Redox-Neutral Photocatalytic Radical Cascade Cyclization for the Synthesis of CH2CN/CF2COOEt/CF3-Containing Benzo[4,5]imidazo[2,1-a]isoquinolin-6(5 H)-One Derivatives

Article abstract of DOI:10.1021/acs.joc.0c01688

A novel method for the synthesis of benzo[4,5]imidazo[2,1-A]isoquinolin derivatives via visible-light-induced radical cascade cyclization is described. By using N-methacryloyl-2-phenylbenzoimidazoles and diverse radical precursors, various benzo[4,5]imidazo[2,1-A]isoquinolin derivatives containing CH2CN/CF2COOEt/CF3 can be formed in good to excellent yields under mild reaction conditions. This method exhibits good functional group tolerance and a wide range of substrate scope.

Full text of DOI:10.1021/acs.joc.0c01688

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Article
Redox-neutral photocatalytic radical cascade cyclization
for the synthesis of CH2CN/CF2COOEt/CF3 containing
benzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one derivatives.
Liang Liu, De-Yong Yang, Yan-Hong He, and Zhi Guan
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.0c01688 • Publication Date (Web): 18 Aug 2020
Downloaded from pubs.acs.org on August 18, 2020
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Page 1 of 9
The Journal of Organic Chemistry
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Redox-neutral photocatalytic radical cascade cyclization for the
synthesis of CH CN/CF COOEt/CF containing benzo[4,5]imidazo[2,1-
a]isoquinolin-6(5H)-one derivatives.
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0
Liang Liu, De-Yong Yang, Yan-Hong He,* and Zhi Guan*
School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China
Supporting Information Placeholder
N
BrCH CN
N
R1
2
or
PC
R2
R2
N
BrCF COOEt
R1
N
2
R
O
or
ClSO CF
O
2
3
R = CH2CN, CF2COOEt, CF3
redox-neutral
visible light
mild reaction conditions
27 examples, up to 98% yield
ABSTRACT: A novel method for the synthesis of benzo[4,5]imidazo[2,1-a]isoquinolin derivatives via visible-light-induced radical
cascade cyclization is described. By using N-methacryloyl-2-phenylbenzoimidazoles and diverse radical precursors, various
benzo[4,5]imidazo[2,1-a]isoquinolin derivatives containing CH CN/CF COOEt/CF can be formed in good to excellent yields under
2 2 3
mild reaction conditions. The method exhibits good functional group tolerance and a wide range of substrate scope.
INTRODUCTION
Therefore, it is necessary to develop more environmentally
Nitrogen-containing heterocyclic compounds are a class of
very important organic compounds, especially those having a
benzo[4,5]imidazo[2,1-a]isoquinoline tetracyclic core skeleton,
which are not only an important part of privileged synthetic
intermediates but also present in some bioactive molecules as
well as functional materials. Some pharmaceutically active
molecules and functionalized material molecules having a
benzimidazole tetracyclic core skeleton are shown in Fig 1.
friendly, mild and efficient methods to construct
benzo[4,5]imidazo[2,1-a]isoquinoline tetracyclic skeleton with
diversified functional groups. In recent years, visible-light-
induced photoredox catalysis has attracted extensive attention
in organic synthesis due to its inherent green and sustainable
1
features, and some landmark achievements have been
12-15
achieved.
Some examples have been reported where C−X
covalent bonds are activated by visible-light catalysis to form
2
Such as A (Modulating the potassium ion flux),
B
corresponding free radical intermediates, which are then
3
4
(
Antitumor), C (Agent for hemoglobinopathies) and D
16-18
subjected to radical addition or cyclization.
However, there
5
(Candidates for organic electronics). In the past decade, several
synthetic methods for the benzo[4,5]imidazo[2,1-
a]isoquinoline tetracyclic skeleton have been proposed, such as
palladium-catalyzed intramolecular cyclization of
are very few reports on the construction of the
benzo[4,5]imidazo[2,1-a]isoquinoline skeleton through visible
light
catalysis.
