O-Perfluoropyridin-4-yl Oximes: Iminyl Radical Precursors for Photo-or Thermal-Induced N-O Cleavage in C(sp2)-C(sp3) Bond Formation

Article abstract of DOI:10.1021/acs.joc.9b03251

O-Perfluoropyridin-4-yl group was first installed onto cycloketone oximes as a new electrophore, which was proven to be efficient iminyl radical precursors under photocatalytic and thermal conditions. A range of O-perfluoropyridin-4-yl oximes were successfully utilized in C(sp²)-C(sp³) bond formations of quinoxalin-2(1H)-ones and alkenes, providing facile accesses to a range of functionalized alkylnitriles.

Full text of DOI:10.1021/acs.joc.9b03251

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Article
O-Perfluoropyridin-4-yl Oximes: Iminyl Radical Precursors for Photo-
or Thermal-Induced N-O Cleavage in C(sp2)-C(sp3) Bond Formation
Peng-Ju Xia, Yuan-Zhuo Hu, Zhi-Peng Ye, Xu-Jie Li, Hao-Yue Xiang, and Hua Yang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b03251 • Publication Date (Web): 23 Jan 2020
Downloaded from pubs.acs.org on January 25, 2020
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O-Perfluoropyridin-4-yl Oximes: Iminyl Radical
Precursors for Photo- or Thermal-Induced N−O Cleavage
2
3
in C(sp )-C(sp ) Bond Formation
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†
, #
†, #
†
†
Peng-Ju Xia, Yuan-Zhuo Hu, Zhi-Peng Ye, Xu-Jie Li, Hao-Yue
,
†
,†,§
Xiang,* and Hua Yang*
†College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, P.
R. China
§Key Laboratory of Hunan Province for Water Environment and Agriculture Product Safety,
Central South University, Changsha 410083, P. R. China
e-mail: hyangchem@csu.edu.cn, xianghaoyue@csu.edu.cn
3
2
New O-aryl oximes
C(sp )-C(sp ) formation
F
F
N
O
F
F
CN
R2
Photo-
N
N
N
R1
O
Ir
N
CN
Ar
Thermal-
sensitive
Ar'
New activation module
Diversified activation pathways
Wide substrate scope
ABSTRACT: O-Perfluoropyridin-4-yl group was firstly installed onto cycloketone
oximes as a new electrophore, which were proven to be efficient iminyl radical
precursors under photocatalytic and thermal conditions. A range of O-perfluoropyridin-
2
3
4-yl oximes were successfully utilized in C(sp )-C(sp ) bond formations of quinoxalin-
2(1H)-ones and alkenes, providing facile accesses to a range of functionalized
alkylnitriles.
INTRODUCTION
1
Over the last decade, iminyl radical chemistry has garnered intensive efforts due
to its unique reactivity in C-C bond-forming events. In general, iminyl radicals are
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prone to proceeding radical transposition to generate C-centered alkyl radicals via the
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classical Norrish type-1 fragmentation or intramolecular hydrogen-atom abstraction
(i.e., 1,5-HAT) (Scheme 1a), providing alternative accesses to C-centered alkyl
4
radicals. Pioneered by Forrester’s group, oxime derivatives have been extensively
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utilized in the generation of iminyl radicals, owing to their readily cleavable N-O bond.
To date, three major activation modes for N-O bond cleavage of oximes, including
6
7
homolytic bond cleavage under harsh conditions, transition-metal-catalyzed or
8,9
visible-light-driven SET-mediated N-O bond cleavage of redox-active oximes, have
progressively evolved. In particular, visible-light-driven photoredox catalysis has
1c
significantly boosted the advance of this field. In general, introducing an electrophore
to oxime is usually necessitated to modulate its redox potential, matching that of the
visible-light-excited photocatalyst. To this end, various oxime esters and oxime ethers
have been designed and used in a range of radical-involved transformations, thus
offering new synthetic opportunities in modern organic chemistry.
Previous reports disclosed that oxime ethers usually deliver the corresponding
iminyl radicals under harsh conditions, such as microwave and elevated
temperature.6a,6b Specifically, electron-poor oxime ethers possess lower reduction
potentials, compatible with single electron transfer (SET) reduction by visible-light-
1
c
excited photocatalysts. Following this rationale, a range of aromatic moieties bearing
strong electron-withdrawing groups were installed onto the oxime skeletons to tailor
9
their redox properties. O-2,4-dinitrophenyl oximes possessing low reduction potentials
and
LUMO energies were found to be suitable for the SET process with the
commonly used photocatalysts. Despite these advances, new readily available
electrophore is still highly desirable to broadly tune the redox potentials of the oxime
derivatives, facilitating the extension of the boundary of the iminyl radical chemistry.
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Scheme 1. Synthetic Profiles of O-aryl Oximes as Iminyl Radical Precursors
a) Generation of iminyl radicals from oxime derivatives and its applications
O
versatile platform
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N-O
cleavage
N
N
HAT
radical-involved
transformations



hv
or
or
scission
iminyl radical
established
O N
2
Me
Ar
COOH
Me
NO2
O
O
unexplored
F
F
F
OH
F
F
N
F
base
N
1
N
O
iminyl radical
F
N
F

2
3
F
b) This work: photo- and thermo-sensitive iminyl radical prescursors
Ir
radical
transposition
3
2
C(sp )-C(sp )
Bond
light or dark
N
3
iminyl
radical
O C F N
radical
addition
5
4
Formation

New activated module
Wide substrate scope
Diversified activation pathways
Broad synthetic potentials
Pentafuoropyridine,10 a readily available multifluorinated arene (1.35 $/g), is
highly electron-deficient and thus susceptible to nucleophilic attack due to the presence
of high electronegative fluorine atoms. Realizing this fact, we envisaged that installing
perfluoropyridin-4-yl moiety onto oximes might offer an effective pathway to markedly
modulate their redox potentials, therefore facilitating the generation of the
corresponding iminyl radicals. Based on our previous work on the radical-mediated N-
O cleavage of strained cycloketone oximes,11 we designed a series of O-
perfluoropyridin-4-yl cycloketone oximes and evaluated their behaviors under both
thermal- and photocatalytic conditions. Interestingly, it turned out that O-
perfluoropyridin-4-yl oximes are able to serve as reliable iminyl racial precursors under
photocatalytic and thermal conditions, enabling the subsequent radical-involved C-C
bond formations (Scheme 1b).
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F
F
N
F
F
F
F
OH
O
N
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K CO
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F
N
F
F
3
MeCN, rt
85%
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E1/2red
≈
-1.52 V vs Ag/AgCl
a)
b)
3
a
0
.2
.0
3a + fac-Ir(ppy)
3
O-aryl oxime 3a
0
3a, Ep/2 = -1.52EV
=-1.52V
p/2
-
0.2
-0.4
3a + f
E
ac
=
-
-
I
1
r
.
(
4
p
0
p
V
y)3,
p/2
Ep/2 = -1.52 V
-
0.6
-
2.2
-2.0
-1.8
-1.6
-1.4
-1.2
-1.0
potential / V
hyz-siyuanhuan-HF.1.fid
hyz-siyuanhuan-HF.2.fid
1H NMR of 3a in CDCl3
19F NMR of 3a in CDCl3
c)
2
2
hyz-siyuanhuan+Irppy3.1.fid
hyz-siyuanhuan+Irppy3.2.fid
1H NMR of 3a+Ir(ppy)3 in CDCl3
19F NMR of 3a+Ir(ppy)3 in CDCl3
1
1
▲
▲
▲
▲
▲
3
.7
3.6
3.5
3.4
3.3
3.2
3.1
3.0
2.9
2.8
2.7
f1 (ppm)
2.6
2.5
2.4
2.3
2.2
2.1
2.0
1.9
1.8
1.7
-85
-90
-95
-100
-105
-110
-115
-120
-125
f1 (ppm)
-130
-135
-140
-145
-150
-155
-160
-165
Figure 1. Preliminary studies on the properties of O-perfluoropyridin-4-yl oxime
a: a) CV studies; b) quenching experiments; c) H NMR and F NMR studies.
1
19
3
RESULTS AND DISSUSSION
Initially, in order to verify the viability of our hypothesis, O-perfluoropyridin-4-yl
cyclobutanone oxime 3a was prepared via a straightforward one-step process in high
yield. The reduction potential of 3a was then examined by cyclic voltammetry, which
would be crucial for the studies on its photochemical behaviors (Figure 1a, see SI for
details). It was found that a reduction wave was recorded at -1.52 V vs. Ag/AgCl (E rp e/ d2
= -1.45 V vs. SCE. in MeCN, see SI for details). Interestingly, adding 1 mol% of fac-
Ir(ppy) resulted in a significant positive-shift for the E value, suggesting that fac-
3
red
Ir(ppy) could enhance the oxidizing ability of 3a. At this stage, we realized that the
3
1
2
photocatalyst fac-Ir(ppy)3 (Ered = -1.73 V vs. SCE. in MeCN) could serve as an
electron donor to directly reduce O-perfluoropyridin-4-yl cyclobutanone oxime 3a
from its excited state, which was further confirmed by the Stern−Volmer plot
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measurements (k = 8.95*10 mL ·s , Figure 1b, see SI for details). The low kq value
q
indicates that a reaction-controlled process might be involved in this photocatalytic
1
19
transformation. Furthermore, H NMR and F NMR experiments were also carried out
to further examine the interaction of fac-Ir(ppy) with 3a (Figure 1c, see SI for details).
3
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Upon mixing 3a with 5 mol% of fac-Ir(ppy) new distinct peaks in H and F spectra
3
,
were observed immediately, suggesting that the N-O bond cleavage of 3a might occur
in the presence of fac-Ir(ppy)3.
Once understanding the inherent features of 3a, we next investigated its reactivity
as an iminyl precursor for the functionalization of C=N or C=C bonds (Scheme 2). As
a result, quinoxalin-2(1H)-ones and alkenes were employed as the radical trapping
reagents to explore the reactivity of 3a. Gratifyingly, under the optimized reaction
2
3
conditions (see SI for details), the resulting C(sp )-C(sp ) coupling products 6a and 7a
were furnished through a homolytic process under elevated temperature (conditions a),
or a photocatalytic SET process (conditions b). Interestingly, 6a and 7a were also
accessible without blue-LED irradiation (conditions c). Based on these results,
incomparable features of O-perfluoropyridin-4-yl oximes can be obviously identified
in the context of radical generation as well as radical-involved transformations.
