Ni-catalyzed direct carboxylation of an unactivated C-H bond with CO2

Article abstract of DOI:10.1021/acs.orglett.0c02429

The transition-metal-catalyzed direct carboxylation of an unactivated C-H bond is rarely reported, and no example of catalysis using abundant and cheap nickel has been reported. In this work, the first Ni-catalyzed direct carboxylation of an unactivated C-H bond under an atmospheric pressure of CO2 is reported. This method affords moderate to high carboxylation yields of various methyl carboxylates under mild conditions. Preliminary mechanistic studies reveal that a Ni(0)-Ni(II)-Ni(I) catalytic cycle may be involved in this reaction.

Full text of DOI:10.1021/acs.orglett.0c02429

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Letter
Ni-Catalyzed Direct Carboxylation of an Unactivated C−H Bond with
CO
2
Chunzhe Pei, Jiarui Zong, Shanglin Han, Bin Li, and Baiquan Wang*
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sı Supporting Information
ABSTRACT: The transition-metal-catalyzed direct carboxylation
of an unactivated C−H bond is rarely reported, and no example of
catalysis using abundant and cheap nickel has been reported. In
this work, the first Ni-catalyzed direct carboxylation of an
unactivated C−H bond under an atmospheric pressure of CO is
2
reported. This method affords moderate to high carboxylation
yields of various methyl carboxylates under mild conditions.
Preliminary mechanistic studies reveal that a Ni(0)−Ni(II)−Ni(I)
catalytic cycle may be involved in this reaction.
espite its significant kinetic inertness and thermodynamic
Scheme 1. Transition-Metal-Catalyzed Direct Carboxylation
of Unactivated C−H Bonds with CO2
D
stability, CO is an abundant, nontoxic, inexpensive, and
2
1
renewable C1 feedstock in synthetic chemistry. The
conversion of CO2 into fine chemicals has attracted
considerable attention, especially the formation of carboxylic
2
,3
acids, which are building blocks in many valuable synthetic
4
compounds.
Compared to traditional coupling methods, the transition-
metal-catalyzed C−H functionalization reactions are consid-
5
ered to be a more efficient and atom-economic strategy. Thus,
transition-metal-catalyzed C−H carboxylation provides a
powerful tool for CO fixation. In recent years, although
2
transition-metal-catalyzed C−H carboxylation with CO has
2
led to great progress in the synthesis of carboxylic acids or their
3
derivatives, the substrates are mainly focused on terminal
alkynes, perfluorinated or perchlorinated benzenes, and
heteroaromatic rings, which possess acidic C−H bonds or an
6a−d
electron-deficient nature.
The carboxylation of these kinds
of C−H bonds can be carried out in the presence of a base
6
e−h
even without a metal catalyst.
The transition-metal-
catalyzed direct carboxylation of unactivated aryl C−H
bonds is rarely reported. The first carboxylation of unactivated
C−H bonds with CO was reported in 1984 by Fujiwara using
2
Pd(OAc) as a catalyst, but with limited examples and low
9
2
Yu, Wang, and Li, but the insertion of CO into the C−M or
7
2
turnover numbers. In 2011 and 2014, Iwasawa’s group
O−M/N−M bond is ambiguous.
As an abundant and cheap first-row transition metal, nickel
has been extensively studied in homogeneous catalysis because
reported Rh(I)-catalyzed direct carboxylation of unactivated
aryl C−H bonds with CO (Scheme 1a). In these reactions,
2
insertion of CO into a C−Rh(I) bond is involved and a
2
stoichiometric methyl aluminum complex plays an important
8
Received: July 21, 2020
role. In 2014, Sato’s group reported cobalt-catalyzed allylic
18
C−H carboxylation.
