Cobalt(II)-Catalyzed Acyloxylation of C-H Bonds in Aromatic Amides with Carboxylic Acids

Article abstract of DOI:10.1021/acs.orglett.7b04020

The cobalt(II)-catalyzed acyloxylation of C-H bonds in aromatic amides containing an 8-aminoquinoline moiety as the directing group with carboxylic acids is reported. Various carboxylic acids including aromatic and aliphatic carboxylic acids are applicable to the reaction. The reaction displays a broad substrate scope and high functional group tolerance. The reaction is carried out under air.

Full text of DOI:10.1021/acs.orglett.7b04020

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Cobalt(II)-Catalyzed Acyloxylation of C−H Bonds in Aromatic Amides
with Carboxylic Acids
Rina Ueno, Satoko Natsui, and Naoto Chatani*
Department of Applied Chemistry, Faculty of Engineering, Osaka University, Suita, Osaka 565-0871, Japan
S
* Supporting Information
ABSTRACT: The cobalt(II)-catalyzed acyloxylation of C−H
bonds in aromatic amides containing an 8-aminoquinoline
moiety as the directing group with carboxylic acids is reported.
Various carboxylic acids including aromatic and aliphatic
carboxylic acids are applicable to the reaction. The reaction
displays a broad substrate scope and high functional group
tolerance. The reaction is carried out under air.
ransition-metal-catalyzed C−H functionalization has
Scheme 1. Co(II)-Catalyzed C−H Acyloxylation of
T
received increasing attention in organic synthesis because
Aromatic Amides with Carboxylic Acids
of its step- and atom-economy advantages, environmental
friendliness, and the fact that prefunctionalized substrates are
not needed.1 The efficiency and scope of C−H functionaliza-
tion reactions at the ortho-position of arenes has been
substantially improved in the past decades. One of the most
powerful and reliable methods for the functionalization of C−
H bonds at the ortho-position involves chelation assistance by
a directing group. New types of chelation systems have been
developed that now permit the characteristic functionalization
of C−H bonds. One such example involves the use of an
N,N′-bidentate chelation system.2 Although noble metals, such
as Pd, Rh, Ir, Pt, and Ru, are typically used as catalysts in
chelation-assisted C−H functionalization, the use of first-row
transition metals,3 such as Fe,4 Co,5 Ni,6 and Cu,7 has also
received much interest because these metals are earth
abundant and therefore less expensive than noble metals. It
is particularly noteworthy that air-stable and inexpensive
Co(II) complexes have been recognized as efficient catalysts
for C−H functionalization due to their unique catalytic
activity. In fact, Co(II) catalysts, such as Co(OAc)2 and
Co(acac)2, have been extensively used in 8-aminoquinoline
chelation-assisted C−H functionalization reactions in recent
years.2g,8 While a wide variety of Co(II)-catalyzed C−H
functionalization reactions exist in which the N,N′-bidentate
directing group has been developed thus far, most involve C−
C bond formation, such as alkylation, allylation, arylation,
alkenylation, alkynylation, and carbonylation. Despite the
success of C−H amination or amidation methods,9 the
formation of a C−O bond with the cleavage of C−H bonds
in the Co(II) catalyst/8-aminoquinoline chelation system
remains undeveloped.10,11 We herein report the Co(II)-
catalyzed acyloxylation of C−H bonds in aromatic amides
with carboxylic acids by taking advantage of an 8-amino-
quinoline chelation system (Scheme 1).12,13
mmol) as an oxidant in 1,2-dichloroethane (DCE) (0.5 mL)
at 100 °C for 3 h under an atmosphere of air resulted in C−
H acyloxylation to give the benzoxylation product 3aa in 77%
NMR yield, along with 7% of 1a being recovered (entry 1 in
Table 1). A trace amount of dimerization product 4a14 was
1
also observed in the H NMR spectrum of the crude reaction
mixture (entry 1). Increasing the reaction temperature failed
to improve the product yield (entry 2). The use of
Co(OAc)2·4H2O as the catalyst resulted in a dramatic
decrease in the product yield (entry 3). When 0.20 mmol
of Ag2CO3 was used, 1a was completely consumed, and the
isolated product yield of 3aa was increased to 78% and no
dimerization product 4a was detected (entry 4). The use of
1.5 equiv of 2a gave 3aa in 84% isolated yield (entry 5).
When 0.3 mmol of Ag2CO3 was used, the yield was essentially
the same as that obtained when 0.2 mmol was used (entry 6).
Among the solvents examined, DCE gave the best results
(entries 7−9). The use of toluene as a solvent also gave good
yield of the product when 2,6-dimethylbenzoic acid was used
as a carboxylic acid. However, lower yields were frequently
observed when other carboxylic acids were used, as a coupling
partner. Gratifyingly, it was found that the use of 10 mol % of
Co(acac)2 gives 3aa in 80%, which is comparable to that
obtained in the reaction with 10 mol % catalyst (entry 10).
Finally, the use of 1a (0.15 mmol), 2a (0.225 mmol),
Co(acac)2 (10 mol %), and Ag2CO3 (0.20 mmol) in DCE
The reaction of amide 1a (0.15 mmol) with 2,6-
dimethylbenzoic acid (2a) (0.15 mmol) in the presence of