Scheme 2. Reactivities of O-Perfluoropyridin-4-yl Oxime 3a
N
N
CN
N
O
N
O
O C F N
5
4
4
a
6a
N
Conditions
CN
3a
7a
5
a
Conditions
MeCN, 100 °C, Ar, 12 h
fac-Ir(ppy) , Na CO ,
6
a
1
00
7a
9
0
A
B
C
80
6a
6a
7
0
7
a
60
50
3
2
3
4
0
7
a
MeCN, blue LED, 12 h
30
2
0
fac-Ir(ppy) , Na CO
10
0
3
2
3
MeCN, in dark, 12 h
Conditions A Conditions B Conditions C
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To gain better mechanistic understanding on the process, additional control
experiments were also carried out (Figure 2). On/off and off/on experiments on the
reaction of 3a and 4a demonstrate that the corresponding product 6a can be formed
upon constant irradiation and in the dark, though a much slower reaction was achieved
in the dark. This suggests a photochemical pathway and a redox process might be
effective concurrently in the process of the title reaction. Radical inhibition experiments
were also conducted by adding 2,2,6,6-tetramethyl-1-piperdinyloxy (TEMPO) under
the corresponding reaction conditions, and all the reactions were significantly inhibited
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(Figure 2c). These results indicate that a free-radical pathway might be involved in the
transformations. Additionally, we also studied the spin-trapping reactions of the
involved radicals by adding N-benzylidene-tert-butylamine N-oxide (PBN) under the
standard reaction conditions (see the Supporting Information). Under irradiation with
1
3
blue LED, a EPR signal for CN(CH ) •/PBN adduct was clearly observed, which was
2
3
also identified by HRMS analysis. On the other hand, upon heating the reaction system,
the superposition of EPR signals for radical CN(CH ) •/PBN and C F NO•/PBN
2
3
5 4
adducts were detected, and their molecular ions were detected in HRMS analysis as
well. The observation of PBN adducts derived from C- and O-centered radicals shows
the difference in the pathway for the photo- and thermal-induced N-O bond cleavage of
3
a (please see structures 10 & 11 in the SI).
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c)
a)
TEMPO
3 equiv
3
a + 4a
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MeCN, Ir(ppy) , Na CO
3 2 3
blue LED, Ar, 12 h
or
MeCN, 100 °C, Ar, 12 h
b)
6
a, 0%
+
O
CN
N
fac-Ir(ppy) , Na CO
detected by HRMS
3
2
3
3a + 4a
6a
MeCN, Ar
Figure 2. Control experiments. a) On/off experiments; b) Off/on experiments; c)
Radical trapping experiments.
On the basis of previous reports and the above-mentioned results, a plausible
mechanism for this process is proposed in Scheme 3. In the case of photocatalytic
pathway (Scheme 3, path a), photocatalyst fac-Ir(ppy) was converted to a highly
3
1
2
reducing excited *fac-Ir(ppy) (E (Ir /*Ir ) = −1.73 V vs SCE) under the irradiation
3
1/2 IV
III
of blue light, which was subsequently oxidatively quenched by oxime 3a. As a result,
a reductive N–O bond cleavage of 3a occurred via a single-electron-transfer process to
deliver iminyl radical A. Alternatively, promoted by fac-Ir(ppy) without irradiation
3
(
path b) or heating (path c), iminyl radical A could be generated via a homolytic N–O
bond fragmentation. A facile radical transposition through a strain relieved C–C single
bond cleavage delivered a cyanoalkyl radical species B, which could be rapidly
intercepted by quinoxalin-2(1H)-one 1 and alkene 2 through a radical addition process
to yield a new radical intermediate C. This radical was further oxidized to cation D by
fac-Ir(IV) species (or oxime 3a, or C F NO•) via a SET process, thus completing the
5
4
photocatalytic cycle with releasing the ground state fac-Ir(ppy) . In the presence of base
3
-
2
3
or C F NO , the subsequent deprotonation of intermediate D gave the final C(sp )-C(sp )
5
4
coupling product.
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Scheme 3. Proposed Mechanism
C F NO

scission
path c
5 4
N
CN
dark
homolysis
3a

B
path b
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radical
addition
A
hv
path a
Ir3+
SET
C F NO
5
4
*
C F NO
5
4
N
N
CN
Ir4+
Photoredox
Cycle
O
SET
C
SET
N
N
Ir3+
CN
O
base or C F NO
5
4
D
- H+
6a
C F NO
5
4
Ultimately, the versatility and reliability of this developed strategy as well as the
compatibility of the reaction conditions were extensively evaluated in various
transformations (Scheme 4). A wide range of quinoxalin-2(1H)-ones and alkenes
bearing various substituents were proven to be suitable partners for this transformation,
2
3
giving the corresponding C(sp )-C(sp ) coupling products in good to excellent yields.
It is worth mentioning that the photocatalytic conditions usually gave superior results,
especially for the alkene substrates. As for the thermal processes, unidentified by-
products were also observed at the elevated reaction temperature, resulting in lower
chemical yields. Interestingly, unprotected quinoxa-lin-2(1H)-one also delivered the
desired product 6d in good yield. Noticeably, this newly developed activation module
is also amenable to other ring systems such as N- or O-heterocyclobutane and
cyclohexane, delivering the corresponding products (6q-6u) in satisfactory yields. It is
noteworthy that oxime ester 3f was unable to furnish the desired product under the
photocatalytic conditions, possibly due to its lower strain of the six-membered ring.
Encouragingly, this strategy was further extended to linear oxime 3g, successfully
giving 8a via a 1,5-HAT process. However, other simple alkenes including styrene and
cyclohexene only rendered a fairly complex reaction, and the corresponding products
was unable to be isolated. Impressively, the practicality and scalability of this protocol
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were demonstrated by running the title reaction of 3a with 4a on a large scale under
sunlight for 12 h, which also proceeded smoothly to give 6a in 72% yield.
3
2
Scheme 4. Scope of the Construction of C(sp )-C(sp ) Bonds based on O-
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
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3
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4
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4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
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1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Perfluoropyridin-4-yl Oximes
3
2
Radical prescursors
N
Acceptors
C(sp )-C(sp ) bond formation
R2
MeCN, 100 °C, Ar, 12 h
R2
CN
N
a

N
Ar
CN
o
or
b
or
O
C5F4N
+
r
Ar
Ar'
hv
N
O
N
R1
O
Ar'
R1
MeCN, fac-Ir(ppy)3, Ar
4
5
6
7
3
Na CO , blue LED, 12 h
2
3
Scope of quinoxalin-2(1H)-ones
R2
N
N
N
N
N
CN
CN
CN
CN
N
O
N
O
N
R1
O
N
O
N
H
O
Me
Bn
Et
4
[
] 76%
[hv] >99%
[] 67%
[hv] 98%
[] 71%
[hv] 96%
[] 47%
[hv] 71%
6a
6b
6c
6d
quinoxalin-2(1H)-ones
Me
N
F3C
N
N
R
N
MeO2C
CN
N
N
Me
N
CN
CN
CN
CN
O
N
O
N
O
N
O
O
6
g R = F 6h R =Cl 6i R = Br
[] 41% [] 43% [] 55%
hv] 77% [hv] 70% [hv] 59%
[
[
] 57%
hv] 95%
[] 70%
[hv] 96%
[] 40%
[hv] 86%
[] 45%
6k
6e
6f
6j
[hv] 76%
[
O2N
N
N
Me
N
N
F
F
N
Br
N
CN
CN
CN
Cl
Cl
N
N
CN
CN
O
Me
O
N
O
O
Br
N
O
[
] 23%
[hv] 65%
[] 74%
[hv] >99%
[] 54%
[hv] 90%
[] 37%
[hv] 78%
[] 41%
[hv] 69%
6l
6m
6n
6o
6p
Scope of alkenes
R
R
R
CN
CN
CN
CN
Ar
Ar'
5
7
bc R = Me 7cc R = Ph
7dc R = F
7ec R = Cl
7f R = Me 7g R = Cl
R
[] 33%
7a
alkenes
[
hv] 90%
[] 46%
[] 21%
[hv] 77%
[] 34%
[hv] 73%
[] 19%
[hv] 49%
[] 35%
[hv] 73%
[] 18%
[hv] 71%
[
hv] 73%
Four-membered prescursors
F
F
F
N
F
N
N
N
N
N
N
N
CN
-Naphth
CN
N
CN
O
CN
2
NHBoc
Boc
O
N
O
O
N
O
O
R3
X
3
b-3e
[] 33%
[hv] 88%
[
] 62%
[] 50%
[hv] >99%
[] trace
6t
6q
6r
6s
O
-aryl oximes
[hv] 87%
[hv] 62%
Six-membered prescursors
Linear prescursors
Run under sunlight
Ph
F
F
N
F
F
N
F
N
3a
mmol
6a
12h,
0.327
g,
72%
yield
Ph
O
N
CN
3
N
1
HAT
,5
O
N
O
N
O
N
O
3f
F
F
4a
2 mmol
3
g F
[] 45%
[hv] trace
[] trace
[hv] 30%
6
u
8a
12 h
O-aryl oximes
O-aryl oximes
a
Conditions A: 3 (0.3 mmol), 4 or 5 (0.2 mmol), CH CN (2 mL), 100 ℃, Ar, 12 h, isolated
3
b
yields; Conditions B: 3 (0.3 mmol), 4 or 5 (0.2 mmol), Na CO (0.4 mmol), fac-Ir(ppy) (5
2
3
3
c
mol%), CH CN (2 mL), blue LED, Ar, 12 h, isolated yields. As mixture of inseparable Z/E
3
isomers.
CONCLUSIONS
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In summary, a range of readily prepared, bench-stable O-perfluoropyridin-4-yl
oximes served as effective iminyl radical precursors for the first time. These newly
developed precursors were demonstrated to be compatible with photocatalytic and
thermal reaction conditions. A variety of quinoxalin-2(1H)-ones and alkenes were
0
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functionalized through facile radical-involved C(sp )−C(sp ) bond-forming processes.
This research opens a door for the synthetic applications of O-perfluoropyridin-4-yl
moiety as an activation module in the generation of radicals, thus building up a platform
for broadly exploring radical-involved transformations.
EXPERIMENTAL SECTION
General Experimental Methods. Unless otherwise noted, all the reagents were purchased
from commercial suppliers and used without further purification. And the light source used for
illuminating the reaction vessel (commercial supplier: Synthware) consisted of blue LEDs (λmax
=
1
4
60 nm) purchased from Taobao (https://gpiled.taobao.com). H NMR spectra were recorded at 400
MHz. The chemical shifts were recorded in ppm relative to tetramethylsilane and with the solvent
resonance as the internal standard. Data were reported as follows: chemical shift, multiplicity (s =
singlet, d = doublet, t = triplet, q = quartet, m = multiplet, br = broad), coupling constants (Hz),
1
3
integration. C NMR data were collected at 100 MHz with complete proton decoupling. Chemical
shifts were reported in ppm from the tetramethylsilane with the solvent resonance as internal
standard. 19F NMR data were collected at 376 MHz with complete proton decoupling. UV–Vis
spectra were recorded using a Shimadzu UV-2600. Infrared spectra (IR) were measured by FT-IR
apparatus. High resolution mass spectroscopy (HRMS) was recorded on TOF MS ES+ mass
spectrometer and acetonitrile was used to dissolve the sample. Cyclic Voltammetry (CV)
experiments were recorded on a CHI650D electrochemical workstation. Emission intensities were
recorded using Perkin-Elemer LS 55 Fluorescence Spectrometer. Continuous-wave (CW) electron
paramagnetic resonance (EPR) measurements were performed on a JEOL JES-FA200 X-band
spectrometer. Column chromatography was carried out on silica gel (200-300 mesh).
