Nitrate promoted mild and versatile Pd-catalysed C(sp2)-H oxidation with carboxylic acids

Article abstract of DOI:10.1039/d0ob01124j

A nitrate-promoted Pd-catalysed mild cross-dehydrogenative C(sp2)-H bond oxidation of oximes or azobenzenes with diverse carboxylic acids has been developed. In contrast to the previous catalytic systems, this protocol features mild conditions (close to room temperature for most cases) and a broad substrate scope (up to 64 examples), thus constituting a versatile method to directly prepare diverse O-aryl esters. Moreover, the superiority of the nitrate additive in this mild transformation was further determined by experimental and computational evidence.

Full text of DOI:10.1039/d0ob01124j

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DOI: 10.1039/D0OB01124J
ARTICLE
Nitrate Promoted Mild and Versatile Pd-catalysed C(sp2)-H
Oxidation with Carboxylic Acids
Received 00th January 20xx,
Accepted 00th January 20xx
Xue Xiong,a Yang-Jie Mao,a Hong-Yan Hao,a Yu-Ting He,a Zhen-Yuan Xu,a Gen Luo,*b Shao-Jie Lou*a
and Dan-Qian Xu*a
DOI: 10.1039/x0xx00000x
A nitrate-promoted Pd-catalysed mild cross-dehydrogenative C(sp2)-H bond oxidation of oximes or azobenzenes with
diverse carboxylic acids has been developed. In contrast to the previous catalytic systems, this protocol features mild
conditions (close to room temperature for most cases) and broad substrate scope (up to 65 examples), thus constituting a
versatile method to prepare diverse O-aryl esters directly. Moreover, the superiority of nitrate additive in this mild
transformation was further determined by the experimental and computational evidence.
a unique nitrate additive could significantly accelerate the
C(sp2)-H bond fluorination of diverse substrates under mild
conditions.6 In particular, nitrate-promoted C(sp2)-H bond
Introduction
O-aryl esters are widely found in medicinal chemistry.1
A
fluorination of oximes and amides even took place at room
temperature.6b,6d A cationic [Pd(NO3)]+ species was proposed
to lower the activation barrier for aromatic C-H bond
metalation. Moreover, a detailed mechanism has revealed that
the poor nucleophilic nitrate additive could also serve as an
anionic ligand, which enables the selective C-F bond reductive
elimination.7,8 In light of our previous work, we envisaged that
a selective C(sp2)-H bond acyloxylation with simple carboxylic
acids in the presence of nitrate additive might render the
transformation under mild conditions. Herein, we report the
preliminary results of this study (Scheme 1b).
variety of synthetic routes have been disclosed to access O-
aryl esters. Among the possible approaches, the direct
formation of O-aryl esters from carboxylic acid with
unactivated aromatics represents one of the most atom-
efficiency ways. Indeed, various catalytic systems using
different transition-metals (Rh, Ru, Pd, Cu, Co, etc.) have been
developed for the rapid synthesis of O-aryl esters (Scheme
1a).2,3,4 However, despite the extensive studies, the
intermolecular CDC (cross-dehydrogenative-coupling) between
carboxylic acid and aromatic C-H bond usually requires high
o
reaction temperature (80-130 C). In this regard, a mild and
versatile method is still attractive and highly demanded for the
sake of broad functional group tolerance.
a) Previous reports: C-O Coupling between C(sp2)-H bond and carboxylic acids
DG
DG
Given the high BDE (bond dissociation energies) of inert C-H
bonds, catalytic C-H bond functionalization usually requires
harsh reaction conditions. Consequently, such transformations
that proceed under mild conditions (e.g. ambient temperature)
would be highly attractive for the organic synthesis.4
Electrophilic cationic palladium catalysts that in-situ generated
from palladium pre-catalyst and anionic additive exhibits
enhanced reactivity and enables C(sp2)-H bond activation at
room temperature. Several additives e.g. CF3COOH, HBF4,
TsOH, were widely used as effective promoters in the previous
reports.5 Besides the acid additives, our group also found that
O
[M] & [O]
O
R
H
+
R
OH
High reaction temperature
(80-130 oC)
O
b) Nitrate promoted mild C-O coupling between C(sp2)-H bond and carboxylic acids (this work)
DG
DG
[Pd] & [O]
Nitrate additive
O
O
R
H
+
R
OH
O
Close to room temperature !