Some elegant works including Pd- or Rh-catalyzed
lactonization or lactamization of unactivated alkenyl or aryl
C−H bonds with CO assisted by an intramolecular hydroxyl
2
or amino group were also reported by the groups of Iwasawa,
©
XXXX American Chemical Society
https://dx.doi.org/10.1021/acs.orglett.0c02429
A
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10
of its distinguishing characteristics. Ni-catalyzed reductive
effective ligand providing 2a in 63% yield. Then, other simple
carboxylation of organic (pseudo)halides with CO is one of
and readily available nickel catalysts were investigated (Table
2
2
,11
the most well-established strategies.
The Ni(0)−Ni(II)−
1, entries 6−9), and NiCl proved to be the most effective.
2
Ni(I) catalytic cycle was suggested for these reactions, and
Some inorganic salts were tested as additives (Table 1, entries
CO was inserted into the more nucleophilic C−Ni(I) bond.
10−13), which were often added in Ni-catalyzed carboxylation
2
11
Very recently, Murakami reported the carboxylation of
of aryl halides with CO . Addition of LiCl improved the yield
2
benzylic and aliphatic C−H bonds with CO induced by
to 84%, while addition of KCl had no influence. Addition of
2
light, ketone, and nickel (Scheme 1b). The mechanism of this
reaction involved the formation of benzylic and aliphatic
radicals and an R−Ni(I) intermediate, and the substance scope
MgCl even suppressed the reaction totally. LiBr was also
2
investigated and less effective than LiCl. The addition of LiCl
may facilitate the carboxylation by accelerating the reduction of
1
2
15
has limitations. Although Ni-catalyzed C−H functionaliza-
Ni(II). The desired product was produced in 87% yield
13
tion reactions have been extensively reported, to the best of
our knowledge, Ni-catalyzed direct carboxylation of unac-
when the temperature was decreased to 100 °C (see Table S1,
entry 21). In addition, product 2a was obtained in 85%
isolated yield with 10 mol % catalyst loading (Table 1, entry
14). Notably, product 2a was detected in only a trace amount
tivated C−H bonds with CO remains unreported. Herein, we
2
report for the first time a Ni-catalyzed direct carboxylation of
unactivated C−H bonds of indole, benzothiophene, benzofur-
in the absence of NiCl with recovery of 1a in 95% yield
2
an, and benzene under an atmospheric pressure of CO . The
(Table 1, entry 15), which revealed that the nickel catalyst is
essential. Other solvents, reductants, and bases were also
2
carboxylation products, especially indole-2-carboxylic acids,
t
and their derivatives are ubiquitous structural motifs in
screened (see Table S1), and DMF, Mn, and KO Bu were the
14
pharmaceuticals and natural products.
best combination, giving an 85% isolated yield.
Our initial attempt was conducted by employing N-quinolyl
-methylindole-3-carboxamide (1a) as a model substrate under
With the established optimal reaction conditions in hand,
the scope of this reaction was investigated (Scheme 2). When
indoles possess an electron-donating or electron-withdrawing
group at the C-5 position, such as alkyl (-Me), alkoxy (-OMe),
1
an atmospheric pressure of CO in the presence of NiCl (20
2
2
t
mol %) with KO Bu (2.0 equiv) as the base and Mn (3.0
equiv) as the reductant in DMF for 24 h; the desired C-2
carboxylation product 2a was obtained in 50% isolated yield
trifluoromethyl (-CF ), and fluoro (-F) groups, the carbox-
3
ylation proceeded smoothly to afford desired products 2b−2e,
(
Table 1, entry 1). Different ligands, including bipyridines and
phenanthrolines, were screened first (Table 1, entries 2−5, and
Table S1, see the Supporting Information for details). 4,7-
Diphenyl-1,10-phenanthroline (L6) proved to be the most
Scheme 2. Substrate Scope of Ni-Catalyzed C−H
b
Carboxylation
a
Table 1. Optimization of Reaction Conditions
entry
Ni catalyst
L
additive
yield (%)
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
NiCl2
NiCl2
NiCl2
NiCl2
NiCl2
NiBr2
NiI2
Ni(COD)2
Ni(OTf)2
NiCl2
NiCl2
NiCl2
NiCl2
NiCl2
−
−
−
−
−
−
−
−
−
−
50
56
46
58
63
60
57
62
15
84
0
L1
L2
L3
L6
L6
L6
L6
L6
L6
L6
L6
L6
L6
L6
−
0
1
2
3
4
5
LiCl
MgCl2
KCl
LiBr
LiCl
LiCl
62
79
85
trace
b
b
a
a
b
Reaction conditions: 1a (0.2 mmol), Ni catalyst (20 mol %), L (40
2g′ as the substrate. Reaction conditions: 1a (0.2 mmol), NiCl (10
2
t
t
mol %), KO Bu (2.0 equiv), Mn (3.0 equiv), additive (1.0 equiv),
DMF (2.0 mL) at 130 °C for 24 h. The isolated yield is given. At
1
mol %), L6 (20 mol %), KO Bu (2.0 equiv), Mn (3.0 equiv), LiCl
(1.0 equiv), DMF (2.0 mL) at 100 °C for 24 h. The isolated yield is
given.