General procedure for the preparation of 3a-3g. Step1: To a mixture of ketone (5 mmol,
1.0 equiv.) and hydroxylamine hydrochloride (6 mmol, 1.2 equiv.) in MeOH (30 mL) was added
NaOAc (7.5 mmol, 1.5 equiv.). The mixture was heated to reflux until the reaction was monitored
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to be completed by TLC analysis. Methanol was then removed under vacuum, and ethyl acetate and
saturated solution of NaHCO were added. The aqueous layer was extracted once with EtOAc (100
3
mL). The combined organic layers were washed twice with water (20 mL), dried over anhydrous
Na SO , filtered and evaporated under reduced pressure to afford crude product oxime. Step2: A
2
4
1
1
1
1
1
1
1
1
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5
6
7
8
9
0
mixture of oxime (3.8 mmol, 1.0 equiv.), potassium carbonate (7.6 mmol, 2.0 equiv.) and MeCN
20 mL) were stirred at room temperature for 3 h. Then pentafluoropyridine (3.8 mmol, 1.0 equiv)
(
was added and the obtained mixture was stirred overnight at room temperature. Afterwards, brine
was added, and the mixture was diluted with EtOAc (100 mL). The organic layer was washed twice
with water (30 mL), dried over Na SO and concentrated. The residue was purified by column
2
4
chromatography (PE/EtOAc = 100:1 or 25:1) to afford the corresponding O-aryl oximes.
General procedure for the preparation of 4a-4q. The starting materials 4a-4q were prepared
14
according to the previously described method. The data of known compounds are consistent with
the previously reports14,15 and the copies of their HNMR spectra are included in the Supporting
Information. The characterization data of new compounds 4b, 4e, 4f, 4j, 4m, 4n and 4p are also
provided herein.
1
General procedure for the synthesis of compound 5a-5g.Compound 5a was purchased from
Energy Chemistry Company and used without any further purification. The starting materials 5b-
1
6
5g were prepared according to the previously described method. The data of known compounds
are consistent with the previously reports16,17 and the copies of their HNMR spectra are included
in the Supporting Information.
1
General procedure for the synthesis of compound 6a-6u, 7a-7g, 8a. Conditions A [Δ]: To
an oven-dried 15 mL Schleck flask equipped with a magnetic stir bar, o-aryl oximes 3 (0.3 mmol,
1
.5 equiv.), quinoxalin-2(1H)-ones 4 or alkenes 5 (0.20 mmol, 1.0 equiv.) and MeCN (2 mL) were
added. The vessel was evacuated and backfilled with Ar. The tube was screw-capped and stirred at
00 ℃ (oil bath) for 12 h. The solvent was removed under reduced pressure, and then the residue
1
was purified by flash column chromatography (PE/EtOAc = 4:1 or 20:1) to afford the desired
products 6 or 7. Conditions B [hv] : To an oven-dried 15 mL Schleck flask equipped with a magnetic
stir bar, o-aryl oximes 3 or 3a (0.3 mmol, 1.5 equiv.), quinoxalin-2(1H)-ones 4 or alkenes 5 (0.20
mmol, 1.0 equiv.) fac-Ir(ppy) (5% mmol), Na CO (0.4 mmol, 2 equiv.) and MeCN (2 mL) were
,
3
2
3
added. The vessel was evacuated and backfilled with Ar. The tube was screw-capped and stirred at
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6
room temperature under irradiation of 30 W blue LEDs (distance app. 5 cm) for 12 h. The solvent
was removed under reduced pressure, and then the residue was purified by flash column
chromatography (PE/EtOAc = 4:1 or 20:1) to afford the desired products 6, 7 or 8.
Scale-up Reaction. To an oven-dried 100 mL Schleck flask equipped with a magnetic stir bar,
o-aryl oximes 3a (3 mmol, 1.5 equiv.), quinoxalin-2(1H)-ones 4a (2 mmol, 1.0 equiv.) fac-Ir(ppy)
0
1
2
3
4
5
6
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9
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0
,
3
(
5% mmol), Na CO (4 mmol, 2 equiv.) and MeCN (20 mL) were added. The vessel was evacuated
2 3
and backfilled with Ar. The tube was screw-capped and stirred at room temperature under sunlight
for 12 h. The solvent was removed under reduced pressure, and then the residue was purified by
flash column chromatography (PE/EtOAc = 4:1) to afford the desired products 6a (327mg, 72 yield).
Characterization Data of Compound 3a-3g, 4b, 4e, 4f, 4j, 4m, 4n, 4p, 6a-6u, 7a-7g, 8a.
Cyclobutanone O-perfluoropyridin-4-yl oxime (3a). Yellow oil, 755.8 mg, yield 85%; IR (neat)
-1
1
ν 1636, 1473, 1412, 1068, 981, 822 cm ; H NMR (400 MHz, Chloroform-d) δ 3.11 (t, J = 8.0 Hz,
1
9
2
H), 3.02 (t, J = 8.0 Hz, 2H), 2.03 – 2.12 (m, 2H); F NMR (376 MHz, Chloroform-d) δ -90.51 –
1
3
1
-90.34 (m), -155.72 – -155.55 (m); C{ H} NMR (100 MHz, Chloroform-d) δ 167.7, 147.4 – 147.7
(m), 145.0 – 145.4 (m), 142.6 – 142.9 (m), 136.0 – 136.3 (m), 133.4 – 133.7 (m), 31.4, 31.2, 14.3;
+
+
HRMS (ESI): C H F N NaO [M+Na] Calcd 257.0308, Found 257.0308.
9
6
4
2
3-(Naphthalen-2-yl)cyclobutan-1-one O-perfluoropyridin-4-yl oxime (3b). White solid, 1.067
-1 1
g, yield 78%, m.p. 114-116 ℃; IR (neat) ν 1469, 1400, 1062, 965, 809, 750, 723, 471 cm ; H NMR
(400 MHz, Chloroform-d) δ 7.80 – 7.86 (m, 3H), 7.69 (s, 1H), 7.45 – 7.52 (m, 2H), 7.38 – 7.40 (m,
1
9
1
H), 3.83 – 3.91 (m, 1H), 3.68 – 3.61 (m, 1H), 3.53 – 3.61 (m, 1H), 3.27 – 3.38 (m, 2H); F NMR
1
3
1
(
376 MHz, Chloroform-d) δ -90.26 – -90.09 (m), -155.55 – -155.38 (m); C{ H} NMR (100 MHz,
Chloroform-d) δ 164.5, 148.0 – 146.7 (m), 145.9 – 144.3 (m), 143.6 – 142.0 (m), 139.9, 137.1 –
1
3
35.5 (m), 134.0 – 133.4 (m), 133.3, 132.4, 128.8, 127.7, 127.7, 126.6, 126.0, 124.8, 124.5, 39.0,
+
+
8.8, 32.8. HRMS (ESI): C H F N NaO [M+Na] Calcd 383.0778, Found 383.0776.
1
9
12
4
2
tert-Butyl (3-(((perfluoropyridin-4-yl)oxy)imino)cyclobutyl)carbamate (3c). White solid,
.061 g, yield 80%, m.p. 155-156 ℃; IR (neat) ν 1680, 1528, 1467, 1275, 1162, 1065, 984, 833
1
-1 1
cm ; H NMR (400 MHz, Chloroform-d) δ 5.02 (s, 1H), 4.31 (s, 1H), 3.56 – 3.62 (m, 1H), 3.42 –
19
3
9
–
.48 (m, 1H), 3.05 – 3.15 (m, 2H), 1.47 (s, 9H); F NMR (375 MHz, Chloroform-d) δ -90.23 – -
13
1
0.06 (m), -155.57 – -157.40 (m); C{ H} NMR (100 MHz, Chloroform-d) δ 162.1, 154.9, 147.1
147.4 (m), 145.0 – 145.4 (m), 142.6 – 142.9 (m), 136.0 – 136.3 (m), 133.4 – 133.7 (m), 80.4, 40.2,
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+
+
4
9
0.0, 39.8, 28.3; HRMS (ESI): C H F N NaO [M+Na] Calcd 372.0942, Found 372.0969.
14 15 4 3 3
tert-Butyl 3-(((perfluoropyridin-4-yl)oxy)imino)azetidine-1-carboxylate (3d). White solid,
-
1
67.5 mg, yield 76%, m.p. 146-147 ℃; IR (neat) ν 1688, 1473, 1401, 1123, 1061, 972, 839 cm ;
1H NMR (400 MHz, Chloroform-d) δ 4.85 – 4.87 (m, 2H), 4.78 – 4.79 (m, 2H), 1.49 (s, 9H); 19F
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
3
1
NMR (376 MHz, Chloroform-d) δ -89.34 – -89.16 (m), -155.26 – -155.09 (m); C{ H} NMR (100
MHz, Chloroform-d) δ 157.5, 155.9, 146.5 – 146.8 (m), 145.0 – 145.3 (m), 142.5 – 142.9 (m), 136.0
+
+
–
136.3 (m), 133.4 – 133.7 (m), 81.3, 58.1, 57.2, 28.2; HRMS (ESI): C H F N NaO [M+Na]
13 13 4 3 3
Calcd 358.0785, Found 358.0796.
Oxetan-3-one O-perfluoropyridin-4-yl oxime (3e). Pale yellow oil, 672.8 mg, yield 75%; IR
-1
1
(
neat) ν 1639, 1469, 1063, 959, 865, 835, 723 cm ; H NMR (400 MHz, Chloroform-d) δ 5.41 –
5
1
1
.42 (m, 2H), 5.33 – 5.35 (m, 2H); 19F NMR (376 MHz, Chloroform-d) δ -90.00 – -89.84 (m), -
55.70 – -155.54 (m); 13C NMR (100 MHz, Chloroform-d) δ 161.9, 146.4 – 146.7 (m), 144.9 –
45.3 (m), 142.5 – 142.9 (m), 135.9 – 136.3 (m), 133.3 – 133.7 (m), 78.0, 77.8; HRMS (ESI):
+
+
C H F N NaO [M+Na] Calcd 259.0101, Found 259.0114.
8
4
4
2
2
5-Methylhexan-2-one O-perfluoropyridin-4-yl oxime (3f). Yellow oil, 1.066 g, yield 83%; as
an inseparable mixture of Z/E isomers (0.66/1.00); IR (neat) ν 1637, 1494, 1471, 1068, 973, 819,
-1 1
698 cm ; H NMR (400 MHz, Chloroform-d) δ 7.28 – 7.38 (m, 8H), 4.95 (br s, 0.66H), 3.71 (dd, J
= 5.2, 8.0 Hz, 1H), 2.80 – 2.86 (m, 1H), 2.62 – 2.69 (m, 1H), 2.48 – 2.55 (m, 1H), 2.06 – 1.80 (m,
1
2
0.41H). 19F NMR (376 MHz, Chloroform-d) δ -90.50 – -90.33 (m, 1.48F), -90.85 – -90.68 (m,
.26F), -155.02 – -155.85 (m, 1.28F), -155.59 – -155.42 (m, 2.00F); 13C{ H} NMR (100 MHz,
1
M
m
M/m
Chloroform-d) δ 169.7 (169.3 ), 147.5 – 147.8
(m), 145.0 – 145.4 (m), 142.6 – 143.0 (m),
M
m
m
M
M
m
M
1
38.7 (137.6 ), 136.0 – 136.7 (m), 133.4 – 134.1 (m), 129.0 (128.5 ), 128.0 (127.2 ), 126.9
m
M
m
M
M
M
m
m
m
M
m
(
126.8 ), 46.8 (38.3 ), 32.6 , 26.1 , 25.1 , (29.0 , 28.8 , 26.8 ), 23.5 (20.7 ); HRMS (ESI):
+
+
C H F N NaO [M+Na] Calcd 361.0934, Found 361.0933.