64 examples
Mild condition;
Broad substrate scope (oximes & azobenzenes);
Unique ligand effect of nitrate additive; Mechanistic insight
Scheme 1 C-O Bond coupling between C(sp2)-H bond and carboxylic acids.
aCollege of Chemical Engineering, Catalytic Hydrogenation Research Center, State
Key Laboratory Breeding Base of Green Chemistry-Synthesis Technology, Key
Laboratory of Green Pesticides and Cleaner Production Technology of Zhejiang
Province, Zhejiang University of Technology, Hangzhou 310014, P. R. China. E-
mail: loushaojie@zjut.edu.cn, chrc@zjut.edu.cn
Results and discussion
At the outset of the project, acetophenone oxime 1a9 and
benzoic acid 2a were treated with Pd catalyst, NFSI (N-
fluorobenzenesulfonimide), and stoichiometric KNO3 in
bInstitutes of Physical Science and Information Technology, Anhui University,
Hefei 230601, China. E-mail: luogen@ahu.edu.cn
†
Electronic Supplementary Information (ESI) available. For ESI see DOI:
10.1039/x0xx00000x
o
CH3NO2 under 30 C (Table 1, entry 1). Gratefully, the desired
O-aryl ester 3a was obtained in a moderate yield (59%) and
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Organic & Biomolecular Chemistry
Page 2 of 6
ARTICLE
Journal Name
Table 2 C(sp2)-H Oxidation of oximes with carboxylic acidsa
Table 1 Screening of the oxidation conditionsa
View Article Online
DOI: 10.1039/D0OB01124J
O
O
O
O
O
N
R1
N
R1
N
Pd(OAc)2 (5 mol%)
nitrate (2.0 equiv.)
oxidant (2.0 equiv.)
N
N
Pd(OAc)2 (5 mol%)
Selectfluor (2.0 equiv.)
KNO3 (2.0 equiv.)
O
H
O
O
F
H
O
O
+
R2
PhCOOH
R2
HO
R
solvent (0.1 M)
30 oC, 24 h
R
CH3NO2, T (oC), 24 h
Ph
1
2
3
2a
1a
3a
3a'
Scope of Oximes
(1.5 equiv)
O
N
O
N
O
O
N
O
N
N
Yield of
O
O
O
O
Ph
O
O
Ph
O
O
Ph
O
O
Ph
Entry
Oxidant
Solvent
Nitrate
3a/3a' (%)
59/26
74/8
72/11b
--/--
trace/--
--/--
--/--
Ph
nBu
3c
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
NFSI
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3CN
DCE
PhCH3
EtOAc
DMF
THF
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
KNO3
KNO3
KNO3
KNO3
KNO3
KNO3
KNO3
KNO3
KNO3
KNO3
KNO3
KNO3
KNO3
KNO3
KNO3
--
O
Me
3b
OAc
3e
3d
3a
Selectfluor
Selectfluor
O2
@60 oC, 85%c
@30 oC, 80%
@30 oC, 80%
@30 oC, 90%b
@30 oC, 70%
O
N
O
N
O
N
O
N
O
N
Na2S2O8
O
O
Me
O
O
O
O
Ph
O
O
Ph
O
O
Ph
PhI(OAc)2
Cu(OAc)2
BQ
Ph
Ph
O
S
O
Ph
F
NO2
3j
3f
3g
3h
--/--
3i
@60 oC, 79%c
@30 oC, 60%
@30 oC, 86%c
@90 oC, 48%
@90 oC, 66%
CAN
65/--
44/--
44/--
15/--
--/--
O
N
O
N
O
N
O
N
O
N
Selectfluor
Selectfluor
Selectfluor
Selectfluor
Selectfluor
Selectfluor
Selectfluor
Selectfluor
Selectfluor
Selectfluor
Selectfluor
Selectfluor
O
O
O
O
O
Ph
F
O
O
O
O
