A phosphine-free, heterogeneous palladium-catalyzed atom-efficient carbonylative cross-coupling of triorganoindiums with aryl halides leading to unsymmetrical ketones

Article abstract of DOI:10.1039/c7nj02969a

The first phosphine-free heterogeneous palladium-catalyzed carbonylative cross-coupling of aryl halides with triorganoindiums has been developed that proceeds smoothly under 1 or 2.5 atm of carbon monoxide in THF at 68 °C and provides a general and powerful tool for the synthesis of various valuable unsymmetrical ketones with high atom-economy, good yield, and recyclability of the catalyst. Our system not only avoids the use of phosphine ligands, but also solves the basic problem of palladium catalyst recovery and reuse.

Full text of DOI:10.1039/c7nj02969a

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A phosphine-free, heterogeneous palladium-catalyzed atom-
efficient carbonylative cross-coupling of triorganoindiums
with aryl halides leading to unsymmetrical ketones
a
b,
a
a,
Shengyong You, Ruian Xiao, * Haiyi Liu and Mingzhong Cai *
a
Key Laboratory of Functional Small Organic Molecule, Ministry of Education and
College of Chemistry & Chemical Engineering, Jiangxi Normal University, Nanchang
30022, P. R. China
3
b
9
12 Lab Jiangxi Bureau of Geology and Mineral Exploration and Development,
Yingtan 335001, P. R. China
Eꢀmail: mzcai@jxnu.edu.cn; xiaoruian@163.com
The first phosphineꢀfree heterogeneous palladiumꢀcatalyzed carbonylative crossꢀ
coupling of aryl halides with triorganoindiums has been developed that proceeds
smoothly under 1 or 2.5 atm of carbon monoxide in THF at 68 ºC and provides a
general and powerful tool for the synthesis of various valuable unsymmetrical ketones
with high atomꢀeconomy, good yield, and recyclability of the catalyst. Our system not
only avoids the use of phosphine ligands, but also solves the basic problem of pallaꢀ
dium catalyst recovery and reuse.
Introduction
1
2
Aryl ketones and α,βꢀacetylenic ketones are important building blocks for a large
number of natural products and pharmaceutical compounds. One general method for
the preparation of aryl ketones is the FriedelꢀCrafts acylation of substituted aromatic
3
rings. The crucial disadvantage of traditional FriedelꢀCrafts acylation is the use of
more than a stoichiometric amount of anhydrous AlCl , which is incompatible with
3
many functional groups and produces a large amount of waste. A common approach
1

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to α,βꢀacetylenic ketones involves the acylation of alkynylmetal reagents such as
4
5
6
7
8
9
silver, copper, lithium, zinc, silicon, and tin with acid chlorides. Generally, the
preparation of unsymmetrical ketones by transitionꢀmetalꢀcatalyzed crossꢀcoupling
reaction is severely limited, since the organometallic partners often react with the
product ketone. The transition metalꢀcatalyzed carbonylative crossꢀcoupling reaction
of organic electrophiles with organometallics in the presence of carbon monoxide has
1
0
provided a straightforward and convenient route to unsymmetrical ketones.
A
11
12
13
14
15
variety of organometallics including magnesium, aluminum, silicon, tin, zinc,
16
17
boron, and bismuth reagents have been reported to undergo the carbonylative
crossꢀcoupling reactions, but the utility of this route is limited by requirements of a
high temperature or a high pressure of carbon monoxide, the transfer of only one of
the organic groups attached to the metal, and βꢀhydride elimination. Recently, we
reported a phosphineꢀfree heterogeneous palladiumꢀcatalyzed atomꢀefficient carbonyꢀ
lative crossꢀcoupling of aryl iodides with triarylbismuths leading to biaryl ketones,
however, the developed method was not applicable to the synthesis of alkyl aryl
18
ketones and α,βꢀacetylenic ketones. Besides these traditional organometallic
reagents, triorganoindium reagents (R In) are increasingly gaining attention as
3
1
9
efficient partners for transitionꢀmetalꢀcatalyzed crossꢀcouplings. The high efficiency,
versatility, atomꢀeconomy, and chemoselectivity of these organoindium reagents make
them useful alternatives to other organometallic compounds in crossꢀcoupling reacꢀ
tions. Lee and Sarandeses reported the palladium(0)ꢀcatalyzed carbonylative crossꢀ
coupling reactions of triorganoindium compounds with aryl (or alkenyl) halides (or
2

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pseudohalides) and CO, providing a new and efficient route for the synthesis of unsyꢀ
2
0
mmetrical ketones. The reaction was carried out in refluxing THF under 1 or 2.5 atm
of CO with 4ꢀ5 mol% Pd(PPh as catalyst. However, homogeneous Pd(PPh is air
3
)
4
3 4
)
and moistureꢀsensitive, expensive, cannot be recycled, and difficult to separate from
the product mixture, which may have a very serious negative impact on their possible
industrial applications, especially the pharmaceutical industry. Therefore, from the
viewpoint of green and sustainable chemistry, the development of a recyclable pallaꢀ
dium catalyst that allows for highly efficient synthesis of unsymmetrical ketones from
a wide range of substrates (aryl halides and triorganoindiums) is highly desirable.
Immobilization of homogeneous catalysts through covalent bond formation with
functional groups on various porous materials is usually the method of choice since
the supported catalysts can be easily separated from the reaction mixture by simple
filtration and reused in successive reactions provided that the active sites have not
become deactivated. Moreover, heterogeneous catalysis also helps decrease wastes
derived from reaction workup, contributing to development of green and sustainable
2
1
chemical process. Mesoporous material MCMꢀ41 has recently emerged as a promisꢀ
ing solid support for immobilization because of its large and uniform pore size,
2
2
ultrahigh surface area, big pore volume and rich silanol groups in the inner walls. So
far, some functionalized MCMꢀ41ꢀimmobilized transitionꢀmetal catalysts such as
18,23
24
25
26
27
palladium,
rhodium, molybdenum, gold and copper complexes have been
successfully used as potentially green and sustainable catalysts in organic reactions.
Recently, we reported the first synthesis of an MCMꢀ41ꢀimmobilized palladium(II)ꢀ
3

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Schiff base complex [MCMꢀ41ꢀN,NꢀPd(OAc)
2
] and its successful application to the
2
8
atomꢀefficient crossꢀcoupling of triarylbismuths with aryl iodides. In continuing our
2
3c,d,26d,27
efforts to develop greener synthetic pathways for organic transformations,
herein we wish to report the first phosphineꢀfree heterogeneous palladiumꢀcatalyzed
carbonylative crossꢀcoupling of aryl halides with triorganoindiums by using MCMꢀ41
2
ꢀN,NꢀPd(OAc) complex as a recyclable catalyst. The reactions proceeded smoothly
in THF at 68 ºC under 1 or 2.5 atm of carbon monoxide, yielding a variety of unsymꢀ
metrical ketones in good yields with high atomꢀeconomy and recyclability of the
catalyst.
Results and discussion
Although phosphine ligands can stabilize palladium and influence its reactivity, the
simplest and cheapest palladium catalysts are of course the phosphineꢀfree systems.
Furthermore, the procedure for synthesizing the immobilized phosphine palladium
complexes is rather complicated since the preparation of the heterogeneous phosphine
ligands requires multiꢀstep sequences. Therefore, the development of phosphineꢀfree
supported palladium complex catalysts having a high activity and good stability is a
topic of enormous importance. The MCMꢀ41ꢀimmobilized palladium(II)ꢀSchiff base
complex [MCMꢀ41ꢀN,NꢀPd(OAc) ] was easily synthesized starting from mesoporous
2
material MCMꢀ41, 3ꢀaminopropyltriethoxysilane, pyridineꢀ2ꢀcarboxaldehyde, and
28
Pd(OAc) as shown in Scheme 1 according to our previous precedure. Firstly, the
2
condensation of 3ꢀaminopropyltriethoxysilane with MCMꢀ41 in toluene at 100 °C for
4