1
7
14
4
2
Oxetan-3-one O-perfluoropyridin-4-yl oxime (3g). Colorless liquid, 709.1 mg, yield 85%; as
an inseparable mixture of Z/E isomers (0.77/2.01); IR (neat) ν 1638, 1496, 1471, 1074, 976, 837
-1 1
cm ; H NMR (400 MHz, Chloroform-d) δ 2.53 – 2.58 (m, 0.77H), 2.31 – 2.35 (m, 2.01H), 2.11 (s,
.03H), 2.11 (s, 1.07H), 1.57 – 1.60 (m, 1.68H), 1.44 – 1.48 (m, 2.80H), 0.93 (d, J = 6.4 Hz, 8.21H);
3
19
13
1
F NMR (376 MHz, Chloroform-d) δ -90.71 – -90.49 (m), -155.57 – -155.40 (m); C{ H} NMR
m
M
(
100 MHz, Chloroform-d) δ 167.0 (166.3 ), 147.43 – 147.67 (m), 145.03 – 145.36 (m), 142.62 –
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8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
M
m
M
m
m
M
1
2
2
42.95 (m), 136.11 – 136.47 (m), 133.52 – 133.88 (m), 34.7 , 34.5 , 33.3 , 28.2 , 28.1 , 27.7 ,
M
m
m
M
+
+
2.25 , 22.23 , 19.37 , 14.73 ; HRMS (ESI): C H F N O [M+H] Calcd 279.1115, Found
1
2
15
4
2
79.1115.
1
-Ethylquinoxalin-2(1H)-one (4b). White solid, 219 mg, yield 42%; m.p. 80-82℃; IR (neat) ν
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
1
656, 1593, 1449, 1316, 1150, 1058, 760; H NMR (400 MHz, Chloroform-d) δ 8.31 (s, 1H), 7.90
(
d, J = 7.6 Hz, 1H), 7.61 (t, J = 7.8 Hz, 1H), 7.35 – 7.39 (m, 2H), 4.33 (q, J = 7.2 Hz, 2H), 1.39 (t,
1
3
1
J = 7.2 Hz, 3H); C{ H} NMR (100 MHz, Chloroform-d) δ 154.6, 150.3, 133.7, 132.2, 131.0, 130.8,
+
+
1
23.6, 113.6, 37.0, 12.5; HRMS (ESI): C H N NaO [M+Na] Calcd 197.0686, Found 197.0709.
10 10 2
1
,5-Dimethylquinoxalin-2(1H)-one (4e). White solid, 378 mg, yield 72%; m.p. 144-146℃; IR
1
(
neat) ν 1653, 1531, 1461, 1309, 1062, 934, 763; H NMR (400 MHz, Chloroform-d) δ 8.31 (s, 1H),
1
7
.48 (t, J = 8.0, 1H), 7.17 – 7.23 (m, 2H), 3.68 (s, 3H), 2.68 (s, 3H); 13C{ H} NMR (100 MHz,
Chloroform-d) δ 155.0, 148.4, 139.2, 133.3, 132.0, 130.8, 125.1, 111.7, 28.9, 17.6; HRMS (ESI):
+
+
C H N NaO [M+Na] Calcd 197.0685, Found 197.0703.
1
0
10
2
1,6-Dimethylquinoxalin-2(1H)-one (4f). White solid, 280 mg, yield 54%; m.p. 133-135℃; IR
1
(neat) ν 1646, 1445, 1311, 1058, 805, 579, 477; H NMR (400 MHz, Chloroform-d) δ 8.26 (d, J =
18.8 Hz, 1H), 7.75 (d, J = 8.0 Hz, 0.5 H), 7.67 (s, 0.5H), 7.41 – 7.43 (m, 0.5H), 7.24 (d, J = 8.4 Hz,
1
3
1
0.5H), 7.18 (d, J = 8.4 Hz, 0.5H), 7.13 (s, 0.5H), 3.68 (s, 3H), 2.50 (d, J = 26.8 Hz, 3H); C{ H}
NMR (101 MHz, Chloroform-d) δ 155.2, 155.0, 150.1, 148.9, 142.0, 133.7, 133.3, 133.1, 132.2,
+
1
31.6, 131.0, 130.3, 130.2, 125.1, 113.9, 113.5, 28.7, 28.7, 22.2, 20.6; HRMS (ESI): C H N NaO
10 10 2
+
[M+Na] Calcd 197.0685, Found 197.0698.
1
-Methyl-6-(trifluoromethyl)quinoxalin-2(1H)-one (4j). White solid, 242 mg, yield 35%; m.p.
1
1
8
1
05-107℃; IR (neat) ν H NMR (400 MHz, Chloroform-d) δ 8.38 (s, 1H), 8.17 (s, 1H), 7.83 (d, J =
.4 Hz, 1H), 7.45 (d, J = 8.8 Hz, 1H), 3.73 (s, 3H); 13C{ H} NMR (100 MHz, Chloroform-d) δ
54.8, 151.7, 135.6, 132.7, 128.0 (q, JC-F = 3.9 Hz), 127.43 (q, JC-F = 3.5 Hz), 126.1 (q, JC-F = 33.8
1
+
+
Hz), 123.6 (q, JC-F = 271.8 Hz), 114.5, 29.0; HRMS (ESI): C H N F NaO [M+Na] Calcd
10
7
2 3
2
51.0403, Found 251.0431.
1
,6,7-Trimethylquinoxalin-2(1H)-one (4m). Pale yellow solid, 538 mg, yield 95%; m.p. 175-
1
1
77℃; IR (neat) ν 1644, 1532, 1447, 1032, 992, 930, 583; H NMR (400 MHz, Chloroform-d) δ
13
1
8
.22 (s, 1H), 7.61 (s, 1H), 7.09 (s, 1H), 3.66 (s, 3H), 2.42 (s, 3H), 2.35 (s, 3H); C{ H} NMR (100
Hz, Chloroform-d) δ 155.1, 148.9, 141.0, 132.7, 131.8, 131.2, 130.4, 114.3, 28.6, 20.6, 19.1; HRMS
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2
3
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5
6
7
8
9
+
+
(
ESI): C H N NaO [M+Na] Calcd 211.0842, Found 211.0861.
11 12 2
6
,7-Difluoro-1-methylquinoxalin-2(1H)-one (4n). White solid, 438 mg, yield 74%; m.p. 124-
1
1
26℃; IR (neat) ν 1667, 1601, 1452, 1308, 1119, 887, 828, 522; H NMR (400 MHz, Chloroform-
1
3
1
d) δ 8.27 (s, 1H), 7.68 – 7.73 (m, 1H), 7.14 – 7.19 (m, 2H), 3.66 (s, 3H); C{ H} NMR (100 MHz,
Chloroform-d) δ 154.5, 152.0 (dd, JC-F = 254.7, 14.3 Hz), 150.5 (d, JC-F = 3.6 Hz), 146.7 (dd, JC-F
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
=
247.8, 14.0 Hz), 130.6 (dd, JC-F = 9.1, 1.7 Hz), 129.6 (dd, JC-F = 9.2, 2.9 Hz), 118.2 (dd, JC-F =
+
+
1
2
8.1, 2.3 Hz), 102.5 (d, JC-F = 23.2 Hz), 29.3; HRMS (ESI): C H F N NaO [M+Na] Calcd
9 6 2 2
19.0340, Found 219.0340.
6
,7-Dibromo-1-methylquinoxalin-2(1H)-one (4p). Pale yellow solid, 249 mg, yield 26%; m.p.
1
2
62-264℃; IR (neat) ν 1659, 1525, 1447, 1392, 1285, 921, 799; H NMR (400 MHz, Chloroform-
13
1
d) δ 8.29 (s, 1H), 8.12 (s, 1H), 7.62 (s, 1H), 3.65 (s, 3H); C{ H} NMR (100 MHz, Chloroform-d)
+
δ 154.3, 151.5, 134.4, 133.1, 133.0, 127.7, 119.0, 118.5, 29.0; HRMS (ESI): C H Br N NaO
9
6
2
2
+
[
M+Na] Calcd 338.8739, Found 338.8728.
6
d
4-(4-Methyl-3-oxo-3,4-dihydroquinoxalin-2-yl)butanenitrile (6a). Pale yellow solid, 34.5 mg,
1
yield: 76% [Δ]; 45.2mg, yield >99% [hv]; m.p. 110-111 ℃; H NMR (400 MHz, Chloroform-d) δ
7.82 (d, J = 8.0 Hz, 1H), 7.56 (t, J = 7.6 Hz, 1H), 7.30 – 7.42 (m, 2H), 3.70 (s, 3H), 3.09 (t, J = 7.2
+
+
Hz, 2H), 2.55 (t, J = 7.2 Hz, 2H), 2.19 – 2.26 (m, 2H); HRMS (ESI): C H N NaO [M+Na] Calcd
1
3
13
3
250.0951, Found 250.0955.
-(4-Ethyl-3-oxo-3,4-dihydroquinoxalin-2-yl)butanenitrile (6b). Pale yellow solid, 32.2 mg,
yield: 67% [Δ]; 47.3mg, yield 98% [hv]; m.p. 102-103 ℃; IR (neat) ν 2921, 1645, 1596, 1463, 1165,
4
-
1 1
1
092, 759, 712 cm ; H NMR (400 MHz, Chloroform-d) δ 7.84 (d, J = 8.0 Hz, 1H), 7.55 (t, J = 7.2
Hz, 1H), 7.33 – 7.36 (m, 2H), 4.33 (q, J = 7.2 Hz, 2H), 3.09 (t, J = 7.2 Hz, 2H), 2.55 (t, J = 7.2 Hz,
1
3
1
2
1
H), 2.20 – 2.27 (m, 2H), 1.38 (t, J = 7.2 Hz, 3H); C{ H} NMR (100 MHz, Chloroform-d) δ 158.5,
54.2, 132.8, 132.0, 130.1, 130.0, 123.5, 119.6, 113.5, 37.4, 32.2, 22.1, 16.8, 12.4; HRMS (ESI):
+
+
C H N NaO [M+Na] Calcd 264.1107, Found 264.1115.
1
4
15
3
6
d
4
-(4-Benzyl-3-oxo-3,4-dihydroquinoxalin-2-yl)butanenitrile (6c). Pale yellow solid, 42.9 mg,
1
yield: 71% [Δ]; 58.3mg, yield 96% [hv]; m.p. 116-117 ℃; H NMR (400 MHz, Chloroform-d) δ
7
.84 (d, J = 8.0 Hz, 1H), 7.43 (t, J = 8.0 Hz, 1H), 7.23 – 7.33 (m, 7H), 5.50 (s, 2H), 3.15 (t, J = 7.2
+
+
Hz, 2H), 2.58 (t, J = 7.6 Hz, 2H), 2.24 – 2.31 (m, 2H); HRMS (ESI): C H N NaO [M+Na] Calcd
1
9
17
3
3
26.1264, Found 326.1272.
