DDQ-promoted direct C–H amination of ethers with N-alkoxyamides under visible-light irradiation and metal-free conditions

Article abstract of DOI:10.1016/j.tet.2019.130516

A C(sp³)–N bond forming reaction between N-alkoxyamides and simple ethers has been developed. In the presence of commercially available 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ), a variety of N-methoxyamides and ethers undergo this transfor

Full text of DOI:10.1016/j.tet.2019.130516

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DDQ-promoted direct C–H amination of ethers with N-alkoxyamides under visible-light
irradiation and metal-free conditions
Yan Zhang, Lei Wang, Zhiming Wang, Wei Chen
PII:
S0040-4020(19)30849-X
https://doi.org/10.1016/j.tet.2019.130516
TET 130516
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 10 June 2019
Revised Date: 30 July 2019
Accepted Date: 7 August 2019
Please cite this article as: Zhang Y, Wang L, Wang Z, Chen W, DDQ-promoted direct C–H amination of
ethers with N-alkoxyamides under visible-light irradiation and metal-free conditions, Tetrahedron (2019),
doi: https://doi.org/10.1016/j.tet.2019.130516.
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DDQ-promoted direct C–H amination
of ethers with N-alkoxyamides under
visible-light irradiation and metal-free
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Yan Zhang, Lei Wang,* Zhiming Wang and Wei Chen*
Advanced Research Institute and Department of Chemistry, Taizhou University, Taizhou, Zhejiang,
318000, P. R. China

Tetrahedron
journal homepage: www.elsevier.com
DDQ-promoted direct C–H amination of ethers with N-alkoxyamides under
visible-light irradiation and metal-free conditions
Yan Zhanga,b, Lei Wanga,b,c*, Zhiming Wanga,c, Wei Chenb,c*
a Advanced Research Institute and Department of Chemistry, Taizhou University, Taizhou, Zhejiang, 318000, P. R. China
b Department of Chemistry, Huaibei Normal University, Huaibei, Anhui 235000, P. R. China
c State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Shanghai 200032, People’s Republic of China
Corresponding author. e-mail: leiwang@chnu.edu.cn, lake688123@163.com
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A C(sp3)–N bond forming reaction between N-alkoxyamides and simple ethers has been
developed. In the presence of commercially available 2,3-dichloro-5,6-dicyano-p-benzoquinone
(DDQ), a variety of N-methoxyamides and ethers undergo this transformation smoothly to
deliver the corresponding products in good yields under visible-light irradiation and metal-free
conditions at room temperature.
Available online
2019 Elsevier Ltd. All rights reserved
.
Keywords:
N-alkoxyamides
tetrahydrofuran (THF)
2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ)
cross-dehydrogenative-coupling (CDC)
visible-light irradiation
1. Introduction
synthesis of aminated ethers from simple amides and ethers
is highly desirable.
Nitrogen-containing compounds are prevalent structural
motifs, which are widely found in natural products,
marketed drugs, material sciences, and synthetic
intermediates.1 As a result, the synthesis of nitrogen-
containing molecules has attracted considerable interest and
a number of methods have been developed over the past
decade.2 On the other hand, simple ether, such as
tetrahydrofuran (THF), is important organic synthon and
organic solvent. It is well known that α-functionalized ether
derivatives abundantly exist in various biologically active
molecules and natural products.3 When both ether unit and
amine moiety are simultaneously introduced into an organic
molecule, a number of nitrogen-containing ethers might be
expected, which can serve as biologically active molecules
and valuable synthetic intermediates.4 The first example of
α-C–H amination of ethers was demonstrated by Li and co-
workers in 2010.5 In the presence of FeCl3 as the catalyst,
the direct coupling of ether derivatives with various azoles
underwent smoothly to generate the corresponding products
in good yields.5 After that, various N–H reagents, such as
purines,6 nucleobases,7 hypervalent sulfonylimino-λ3–
bromanes,8 phthalimides,9 saccharins,10 and specific nitrogen
heterocycles,11 have been used to provide the nitrogen
sources for the construction of aminated alkyl ethers.
