3) under the thermomorphic mode.
◦
Yield (%) a
Cycle No.
Time (h)
Temp ( C)
TON
1
2
3
4
5
6
7
8
4
5
5
6
6
7
10
18
140
140
140
140
140
140
140
140
100
100 (98) b
100
100 (98)
100
100 (97)
100
100
10
10
10
10
10
10
10
10
◦
Reaction conditions: T = 140 C, cat. 2a (10 mol%),
measured by GC/MS; : isolated yield in parenthesis.
9 (182 mg, 1 mmol), 3 (475.6 mg, 1.5 mmol), solvent: 5 mL
a
b
:

Molecules 2021, 26, 1414
7 of 15
Table 7. Recycling results of 2a-catalyzed Stille reaction of 4-nitrobromobenzene (10) and vinyl
tributyltin (3) under the thermomorphic mode.
◦
Yield (%) a
Cycle No.
Time (h)
Temp ( C)
TON
1
2
3
4
5
6
7
8
4
4
4
4
4
5
15
20
120
120
120
120
120
150
150
150
100
100
10
10
10
10
10
10
10
10
100 (98) b
100
100 (98)
100
100
100
◦
Reaction conditions: T = 120–150 C, cat. 2a (10 mol%), 10 (202 mg, 1 mmol),
mL : measured by GC/MS; : isolated yield in parenthesis.
3
(475.6 mg, 1.5 mmol), solvent:
a
b
5
Lerebours and Wolf [50] have reported that they have used 6 mol% of Pd-catalyst
◦
at 140 C for 24 h to catalyze a similar kind of Stille reaction (Scheme 3) which uses
bromobenzene as a substrate. As a result, they have obtained a product in 95–96% yield
−
1
with a TOF = 0.67 h , after the first two cycles of reactions, but it was found that the
catalytic performance of the recovered Pd catalyst slightly diminished after each step to
the 4th cycle. However, at similar temperature we have obtained a better yield in 12 h (for
−
1
the first two cycles) by using unsubstituted aryl bromide substrate with a TOF = 0.83 h
.
Thus, a catalytic efficiency of 2a was proved to be better comparatively. Additionally, for
the EWG substituted aryl bromides, only 6 h was required to reach a yield of 100% in the
◦
first 5 cycles, even at a slightly reduced temperature (120 C; see Table 7). Additionally,
catalyst 2a can be recovered and reused for up to 8 cycles by keeping their activity used for
all kinds of substrates.
2.3.3. Purification of Crude Product Mixture from Pd-Catalyzed Stille Reaction
At the end of the reaction, a two-step procedure was followed to obtain a pure product.
On the first step, the crude reaction mixture obtained was added to an aqueous solution of
potassium fluoride (KF) according to a reported literature procedure using an alcoholic KF
solution [51]. The KF solution was allowed to react with the tin by-product in the mixture,
so that the tin by-product precipitates into a white powder of polymeric Bu SnF [
2
] and is
removed by filtration. This was repeated until no residue was observed in the flask. Finally,
water and CH Cl were used for extraction in the second step, so that the solvent (NMP)
3
2
2
would be trapped into the water layer with the KI after several extractions to achieve the
pure product in the CH Cl layer (Scheme 4). Therefore, the recoverability of Pd catalyst
2
2
and easy isolation of product demonstrated that 2a-catalyzed Stille reactions of aryl halides
are good examples of sustainable catalysis.
Scheme 4. Schematic drawing of the purification process of the Stille reaction product mixture.

Molecules 2021, 26, 1414
8 of 15
2.4. Recoverable Pd Complex-Catalyzed Suzuki-Miyaura Reaction of Aryl Halides
2.4.1. Aryl Iododes
We also evaluated complex 2a in Suzuki-Miyaura reaction of aryl iodides (13
–
15) with
phenyl boronic acid derivatives (11, 12) as indicated in Scheme 5. The results showed that
2a could effectively catalyze the Suzuki-Miyaura reactions as shown in Table 8. The catalyst
could be recycled and reused several times. The electron withdrawing phenyl substituent
on the 4-biphenylboronic acid (12) was seen to speed up the reaction (see entries 1–3 in
Table 8). It is known that the electron-withdrawing CN substituent on aryl iodide (14
could speed up Suzuki-Miyaura reactions. Thus, the entries 1–6 in Table 8 were tested
first for 2a-catalyzed Suzuki-Miyaura reaction of 4-cyanoiodobenzene (when Y = CN) (14).
After the 1st run, the recovered catalyst was subjected to the normal washing steps and
then reused for the next runs. For two sets (entries 1–3 and entries 4–6) of three runs, the
)
◦
reactions were all completed with high yields within 4 h at 135 and 140 C for 4-biphenyl
boronic acid (12) and phenyl boronic acid (11), respectively.
Scheme 5. The Pd catalyst (2a)-catalyzed Suzuki-Miyaura reaction of two phenyl boronic acid derivatives with three
iodobenzene derivatives under the thermomorphic condition.
Table 8. Recycling results of 2a-catalyzed Suzuki-Miyaura reaction of two phenyl boronic acid
derivatives, 4-X-C H -B(OH) [X = H (11) or Ph (12)], with three iodobenzene derivatives, 4-Y-C H -
6
4
2
6
4
I, [Y = CN (13), H (14) or OCH (15)] under the thermomorphic condition.