O
O
Ph
Ph
Ph
Ph
O
Me
3k
3l
3m
3o
3n
--/--
--/--
@40 oC, 90%b
@60 oC, 73%c
@70 oC, 65%c
@30 oC, 91%b
@30 oC, 81%
O
N
O
N
O
N
O
N
O
N
13/--
59/--c
73/18
73/16
54/5
KNO3
NaNO3
AgNO3
LiNO3
o'
o
O
O
Ph
O
O
Ph
O
O
O
O
Ph
O
O
Ph
Ph
F
Cl
Br
F3C
3q
3p:3p'
3r
3s
@70 oC, 82%
3t
(2 : 1)
@30 oC, 90%c
@30 oC, 86%
@70 oC, 80%
@30 oC, 83%
Mg(NO3)2•6H2O
30/--
O
N
O
N
O
N
O
N
Ph
O
N
aReaction conditions: 1a (0.1 mmol), 2a (1.5 equiv.), Pd(OAc)2 (5 mol%), oxidant
(2.0 equiv.), nitrate (2.0 equiv.), solvent (1.0 mL), 30 oC, ambient atmosphere, 24
h, GC-MS yield (unless otherwise noted). bUnder N2 atmosphere. cKNO3 (0.2
equiv.).
F
O
O
O
O
O
O
O
O
Ph
O
O
Ph
Ph
Ph
Ph
O
3w
3v
3x
3y
3u
@30 oC, 65%c
@30 oC, 68%c
@60 oC, 64%c
@40 oC, 62%
@40 oC, 80%b,c
fluorinated oxime 3a' was also detected as a side-product
(26%). Switching the oxidant from NFSI to another F+ reagent
Selectfluor enhanced the oxidation/fluorination selectivity
under ambient atmosphere (3a/3a' = 74/8) (entries 2-3).
Several other oxidants such as oxygen (entry 4), peroxides
(entry 5), PhI(OAc)2 (entry 6), copper salt (entry 7), and
benzoquinone (entry 8) were inefficient in this transformation.
Interestingly, inorganic oxidant CAN (Ceric ammonium nitrate),
which contains nitrate anion, promoted the oxidation
efficiently (entry 9). CH3NO2 performed the best among the
solvents tested (entries 10-15). As anticipated, the oxidation
reaction became sluggish in the absence of nitrate additive
(entry 16). Catalytic amount of KNO3 additive could
dramatically improve the reaction efficiency (entry 17). Other
nitrate additives were also investigated. NaNO3 and AgNO3
gave comparable results, albeit with lower selectivity (entries
18-19). LiNO3 or Mg(NO3)2•6H2O could also serve as a
promoter (entries 20-21). These results further demonstrate
the crucial role of nitrate additive in this mild C-H bond
oxidation.
O
N
Cl
O
N
O
N
O
N
O
N
Cl
O
O
O
O
O
O
O
O
Ph
O
O
Ph
Ph
Ph
Ph
3aa
3ad
@40 oC, 47%
3z
3ab
@80 oC, 90%
3ac
@40 oC, 73%c
@60 oC, 60%c
@40 oC, 55%
Scope of Carboxylic acids
O
N
O
N
O
N
O
N
O
N
O
O
O
S
O
O
O
O
O
O
O
Ph
F
3ae
@70 oC, 64%
Ph
3ai
3ag
@30 oC, 60%
3ah
@30 oC, 89%
3af
@40 oC, 80%
@30 oC, 90%
O
N
O
O
O
N
N
N
O
O
O
O
O
O
O
O
3aj
3ak
@30 oC, 89%c
3al
3am
@40 oC, 84%
@30 oC, 88%
@30 oC, 84%
aReaction conditions: 1 (0.30 mmol), 2 (1.5 equiv.), Pd(OAc)2 (5 mol%),
Selectfluor (2.0 equiv.), KNO3 (2.0 equiv.) in CH3NO2 (3.0 mL) under air at
the indicated temperature for 24 h, isolated yield, unless otherwise noted.
bDCE (3.0 mL). cThe isolated product contains small amount of the Z-isomer
as minor product (see ESI).
