Rhodium-catalyzed reductive carbonylation of aryl iodides to arylaldehydes with syngas

Article abstract of DOI:10.3762/bjoc.16.61

The reductive carbonylation of aryl iodides to aryl aldehydes possesses broad application prospects. We present an efficient and facile Rh-based catalytic system composed of the commercially available Rh salt RhCl₃·3H₂O, PPh₃ as phosphine ligand, and Et₃N as the base, for the synthesis of arylaldehydes via the reductive carbonylation of aryl iodides with CO and H₂ under relatively mild conditions with a broad substrate range affording the products in good to excellent yields. Systematic investigations were carried out to study the experimental parameters. We explored the optimal ratio of Rh salt and PPh₃ ligand, substrate scope, carbonyl source and hydrogen source, and the reaction mechanism. Particularly, a scaled-up experiment indicated that the catalytic method could find valuable applications in industrial productions. The low gas pressure, cheap ligand and low metal dosage could significantly improve the practicability in both chemical researches and industrial applications.

Full text of DOI:10.3762/bjoc.16.61

Rhodium-catalyzed reductive carbonylation of aryl iodides
to arylaldehydes with syngas
Zhenghui Liu*1, Peng Wang2,3, Zhenzhong Yan1, Suqing Chen1, Dongkun Yu4,
Xinhui Zhao4 and Tiancheng Mu*4
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2020, 16, 645–656.
1School of Pharmaceutical and Materials Engineering, Taizhou
University, Taizhou 318000, Zhejiang, China, 2Beijing National
Laboratory for Molecular Sciences, CAS Research/Education Center
for Excellence in Molecular Sciences, Institute of Chemistry, Chinese
Academy of Sciences, Beijing 100190, China, 3Key Laboratory of
Green Chemical Media and Reactions, Ministry of Education, School
of Chemistry and Chemical Engineering, Henan Normal University,
Xinxiang 453007, Henan, China, and 4Department of Chemistry,
Renmin University of China, Beijing 100872, China
doi:10.3762/bjoc.16.61
Received: 29 January 2020
Accepted: 28 March 2020
Published: 08 April 2020
Associate Editor: K. Grela
© 2020 Liu et al.; licensee Beilstein-Institut.
License and terms: see end of document.
Email:
Zhenghui Liu* - liuzhenghui@iccas.ac.cn; Tiancheng Mu* -
tcmu@ruc.edu.cn
* Corresponding author
Keywords:
cost-effective ligand; industrial catalysis; reductive carbonylation;
rhodium catalyst; syngas
Abstract
The reductive carbonylation of aryl iodides to aryl aldehydes possesses broad application prospects. We present an efficient and
facile Rh-based catalytic system composed of the commercially available Rh salt RhCl3·3H2O, PPh3 as phosphine ligand, and Et3N
as the base, for the synthesis of arylaldehydes via the reductive carbonylation of aryl iodides with CO and H2 under relatively mild
conditions with a broad substrate range affording the products in good to excellent yields. Systematic investigations were carried
out to study the experimental parameters. We explored the optimal ratio of Rh salt and PPh3 ligand, substrate scope, carbonyl
source and hydrogen source, and the reaction mechanism. Particularly, a scaled-up experiment indicated that the catalytic method
could find valuable applications in industrial productions. The low gas pressure, cheap ligand and low metal dosage could signifi-
cantly improve the practicability in both chemical researches and industrial applications.
Introduction
The exploration of environmentally friendly and highly effec- goals. Carbonylation processes are important transformations in
tive synthetic methods has been a significant goal of research the refinement and reprocessing of readily available industrial
[1-5]. In this aspect, effective catalytic systems and organome- raw materials into more functionalized products. These pro-
tallic chemistry are suitable technologies to accomplish these cesses generally utilize carbon monoxide (CO), currently the
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most important C1 building block used in numerous industrial K2CO3 [33], MCM-41-S-PdCl2 [34], and MCM-41-2P-PdCl2
carbonylation processes [6-8] and widely applied in industrial [35]. However, the aforementioned systems often suffer from
productions [9-12]. Carbonylations are one of the industrial high toxicity of solvents, high pressure of gases or high reac-
core technologies for transforming various bulk chemicals into tion temperatures, which make these protocols inapplicable for
useful products that are used in our daily life. Carbonylation large scale applications. Actually, in 2004, Eliseev et al. re-
reactions, together with polymerizations and oxidations, consti- ported a catalytic system based on RhCl(CO)(PPh3)2 to achieve
tute the largest industrial applications in the field of homoge- the conversion of iodobenzene to benzaldehyde in toluene using
neous catalysis, and substantial value-added bulk and fine CO and H2 [36]. We sought for a commercially available Rh
chemicals are available through this technology [13]. In spite of salt for this conversion at lower cost and higher potential for
the existing plentiful progress in this conversion, the exploita- practical application.