Despite significant achievements have been achieved, there
are some drawbacks, such as requirement of transition-metal
catalysts, harsh reaction conditions and the limited scope of
substrates in the most of cases. Therefore, the direct
Scheme 1. The oxidative C−H/N−H cross dehydrogenative
coupling reaction between N-alkoxyamides and ethers
In 2014, Lei et al. reported a first example of Ni(II)-
catalyzed oxidative radical/radical cross-coupling reaction
between N
-alkoxyamides and ethers to form C(sp3)–N bonds
in the presence of an organic oxidant DTBP (Scheme 1a).12
Most recently, Li’s group explored an intermolecular α-C−H

2
Tetrahedron
amination of simple ethers with picolinamide or
N-(8-
While the amount of THF used in the reaction was
quinolyl)amides as the N−H sources through a Cu(II)-
catalyzed C−H/N−H cross dehydrogenative coupling (CDC)
reaction (Scheme 1b and 1c).13 From the synthetic point of
view, the development of an alternative approach for direct
α-C−H amination of ethers using readily available
precursors under transition-metal free conditions is highly
practical.8,9,14 Most recently, a halogen-bond-promoted,
transition-metal-free and photosensitizer-free, direct
C(sp3)−H amination in the presence of readily available
perfluorobutyl iodide under mild conditions was reported.14b
Visible-light photoredox catalysis as a versatile and
environmentally friendly synthetic methodology has been
used as a powerful tool for the construction of new chemical
bonds via oxidative C–H/N–H CDC reactions.15 2,3-
decreased from 30.9 equiv to 26.5, 20.0 and 15.0 equiv, the
yield of 3a was decreased from 78% to 75%, 73% and 68%,
respectively (Table 1, entries 21−23). Further experiments
showed that no product was formed in the absence of DDQ
or visible-light irradiation (Table 1, entries 24 and 25).
Table 1. Optimization of the reaction conditionsa
Entry
1
Oxidant
Light Source
450–455 nm
450–455 nm
450–455 nm
450–455 nm
450–455 nm
450–455 nm
450–455 nm
520–525 nm
420–425 nm
365–370 nm
380–385 nm
450–455 nm
450–455 nm
450–455 nm
450–455 nm
450–455 nm
450–455 nm
450–455 nm
450–455 nm
450–455 nm
450–455 nm
450–455 nm
450–455 nm
450–455 nm
Dark
Solvent
THF
Yield (%)b
8
Dichloro-5,6-dicyano-p-benzoquinone (DDQ) as a cheap
and commercially available chemical reagent has been
frequently employed as an organic oxidizing reagent for the
DDQ (10 mol%)
DDQ (10 mol%)
DDQ (10 mol%)
DDQ (50 mol%)
DDQ (1.0 equiv.)
DDQ (1.5 equiv.)
DDQ (2.0 equiv.)
DDQ (1.5 equiv.)
DDQ (1.5 equiv.)
DDQ (1.5 equiv.)
DDQ (1.5 equiv.)
DDQ (1.5 equiv.)
DDQ (1.5 equiv.)
DDQ (1.5 equiv.)
DDQ (1.5 equiv.)
DDQ (1.5 equiv.)
DDQ (1.5 equiv.)
DDQ (1.5 equiv.)
DDQ (1.5 equiv.)
DDQ (1.5 equiv.)
DDQ (1.5 equiv.)
DDQ (1.5 equiv.)
DDQ (1.5 equiv.)
–
2
THF
11c
10d
35
organic
transformations.16
Recently,
the
related
3
THF
investigations revealed that DDQ also could be used as a
photosensitizer for the C–N bond formation in organic
synthesis.17 Herein, we wish to report a mild and efficient
strategy toward direct oxidative C−H/N−H cross
4
THF
5
THF
43
6
THF
54
dehydrogenative coupling (CDC) reaction between
N-
7
THF
47
alkoxyamides and ethers using DDQ as an oxidant under
visible-light irradiation and metal-free conditions (Scheme
1d).
8
THF
50
9
THF
N. R.
N. R.
N. R.
57
10
11
12
13
14
15
16
17
18
19
20
21
21
22
23
24
THF
THF
DCE/THFe
CH3CN/THFf
PhCl/THFg
DCM/THFh
EtOAc/THFi
DCE/THFj
DCE/THFk
DCE/THFl
DCE/THFm
DCE/THFn
DCE/THFo
DCE/THFp
DCE/THF
DCE/THF
2. Results and discussion
53
Initially, the reaction of
N-methoxybenzamide (1a) with
50
tetrahydrofuran (THF, 2a) was conducted to optimize the
reaction conditions. The corresponding C−H/N−H cross
dehydrogenative coupling product 3a was isolated in 8%
yield when 10 mol% DDQ was used as the photocatalyst
under the irradiation of blue LED (450−455 nm, 1.5 W) in
air at room temperature for 20 h (Table 1, entry 1). It must
be mentioned that there was only 11% yield of the desired
product was obtained when 10 mol% of tert-butyl nitrite
(TBN) was added as the co-catalyst. Moreover, when
oxygen instead of air as a reaction gas atmosphere was used,
the transformation gave no improvement in the yield (Table
1, entry 3). To our delight, the yield of 3a improved to 35%
when 50 mol% DDQ was added to the reaction (Table 1,
entry 4). While the amount of DDQ used in the reaction was
increased from 1.0 equiv to 1.5 equiv, 54% yield of 3a was
isolated. No improvement of product yield was observed
more than 1.5 equiv of DDQ (Table 1, entries 5−7).