With the optimized conditions in hand, the substrate scope
of the oxidation was investigated. Diverse oximes were
prepared and tested (Table 2). Generally, the reaction
tolerated well with various substituents, e.g. alkyl (3b, 3c, 3j,
2 | J. Name., 2012, 00, 1-3
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ARTICLE
Table 3 C(sp2)-H Oxidation of azobenzenes with carboxylic acidsa
H bond oxidation efficiently to give poly-substituted products
View Article Online
(3t, 3u) in good yield. To be noted, theDoOxI:id10a.t1i0o3n9/Dto0oOkB0p1l1a2c4eJ
close to room temperature in most cases. The substrates
bearing strong electron-withdrawing functional groups (NO2,
CH3SO2, CF3) required elevated reaction temperatures to reach
comparable yields. Sterically demanding ortho-substituted
oximes needed higher reaction temperature (3j-3m). For the
meta-substituted oximes, C-H bond oxidation took place at the
less sterically hindered position (3n-3t). However, a mixture of
regioisomers was detected in the case of meta-fluoro
acetophenone oxime due to the small size of fluorine atom
(3p:3p' = 2:1).
R
N
O
PdCl2 (10 mol%)
Selectfluor (2.5 equiv.)
AgNO3 (40 mol%)
H
N
R3
O
N
+
R-COOH
N
R3
Ar
DCE, T (oC), 24 h
Ar
4
2
5
(1.5 equiv.)
Scope of symmetric azobenzenes:
O
Ph
O
N
Ph
O
N
Ph
O
N
Ph
O
O
O
N
Et
O
N
O
N
N
N
O
Et
5c
5a
5d
5b
@30 oC, 75%
@30 oC, 80%
@80 oC, 83%
@30 oC, 70%
O
Ph
O
Ph
O
Ph
O Ph
Aromatic carbonyl oximes other than acetophenone derived
oximes were also investigated (3v-3ae). Strained cyclopropanyl
is compatible with the oxidative condition (3y). The sensitive
dichloromethyl group also survived the reaction condition
(3ab). The reaction of cyclic ketone oximes bearing different
ring size took place smoothly as well (3ac, 3ad). Notably,
benzaldehyde oxime was also accommodated to the C-H bond
oxidation with benzoic acid in a decent yield (3ae).
O
N
CF3
O
OCF3
O
F
O
N
N
N
N
N
N
N
F3C
F3CO
F
5f
5g
@110 oC, 68%b
5e
@90 oC, 70%b
5h
@60 oC, 72%b
@60 oC, 61%b
O
Ph
O
N
Ph
O
O
Ph
O
N
O
N
N
N
Et
N
F
O
Next, different aromatic acids and aliphatic acids were
tested. Substituted benzoic acids (3af, 3ag), 1-naphthoic acid
(3ah), and even 2-thiophenecarboxylic acid (3ai) underwent
cross-dehydrogenative O-arylation with 1a under mild
conditions. Moreover, small isobutyric acid also worked well to
give the corresponding O-aryl ester in high yield at 30 oC (3aj).
Other aliphatic acids containing cyclopropanyl (3ak), cyclobutyl
(3al), and adamantyl (3am) groups did not hamper the
reaction efficiency.