tion of advanced and more effective catalytic systems to the ac-
tivity and to widen the range of substrates is crucial for new In this work, we established a catalytic system composed of
practical applications.
RhCl3·3H2O and PPh3, which allows the reductive carbonyla-
tion of aryl iodides using CO and H2 in the presence of Et3N as
Syngas is a mixture of CO and H2, which is cheap, abundant the base at 90 °C. In addition, the reported catalytic system
and widely used in chemical industry productions [14-16]. In demonstrates high catalytic activity affording the arylaldehydes
spite of its comprehensive utilization in industry, reactions in- in good to excellent yields, displays high functional-group toler-
volving CO are relatively seldom employed in fine chemicals ance, and broad substrate scope. In particular, the catalytic
syntheses. This could be due to the general difficulty of using system could be applied in a scaled-up experiment and thus has
gases as raw materials and the requirement of high-pressure potential for applications in industrial productions. The reac-
equipment. In addition, relatively little attention has been paid tion mechanism study revealed that RhCl3·3H2O reacts with
to carbonylation chemistry using CO in academic research. PPh3 to form RhCl(PPh3)3, which is able to activate C–I bonds
Also, H2 as representative clean energy source is far more envi- in aryl iodides realizing the insertion of CO and hydrogenolysis
ronmentally friendly than other frequently used hydrogen with H2. The final trapping of HI by the base Et3N regenerates
sources like hydrosilanes [17], tributyltin hydride (Bu3SnH) the catalyst to complete the reaction cycle. As far as we know,
(often used in natural product syntheses) [18-20] and hydrobo- this is the first time that commercially available Rh salts with
ranes [21-23], since the only byproduct is water. The produc- PPh3 as the ligand were utilized to complete the conversion of
tion, storage and use of H2 received much attention and plen- aryl iodides into arylaldehydes using CO and H2 with system-
tiful achievements promoted the application of H2 into more atic researches. Considering the efficiency and generality, this
and more chemistry researches and industrial productions [24- catalytic system is expected to powerfully influence both labo-
27].
ratory research and chemical industry by offering a practical
synthetic tool for the conversion of aryl iodides to arylalde-
Aromatic aldehydes are highly valuable organic compounds hydes.
that are widely employed as indispensable building blocks in
Results and Discussion
numerous areas of chemistry, especially for the preparation
of biologically active molecules or their intermediates Effects of Rh species
[28,29]. Generally, aromatic aldehydes are synthesized by Rhodium salts coordinated with proper ligands have been re-
Reimer–Tiemann, Gattermann–Koch, Vielsmeier–Haag, or ported to be able to realize the activation of CO and H2 and thus
Duff reactions and so forth. Unfortunately, these reactions might achieve the reductive carbonylation of aryl iodides to
usually use auxiliary reagents and thus generate large amounts afford aromatic aldehydes [37-40]. Rh salts generally play vital
of industrial waste and other side products. Particularly, the re- roles in the catalytic results. Therefore, we tested 20 different
ductive carbonylation of aryl iodides to produce arylaldehydes Rh salts and the results are summarized in Table 1. The initial
with CO and H2 was seldom reported. Some homogeneous and reaction conditions were set as PhI (1 mmol), Rh species
heterogeneous catalytic systems based on palladium species (2.5 mol %), PPh3 (10 mol %), Et3N (1.2 mmol), DMA (2 mL),
using CO and H2 to complete the reductive carbonylation of CO/H2 (5 bar:5 bar), 90 °C and 12 h. As can be seen from
aryl halogens to arylaldehydes have been developed. The homo- Table 1, most of the Rh salts gave unsatisfactory results with
geneous systems included Pd(OAc)2 with propyl di-tert- yields of benzaldehyde below 50%. However, three Rh salts
butylphosphinite ligand [30], Pd(acac)2 with dppm ligand [31], provided yields over 50%, namely [RhCl(CO)2]2 (64%),
Pd(OAc)2 with CataCXium A ligand [32], and all of the three RhCl3·3H2O (97%) and RhI3 (89%) (Table 1, entries 1, 18 and
systems employed TMEDA as the base and toluene as the sol- 20). Interestingly, RhCl3·3H2O and RhI3 performed well,
vent. The heterogeneous systems contained: PdO/Co3O4 with whereas RhCl3 and RhBr2·2H2O afforded the product in very
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Table 1: Rhodium-catalyzed reductive carbonylation of iodobenzene with CO and H2 to afford benzaldehyde: effects of the Rh speciesa.
