One-Pot Palladium-Catalyzed Carbonylative Sonogashira Coupling using Carbon Dioxide as Carbonyl Source

Article abstract of DOI:10.1002/cctc.202100051

Carbonylation coupling reaction has emerged as a powerful and versatile strategy for the construction of carbonyl-containing compounds in modern synthetic chemistry over the past years. Carbon dioxide, a renewable one carbon molecule, has become one of the most attractive and promising alternative carbonyl sources due to its highly abundance, nontoxicity and stability in comparison with CO in recent years. However, in most cases, a two-chamber technique was generally necessary to allow the CO-producing and CO-consuming processes to perform successfully because of the complexities and incompatibility of reaction conditions, when carbon dioxide was utilized as carbonyl source. Herein, a practical one-pot protocol using carbon dioxide as the carbonyl source for the palladium-catalyzed carbonylative Sonogashira coupling has been established, providing an expedient and practical route to a wide range of functionalized alkynones and indoxyls under mild reaction conditions. By finding a suitable catalytic system, the method allowed the CO-generating and CO-consuming processes to proceed in one pot, wherein carbon monoxide was generated in situ from the reduction of carbon dioxide in the absence of any fluoride reagents. Simple and safe operation, readily available substrates, good functional group tolerance and mild reaction conditions are the features of the method.

Full text of DOI:10.1002/cctc.202100051

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One-Pot Palladium-Catalyzed Carbonylative Sonogashira
Coupling using Carbon Dioxide as Carbonyl Source
Wenfang Xiong+,[a] Bowen Wu+,[a] Baiyao Zhu,[a] Xiaobin Tan,[a] Lu Wang,[a] Wanqing Wu,[a]
Chaorong Qi,*[a] and Huanfeng Jiang*[a]
Carbonylation coupling reaction has emerged as a powerful
and versatile strategy for the construction of carbonyl-contain-
ing compounds in modern synthetic chemistry over the past
years. Carbon dioxide, a renewable one carbon molecule, has
become one of the most attractive and promising alternative
carbonyl sources due to its highly abundance, nontoxicity and
stability in comparison with CO in recent years. However, in
most cases, a two-chamber technique was generally necessary
to allow the CO-producing and CO-consuming processes to
perform successfully because of the complexities and incompat-
ibility of reaction conditions, when carbon dioxide was utilized
as carbonyl source. Herein, a practical one-pot protocol using
carbon dioxide as the carbonyl source for the palladium-
catalyzed carbonylative Sonogashira coupling has been estab-
lished, providing an expedient and practical route to a wide
range of functionalized alkynones and indoxyls under mild
reaction conditions. By finding a suitable catalytic system, the
method allowed the CO-generating and CO-consuming proc-
esses to proceed in one pot, wherein carbon monoxide was
generated in situ from the reduction of carbon dioxide in the
absence of any fluoride reagents. Simple and safe operation,
readily available substrates, good functional group tolerance
and mild reaction conditions are the features of the method.
Introduction
source highly valuable in synthetic chemistry. Actually, the
exploitation of catalytic methods for the reduction of CO2 to CO
have been well documented in the presence of appropriate
reductants in recent years,[10] including the photo- and electro-
chemical catalytic approaches. However, due to the complex-
ities and incompatibility of reaction conditions between the
CO-producing and CO-consuming process, the direct applica-
tion of CO2 as the carbonyl source to catalytic carbonylation
Palladium-catalyzed carbonylation reactions represent a power-
ful and versatile tool for the preparation of many fine
chemicals,[1] such as aldehydes, carboxylates, heterocycles,
hydrocarbon fuels, and the construction of bioactive natural
products, pharmaceutical agrochemical compounds containing
carbonyl structural motif[2] over the past few years. Traditionally,
carbon monoxide (CO) was used as the carbonyl source in the
transformations. However, the high toxicity, flammability as well
as the difficulties in handling of CO might remain to be
formidable problems, which have limited its applications in the
carbonylative coupling. To circumvent these issues, various CO
surrogates, such as formates,[3] formamides,[4] aldehydes,[5]
pivaloyl chloride,[6] and metal carbonyls,[7] have been exploited
in recent years.[8] However, the transition metal catalyst, strong
base and high temperatures are generally employed in order to
release CO successfully in these cases, which inspire the
development of efficient and sustainable CO surrogates. Carbon
dioxide (CO2) has recently been regarded as a more attractive
and promising one-carbon source because of its highly
abundance, nontoxicity and stability in comparison with CO,[9]
which renders the replacement of CO with CO2 as the carbonyl
coupling in
challenge.