Et
F
O
5i
5k
@60 oC, 77%c
5j
@30 oC, 80%
@80 oC, 65%b
O
Ph
O
Ph
O
Ph
O
N
O
N
O
N
N
N
N
Cl
F
Br
Cl
F
Br
5n
5m
5l
@60 oC, 68%b
@60 oC, 62%c
@90 oC, 75%
Scope of unsymmetric azobenzenes:
To further examine the application prospects of this Pd-
nitrate catalysis in the mild aromatic C-H bond oxidation with
carboxylic acids, diverse azobenzenes were also investigated
(Table 3).10 To our delight, the desired product 5a was
obtained in high yield under mild reaction condition (see SI).11
Similar to the C-H bond oxidation of oximes, diverse functional
groups (alkyl, alkoxyl, CF3O, CF3, F, Cl, Br) tethered at different
positions of azobenzenes were well tolerated (5a-5n). Notably,
O
Ph
O
N
Ph
O
Ph
O
N
Ph
O
N
O
N
O
N
O
N
N
N
Cl
Cl
Cl
5r
5q
5o
5p
@40 oC, 58%b
@60 oC, 67%
@30 oC, 88%
@60 oC, 66%b
Scope of carboxylic acids:
Ph
F
S
O
O
O
O
O
O
O
O
o
the reaction temperatures were below 80 C in most cases.
N
N
The C-H bond oxidation of unsymmetrical azobenzenes
bearing 2,6-diblocked mesityl group also took place smoothly
(5o, 5p). For the unsymmetrical azobenzenes bearing
electronically biased aryl groups, C-H oxidation selectively took
place at the more electron-rich aromatic side (5q, 5r). Again,
the O-arylation of different aromatic acids and aliphatic acids
with azobenzene 4a proceeded smoothly under mild
conditions (5s-5y).
To gain further information of the nitrate-promoted C(sp2)-H
bond oxidation protocol, several mechanistic experiments
were carried out (Scheme 2). Firstly, a key aryl-Pd-NO3
intermediate (Int-II) was prepared from Int-I in high yield
according to the previous reports (Scheme 2, a).7,8c,12 Treating
the Int-II and 2a with 2.5 equivalents of Selectfluor at room
temperature for 24 hours gave the desired oxidation product
5a in 82% yield (Scheme 2, b). Furthermore, using Int-II as the
sole catalyst in the absence of nitrate additive could promote
the C-H bond oxidation to afford 5a in 58% yield. The yield of
N
N
N
N
N
N
5v
5t
5s
5u
@40 oC, 81%
@40 oC, 46%
@40 oC, 82%
@40 oC, 82%
O
O
O
N
O
N
O
N
O
N
N
N
5w
5x
@60 oC, 66%
5y
@60 oC, 60%
@60 oC, 65%
aReaction
conditions: 1 (0.30 mmol), 2 (1.5 equiv.), PdCl2 (10 mol%),
Selectfluor (2.5 equiv.), AgNO3 (0.4 equiv.) in 1,2-dichloroethane (3.0 mL)
under air at the indicated temperature for 24 h, isolated yield, unless
otherwise noted. bThe isolated product contains small amount of the Z-
isomer as minor product (see ESI). cThe isolated product contains small
amount of unseparable regioisomer as minor product (see ESI).
3n), alkoxyl (3d, 3k, 3o), ester (3e), aryl (3f), halo (3g, 3l, 3q, 3r),
nitro (3h), sulfonyl (3i), and trifluoromethyl (3s) functional
groups. Disubstituted acetophenone oximes also underwent C-
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
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Organic & Biomolecular Chemistry
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ARTICLE
Journal Name
catalytic cycle (see SI, Figure S1). These stoichVioiemw AerttircilecOanlninde
a) Preparation of aryl-PdII-NO3 intermediate:
DOI: 10.1039/D0OB01124J
catalytic reactions demostrated a significant accelerating
effect of nitrate additive in the present mild C(sp2)-H bond
oxidation.