Entry
Rh species
Conversion [%]b
Yield [%]b
1
2
3
4
5
6
7
8
[RhCl(CO)2]2
89
37
21
16
15
27
21
23
71
43
29
48
42
25
51
38
22
100
31
92
64
31
15
14
12
21
18
19
33
12
22
42
36
10
46
21
18
97
28
89
RhCl(CO)(PPh3)2
Rh(acac)(CO)2
[RhCl(COD)]2
Rh(MeCN)2(COD)BF4
Rh(COD)BF4
Rh(COD)2OTf
[Rh(OMe)(COD)]2
Rh(OAc)2
[Rh(CF3COO)]2
[Rh(CH3(CH2)6CO2)2]2
Rh(ethylene)2(acac)
[Rh(ethylene)2Cl]2
Rh(norbornadiene)2BF4
[Cp*RhCl2]2
9
10
11
12
13
14
15
16
17
18
19
20
Rh/C
RhCl3
RhCl3·3H2O
RhBr2·2H2O
RhI3
aStandard conditions: PhI (1 mmol), Rh species (2.5 mol %), PPh3 (10 mol %), Et3N (1.2 mmol), DMA (2 mL), CO/H2 (5 bar:5 bar), 90 °C, 12 h.
bDetermined by GC using dodecane as an internal standard.
low yield (Table 1, entries 17–20). This strongly implied that obtain the optimized conditions, 13 kinds of ligands were tested
not only the valence state of Rh and the species of anions were and their structures are included in Table 2. In accordance with
crucial for the conversion (even if all with halogen anions), but the expectations, only PPh3 was effective and afforded
also structural differences (e.g., crystal water, RhCl3 vs benzaldehyde in 97% yield, whereas the majority of the other
RhCl3·3H2O) of analogous Rh salts played an important role in ligands did not afford any product (Table 2). Therefore, PPh3
the catalytic synthesis of benzaldehyde. Among all tested was selected as the proper ligand employed in the subsequent
rhodium salts, RhCl3·3H2O afforded benzaldehyde in the reactions.
highest yield and was chosen as the most suitable Rh salt for the
conversion. In addition, in spite of low yields, Rh species with
valence states of 0, +1, +2 or +3 all promoted the reaction at
least to some extent. It is worth noting that as a good leaving
group, I− tends to leave in an alkaline environment, and dehalo-
genation and direct coupling products (namely, benzene and
biphenyl) were detected as the main byproducts by GC–MS.
This observation also explains why the conversions were
always higher than the yields.
Effects of bases
As explored in the mechanism study, the acid HI is produced
during the reaction process, since H+ and I− were generated
from the reaction system. In order to make the reaction proceed
continuously, HI produced needs to be removed effectively and
in time. Five different bases were examined to assess their
ability to bind HI. All of them were found suitable for the reac-
tion and provided benzaldehyde with yields higher than 70%,
except for TMEDA (53%, Figure 1a). The best results were ob-
tained with Et3N, which was selected as the most appropriate
Effects of ligands
Ligands play a decisive role in adjusting the catalytic ability of base.
metal cations [12,13,41-51]. Different ligands coordinating with
the same metal cations could make a difference between full The optimized base concentration was explored next and the
conversion with nearly quantitative yields and no reactions. To results are shown in Figure 1b. Since the base held the post of
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Table 2: Rhodium-catalyzed reductive carbonylation of iodobenzene with CO and H2 to afford benzaldehyde: effects of the ligandsa.