Subsequently, the light sources, such as LED (365−370 nm),
LED (380−385 nm), blue LED (420−425 nm) and green
LED (520−525 nm) were scanned, and blue LED (450−455
nm) was the best choice for the reaction (Table 1, entries
8−11). Next, the effect of solvent on the reaction was also
examined. To our delight, the yield of 3a could be improved
to 57% when a mixed solvent of DCE and THF (1:1, volume
ratio) was used for the model reaction in the presence of
DDQ (Table 1, entry 12). Other mixed solvent of THF with
CH3CN, PhCl, DCM and EtOAc all in 1:1 volume ratio was
also tested, and all of them provided the inferior reactivity
comparing with mixed solvent DCE/THF (1:1, volume ratio)
(Table 1, entries 13−16). Furthermore, the effect of
DCE/THF volume ratio on the reaction was shown to be
comparatively significant. When DCE/THF (5:1, volume
ratio) was used as a reactant, as well as reaction medium, the
yield of 3a was increased to 78% (Table 1, entries 17−20).
55
55
60
65
70
78
75
73
68
N. R.
N. R.
DDQ (1.5 equiv.)
aReaction conditions:
N-methoxybenzamide (1a, 0.20 mmol), THF (2a,
3.0 mL) and DDQ at room temperature under light irradiation in air for
20 h.
bIsolated yield.
c10 mol% of tert-butyl nitrite (TBN) was added.
d10 mol% of tert-butyl nitrite (TBN) was added and the reaction
performed in oxygen-balloon.
eDCE/THF = (1:1, 3.0 mL).
fCH3CN/THF = (1:1, 3.0 mL).
gPhCl/THF = (1:1, 3.0 mL).
hDCM/THF = (1:1, 3.0 mL).
iEtOAc/THF = (1:1, 3.0 mL).
jDCE/THF = (2:1, 3.0 mL).
kDCE/THF = (3:1, 3.0 mL).
lDCE/THF = (4:1, 3.0 mL).
mDCE/THF = (5:1, 3.0 mL; containing 30.9 equiv of THF).
nDCE/THF = (6:1, 3.0 mL; containing 26.5 equiv of THF).
oTHF (20.0 equiv).
pTHF (15.0 equiv).
N. R. = No Reaction.

With the optimized reaction conditions established, the
scope of substrates was investigated, as shown in Scheme 2.
3n and 3o in 76% and 73% yields, respectively. Notably, N-
methoxyamide with a sterically hindered naphthyl ring,
instead of phenyl ring, was used as a substrate in the
reaction with THF, generating the product 3p in 53% yield.
First, the reaction between the substituted
) and THF (2a) were carried out under the standard
reaction conditions. -Methoxyamides ( ) bearing with
N-alkoxyamides
(1
N
1
Interestingly,
N-alkoxy(heterocylic)amides, such as
N-
t
substituents including electron-donating groups (Me, Bu
and MeO) and electron-withdrawing groups (F, Cl, Br and
CF3) on the para-position of phenyl rings underwent the
transformation with THF smoothly to afford the desired
methoxyfuran-2-carboxamide and
N
-methoxythiophene-2-
carboxamide were also suitable substrates for the reaction to
yield the CDC products 3q and 3r in satisfactory yields.
Finally, other cyclic ethers, such as tetrahydropyran was
products (3b
−
3h) in good yields. This brief screening
evaluated. The reactions of tetrahydropyran with
N-
reveals that the electronic properties of the above substitutes
have no significant influence on the reaction efficiency.
alkoxyamides provided the anticipated products (3s 3u) in
–
52–56% yields, less than that with THF. When acyclic alkyl
ether such as diethyl ether and alkyl thioether such as
tetrahydrothiophene were used to react with 1a under the
present reaction conditions, however, no desired products
were obtained.
Additionally, representative
N-methoxyamides (1) with an
electron-donating group (Me or MeO) and an electron-
withdrawing group (F, Cl or Br) at the meta-position of
benzene rings could also react with THF to give the
corresponding products (3i
–
3m) in 71–79% yields. It was
To gain insight into the reaction mechanism, the control
experiments were conducted, as shown in Scheme 3. The
model reaction of 1a with 2a was completely inhibited when
a radical scavenger, 2,2,6,6-tetramethyl-1-piperidinyloxy
(TEMPO) was added to the reaction under the standard
found that -methoxyamides having di-substituted groups
N
(3,5-dimethyl or 3,5-dichloro) on the aromatic rings were
competent substrates, which proceeded normally under the
optimal conditions to generate the corresponding products
conditions, along with the formation of a TEMPO adduct (
4)
Scheme 2. The scope of N-alkoxyamides and ethersa
with -oxo radical (Scheme 3a), which was detected by
α
HRMS (ESI for detail). These results indicated a radical
process was involved in this transformation. On the other
hand, when 1a was performed in DCE without THF under
the standard conditions, the corresponding
N′-benzoyl-N,N′-
dimethoxybenzohydrazide ( ) was detected by HRMS
5
analysis (Scheme 3b), which was generated from the
homocoupling of nitrogen free radical. Therefore, from this
point of view, the nitrogen free radical did exist in this
oxidative condition. In addition, a kinetic isotope effect of
KH
THF-d8
/
KD = 3:2 was obtained using a mixture of THF (2a) and
[D8]-2a) in the reaction (Scheme 3c), illustrating
(
that C–H bond cleavage of THF might be a rate-determining
step.