3
Reactant A
Reactant B
(Y=)
Temp ( C) Yield (%) a
◦
TON
Entry
Cycle
(X=)
1
2
3
4
5
6
7
8
9
1st
2nd
3rd
1st
2nd
3rd
1st
2nd
1st
2nd
Ph
Ph
Ph
H
H
H
H
H
H
H
CN
CN
CN
CN
CN
CN
H
H
OCH3
OCH3
135
135
135
140
140
140
140
140
140
140
100
100
100
95
92
85
80
75
70
60
33.3
33.3
33.3
31.7
30.7
28.3
26.7
25
23.3
20
1
0
◦
Reaction conditions: Time = 4 h (for all entries), T = 135 or 140 C, cat. 2a (3 mol%), 11 or 12 (0.2 mmol), 13
5 (0.3 mmol), solvent: 5 mL. : measured by GC/MS.
,
14 or
a
1
For entries 7 and 8 of Table 8, iodobenzene (when Y = H) (14) with phenyl boronic
acid (11) were used as the substrates for the 2a-catalyzed Suzuki-Miyaura reaction. The
results demonstrated that complex 2a, was a good recoverable catalyst for the two runs
with the respective yields of 80% and 75% under the conditions outlined in Scheme 5. For
entries 9 and 10, these two results also showed that 2a-catalyzed Suzuki-Miyaura reactions
were efficient and recyclable. Although these two Suzuki-Miyaura reactions using the less
reactive 4-methoxyiodobenzene (when Y = OCH ) (15) were found to be slower with the
3
reduced yields of 70% and 60% within 4 h for entries 9 and 10, respectively. Thus, the
results in Table 8 have clearly demonstrated that the fluorous long-chained Pd complex

Molecules 2021, 26, 1414
9 of 15
(
2a) is an excellent thermomorphic catalyst for C–C forming Suzuki-Miyaura reactions of
aryl iodides.
2.4.2. Aryl Bromides
The catalytic recovery of fluorous long-chained Pd complexes 2a–c were then examined
for the following Suzuki-Miyaura reaction experiment to catalyze the coupling of phenyl
boronic acid (11) with 4-cyanobromobenzene (16) under the thermomorphic condition.
The Pd-catalyzed Suzuki-Miyaura reactions of phenyl boronic acid (11) with 4-cyanobr
omobenzene (12) (see Scheme 6) were successfully carried out under the thermomorphic
condition at a 3 mol% of catalytic loading. It was shown that, at an elevated temperature a
higher yield was obtained within 8 h. The catalytic recovery has was proven to be robust
for 8, 8 and 9 consecutive cycles for 2a, 2b and 2c, respectively. Their good results are
shown in Tables 9–11, respectively.
Scheme 6. The Pd catalyst (2a–c)-catalyzed Suzuki-Miyaura reaction of phenyl boronic acid (11) with 4-cyanobromobenzene
12) under the thermomorphic condition.
(
Table 9. Recycling results of 2a-catalyzed Suzuki-Miyaura reaction of aryl boronic acid (11) with
-cyanobromobenzene (16) under the thermomorphic mode.
4
◦
Yield (%) a
Cycle No.
Time (h)
Temp ( C)
TON
1
2
3
4
5
6
7
8
8
8
8
8
8
8
8
150
150
150
150
150
150
150
150
99
99
33
33
33
30.7
27
26
99 (98) b
92
81
78 (77)
73
24.3
26
8
78
◦
Reaction conditions: T = 150 C, cat. 2a (3 mol%), 11 (202 mg, 1 mmol), 16 (475.6 mg, 1.5 mmol), solvent: 5 mL.
measured by GC/MS. : isolated yield in parenthesis.
a
b
:
Table 10. Recycling results of 2b-catalyzed Suzuki-Miyaura reaction of aryl boronic acid (11) with
-cyanobromobenzene (16) under the thermomorphic mode.
4
◦
Yield (%) a
Cycle No.
Time (h)
Temp ( C)
TON
1
2
3
4
5
6
7
8
8
8
8
8
8
8
8
150
150
150
150
150
150
150
150
99
97
33
32.3
33
33
33
33
33
30.7
99 (97) b
99
99
99
99
92
8
◦
Reaction conditions: T = 150 C, cat. 2b (3 mol%), 11 (202 mg, 1 mmol), 16 (475.6 mg, 1.5 mmol), solvent: 5 mL.
measured by GC/MS. : isolated yield in parenthesis.
a
b
:

Molecules 2021, 26, 1414
10 of 15
Table 11. Recycling results of 2c-catalyzed Suzuki-Miyaura reaction of aryl boronic acid (11) with
4
-cyanobromobenzene (16) under the thermomorphic mode.
◦
Yield (%) a
Cycle No.