Co(acac)2 (0.06 mmol) as the catalyst and Ag2CO3 (0.15
Received: December 26, 2017
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.7b04020
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Table 1. Optimization of Reaction Conditions
Scheme 2. Co(II)-Catalyzed C−H Acyloxylation of
Aromatic Amide 1a with Various Carboxylic Acids 2
a
a
Yields were determined by 1H NMR. The value in parentheses is the
isolated yield.
a
b
Products were isolated by column chromatography. The reaction
c
was carried out on a 1 mmol scale. Co(acac)2 (20 mol %) was used.
d
NMR yield.
(0.5 mL) under air was chosen as the standard reaction
conditions (entry 10).
With the optimized reaction conditions in hand, the scope
of the reaction with respect to carboxylic acids was examined
(Scheme 2). A wide variety of carboxylic acids, including
aromatic and aliphatic acids, was found to be applicable to the
present C−H acyloxylation. The reaction was affected by the
steric nature of the carboxylic acid used. The product yields
increased with increasing bulkiness of the carboxylic acid (3aa
> 3ab > 3ac). In contrast, the electronic nature of a
substituent on a benzene ring had only a marginal effect on
the efficiency of the reaction (3ae ≈ 3af ≈ 3ag). A bromide
was tolerated in the reaction. Aliphatic carboxylic acids, such
as pivalic acid, cyclohexancarboxylic acid, and acetic acid, also
react to give the corresponding products 3aj−al. However,
acetic acid was less reactive and 20 mol % of Co(acac)2 was
required to obtain a reasonably good product yield.
To examine the scope of the aromatic amides, we chose 2a
as a standard carboxylic acid (Scheme 3). Moderate to
excellent yields were obtained, and aromatic amides
containing a substituent at the ortho-position gave higher
yields. In the reaction of the m-methoxy-substituted substrate
1i, the reaction proceeded only at the less hindered C−H
bonds to give the corresponding product 3ia in 43% yield. In
the cases of o-methyl-m-bromobenzoic amide 1k, the
corresponding product 3ka was formed, while the C−H
bond is sterically congested. Although the reaction of
thiophenecarboxamide 1o afforded the corresponding product
3oa in good yield, furancarboxamide failed to react. The
reaction was not applicable to the acyloxylation of C(sp3)−H
bond in 1p, and the substrate was recovered in 91% yield.
Some mechanistic studies were conducted to gain insight
into the reaction mechanism. The reaction was not inhibited
when (2,2,6,6-tetramethylpiperidin-1-yl)oxy (TEMPO) was
added to the reaction mixture, indicating that a free radical
is not involved in this reaction (Scheme 4a). The deuterated
amide 1a-d7 was reacted with 2a under the standard
conditions for 30 min. No proton atoms were incorporated
into unreacted starting amide 1a-d7 (Scheme 4b). Notably, no
H/D exchange was observed, even in the absence of 2a
(reaction scheme not shown). These experimental results
indicate that C−H bond cleavage is an irreversible step in the
present system, as is often observed in the Co(II)-catalyzed,
aminoquinoline-directed C−H functionalization reactions.2g
We next conducted competitive experiments to detect a
possible kinetic isotopic effect; in this regard, two parallel
experiments were carried out using 1a and 1a-d7 under
standard reaction conditions for 30 min. The result revealed a
KIE of 1.84, indicating that C−H bond cleavage is not the
rate-determining step (reaction scheme not shown).
A proposed mechanism for the reaction is shown in
Scheme 5. The reaction of amide 1 with Co(II) gives the
amide-coordinated Co(II) species I, which is oxidized by
Ag(I) to generate the Co(III) species II.15 Cleavage of the
ortho C−H bonds in II through a CMD process results in the
formation of the cobaltacycle III.16 The reaction of III with
the carboxylic acid 2 gives the Co(III)species IV, which
undergoes reductive elimination, protonation, and oxidation
by Ag(I) to afford 3 with Co(II) being regenerated.
B
DOI: 10.1021/acs.orglett.7b04020
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Scheme 3. Co(II)-Catalyzed C−H Acyloxylation of
Scheme 5. Proposed Mechanism
a
Aromatic Amides 1 with Carboxylic Acid 2a
use of stable and inexpensive Co(acac)2 as the catalyst and
carried out under air.
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.7b04020.
a
b
Products were isolated by column chromatography. Co(acac)2 (40
c
d
mol %) was used. Co(acac)2 (20 mol %) was used. Ag2(Co)3 (0.30
mol %) was used. Diacycloxylation products were formed in 32%.
e
Experimental procedures and characterizations of new
compounds (PDF)
Scheme 4. Mechanic Studies
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: chatani@chem.eng.osaka-u.ac.jp.
ORCID
Naoto Chatani: 0000-0001-8330-7478
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
This work was supported by a Grant in Aid for Specially
Promoted Research by MEXT (17H06091).
■
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DOI: 10.1021/acs.orglett.7b04020
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Letter
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D
DOI: 10.1021/acs.orglett.7b04020
Org. Lett. XXXX, XXX, XXX−XXX