N
Dioxane : H2O = 3 : 1
Reflux, 1 h
N
N
N
PdCl2
+
Cl
Cl
N
N
Pd
Pd
To have a better understanding of the role of the nitrate
additive, we performed the density functional theory (DFT)
calculations on this reaction. Firstly, the C‒H activation of 4a
4a
Int-I
‒
by Pd catalysts in combination with Cl‒ or NO3 anions was
N
N
DCM : CH3CN = 3 : 1
r.t., 24 h
Int-I
+
AgNO3
comparatively investigated and the most favorable pathways
for each case were shown Scheme 3 (see also SI, Figures S3
and S4 for more details). Indeed, the C‒H activation via TSCl
has to overcome an energy barrier of 27.6 kcal mol-1 in the
PdCl2-catalyzed reaction (Scheme 3). In contrast, when nitrate
was added into the reaction system, the computational result
clearly suggested that the energy barrier of the C‒H activation
via TSNO3 was significantly reduced to 19.8 kcal mol-1,
indicating that the nitrate could promote the reaction to take
place under mild conditions by facilitating the C-H bond
cleavage.13
Pd
ONO2
NCCH3
(2.4 equiv.)
Int-II
Int-II
b) Stoichiometric transformation of
:
Ph
N
N
Selectfluor (2.5 equiv.)
DCE, r.t., 24 h
O
Int-II
+
PhCOOH
O
Ph
then treated with AcOH
2a
(1.5 equiv.)
5a
, 82%
Int-II
c) Catalytic activity of
:
Ph
Int-II
(10 mol%)
N
N
Selectfluor (2.5 equiv.)
AgNO3 (x equiv.)
N
N
Pd
Cl2 + AgNO3
O
+
PhCOOH
DCE, r.t., 24 h
O
Ph
-
4a,
NO3
2a
(1.5 equiv.)
5a
PdII
4a
5a
ONO2
AgNO3 (0 equiv.): 58%
AgNO3 (0.4 equiv.): 86%
A
HNO3
Int-I
d) Catalytic activity of
:
Ph
N
Int-I
(10 mol%)
Selectfluor (2.5 equiv.)
AgNO3 (x equiv.)
N
O
N
N
O
N
N
N
N
O
N
O
O
PdIV
+
PhCOOH
PdII
O
Ph
O
N
DCE, r.t., 24 h
O
Ph
O
2a
(1.5 equiv.)
4a
5a
B
D
O
AgNO3 (0 equiv.): 27%
AgNO3 (0.4 equiv.): 70%
Scheme 2 Mechanistic experiments.
F
N
N
O
PdIV
PhCOOH
O
N
O
Cl
2a
G‡ = 27.6
F
Cl

N
H
N
Pd
N
C
N
N
Pd
Pd
N
HCl
Cl
Cl
Cl
Figure 1 Possible reaction mechanism.
ICl
TSCl
27.6
BCl
-3.3
Based on the above experimental and computational results,
as well as the previous literatures,14 a possible mechanism is
shown in Figure 1. The cationic Pd-NO3 species A was in-situ
0.0
O
N
O
O
O
N
O
O
generated from Pd precatalyst and nitrate additive.
A
G‡ = 19.8

N
chelation-assisted electrophilic C(sp2)-H bond palladation of
substrate 4a with A occurs subsequently, followed by an
oxidative addition with F+ reagent to give the high-valent PdIV
intermediate C. Given the poor nucleophilicity of fluoro anion
and nitrate anion, the C-F bond formation or C-ONO2 bond
formation is disfavored under mild conditions.15 In contrast, a
nucleophilic ligand exchange of C with the carboxylic acid 2a
takes place to give intermediate D, which undergoes a
selective C-O bond reductive elimination subsequently to
provide the desired product 5a and regenerate cationic Pd-
NO3 species A for the next catalytic cycle.