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2
4 h, followed by the silylation with Me
3
SiCl in toluene at room temperature for 24 h
). The latter was
gave 3ꢀaminopropylꢀfunctionalized MCMꢀ41 material(MCMꢀ41ꢀNH
2
subsequently treated with pyridineꢀ2ꢀcarboxaldehyde in dry ethanol at 80 °C for 12 h
to afford the Schiff baseꢀfunctionalized MCMꢀ41 (MCMꢀ41ꢀN,N), which was then
2
reacted with Pd(OAc) in acetone under reflux for 72 h to generate the MCMꢀ41ꢀ
immobilized palladium(II)ꢀSchiff base complex [MCMꢀ41ꢀN,NꢀPd(OAc)
yellow powder.
2
] as a light
The MCMꢀ41ꢀimmobilized palladium(II)ꢀSchiff base complex [MCMꢀ41ꢀN,Nꢀ
Pd(OAc) ] was then used as the catalyst for the carbonylative crossꢀcoupling of aryl
halides with triorganoindiums. In our initial screening experiments, the carbonylative
crossꢀcoupling of 4ꢀiodotoluene with Me In (0.37 equiv.) in the presence of 1.0 mol%
2
3
MCMꢀ41ꢀN,NꢀPd(OAc) was chosen as the model reaction to optimize the reaction
2
conditions and the results are summarized in Table 1. Of the optimized reaction
conditions screened, the best result was obtained with 0.37 equiv of Me
3
In and 1.0
mol% of MCMꢀ41ꢀN,NꢀPd(OAc) in THF at 68 ºC under atmospheric pressure of CO
2
5

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gas, and the desired 4'ꢀmethylacetophenone 3a was produced in 81% yield (Table 1,
entry 1). This result means that all of the methyl groups attached to the indium were
clearly entered into the product. Surprisingly, however, a decreased yield of 3a was
observed under higher pressure (5 and 10 atm) of CO gas (entries 2 and 3). The
carbonylative crossꢀcoupling reaction did not occur at 25 ºC even under 5 atm of CO
gas (entries 4 and 5). Lowering the reaction temperature to 50 ºC resulted in a
20a
3 4
decreased yield (entries 6 and 7). When 4 mol% of Pd(PPh ) was used as catalyst,
the desired product 3a was obtained in 72 % yield after 4 h (entry 8), indicating that
the phosphineꢀfree heterogeneous palladium catalyst exhibited higher activity than
3 4
Pd(PPh ) . Increasing the amount of the catalyst to 2.0 mol% could shorten the
reaction time, but did not improve the yield significantly (entry 9). Reducing the
amount of the catalyst to 0.5 mol% resulted in a decreased yield and required a longer
reaction time (entry 10).
Table 1 Carbonylative crossꢀcoupling reaction of 4ꢀiodotoluene with Me
equiv.) in different conditions.
3
In (0.37
a
Entry
Pressure of CO (atm) Temp. (ºC)
Time (h)
Isolated yield (%)
1
2
3
4
5
6
1
68
68
68
25
25
50
2
2
2
6
6
6
81
63
49
0
5
10
1
5
0
1
31
6

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7
8
9
1
5
1
1
1
50
68
68
68
6
4
1
5
34
72
82
65
b
c
d
0
a
3
All reactions were performed using 1.0 mmol of 4ꢀiodotoluene, 0.37 mmol of Me In in 4.0 mL of
b
c
d
THF. 4 mol% Pd(PPh
3 4 2
) was used. 2 mol% of MCMꢀ41ꢀN,NꢀPd(OAc) was used. 0.5 mol%
of MCMꢀ41ꢀN,NꢀPd(OAc) was used.
2
To examine the scope for this heterogeneous carbonylative crossꢀcoupling reaction,
we have investigated the reaction using a variety of aryl halides and different triorgꢀ
anoindiums as the substrates under the optimized reaction conditions (Scheme 2) and
the results are outlined in Table 2. As shown in Table 2, the carbonylative crossꢀcoupꢀ
ling reactions of Me In with a variety of aryl iodides bearing either electronꢀdonating
3
or electronꢀwithdrawing groups proceeded smoothly under the optimized conditions,
giving the corresponding substituted acetophenones 3b-3e in 80ꢀ87% yields (entries
2
ꢀ5). The results indicate that the electronic nature of the substituent on the benzene
ring has limited influence on this heterogeneous palladiumꢀcatalyzed carbonylative
crossꢀcoupling reaction. Reactions of sterically hindered 2ꢀiodotoluene and bulky
1
ꢀiodonaphthalene also proceeded effectively to furnish the desired 2'ꢀmethylacetoꢀ
phenone 3f and 1ꢀacetylnaphthalene 3g in 79 and 83% yield, respectively (entries 6
and 7). Heteroatoms turned out to be compatible with the employed reaction condiꢀ
tions, the reaction of 2ꢀiodothiophene with Me
ꢀacetylthiophene 3h in 80% yield (entry 8). Triꢀnꢀbutylindium exhibited a similar
reactivity with trimethylindium. Both electronꢀdeficient and electronꢀrich aryl iodides
3
In and CO produced the desired
2
3
could undergo the carbonylative crossꢀcoupling reactions with nꢀBu In under atmosꢀ
7