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1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
6
d
4
-(3-oxo-3,4-Dihydroquinoxalin-2-yl)butanenitrile (6d). Pale yellow solid, 20.1 mg, yield:
1
4
7% [Δ]; 30.3mg, yield 71% [hv]; m.p. 190-192 ℃; H NMR (400 MHz, DMSO-d ) δ 12.34 (s,
6
1
H), 7.73 (d, J = 8.0 Hz, 1H), 7.49 (t, J = 7.6 Hz, 1H), 7.26 – 7.30 (m, 2H), 2.90 (t, J = 7.2 Hz, 2H),
+
+
2
.64 (t, J = 7.2 Hz, 2H), 2.00 – 2.07 (m, 2H); HRMS (ESI): C H N NaO [M+Na] Calcd 236.0794,
12 11 3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Found 236.0809.
8
g
4
-(4,8-Dimethyl-3-oxo-3,4-dihydroquinoxalin-2-yl)butanenitrile (6e). Pale yellow solid, 27.5
1
mg, yield: 57% [Δ]; 45.7mg, yield 95% [hv]; m.p. 128-130 ℃; H NMR (400 MHz, Chloroform-d)
δ 7.42 (t, J = 8.0 Hz, 1H), 7.21 (d, J = 7.6 Hz, 1H), 7.15 (d, J = 8.4 Hz, 1H), 3.70 (s, 3H), 3.10 (t, J
=
6.8 Hz, 2H), 2.67 (s, 3H), 2.58 (t, J = 7.2 Hz, 2H), 2.22 – 2.29 (m, 2H); HRMS (ESI):
+
+
C H N NaO [M+Na] Calcd 264.1107, Found 264.1120.
1
4
15
3
6d
4
-(4,7-Dimethyl-3-oxo-3,4-dihydroquinoxalin-2-yl)butanenitrile(6f). Pale yellow solid, 33.7
mg, yield: 70% [Δ]; 46.2 mg, yield 96% [hv]; m.p. 112-114 ℃; as an inseparable (1:1) mixture of
1
6
-methyl and 7-methylquinoxalin-2(1H)-ones was used as the substrate; H NMR (400 MHz,
Chloroform-d) δ 7.70 (d, J = 8.0 Hz, 0.5H), 7.63 (s, 0.5H), 7.37 (d, J = 8.4 Hz, 0.5H), 7.16 – 7.22
(m, 1H), 7.10 (s, 0.5H), 3.69 (s, 3H), 3.07 (q, J = 6.8 Hz, 2H), 2.52 – 2.56 (m, 3.5H), 2.46 (s, 1.5H),
+
+
2.23 (m, 2H); HRMS (ESI): C H N NaO [M+Na] Calcd 264.1107, Found 264.1102.
1
4
15
3
4-(7-Fluoro-4-methyl-3-oxo-3,4-dihydroquinoxalin-2-yl)butanenitrile (6g).6d Pale yellow
1
solid, 20.1 mg, yield: 41% [Δ]; 37.9 mg, yield 77% [hv]; m.p. 101-103 ℃; H NMR (400 MHz,
Chloroform-d) δ 7.53 (dd, J = 8.8, 2.4 Hz, 1H), 7.28 – 7.33 (m, 2H), 3.71 (s, 3H), 3.10 (t, J = 6.8
+
+
Hz, 2H), 2.54 (t, J = 7.2 Hz, 2H), 2.18 – 2.26 (m, 2H); HRMS (ESI): C H FN NaO [M+Na]
13 12
3
Calcd 268.0857, Found 268.0859.
4
-(7-Chloro-4-methyl-3-oxo-3,4-dihydroquinoxalin-2-yl)butanenitrile (6h).6d Pale yellow
1
solid, 22.2 mg, yield: 43% [Δ]; 36.8 mg, yield 70% [hv]; m.p. 112-114 ℃; H NMR (400 MHz,
Chloroform-d) δ 7.83 (d, J = 2.4 Hz, 1H), 7.51 (dd, J = 2.4, 8.8 Hz, 1H), 7.26 (d, J = 8.9 Hz, 1H),
3
.69 (s, 3H), 3.09 (t, J = 7.2 Hz, 2H), 2.55 (t, J = 7.2 Hz, 2H), 2.18 – 2.25 (m, 2H); HRMS (ESI):
+
+
C H ClN NaO [M+Na] Calcd 284.0561, Found 284.0574.
1
3
12
3
6
d
4
-(7-Bromo-4-methyl-3-oxo-3,4-dihydroquinoxalin-2-yl)butanenitrile (6i). Pale yellow solid,
1
3
3.7 mg, yield: 55% [Δ]; 35.8mg, yield 59% [hv]; m.p. 100-102 ℃; H NMR (400 MHz,
Chloroform-d) δ 7.98 (d, J = 2.0 Hz, 1H), 7.63 (dd, J = 2.0, 8.8 Hz, 1H), 7.19 (d, J = 8.8 Hz, 1H),
3
.68 (s, 3H), 3.09 (t, J = 7.2 Hz, 2H), 2.55 (t, J = 7.2 Hz, 2H), 2.18 – 2.25 (m, 2H); HRMS (ESI):
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+
+
C H BrN NaO [M+Na] Calcd 328.0056, Found 328.0074.
1
3
12
3
4
-(4-Methyl-3-oxo-7-(trifluoromethyl)-3,4-dihydroquinoxalin-2-yl)butanenitrile (6j). Pale
yellow solid, 23.6 mg, yield: 40% [Δ]; 50.8mg, yield 86% [hv]; m.p. 110-112 ℃; IR (neat) ν 1663,
-1 1
1
7
7
1
2
3
618, 1312, 1218, 1169, 1106, 831, 655 cm ; H NMR (400 MHz, Chloroform-d) δ 8.12 (s, 1H),
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
.78 (d, J = 8.8 Hz, 1H), 7.42 (d, J = 8.4 Hz, 1H), 3.73 (s, 3H), 3.12 (t, J = 7.2 Hz, 2H), 2.56 (t, J =
1
3
1
.2 Hz, 2H), 2.20 – 2.27 (m, 2H); C{ H} NMR (100 MHz, Chloroform-d) δ 160.3, 154.5, 135.4,
31.8, 127.2 (q, JC-F = 4.0 Hz, ), 126.4 (q, JC-F = 3.5 Hz), 126.0 (q, JC-F = 33.7 Hz), 123.7 (q, JC-F
=
+
+
71.8 Hz), 119.5, 114.3, 32.2, 29.4, 21.7, 16.7; HRMS (ESI): C H F N NaO [M+Na] Calcd
1
4
12
3
3
18.0825, Found 318.3008.
Methyl 3-(3-cyanopropyl)-1-methyl-2-oxo-1,2-dihydroquinoxaline-6-carboxylate (6k).6d Pale
1
yellow solid, 25.6 mg, yield: 45% [Δ]; 43.2 mg, yield 76% [hv]; m.p. 134-136 ℃; H NMR (400
MHz, Chloroform-d) δ 7.98 – 8.02 (m, 2H), 7.87 (d, J = 8.4 Hz, 1H), 3.99 (s, 3H), 3.75 (s, 3H), 3.12
+
(
t, J = 7.2 Hz, 2H), 2.56 (t, J = 7.2 Hz, 2H), 2.21 – 2.28 (m, 2H); HRMS (ESI): C H N NaO
15 15 3 3
+
[M+Na] Calcd 308.1006, Found 308.1018.
4-(4-Methyl-7-nitro-3-oxo-3,4-dihydroquinoxalin-2-yl)butanenitrile (6l).6d Pale yellow solid,
1
12.5 mg, yield: 23% [Δ]; 35.1 mg, yield 65% [hv]; m.p. 127-129 ℃; H NMR (400 MHz,
Chloroform-d) δ 8.72 (d, J = 2.4 Hz, 1H), 8.41 (dd, J = 9.2, 2.4 Hz, 1H), 7.42 (d, J = 9.2 Hz, 1H),
3.76 (s, 3H), 3.15 (t, J = 6.8 Hz, 2H), 2.58 (t, J = 7.2 Hz, 2H), 2.21 – 2.28 (m, 2H); HRMS (ESI):
+
+
C H N NaO [M+Na] Calcd 295.0802, Found 295.0821.
13 12
4
3
4
-(4,6,7-Trimethyl-3-oxo-3,4-dihydroquinoxalin-2-yl)butanenitrile (6m). Pale yellow solid,
3
1
7.6 mg, yield: 74% [Δ]; 50.8 mg, yield >99% [hv]; m.p. 162-164 ℃; IR (neat) ν 1614, 1583, 1463,
-1 1
172, 1088, 1013, 502 cm ; H NMR (400 MHz, Chloroform-d) δ 7.57 (s, 1H), 7.07 (s, 1H), 3.67
(
s, 3H), 3.05 (t, J = 7.2 Hz, 2H), 2.53 (t, J = 7.2 Hz, 2H), 2.42 (s, 3H), 2.35 (s, 3H), 2.17 – 2.24 (m,
1
2
1
2
H); 13C{ H} NMR (100 MHz, Chloroform-d) δ 157.1, 154.8, 139.8, 132.7, 131.1, 130.9, 129.9,
+
+
19.7, 114.2, 32.3, 29.0, 22.2, 20.5, 19.2, 16.8; HRMS (ESI): C H N NaO [M+Na] Calcd
1
5
17
3
78.1264, Found 278.1260.
-(6,7-Difluoro-4-methyl-3-oxo-3,4-dihydroquinoxalin-2-yl)butanenitrile (6n). Pale yellow
solid, 28.3 mg, yield: 54% [Δ]; 47.1 mg, yield 90% [hv]; m.p. 136-138 ℃; IR (neat) ν 1648, 1603,
4
-1
1
1
7
366, 1255, 918, 780 cm ; H NMR (400 MHz, Chloroform-d) δ 7.65 (dd, J = 9.9, 8.4 Hz, 1H),
.12 (dd, J = 11.2, 7.0 Hz, 1H), 3.66 (s, 3H), 3.08 (t, J = 7.1 Hz, 2H), 2.54 (t, J = 7.2 Hz, 2H), 2.36
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1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
1
3
1
–
1.90 (m, 2H); C{ H} NMR (100 MHz, Chloroform-d) δ 159.1 (d, J = 3.5 Hz), 154.3, 151.3
C-F
(
dd, JC-F = 253.3, 14.4 Hz), 146.7 (dd, JC-F = 247.3, 13.9 Hz), 130.3 (dd, JC-F = 8.8, 1.7 Hz), 128.7
(
dd, JC-F = 9.3, 2.9 Hz), 119.5, 117.5 (dd, JC-F = 18.0, 2.0 Hz), 102.4 (d, JC-F = 23.1 Hz), 32.2, 29.6,
+
+
2
1.8, 16.7; HRMS (ESI): C H F N NaO [M+Na] Calcd 286.0762, Found 286.0763.