As
far
as
we
know,
only
N
6
H N
2
benzimidazoles, dehydrogenative coupling of 2-[3,4-
N
(
MeO)2
7
OMe
dihydroisoquinolin-2(1H)-yl]aniline derivatives, TEMPO-
promoted C(sp )−H amination, Cp*Rh -catalyzed [4+2]
3
annulation of 2-arylimidazoles and α-diazoketoesters, silver-
catalyzed decarboxylative radical cascade cyclization, and
oxidative radical relay functionalization for the synthesis of
benzimidazo[2,1-a]iso-quinolin-6(5H)-ones, etc. Although
these methods have synthesized benzo[4,5]imidazo[2,1-
a]isoquinoline tetracyclic core skeleton, there are still some
limitations, such as the difficulty in preparing starting materials,
the use of explosive peroxides, the unitary functional group and
high reaction temperatures.
N
8
III
N
9
n-Bu
10
A
B
D
N
N
N
N
11
R
N
N
O
O
O
R'
C
Fig 1. Representative examples of benzoxazines.
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Page 2 of 9
Yu's group has reported a method of constructing the
benzo[4,5]imidazo[2,1-a]isoquinoline skeleton via visible light
intermediate is more easily oxidized by the oxidized
photocatalyst (as shown in Scheme 2). In addition, when the
ortho and meta positions of
1
2
3
4
5
6
7
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
1
9
catalysis.
Although
Yu
et.al.
synthesized
benzo[4,5]imidazo[2,1-a]isoquinoline by visible light catalysis,
this method used only one free radical precursor and the product
yield is not high. Inspired by these works, we designed a visible-
light-induced photocatalyzed radical cascade cyclization to
construct benzo[4,5]imidazo[2,1-a]isoquinoline tetracyclic
skeleton. This is the first work for the synthesis of
Table
1.
Optimization
of
reaction
conditions.a
N
Photocatalyst
N
N
Br
CN
N
O
Base, Solvent
rt, 9 W blue LEDs
O
CN
1a
2a
3a
Entry
Photocatalyst
Base
Solvent
Yieldb
(%)
benzo[4,5]imidazo[2,1-a]isoquinolines
CH CN/CF COOEt/CF from
phenylbenzoimidazoles
3 2
BrCH CN/BrCF COOEt/CF (SO )Cl under visible-light-
containing
N-methacryloyl-2-
and
2
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
1
2
3
4
5
6
7
8
9
1
1
1
fac-Ir(ppy)
3
Na
Na
Na
Na
2
2
2
2
CO
CO
CO
CO
3
3
3
3
CH
CH
CH
CH
CH
3
3
3
3
3
CN
CN
CN
CN
CN
84
2
2
Eosin Y
Trace
Trace
Trace
91
induced photocatalysis. This strategy not only avoids
cumbersome preparation of raw materials, stoichiometric
oxidants and high reaction temperatures, but also introduces a
variety of valuable functional groups such as CN/CF /CF to
2 3
benzo[4,5]imidazo[2,1-a]isoquinoline with excellent yield (up
to 98%).
3 2 2
Ru(bpy) Cl ·6H O
[Ir(dtbbpy)(ppy)
2
6
][PF ]
fac-Ir(ppy)
fac-Ir(ppy)
fac-Ir(ppy)
fac-Ir(ppy)
fac-Ir(ppy)
fac-Ir(ppy)
fac-Ir(ppy)
fac-Ir(ppy)
-
3
3
3
3
3
3
3
3
KOAc
NaHCO
HPO
3
CH3CN
84
RESULTS AND DISCUSSION
K
2
4
CH
3
3
CN
CN
54
Initially, we chose N-methacryloyl-2-phenylbenzoimidazole
1
a and bromoacetonitrile 2a as model substrates (1a/2a = 1:2,
molar ratio) to access the target product 3a. In the presence of
fac-Ir(ppy) (3% mol), Na CO (1.5 equiv) and CH CN (1 mL),
Et
3
N
CH
55
KOAc
KOAc
KOAc
KOAc
DMF
48
3
2
3
3
the desired product 3a was obtained in 84% isolated yield by
irradiation of 9 W blue LEDs at room temperature for 24 hours
(Table 1, entry 1). Next, some parameters affecting the reaction
were screened, such as photocatalyst, base andsolvent. It was
found that some commonly used photocatalysts, such as Eosin
0
1
2
DCM
acetone
51
86
isopropan
ol
Trace
Trace
Trace
32
13c
Na CO
CH CN
Y, Ru(bpy)
3
Cl
2
·6H
2
O and [Ir(dtbbpy)(ppy)
2
][PF
6
] did not show
2
3
3
catalytic activity (Table 1, entries 2-4). After comparing the
reduction potentials of Eosin Y (E1/2* = -1.06 V vs. SCE in
4d
1
1
fac-Ir(ppy)
fac-Ir(ppy)
fac-Ir(ppy)
3
3
3
Na
-
2
CO
3
CH
CH
CH
3
3
3
CN
CN
CN
2
0
II
III
CH
SCE in CH
0.89 V vs. SCE in CH
1.63 V vs. SCE in CH CN) (Fig. S8), it can be seen that their
reducibility is insufficient to reduce bromoacetonitrile. A series
of bases were also screened, such as KOAc, NaHCO , K HPO
and NEt , and an excellent yield of 91% can be satisfactorily
3
CN), Ru(bpy)
3
Cl
2
·6H
2
O (E1/2* Ru /Ru = -0.81 V vs.