N
H
O
O
O
N
Pd
N
Pd
N
O
N
Pd
N
O
O
N
O
HNO3
O
N
O
INO3
BNO3
-10.3
TSNO3
0.0
19.8
Scheme
3 Computed C‒H activation of 4a catalyzed by PdCl2 and Pd(NO3)2,
respectively, calculated at the level of M06/6-311+G(d,p)-SDD(Pd) (DCE,
SMD)//B3LYP/6-31G(d)-SDD(Pd). See Supporting Information for computational details.
the desired product was further improved with the extra
addition of a catalytic amount of nitrate (Scheme 2, c). In sharp
contrast, using Int-I as the catalyst was less efficient in the
absence of nitrate additive (Scheme 2, d). In addition, a lack of
induction period was observed in the kinetic experiment that Conclusions
using Int-II as the catalyst, indicating that the nitrate-
containing palladacycle complex should be involved in the
4 | J. Name., 2012, 00, 1-3
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Organic & Biomolecular Chemistry
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Journal Name
ARTICLE
In conclusion, a nitrate-promoted mild C(sp2)-H oxidation of
diverse oximes or azobenzenes with diverse aromatic and
aliphatic acids was developed for the first time. A variety of
desired O-aryl esters were obtained in high yield under mild
conditions (close to the ambient temperature for most cases).
More importantly, the unique effect of nitrate additives was
established by detailed studies on the well-defined aryl-Pd(II)-
NO3 intermediate. DFT studies also demostrated that nitrate
additive could significantly lower the energy barrier of the C‒H
bond cleavage. The procotol not only provides a mild synthetic
method towards useful O-aryl esters, but also shows new
insight into the powerful Pd-nitrate catalysis in C-H bond
activation. Utilizing this Pd-nitrate catalytic platform for the
selective reductive elimination of other challenging chemical
bonds is ongoing in our laboratory.
Ridnour, V. M. Caceres, R. C. Spadari-BratfischV,ieNw.APrtiacloelOonclicnie,
C. A. Velázquez-Martínez, D. A. Wink DaOnId: 1K0..10M39. /MD0iOraBn0d11a2,4JJ.
Med. Chem., 2013, 56, 7804-7820; (c) D. F. McComsey, V. L.
Smith-Swintosky, M. H. Parker, D. E. Brenneman, E.
Malatynska, H. S. White, B. D. Klein, K. S. Wilcox, M. E.
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A. B. Reitz and B. E. Maryanoff, J. Med. Chem., 2013, 56,
9019-9030.
2
3
For the review on C-H bond oxidation with carboxylic acids:
S. Arshadi, A. Banaei, A. Monfared, S. Ebrahimiasl and A.
Hosseinian, RSC Adv., 2019, 9, 17101-17118.
For the recent reports on C-H bond oxidation with carboxylic
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Shi, Synlett, 2011, 7, 883-886; (b) K. Padala and M.
Jeganmohan, Chem. Commun., 2013, 49, 9651-9653; (c) S. K.
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Chem., 2015, 2015, 350-356. (d) F. Wang, Q. Hu, C. Shu, Z.
Lin, D. Min, T. Shi and W. Zhang, Org. Lett. 2017, 19, 3636-
3639; (e) J. Lan, H. Xie, X. Lu, Y. Deng, H. Jiang and W. Zeng,
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M. Jeganmohan, J. Org. Chem., 2017, 82, 12691-12700; (g)
C.-J. Chen, Y.-X. Pan, H.-Q. Zhao, X. Xu, J.-B. Xu, Z.-Y. Zhang,
S.-Q. Xi, L.-J. Xu and H.-R. Li, Org. Chem. Front., 2018, 5, 415-
422; (h) Y.-C. Yuan, C. Bruneau, T. Roisnel and R. Gramage-
Doria, Org. Biomol. Chem., 2019, 17, 7517-7525; (h) E.
Kianmehr and S. B. Nasab, Eur. J. Org. Chem., 2019, 2019,
1038-1044.
Conflicts of interest
The authors declare no competing financial interests.
