Co(II)-Catalyzed Regioselective Cross-Dehydrogenative Coupling of Aryl C-H Bonds with Carboxylic Acids

Article abstract of DOI:10.1021/acs.orglett.7b01942

A cobalt(II)-catalyzed regioselective aryl C-H bond oxygenation between arenes and aryl or aliphatic carboxylic acids under bidendate-chelation assistance is developed. This method provides an efficient approach to acyoxy-substituted arenes with a broad range of functional group tolerance. Furthermore, this reaction system could be further applied to the preparation of polyfunctional naphthylenes.

Full text of DOI:10.1021/acs.orglett.7b01942

Letter
pubs.acs.org/OrgLett
Co(II)-Catalyzed Regioselective Cross-Dehydrogenative Coupling of
Aryl C−H Bonds with Carboxylic Acids
Jianyong Lan,† Haisheng Xie,† Xiaoxia Lu,‡ Yuanfu Deng,† Huanfeng Jiang,† and Wei Zeng*,†
†Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of Chemistry and Chemical Engineering,
South China University of Technology, Guangzhou 510641, China
‡Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, China
S
* Supporting Information
ABSTRACT: A cobalt(II)-catalyzed regioselective aryl C−H bond oxygenation between arenes and aryl or aliphatic carboxylic
acids under bidendate-chelation assistance is developed. This method provides an efficient approach to acyoxy-substituted arenes
with a broad range of functional group tolerance. Furthermore, this reaction system could be further applied to the preparation of
polyfunctional naphthylenes.
ryl esters are commonly encountered in pharmaceutical
molecules, natural products, and synthetic intermediates.1
Recently, much attention has been turned to developing
catalysts of earth-abundant first row transition metals due to its
low cost and environmental benignity. Particularly for the
cobalt catalysts, the existing examples of C−H functionalization
demonstrated that a cobalt-based catalytic system could also be
applied to the CDC reaction via a cyclometalation process.7 In
this context, although Glorius,8 Song,9 and Niu10 successively
reported cobalt-catalyzed cross-dehydrogenative coupling re-
actions of aryl C−H bonds with amines, thiols, and alcohols
using different chelating auxilaries, the cobalt-catalyzed CDC
reaction of aryl C−H bonds with acids has not yet been well-
established.11 More recently, we described a cobalt(III)-
catalyzed [4 + 1] cycloaddition of 2-arylpyridines with
aldehydes through aryl C−H activation, in which cobalt
catalysts play a dual role as a metal catalyst and Lewis acid.12
To further expand the catalytic versatility of cobalt catalysts in
organic transformations, herein we report a novel Co(II)-
catalyzed CDC reaction of aryl C−H bonds with acids via
bidentate-chelation assistance, in which the substrate scope of
acids could be further extended to both aryl and aliphatic acids
(Scheme 1b).
A
The traditional synthetic methodologies for these compounds
relied on cross-coupling reactions of arenols or arylsilicons with
carbonyl compounds.2 In comparison, a transition-metal-
catalyzed cross-dehydrogenative coupling (CDC) strategy
provides an atom- and step-economic platform to assemble
aryl esters.3 In this regard, heteroatom-containing directing
groups have been identified as versatile auxiliaries to enable the
CDC reaction of aryl C−H bonds with acids. To date,
Ackermann,4 Cheng,5 and Zhou6 reported that sulfoximine and
pyridine groups could efficiently enhance the CDC reaction of
arenes with acids via a C−H activation process in the presence
of Rh and Ru catalysts (Scheme 1a), respectively. Unfortu-
nately, these transformations have been limited to noble
transition metals and aryl carboxylic acids. Therefore,
developing inexpensive metal-catalyzed C−H oxygenations
with a broad substrate scope is desired.
Scheme 1. Transition-Metal-Catalyzed CDC of Aryl C−H
Bonds with Acids
Innitially, the cobalt-catalyzed CDC reaction of 1-acylamido-
substituted naphthalene (1a, 0.10 mmol) with benzoic acid (2a,
0.15 mmol) was performed by employing AgOAc (2.0 equiv)
as an oxidant in the presence of NaHCO3 (2.0 equiv) in
toluene (2.0 mL) at 120 °C under an Ar atmosphere for 12 h.