Time (h)
Temp ( C)
TON
1
2
3
4
5
6
7
8
9
8
8
8
8
8
8
8
8
150
150
150
150
150
150
150
150
150
99
98
33
32.7
33
33
32.7
33
33
30.7
27.7
99 (98) b
99
98
99
99
92 (89)
83
8
◦
Reaction conditions: T = 150 C, cat. 2c (3 mol%), 11 (40 mg, 0.2 mmol), 16 (36.6 mg, 1.5 mmol), solvent: 5 mL.
measured by GC/MS. : isolated yield in parenthesis.
a
b
:
Note: after 8 cycles, the recovered Pd catalyst (2b) was checked by the 19F NMR
method. The results show that the 19F NMR spectrum of catalyst 2b are exactly the same
before and after (8 cycles) reactions (see Figure S1 in Supplementary Materials).
2.5. Detection of Metal Recovery by ICP-MS
The amount of Pd leaching of catalyst (2a) in the product solution of Stille reaction
after centrifugation from the two randomly selected specific runs from each table were
determined by inductively coupled plasma mass spectrometry (ICP-MS). The results
indicate that less than 1% of the Pd was leached out to the solution from the catalyst as
shown in Tables 12 and 13. Most of the recovery studies in Stille reaction reported so far
have not included ICP-MS data in their works.
Table 12. Pd leaching (%) after 2a-catalyzed Stille coupling of aryl iodides from inductively coupled
plasma mass spectrometry (ICP-MS).
Table No.-Cycle
No.
Pd Detected from
ICP-MS (In ppm)
Wt of the Catalyst
Used (mg)
Pd Leaching (%)
Pd Recovery (%)
a
1–1
1–8
2–1
2–5
3–2
3–6
4–3
4–7
2.932
5.953
4.109
1.372
0.37
0.393
2.673
21.86
80
80
16
16
16
16
128
128
0.11
0.21
0.72
0.27
0.06
0.08
0.07
0.46
99.89
99.79
99.28
99.73
99.94
99.92
99.93
99.54
a: Pd (in ppm) detected from ICP-MS analysis.
Table 13. Pd leaching (%) after 2a-catalyzed Stille coupling of aryl bromides from ICP-MS.
Table No.-Cycle
No.
Pd Detected from
ICP-MS (In ppm)
Wt of the Catalyst
Used (mg)
Pd Leaching
(%)
Pd Recovery
(%)
a
5–1
5–3
6–2
6–4
7–5
7–8
2.514
4.398
34.89
15.08
0.62
160
160
160
160
160
160
0.05
0.08
1.18
0.63
0.03
0.76
99.95
99.92
98.82
99.37
99.97
99.24
21.76
a: Pd (in ppm) detected from ICP-MS analysis.
Similarly, a Pd leaching study was done for two randomly selected specific runs from
each table of Suzuki-Miyaura reactions (see Table 14). From these tables, we can find that
the recovery rate of the fluorous long-chained palladium, catalysts 2a–c can reach up to
99%, under the thermomorphic system. Almost all the metal catalysts could be recycled for
the next reaction and get reused. The negligible Pd loss during the 8 cycles did not seem to

Molecules 2021, 26, 1414
11 of 15
affect the catalytic activity much, which proves that metal catalysts 2a–c can achieve the
goals of sustainable catalysis.
Table 14. Pd leaching (%) after 2a–c-catalyzed Suzuki-Miyaura coupling of aryl bromides from ICP-MS.
Table No.-Cycle
No.
Pd Detected from
ICP-MS (In ppm)
Wt of the Catalyst
Used (mg)
Pd Recovery
(%)
Pd Leaching (%)
a
8
8
9
9
–1
–3
–1
–5
5.12
7.69
4.08
12.32
3.33
13.03
47
47
44
44
41
41
0.40
0.60
0.31
0.99
0.26
1.06
99.6
99.4
99.69
99.01
99.74
98.94
1
1
0–3
0–5
a: Pd (in ppm) detected from ICP-MS analysis.
3. Experimental
3.1. General Procedures
Gas chromatographic/mass spectrometric data were obtained using an Agilent 6890 Se-
ries gas chromatograph (Taipei, Taiwan) with a series 5973 mass selective detector. Reactions
were monitored with a HP 6890 GC using a 30 m 0.250 mm HP-1 capillary column with a
0
.25 mm stationary phase film thickness. The flow rate was 1 mL/min and split-less. Fourier
transform infrared (FT-IR) spectra were obtained on a PerkinElmer RX I FT-IR spectrometer
Taipei, Taiwan). NMR spectra were recorded on Bruker AM 500 and 300 spectrometers
Taipei, Taiwan) using 5 mm o.d. sample tubes.
(
(
3.2. Starting Materials
The chemicals, reagents and solvents employed were commercially available and used
as received. R CH OH where R = n-C F (a
), n-C10F21
(b), n-C9F19 (c) and n-C8F17 (d),
f
2
f
11 23
and C F (e) were purchased from either Aldrich or SynQuest (Taipei, Taiwan).
87 15
3.3. Preparation of Palladium Complexes
The fluorous bipyridyl ligandes were prepared using the literature method [42].
0
The reaction of [PdCl (CH CN) ] with fluorinated bipyridine derivatives, bis-4,4 -(n-
2
3
2
0
0
R CH OCH )-2,2 -bpy (1a–d), resulted in the synthesis of [PdCl [4,4 -bis-(n-CF (CF ) CH
f
2
2
2
3
2 10
2
0
OCH )-2,2 -bpy] (2a–d) as pale yellow solids, where R = n-C F
(a), n-C10F21
(b), n-C9F19
2
f
11 23
(
c) and n-C8F17
(
d
), respectively [44
–48
,
52–
57]. The reaction was stirred in CH Cl under
2
2
nitrogen for 6 h, and the complexes 2a–d would then precipitate from the reaction mixture.