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pheric pressure of CO gas smoothly to afford the corresponding nꢀbutyl aryl ketones
3i-3m in 81ꢀ86% yields (entries 9ꢀ13). In addition, bulky 1ꢀiodonaphthalene and
2ꢀiodothiophene gave the expected products 3n and 3o in good yields (entries 14 and
15). Triꢀsecꢀbutylindium could also react with iodobenzene under an atmospheric
pressure of CO to produce the desired 2ꢀmethylꢀ1ꢀphenylbutanꢀ1ꢀone 3p in 76% yield
entry 16). However, the reaction did not work with tricyclopropylindium (cꢀPr In).
Besides trialkylindiums, triarylꢀ and trialkynylindiums also proved to be suitable
coupling partners. However, under the reaction conditions optimized for Me In, the
(
3
3
carbonylative crossꢀcoupling reactions of Ph In or trialkynylindiums with aryl iodides
3
afforded only moderate yields of unsymmetrical ketones due to the easy formation of
the direct crossꢀcoupling products. To our delight, the direct crossꢀcoupling reactions
of aryl iodides with Ph
3
In or trialkynylindiums could be greatly suppressed by
In
increasing the pressure of CO from 1 to 2.5 atm. For example, the reactions of Ph
3
with aryl iodides bearing various substituents, regardless of their electronic properties
and substitution positions, produced the desired diaryl ketones 3q-3u in 68ꢀ88%
yields (entries 17ꢀ21). It is noteworthy that under the optimized reaction conditions,
bulky 1ꢀiodonaphthalene and heteroaryl iodides such as 2ꢀiodothiophene and 3ꢀiodoꢀ
3
pyridine could undergo the carbonylative crossꢀcoupling reactions with Ph In
effectively, affording the desired products 3v-3x in good yields (entries 22ꢀ24). The
reactions of tri(phenylethynyl)indium and tri(hexꢀ1ꢀynyl)indium with various aryl
iodides also proceeded smoothly under 2.5 atm of CO to furnish the corresponding
aryl alkynyl ketones 3y-3c' in 74ꢀ86% yields (entries 25ꢀ29). Interestingly, 4ꢀchloroꢀ
8

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iodobenzene was selectively subjected to carbonylative crossꢀcoupling reactions to
produce the desired 4'ꢀchloroacetophenone 3d, 1ꢀ(4ꢀchlorophenyl)pentanꢀ1ꢀone 3k,
and 1ꢀ(4ꢀchlorophenyl)ꢀ3ꢀphenylpropꢀ2ꢀynꢀ1ꢀone 3z in high yields (entries 4, 11 and
2
6). The present method provides a quite general and practical route for the synthesis
of a variety of unsymmetrical ketones. A wide range of electronꢀdonating and electron
withdrawing groups such as methyl, methoxy, chloro, fluoro, trifluoromethyl, cyano,
ꢀ
ketone and ester on aryl iodides were well tolerated.
Encouraged by the above results, the carbonylative crossꢀcoupling reactions of
triorganoindiums with a variety of aryl bromides were then examined under optimized
reaction conditions and the results are also listed in Table 2. Generally, the reactivity
of aryl bromides was lower than that of aryl iodides. The reactions of electronꢀ
deficient aryl bromides with trialkylindiums could proceed smoothly to afford the
desired alkyl aryl ketones in good yields (entries 30ꢀ33), whilst electronꢀrich aryl
bromides gave only low yields (entries 34 and 35). Similarly, the reactions of bromoꢀ
3
benzene and electronꢀdeficient aryl bromides with Ph In or trialkynylindiums could
give moderate yields of the desired products (entries 36ꢀ40), but the electronꢀrich aryl
9

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bromides were poor substrates (entries 41 and 42). We also applied the present
protocol to dihalogenated aromatic compounds to prepare diacylbenzenes, which can
be used effectively in materials and dendrimer sciences (Scheme 3). Reaction of 1,4ꢀ
diiodobenzene with 1.1 equiv of triꢀnꢀbutylindium under 1 atm of CO gas for 3 h
produced the expected 1,1'ꢀ(1,4ꢀphenylene)dipentanꢀ1ꢀone 4a in 70% yield. We were
pleased to observe that treatment of 1,4ꢀdiiodobenzene with 1.1 equiv of tri(4ꢀfluoroꢀ
phenyl)indium under 2.5 atm of CO gas for 3 h afforded the desired 1,4ꢀbis(4ꢀ
fluorobenzoyl)benzene 4b in 72% yield.
a
Table 2 Synthesis of a variety of unsymmetrical ketones.
b
Entry
ArꢀX
R
Time (h)
Product
Yield (%)
1
2
3
4
5
6
7
8
9
4ꢀMeC
6
H
4
I
Me
2
3a
3b
3c
3d
3e
3f
81
87
82
80
82
79
83
80
82
86
81
83
81
75
78
76
84
4ꢀMeOC
6
H
4
I
Me
2.5
2
4ꢀFC
6
H
4
I
Me
4ꢀClC
6
H
4
I
Me
2
4ꢀMeOCOC
2ꢀMeC
6
H
4
I
Me
1.5
3
6
H
4
I
Me
1ꢀiodonaphthalene
2ꢀiodothiophene
Me
2.5
2
3g
3h
3i
Me
3ꢀMeC
4ꢀMeOC
4ꢀClC
4ꢀMeCOC
4ꢀNCC
6
H
4
I
nꢀBu
nꢀBu
nꢀBu
nꢀBu
nꢀBu
nꢀBu
nꢀBu
secꢀBu
Ph
2
1
0
6
H
4
I
2.5
2
3j
1
1
6
H
4
I
3k
3l
1
1
1
1
1
1
2
3
4
5
6
7
6
H
4
I
1.5
1.5
2.5
2
6
H
4
I
3m
3n
3o
3p
3q
1ꢀiodonaphthalene
2ꢀiodothiophene
C
C
6
6
H
5
5
I
I
2.5
2
c
H
1
0

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c
c
c
c
c
c
c
c
c
c
c
c
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
4ꢀMeOC
4ꢀMeOCOC
3ꢀCF
2ꢀMeC
6
H
4
I
Ph
2.5
1.5
2
3r
88
85
80
68
79
77
71
86
83
74
79
85
71
63
67
69
43
29
50
46
59
61
51
26
32
6
H
4
I
Ph
3s
3
C
6
H
4
I
Ph
3t
6
H
4
I
Ph
3
3u
3v
3w
3x
3y
3z
1ꢀiodonaphthalene
2ꢀiodothiophene
3ꢀiodopyridine
Ph
2.5
2
Ph
Ph
2
4ꢀCH
3
C
6
H
4
I
PhC≡C
PhC≡C
nꢀBuC≡C
nꢀBuC≡C
nꢀBuC≡C
Me
2
4ꢀClC
6
H
4
I
2
C
6
H
5
I
2
3a'
3b'
3c'
3e
4ꢀCH
3
C
6
H
4
I
2
4ꢀMeOC
6
H
4
I
2
4ꢀMeOCOC
4ꢀClC Br
4ꢀMeCOC
4ꢀNCC
4ꢀCH
4ꢀMeOC
6
H
4
Br
2.5
3
6
H
4
Me
3d
3l
6
H
4
Br
nꢀBu
nꢀBu
Me
2.5
2.5
4
6
H
4
Br
Br
3m
3a
3j
3
C
6
H
4
6
H
4
Br
nꢀBu
Ph
6
c
c
c
c
c
c
c
C
C
6
6
H
5
Br
Br
3
3q
3a'
3d'
3e'
3z
H
5
nꢀBuC≡C
Ph
4
4ꢀMeCOC
4ꢀNCC
4ꢀClC
4ꢀMeOC
4ꢀCH
6
H
4
Br
3
6
H
4
Br
Ph
3
6
H
4
Br
PhC≡C
Ph
4
6
H
4
Br
6
3r
3
C
6
H
4
Br
PhC≡C
5
3y
a
Reaction was carried out with R
N,NꢀPd(OAc) in THF (4 mL) at 68 °C under atmospheric pressure of CO gas. Isolated yields.
Under 2.5 atm of CO.
3
In (0.37 mmol), aryl halide (1.0 mmol), and 1 mol% MCMꢀ41ꢀ
b
c
2
To verify whether the observed catalysis was due to the MCMꢀ41ꢀN,NꢀPd(OAc)2
complex or to a leached palladium species in solution, we performed the hot filtration
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2
9
test. We focused on the carbonylative crossꢀcoupling reaction of 4ꢀiodotoluene with
Me In. We filtered off the MCMꢀ41ꢀN,NꢀPd(OAc) complex after 0.5 h of reaction
3
2
time and allowed the filtrate to react further. The catalyst filtration was performed at
the reaction temperature (68 °C) to avoid possible recoordination or precipitation of
soluble palladium upon cooling. We found that, after this hot filtration, no significant
increase in conversion of 4ꢀiodotoluene was observed and the desired 3a was isolated
in only 39% yield, demonstrating that leached palladium species from the supported
catalyst (if any) are not responsible for the observed catalytic activity. It was conꢀ
firmed by ICPꢀAES analysis that no palladium species could be detected in the filtrate
(below the detection limit). These results rule out any contribution to the observed
catalysis from a homogeneous palladium species indicating that the catalyst was
stable during the reaction and the observed catalysis was intrinsically heterogeneous.
A plausible mechanism for this heterogeneous palladiumꢀcatalyzed carbonylative
2
0b
crossꢀcoupling of triorganoindiums with aryl halides is illustrated in Scheme 4.
30
First, the MCMꢀ41ꢀN,NꢀPd(OAc) complex is reduced by CO gas or R In to the
2
3
MCMꢀ41ꢀN,NꢀPd(0) complex. Oxidative addition of ArꢀX (1) to the MCMꢀ41ꢀN,Nꢀ
1
2