b
00 °C. Ni catalyst (10 mmol %), L (20 mmol %).
B
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Letter
respectively, in 70−86% yields. However, when chloro (-Cl) or
bromo (-Br) was introduced at the C-5 position of indole,
desired products 2f (30%) and 2g (8%) were obtained in low
yields. Meanwhile, two byproducts, including 5-carboxylation
atmospheric pressure of CO at position 2, but this is a two-
step reaction. The first step is the deprotonative alumination
2
with a mixed alkyl amido lithium aluminate compound
i
Bu Al(TMP)Li. The second step is the NHC copper-catalyzed
3
19c
(
1
2g′) and 2,5-dicarboxylation (2g″) products, were isolated in
carboxylation of the resulting arylaluminum species. There-
fore, our work provides an efficient direct C2−H carboxylation
strategy for indole and benzothiophene derivatives.
8% and 32% yields, respectively, indicating the presence of
C−Br carboxylation as a competition reaction. When an ester
group was introduced at the C-5 position (2g′), desired
product 2g″ was obtained in 65% yield. Indoles with a
substituent at the ortho position gave the desired products in
slightly low yields (2h, 63%; 2i, 45%), possibly due to the
steric hindrance. Various functional groups at the C-6 and C-7
positions of indole were well tolerated, affording the desired
products 2j−2l and 2n−2p, respectively, in 64−94% yields.
The low yield of 2m (24%) is also due to the presence of C−
Cl carboxylation. However, when a vinyl group was introduced
at the C-6 position of indole, no reaction was detected,
probably because the vinyl group can coordinate with nickel
and suppress the carboxylation. The N-protecting groups of
indole were next examined. Without the N-protecting group,
no carboxylation was observed (2q). N-MOM- or N-Bn-
protected indole afforded corresponding carboxylation product
To better clarify the reaction mechanism, some preliminary
studies were carried out. First, a H/D scrambling experiment
was conducted. Reaction of 1a with D O with a Ni catalyst
2
under Ar instead of CO2 afforded [2-D]-1a with 96%
deuteration (Scheme 4a), indicating that C−H activation
Scheme 4. Preliminary Mechanistic Studies
2r or 2s in 87% or 55% yield, respectively. In addition to
indoles, other nitrogen-, oxygen-, and sulfur-containing hetero-
cycles could also undergo direct carboxylation in 34−81%
yields (2t−2x, respectively). It seems that the fused aromatic
substrates may facilitate the carboxylation. When benzamide
with more inert C−H bonds was employed as a substrate, the
corresponding product 2y was obtained in 51% yield under
standard conditions.
To demonstrate the synthetic potential of this method, a
gram-scale reaction was conducted and product 2a was
obtained in 71% yield. Furthermore, the 8-aminoquinoline
directing group could be easily removed by using IBX as an
16
oxidant under mild conditions to give the primary amide 3l
in 78% yield (Scheme 3).