The precipitate was collected after removing the solvent by using vacuum pump and finally
washed with methanol to remove the excess metal. The yield was about 85%.
3.4. Analytical Data for the Ligands and Pd Metal Complexes
Analytical data of ligand 1e (as a representative example; for others, see refs [44–48]).
◦
−1
Yield: 90%. m.p.: 93–96 C. FT-IR (cm ): v (bpy, m) 1602, 1561; v (CF stretch, s) 1242,
2
1
1
208, 1147. H-NMR (500 MHz, DMSO-d , rt):
δ
(ppm) 8.67 (d, J = 5.0 Hz, 2H, H6), 8.34
6
(
s, 2H, H3), 7.34 (d, J = 5.0 Hz, 2H, H5), 4.77 (s, 4H, bpy-CH ), 4.04 (t, J = 14.6 Hz, 4H,
2
13
-CH CF -); C-NMR (113 MHz, CDCl , 350 K): δ (ppm) 155.9, 149.5, 146.8, 121.8, 119.1
2 2 3
19
(10C, bpy), 118–108 (-C F ), 72.9 (bpy-CH O-), 67.6 (-CH CF -); F-NMR (470 MHz,
7 15 2 2 2
CDCl , 350 K):
δ
(ppm)
−
80.8 (t, J = 9.7 Hz, 6F, -CF CF ),
−
119.3 (t, J = 8.6 Hz, 4F, -CH CF ),
2 2
3
2
3
+
−
122.0 (8F),
M -2 (OCH C F )), 91 (C H N ).
−
122.7 (4F),
7
−
123.2 (4F),
5
−
126.1 (4F). GC/MS: 582 (M -OCH C F ), 183
2 7 15
+
+
(
2
15
6
For Analytical data of complexes 2a–d, see the literature methods in [42–44].
3.5. Procedures in Catalytic Stille Reaction and Recovery
In a typical run, an aryl iodide (1 mmol) and vinyl tributyltin (1.02 mmol) were
charged into a 10 mL reaction tube containing a magnetic stirrer bar, then the Pd catalyst
1 mol%) and followed by NMP solvent (5 mL). Then the reaction mixture was set to
(

Molecules 2021, 26, 1414
12 of 15
◦
react at 120 C for the given period of time before GC/MS analysis was done to confirm
the completion of the reaction. Once the catalytic recovery was done, the pure product
was isolated by using CH Cl /H O extraction and the CH Cl layer was pumped under
2
2
2
2
2
reduced pressure to obtain the pure product. The product was finally analyzed by using
1
H-NMR spectroscopy.
The Pd-catalyzed Stille reactions of all the aryl halide substrates with 3 were carried
out under the thermomorphic condition that effectively confirmed the practicability of
reutilizing the catalyst in NMP solvent. For every round, the catalytic reaction was per-
◦
formed at 120–150 C under N gas. At the end of each run, the product mixtures were put
2
◦
into a freezer (
−
10 C) for about five minutes and then centrifuged to separate the catalyst
and reaction mixture. After the catalyst was recovered by decantation and washed three
times by the same solvent, it was again supplied with the same amounts of NMP solvent,
aryl halide and vinyl tributyltin to continue to the next round. The products were tracked
1
with GC/MS (see Section 3 in Supplementary Materials) and H NMR, using anisole as an
internal standard until the completion of the reaction was confirmed.
3.6. Procedures in Catalytic Suzuki-Miyaura Reaction and Recovery
In a typical run, 4-cyanoiodobenzene (0.3 mmol) and phenylboronic acid (0.2 mmol)
were charged into 10 mL reaction tube containing a magnetic stirrer bar, then the Pd
catalyst (3 mol%) and followed by DMF solvent (5 mL). Then the reaction mixture was set
◦
to react at 150 C for 8 h before GC/MS analysis was done to confirm the completion of the
reaction. The Pd-catalyzed Suzuki-Miyaura reactions of boronic acid substrates with aryl
halides were carried out under the thermomorphic condition that effectively confirmed
the practicability of reutilizing the catalyst in a DMF solvent. Every round the catalytic
◦
reaction was performed at 135, 140 or 150 C under N gas. At the end of each run, the
2
◦
product mixtures were put into a freezer (
−
10 C) for about 2 h and then centrifuged to
separate the catalyst and reaction mixture. After the catalyst was recovered by decantation
and washed three times, it was again supplied with the same amounts of DMF solvent and
the substrates to continue to the next round. The products were tracked with GC/MS (see
1
Section 3 in Supplementary Materials) and H NMR.
4. Conclusions
The recovery and recycling of catalysts in Pd-catalyzed Stille and Suzuki-Miyaura cou-
pling reactions employing the thermomorphic condition were successfully demonstrated.