Entry
Ligand
Conversion [%]b
Yield [%]b
1
2
3
4
5
6
7
8
PP3
8
5
12
7
6
11
16
13
8
9
3
0
0
0
3
0
0
0
0
2
4
0
0
97
triphos
dpp-BINAP
dpp-OPh
dppb
dppe
P(PhF5)3
P(4-FPh)3
Cydpp
Bipy
DBU
Im
9
10
11
12
13
2
100
PPh3
aStandard conditions: PhI (1 mmol), RhCl3·3H2O (2.5 mol %), ligand (10 mol %), Et3N (1.2 mmol), DMA (2 mL), CO/H2 (5 bar:5 bar), 90 °C, 12 h.
bDetermined by GC using dodecane as an internal standard.
absorber for acids produced during the reaction, sufficient respectively. However, a slight excess of Et3N (1.2 mmol)
amounts are necessary to ensure high yields. As shown in allowed the reaction to be completed with a product yield of
Figure 1b, amounts of Et3N less than 1 mmol led to lower 97%. In addition, further increasing the amount of the base was
yields of 33% for 0.5 mmol Et3N and 61% for 0.8 mmol Et3N, not beneficial for the yield of benzaldehyde (1.5 mmol Et3N,
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Figure 1: Rhodium-catalyzed reductive carbonylation of iodobenzene with CO and H2 to afford benzaldehyde. a) Effects of the tested bases;
b) effects of base amount; c) effects of tested solvents; d) temperature screen; e) yields at different times for reactions performed at 80, 90 and
100 °C (every point represents an average result of three parallel experiments). Conversions and yields were determined by GC using dodecane as
an internal standard. Standard conditions: PhI (1 mmol), RhCl3·3H2O (2.5 mol %), PPh3 (10 mol %), base (1.2 mmol, if not stated otherwise), DMA
(2 mL, if not stated otherwise), CO/H2 (5 bar:5 bar), temperature 90 °C (if not stated otherwise), time 12 h (if not stated otherwise).
95% yield; 2 mmol Et3N, 92% yield; 3 mmol Et3N, 89% yield). nonpolar solvents like THF or toluene were inappropriate for
Thus, the appropriate amount of Et3N was set at 1.2 mmol.
the reaction leading to yields lower than 10%. Medium polar
solvents like MeCN or 1,4-dioxane afforded slightly higher
yields but still below 15%. To our delight, polar solvents with
Effect of solvents
Solvents act as the reaction media and strongly influence the high boiling points, NMP, DMI or DMA proved to be more
catalytic reactions [52,53]. We screened nine representative sol- suitable, and afforded benzaldehyde in 32%, 54% and 97%
vents in the catalytic reaction and the results are summarized in yield, respectively, likely owing to the high boiling point and
Figure 1c. Apparently, protic solvents like EtOH or MeOH and better CO and H2 dissolution ability, highlighting a strong sol-
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vent dependency of the system [54,55]. Therefore, DMA was
selected as the most suitable solvent for the reaction.
Table 3: Rhodium-catalyzed reductive carbonylation of iodobenzene
with CO and H2 to afford benzaldehyde: effect of pressures of CO and
H2a.
Effects of temperature and time
To further optimize the performance of the catalytic system, the
effect of the reaction temperature was screened in the range of
50 °C to 100 °C. The results revealed that the reaction tempera-
ture had an important influence on the catalytic process and the
product yield increased with increasing temperature. At low
temperature the reaction did not proceed at all, however, at
90 °C or higher, a nearly quantitative yield of benzaldehyde was
obtained (Figure 1d). Next, parallel experiments were con-
ducted at three selected temperatures (80 °C, 90 °C, and
100 °C) to study the yields at different reaction times. The
results revealed that equally high yields were obtained at 90 °C
and 100 °, but the reaction was much faster at 100 °C than at
90 °C (Figure 1e). On the other hand, when performing the
reaction at 80 °C, the product yield was lower and required
longer times to be reached.