Experimental Section
Typical procedure for the mild C(sp2)-H oxidation of 1 with
carboxylic acids 2: In a 10 mL test tube equipped with a stir
bar, oxime 1 (0.3 mmol), 2 (0.45 mmol), Pd(OAc)2 (0.015
mmol), Selectfluor (0.6 mmol), KNO3 (0.6 mmol) and CH3NO2
(3.0 mL) were added successively. Then the tube was sealed
and stirred at the indicated temperature for 24 h. Upon
completion, the mixture was purified by silica gel
chromatography (petroleum ether/EtOAc = 30:1) to afford the
desired products 3.
4
5
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2018, 57, 14085-14089.
6
Typical procedure for the mild C(sp2)-H oxidation of 4 with
carboxylic acids 2: In a 10 mL test tube equipped with a stir
bar, azobenzene 4 (0.3 mmol), 2 (0.45 mmol), PdCl2 (0.03
mmol), Selectfluor (0.75 mmol), AgNO3 (0.12 mmol) and 1,2-
dichloroethane (3.0 mL) were added successively. Then the
tube was sealed and stirred at the indicated temperature for
24 h. Upon completion, the mixture was purified by silica gel
chromatography (petroleum ether/EtOAc = 30:1) to afford the
desired products 5.
7
8
Y.-J. Mao, G. Luo, H.-Y. Hao, Z.-Y. Xu, S.-J. Lou and D.-Q. Xu,
Chem. Commun., 2019, 55, 14458-14461.
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T. W. Bray, J. M. Lynam, P. M. Aguiar, C. Reed, J. D. Lee, J. F.
Hamilton, A. C. Whitwood and I. J. S. Fairlamb, J. Am. Chem.
Soc., 2017, 139, 1177-1190.
9
J. Li, Y.-T. Hu, D.-P. Zhang, Q. Liu, Y.-H. Dong and H. Liu, Adv.
Synth. Catal., 2017, 359, 710-771.
Acknowledgements
The authors acknowledge the National Nature Science
Foundation of China (No. 21361130021), China Postdoctoral
Science Foundation (No. 2014M560494) and the Postdoctoral
Science Foundation of Zhejiang Province for financial support.
G. Luo thanks the High-performance Computing Platform of
Anhui University for computational resources.
10 T. H. L. Nguyen, N. Gigant and D. Joseph, ACS Catal., 2018, 8,
1546-1579.
11 For detailed information, see the Supporting Information.
12 T. Janecki, J. A. D. Jeffreys, P. L. Pauson, A. Pietrzykowski and
K. J. McCullough, Organometallics, 1987, 6, 1553-1560.
13 The possible role of different anions in the reductive
elimination processes was also investigated and the results
showed that the C‒O bond coupling step was very easy to
achieve for both cases (see SI, Figure S5).
14 K. M. Engle, T.-S. Mei, X.-S Wang and J.-Q. Yu, Angew. Chem.,
Int. Ed., 2011, 50, 1478-1491.
15 M. H. Pérez-Temprano, J. M. Racowski, J. W. Kampf and M. S.
Sanford, J. Am. Chem. Soc., 2014, 136, 4097-4100.
Notes and references
1
(a) N. Hulsman, J. P. Medema, C. Bos, A. Jongejan, R. Leurs,
M. J. Smit, I. J. P. de Esch, D. Richel and M. Wijtmans, J. Med.
Chem., 2007, 50, 2424-2431; (b) D. Basudhar, G. Bharadwaj,
R. Y. Cheng, S. Jain, S. Shi, J. L. Heinecke, R. J. Holland, L. A.
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ARTICLE
Journal Name
View Article Online
DOI: 10.1039/D0OB01124J
DG
DG
[Pd] & [O]
Nitrate additive
O
O
R
H
+
HO
R
O
Close to room temperature !
64 examples
Mild condition; Broad substrate scope; Mechanistic insight
A nitrate-promoted Pd-catalysed cross-dehydrogenative C(sp2)-H oxidation of oximes or azobenzenes with diverse aromatic and aliphatic
acids was developed, allowing the versatile formation of O-aryl esters under mild reaction conditions.
6 | J. Name., 2012, 00, 1-3
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