5e
21
III IV
3
CN) and [Ir(dtbbpy)(ppy)
2
][PF
6
] (E1/2* Ir /Ir
=
21
16f
-
3
CN) with bromoacetonitrile (E1/2 = -
Na
2
CO
3
68
3
aUnless otherwise noted, reaction conditions: the mixture of
1
a (1.0 equiv, 0.2 mmol), 2a (2.0 equiv, 0.4 mmol),
3
2
4
photocatalyst (3 mol%) and base (1.5 equiv, 0.3 mmol) in
degassed dry solvent (1 mL) was irradiated by 9 W blue LEDs
3
obtained when using KOAc (Table 1, entries 5-8). Meanwhile,
a set of solvents including DMF, DCM, acetone, and
b
under Ar atmosphere at rt for 14-24 h. Isolated yield by flash
c
d
e
chromatography. No photocatalyst. In the dark. No base.
isopropanol were tested, but they were not as good as CH
3
CN
f
Under air atmosphere.
(Table 1, entries 9-12). Additionally, control experiments
revealed that the photocatalyst and continuous illumination
were necessary for the reaction, and the base as well as argon
atmosphere greatly improved the reaction yield (Table 1,
entries 13-16).
2
-benzene ring were both substituted by -Cl, the reaction could
still proceed smoothly, giving the desired product 3i in
moderate yield (58%). As expected, when the benzene ring of
benzimidazole was substituted or both benzene rings in the
substrate (1) were substituted, the desired products still could
be successfully obtained (3j-3l, 63-98% yields).
Under the optimized reaction conditions, using 2a as the
cyanomethylation reagent, the scope and limitations of visible-
light-induced cyanomethylation/cyclization of N-methacryloyl-
2-phenylbenzoimidazoles (1) were evaluated. It can be seen
from Table 2 that when the para-position/ortho-position of the
To verify the versatility of this method, we expanded the
source of free radicals for the reaction. Due to the importance
of fluorine-containing compounds, we introduced F-containing
groups into benzo[4,5]imidazo[2,1-a]isoquinoline. We tried to
2
-benzene ring of benzimidazole was substituted with an
electron-donating group (-Me, -OMe or -OEt), the desired
products 3b-3e could be obtained in excellent yields (79-92%).
However, when the para-position of the 2-benzene ring was
substituted with an electron-withdrawing group (-F, -Cl or -Br),
the corresponding products 3f-3h were only obtained in
moderate yields (63-74%). This indicates that electron-donating
groups conducive to the improvement of the reaction yield,
which may be because the electron-donating group increases
the density of the electron cloud of the molecule, so that its
replace
bromoacetonitrile
2a
with
ethyl
difluorobromobromoacetate 2b to react with 1a under the
optimal reaction conditions used in Table 2. It is gratifying that
the difluoroalkylated product 4a was successfully obtained in
8
7% yield (Table 3). In addition, the structure of 4a was
determined by X-ray crystallography analysis (Fig. S9). Next,
the effects of different substituents on the reaction were
explored. It was found that substrates (1) with either electron-
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The Journal of Organic Chemistry
donating groups (-Me, -OMe, -OEt) or electron-withdrawing
groups (-F, -Cl, -Br) could be converted into corresponding
products 4a-4g in good yields (76-91%). In addition, when two
benzene rings in the substrate (1) were substituted, the reaction
could still proceed smoothly, giving the desired products in
satisfactory yields (4h-4i, 65-85%).