Entry p(CO)
p(H2)
Conversion
[%]b
Yield
[%]b
[bar]
[bar]
1
1
2
3
4
5
6
7
2
4
3
6
4
6
1
2
3
4
5
6
7
4
2
6
3
6
4
32
63
74
92
100
100
100
72
66
85
24
51
62
81
97
97
97
63
58
72
68
94
89
2
3
4
5
6
7
8
9
10
11
12
13
74
99
95
Effects of pressure of CO and H2
The influence of the pressures of CO and H2 was explored next.
As expected, a low pressure of both, CO (1 atm) and H2
(1 atm), resulted in a lower yield of benzaldehyde (24% yield,
Table 3, entry 1). When the pressures of both gases were in-
creased to 2, 3, 4, or 5 bar, the yield of benzaldehyde according-
ly increased to 51%, 62% 81%, and 97%, respectively (Table 3,
entries 2–5). However, further increasing the pressures did not
lead to higher yields (Table 3, entries 6 and 7). After that, we
examined the proportions of the syngas components on the
reaction and it was found that the optimized proportions of
syngas were 5 bar CO and 5 bar H2 (1:1, (Table 3, entries
8–13).
aStandard conditions: PhI (1 mmol), RhCl3·3H2O (2.5 mol %), PPh3
(10 mol %), Et3N (1.2 mmol), DMA (2 mL), CO/H2, 90 °C, 12 h.
bDetermined by GC using dodecane as an internal standard.
Scheme 1: Scaled-up experiment of the reductive carbonylation of
iodobenzene to benzaldehyde under the optimized conditions.
Scaled-up experiment
Noteworthy, when conducting the reaction at a larger scale 1–4). Next, the concentration of RhCl3·3H2O was increased to
(10 mmol), benzaldehyde was obtained with a high yield of 2 mol % and 2.5 mol %, leading to the same results. In other
93%, indicating that our system could be suitable for industrial words, the optimal ratio of RhCl3·3H2O and the PPh3 ligand
application (Scheme 1).
was always 1:4 (Table 4, entries 5–12). No higher yields
(Table 4, entries 13–15) could be obtained by increasing the
loadings of RhCl3·3H2O and PPh3.
Optimal ratio of Rh salt and PPh3 ligand and
active species participating in the catalytic
process
The effects of PPh3 dosage on the catalytic ability demon-
strated that under otherwise identical conditions, a maximum
yield of benzaldehyde (97%) was obtained with a 1:4 molar
ratio of RhCl3·3H2O/PPh3, while higher or lower concentra-
tions of PPh3 both led to decreased yields (Table 4). This indi-
cated that in the active catalytic species the molar ratio of
[Rh]:PPh3 was exactly 1:3 (not 1:4 because of the consumption
of 1 equiv PPh3 during the redox process), which might be
Rh(PPh3)3Cl. The mentioned redox reaction can be explained
In order to ascertain the optimized ratio of RhCl3·3H2O and the
PPh3 ligand, a series of experiments with different concentra-
tions and ratios of RhCl3·3H2O and PPh3 were conducted. At
first, the concentration of RhCl3·3H2O was fixed at 1 mol %.
When changing the amount of PPh3 from 2 mol % to 5 mol %,
the yield gradually increased reaching a maximum yield of 74%
at 4 mol % PPh3. Further increasing the amount of the ligand
resulted in a decrease of the product yield (Table 4, entries
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Beilstein J. Org. Chem. 2020, 16, 645–656.
To test this assumption, we synthesized Rh(PPh3)3Cl according
to the literature [56] on account of no commercial sources and
employed it as the catalyst in the reaction instead of
RhCl3·3H2O and PPh3 and a 93% yield of benzaldehyde was
obtained under otherwise identical reaction conditions
(Scheme 2b). This could be an evidence that after the reduction
of one equivalent RhCl3 complexation with three molecular
PPh3 takes place forming Rh(PPh3)3Cl, which participated in
the subsequent catalytic process. Herein, Rh(III) is reduced to
Rh(I), with concomitant oxidation of PPh3 to PPh3=O. A quite
interesting fact is that Rh(PPh3)3Br and Rh(PPh3)3I afforded
much lower yields of the aldehyde compared to Rh(PPh3)3Cl
although they share the identical metal center and ligand
(Scheme 2c and 2d). This indicated that the anion plays an im-
portant role in the catalytic process.