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Pd(0) complex provides an MCMꢀ41ꢀbound arylpalladium(II) complex (A), which is
followed by migratory insertion of carbon monoxide to afford an MCMꢀ41ꢀbound
acylpalladium(II) complex (B). Transmetalation between intermediate B and
triorganoindium reagent (2) gives intermediate (C), which undergoes reductive
elimination to afford the expected unsymmetrical ketone (3) and regenerate the
MCMꢀ41ꢀN,NꢀPd(0) complex.
MCM-41-N,N-Pd(OAc)2
CO or R In
3
O
MCM-41
(3)
Ar
Ar-X (1)
R
N
N
Pd(0)
MCM-41
MCM-41
N
N
R
(C)
N
N
X
(A)
Pd
Pd
Ar
Ar
O
MCM-41
R InX
2
(B)
N
N
X
Pd
Ar
CO
R In (2)
3
O
Scheme 4. Proposed catalytic cycle.
For a supported precious metal catalyst, it is important to examine its ease of
separation, recoverability and reusability. The MCMꢀ41ꢀN,NꢀPd(OAc) complex can
2
be easily separated and recovered by a simple filtration of the reaction solution. We
next investigated the recyclability of the catalyst by using the carbonylative crossꢀ
1
3

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3
coupling reaction of 4ꢀiodoanisole with Me In. After carrying out the reaction, the
catalyst was recovered by simple filtration and washed with DMF and diethyl ether.
After being airꢀdried, it can be reused directly without further purification. It should
be noted that the palladium in the recovered catalyst is in Pd(0) form. The recovered
palladium catalyst was used in the next run, and almost the same yield of 3b was
obtained for 8 consecutive cycles (Figure 1). In addition, palladium leaching in the
heterogeneous catalyst was also determined by ICPꢀAES analysis on the recovered
catalyst after eight consecutive runs and the palladium content of the recovered
catalyst was found to be 0.41 mmol/g, which revealing almost the same palladium
content as the fresh one. In our opinion, the high catalytic activity and excellent
reusability of the palladium catalyst relates to the efficient site isolation, to the
optimal dispersion of the active sites on the inner channel walls and to the relatively
strong interaction between bidentate Schiff base ligand and the palladium centre
supported on the MCMꢀ41. The result is important from the standpoint of green and
sustainable chemistry.
90
80
70
60
50
40
30
20
10
0
1
2
3
4
5
6
7
8
Recycled times
1
4

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2
Fig. 1 Recycle of the MCMꢀ41ꢀN,NꢀPd(OAc) complex.
Conclusion
In summary, we first developed the heterogeneous carbonylative crossꢀcoupling
reaction of readily available, stable and environmentally benign triorganoindium comꢀ
pounds with various aryl halides leading to a variety of unsymmetrical ketones in
good yields. This heterogeneous carbonylative crossꢀcoupling has many attractive
features, such as: (1) triorganoindiums act as low toxic and atomꢀefficient coupling
reagents; (2) 1 equiv of triorganoindiums gives 3 equiv of carbonylative coupling
products; (3) the reaction is tolerant of a wide range of functional groups; (4) only 1
mol% of MCMꢀ41ꢀN,NꢀPd(OAc) is used compared with 4ꢀ5 mol% of Pd(PPh ) in
2
3 4
homogeneous reaction; (5) this phosphineꢀfree heterogeneous palladium catalyst can
easily be prepared from commercially available reagents and recovered by a simple
filtration of the reaction solution, and recycled at least eight times without significant
loss of activity.
Experimental
General comments
All chemicals were reagent grade and used as purchased. All solvents were dried and
distilled before use. The MCMꢀ41ꢀN,NꢀPd(OAc)
2
catalyst was prepared according to
28
our previous procedure, the palladium content was determined to be 0.42 mmol/g.
1
5

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The products were purified by flash chromatography on silica gel. Mixture of EtOAc
and hexane was generally used as eluent. All carbonylative crossꢀcoupling products
were characterized by comparison of their spectra and physical data with authentic
1
samples. H NMR spectra were recorded on a Bruker Avance 400 MHz spectrometer
1
3
with TMS as an internal standard in CDCl
3
as solvent. C NMR spectra (100 MHz)
were recorded on a Bruker Avance 400 MHz spectrometer in CDCl
3
as solvent.
HRMS spectra were recorded on a QꢀTof spectrometer with micromass MS software
using electrospray ionization (ESI). Melting points are uncorrected. Palladium content
was determined with inductively coupled plasma atom emission Atomscan16 (ICPꢀ
AES, TJA Corporation).
General procedure for preparation of triorganoindium reagents
3
A 25 mL roundꢀbottomed flask containing a stirrer bar was charged with InCl (0.37
mmol) and dried under vacuum with a heat gun. The flask was cooled, a positive
argon pressure was established and anhydrous THF (2 mL) was added. The resulting
solution was cooled to –78 ºC and a solution of RLi or RMgBr (1.1 mmol, 1.0ꢀ2.5 M
in hexane, THF, or Et O) was slowly added (15ꢀ30 min). The reaction mixture was
2
stirred for 30 min, the cooling bath was removed, and the mixture was warmed to
room temperature over 30 min.
General procedure for the heterogeneous palladium-catalyzed carbonylative
cross-coupling of aryl halides with trialkylindiums
A solution of Me In or nꢀBu In (0.37 mmol, ca. 0.18 M in dry THF) was added to a
3
3
2
mixture of MCMꢀ41ꢀN,NꢀPd(OAc) (24 mg, 1 mol%) and aryl halide (1 mmol) in
1
6