Scheme 3. The control experiments
To further elucidate the possible reaction pathway,
fluorescence quenching experiments were also performed. It
was found that both of
N-methoxybenzamide (1a, 0.20
mmol in 2.5 mL DCE) and THF (THF/DCE in V/V = 1/5,
3.0 mL) can obviously quench the fluorescence of DDQ
(0.005 mol/L in DCE), shown in Figure 1. From Figure 1, it
indicated that the quenching effect of 1a to DDQ is greater
than that of THF to DDQ under the standard conditions.
aReaction conditions: N-alkoxyamide (1, 0.20 mmol), DCE/THF (5:1, 3.0
mL), and DDQ (1.5 equiv) at room temperature under irradiation of blue LED
(450–455 nm) in air for 20 h; isolated yields of the products.

4
Tetrahedron
broad substrate scope for the synthesis of various N-containing
compounds at room temperature without transition metal. Further
studies on more mechanistic details and synthetic applications of
this transformation are currently underway in our laboratory.
DDQ (0.005 mol/L)
DDQ (0.005 mol/L) + THF (0.5 mL)
DDQ (0.005 mol/L) + 1a (0.08 mol/L)
3000
2500
2000
1500
1000
500
4. Experimental Section
General Considerations
1
All H NMR and 13C NMR spectra were recorded on a 400
MHz Bruker FT-NMR spectrometer (400 MHz or 100 MHz,
respectively). All chemical shifts are given as δ value (ppm) with
reference to tetramethylsilane (TMS) as an internal standard. The
peak patterns are indicated as follows: s, singlet; d, doublet; t,
triplet; m, multiplet; q, quartet. The coupling constants, J, are
reported in Hertz (Hz). High resolution mass spectroscopy data
of the product were collected on a Waters Micromass GCT
instrument. High resolution mass spectroscopy data of the
products were collected on an Agilent Technology 6540 UHD
Accurate-Mass Q-TOF LC/MS (ESI) or a Waters Micromass
GCT Premier (oa-TOF) Mass Spectrometer (EI). The chemicals
and solvents were purchased from commercial suppliers either
Aldrich (USA), or Shanghai Chemical Company (P. R. China).
All the reactions were carried out under air atmosphere. Products
were purified by flash chromatography on 200–300 mesh silica
gels, SiO2.
0
300
350
400
450
500
550
600
650
700
750
Wavelength (nm)
Figure 1: Fluorescence quenching experiments
On the basis of the above investigation on the control
experiments and fluorescence quenching experiments, a
possible reaction mechanism is proposed, shown as in
Scheme 4.12,17,18 First, DDQ is excited by visible-light
irradiation to generate the excited-state of DDQ*. The
obtained DDQ* reacts with substrate 1a via a single electron
transfer (SET) process to afford an aminyl radical
intermediate
A
and [DDQH]•. The cyclic voltammetry (CV)
determination of N-methoxybenzamide and DDQ was
conducted, and the results were presented in Figure S4 of
ESI. From Figure S4, the single electron transfer (SET)
oxidation of N-methoxybenzamide by DDQ is possible
because the oxidant potential of DDQ (Eox = 0.78 V vs.
Ag/AgCl in DCE) is higher than the oxidation potential of
N-methoxybenzamide (Eox = 0.37 V vs. Ag/AgCl in
DCE).17a,e On the other hand, the formed DDQ* reacts with
THF (2a) via a single electron transfer pathway to generate
Typical procedure for the reaction of N-methoxybenzamide with
tetrahydrofuran (THF)
A 10 mL oven-dried reaction vessel equipped with a magnetic
stir bar was charged with N-methoxybenzamide (1a, 0.20 mmol),
DCE/THF (5:1, 3.0 mL) and DDQ (0.30 mmol) with blue LED
(450–455 nm, 1.5 W) irradiation at room temperature. The
solution was left to react for 20 h. After completion of the
reaction, the mixture was concentrated to yield the crude product,
which was purified by flash chromatography (silica gel,
petroleum ether/ethyl acetate = 7:1) to give the desired product
3a as a colorless liquid.