The prepared Pd complexes 2a–c had very high fluorine contents and worked well in both
Stille and Suzuki-Miyaura reactions up to 8 cycles. The product yield was also higher in
most reaction runs; sometimes it even reached 100%. In the Stille reaction by using catalyst
2a, when aryl iodides were used as the substartes, good catalytic activities and recoverabil-
ity were observed for all the cases while the R group was unsubstituted, EWG or ERG. The
electronic effects from the R group could also be easily observed with R = EWG speeding up
the reaction and R = ERG slowing down the reaction. The metal leaching study for the Stille
reaction via the ICP-MS method showed that the Pd metal in the complex was effectively
recovered throughout the catalytic cycles with almost no loss in activity. Similarly, the
2a-catalyzed Suzuki-Miyaura reaction of iodobenzene derivatives with biphenyl boronic
acid derivatives took place with good catalytic activities and recoverability. Additionally, in
the extended work, the metal complexes 2a–c were also shown to be active in Pd-catalyzed
Suzuki-Miyaura reactions of 4-cyanobromobenzene with phenyl boronic acid. Previously,
we have reported that this type of fluorous long-chained Pd complexes have good catalytic
activity for Heck and Sonogashira reactions under the thermorphic mode. Therefore, we
can conclude that the catalysts 2a–c are effective in all major Pd-catalyzed C-C coupling
reactions for the sustainable research.
Supplementary Materials: The materials are available online. They include thermomorphic curve
1
9
studies, GC/MS data of products, and Figure S1. F NMR spectrum of the catalyst 2b.

Molecules 2021, 26, 1414
13 of 15
Author Contributions: N.L., C.-F.C. and C.-R.S. performed the conceptualization and had the
research idea; E.T., V.E., Z.-L.T., H.-C.S. and K.L.C. performed syntheses and characterization of the
palladium complexes and conducted the catalytic studies. N.L. and C.-F.C. analyzed the obtained
data and wrote the manuscript. All authors have read and agreed to the published version of
the manuscript.
Funding: This research was funded by MOST, 106–2113-M-027–001 and university joint grants:
NTUT-CGMH-108–03 and NTUTCGMH-106–7 (or CORPG3G0071).
Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Data Availability Statement: The data presented in this study are available in the article.
Acknowledgments: We gratefully acknowledge the Ministry of Science and Technology in Taiwan
and university joint grants. All authors thank R. L. Sobocinski for proof-reading.
Conflicts of Interest: The authors declare no conflict of interest.
Sample Availability: Some of the fluorous palladium complexes are available from the authors.
References
1.
2.
3.
4.
5.
6.
Cordovilla, C.; Bartolomé, C.; Martínez-Ilarduya, J.S.M.; Espinet, P. The Stille reaction, 38 years later. ACS Catal. 2015, 5, 3040–3053.
CrossRef]
Lee, V. Application of copper (i) salt and fluoride promoted Stille coupling reactions in the synthesis of bioactive molecules. Org.
Biomol. Chem. 2019, 17, 9095–9123. [CrossRef] [PubMed]
Nikoorazm, M.; Ghorbani-Choghamarani, A.; Khanmoradi, M. Application of Pd-2A3HP-MCM-41 to the Suzuki, Heck and Stille
coupling reactions and synthesis of 5-substituted 1H-tetrazoles. Appl. Organomet. Chem. 2016, 30, 705–712. [CrossRef]
Wang, D.-Y.; Kawahata, M.; Yang, Z.-K.; Miyamoto, K.; Komagawa, S.; Yamaguchi, K.; Wang, C.; Uchiyama, M. Stille coupling via
C–N bond cleavage. Nat. Commun. 2016, 7, 1–9. [CrossRef] [PubMed]
[
Miyaura, N.; Suzuki, A. Palladium-catalyzed cross-coupling reactions of organoboron compounds. Chem. Rev. 1995, 95, 2457–2483.
[CrossRef]
Suzuki, A.J. Recent advances in the cross-coupling reactions of organoboron derivatives with organic electrophiles, 1995–1998. J.
Organomet. Chem. 1999, 576, 147–168. [CrossRef]
7
8
.
.
Sofiyev, V.; Navarro, G.; Trauner, D. Biomimetic synthesis of the shimalactones. Org. Lett. 2008, 10, 149–152. [CrossRef]
Souris, C.; Frébault, F.; Patel, A.; Audisio, D.; Houk, K.N.; Maulide, N. Stereoselective synthesis of dienyl-carboxylate building
blocks: Formal synthesis of inthomycin C. Org. Lett. 2013, 15, 3242–3245. [CrossRef]
9
1
1
.
Heravi, M.M.; Hashemi, E.; Azimian, F. Recent developments of the Stille reaction as a revolutionized method in total synthesis.