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THF (2 mL) under argon atmosphere. The resulting mixture was bubbled with CO gas
for 5 min at room temperature to flush out argon, then a positive CO pressure was
established. The reaction mixture was warmed to 68 ºC over 30 min and stirred under
atmospheric pressure of CO gas for 1.5ꢀ6 h at 68 ºC. After being cooled to room
temperature, the mixture was diluted with Et
catalyst was washed with DMF (2 × 5 mL), Et
run. The filtrate was washed with sat. aq NaHCO
MgSO ), filtered, and concentrated under vacuum. The residue was purified by flash
2
O (20 mL) and filtered. The palladium
O (2 × 5 mL) and reused in the next
(5 mL), water (3 × 5 mL) and dried
2
3
(
4
column chromatography on silica gel (EtOAc:hexane = 1:25) to give the carbonyꢀ
lative crossꢀcoupling product.
31 1
4
'-Methylacetophenone 3a. Colorless oil. H NMR (400 MHz, CDCl ): δ = 7.85 (d,
3
13
J = 8.0 Hz, 2H), 7.25 (d, J = 8.0 Hz, 2H), 2.57 (s, 3H), 2.41 (s, 3H). C NMR (100
MHz, CDCl ): δ = 197.7, 143.8, 134.7, 129.2, 128.4, 26.4, 21.6.
'-Methoxyacetophenone 3b. White solid, m.p. 36–37 °C (ref. m.p. 36–38 °C). H
NMR (400 MHz, CDCl ): δ = 7.93 (d, J = 8.4 Hz, 2H), 6.93 (d, J = 8.8 Hz, 2H), 3.86
3
31
1
4
3
13
(
s, 3H), 2.55 (s, 3H). C NMR (100 MHz, CDCl ): δ = 196.7, 163.5, 130.6, 130.4,
3
1
13.7, 55.5, 26.3.
3
'-Fluoroacetophenone 3c. Colorless oil. H NMR (400 MHz, CDCl ): δ = 7.99
3
1 1
4
13
(
dd, J = 8.8, 5.6 Hz, 2H), 7.13 (t, J = 8.6 Hz, 2H), 2.59 (s, 3H). C NMR (100 MHz,
1
3
3
CDCl ): δ = 196.4, 165.7 (d, JCꢀF = 251.9 Hz), 133.6, 130.9 (d, JCꢀF = 9.3 Hz), 115.6
2
(
d, J = 21.8 Hz), 26.4.
CꢀF
3
1 1
4
3
'-Chloroacetophenone 3d. Colorless oil. H NMR (400 MHz, CDCl ): δ = 7.89 (d,
1
7

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1
3
J = 8.8 Hz, 2H), 7.43 (d, J = 8.4 Hz, 2H), 2.59 (s, 3H). C NMR (100 MHz, CDCl
3
):
δ = 196.6, 139.4, 135.3, 129.7, 128.8, 26.4.
32
1
Methyl 4-acetylbenzoate 3e. White solid, m.p. 87–89 °C (ref. m.p. 89–91 °C). H
13
NMR (400 MHz, DMSOꢀd ): δ = 8.07 (s, 4H), 3.90 (s, 3H), 2.64 (s, 3H). C NMR
6
(
100 MHz, DMSOꢀd
'-Methylacetophenone 3f. Colorless oil. H NMR (400 MHz, CDCl
J = 8.4 Hz, 1H), 7.36 (t, J = 7.6 Hz, 1H), 7.27ꢀ7.21 (m, 2H), 2.56 (s, 3H), 2.52 (s, 3H).
6
): δ = 198.1, 166.0, 140.6, 133.7, 129.9, 128.9, 52.9, 27.4.
3
1 1
2
3
): δ = 7.68 (d,
1
3
C NMR (100 MHz, CDCl
3
): δ = 201.7, 138.4, 137.7, 132.0, 131.5, 129.3, 125.7,
2
9.5, 21.5.
31 1
1
-Acetylnaphthalene 3g. Colorless oil. H NMR (400 MHz, CDCl
3
): δ = 8.74 (d, J
=
8.4 Hz, 1H), 7.97 (d, J = 8.0 Hz, 1H), 7.91 (d, J = 7.2 Hz, 1H), 7.85 (d, J = 8.0 Hz,
1
3
1
H), 7.61ꢀ7.58 (m, 1H), 7.57ꢀ7.45 (m, 2H), 2.72 (s, 3H). C NMR (100 MHz, CDCl
3
):
δ = 201.8, 135.5, 134.0, 133.0, 130.2, 128.7, 128.5, 128.1, 126.5, 126.1, 124.4, 30.0.
3
1 1
2
-Acetylthiophene 3h. Colorless oil. H NMR (400 MHz, CDCl ): δ = 7.70 (d, J =
3
13
4
.0 Hz, 1H), 7.64 (d, J = 5.2 Hz, 1H), 7.13 (t, J = 4.4 Hz, 1H), 2.57 (s, 3H). C NMR
(100 MHz, CDCl
3
): δ = 190.7, 144.5, 133.8, 132.5, 128.1, 26.8.
1
1
-(m-Tolyl)pentan-1-one 3i. Pale yellow oil. H NMR (400 MHz, CDCl
3
): δ =
7
.78ꢀ7.73 (m, 2H), 7.37ꢀ7.31 (m, 2H), 2.95 (t, J = 7.4 Hz, 2H), 2.41 (s, 3H), 1.76ꢀ1.66
1
3
(
m, 2H), 1.46ꢀ1.35 (m, 2H), 0.95 (t, J = 7.4 Hz, 3H). C NMR (100 MHz, CDCl ): δ
3
=
200.9, 138.3, 137.2, 133.6, 128.6, 128.4, 125.3, 38.4, 26.6, 22.5, 21.4, 13.9. HRMS
+
+
calcd for C12H16O [M ]: 176.1201, found 176.1206.
20a 1
1
-(4-Methoxyphenyl)pentan-1-one 3j. Pale yellow oil.
H NMR (400 MHz,
1
8