an alkyl radical intermediate
the formed nitrogen radical
carbon radical
B
and [DDQH]•. Subsequently,
couples with the transient sp3
A
B
to result in the cross-coupling product 3a in
a highly selective manner according to persistent radical
effect.12,19 We also tried the reaction using a combination of
DDQ/TBN/O2 catalytic system,17,20 but failed (Table 1,
entries 1 and 2). The lower oxidation potential of [DDQH]'
5. Spectral Data
5.1. N-Methoxy-N-(tetrahydrofuran-2-yl)benzamide (3a):12
1
to substrates (1 and 2) for being unreduced into DDQH2 to
Colorless liquid; 78% yield; H NMR (400 MHz, CDCl3)
complete the catalytic cycle in the presence of TBN/O2 was
δ: 7.64 (d,
J
= 6.8 Hz, 2H), 7.47-7.37 (m, 3H), 5,84 (q,
J =
speculated.21
3.9 Hz, 1H), 4.09 (q,
J
= 7.3 Hz, 1H), 3.83–3.78 (m, 4H),
2.31–2.23 (m, 1H), 2.18–2.10 (m, 1H), 2.03–1.97 (m, 1H),
1.91–1.88 (m, 1H); 13C NMR (100 MHz, CDCl3) δ: 169.0,
134.4, 130.7, 128.2, 128.0, 89.2, 68.9, 64.4, 28.3, 25.6.
5.2. N-Methoxy-4-methyl-N-(tetrahydrofuran-2-yl)benzamide
(3b):
Colorless liquid; 70% yield; 1H NMR (400 MHz, CDCl3)
δ: 7.56 (d,
J = 8.1 Hz, 2H), 7.20 (d, J = 7.9 Hz, 2H), 5.85 (q,
J
= 4.0 Hz, 1H), 4.12–4.07 (m, 1H), 3.83–3.78 (m, 4H), 2.37
(s, 3H), 2.31–2.23 (m, 1H), 2.18–2.08 (m, 1H), 2.05–1.96
(m, 1H), 1.91–1.88 (m, 1H); 13C NMR (100 MHz, CDCl3) δ:
169.1, 141.2, 131.5, 128.9, 128.2, 89.3, 68.8, 63.3, 28.2,
25.6, 21.4. HRMS (EI) Calcd. for C13H17NO3: 235.1208,
found: 235.1218.
Scheme 4. The proposed mechanism
5.3. 4-(tert-Butyl)-N-methoxy-N-(tetrahydrofuran-2-
yl)benzamide (3c): 12
3. Conclusions
Colorless liquid; 73% yield; 1H NMR (400 MHz, CDCl3)
In summary, we have demonstrated a novel visible-light-
induced direct α-C−H amination of simple ethers in the presence
of cheap and readily available DDQ. This protocol exhibits a
δ: 7.57 (d,
J
= 7.9 Hz, 2H), 7.39 (d,
J = 8.0 Hz, 2H), 5.83(q,
J
= 3.9 Hz, 1H), 4.08 (q,
J
= 6.9 Hz, 1H), 3.80–3.75 (m, 4H),

2.29–2.21 (m, 1H), 2.14–2.08 (m, 1H), 2.01–1.94 (m, 1H),
1.90–1.86 (m, 1H), 1.29 (s, 9H); 13C NMR (100 MHz,
CDCl3) δ: 168.9, 154.1, 131.4, 127.9, 125.1, 89.3, 68.8, 64.2,
34.7, 31.0, 28.2, 25.5.
169.2, 138.1, 134.4, 131.5, 128.5, 128.0, 124.9, 89.3 68.8,
64.3, 28.2, 25.5, 21.2. HRMS (EI) Calcd. for C13H17NO3:
235.1208, found: 235.1209.
5.10. N-Methoxy-3-methoxy-N-(tetrahydrofuran-2-
yl)benzamide (3j):
5.4. 4-Methoxy-N-methoxy-N-(tetrahydrofuran-2-
yl)benzamide (3d):
Colorless liquid; 78% yield; 1H NMR (400 MHz, CDCl3)
1
Colorless liquid; 82% yield; H NMR (400 MHz, CDCl3)
δ: 7.68–7.65 (m, 2H), 6.90–6.88 (m, 2H), 5.89 (q,
δ: 7.30 (t,
J
= 7.9 Hz, 1H), 7.21–7.16 (m, 2H), 6.98 (dd, J1
= 3.9 Hz, 1H), 4.09 (q,
=
J
= 4.0 Hz,
8.2 Hz, J2 = 2.5 Hz, 1H), 5.82 (q,
J
J
1H), 4.12–4.06 (m, 1H), 3.82–3.77 (m, 4H), 3.76 (s, 3H),
2.30–2.23 (m, 1H), 2.17–2.08 (m, 1H), 2.05–1.98 (m, 1H),
1.95–1.87 (m, 1H); 13C NMR (100 MHz, CDCl3) δ: 168.67,
161.7, 130.3, 126.3, 113.4, 89.3, 68.7, 64.2, 55.2, 28.2, 25.5.
HRMS (EI) Calcd. for C13H17NO4: 251.1158, found:
251.1161.