a one-pot manner still remain a significant
To address these problems, a two-chamber technique,
which can allow the CO-producing and CO-consuming proc-
esses to take place separately, has been developed by
Skrydstrup and coworkers.[11] For example, recently, they
reported a low-pressure, low-temperature and near-stoichio-
metric hydroformylation efficient operation on a diverse array
of terminal olefins without the need for expensive equipment
by decoupling the syngas formation and consumption via a
two-chamber reactor.[11c] By using the technique, several elegant
processes for the carbonylation reactions using CO2 as the CO
source have been successfully demonstrated (Scheme 1, a).[12]
Skrydstrup and Gee et al. reported that silacarboxylic acids,
which were produced from CO2 and chlorosilane in the
presence of lithium, could be utilized as efficient CO releasing
molecules and further applied in the carbonylation process.[12a–d]
The merges of fluoride-catalyzed reduction of CO2 by using
stoichiometric amount of disilane and aminocarbonylations
have also been reported respectively by the groups of
Skrydstrup, Sundararaju and He.[12e–g] Additionally, Fleischer and
coworkers proved that N-formyl saccharin derived from CO2
could also be used as CO surrogate and applied in the Pd-
catalyzed alkoxycarbonylation of alkenes.[12h] Moreover, photo-
catalysis is also effective for the reduction of CO2 and applied in
[a] W. Xiong,+ B. Wu,+ B. Zhu, X. Tan, L. Wang, Prof. W. Wu, Prof. C. Qi,
Prof. H. Jiang
School of Chemistry and Chemical Engineering, Key Lab of Functional
Molecular Engineering of Guangdong Province
South China University of Technology
510640 Guangzhou (P. R. China)
E-mail: crqi@scut.edu.cn
jianghf@scut.edu.cn
[+] These authors contributed equally to this work.
Supporting information for this article is available on the WWW under
https://doi.org/10.1002/cctc.202100051
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Scheme 1. Pd-catalyzed carbonylation reactions using carbon dioxide as carbonyl source
carbonylation with this strategy.[13] Although great progress has
been made in this research field, the two-chamber technique
was necessary in these cases to enable the CO-producing and
CO-consuming process performing smoothly. Moreover, the
pre-preparation of carboxylation reagents such as silacarboxylic
acids and N-formyl saccharin, or a catalytic amount of fluoride
reagents were required. To our knowledge, the one-pot green
technique for the carbonylation reactions with CO2 as the
carbonyl source, in which CO is generated in situ, has remained
unexplored but is more desirable and appealing due to the
operation convenience. With our continuous interest in devel-
oping efficient methods for the transformation of CO2,[14] we
envisioned that the CO-producing and CO-consuming might be
conducted simultaneously in one chamber through finding a
suitable catalytic system between the CO2 reduction and the
carbonylative coupling. Herein, we reported a new one-pot
method for the Pd-catalyzed carbonylation of aryl iodides/2-
iodoaniline, alkynes and CO2 under mild reaction conditions,
wherein CO was acted as intermediate and generated in situ
under the fluoride-free conditions in the presence of phenyl-
silane. A wide array of alkynones and indoxyls were obtained,
which are important building blocks found in numerous
biologically active compounds and valuable intermediates
widely utilized in cycloadditions for the efficient synthesis of
heterocycles, such as oxazole, pyrazole, etc.[1,2]
contrast to the previous report,[12g] the introduction of a fluoride
inhibited the formation of the desired product, which might be
due to the reason that fluoride was not conducive to the
carbonylation reaction (entry 5). Moreover, we observed the
amount of reductant had great impact on the reaction.