1
2
3
4
5
6
7
8
9
Table 2. Substrate scope of photoredox-catalyzed
a
cyanomethylation/cyclization.
N
N
fac-Ir(ppy)3 (3 mol%)
KOAc (1.5 equiv)
This reaction can also be easily used for the synthesis of
R1
N
R2
R2
trifluoromethylated
products.
The
reaction
of
Br
CN
R1
N
CH3CN (1 mL)
O
trifluoromethanesulfonyl chloride with 1a proceeded smoothly
to give the desired product 5a in 56% isolated yield (Table 4).
The exploration of the substrate scope showed that substrates
containing electron-donating or electron-withdrawing groups
were suitable for the reaction. By using this method, various
9
W blue LEDs, rt, 14-24 h
O
CN
1
2a
3
N
N
O
N
N
N
N
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
O
CN
O
CN
O
CN
CF -containing benzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-
3
3a, 91%
3b, 84%
3c, 88%
ones (5a-5f) could be obtained in moderate yields (46-67%).
O
N
N
N
F
N
N
Table 4. Substrate scope of photoredox-catalyzed
trifluoroalkylation/cyclization.
N
O
a
N
fac-Ir(ppy)3 (3 mol%)
KOAc (1.5 equiv)
O
CN
Cl
CN
O
CN
R1
N
3
e, 79%
3f, 74%
R2
O
S
R2
N
3d, 92%
Cl
CF3
Cl
Cl
O
3
CH CN (1 mL)
R1
N
CF3
Br
O
N
9 W blue LEDs, rt, 14-24 h
N
N
O
N
1
2c
5
N
N
O
CN
O
CN
O
O
CN
Cl
N
N
N
3g, 63%
3h, 69%
3i, 58%
N
CF3
N
CF3
N
CF3
N
N
N
N
O
O
O
5a, 56%
5b, 64%
5c, 63%
N
N
O
CN
O
Br
CF3
N
N
O
CN
CN
N
N
b
3j, 80%
3k, 98%
3l , 63%
CF3
N
CF3
N
aUnless otherwise noted, reaction conditions: 1 (0.2 mmol),
2a (0.4 mmol), fac-Ir(ppy) (3 mol%), KOAc (1.5 equiv),
CH CN (1.0 mL), 9 W blue LEDs, at rt under argon atmosphere,
4-24 h. Isolated yield. DCM instead of CH
O
O
O
5d, 46%
5e, 57%
5f, 67%
3
3
aUnless otherwise noted, reaction conditions: 1 (0.2 mmol),
b
1
3
CN.
2c (0.4 mmol), fac-Ir(ppy)
CH CN (1.0 mL), 9 W blue LEDs, at rt under argon atmosphere,
14-24 h. Isolated yield.
3
(3 mol%), KOAc (1.5 equiv),
Table 3. Substrate scope of photoredox-catalyzed
3
a
difluoroalkylation/cyclization.
N
N
fac-Ir(ppy)3 (3 mol%)
R2
In addition, we explored the reaction of 1a with other free
radical precursors, such as diethyl bromide difluoromethane
diphosphonate 2d, perfluoroiodide 2e, and diethyl
bromomalonate 2f. It was found that 1a can react with 2f to
produce 6a, but the reaction between 1a and 2d/2e is not
obvious, and a large amount of raw materials remain. The above
experimental results show that 1a can react with a variety of
free radical precursors, but there are still some limitations
(Scheme 1).
R1
R2
O
KOAc (1.5 equiv)
R1
N
N
Br
CH3CN (1 mL)
O
O
O
F
F
F
9 W blue LEDs, rt, 14-24 h
F
O
1
2b
4
O
O
N
N
N
N
N
N
O
O F
F
O
F
F
O
O
F
O
F
O
O
Scheme 1. The reaction of 1a with other free radical precursors.