Table 4: Rhodium-catalyzed reductive carbonylation of iodobenzene
with CO and H2 to afford benzaldehyde: effects of dosage of
RhCl3·3H2O and PPh3a.
Entry
RhCl3·3H2O
[mol %]
PPh3
[mol %]
Conversion Yield
[%]b
[%]b
1
2
3
4
5
6
7
8
1
1
1
1
2
2
2
2
2.5
2.5
2.5
2.5
3
2
3
4
5
4
6
8
10
5
7.5
10
12.5
12
16
20
35
51
78
72
34
65
92
88
28
47
74
70
31
62
88
84
42
73
97
92
97
97
97
Substrate scope
Next, the scope of the reductive carbonylation reaction was
explored (shown in Scheme 3), after having identified the opti-
mized conditions for benzaldehyde synthesis from iodobenzene.
The results showed that electronic effects had little impact on
the reaction. Both, substrates with electron-withdrawing or elec-
tron-donating groups afforded similar yields. However, steric
effects played an important role in the catalytic process, i.e., the
yields were influenced by the substituent group positions
following the order of ortho < meta < para. The obtained isolat-
ed yields were slightly lower than the NMR yields owing to a
loss of products during the workup process. Iodobenzene with
9
47
81
10
11
12
13
14
15
100
100
100
100
100
4
5
aStandard conditions: PhI (1 mmol), RhCl3·3H2O, PPh3, Et3N
(1.2 mmol), DMA (2 mL), CO/H2 (5 bar:5 bar), 90 °C, 12 h.
bDetermined by GC using dodecane as an internal standard.
as shown in Scheme 2a. Initially, RhCl3·3H2O is reduced by no substituent group provided benzaldehyde (1) with 93% yield.
1 equiv PPh3 to form a Rh(I) species that subsequently For iodobenzene derivatives with electron-donating groups
combines with 3 equiv PPh3 forming Rh(PPh3)3Cl. During this (Me, OMe), 83–95% yield of aldehydes 2–7 were obtained. As
process PPh3 is oxidized to O=PPh3, and HCl and H2O are re- expected, the yields increased in the order of ortho < meta <
leased.
para-substituted compounds. As for aryl iodides with halide
Scheme 2: Catalytic species participating in the catalytic process.
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Scheme 3: Substrate scope for the Rh-catalyzed reductive carbonylation of aryl iodides using CO and H2. Reaction conditions: PhI (1 mmol),
RhCl3·3H2O (2.5 mol %), PPh3 (10 mol %), Et3N (1.2 mmol), DMA (2 mL), CO (5 bar), H2 (5 bar), 90 °C, 12 h. Isolated yields of the products are
given and the structures were determined by NMR. Detailed information is given in Supporting Information File 1.
substituents (F, Cl, Br), these were also compatible with the position still provided the corresponding aldehydes 17 and 18 in
reaction system, affording 79−89% yields of the halogenated ar- relatively high yields (85% and 81%, respectively). 2-Iodonaph-
omatic aldehydes 8–16. Iodobenzene derivatives with phenyl or thalene with smaller steric hindrance performed a little better
tert-butyl groups displaying larger steric hindrance in the para- than 1-iodonaphthalene (19, 84% and 20, 77%). However,
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Beilstein J. Org. Chem. 2020, 16, 645–656.
starting iodides having methyl substituents in both ortho-posi- proposed, as shown in Scheme 5 [57]. First, RhCl3·3H2O
tions afforded the corresponding aldehydes in much lower reacted with PPh3 to form Rh(PPh3)3Cl (A), followed by an ox-
yields (21 61% and 22 60%). Also, iodobenzenes with an acetyl idative addition of Rh(PPh3)3Cl (A) to the aryl iodide, produc-
group in either ortho, meta, or para-position gave the products ing the corresponding arylrhodium complex (B). Then, the
in satisfactory yields (23 79%, 24 81% and 25 87%). 1-Iodo- coordination and insertion of CO led to the formation of
3,4-methylenedioxybenzene performed well providing alde- benzoylrhodium complex (C). Next, metathesis with H2
hyde 26 with 92% yield. Aryl iodide with an acetamido group afforded the aldehyde product. The base, Et3N neutralized the
in the para-position gave a medium yield (27 82%). Aryl proton in the rhodium hydroiodide complex (D) and regener-
iodides containing one or two trifluoromethyl groups in their ated the active Rh species [11].
structure worked slightly less efficient producing arylaldehydes
28–30 with yields of 72–79%. It is worth noticing that a cyano
group in the substrate stayed intact in the catalytic process
giving aldehyde 31 with 77% yield. Also substrates comprising
two halogen substituents performed well offering access to
dihalogenated aldehydes 32–35 with yields between 76–81%.