Decreasing the amount of PhSiH3 led to lower yields, whereas
the result was not improved when it was further increased to 6
equivalents (entries 6–8). Among the palladium precursors
investigated, including Pd(PPh3)2Cl2, Pd(dppp)Cl2, Pd(OAc)2,
PdCl2 and Pd(PPh3)4, Pd(PCy3)2Cl2 gave the best result (entries 9–
13). However, the yield of product 3a decreased when the
combination of PdCl2 and PCy3 was used as the catalyst system
(entry 14). During the screening of bases, NEt3 was found to be
the best out of a variety bases such as DBU, DABCO and NEt
(iPr)2 (entries 15–17). Further experiments were carried out to
test the influence of the stirring time of CO2 reacting with
reductant (entries 18–20). Finally, The optimal result was
obtained when the stirring time was increased to 3 h, affording
the desired product with 79% isolated yield, while a further
increase demonstrated to be not beneficial.
With the optimized reaction conditions in hand, the
generality of the one-pot palladium-catalyzed carbonylative
Sonogashira coupling by the use of CO2 as carbonyl source was
then investigated with a variety of terminal alkynes (Scheme 2).
In general, various alkynes containing various substituents
including electron-donating and electron-withdrawing on the
phenyl groups were all tolerated under the optimized reaction
conditions (3a–3j). Notably, aryl alkynes with electron-donating
groups (3b–3e) gave the corresponding products in higher
yields than those with electron-withdrawing groups (3f–3j),
which revealed that the electronic nature of the substituents
had significant influence on this transformation. Moreover,
meta-substituted substrates, such as 1-ethynyl-3-meth-
ylbenzene (2k), 1-ethynyl-3-methoxybenzene (2l), 1-ethynyl-3-
fluorobenzene (2m), 2-ethynylnaphthalene (2o), and ortho-
substituted aryl acetylene (2n) also could undergo the reaction
smoothly, affording the corresponding products with atisfactory
yields. It was worth mentioning that 3-ethynylthiophene (2p)
could also be employed in this one-pot transformation, albeit
with moderate yield. Moreover, aliphatic terminal alkynes such
Results and Discussion
Our initial studies were directed towards finding an appropriate
combination of reductant and catalyst by employing iodoben-
zene (1a) and phenyl acetylene (2a) as the model substrates,
and the representative optimization conditions were summar-
ized in Table 1. To our delight, when the reaction was
performed via a two-step, one-pot procedure with phenylsilane
as reductant, Pd(PCy3)2Cl2 as the catalyst and NEt3 as the base in
°
N,N-dimethyl formamide (DMF) at 60 C, the desired product 3a
could be obtained with 63% yield (entry 1). No better results
were obtained when Et2SiH2, Ph3SiH and PhSi(OEt)3 were
examined (entries 2–4) in comparison with PhSiH3. Notably, in
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Table 1. Optimization of reaction conditions.[a]
Entry
Catalyst [mol %]
[H] [equiv.]
Base [equiv.]
Yield[%][a]
1
2
3
4
Pd(PCy3)2Cl2
Pd(PCy3)2Cl2
Pd(PCy3)2Cl2
Pd(PCy3)2Cl2
Pd(PCy3)2Cl2
Pd(PCy3)2Cl2
Pd(PCy3)2Cl2
Pd(PCy3)2Cl2
Pd(PPh3)2Cl2
Pd(dppp)Cl2
Pd(OAc)2
PdCl2
Pd(PPh3)4
PdCl2
Pd(PCy3)2Cl2
Pd(PCy3)2Cl2
Pd(PCy3)2Cl2
Pd(PCy3)2Cl2
Pd(PCy3)2Cl2
Pd(PCy3)2Cl2
PhSiH3
(Et)2SiH2
(Ph)3SiH
PhSi(OEt)3
PhSiH3
PhSiH3
PhSiH3
phSiH3
PhSiH3
PhSiH3
PhSiH3
PhSiH3
PhSiH3
PhSiH3
PhSiH3
PhSiH3
PhSiH3
PhSiH3
PhSiH3
PhSiH3
NEt3
NEt3
NEt3
NEt3
NEt3
NEt3
NEt3
NEt3
NEt3
NEt3
NEt3
NEt3
NEt3
NEt3
DBU
DABCO
NEt(iPr)2
NEt3
NEt3
NEt3
63
trace
n.d.
n.d.
n.d.