O
4c, 85%
4a, 87%
4b, 81%
N
fac-Ir(ppy)3 (3 mol%)
KOAc (1.5 equiv)
N
Br
O
N
N
F
Cl
N
N
N
N
2
EtO C
N
CO Et
CO2Et
2
CH3CN (1 mL)
O
N
9 W blue LEDs, rt, Ar, 20 h
O
2
CO Et
O
F
1a
2f
6a, 63%
O
O
F
F
F
O
O
F
F
O
N
N
fac-Ir(ppy)3 (3 mol%)
KOAc (1.5 equiv)
O
N
O
O
F
F
PO(OEt)2
4
e, 76%
4f, 82%
Br
N
F
4
d, 91%
CH3CN (1 mL)
O
PO(OEt)2
Br
9 W blue LEDs, rt, Ar, 20 h
O
F
N
Cl
N
N
N
N
1a
2d
Not isolated
N
N
fac-Ir(ppy)3 (3 mol%)
KOAc (1.5 equiv)
O
N
F
O
O
F
F
F
O
O
O
N
IC4F
F
F
9
N
C4F9
CH3CN (1 mL)
O
O
O
O
9
W blue LEDs, rt, Ar, 20 h
b
O
4
g, 86%
4h, 85%
4i , 65%
1a
2e
Not isolated
aUnless otherwise noted, reaction conditions: 1 (0.2 mmol),
b (0.4 mmol), fac-Ir(ppy) (3 mol%), KOAc (1.5 equiv),
CH CN (1.0 mL), 9 W blue LEDs, at rt under argon atmosphere,
4-24 h. Isolated yield. DCM instead of CH
In order to investigate the reaction mechanism, a series of
control experiments were carried out using the reactions of N-
2
3
3
b
methacryloyl-2-phenylbenzimidazole
1a
with
1
3
CN.
bromoacetonitrile 2a and ethyl difluorobromoacetate 2b,
respectively (Scheme 2). First, when the radical scavengers
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,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO, 2.0 eq) and 2,6-
Page 4 of 9
2
various radical precursors. This reaction uses visible light as an
energy source with mild, green and sustainable characteristics.
In addition, this method has the advantages of simple operation,
good functional group compatibility, wide range of substrate
scope and good to excellent yields.
1
2
3
4
5
6
7
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
ditert-butyl-4-methylphenol (BHT, 2.0 eq) were separately
added to the reaction system under standard reaction conditions,
the reaction was completely inhibited. Meanwhile, the
2 2
TEMPO−CH CN and TEMPO−CF COOEt were detected by
high resolution mass spectrometry (HRMS) analysis. The above
experimental results indicated that a radical process might be
involved in this transformation and ·CH CN/·CF COOEt
2 2
Scheme 3. Proposed reaction mechanism.
R-X (X=Br/SO2Cl)
2
IrIII
*
N
radical might be formed. In order to confirm whether a radical
chain process existed in this reaction, the light on/off
experiments were performed (Fig. S1). The experiments results
showed that the product yield still increases slightly under dark
conditions, indicating a free radical chain propagation process
in the reaction. The emission spectrum of the lamp and the
ultraviolet-visible absorption spectra of substrates indicated that
R2
R1
N
R
SET
R
O
3
/4/5
N
N
IrIII
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
IrIV
R1
R2
KOAc
SET
O
Aromatization
1
N
N
N
R2
R2
R2
R
fac-Ir(ppy)
Fig. S2-S3). Furthermore, fluorescence quenching
experiments showed that the excited fac-Ir(ppy) * can be
significantly quenched by 2a/2b (Fig. S4-S7). The CV
experimrnts (Fig. S8) of 2a (E1/2 = -1.63 V vs. SCE in CH CN)
and 2b (E1/2 = -1.60 V vs. SCE in CH CN) showed that they can
oxidize the excited fac-Ir(ppy) * (E1/2* Ir /Ir = -1.73 V vs.
CN) to a higher valence state, which indicates that
a/2b may be involved in the oxidative quenching process of
the excited fac-Ir(ppy) *.
3
is the only light-absorbing substance in the reaction
R1
N
R1
N
R1
N
R
(
O
R
O
O
I
II
III
3
3
R-X (X=Br/SO2Cl)
2
3
R
III IV
3
21
SCE in CH
3
EXPERIMENTAL SECTION
2
General Information. Unless otherwise noted, materials
obtained from commercial suppliers were used directly without
3
further purification. Flash column chromatography was
Scheme 2. Control experiments.
performed using 200–300 mesh silica gel. All 1H NMR
N
N
13
19
Standard conditions
N
spectra, C NMR and F NMR spectra were respectively
recorded on 600 MHz, 150 MHz and 565 MHz NMR
Br
CN
N
N
O
O
TEMPO/BHT (2.0 equiv)
O
CN
1a
2a
3a, 0%
3z CN
spectrometers using deuterochloroform (CDCl ) as solvent at
3
Detected by HRMS,
When used TEMPO
room temperature, 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
spectra were obtained by using ESI ionization sources (Varian
7.0T FTICR-MS). Fluorescence emission was determined by
fluorescence spectrophotometer (F-320 Gangdong, Tianjin).