= 7.3 Hz, 1H), 3.81 (s, 3H), 3.80–3.77 (m, 4H), 2.30–2.22
(m, 1H), 2.17–2.07 (m, 1H), 2.05–1.96 (m, 1H), 1.94–1.88
(m, 1H); 13C NMR (100 MHz, CDCl3) δ: 168.7 159.3, 135.6,
129.3, 120.2 116.9 113.1 89.3 68.9 64.5 55.3, 28.2, 25.6
HRMS (EI) Calcd. for C13H17NO4: 251.1158, found:
251.1166.
5.5. 4-Fluoro-N-methoxy-N-(tetrahydrofuran-2-yl)benzamide
5.11. 3-Fluoro-N-methoxy-N-(tetrahydrofuran-2-
(3e):
yl)benzamide (3k):
Colorless liquid; 69% yield; 1H NMR (400 MHz, CDCl3)
Colorless liquid; 71% yield; 1H NMR (400 MHz, CDCl3)
δ: 7.72–7.68 (m, 2H), 7.08 (t,
J
= 8.6 Hz, 2H), 5.87 (q,
J
=
δ: 7.44 (d,
J
= 7.6 Hz, 1H), 7.40–7.35 (m, 2H), 7.17–7.12
= 7.2
4.0 Hz, 1H), 4.10 (q, = 7.4 Hz, 1H), 3.81 (q,
J
J
= 7.1 Hz,
(m, 1H), 5.85 (s, 1H), 4.12–4.06 (m, 1H), 3.81 (q, J
1H), 3.75 (s, 3H), 2.31–2.23 (m, 1H), 2.18–2.10 (m, 1H),
Hz, 1H), 3.76 (s, 3H), 2.30–2.23 (m, 1H), 2.18–2.10 (m,
2.09–2.01 (m, 1H), 1.93–1.87 (m, 1H); 13C NMR (100 MHz,
1H), 2.08–1.99 (m, 1H), 1.95–1.89 (m, 1H); 13C NMR (100
CDCl3) δ: 168.0, 164.1 (d,
J
= 249.9 Hz), 130.6 (d,
J
= 8.7
MHz, CDCl3) δ: 167.6, 162.2 (d,
7.1 Hz), 130.0 (d, = 7.9 Hz), 123.8 (d,
(d, = 21.1 Hz), 115.3 (d, = 23.2 Hz), 88.9, 68.9, 64.6,
28.3, 25.5. HRMS (EI) Calcd. for C12H14FNO3: 239.0958,
found: 239.0955.
J
= 246.1 Hz), 136.3 (d,
J=
Hz), 130.3 (d, = 3.5 Hz), 115.3 (d,
J
J
= 21.6 Hz), 88.9,
J
J
= 3.2 Hz), 117.8
68.8, 64.49, 28.2, 25.5. HRMS (EI) Calcd. for C12H14FNO3:
239.0958, found: 239.0956.
J
J
5.6. 4-Chloro-N-methoxy-N-(tetrahydrofuran-2-yl)benzamide
(3f):
5.12. 3-Chloro-N-methoxy-N-(tetrahydrofuran-2-
yl)benzamide (3l):
Colorless liquid; 67% yield; 1H NMR (400 MHz, CDCl3)
δ: 7.62 (d,
J
= 8.3 Hz, 2H), 7.38 (d,
J
= 8.2 Hz, 2H), 5.86 (q,
= 7.2
Colorless liquid; 73% yield; 1H NMR (400 MHz, CDCl3)
δ: 7.65 (t, J = 1.7 Hz, 1H), 7.55 (d, J = 7.6 Hz, 1H), 7.45–
J
= 4.0 Hz, 1H), 4.09 (q,
J
= 7.2 Hz, 1H), 3.81 (q,
J
Hz, 1H), 3.75 (s, 3H), 2.30–2.23 (m, 1H), 2.18–2.10 (m,
1H), 2.06–1.99 (m, 1H), 1.95–1.89 (m, 1H); 13C NMR (100
MHz, CDCl3) δ: 168.0, 137.0, 132.7, 129.7, 128.5, 88.9,
68.9, 64.6, 28.3, 25.5. HRMS (EI) Calcd. for C12H14ClNO3:
255.0662, found: 255.0667.
7.43 (m, 1H), 7.35 (t,
4.08 (m, 1H), 3.83 (q,
J
J
= 7.8 Hz, 1H), 5.86 (s, 1H), 4.13–
= 7.0 Hz, 1H), 3.77 (s, 3H), 2.31–
2.24 (m, 1H), 2.20–2.12 (m, 1H), 2.10–2.03 (m, 1H), 1.97–
1.91 (m, 1H); 13C NMR (100 MHz, CDCl3) δ: 167.6, 136.1,
134.3, 130.9, 129.6, 128.2, 126.2, 88.9, 69.0, 64.7, 28.4,
25.6. HRMS (EI) Calcd. for C12H14ClNO3: 255.0662, found:
255.0659.