Among a variety of cobalt catalysts, inexpensive Co(OAc)2
proved to be the most effective for installing a benzoxyl group
into the 8-position of naphthalen-1-ylamine 1a and furnished
Received: June 25, 2017
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.7b01942
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Letter
a b
,
the desired aryl ester 3a in 52% yield (compare Table 1 entries
1−4 with 5). In contrast, other transition metal catalysts such as
Scheme 2. Substrate Scope
a
Table 1. Optimization of the Reaction Parameters
b
entry
catalysts
oxidant
base
yield (%)
1
Co(acac)2
CoCl2
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
Cu(OAc)2
MnO2
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaOAc
44
35
24
45
52
0
2
3
CoSO4·7H2O
Co(acac)3
Co(OAc)2
Pd(OAc)2
RuCl3
4
5
6
7
0
8
Cu(OAc)2
[Cp*RhCl2]2
Co(OAc)2
Co(OAc)2
Co(OAc)2
Co(OAc)2
Co(OAc)2
Co(OAc)2
Co(OAc)2
Co(OAc)2
Co(OAc)2
Co(OAc)2
Co(OAc)2
<5
0
9
10
11
12
13
14
15
16
17
18
19
20
35
0
O2
0
K2S2O8
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
0
73
71
76
83
K2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
c
62
d
48
e
43
a
Unless otherwise noted, all the reactions were carried out using
pyridine-2-carboxylic acid naphthalen-1-ylamide (1a) (0.10 mmol)
and benzoic acid (2a, 0.15 mmol) with cobalt catalysts (10 mol %) in
the presence of oxidant (2.0 equiv) and base (2.0 equiv) in toluene
(2.0 mL) at 120 °C for 12 h under Ar in a sealed reaction tube.
b
c
Followed by flash chromatography on SiO2. Isolated yield. DCE was
a
d
e
All the reactions were carried out using N-naphthyl-2-pyridylcarbox-
amides or N-benzyl-2-pyridylcarboxamides (1) (0.10 mmol) and
carboxylic acids (2, 0.15 mmol) with Co(OAc)2 catalysts (10 mol %)
in the presence of Ag2CO3 (2.0 equiv) and Na2CO3 (2.0 equiv) in
toluene (2.0 mL) at 120 °C for 12 h under Ar in a sealed reaction tube.
used as solvent. 1,4-Dioxane was used as solvent. The reaction
temperature was 100 °C.
Pd(OAc)2, RuCl3, Cu(OAc)2, and [Cp*RhCl2]2 could not
enable this transformation (entries 6−9). Subsequently, we
employed Co(OAc)2 as catalysts, switched the AgOAc oxidant
to other oxidants, and soon found that Ag2CO3 could
significantly increase the yield of 3a from 52% to 73%
(compare entries 10−13 with 14). Except Ag2CO3, AgOAc, and
Cu(OAc)2, the other oxidants including MnO2, O2, and K2S2O8
were not effective at all (entries 11−13). Moreover, we also
continued to evaluate the effect of bases on this CDC reaction
of 1-acylamido-substituted naphthalene 1a with benzoic acid
2a, and Na2CO3 was found to be a suitable base which could
further improve the yield of 3a from 73% to 83% (compare
entries 14−16 with 17). It should be noted that utilization of
other solvents or changing the reaction temperature did not
favor this transformation (entries 18−20).
With the optimized catalytic system in hand, we then
examined its versatility in the cross-dehydrogenative coupling
between pyridine-2-carboxylic acid naphthalen-1-ylamide (1a)
and various carboxylic acids (2). As summarized in Scheme 2,
the aryl C−H bond oxygenations are successful for both
electron-rich (3b−3f) and electron-poor (3g−3l) aryl carbox-
ylic acids. Among them, ortho- or meta- or para-alkyl-
substituted benzoic acids could afford 42−66% yields of aryl
b
Followed by flash chromatography on SiO2. Isolated yield.
esters (3b−3e), and 2- or 4-halobenzoic acids could also lead to
42−85% yields of the cross-coupling products (3g−3j).
Particularly, 4-trifluoromethylbenzoic acid and 4-cynobenzoic
acids could still exhibit excellent reactivity with 79% and 92%
yields for 3k and 3l, respectively. Most importantly, aliphatic
acids and thiophene-2-carboxylic acid are also reactive, thus
showing the broad compatibility of the reaction conditions
(3m−3o). The structure of 3o was already unambiguously
assigned by its single crystal X-ray analysis.13 It should be noted
that 4-alkoxybenzoic acid could not be converted into the
corresponding arylester 3f possibly due to the stonger electron-
donating methoxyl group improving the pKa value of aryl acid
and decreasing its reactivity.