Scheme 3. Gram-Scale Synthesis and Removal of the
Directing Group
was reversible. Second, parallel kinetic experiments with 1a or
[
2-D]-1a (96% D) with CO and a competition experiment
2
between 1a and [N-CD -2-D]-1a were performed, and k /k
3
H
D
values of 1.25 and 1.54 were obtained, respectively (Scheme
4
b), suggesting that the C−H bond cleavage may not be
involved in the rate-limiting step. Meanwhile, intermolecular
competition experiments between 5-CF - and 5-OMe-sub-
3
stituted indoles were conducted. The corresponding carbox-
ylation products were obtained in a ratio of 1:0.25 (Scheme
4
c), revealing that the electron-deficient substrate (1f) has
There are several reports of acid- or base-promoted C−H
better reactivity.
19
carboxylation of indole and benzothiophene. The Lewis acid
When Ni(cod) was used instead of NiCl under standard
2
2
Me AlCl-mediated C−H carboxylation of indole involved the
conditions, the carboxylation product was obtained in 82%
yield (Scheme 5a), indicating that Ni(0) may be the
catalytically active species. When the N−H group of the
substrate was protected with methyl (1z), no product was
observed (Scheme 5b), indicating that the N−H bond in the
bidentate directing group also played an important role. The
isolation of the cyclonickel intermediate in the reaction was
tried, but many attempts failed. Fortunately, when the catalyst
loading was increased to 40 mol % and the reaction was
stopped at 4 h under the standard conditions, the cyclo-
2
electrophilic substitution of indole to form indolylaluminum
species, which then reacted with CO to form aluminum
2
carboxylate. The carboxylation of indole occurred at position 3,
and a high pressure (3.0 MPa) is needed to shift the reversible
19a
t
equilibrium to the carboxylation direction. LiO Bu-mediated
C−H carboxylation of indole could occur at position 3 with an
atmospheric pressure of CO but only limited to the
2
19b
unprotected indole. Copper-catalyzed formal C−H carbox-
ylation of indole and benzothiophene occurred with an
C
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Scheme 5. Control Experiments and Intermediate Studies
is activated via σ-bond metathesis, providing cyclometalated
Ni(II) intermediate B (detected by HRMS). The detection of
H2 by gas chromatography during the reaction (see the
Supporting Information) supported this process. Reduction of
B by Mn via SET reaction forms Ni(I) species C, which can
occur via a proton exchange with substrate 1a to produce
intermediate INT 1 (detected by HRMS). Then CO is
2
inserted into the C−Ni(I) bond to produce carboxylate Ni(I)
intermediate D, which also can occur via a proton exchange to
produce intermediate INT 2 (detected by HRMS). Finally, D
is reduced to Ni(0) by Mn for the next catalytic cycle.
Meanwhile, lithium salts of carboxylate and amide anion are
formed in the presence of LiCl and further acidified and
t
reacted with TMSCHN to afford product 2a. KO Bu played a
2
vague but indispensable role in the catalytic cycle (see Table
S1, entries 18−20). It may facilitate the insertion of CO into
2
t
the C−Ni(I) bond because CO might react with KO Bu to
2
t
9b,e,f
generate BuOCO K, which is more active than CO .
use of an excess of KO Bu may also suppress the undesired
The
2
2
t
19b
decarboxylation side reaction.
In summary, we developed the first Ni-catalyzed direct
carboxylation of the unactivated C−H bond of indoles using
an 8-aminoquinoline auxiliary under an atmospheric pressure
of CO . Various methyl carboxylates were accessed easily. This
2
straightforward and novel carboxylation strategy will provide a
new approach to CO fixation. Further exploration of this
2
reaction with other types of substrates and the capture of
reaction intermediates are being carried out in our laboratory.
metalated Ni(II) complex (B) and Ni(I) intermediates INT 1
and INT 2 were detected by HRMS (Scheme 5c). The
electron paramagnetic resonance experiment (see the Support-
ing Information for details) was also conducted, but only the
ASSOCIATED CONTENT
sı Supporting Information
■
*
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.0c02429.