Melting points were taken on a WPX-4 apparatus and were
uncorrected (Yice instrument equipment Co Ltd, Shanghai).
The round bottom flask was made of borosilicate glass. The 9
W blue LEDs (Epistar Amou-0708, 220 V, 50 Hz, 420-500 nm)
without any filters, and the spectral distribution and intensity of
the lamp was shown in Fig. S2. The distance from the light
source to the irradiation vessel about 4 cm. The starting
materials 2 were obtained from commercial suppliers and
starting materials 1 were prepared according to the reported
N
N
N
N
O
N
O
Br
Standard conditions
O
O
O
O F
O
F
F
TEMPO/BHT (2.0 equiv)
O
F
F
F
1a
2b
4a, 0%
4
z
O
Detected by HRMS,
When used TEMPO
On the basis of the above experiments and previous works,16-
1
8
a
plausible mechanism of this visible-light-induced
photocatalytic radical cascade cyclization reaction was
described in Scheme 3. Initially, the ground-state [fac-Ir(ppy)
is converted into an excited-state [fac-Ir(ppy) *] under the
irradiation of visible light, and then excited-state [fac-Ir(ppy) *]
undergoes a single electron transfer (SET) process with 2 to
3
]
3
3
3
+
form radical · R, halogen anion and [fac-Ir(ppy) ].
Subsequently, the radical ·R attacks the C−C double bond in
the olefinic amide unit of the substrate 1 to form the radical
intermediate I, which is converted into the radical intermediate
II by radical addition cyclization to the benzene ring. Next, the
radical intermediate II undergoes a single electron oxidation to
1
0,11,22
procedures.
General Procedures for Preparation of 1. Step1: According
2
2
to the reported procedures. To a 10 mL test tube was added
CuBr (1 mol%), o-phenylenediamine (0.2 mmol), benzylamine
0.3 mmol) and toluene (2 mL). The reaction mixture was
3
produce the carbocation III, during which the [fac-Ir(ppy) ] is
2
(
regenerated. In addition, intermediate II may be oxidized by 2
to generate intermediate III, with the formation of ·R. Finally,
the carbocation intermediate III is deprotonated under the
action of a base to give the eventual product 3.
o
stirred at 100 C under air for 24 h. After cooling to room
temperature, the resulting mixture was filtered through a short
path of silica gel, eluting with ethyl acetate. The volatile
compounds were removed in vacuo and the residue was purified
by flash column chromatography on silica gel (eluent:
hexane/ethyl acetate 5 :1). Finally get the 2-phenylimidazole
derivatives.
CONCLUSIONS
In conclusion, we have disclosed the first visible-light-
induced photocatalytic radical cascade cyclization strategy for
the synthesis of CH
2
CN/CF
2
COOEt/CF
3
containing
Step2: According to the reported procedures.10-11 To the solution
of benzimidazole (5 mmol, 1.0 equiv.) and DMAP (1.0 mmol,
benzo[4,5]imidazo[2,1-a]isoquinolin derivatives from N-
methacryloyl-2-phenylbenzoimidazoles and readily available
0
3
.2 equiv.) in DCM (0.5 M) was added Et N (10 mmol, 2.0
ACS Paragon Plus Environment

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The Journal of Organic Chemistry
o
equiv.) and methacryloyl chloride (10 mmol, 2.0 equiv.) at 0 C.
= 7.9 Hz, 1H), 7.25 (s, 1H), 2.89-2.84 (m, 1H), 2.50 (s, 3H),
2.41-2.36 (m,1H), 2.10-2.05 (m, 1H), 2.00- 1.94 (m, 1H), 1.74
(s, 3H); C{ H} NMR (150 MHz, CDCl ): δ 171.7, 149.3,
3
1
2
3
4
5
6
7
8
9
The solution was warmed up to room temperature and stirred
for 12–24 h. Reaction progress was checked by thin layer
chromatography (TLC). The mixture was diluted with DCM
1
3
1
144.1, 143.2, 139.1, 131.1, 129.7, 126.5, 126.2, 126.1, 125.7,
(20 mL) and saturated NaHCO
3
solution (20 mL). The organic
120.5, 119.8, 118.2, 115.6, 48.7, 36.7, 29.7, 22.0, 13.6; HRMS
+
and aqueous layers were separated. The aqueous layer was
extracted with DCM (20 mL ×2). The combined organic layer
was washed with brine, dried over Na SO , filtered and
2 4
concentrated in vacuo to give a residue, which was purified by
flash chromatography and then recrystallized from n-
hexane/EtOAc to afford the product 1.