Subsequently, we further investigated the effect of the
substituted pyridine ring from N-(1-naphthyl)-2-pyridyl
carboxamides on this transformation. It was found that the
ortho-Csp2−H bond oxygenation was obviously dependent on
the electronic properties of substituents at the 3- or 4-position
of the pyridine ring. For examples, 3-methyl-2-pyridyl
B
DOI: 10.1021/acs.orglett.7b01942
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Letter
carboxamide and 4-halo-2-pyridyl carboxamides could be
effectively converted to the desired aryl esters (3q−3r) in
60−75% yields, but 4-nitro-2-pyridyl carboxamide could not
tolerate this reaction system (3s), and quinoline-2-carboxylic
acid naphthalen-1-ylamide only afforded a 25% yield of aryl C−
H oxygenation product (3t). In comparsion, the effect of the
substituted naphthalene moiety from carboxamides in this
transformation indicated that 1-carboxamido-4-or 5-substituted
naphthalenes could all furnish moderate to good yields of aryl
esters 3u−3z, regardless of whether electron-deficient or -rich
substituents were introduced into the 4- or 5-position of the
naphthalene ring. Gratifyingly, the aryl C−H oxygenation could
still be extended to N-benzyl substituted 2-pyridyl carbox-
amides, providing the corresponding phenyl esters 3z-1 and 3z-
2 in acceptable yields. Unfortunately, N-phenyl-pyridine-2-
carboxylic acid amide did not give the desired Csp2−H
oxygenation product 3z-3.
Scheme 4. Preliminary Mechanistic Studies
The synthetic utility of the cobalt(II)-catalyzed regioselective
aryl C−H bond oxygenation by means of pyridyl assistance was
performed for the postsynthetic diversification of naphthyl ester
3a (Scheme 3). As we know, different types of aryl esters could
= 1.60) further indicated that Csp2−H bond-breaking was
possibly involved in the rate-limiting step of this reaction
(Scheme 4e) (see Supporting Information (SI) for more
details).
Scheme 3. Synthetic Application for This Transformation
On the basis of the above-mentioned results and previous
reports,17 a plausible mechanism is proposed in Scheme 5.
Scheme 5. Proposed Mechanism
be widely used to assemble complex molecules in synthetic
chemistry. We therefore continued to employ a pyridyl ring as a
directing group to regioselectively install an amino group at the
7-position of the 1,8-disubstituted naphthalene ring of ester 3a
in 51% yield under a Cu(OAc)2 catalytic system.14 This
method could conveniently produce 1-acyloxy-7,8-diamino-
substituted naphthalene 3a-1 in 52% yields. Of course, benzoic
acid 8-[(pyridine-2-carbonyl)amino]naphthalen-1-yl ester (3a)
could be easily converted into N-(8-hydroxynaphthalen-1-
yl)benzamide (3a-2, 81% yield) in the presence of NaOH, in
which the pyridine moiety was also replaced by the phenyl
group (Scheme 3).
Several control experiments were carried out to gain some
insight into the possible mechanism (Scheme 4). Initially, the
Co(II)-catalyzed CDC reaction of N-naphthalen-1-yl-benza-
mide (1p) and acetic acid (2m) was performed under the
standard reaction conditions, no desired aryl C−H oxygenation
product 4a was formed (Scheme 4a). This experiment
demonstrated that pyridine “N” plays a key role in chelation
assistance. Also, a Co(OAc)2-promoted CDC reaction without
the presence of Ag2CO3 suggested that the active Co(III)
species was possibly involved in this aryl C−H oxygenation
(Scheme 4b). It was still found that the addition of the typical
radical scavergers including TEMPO, 1,1-diphenylethene, and
p-benzoquinone (BQ) (2.0 equiv) did not significantly reduce
the yields of this reaction15 (Scheme 4c), implying that a radical
mechanism should not be ruled out. In addition, the H/D
exchange experiment of carboxamide 1a in the absence of acids
showed that no deuterium incorporation occurred, which
suggested that the transformation perhaps proceeded through
an irreversible cyclometalation pathway (Scheme 4d).16 Finally,
the kinetic isotope effect (KIE) has been determined through
parallel experiments, and the corresponding KIE value (kH/kD
First, treatment of Co(OAc)2 with Ag2CO3 produces an active
cobalt(III) catalyst (CoX3).17b,18 Then, pyridyl N- and amide
N-coordination of substrate 1a to Co(III) species followed by
naphthyl Csp2−H bond activation affords a bis-chelated
metallacyclic Co(III) complex B via a concerted metalation/
deprotonation process. Subsequently, the ligand-exchange
process between benzoic acid 2a and Co(III) complex B
gives the intermediate C, which further undergoes reductive
elimination to yield the corresponding naphthyl ester 3a and
generates the Co(I) salts. The oxidation of Co(I) to Co(III) by
oxidant Ag2CO3 continues the catalytic cycles.