2
+
signal of Mn was detected. The signal of Ni(I) may be
2+
covered by the strong signal of Mn .
Experimental details, optimization studies, and charac-
terization data (PDF)
On the basis of our preliminary investigations and previous
17
reports on Ni-catalyzed C−H bond activation and reductive
1
1
carboxylation of organic (pseudo)halides with CO ,
a
2
Accession Codes
plausible mechanistic pathway via a Ni(0)−Ni(II)−Ni(I)
catalytic cycle was postulated (Scheme 6). First, a catalytically
active Ni(0) species is formed in situ by the reduction of NiCl2
with Mn. Then, the pyridine nitrogen of amide 1a coordinates
to Ni(0) and promotes the oxidative addition of an N−H bond
to afford nickel hydride intermediate A. The ortho-C−H bond
CCDC 1977331 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
via www.ccdc.cam.ac.uk/data_request/cif, or by emailing
data_request@ccdc.cam.ac.uk, or by contacting The Cam-
bridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
Scheme 6. Proposed Mechanistic Pathway
AUTHOR INFORMATION
■
Corresponding Author
Baiquan Wang − State Key Laboratory of Elemento-Organic
Chemistry, College of Chemistry, Nankai University, Tianjin
3
00071, People’s Republic of China; State Key Laboratory of
Organometallic Chemistry, Shanghai Institute of Organic
Chemistry, Chinese Academy of Sciences, Shanghai 200032,
People’s Republic of China; orcid.org/0000-0003-4605-
1
607; Email: bqwang@nankai.edu.cn
Authors
Chunzhe Pei − State Key Laboratory of Elemento-Organic
Chemistry, College of Chemistry, Nankai University, Tianjin
00071, People’s Republic of China
3
Jiarui Zong − State Key Laboratory of Elemento-Organic
Chemistry, College of Chemistry, Nankai University, Tianjin
3
00071, People’s Republic of China
D
https://dx.doi.org/10.1021/acs.orglett.0c02429
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Letter
Shanglin Han − State Key Laboratory of Elemento-Organic
Catalytic Functionalization II; Springer, 2016. (c) Rouquet, G.;
Chatani, N. Catalytic Functionalization of C(sp )−H and C(sp )−
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2
3
Chemistry, College of Chemistry, Nankai University, Tianjin
3
00071, People’s Republic of China
2013, 52, 11726−11743. (d) Yang, L.; Huang, H. Transition-Metal-
Bin Li − State Key Laboratory of Elemento-Organic Chemistry,
College of Chemistry, Nankai University, Tianjin 300071,
People’s Republic of China; orcid.org/0000-0003-3909-
Catalyzed Direct Addition of Unactivated C−H Bonds to Polar
Unsaturated Bonds. Chem. Rev. 2015, 115, 3468−3571. (e) Hummel,
J. R.; Boerth, J. A.; Ellman, J. A. Transition-Metal-Catalyzed C−H
Bond Addition to Carbonyls, Imines, and Related Polarized π Bonds.
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3
796
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.0c02429
(6) (a) Fukue, Y.; Oi, S.; Inoue, Y. Direct Synthesis of Alkyl 2-
Alkynoates from Alk-l-ynes, CO , and Bromoalkanes Catalysed by
2
Copper(I) or Silver(I) salt. J. Chem. Soc., Chem. Commun. 1994, 2091.
Notes
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using N-Heterocyclic Carbene Gold(I) Complexes. J. Am. Chem. Soc.
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The authors declare no competing financial interest.
2
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using N-Heterocyclic Carbene Copper(I) Complexes. Angew. Chem.,
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ACKNOWLEDGMENTS
■
The authors thank the National Natural Science Foundation of
China for financial support (21871151 and 21672108).
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