5.7. 4-Bromo-N-methoxy-N-(tetrahydrofuran-2-yl)benzamide
(3g):12
5.13. 3-Bromo-N-methoxy-N-(tetrahydrofuran-2-
yl)benzamide (3m):
Colorless liquid; 75% yield; 1H NMR (400 MHz, CDCl3)
δ: 7.56 (s, 4H), 5.87 (q,
J = 4.1 Hz, 1H), 4.13–4.08 (m, 1H),
1
3.85–3.80 (m, 1H), 3.76 (s,3H), 2.31–2.24 (m, 1H), 2.19–
2.11 (m, 1H), 2.09–2.02 (m, 1H), 1.96–1.90 (m, 1H); 13C
NMR (100 MHz, CDCl3) δ: 168.1, 133.22, 131.5, 129.9,
125.4, 88.9, 68.9, 64.7, 28.3, 25.6.
Colorless liquid; 79% yield; H NMR (400 MHz, CDCl3)
δ: 7.80 (t,
2H), 7.29 (t,
J
= 1.7 Hz, 1H), 7.59 (dd, J1 = 7.9 Hz, J2 = 1.8 Hz,
= 7.9 Hz, 1H), 5.86 (s, 1H), 4.13–4.07 (m,
J
1H), 3.85-3.80 (m, 1H), 3.76 (s, 3H), 2.31–2.23 (m, 1H),
2.19–2.11 (m, 1H), 2.10–2.03 (m, 1H), 1.96–1.92 (m, 1H);
13C NMR (100 MHz, CDCl3) δ: 167.4, 136.3, 133.7, 131.0,
129.8, 126.6, 122.2, 88.8, 68.9, 64.6, 28.3, 25.5. HRMS (EI)
Calcd. for C12H14BrNO3: 299.0157, found: 299.0153.
5.8. N-Methoxy-N-(tetrahydrofuran-2-yl)-4-
(trifluoromethyl)benzamide (3h):12
1
White solid; 72% yield; H NMR (400 MHz, CDCl3) δ:
7.75 (d,
1H), 4.08 (q,
J
= 8.1 Hz, 2H), 7.65 (d,
J
= 8.1 Hz, 2H), 5.83 (s,
= 7.2 Hz, 1H), 3.74
5.14. N-Methoxy-3,5-dimethyl-N-(tetrahydrofuran-2-
yl)benzamide (3n):
J
= 7.0 Hz, 1H), 3.80 (q,
J
(s, 3H), 2.30–2.22 (m, 1H), 2.15–2.08, (m, 1H), 2.06–1.99
(m, 1H), 1.94–1.88 (m, 1H); 13C NMR (100 MHz, CDCl3) δ:
Colorless liquid; 76% yield; 1H NMR (400 MHz, CDCl3)
167.7, 137.9, 132.4 (q,
J
= 32.5 Hz), 128.4, 125.2 (q,
J
= 3.5
δ: 7.21 (s, 2H), 7.07 (s, 1H), 5.80 (q,
J = 3.8 Hz, 1H), 4.09
Hz), 123.6 (q, = 270.8 Hz), 88.7, 68.9, 64.7, 28.3, 25.5.
J
(q, = 7.0 Hz, 1H), 3.82–3.76 (m, 4H), 2.32 (s, 6H), 2.28–
J
2.21 (m, 1H), 2.16–2.09 (m, 1H), 2.01–1.96 (m, 1H), 1.91–
1.85 (m, 1H); 13C NMR (100 MHz, CDCl3) δ: 169.4, 137.9,
134.4, 132.3, 125.5, 89.4, 68.9, 64.2, 28.3, 25.6, 21.1.
HRMS (EI) Calcd. for C14H19NO3: 249.1365, found:
249.1370.
5.9. N-Methoxy-3-methyl-N-(tetrahydrofuran-2-yl)benzamide
(3i):
Colorless liquid; 77% yield; 1H NMR (400 MHz, CDCl3)
δ: 7.45–7.41 (m, 2H), 7.31–7.25 (m, 2H), 5.83 (q,
J = 3.9
Hz, 1H), 4.10 (q, = 7.2 Hz, 1H), 3.83–3.78 (m, 4H), 2.37
J
5.15. 3,5-Dichloro-N-methoxy-N-(tetrahydrofuran-2-
yl)benzamide (3o):
(s, 3H), 2.31–2.23 (m,1H), 2.19–2.10 (m, 1H), 2.03–1.98
(m, 1H), 1.94–1.86 (m, 1H); 13C NMR (100 MHz, CDCl3) δ:

6
Tetrahedron
Colorless liquid; 73% yield; 1H NMR (400 MHz,
J = 32.5 Hz), 128.5, 125.0 (q, J = 3.7 Hz), 123.7 (q, J =
CDCl3) δ: 7.52 (s, 2H), 7.423–7.418 (m, 1H), 5.85 (s, 1H),
4.08–4.04 (m, 1H), 3.82–3.79 (m, 1H), 3.72 (s, 3H), 2.26–
2.21 (m, 1H), 2.14–2.03 (m, 2H), 1.95–1.90 (m, 1H); 13C
NMR (100 MHz, CDCl3) δ: 166.2, 137.1, 134.9, 130.7,
126.5, 88.6, 68.9, 64.9, 28.4, 25.4. HRMS (EI) Calcd. for
C12H13Cl2NO3: 289.0272, found: 289.0279.