6
34
61
16
49
35
47
35
35
18
10
62
37
5[b]
6[c]
7[d]
8[e]
9
10
11
12
13
14[f]
15
16
17
18[g]
19[h]
20[i]
85(79)
72
°
[a] Reaction conditions: The mixture of CO2 (1 atm), [H] (0.8 mmol), DMF (2 ml) was first stirred at 60 C for 2 h; then another mixture of 1a (0.2 mmol), 2a
(0.3 mmol), [Pd] (0.01 mmol) and base (0.6 mmol) was added dropwise with syringe and stirred for overnight. The yield was GC yield with dodecane as the
internal standard, the number in parentheses was the isolated yield. “n.d.” was “not detected”. [b] CsF (0.8 mmol) was added. [c] PhSiH3 (0.4 mmol). [d] PhSiH3
(0.6 mmol). [e] PhSiH3 (1.2 mmol). [f] PCy3 (0.04 mmol) was added. [g] The mixture of CO2, PhSiH3 in DMF was first stirred for 1 h. [h] The mixture of CO2,
PhSiH3 in DMF was first stirred for 3 h. [i] The mixture of CO2, PhSiH3 in DMF was first stirred for 5 h.
as n-butyl, 3-phenyl-propyl, 1- cyclohexyl-methyl and cyclo-
propane were all compatible with the standard reaction
conditions, giving the corresponding products in moderate to
high yields (3q–3t).
Encouraged by the above results, we attempted to extend
our methodology for the synthesis of indoxyls through a
carbonylation / intramolecular cyclization process by using 2-
iodoanilines as the coupling partner. Pleasingly, with the above
slightly modified conditions, various indoxyls could be pro-
duced as well by using the Pd(PPh3)4/PPh3 catalytic system,
wherein PPh3 might not only function as the ligand but also
serve as the organocatalyst to promote the intramolecular
cyclization of in-situ generated alkynones.[15a] As shown in
Scheme 4, 2-iodoanilines with simple methyl- and methoxy-
substituted on the phenyl ring proceeded smoothly to give the
desired products 5a–5c in moderate yields. Electron-withdraw-
ing substituents (F, Cl, Br, CO2Me, CN, CF3) were also compatible
with the standard reaction conditions, finishing the expected
products in 52–72% yields (5d–5i). The structure of product 5d
was characterized by X-ray crystallographic analysis.[16]
Besides mono-substituted substrates, the substrate bearing
3,4-dimethyl on the aromatic ring could also be extended to
the protocol, giving product 5j with 71% yield. Heteroaromatic
moieties could also be contained in substrate and allowing the
formation of the desired product 5k in acceptable yields.
However, the use of 2-iodoaniline protected by N-acetyl failed
to yield the desired product 5l, but led to the formation of a
small amount of unidentified product and most of the raw
material could be recovered. Subsequently, various alkynes with
2-iodoaniline under standard conditions were examined. Al-
kynes containing electron-rich 4-methyl, 4-t-butyl or 4-n-amyl
yielded the desired products 5m–5o in 61–72% yield, and
We subsequently turned our attention to the scope of this
transformation with various aryl iodides. As shown in Scheme 3,
aryl iodides bearing different electron-donating groups on the
aryl ring, including 4-methoxy (1b), 4-tbutyl (1c) and 4-
morpholino (1d), could furnish the corresponding products
(3u–3w) in 63%, 75% and 80% yields, respectively. Aryl iodides
bearing electron-withdrawing groups, such as 4-chloro (1e), 4-
bromo (1f), 4- trifluoromethyl (1g), 4-acetyl (1h) and 4-ester
(1i), could also undergo the reaction and delivered the
corresponding products with moderate yields. Similarly, aryl
iodides with electron-donating substituents gave higher yields
in comparison with those with electron-withdrawing ones.