In addition, heterocyclic iodides were also amenable to the re-
ductive carbonylation reaction and the corresponding alde-
hydes 36–42 were isolated with yields of 65−73%.
Isotope labeling experiments
Isotope labeling experiments were conducted to study the
mechanism of the reductive carbonylation of aryl iodide with
CO and H2 under our optimized conditions, using 13CO and D2
instead of CO and H2, respectively, as the sources of the car-
bonyl group and hydrogen in the formyl group. C6H513CHO,
C6H5CDO, and C6H513CDO could be verified by the molecu-
lar ion peaks at m/z 107, 107, and 108 in the GC–MS spectrum
of the reaction solution (for the spectrum, see Supporting Infor-
mation File 1). This result confirmed that both CO and H2
participated in the formation of the formyl group in the product
Scheme 5: Proposed reaction mechanism for the Rh-catalyzed reduc-
tive carbonylation of aryl iodides using CO and H2.
(Scheme 4a–c).
In the catalytic system, CO and H2 (or syngas) were used as the
carbonyl and hydrogen sources, respectively. The catalyst
RhCl3·3H2O and PPh3 reacted via a redox reaction to form
Rh(PPh3)3Cl, which is the active catalytic species able to acti-
vate C–I bonds in the aryl iodides for the insertion of CO in the
next step. The base Et3N neutralized the proton in the interme-
diate rhodium hydroiodide (D) complex and regenerated the
active Rh species completing the catalytic cycle.
Conclusion
An efficient and facile Rh-based catalytic system composed of a
commercially available Rh salt, RhCl3·3H2O, a phosphine
ligand PPh3, and a base Et3N, was evaluated for the synthesis of
Scheme 4: Isotope-labeling experiments.
arylaldehydes via the reductive carbonylation of aryl iodides
using CO as carbonyl source and H2 as hydrogen source under
relatively mild conditions with a broad substrate range. The low
Reaction mechanism and role of each
component
Based on the results from the labeling experiments a reaction gas pressure, cost-effective ligand and low metal dosage signifi-
mechanism for the reductive carbonylation of aryl iodides was cantly improved the practicability of the system for industrial
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Beilstein J. Org. Chem. 2020, 16, 645–656.
productions. Another advantage of the method includes the use (2 mL) were loaded into the reactor. Then, the autoclave was
of cheap and abundant syngas (mixtures of CO and H2) in the screwed up, charged with CO and H2 to a total pressure of
catalytic system as an effective and convenient formyl source at 10 bar (1:1) and transferred to an oil bath preheated at 90 °C,
relatively low pressures, which further enhanced the possibility which was controlled by a Haake-D3 temperature controller.
of practical application of the proposed system.
After completion of the reaction, the reactor was cooled in iced
water and the gas carefully vented. The conversion and yield of
the aryl iodides and arylaldehydes were determined by GC anal-
ysis using dodecane as an internal standard. For yield determi-
Experimental
Materials
Rhodium species ([RhCl(CO)2]2, RhCl(CO)(PPh3)2, nation of the other products, the reaction mixture was first
Rh(acac)(CO)2, [RhCl(COD)]2, Rh(MeCN)2(COD)BF4, analyzed by GC–MS to determine the structures of the aromat-
Rh(COD)BF4, Rh(COD)2OTf, [Rh(OMe)(COD)]2, Rh(OAc)2, ic aldehyde products. Then, CH2Cl2 (5 mL) was added to the
[Rh(CF3COO)]2, [Rh(CH3(CH2)6CO2)2]2, Rh(acac)3, Rh(ethyl- reaction mixture, after which deionized water (10 mL) was
ene)2(acac), [Rh(ethylene)2Cl]2, Rh(norbornadiene)2BF4, added to extract the solvent DMA for 5 times. The organic layer
[Cp*RhCl2]2, Rh/C, and RhCl3·3H2O), ligands containing was dried over anhydrous Na2SO4, concentrated by rotary evap-
nitrogen or phosphorus (PP3, triphos, dpp-BINAP, dpp-OPh, oration and finally purified by column chromatography on silica
dppb, dppe, P(PhF5)3, P(4-FPh)3, Cydpp, Bipy, DBU, Im, and gel using n-hexane/ethyl acetate as eluent to obtain the pure
PPh3 (their structures are shown in Table 2)), bases (Et3N, 1,4- products and isolated yields.