In conclusion, we have developed an efficient and convenient
approach for aryl Csp2−H bond oxygenation of naphthylalenes
with aryl and aliphatic acids employing inexpensive Co(OAc)2
as the catalyst. This transformation could proceed smoothly
under bidendate-chelation assistance to regioselectively assem-
ble acyoxy-substituted naphthylenes. These naphthyl esters
could be further converted to more complex naphthylene
analogues.
C
DOI: 10.1021/acs.orglett.7b01942
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
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ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.7b01942.
■
S
(9) (a) Zhang, L.-B.; Zhang, S.-K.; Wei, D.; Zhu, X.; Hao, X.-Q.; Su,
J.-H.; Niu, J.-L.; Song, M.-P. Org. Lett. 2016, 18, 1318. (b) Zhang, L.-
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(10) Guo, X.-K.; Zhang, L.-B.; Wei, D.; Niu, J.-L. Chem. Sci. 2015, 6,
7059.
Detailed experimental procedures, characterization data,
copies of 1H NMR and 13C NMR spectra for all isolated
compounds (PDF)
Crystallographic data for 3o (CIF)
(11) Kochi, J. K.; Tang, R. T.; Bernath, T. J. Am. Chem. Soc. 1973, 95,
7114.
(12) Chen, X.; Hu, X. W.; Deng, Y.; Jiang, H. F.; Zeng, W. Org. Lett.
2016, 18, 4742.
(13) See SI for the single crystal structure and data of 3o.
(14) Li, Q.; Zhang, S.-Y.; He, G.; Ai, Z.; Nack, W. A.; Chen, G. Org.
Lett. 2014, 16, 1764.
(15) When the radical scavenger 2,6-di-tert-butyl-4-methylphenol
(BHT) was used, no desired 3m was observed by TLC and 1H NMR
methods.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: zengwei@scut.edu.cn.
ORCID
Yuanfu Deng: 0000-0002-2460-7224
Huanfeng Jiang: 0000-0002-4355-0294
Wei Zeng: 0000-0002-6113-2459
Notes
(16) (a) Sen, M.; Emayavaramban, B.; Barsu, N.; Premkumar, J. R.;
Sundararaju, B. ACS Catal. 2016, 6, 2792. (b) Ma, W.; Ackermann, L.
ACS Catal. 2015, 5, 2822.
The authors declare no competing financial interest.
(17) (a) Ma, W.; Ackermann, L. ACS Catal. 2015, 5, 2822. (b) Zhu,
X.; Su, J.-H.; Du, C.; Wang, Z.-L.; Ren, C.-J.; Niu, J.-L.; Song, M.-P.
Org. Lett. 2017, 19, 596. (c) Zaitsev, V. G.; Shabashov, D.; Daugulis,
O. J. Am. Chem. Soc. 2005, 127, 13154. (d) Daugulis, O.; Roane, J.;
Tran, L. D. Acc. Chem. Res. 2015, 48, 1053. (e) Rouquet, G.; Chatani,
N. Angew. Chem., Int. Ed. 2013, 52, 11726.
ACKNOWLEDGMENTS
■
The authors thank the National Key Research and Develop-
ment Program of China (No. 2016YFA0602900), NSFC (No.
21372085), and Science and Technology Service Network
Initiative of Chinese Academy of Sciences (No. KFJ-SW-STS-
143-1) for financial support.
(18) Ni, J.; Li, J.; Fan, Z.; Zhang, A. Org. Lett. 2016, 18, 5960.
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