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CDCl
7.4 Hz, 2H), 1.75ꢀ1.67 (m, 2H), 1.45ꢀ1.36 (m, 2H), 0.95 (t, J = 7.2 Hz, 3H). C
NMR (100 MHz, CDCl ): δ = 199.3, 163.3, 130.3, 130.2, 113.7, 55.4, 38.0, 26.8, 22.5,
3
): δ = 7.94 (d, J = 8.4 Hz, 2H), 6.93 (d, J = 8.8 Hz, 2H), 3.87 (s, 3H), 2.91 (t, J
13
=
3
1
3.9.
-(4-Chlorophenyl)pentan-1-one 3k. Pale yellow oil.
20a 1
1
3
H NMR (400 MHz, CDCl ):
δ = 7.89 (d, J = 8.4 Hz, 2H), 7.42 (d, J = 8.4 Hz, 2H), 2.93 (t, J = 7.4 Hz, 2H),
1
3
1
.74ꢀ1.66 (m, 2H), 1.45ꢀ1.35 (m, 2H), 0.95 (t, J = 7.4 Hz, 3H). C NMR (100 MHz,
CDCl ): δ = 199.2, 139.3, 135.4, 129.5, 128.8, 38.3, 26.4, 22.4, 13.9.
-(4-Acetylphenyl)pentan-1-one 3l. Pale yellow oil.
δ = 7.96 (s, 4H), 2.93 (t, J = 7.4 Hz, 2H), 2.58 (s, 3H), 1.71ꢀ1.62 (m, 2H), 1.40ꢀ1.30
3
2
0a 1
1
H NMR (400 MHz, CDCl3):
13
(
3
m, 2H), 0.89 (t, J = 7.2 Hz, 3H). C NMR (100 MHz, CDCl ): δ = 200.1, 197.6,
1
40.2, 140.0, 128.5, 128.3, 38.8, 26.9, 26.3, 22.4, 14.0.
1
1
3
-(4-Cyanophenyl)pentan-1-one 3m. Pale yellow oil. H NMR (400 MHz, CDCl ):
δ = 7.97 (d, J = 8.4 Hz, 2H), 7.70 (d, J = 8.0 Hz, 2H), 2.92 (t, J = 7.4 Hz, 2H),
1
3
1
.70ꢀ1.61 (m, 2H), 1.38ꢀ1.30 (m, 2H), 0.89 (t, J = 7.2 Hz, 3H). C NMR (100 MHz,
CDCl ): δ = 199.1, 140.0, 132.5, 128.5, 118.0, 116.2, 38.7, 26.1, 22.4, 13.9. HRMS
calcd for C12
-(Naphthalen-1-yl)pentan-1-one 3n. Pale yellow oil. H NMR (400 MHz, CDCl
δ = 8.54 (d, J = 8.0 Hz, 1H), 7.94 (d, J = 8.0 Hz, 1H), 7.86ꢀ7.80 (m, 2H), 7.58ꢀ7.44 (m,
H), 3.03 (t, J = 7.4 Hz, 2H), 1.79ꢀ1.71 (m, 2H), 1.46ꢀ1.38 (m, 2H), 0.95 (t, J = 7.4
3
+
+
H
13NO [M ]: 187.0997, found 187.0995.
1
1
3
):
3
1
3
Hz, 3H). C NMR (100 MHz, CDCl
3
): δ = 205.1, 136.5, 134.0, 132.3, 130.2, 128.4,
+
1
16
27.8, 127.1, 126.4, 125.8, 124.4, 42.1, 26.9, 22.5, 14.0. HRMS calcd for C15H O
1
9

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+
[
M ]: 212.1201, found 212.1207.
1
1
-(Thiophen-2-yl)pentan-1-one 3o. Pale yellow oil. H NMR (400 MHz, CDCl
3
): δ
=
7.73ꢀ7.69 (m, 1H), 7.62 (t, J = 4.8 Hz, 1H), 7.16ꢀ7.10 (m, 1H), 2.89 (t, J = 7.4 Hz,
1
3
2
H), 1.79ꢀ1.70 (m, 2H), 1.47ꢀ1.36 (m, 2H), 0.96 (t, J = 6.4 Hz, 3H). C NMR (100
MHz, CDCl ): δ = 193.5, 144.5, 133.3, 131.6, 128.0, 39.2, 26.9, 22.5, 13.9. HRMS
calcd for C
3
+
+
9
H12OS [M ]: 168.0609, found 168.0612.
20a 1
2
-Methyl-1-phenylbutan-1-one 3p. Colorless oil.
H NMR (400 MHz, CDCl
3
): δ
=
7.95 (dd, J = 8.4, 1.2 Hz, 2H), 7.54ꢀ7.48 (m, 1H), 7.45ꢀ7.40 (m, 2H), 3.42ꢀ3.36 (m,
1
7
2
H), 1.87ꢀ1.79 (m, 1H), 1.52ꢀ1.44 (m, 1H), 1.18 (dd, J = 6.8, 1.2 Hz, 3H), 0.90 (t, J =
13
.6 Hz, 3H). C NMR (100 MHz, CDCl
3
): δ = 204.2, 136.8, 132.7, 128.5, 128.2, 42.0,
6.6, 16.7, 11.7.
General procedure for the heterogeneous palladium-catalyzed carbonylative
cross-coupling of aryl halides with triphenylindium or trialkynylindiums
In a Schlenk tube, a solution of Ph In or (RC≡C) In (0.37 mmol, ca. 0.18 M in dry
3
3
2
THF) was added to a mixture of MCMꢀ41ꢀN,NꢀPd(OAc) (24 mg, 1 mol%) and aryl
halide (1 mmol) in THF (2 mL). The tube was charged with CO (2.5 atm) and the
resulting mixture was warmed to 68 ºC over 30 min and stirred for 1.5ꢀ6 h at 68 ºC.
After being cooled to room temperature, the pressure was released and the mixture
was diluted with Et O (20 mL) and filtered. The palladium catalyst was washed with
2
DMF (2 × 5 mL), Et
with sat. aq NaHCO
concentrated under vacuum. The residue was purified by flash column chromatoꢀ
2
O (2 × 5 mL) and reused in the next run. The filtrate was washed
3
(5 mL), water (3 × 5 mL) and dried (MgSO ), filtered, and
4
2
0

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graphy on silica gel (EtOAc:hexane = 1:25) to give the carbonylative crossꢀcoupling
product.
18
1
Benzophenone 3q. White solid, m.p. 46–47 °C (ref. m.p. 47–48 °C). H NMR (400
MHz, CDCl ): δ = 7.81 (d, J = 7.2 Hz, 4H), 7.59 (t, J = 7.6 Hz, 2H), 7.49 (t, J = 7.6
Hz, 4H). C NMR (100 MHz, CDCl ): δ = 196.8, 137.6, 132.4, 130.1, 128.3.
3
1
3
3
18
1
4
-Methoxybenzophenone 3r. White solid, m.p. 60–61 °C (ref. m.p. 59–60 °C). H
3
NMR (400 MHz, CDCl ): δ = 7.85ꢀ7.82 (m, 2H), 7.77ꢀ7.74 (m, 2H), 7.58ꢀ7.54 (m,
13
1
H), 7.47 (t, J = 7.6 Hz, 2H), 6.96 (dd, J = 8.8, 2.0 Hz, 2H), 3.88 (s, 3H). C NMR
(
100 MHz, CDCl ): δ = 195.6, 163.2, 138.3, 132.6, 131.9, 130.1, 129.8, 128.2, 113.6,
3
5
5.5.
1
8
Methyl 4-benzoylbenzoate 3s. White solid, m.p. 107–108 °C (ref. m.p. 108–
1
1
6
3
1
3
5
7
09 °C). H NMR (400 MHz, CDCl
3
): δ = 8.15 (dd, J = 6.6, 1.8 Hz, 2H), 7.84 (dd, J =
.8, 2.0 Hz, 2H), 7.81 (d, J = 8.0 Hz, 2H), 7.65ꢀ7.60 (m, 1H), 7.50 (t, J = 7.6 Hz, 2H),
1
3
.97 (s, 3H). C NMR (100 MHz, CDCl
3
): δ = 196.0, 166.3, 141.3, 137.0, 133.2,
33.0, 130.1, 129.8, 129.5, 128.5, 52.5.
18
-(Trifluoromethyl)benzophenone 3t. White solid, m.p. 48–49 °C (ref. m.p.
1
0–51 °C). H NMR (400 MHz, CDCl
3
): δ = 8.07 (s, 1H), 7.98 (d, J = 7.6 Hz, 1H),
.85 (d, J = 7.6 Hz, 1H), 7.81ꢀ7.77 (m, 2H), 7.69ꢀ7.60 (m, 2H), 7.52 (t, J = 7.6 Hz,
13
2
3
H). C NMR (100 MHz, CDCl ): δ = 195.1, 138.3, 136.8, 133.1, 133.0, 131.0 (q,
2
3
3
J
CꢀF = 36.4 Hz), 130.0, 128.9, 128.8 (q, JCꢀF = 3.6 Hz), 128.6, 126.7 (q, JCꢀF = 3.8
1
Hz), 123.5 (q, J = 272.0 Hz).
CꢀF
1
8 1
2
3
-Methylbenzophenone 3u. Colorless oil. H NMR (400 MHz, CDCl ): δ = 7.80 (d,
2
1