Tetrahedron 2014, 70, 7–21. [CrossRef]
0. Lord, A.M.; Mahon, M.F.; Lloyd, M.D.; Threadgill, M.D. Design, synthesis, and evaluation in vitro of quinoline-8-carboxamides, a
new class of poly (adenosine-diphosphate-ribose) polymerase-1 (PARP-1) inhibitor. J. Med. Chem. 2009, 52, 868–877. [CrossRef]
1. Cullen, M.D.; Deng, B.L.; Hartman, T.L.; Watson, K.M.; Buckheit, R.W.; Pannecouque, C.; Cushman, M. Synthesis and biological
evaluation of alkenyldiarylmethane HIV-1 non-nucleoside reverse transcriptase inhibitors that possess increased hydrolytic
stability. J. Med. Chem. 2007, 50, 4854–4867. [CrossRef] [PubMed]
1
1
1
1
2. Nicolaou, K.C.; King, N.P.; Finlay, M.R.V.; He, Y.; Roschangar, F.; Vourloumis, D.; Hepworth, D. Total synthesis of epothilone E
and related side-chain modified analogues via a Stille coupling based strategy. Bioorg. Med. Chem. 1999, 7, 665–697. [CrossRef]
3. Johansson Seechurn, C.C.; Kitching, M.O.; Colacot, T.J.; Snieckus, V. Palladium-catalyzed cross-coupling: A historical contextual
perspective to the 2010 Nobel Prize. Angew. Chem. Int. Ed. 2012, 51, 5062–5085. [CrossRef] [PubMed]
4. Carsten, B.; He, F.; Son, H.J.; Xu, T.; Yu, L. Stille polycondensation for synthesis of functional materials. Chem. Rev. 2011, 111,
1
493–1528. [CrossRef]
5. Choudary, B.M.; Madhi, S.; Chowdari, N.S.; Kantam, M.L.; Sreedhar, B. Layered double hydroxide supported nanopalladium
catalyst for Heck-, Suzuki-, Sonogashira-, and Stille-type coupling reactions of chloroarenes. J. Am. Chem. Soc. 2002, 124,
1
4127–14136. [CrossRef]
1
1
1
1
6. Mosleh, I.; Shahsavari, H.R.; Beitle, R.; Beyzavi, M.H. Recombinant Peptide Fusion Protein-templated Palladium Nanoparticles
for Suzuki-Miyaura and Stille Coupling Reactions. ChemCatChem 2020, 12, 2942–2946. [CrossRef]
7. Ghorbani-Choghamarani, A.; Norouzi, M. Palladium supported on modified magnetic nanoparticles: A phosphine-free and
heterogeneous catalyst for Suzuki and Stille reactions. Appl. Organomet. Chem. 2016, 30, 140–147. [CrossRef]
8. Mohazzab, B.F.; Jaleh, B.; Issaabadi, Z.; Nasrollahzadeh, M.; Varma, R.S. Stainless steel mesh-GO/Pd NPs: Catalytic applications
of Suzuki–Miyaura and Stille coupling reactions in eco-friendly media. Green Chem. 2019, 21, 3319–3327. [CrossRef]
9. Dell’Anna, M.M.; Lofù, A.; Mastrorilli, P.; Mucciante, V.; Nobile, C.F. Stille coupling reactions catalysed by a polymer supported
palladium complex. J. Organomet. Chem. 2006, 691, 131–137. [CrossRef]

Molecules 2021, 26, 1414
14 of 15
2
0. Yin, X.; Guo, F.; Lalancette, R.A.; Jäkle, F. Luminescent main-chain organoborane polymers: Highly robust, electron-deficient poly
oligothiophene borane) s via Stille coupling polymerization. Macromolecules 2016, 49, 537–546. [CrossRef]
(
2
1. Ryu, S.H.; Choi, S.J.; Seon, J.H.; Jo, B.; Lee, S.M.; Kim, H.J.; Ko, Y.-J.; Ko, K.C.; Ahn, T.K.; Son, S.U. Visible light-driven Suzuki–
Miyaura reaction by self-supported Pd nanocatalysts in the formation of Stille coupling-based photoactive microporous organic
polymers. Catal. Sci. Technol. 2020, 10, 5535–5543. [CrossRef]
2
2
2
2
2
2. McAfee, S.M.; McCahill, J.S.; Macaulay, C.M.; Hendsbee, A.D.; Welch, G.C. Utility of a heterogeneous palladium catalyst for the
synthesis of a molecular semiconductor via Stille, Suzuki, and direct heteroarylation cross-coupling reactions. RSC Adv. 2015, 5,
2
6097–26106. [CrossRef]
3. Saha, D.; Sen, R.; Maity, T.; Koner, S. Anchoring of palladium onto surface of porous metal–organic framework through post-
synthesis modification and studies on Suzuki and Stille coupling reactions under heterogeneous condition. Langmuir 2013, 29,
3
140–3151. [CrossRef] [PubMed]
4. Ghorbani-Choghamarani, A.; Nikpour, F.; Ghorbani, F.; Havasi, F. Anchoring of Pd (II) complex in functionalized MCM-41 as
an efficient and recoverable novel nano catalyst in C–C, C–O and C–N coupling reactions using Ph SnCl. RSC Adv. 2015, 5,
3
3
3212–33220. [CrossRef]
5. Khanmoradi, M.; Nikoorazm, M.; Ghorbani-Choghamarani, A. Synthesis and characterization of Pd schiff base complex
immobilized onto functionalized nanoporous MCM-41 and its catalytic efficacy in the Suzuki, Heck and Stille coupling reactions.