Substituents at the meta and ortho positions were also assessed
and all of them were compatible with the conditions, affording
the desired products in moderate yields (3ac–3ae). Moreover,
polysubstituted aryl iodides were also well-tolerated to give the
corresponding alkynones (3af–3ah) in 71%, 74% and 78%
yield, respectively. A fused ring containing aryl iodides could
also enter into the reaction without difficulty, furnishing
alkynone 3ai in 68% yield. It is worth noting that other aryl
halides including aryl bromide and aryl chloride exhibited very
low reactivity, and only trace amounts of the desired product
was detected by GC-MS analysis, and most of the starting
materials were recovered.
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Scheme 2. Carbonylative synthesis of alkynones with various alkynes. Reaction conditions: the mixture of CO2 (1 atm), PhSiH3 (0.8 mmol), DMF (2 ml) was first
°
stirred at 60 C for 3 h, then another mixture of 1a (0.2 mmol), 2 (0.3 mmol), Pd(PCy3)2Cl2 (0.01 mmol), NEt3 (0.6 mmol) in DMF (1 mL) was added dropwise and
stirred for overnight. The yield was the isolated yield.
electron-deficient 4-phenyl, 4-fluoro, 4-chloro, 4-bromo or 4-
trifluomethyl derivatives yielded the desired products 5p–5t
smoothly. Moreover, meta-substituted substrates also could be
subjected to the reaction conditions, and the desired products
5u–5w were obtained in acceptable yields. In addition, alkyne
containing pyridine heterocyclic was tested, and gave the
product 5x with a moderate yield.
7 and 8 could be produced by conducting the reaction of
alkynone and hydrazine at room temperature in DMF. The
intermolecular cycloaddition at the triple bond could be readily
achieved by the reaction of alkynone with TMSN3 or S8,
generating triazole derivative 9 or tetra- substituted thiophene
derivative 10, which represented a useful structural motif found
in numerous luminescent functional molecules.
To further extend the application of this transformation, a
series of heterocycles were prepared (Scheme 5). As expected,
the treatment of 3a with NH2OH·HCl in the presence of KOH at
room temperature in a mixture solvent of MeOH/H2O (9:1) gave
oxazole derivative 6 in 81% yield. Moreover, pyrazole derivative
Moreover, in order to unambiguously determine the source
of C atom of carbonyl group in alkynone, an isotopic tracing
experiment by replacing CO2 with 13CO2 under the standard
conditions was conducted, and 99% 13C incorporation was
found in the desired product (Scheme 6a). Subsequently, to get
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Scheme 3. Carbonylative synthesis of alkynones with various aryl iodides. Reaction conditions: the mixture of CO2 (1 atm), PhSiH3 (0.8 mmol), DMF (2 ml) was
°
first stirred at 60 C for 3 h, then another mixture of 1 (0.2 mmol), 2a (0.3 mmol), Pd(PCy3)2Cl2 (0.01 mmol), NEt3 (0.6 mmol) in DMF (1 mL) was added dropwise
and stirred for overnight. The yield was the isolated yield.
a deeper understanding of the cyclization process, several
control experiments were designed. First, the reaction of CO2
with 4a and 2a under the standard conditions without PPh3
was carried out, trace amount of the desired product was
observed together with the formation of a small amount of
non-cyclized product (Scheme 6b). Then, when the intermediate
11 was synthesized and treated with PPh3 and NEt3 in DMF at
oxidative addition of palladium(0) A with aryl halide 1 or 4 to
form intermediate C. Then, the intermediate C will react with
alkynes to give intermediate D and release HI in the presence of
base, followed by the reductive elimination to afford product
3a or intermediate 11. Intermediate 11 can further react with
PPh3 to produce intermediate E, which undergoes the isomer-
ization and intramolecular cyclization to yield the product 5a
and release PPh3.