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J = 7.6 Hz, 2H), 7.57 (d, J = 7.6 Hz, 1H), 7.45 (t, J = 7.6 Hz, 2H), 7.39 (t, J = 7.6 Hz,
1
3
1
1
1
H), 7.33ꢀ7.24 (m, 3H), 2.33 (s, 3H). C NMR (100 MHz, CDCl
3
): δ = 198.1, 138.2,
37.3, 136.2, 132.6, 130.5, 129.7, 129.6, 128.0, 127.9, 124.7, 19.5.
18 1
-Benzoylnaphthalene 3v. Colorless oil. H NMR (400 MHz, CDCl ): δ = 8.09 (d,
3
13
J = 7.6 Hz, 1H), 7.95 (d, J = 8.4 Hz, 1H), 7.89–7.83 (m, 3H), 7.56–7.37 (m, 7H). C
NMR (100 MHz, CDCl ): δ = 198.0, 138.4, 136.5, 133.8, 133.3, 131.3, 131.1, 130.5,
28.5, 128.4, 127.8, 127.3, 126.5, 125.8, 124.4.
-Benzoylthiophene 3w. White solid, m.p. 52–53 °C (ref. m.p. 54–55 °C). H NMR
3
1
18
1
2
(
400 MHz, CDCl ): δ = 7.88ꢀ7.85 (m, 2H), 7.74–7.71 (m, 1H), 7.66–7.64 (m, 1H),
3
13
7
.60 (t, J = 7.4 Hz, 1H), 7.50 (t, J = 7.6 Hz, 2H), 7.18–7.15 (m, 1H). C NMR (100
MHz, CDCl
-Benzoylpyridine 3x. White solid, m.p. 40–41 °C (ref. m.p. 39–41 °C). H NMR
400 MHz, CDCl ): δ = 9.02 (s, 1H), 8.83 (s, 1H), 8.13 (d, J = 8.0 Hz, 1H), 7.81 (d, J
7.6 Hz, 2H), 7.64 (t, J = 7.4 Hz, 1H), 7.51 (t, J = 7.6 Hz, 2H), 7.48ꢀ7.44 (m, 1H).
3
): δ = 188.2, 143.7, 138.2, 134.8, 134.2, 132.3, 129.2, 128.4, 128.0.
18
1
3
(
3
=
1
3
C NMR (100 MHz, CDCl
3
): δ = 194.7, 152.5, 150.7, 137.3, 136.7, 133.2, 130.0,
1
28.6, 127.6, 123.5.
33
1
-(4-Methylphenyl)-3-phenylpropynone 3y. White solid, m.p. 105–106 °C (ref.
1
m.p. 106–107 °C). H NMR (400 MHz, CDCl
3
): δ = 8.12 (d, J = 8.0 Hz, 2H), 7.68 (d,
J = 6.8 Hz, 2H), 7.48 (t, J = 6.8 Hz, 1H), 7.42 (t, J = 7.2 Hz, 2H), 7.31 (d, J = 8.0 Hz,
1
3
2
1
1
H), 2.45 (s, 3H). C NMR (100 MHz, CDCl
3
): δ = 177.7, 145.2, 134.7, 133.0, 130.7,
29.7, 129.4, 128.7, 120.3, 92.6, 87.0, 21.8.
33
-(4-Chlorophenyl)-3-phenylpropynone 3z. White solid, m.p. 85–86 °C (ref. m.p.
2
2

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1
8
2
1
1
8
3
6–87 °C). H NMR (400 MHz, CDCl ) δ (ppm): 8.16ꢀ8.13 (m, 2H), 7.69ꢀ7.66 (m,
1
3
H), 7.52ꢀ7.40 (m, 5H). C NMR (100 MHz, CDCl
3
) δ (ppm): 176.7, 140.7, 135.4,
33.1, 131.0, 130.9, 129.0, 128.8, 119.9, 93.7, 86.6.
3
3 1
-Phenylhept-2-yn-1-one 3a'. Pale yellow oil. H NMR (400 MHz, CDCl ): δ =
3
.14 (d, J = 7.2 Hz, 2H), 7.59 (t, J = 7.2 Hz, 1H), 7.47 (t, J = 7.6 Hz, 2H), 2.52ꢀ2.47
13
(
m, 2H), 1.69ꢀ1.61 (m, 2H), 1.54ꢀ1.46 (m, 2H), 0.98ꢀ0.94 (m, 3H). C NMR (100
MHz, CDCl ): δ = 178.2, 136.9, 133.9, 129.5, 128.5, 96.8, 79.7, 29.8, 22.1, 18.9,
3
1
3.5.
-(4-Methylphenyl)hept-2-yn-1-one 3b'. Pale yellow oil.
): δ = 8.03 (d, J = 8.0 Hz, 2H), 7.26 (d, J = 7.6 Hz, 2H), 2.49 (t, J = 7.2 Hz, 2H),
33 1
1
H NMR (400 MHz,
CDCl
.42 (s, 3H), 1.68ꢀ1.61 (m, 2H), 1.54ꢀ1.46 (m, 2H), 0.96 (t, J = 7.4 Hz, 3H). C NMR
100 MHz, CDCl ): δ = 177.9, 144.9, 134.6, 129.6, 129.2, 96.3, 79.7, 29.9, 22.1, 21.7,
3
13
2
(
3
1
8.9, 13.5.
-(4-Methoxyphenyl)hept-2-yn-1-one 3c'. Pale yellow oil. H NMR (400 MHz,
): δ = 8.10 (dd, J = 7.2, 1.8 Hz, 2H), 6.95 (d, J = 8.8 Hz, 2H), 3.88 (s, 3H), 2.49
33 1
1
CDCl
t, J = 7.2 Hz, 2H), 1.69ꢀ1.62 (m, 2H), 1.54ꢀ1.46 (m, 2H), 0.96 (t, J = 7.2 Hz, 3H). C
NMR (100 MHz, CDCl ): δ = 176.9, 164.3, 131.9, 130.4, 113.7, 95.9, 79.7, 55.5, 29.9,
3
1
3
(
3
2
2.1, 18.9, 13.5.
-Acetylbenzophenone 3d'. White solid, m.p. 82–83 °C (ref. m.p. 83–84 °C). H
): δ = 8.06 (dd, J = 6.6, 1.8 Hz, 2H), 7.87 (dd, J = 6.6, 1.8 Hz,
H), 7.81 (d, J = 7.6 Hz, 2H), 7.65ꢀ7.61 (m, 1H), 7.51 (t, J = 7.6 Hz, 2H), 2.68 (s, 3H).
18
1
4
NMR (400 MHz, CDCl
3
2
1
3
3
C NMR (100 MHz, CDCl ): δ = 197.5, 196.0, 141.4, 139.6, 136.9, 133.0, 130.1,
2
3