13 11 2 3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
4
-(6,7-Dichloro-4-methyl-3-oxo-3,4-dihydroquinoxalin-2-yl)butanenitrile (6o).6d Pale yellow
1
solid, 21.6 mg, yield: 37% [Δ]; 46 mg, yield 78% [hv]; m.p. 143-145 ℃; H NMR (400 MHz,
Chloroform-d) δ 7.92 (s, 1H), 7.41 (s, 1H), 3.66 (s, 3H), 3.08 (t, J = 6.8 Hz, 2H), 2.54 (t, J = 7.2 Hz,
+
+
2
3
H), 2.17 – 2.24 (m, 2H); HRMS (ESI): C H Cl N NaO [M+Na] Calcd 318.0171, Found
13 11 2 3
18.0182.
-(6,7-Dibromo-4-methyl-3-oxo-3,4-dihydroquinoxalin-2-yl)butanenitrile (6p). Pale yellow
solid, 31.2 mg, yield: 41% [Δ]; 52.5 mg, yield 69% [hv]; m.p. 143-145 ℃; IR (neat) ν 2919, 1657,
4
-1
1
1
456, 1393, 1102, 406 cm ; H NMR (400 MHz, Chloroform-d) δ 8.07 (s, 1H), 7.58 (s, 1H), 3.65
1
3
1
(
s, 3H), 3.07 (t, J = 7.2 Hz, 2H), 2.54 (t, J = 7.2 Hz, 2H), 2.17 – 2.24 (m, 2H); C{ H} NMR (100
MHz, Chloroform-d) δ 160.3, 154.1, 133.8, 133.0, 132.2, 126.3, 119.4, 118.9, 118.4, 32.3, 29.3,
+
+
21.7, 16.7; HRMS (ESI): C H Br N NaO [M+Na] Calcd 405.9161, Found 405.9185.
1
3
11
2
3
4-(4-Methyl-3-oxo-3,4-dihydroquinoxalin-2-yl)-3-(naphthalen-2-yl)butanenitrile (6q). Pale
yellow solid, 43.9 mg, yield: 62% [Δ]; 61.6 mg, yield 87% [hv]; m.p. 170-172 ℃; IR (neat) ν 2978,
-1 1
2905, 1649, 1405, 1063, 750 cm ; H NMR (400 MHz, Chloroform-d) δ 7.77 – 7.83 (m, 5H), 7.40
–
3
7.52 (m, 4H), 7.31 (t, J = 7.6 Hz, 1H), 7.23 (d, J = 4.8 Hz, 1H), 4.06 (p, J = 7.2, 1H), 3.62 (s, 3H),
1
3
1
.56 (dd, J = 16.4, 6.3 Hz, 1H), 3.44 (dd, J = 16.4, 8.4 Hz, 1H), 2.83 – 2.94 (m, 2H); C{ H} NMR
(
100 MHz, Chloroform-d) δ 157.3, 154.8, 139.1, 133.5, 133.0, 132.8, 132.5, 130.2, 129.8, 128.7,
27.9, 127.6, 126.3, 126.2, 125.9, 125.5, 123.7, 118.5, 113.7, 39.0, 38.6, 29.1, 24.4; HRMS (ESI):
1
+
+
C H N NaO [M+Na] Calcd 376.1420, Found 376.1425.
2
3
19
3
tert-Butyl
(1-cyano-3-(4-methyl-3-oxo-3,4-dihydroquinoxalin-2-yl)propan-2-yl)carbamate
6
d
1
(
6r). Pale yellow solid, 36.7 mg, yield: 50% [Δ]; 67.7 mg, yield >99% [hv]; m.p. 151-153 ℃; H
NMR (400 MHz, Chloroform-d) δ 7.84 (d, J = 8.0 Hz, 1H), 7.56 – 7.60 (m, 1H), 7.32 – 7.39 (m,
H), 5.56 (d, J = 6.4 Hz, 1H), 4.46 (d, J = 5.2 Hz, 1H), 3.72 (s, 3H), 3.28 (d, J = 6.4 Hz, 2H), 2.95
dd, J = 16.7, 5.1 Hz, 1H), 2.84 (dd, J = 16.6, 4.2 Hz, 1H), 1.37 (s, 9H); HRMS (ESI):
2
(
+
+
C H N NaO [M+Na] Calcd 365.1584, Found 365.1568.
1
8
22
4
3
tert-Butyl (cyanomethyl)((4-methyl-3-oxo-3,4-dihydroquinoxalin-2-yl)methyl)carbamate (6s).
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Pale yellow solid, 21.6 mg, yield: 33% [Δ]; 58.0 mg, yield 88% [hv]; m.p. 153-155 ℃, as an
-1
inseparable mixture of atropisomers; IR (neat) ν 1708, 1647, 1456, 1256, 1159, 1130, 757, 727 cm ;
1H NMR (400 MHz, Chloroform-d,) δ 7.86 M/m (d, J = 7.6 Hz, 1H), 7.55 – 7.61M/m (m, 1H), 7.30 –
7
3
1
.39M/m (m, 2H), 4.77 – 4.79M/m (m, 2H), 4.45 M (s, 1.11H), 4.32 m (s, 0.88H), 3.72 (s, 1.66H),
M
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
m
m
M
13
1
.68 (s, 1.33H), 1.56 (s, 4.00H), 1.39 (s, 5.00H); C{ H} NMR (100 MHz, Chloroform-d) δ
55.2 , 154.4 , 154.1, 153.8, 153.7 , 133.1 , 132.4 , (132.3 ), 130.6 (130.5 , 130.22M/m, 124.0M
M
m
M
m
M
M
m)
(
(
123.8 ), 116.1M/m, 113.8M (113.7 ), 82.1 (81.7 M), 49.9m (49.5 ), 37.34 (36.29 ), 28.91
m
m
m
M
m
M
M
m
m
M
+
+
28.85 ), 28.2 (28.1 ); HRMS (ESI): C H N NaO [M+Na] Calcd 351.1428, Found 351.1454.
1
7
20
4
3
-((4-Methyl-3-oxo-3,4-dihydroquinoxalin-2-yl)methoxy)acetonitrile (6t).6d Pale red solid,
2
1
2
8.5 mg, yield 62% [hv]; m.p. 112-113 ℃; H NMR (400 MHz, Chloroform-d) δ 7.94 (d, J = 8.0
Hz, 1H), 7.61 (t, J = 7.6 Hz, 1H), 7.35 – 7.42 (m, 2H), 4.95 (s, 2H), 4.58 (s, 2H), 3.72 (s, 3H);
+
+
HRMS (ESI): C H N NaO [M+Na] Calcd 252.0743, Found 252.0764.
1
2
11
3
2
6
-(4-Methyl-3-oxo-3,4-dihydroquinoxalin-2-yl)-6-phenylhexanenitrile (6u).8g Pale yellow
1
solid, 29.8 mg, yield: 45% [Δ]; m.p. 111-112 ℃; H NMR (400 MHz, Chloroform-d) δ 7.92 (d, J =
8.0 Hz, 1H), 7.52 (t, J = 8.4 Hz, 1H), 7.43 (d, J = 7.2 Hz, 2H), 7.35 (t, J = 7.2 Hz, 1H), 7.25 – 7.29
(m, 3H), 7.18 (t, J = 7.6 Hz, 1H), 4.67 (t, J = 7.6 Hz, 1H), 3.62 (s, 3H), 2.32 (t, J = 7.2 Hz, 3H), 2.04
+
+
– 2.13 (m, 1H), 1.67 – 1.76 (m, 2H), 1.40 – 1.54 (m, 2H); HRMS (ESI): C H N NaO [M+Na]
2
1
21
3
Calcd 354.1577, Found 354.1566.
8
b
6
,6-Diphenylhex-5-enenitrile (7a). Colorless oil, 16.4 mg, yield: 33% [Δ]; 44.4 mg, yield 90%
1
[
hv]; H NMR (400 MHz, Chloroform-d) δ 7.31 – 7.39 (m, 3H), 7.20 – 7.27 (m, 5H), 7.15 (d, J =
6
.8 Hz, 2H), 6.01 (t, J = 7.2 Hz, 1H), 2.22 – 2.30 (m, 4H), 1.74 – 1.81 (m, 2H); HRMS (ESI):
+
+
C H NNa [M+Na] Calcd 270.1253, Found 270.1273.
1
8
17
6
-Phenyl-6-(p-tolyl)hex-5-enenitrile (7b).8b Colorless oil, 24.0 mg, yield: 46% [Δ]; 38.3mg,
yield 73% [hv]; as an inseparable mixture of Z/E isomers; IR (neat) ν 1648, 1597, 1464, 1312, 752,
-
1 1
7
–
1
1
03 cm ; H NMR (400 MHz, Chloroform-d) δ 7.03 – 7.39 (m, 9H), 5.97 (t, J = 7.2 Hz, 1H), 2.22
1
3
1
2.38 (m, 7H), 1.75 – 1.83 (m, 2H); C{ H} NMR (100 MHz, Chloroform-d) δ 143.74 (143.65),
42.4, 139.8 (139.34), 137.1 (136.9), 136.61, 129.68 (129.60), 129.07 (128.89), 128.34 (128.15),
27.24 (127.19), 127.07, 126.5, 125.7, 119.59 (119.58), 28.77 (28.68), 25.82, 21.26 (21.08), 16.71
+
+
(
16.69); HRMS (ESI): C H NNa [M+Na] Calcd 284.1410, Found 284.1424.
19 19
6
-([1,1'-Biphenyl]-4-yl)-6-phenylhex-5-enenitrile (7c). Colorless oil, 13.6 mg, yield: 21% [Δ];
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9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
5
1
7
0.0mg, yield 77% [hv]; as an inseparable mixture of Z/E isomers (0.28/0.68); IR (neat) ν 1487,
-1 1
445, 840, 762, 736, 696 cm ; H NMR (400 MHz, Chloroform-d) δ 7.56 – 7.64 (m, 3.5H), 7.32 –
.51 (m, 4.5H), 7.18 – 7.30 (m, 6H), 6.01 – 6.10 (m, 1H), 2.25 – 2.36 (m, 4H), 1.79 – 1.86 (m, 2H);
1
3
1
M
m
m
M
M
C{ H} NMR (100 MHz, Chloroform-d) δ 143.5 (143.4 ), 142.2, 141.0 (140.7 ), 140.1
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
m
M
m
M
m
m
M
m
M
(139.5 ), 138.6, 130.2 (129.7 ), 128.81 (128.77 ), 128.5 (128.2 ), 127.5 (127.4 ), 127.3,
M
m
M
m
M
m
M
m
M
m
M
1
27.1 (127.0 ), 126.9 (126.6 ), 119.53 (119.51 ), 28.84 (28.78 ), 25.83 (25.78 ), 16.74
m
+
+
(16.72 ); HRMS (ESI): C H NNa [M+Na] Calcd 346.1566, Found 346.1570.