°
60 C for 24 h, the reaction afforded 5a with 55% isolated yield
and the intermediate 11 with 40% recovered (Scheme 6c). In
contrast, the product 5a could not be obtained without the
addition of PPh3 (Scheme 6d). These results demonstrated that Conclusions
PPh3 might not only serve as the ligand but also function as the
organocatalyst to promote the intramolecular cyclization of in-
situ generated alkynones.
In summary, we have successfully developed a protocol for the
palladium-catalyzed carbonylative Sonogashira coupling with
CO2 as the CO source, providing an efficient and practical route
to a range of functionalized alkynones and indoxyls under mild
reaction conditions. Notably, this method allowed the CO-
generating and CO-consuming process to proceed in one pot,
thus avoiding the use of two-chamber technique that requires a
special apparatus. Simple and safe operation, readily available
With respect to this transformation, a reaction mechanism
was tentatively proposed based on the experimental results as
well as the previous works,[15] as showed in Scheme 7. The
reduction of CO2 with the assistance of PhSiH3 will generate CO
and release PhSiH2OH. And the generated CO can undergo the
insertion with (σ-aryl)palladium species B derived from the
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°
Scheme 4. Carbonylative synthesis of indoxyls. Reaction conditions: the mixture of CO2 (1 atm), PhSiH3 (1.6 mmol), DMF (2 ml) was first stirred at 60 C for 3 h,
then another mixture of 4 (0.2 mmol), 2 (0.3 mmol), Pd(PPh3)4 (0.01 mmol), PPh3 (0.04 mmol), NEt3 (0.6 mmol) in DMF (1 ml) was added dropwise and stirred
for 24 h. The yield was the isolated yield.
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Scheme 5. The synthesis of heterocycles. Reaction conditions: (a) 3a (0.2 mmol), NH2OH·HCl (4 equiv.), KOH (4 equiv.), MeOH/H2O (v:v=9:1) (4 mL), room
temperature; (b) 3a (0.2 mmol), PhNHNH2 (0.3 mmol), room temperature, 1 h; (c) 3a (0.2 mmol), TMSN3 (0.6 mmol), CuI (5 mol%), DMF:MeOH=5:1, reflux,
°
24 h. (d) 3a (0.4 mmol), S8 (3/8 mmol), KOH (1 equiv.), toluene (2.0 mL), 100 C, 3 h.
Scheme 6. The isotopic tracing experiment and control experiments.
Melting Point B-545 instrument and were uncorrected. The data of
substrates, good functional group tolerance and mild reaction
conditions were the features of this reaction. Further applica-
tion of this strategy to the efficient conversion of CO2 into
valuable chemicals are underway in our laboratory.
HR-MS was conducted on a high-resolution mass spectrometer
(LCMS-IT-TOF). Thin-layer chromatography was performed using
Qingdao-Haiyang 600 mesh silica gel plates (GF254) and samples
were made visual with short-wavelength UV light (254 nm). X-ray
structural analyses were carried out an x-ray analysis instrument. All
new compounds were characterized by 1H NMR, 13C NMR and
1
HRMS. The known compounds were characterized by H NMR and
13C NMR. Unless otherwise stated, all manipulations were carried
out by using standard Schlenk techniques, and all anhydrous
solvents and reagents were commercially purchased and used
without further purification.
Experimental Section
1H and 13C NMR spectra were recorded using a Bruker DRX-400
spectrometer in solutions of CDCl3 or CD3SOCD3 with tetrameth-
ylsilane as an internal standard. The chemical shifts (δ) are
referenced to signals at 7.26 and 77.0 ppm, respectively. Multiplicity
was indicated as follows: s(singlet), d(doublet), t(triplet), q(quartet),
m(multiplet). Coupling constants were given in Hertz (Hz). IR
spectra were obtained either as potassium bromide pellets or as
liquid films between two potassium bromide pellets with a Bruker
TENSOR 27 spectrometer. Melting points were measured on a Büchi
General procedure for the Pd-catalyzed carbonylative
Sonogashira coupling of aryl iodides, alkynes and CO2
In a glove box, a solution of the phenylsilane (0.8 mmol) in DMF
(2 mL) was added to a 25 mL Schlenk tube equipped with a Teflon
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Scheme 7. Proposed reaction mechanism.