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1
30.0, 128.5, 128.2, 26.9.
-Cyanobenzophenone 3e'. White solid, m.p. 109–111 °C (ref. m.p. 110– 112 °C).
18
4
1
3
H NMR (400 MHz, CDCl ): δ = 7.88 (d, J = 8.8 Hz, 2H), 7.81ꢀ7.77 (m, 4H), 7.65 (t,
13
J = 7.6 Hz, 1H), 7.52 (t, J = 7.6 Hz, 2H). C NMR (100 MHz, CDCl ): δ = 194.5,
3
1
40.7, 135.9, 132.8, 131.7, 129.7, 129.5, 128.1, 117.5, 115.2.
General procedure for the heterogeneous palladium-catalyzed double car-
bonylative cross-coupling of 1,4-diiodobenzene with n-Bu In or (4-FC In
3
6 4 3
H )
3 6 4 3
In a Schlenk tube, a solution of nꢀBu In or (4ꢀFC H ) In (1.1 mmol, ca. 0.18 M in dry
THF) was added to a mixture of MCMꢀ41ꢀN,NꢀPd(OAc) (48 mg, 2 mol%) and
2
1
,4ꢀdiiodobenzene (1 mmol) in THF (1 mL). The tube was charged with CO (1 or 2.5
atm) and the resulting mixture was warmed to 68 ºC over 30 min and stirred for 3 h at
8 ºC. After being cooled to room temperature, the mixture was diluted with Et O (20
mL) and filtered. The palladium catalyst was washed with DMF (2 × 5 mL), Et O (2 ×
mL) and reused in the next run. The filtrate was washed with sat. aq NaHCO (5
6
2
2
5
3
4
mL), water (3 × 5 mL) and dried (MgSO ), filtered, and concentrated under vacuum.
The residue was purified by flash column chromatography on silica gel (EtOAc:
hexane = 1:25) to give the expected product.
20a 1
1
,1'-(1,4-Phenylene)dipentan-1-one 4a. Pale yellow oil.
H NMR (400 MHz,
CDCl
3
): δ = 8.02 (s, 4H), 2.99 (t, J = 7.4 Hz, 4H), 1.76ꢀ1.68 (m, 4H), 1.46ꢀ1.37 (m,
1
3
4
3
H), 0.96 (t, J = 7.4 Hz, 6H). C NMR (100 MHz, CDCl ): δ = 200.0, 140.1, 128.2,
3
8.7, 26.3, 22.4, 13.9.
2
4

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3
4
1
2
4
(
,4-Bis(4-fluorobenzoyl)benzene 4b. White solid, m.p. 207ꢀ209 °C (ref. m.p.
1
09–210 °C). H NMR (400 MHz, CDCl
3
): δ = 7.91ꢀ7.86 (m, 8H), 7.20 (t, J = 8.6 Hz,
13
1
H). C NMR (100 MHz, CDCl
3
): δ = 194.4, 165.7 ( JCꢀF = 255.6 Hz), 140.7, 133.2
4
3
2
JCꢀF = 3.0 Hz), 132.8 ( J = 10.1 Hz), 129.6, 115.7 ( J = 22.1 Hz).
CꢀF
CꢀF
The experimental procedure for the hot filtration test
A 25 mL roundꢀbottomed flask equipped with a gas inlet tube, a reflux condenser, and
a magnetic stirring bar was charged with MCMꢀ41ꢀN,NꢀPd(OAc) (24 mg, 1 mol%)
2
and 4ꢀiodotoluene (1.0 mmol) under Ar. The flask was flushed with carbon monoxide
for 5 min and a positive CO pressure was established. THF (2 mL) and a solution of
Me In (0.37 mmol, ca. 0.18 M in dry THF) were then added via syringe. After being
3
stirred at 68 °C for 0.5 h under CO (1 atm), the reaction mixture was filtered at 68 °C
to remove the supported palladium catalyst and the filtrate was transferred to another
2
5 mL roundꢀbottomed flask under Ar. The hot filtration solution was bubbled with
CO gas at room temperature for 5 min to flush out argon and then stirred at 68 °C
under CO (1 atm) for 3 h. After being cooled to room temperature, the mixture was
diluted with Et
2
O (20 mL). The ether solution was washed with sat. aq NaHCO
3
(5
mL), water (3 × 5 mL) and dried (MgSO
4
), filtered, and concentrated under vacuum.
The residue was purified by flash column chromatography on silica gel (EtOAc:
hexane = 1:25) to give the desired 3a (52.3 mg, 39%).
The experimental procedure for the recycle of the catalyst
2
5

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A solution of Me
3
In (0.37 mmol, ca. 0.18 M in dry THF) was added to a mixture of
(24 mg, 1 mol%) and 4ꢀiodoanisole (1 mmol) in THF (2 mL)
MCMꢀ41ꢀN,NꢀPd(OAc)
2
under Ar. The resulting mixture was bubbled with CO gas for 5 min at room temꢀ
perature to flush out argon and then stirred at 68 ºC under CO (1 atm) for 2.5 h. After
being cooled to room temperature, the mixture was diluted with Et
filtered. The palladium catalyst was washed with DMF (2 × 5 mL), Et
and airꢀdried. The filtrate was washed with sat. aq NaHCO (5 mL), water (3 × 5 mL)
and dried (MgSO ), filtered, and concentrated under vacuum. The residue was
2
O (20 mL) and
2
O (2 × 5 mL)
3
4
purified by flash column chromatography on silica gel (EtOAc:hexane = 1:25) to give
the desired 3b in 87% yield. The recovered palladium catalyst was subjected to a
second run of the reaction by using the same substrates (4ꢀiodoanisole and Me
under the same conditions and the procedure was repeated up to seven times.
3
In)
Acknowledgements
We thank the National Natural Science Foundation of China (No. 21462021) and Key
Laboratory of Functional Small Organic Molecule, Ministry of Education (No.
KLFSꢀKFꢀ201409) for financial support.
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