24 21
6
-(4-Fluorophenyl)-6-phenylhex-5-enenitrile (7d). Colorless oil, 18.1 mg, yield: 34% [Δ]; 38.7
mg, yield 73% [hv]; as an inseparable mixture of Z/E isomers (0.41:0.49); IR (neat) ν 1503, 1223,
-1
1
1
158, 835, 764, 701 cm ; H NMR (400 MHz, Chloroform-d) δ 7.06 – 7.41 (m, 8H), 6.93 – 6.97
(
m, 1H), 5.93 – 6.03 (m, 1H), 2.23 – 2.34 (m, 4H), 1.76 – 1.84 (m, 2H); 13C NMR (100 MHz,
Chloroform-d) δ 162.2 (d, JC-F = 246.5.2 Hz) [162.0 (d, JC-F = 246.3 Hz)], 142.8, 142.0 (139.43),
38.29 (d, JC-F = 3.3 Hz) [135.45 (d, JC-F = 3.5 Hz)], 131.3 (d, JC-F = 7.9 Hz) [128.8, (d, JC-F = 7.9
1
Hz)], 129.6 (128.5), 128.3 (127.2), 127.41 (127.40), 127.0, 126.47 (126.46), 119.46 (119.43), 115.4
(d, JC-F = 21.3 Hz) [115.0 (d, JC-F = 21.4 Hz)], 28.72 (28.70), 25.71 (25.69), 16.7; HRMS (ESI):
+
+
C H FNNa [M+Na] Calcd 288.1159, Found 288.1171.
1
8
16
6-(4-Chlorophenyl)-6-phenylhex-5-enenitrile (7e). Colorless oil, 10.8 mg, yield: 19% [Δ]; 27.5
mg, yield 49% [hv]; as an inseparable mixture of Z/E isomers; IR (neat) ν 1590, 1562, 1445, 1419,
-1 1
1
1
078, 775, 699 cm ; H NMR (400 MHz, Chloroform-d) δ 7.05 – 7.41 (m, 9H), 6.00 – 6.05 (m,
H), 2.23 – 2.34 (m, 4H), 1.76 – 1.84 (m, 2H), 1.57 – 1.58 (m, 1H); 13C{ H} NMR (100 MHz,
1
M
M
M
m
m
m
M
m
m
Chloroform-d) δ 142.6 , 141.47 , 141.44 (144.0 , 142.7 , 138.9 ), 134.3 (134.2 ), 129.71
M
M
m
m
M
M
m
m
M)
(129.65 ), 129.6 (129.4 ), 128.6 (128.3 ), 127.93 (127.89 ), 127.6 (127.5 , 127.4, 127.24,
M
M
m
M
m
+
1
27.21, 127.1 125.4, 119.4, 28.73 (28.70 ), 25.66 (25.63 ), 16.7; HRMS (ESI): C H ClNNa
18 16
+
[M+Na] Calcd 304.0863, Found 304.0888.
6
-(4-Chlorophenyl)-6-phenylhex-5-enenitrile (7f).8b Colorless oil, 19.1 mg, yield: 35% [Δ];
1
4
0.4mg, yield 73% [hv]; H NMR (400 MHz, Chloroform-d) δ 7.18 (d, J = 7.6 Hz, 2H), 7.02 – 7.12
(m, 6H), 5.94 (t, J = 7.6 Hz, 1H), 2.38 (s, 3H), 2.32 (s, 3H), 2.23 – 2.29 (m, 4H), 1.78 (q, J = 7.2
+
+
Hz, 2H); HRMS (ESI): C H NNa [M+Na] Calcd 298.1566, Found 298.1572.
2
0
21
6
,6-Bis(4-chlorophenyl)hex-5-enenitrile (7g). Colorless oil, 11.3 mg, yield: 18% [Δ]; 44.7 mg,
-1
1
yield 71% [hv]; IR (neat) ν 2916, 1488, 1089, 1012, 823, 516 cm ; H NMR (400 MHz, Chloroform-
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d) δ 7.37 (d, J = 8.0 Hz, 2H), 7.22 – 7.26 (m, 2H), 7.07 – 7.23 (m, 4H), 6.01 (t, J = 7.6 Hz, 1H),
1
3
1
2
1
.23 – 2.33 (m, 4H), 1.76 – 1.83 (m, 2H); C{ H} NMR (100 MHz, Chloroform-d) δ 141.6, 140.2,
37.5, 133.5, 133.4, 131.0, 128.8, 128.44, 128.42, 127.7, 119.3, 28.8, 25.6, 16.8; HRMS (ESI):
+
+
C H Cl NNa [M+Na] Calcd 338.0474, Found 338.0501.
1
8
15
2
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
-Methyl-3-(2-methyl-5-oxohexan-2-yl)quinoxalin-2(1H)-one (8a).17 Pale yellow solid, 16.2
1
mg, yield 30% [hv]; m.p. 71-72 ℃; H NMR (400 MHz, Chloroform-d) δ 7.75 (d, J = 8.0 Hz, 1H),
7
.46 (t, J = 7.6 Hz, 1H), 7.25 (m, 2H), 3.60 (s, 3H), 2.20 – 2.27 (m, 4H), 2.03 (s, 3H), 1.39 (s, 6H);
+
+
HRMS (ESI): C H N NaO [M+Na] Calcd 295.1417, Found 295.1410.
1
6
20
2
2
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the ACS Publications website at DOI:
1
0.1021/acs.joc.xxxxxxx
The setup for the photocatalytic procedure.
Reaction optimization and mechanistic studies.
1
19
13
H NMR, F NMR and C NMR spectra for compounds 3.
1H NMR spectra for compounds 4a, 4c-4d, 4g-4i, 4k, 4o, 5b-5g, 6a, 6c-6i, 6k, 6o, 6r, 6t-6u, 7a, 7f
and 8a.
1
13
H NMR and C NMR spectra for compounds 4b, 4e-4f, 4j, 4m-4n, 4p, 6b, 6j, 6m-6n, 6p-6q, 6s,
7
b-7e and 7g.
AUTHOR INFORMATION
Corresponding Author
*
*
Email: hyangchem@csu.edu.cn (H. Yang)
Email: xianghaoyue@csu.edu.cn (H. Y. Xiang)
Author Contributions
#
These authors contributed equally.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
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We gratefully acknowledge the financial support from the National Natural Science Foundation of
China (21576296, 21776318, 21676302 & 81703365), and the Fundamental Research Funds for
Central South University (grant number 2019zzts222).
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REFERENCES
(1) (a) Zard, S. Z. Recent Progress in the Generation and Use of Nitrogen-centred Radicals. Chem.
Soc. Rev. 2008, 37, 1603–1618. (b) Karkas, M. D. Photochemical Generation of Nitrogen-Centered
Amidyl, Hydrazonyl, and Imidyl Radicals: Methodology Developments and Catalytic Applications.
ACS Catal. 2017, 7, 4999–5022. (c) Davies, J.; Morcillo, S. P.; Douglas, J. J.; Leonori, D.
Hydroxylamine Derivatives as Nitrogen‐Radical Precursors in Visible-Light Photochemistry. Chem.
Eur. J. 2018, 24, 12154–12163. (d) Yin, W.; Wang, X. Recent Advances in Iminyl Radical-
Mediated Catalytic Cyclizations and Ring-opening Reactions. New J. Chem., 2019, 43, 3254−3264.
(2) (a) Lu, B.; Cheng, Y.; Chen, L.-Y.; Chen, J.-R.; Xiao, W.-J. Photoinduced Copper-Catalyzed
Radical Aminocarbonylation of Cycloketone Oxime Esters. ACS Catal. 2019, 9, 8159−8164. (b) Li,
L.; Chen, H.; Mei, M.; Zhou, L. Visible-light Promoted γ-Cyanoalkyl Radical Generation: Three-
component Cyanopropylation/etherification of Unactivated Alkenes. Chem. Commun. 2017, 53,
1
1544−11547. (c) Yin, Z.; Rabeah, J.; Brückner, A.; Wu, X. F. Gallic Acid-Promoted SET Process
for Cyclobutanone Oximes Activation and (Carbonylative-)Alkylation of Olefins. ACS Catal. 2018,
, 10926−10930.
3) (a) Shu, W.; Nevado, C. Visible-Light-Mediated Remote Aliphatic C−H Functionalizations
8
(
through a 1,5‐Hydrogen Transfer Cascade. Angew. Chem. Int. Ed. 2017, 56, 1881−1884. (b) Jiang,
3
H.; Studer, A. α-Aminoxy-Acid-Auxiliary-Enabled Intermolecular Radical γ-C(sp )-H
Functionalization of Ketones. Angew. Chem. Int. Ed. 2018, 57, 1692−1696.
(
4) Atmaram, S.; Forrester, A. R.; Gill, M.; Thomson, R. H. Iminyls. Part 9. Intramolecular
Addition of an lminyl to an Alkene. J. Chem. Soc. Perkin Trans. 1. 1981, 1, 1721−1724.
5) (a) Faulkner, A.; Scott, J. S.; Bower, J. F. An Umpolung Approach to Alkene Carboamination:
(
Palladium Catalyzed 1,2-Amino-Acylation, -Carboxylation, -Arylation, -Vinylation, and –
Alkynylation. J. Am. Chem. Soc. 2015, 137, 7224–7230. (b) Chen, C.; Hou, L.-L.; Cheng, M.; Su,
J.-H.; Tong X.-F. Palladium(0)-Catalyzed Iminohalogenation of Alkenes: Synthesis of 2-
Halomethyl Dihydropyrroles and Mechanistic Insights into the Alkyl Halide Bond Formation.
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Angew. Chem. Int. Ed. 2015, 54, 3092–3096. (c) Ai, W.-Y.; Liu, Y.-Q.; Wang, Q.; Lu, Z.-L.; Liu,
Q. Cu-Catalyzed Redox-Neutral Ring Cleavage of Cycloketone O-Acyl Oximes: Chemodivergent
Access to Distal Oxygenated Nitriles. Org. Lett. 2018, 20, 409–412. (d) An, Z.-Y.; Jiang, Y.; Guan,
X.; Yan, R.-L. Copper-catalyzed Tandem Aerobic Oxidative Cyclization for the Synthesis of 4-
Cyanoalkylpyrrolo[1,2-a]quinoxalines from 1-(2-Aminophenyl)pyrroles and Cyclobutanone
Oxime Esters. Chem. Commun. 2018, 54, 10738–10741. (e) Yu, X.-Y.; Zhao, Q.-Q.; Chen, J.; Chen,
J.-R.; Xiao, W.-J. Copper‐Catalyzed Radical Cross-Coupling of Redox-Active Oxime Esters,
Styrenes, and Boronic Acids. Angew. Chem. Int. Ed. 2018, 57, 15505–15509. (f) Chen, J.-R.; Hu,
X.-Q.; Lu, L.-Q.; Xiao, W.-J. Visible Light Photoredox-controlled Reactions of N-Radicals and
Radical Ions. Chem. Soc. Rev. 2016, 45, 2044–2056.
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
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9
0
(6) (a) Jackman, M. M.; Im, S.; Bohman, S. R.; Lo, C. C. L.; Garrity, A. L.; Castle, S. L. Synthesis
of Functionalized Nitriles by Microwave-Promoted Fragmentations of Cyclic Iminyl Radicals.