Catal. Lett. 2017, 147, 1114–1126. [CrossRef]
6. Su, W.; Urgaonkar, S.; McLaughlin, P.A.; Verkade, J.G. 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. 2004, 126, 16433–16439. [PubMed]
2
7. Li, X.; Zhu, T.; Shao, Z.; Li, Y.; Chang, H.; Gao, W.; Zhang, Y.; Wei, W. Newly-generated Al(OH) -supported Pd nanoparticles-
3
catalyzed Stille and Kumada coupling reactions of diazonium salts,(Het) aryl chlorides. Tetrahedron 2016, 72, 69–75. [CrossRef]
8. Holz, J.; Pfeffer, C.; Zuo, H.; Beierlein, D.; Richter, G.; Klemm, E.; Peters, R. In Situ Generated Gold Nanoparticles on Active
Carbon as Reusable Highly Efficient Catalysts for a C–C Stille Coupling. Angew. Chem. Int. Ed. 2019, 58, 10330–10334. [CrossRef]
2
[PubMed]
2
3
9. Ghorbani-Choghamarani, A.; Naghipour, A.; Heidarizadi, F.; Shirkhani, R.; Notash, B. Bis[(2-methylacetatobenzyl)tri(p-tolyl)
phosphonium] hexabromodipalladate (II); Synthesis, characterization, structural study and application as a retrievable het-
erogeneous catalyst for the amination of aryl halides and Stille cross-coupling reaction. Inorg. Chim. Acta 2016, 446, 97–102.
[
CrossRef]
0. Naghipour, A.; Ghorbani-Choghamarani, A.; Heidarizadi, F.; Notash, B. Synthesis, characterization and structural study of a
phosphonium salt containing the [Pd Br6]2 ion and its application as a novel, efficient and renewable heterogeneous catalyst for
amination of aryl halides and the Stille cross-coupling reaction. Polyhedron 2016, 105, 18–26. [CrossRef]
−
2
0
3
3
3
3
3
3
3
3
3
4
1. Wu, W.-Y.; Liu, L.-J.; Chang, F.-P.; Cheng, Y.-L.; Tsai, F.-Y. A Highly Efficient and Reusable Palladium (II)/Cationic 2, 2 -Bipyridyl-
Catalyzed Stille Coupling in Water. Molecules 2016, 21, 1205. [CrossRef]
2. Ogo, S.; Takebe, Y.; Uehara, K.; Yamazaki, T.; Nakai, H.; Watanabe, Y.; Fukuzumi, S. pH-Dependent C C Coupling Reactions
−
Catalyzed by Water-Soluble Palladacyclic Aqua Catalysts in Water. Organometallics 2006, 25, 331–338. [CrossRef]
3. Fareghi-Alamdari, R.; Golestanzadeh, M.; Bagheri, O. An efficient and recoverable palladium organocatalyst for Suzuki reaction
in aqueous media. Appl. Organomet. Chem. 2017, 31, e3698. [CrossRef]
4. Hao, W.; Xi, Z.; Cai, M. A practical synthesis of biaryls and aromatic acetylenes by Stille coupling in room-temperature ionic
liquids. Synth. Commun. 2012, 42, 2396–2406. [CrossRef]
5. Chiappe, C.; Imperato, G.; Napolitano, E.; Pieraccini, D. Ligandless Stille cross-coupling in ionic liquids. Green Chem. 2004, 6,
3
3–36. [CrossRef]
6. Baran, T.; Baran, N.Y.; Mente s¸ , A. An easily recoverable and highly reproducible agar-supported palladium catalyst for Suzuki-
Miyaura coupling reactions and reduction of o-nitroaniline. Int. J. Biol. Macromol. 2018, 115, 249–256. [CrossRef]
7. Okamoto, K.; Akiyama, R.; Kobayashi, S. Suzuki–Miyaura Coupling Catalyzed by Polymer-Incarcerated Palladium, a Highly
Active, Recoverable, and Reusable Pd Catalyst. Org. Lett. 2004, 6, 1987–1990. [CrossRef]
8. Lin, B.; Liu, Z.; Liu, M.; Pan, C.; Ding, J.; Wu, H.; Cheng, J. Aminophosphine supported on Al O as recoverable catalyst for the
2
3
Suzuki coupling. Catal. Commun. 2007, 8, 2150–2152. [CrossRef]
9. Smith, M.D.; Stepan, A.F.; Ramarao, C.; Brennan, P.E.; Ley, S.V. Palladium-containing perovskites: Recoverable and reuseable
catalysts for Suzuki couplings. Chem. Commun. 2003, 21, 2652–2653. [CrossRef]
0. Guerra, R.R.; Martins, F.C.; Lima, C.G.; Goncalves, R.H.; Leite, E.R.; Pereira-Filho, E.R.; Schwab, R.S. Factorial design evaluation
of the Suzuki cross-coupling reaction using a magnetically recoverable palladium catalyst. Tetrahedron Lett. 2017, 58, 903–908.
[CrossRef]
4
4
4
1. Rangraz, Y.; Nemati, F.; Elhampour, A. A novel magnetically recoverable palladium nanocatalyst containing organoselenium
ligand for the synthesis of biaryls via Suzuki-Miyaura coupling reaction. J. Phys. Chem. Solids 2020, 138, 109251–109258. [CrossRef]
2. Lu, N.; Chen, S.-C.; Chen, T.-C.; Liu, L.-K. Palladium-catalyzed Heck reaction under thermomorphic mode. Tetrahedron Lett. 2008
9, 371–375. [CrossRef]
,
4
3. Li, C.-K.; Ghalwadkar, A.; Lu, N. Recoverable cationic Pd-catalyzed Heck reaction under thermomorphic mode. J. Organomet.