diaza[2.2.2]bicyclooctane (DABCO), N,N-diisopropylethyl-
amine (DIPEA), N,N,N',N'-tetramethylethylenediamine
Procedures for the preparations of
(TMEDA) and 1,2,2,6,6-pentamethylpiperidine (PMP)), and RhCl(PPh3)3, RhBr(PPh3)3 and RhI(PPh3)3
solvents (N,N-dimethylacetamide (DMA), 1,3-dimethyl-2- Preparation of RhCl(PPh3)3: A round-bottomed flask filled with
imidazolidinone (DMI), N-methyl-2-pyrrolidinone (NMP), anhydrous ethanol (60 mL) and triphenylphosphine (10 mmol)
tetrahydrofuran (THF), 1,4-dioxane, ethanol, methanol, aceto- was put in an oil bath at 70 °C under a nitrogen atmosphere.
nitrile, and toluene) together with aryl iodides and other Then, hydrated rhodium(III) chloride (1.5 mmol) dissolved in
reagents were purchased from commercial sources (namely anhydrous ethanol (10 mL) was added to the solution under stir-
J&K Scientific Ltd. and Innochem Science & Technology Co., ring and the resulting solution was kept at gentle reflux for
Ltd.) and used without further purification. CO and H2 with 2.5 h. Afterwards, the hot mixture was filtered. Finally, the
high purity (99.99%) were supplied by Beijing Analytical solid was washed with ether and dried under vacuum overnight
Instrument Factory.
to afford RhCl(PPh3)3 as maroon powder. The preparations of
RhBr(PPh3)3 and RhI(PPh3)3 were similar only with different
halide ions.
Instrumentation
1H NMR spectra in solution were recorded in CDCl3 using the
residual CHCl3 as internal reference (7.26 ppm) on a Bruker
400 spectrometer. 1H NMR peaks were labeled as singlet (s),
doublet (d), triplet (t), and multiplet (m). The coupling con-
stants, J, are reported in hertz (Hz). 13C NMR spectra in solu-
tion were recorded at 101 MHz in CDCl3 using the solvent as
internal reference (77.0 ppm). GC analysis was performed on
Agilent 4890D with a FID detector and a nonpolar capillary
column (DB-5) (30 m × 0.25 mm × 0.25 μm). The column oven
was temperature-programmed with a 2 min initial hold at 50 °C,
followed by heating to 265 °C at a rate of 10 °C /min and kept
at 265 °C for 10 min. High purity nitrogen was used as the
carrier gas.
Supporting Information
Supporting Information File 1
MS spectra of isotope-labeling experiments and
characterization of products.
[https://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-16-61-S1.pdf]
Acknowledgements
We thank Institute of Chemistry, Chinese Academy of Sciences
for the supply of CO gas and corresponding safety protection.
General procedure for reductive
carbonylation of aryl iodides with CO and H2
Funding
This work was supported by the National Natural Science Foun-
All reactions were carried out in an 80 mL Teflon-lined stain- dation of China (21773307), Zhejiang Provincial Natural
less steel reactor equipped with a magnetic stirring bar. Typical- Science Foundation of China (LTY20B050001) and Zhejiang
ly, in a glovebox, the aryl iodides (1.0 mmol), RhI3 Provincial Basic Public Welfare Research Project
(0.025 mmol), PPh3 (0.1 mmol), Et3N (1.2 mmol), and DMA (LGG19B060002).
654

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Tiancheng Mu - https://orcid.org/0000-0001-8931-6113
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