Chem. Eur. J. 2018, 24, 594–598. (b) Cai. Y; Jalan, A.; Kubosumi, A. R.; Castle, S. L. Microwave-
Promoted Tin-Free Iminyl Radical Cyclization with TEMPO Trapping: A Practical Synthesis of 2-
Acylpyrroles. Org. Lett. 2015, 17, 488–491. (c) Yin, Z.; Rabeah, J.; Brückner, A.; Wu, X. F.
Vinylboron Self-Promoted Carbonylative Coupling with Cyclobutanone Oxime Esters. Org. Lett.
2019, 21, 1766–1769. (d) Yang, L.; Gao, P.; Duan, X.-H.; Gu, Y.-R.; Guo, L.-N. Direct C–H
Cyanoalkylation of Quinoxalin-2(1H)-ones via Radical C–C Bond Cleavage. Org. Lett. 2018, 20,
1
034-1037.
7) (a) Ding, D.; Wang, C. Nickel-Catalyzed Reductive Electrophilic Ring Opening of
(
Cycloketone Oxime Esters with Aroyl Chlorides. ACS Catal. 2018, 8, 11324–11329. (b) Yang, H.-
B.; Pathipati, R. S.; Selander, N. Nickel-Catalyzed 1,2-Aminoarylation of Oxime Ester-Tethered
Alkenes with Boronic Acids. ACS Catal. 2017, 7, 8441–8445. (c) Zhao, J.-F.; Duan, X.-H.; Gu, Y.-
R.; Gao, P.; Guo, L.-N. Iron-Catalyzed Decarboxylative Olefination of Cycloketone Oxime Esters
with α,β-Unsaturated Carboxylic Acids via C–C Bond Cleavage. Org. Lett. 2018, 20, 4614–4617.
(
d) Zhao, B,-L.; Shi, Z.-Z. Copper-Catalyzed Intermolecular Heck-Like Coupling of Cyclobutanone
Oximes Initiated by Selective C−C Bond Cleavage. Angew. Chem. Int. Ed. 2017, 56, 12727–12731.
e) Gu, Y.-R.; Duan, X.-H.; Yang, L.; Guo, L.-N. Direct C–H Cyanoalkylation of Heteroaromatic
N-Oxides and Quinones via C–C Bond Cleavage of Cyclobutanone Oximes. Org. Lett. 2017, 19,
908–5911.
(
5
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The Journal of Organic Chemistry
Page 24 of 26
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5
5
5
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5
5
6
(
8) (a) Narasaka, K. Synthesis of Azaheterocycles from Oxime Derivatives. Pure Appl. Chem.
2
003, 75, 19–28. (b) Yu, X.-Y.; Chen, J.-R.; Wang, P.-Z.; Yang, M.-N.; Liang, D.; Xiao, W.-J. A
Visible-Light-Driven Iminyl Radical-Mediated C−C Single Bond Cleavage/Radical Addition
Cascade of Oxime Esters. Angew. Chem. Int. Ed. 2018, 57, 738–743. (c) Vaillant, F. L.; Garreau, M.;
Nicolai, S.; Grynova, G.; Corminboeuf, C.; Waser, J. Fine-tuned Organic Photoredox Catalysts for
Fragmentation-alkynylation Cascades of Cyclic Oxime Ethers. Chem. Sci. 2018, 9, 5883–5889. (d)
Dauncey, E. M.; Morcillo, S. P.; Douglas, J. J.; Sheikh, N. S.; Leonori, D. Photoinduced Remote
Functionalisations by Iminyl Radical Promoted C-C and C-H Bond Cleavage Cascades. Angew.
Chem. Int. Ed. 2018, 57, 744–748. (e) Svejstrup, T. D.; Ruffoni, A.; Julia, F.; Aubert, V. M.; Leonori
0
1
2
3
4
5
6
7
8
9
0
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0
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2
3
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6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
,
D. Synthesis of Arylamines via Aminium Radicals . Angew. Chem. Int. Ed. 2017, 56, 14948–14952.
(
f) Davies, J.; Booth, S. G.; Essafi, S.; Dryfe, R. A. W.; Leonori, D. Visible-Light-Mediated
Generation of Nitrogen-Centered Radicals: Metal-Free Hydroimination and Iminohydroxylation
Cyclization Reactions. Angew. Chem. Int. Ed. 2015, 54, 14017–14021. (g) Dauncey, E. M.; Morcillo,
S. P.; Douglas, J. J.; Sheikh, N. S.; Leonori, D. Photoredox Imino Functionalizations of Olefins.
Angew. Chem. Int. Ed. 2017, 56, 13361–13365. (h) Li, J.; Zhang, P.; Jiang, M.; Yang, H.; Zhao, Y.;
3
Fu, H.; Visible Light as a Sole Requirement for Intramolecular C(sp )–H Imination. Org. Lett. 2017,
19, 1994–1997. (i) Wang, P.-Z.; He, B.-Q.; Cheng, Y.; Chen, Y.; Xiao, W.-J. Radical C–C Bond
Cleavage/Addition Cascade of Benzyl Cycloketone Oxime Ethers Enabled by Photogenerated
Cyclic Iminyl Radicals. Org. Lett. 2019, 21, 6924–6929.
(9) (a) He, Y.-W.; Anand, D.; Sun, Z.-C.; Zhou, L. Visible-Light-Promoted Redox Neutral γ,γ-
Difluoroallylation of Cycloketone Oxime Ethers with Trifluoromethyl Alkenes via C–C and C–F
Bond Cleavage. Org. Lett. 2019, 21, 3769–3773. (b) Zhang, W.; Pan, Y.-L.; Yang, C.; Chen, L.; Li,
X.; Cheng J.-P. Metal-Free Direct C−H Cyanoalkylation of Quinoxalin-2(1H)‑Ones by Organic
Photoredox Catalysis. J. Org. Chem. 2019, 84, 7786−7795. (c) Jelier, B. J.; Tripet, P. F.; Pietrasiak,
E.; Franzoni, I.; Jeschke, G.; Togni, A. Radical Trifluoromethoxylation of Arenes Triggered by a
VisibleLight-Mediated N-O Bond Redox Fragmentation. Angew. Chem. Int. Ed. 2018, 57, 13784–
1
3789.
10) (a) Arora, A.; Weaver, J. D. Visible Light Photocatalysis for the Generation and Use of
(
Reactive Azolyl and Polyfluoroaryl Intermediates. Acc. Chem. Res. 2016, 49, 2273–2283. (b) Singh,
A.; Kubik, J. J.; Weaver, J. D. Photocatalytic C–F Alkylation: Facile Access to Multifluorinated
ACS Paragon Plus Environment

Page 25 of 26
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Arenes. Chem. Sci. 2015, 6, 7206–7212. (c) Matsunami, A.; Kuwata, S.; Kayaki, Y.
Hydrodefluorination of Fluoroarenes Using Hydrogen Transfer Catalysts with a Bifunctional
Iridium/NH Moiety. ACS Catal. 2016, 6, 5181−5185.
(
11) Xia, P.-J.; Ye, Z.-P.; Hu, Y.-Z.; Song, D. Xiang, H.-Y.; Chen, X.-Q.; Yang, H. Photocatalytic,
Phosphoranyl Radical-Mediated N–O Cleavage of Strained Cycloketone Oximes. Org. Lett. 2019,
1, 2658–2662.
12) Arias-Rotondo, D. M.; McCusker, J. K. The Photophysics of Photoredox Catalysis: a
Roadmap for Catalyst Design. Chem. Soc. Rev. 2016, 45, 5803-5820.
13) (a) Stoyanovsky, D. A.; Cederbaum, A. I.; Metabolism of Carbon Tetrachloride to
Trichloromethyl Radical:ꢀ An ESR and HPLC-EC Study. Chem. Res. Toxicol. 1999, 12, 730-736.
b) Zhao. B.; Liang, H.-W.; Yang, J.; Yang, Z.; Wei, Y. Copper-Catalyzed Intermolecular
Cyclization between Oximes and Alkenes: A Facile Access to Spiropyrrolines. ACS Catal. 2017, 7,
1
1
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0
1
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8
9
0
1
2
3
4
5
6
7
8
9
0
2
(
(
(
5
612−5617.
(14) (a) Dhameliya, T. M.; Chourasiya, S. S.; Mishra, E.; Jadhavar, P. S.; Bharatam, P. V.;
Chakraborti, A. K. Rationalization of Benzazole-2-carboxylate versus Benzazine-3-one/Benzazine-
2,3-dione Selectivity Switch during Cyclocondensation of 2-Aminothiophenols/Phenols/Anilines
with 1,2-Biselectrophiles in Aqueous Medium. J. Org. Chem. 2017, 82, 10077−10091.(b) Carrer,
A.; Brion, J.-D.; Messaoudi, S.; Alami, M. Palladium(II)-Catalyzed Oxidative Arylation of
Quinoxalin-2(1H)-ones with Arylboronic Acids. Org. Lett. 2013, 15, 5606-5609.
(15) (a) Chen, D.-B.; Wang, Z.-J.; B, W.-L. Copper-catalyzed Cascade Syntheses of 2H-
benzo[b][1,4]thiazin-3(4H)-ones and Quinoxalin-2(1H)-ones through Capturing S and N Atom
respectively from AcSH and TsNH2. J. Org. Chem. 2010, 75, 5768–5771. (b) Li, Z.-S.; Wang, W.-
X.; Yang, J.-D.; Wu, Y.-W.; Zhang, W. Photoinduced and N-Bromosuccinimide Mediated
Cyclization of 2-Azido-N-phenylacetamides. 2013, 15, 3820–3823.
(
16) Onuigbo, L.; Raviola, C.; Fonzo, A. D.; Protti, S.; Fagnoni, M. Sunlight-Driven Synthesis
of Triarylethylenes (TAEs) via Metal-Free Mizoroki–Heck-Type Coupling. Eur. J. Org. Chem.
018, 38, 5297–5303.
17) (a) Tang, J.; Hackenberger, D.; Goossen, L. J. Branched Arylalkenes from Cinnamates:
2
(
Selectivity Inversion in Heck Reactions by Carboxylates as Deciduous Directing Groups. Angew.
Chem. Int. Ed. 2016, 55, 11296–11299. (b) Shen, R.-W.; Yang, J.-J.; Zhu, S.-G.; Chen, C.; Wu,
ACS Paragon Plus Environment

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Page 26 of 26
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5
6
L.-L. Gold(I)-Catalyzed Decarboxylation of Propargyl Carbonates: Reactivity Reversal of the Gold
Catalyst from π-Lewis Acidity to σ-Lewis Acidity. Adv. Synth. Catal. 2015, 6, 1259–1269.
(18) Gu, Y.-R.; Duan, X.-H.; Chen, L.; Ma, Z.-Y.; Gao, P.; Guo, L.-N. Iminyl Radical-Triggered
3
Intermolecular Distal C(sp )-H Heteroarylation via 1,5-Hydrogen-Atom Transfer (HAT) Cascade.
0
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Org. Lett. 2019, 21, 917-920.
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