270.6 Hz), 85.5, 68.2, 65.2, 27.6, 24.9, 23.0.
Acknowledgements
We gratefully acknowledge the National Natural Science
Foundation of China (21772062, 21572078), and the Young
Talent Key Project of Anhui Province (170808J02) for
financial support.
5.16. N-Methoxy-N-(tetrahydrofuran-2-yl)-2-naphthamide
(3p):12
Colorless liquid; 53% yield; 1H NMR (400 MHz, CDCl3)
References and notes
δ: 8.21 (s, 1H), 7.93–7.85 (m, 3H), 7.73 (dd, J1 = 8.5 Hz, J2
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J = 4.0 Hz, 1H),
4.16–4.11 (m, 1H), 3.86–3.80 (m, 4H), 2.37–2.29 (m, 1H),
2.21–2.11 (m, 1H), 2.08–1.99 (m, 1H), 1.95–1.88 (m, 1H);
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carboxamide (3q):12
Colorless liquid; 57% yield; 1H NMR (400 MHz, CDCl3)
δ: 7.57 (s, 1H), 7.16 (q,
J
= 3.5 Hz, 1H), 6.50–6.49 (m, 1H),
= 6.6 Hz, 1H), 3.87–3.82
6.24 (q, = 4.7 Hz, 1H), 4.08 (q,
J
J
(m, 4H), 2.25–2.18 (m, 1H), 2.15–2.07 (m, 2H), 1.97–1.91
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J
= 3.8 Hz, 1H), 7.56 (d,
J
= 5.1 Hz, 1H), 7.09 (t,
= 6.4
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J
= 4.5 Hz, 1H), 4.10 (q, J
Hz, 1H), 3.88 (s, 3H), 3.86–3.84 (m, 1H), 2.27–2.20 (m,
1H), 2.16–2.09 (m, 2H), 1.99–1.93 (m, 1H); 13C NMR (100
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68.8, 65.9, 28.5, 25.4.
5.19. N-Methoxy-N-(tetrahydro-2H-pyran-2-yl)benzamide
(3s):12
1
Colorless liquid; 56% yield; H NMR (400 MHz, CDCl3)
δ: 7.69–7.67 (m, 2H), 7.48–7.44 (m, 1H), 7.41–7.38 (m,
2H), 5.24 (d,
J = 9.9 Hz, 1H), 4.08–4.05 (m, 1H), 3.70 (s,
3H), 3.48 (t, J = 11.5 Hz, 1H), 2.10–1.95 (m, 2H), 1.76–1.73
(m, 1H), 1.59–1.49 (m, 3H); 13C NMR (100 MHz, CDCl3) δ:
169.4, 134.2, 130.7, 128.0, 85.9, 68.1, 64.8, 27.7, 24.9, 23.0.
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J
= 8.2 Hz, 2H), 7.66 (d,
J
= 8.4 Hz, 2H), 5.26 (s,
= 11.0 Hz,
1H), 4.08–4.05 (m, 1H), 3.67 (s, 3H), 3.50 (t,
J
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Supplementary Material
Supplementary data associated with this article can be found
in the online version at…

DDQ-promoted direct C–H amination of ethers with
N-alkoxyamides under visible-light irradiation and
metal-free conditions
Yan Zhang,a,b Lei Wang,*a,b,c Zhiming Wang,a,c and Wei Chen*b,c
Highlights:
In
the
presence
of
commercially
available
2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) as an efficient oxidant, a
variety of N-methoxyamides and ethers undergo C(sp3)–N bond forming
reaction smoothly to deliver the corresponding products in good yields under
visible-light irradiation and metal-free conditions at room temperature.
a Advanced Research Institute and Department of Chemistry
Taizhou University, Taizhou, Zhejiang, 318000, P. R. China
b Department of Chemistry, Huaibei Normal University
Huaibei, Anhui 235000, P. R. China
c State Key Laboratory of Organometallic Chemistry
Shanghai Institute of Organic Chemistry
Shanghai 200032, P. R. China
Email: Lei Wang*- leiwang@chnu.edu.cn, Wei Chen*-lake688123@163.com
[journal], [year], [vol], 00–00
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