Chem. 2011, 696, 3637–3642. [CrossRef]

Molecules 2021, 26, 1414
15 of 15
4
4. Lu, N.; Lin, Y.-C.; Chen, J.-Y.; Fan, C.-W.; Liu, L.-K. New bis (fluoro-ponytailed) bipyridine ligands for Pd-catalyzed Heck
reactions under fluorous biphasic catalysis condition. Tetrahedron 2007, 63, 2019–2023. [CrossRef]
4
5. Lu, N.; Ou, Y.-M.; Feng, T.-Y.; Cheng, W.-J.; Tu, W.-H.; Su, H.-C.; Wang, X.; Liu, L.; Hennek, M.D.; Sayler, T.S. Synthesis and
0
characterization of polyfluorinated 2, 2 -bipyridines and their palladium and platinum complexes [MX (bis(R CH OCH )-2,
2
f
2
2
0
2
-bpy)](X = Cl, Br). J. Fluor. Chem. 2012, 137, 54–63. [CrossRef]
4
4
4
6. Lu, N.; Lin, K.Y.; Li, C.K.; Kung, C.C.; Yeh, Y.P.; Cheng, Y.Y.; Liu, L.K. Recyclable palladium catalysts for the Heck/Sonogashira
reaction under microwave-assisted thermomorphic conditions. J. Chin. Chem. Soc. 2015, 62, 64–72. [CrossRef]
7. Lu, N.; Chen, Y.-C.; Chen, W.-S.; Chen, T.-L.; Wu, S.-J. Efficient, Recoverable, Copper-Free Sonogashira Reaction under FBS and
Thermomorphic Mode. J. Organomet. Chem. 2009, 694, 278–284. [CrossRef]
8. Lu, N.; Chen, S.C.; Lin, Y.C.; Cheng, Y.Y.; Liu, L.K. High Fluorine Content Bis (fluoro-Ponytailed) Bipyridine Palladium Complexes
as Catalyst for Mizoroki-Heck Reactions under Fluorous Biphasic Catalysis Conditions. J. Chin. Chem. Soc. 2008, 55, 89–96.
[
CrossRef]
9. Yabe, Y.; Maegawa, T.; Monguchi, Y.; Sajiki, H. Palladium on charcoal-catalyzed ligand-free Stille coupling. Tetrahedron 2010, 66,
654–8660. [CrossRef]
0. Wolf, C.; Lerebours, R. Efficient Stille cross-coupling reaction using aryl chlorides or bromides in water. J. Org. Chem. 2003, 68,
551–7554. [CrossRef] [PubMed]
4
5
5
5
5
5
8
7
1. Milstein, D.; Stille, J.K. A general, selective, and facile method for ketone synthesis from acid chlorides and organotin compounds
catalyzed by palladium. J. Am. Chem. Soc. 1978, 100, 3636–3638. [CrossRef]
2. Lu, N.; Yeh, Y.P.; Wang, G.B.; Feng, T.Y.; Shih, Y.H.; Chen, D. Dye-sensitized TiO -catalyzed photodegradation of sulfamethoxazole
2
under blue or yellow light. Environ. Sci. Pollut. Res. 2017, 24, 489–499. [CrossRef]
3. Howell, J.L.; Lu, N.; Friesen, C.M. New derivatives of poly-hexafluoropropylene oxide from the corresponding alcohol. J. Fluor.
Chem. 2005, 126, 281–288. [CrossRef]
0
4. Lu, N.; Tu, W.H.; Hou, H.C.; Lin, C.T.; Li, C.K.; Liu, L.K. Synthesis, structure and spectroelectrochemical property of (2, 2 -
0
bipyridine)–metal (M = Pt, Pd) dichloride with 4, 4 -bis (fluorous-ponytail) on bipyridine. Polyhedron 2010, 29, 1123–1129.
[CrossRef]
5
5. Periyanagounder, D.; Wei, T.C.; Li, T.Y.; Lin, C.H.; Gonçalves, T.P.; Fu, H.C.; Tsai, D.S.; Ke, J.J.; Kuo, H.W.; Huang, K.W.; et al.
Fast-Response, Highly Air-Stable, and Water-Resistant Organic Photodetectors Based on a Single-Crystal Pt Complex. Adv. Mater.
2
020, 32, 1904634. [CrossRef] [PubMed]
0
5
5
6. Lu, N.; Chen, J.Y.; Fan, C.W.; Lin, Y.C.; Wen, Y.S.; Liu, L.K. (2, 2 -Bipyridine) palladiumdichloride Derivatives as Recyclable
Catalysts in Heck Reactions. J. Chin. Chem. Soc. 2006, 53, 1517–1521. [CrossRef]
7. Howell, J.L.; Lu, N.; Perez, E.W.; Friesen, C.M.; Novak, I.; Waterfeld, A.; Thrasher, J.S. The preparation of primary poly-
hexafluoropropylene oxide halides (poly-HFPO-CF2X where X = I, Br, Cl and F). J. Fluor. Chem. 2004, 125, 1513–1518. [CrossRef]