cap and a magnetic stirring bar. After the sealed tube was taken
out of the glovebox, the mixture was subjected to vacuum for a
while and CO2 (1 atm) was introduced into the reaction vessel. After
(2018M640774) and the Fundamental Research Funds for the
Central Universities (D2191970 and D2190580) for financial
support.
°
the reaction mixture was stirred at 60 C for 3 h, a solution of aryl
iodides
1
(0.2 mmol), alkynes
2
(0.3 mmol), Pd(PCy3)2Cl2
(0.01 mmol), NEt3 (0.6 mmol) in DMF (1 mL) was added dropwise
and stirred for overnight. After completion of the reaction, the
residual material was carefully quenched with water and extracted
several times with ethyl acetate. The combined organic layers were
washed with brine and dried over anhydrous MgSO4 and concen-
trated in vacuo. Further purification by flash column chromatog-
raphy on silica gel (eluting with petroleum ether/ethyl acetate)
provided the product 3.
Conflict of Interest
The authors declare no conflict of interest.
Keywords: Pd-catalyzed · carbonylative Sonogashira · carbon
dioxide · simple and safe operation
General procedure for the one-step Pd-catalyzed
carbonylative Sonogashira coupling of 2-iodoanilines, phenyl
acetylene and CO2
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Yin, J.-X. Xu, X.-F. Wu, ACS Catal. 2020, 10, 6510–6531.
In a glove box, a solution of the phenylsilane (1.6 mmol) in DMF
(2 mL) was added to a 25 mL Schlenk tube equipped with a Teflon
cap and a magnetic stirring bar. After the sealed tube was taken
out of the glovebox, the mixture was subjected to vacuum for a
while and CO2 (1 atm) was introduced into the reaction vessel. After
[2] a) B. L. Flynn, E. Hamel, M. K. Jung, J. Med. Chem. 2002, 45, 2670–2673;
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°
the reaction mixture was stirred at 60 C for 3 h, a solution of 2-
iodoanilines
4
(0.2 mmol), alkynes
2
(0.3 mmol), Pd(PPh3)4
(0.01 mmol), PPh3 (0.04 mmol), NEt3 (0.6 mmol) in DMF (1 mL) was
added dropwise and stirred for 24 h. After completion of the
reaction, the residual material was carefully quenched with water
and extracted several times with ethyl acetate. The combined
organic layers were washed with brine and dried over anhydrous
MgSO4 and concentrated in vacuo. Further purification by flash
column chromatography on silica gel (eluting with petroleum
ether/ethyl acetate) provided the product 5.
Acknowledgements
This work was supported by the Ministry of Science and
Technology of the People’s Republic of China (2016YFA0602900),
the National Natural Science Foundation of China (21971073 and
22001075) and the Guangdong Natural Science Foundation
(2019A1515011468), China Postdoctoral Science Foundation
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Manuscript received: March 10, 2021
Revised manuscript received: March 27, 2021
Accepted manuscript online: March 29, 2021
Version of record online: ■■■, ■■■■
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FULL PAPERS
W. Xiong, B. Wu, B. Zhu, X. Tan, L.
Wang, Prof. W. Wu, Prof. C. Qi*,
Prof. H. Jiang*
1 – 10
One-Pot Palladium-Catalyzed Car-
bonylative Sonogashira Coupling
using Carbon Dioxide as Carbonyl
Source
One-pot synthesis: We report a
practical one-pot protocol using
carbon dioxide as the carbonyl source
for the palladium-catalyzed carbonyla-
tive Sonogashira coupling, providing
an efficient and practical route to a
wide range of functionalized
alkynones and indoxyls under mild
reaction conditions.