(ESI) m/z: [M+H] Calcd for C20
316.1445.
18 3
H N O 316.1444; Found
3
-(3-methoxy-5-methyl-6-oxo-5,6-
dihydrobenzo[4,5]imidazo[2,1-a]isoquinolin-5-
yl)propanenitrile (3c): Isolated yield (58.3 mg, 88%), White
o
1
solid, Melting range: 145.0-148.8 C; H NMR (600 MHz,
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
General Procedures for Preparation of 3/4/5. A round
bottomed flask equipped with a magnetic stirrer bar was
charged with fac-Ir(ppy) (3 mol %), olefinic amide 1 (0.2
3
mmol), KOAc (0.3 mmol) and bromoacetonitrile 2a /ethyl
bromodifluoroacetate 2b /trifluoromethane chloride 2c (0.4
mmol). The flask was evacuated and backfilled with Ar (three
CDCl ): δ 8.45 (d, J = 8.6 Hz, 1H), 8.30 (d, J = 7.6 Hz, 1H),
3
7.78 (d, J = 7.6 Hz, 1H), 7.45-7.39 (m, 2H), 7.09 (d, J = 8.4 Hz,
1H), 6.94 (s, 1H), 3.94 (s, 3H), 2.90-2.85 (m, 1H), 2.37-2.32
(m,1H), 2.12-2.07 (m, 1H), 2.03-1.98 (m, 1H), 1.75 (s, 3H);
C{ H} NMR (150 MHz, CDCl ): δ 171.6, 163.1, 149.3, 144.1,
141.2, 131.1, 128.6, 126.2, 125.5, 119.6, 118.1, 115.9, 115.5,
13
1
3
times). Then degassed dry CH
3
CN (1 mL) was injected under
114.2, 111.6, 55.7, 48.9, 36.8, 29.7, 13.6; HRMS (ESI) m/z:
[M+H] Calcd for C H N O 332.1394; Found 332.1392.
+
Ar. The resultant mixture was stirred at room temperature under
irradiation of 9 W blue LEDs. The reaction was monitored by
thin-layer chromatography (TLC). After completion of the
reaction, water (10 mL) was added into the reaction mixture.
The resulting mixture was extracted with ethyl acetate (10 mL
20 18
3
2
3
-(3-ethoxy-5-methyl-6-oxo-5,6-
dihydrobenzo[4,5]imidazo[2,1-a]isoquinolin-5-
yl)propanenitrile (3d): Isolated yield (63.6 mg, 92%), White
o
1
solid, Melting range: 117.2-122.5 C; H NMR (600 MHz,
CDCl ): δ 8.44 (d, J = 8.7 Hz, 1H), 8.30 (d, J = 7.8 Hz, 1H),
.77 (d, J = 7.7 Hz, 1H), 7.44-7.39 (m, 2H), 7.06 (dd, J = 8.7,
×
3). The organic layers were combined, and dried with
anhydrous Na SO . The solvent was removed in vacuo, and the
residue was purified by flash column chromatography
petroleum ether/EtOAc = 3:1 to 10:1, v/v) to give the desired
3
2
4
7
1
2
.9 Hz, 1H), 6.93 (d, J = 2.2 Hz, 1H), 4.18-4.15 (m, 2H), 2.89-
.84 (m, 1H), 2.37-2.32 (m,1H), 2.12-2.06 (m, 1H), 2.03-1.98
m, 1H), 1.74 (s, 3H), 1.49 (t, J = 6.9 Hz, 3H); C{ H} NMR
150 MHz, CDCl ): δ 171.7, 162.5, 149.3, 144.0, 141.2, 131.1,
128.6, 126.2, 125.5, 119.6, 118.1, 115.6, 115.6, 114.5, 112.1,
(
product 3/4/5.
1
3
1
(
Gram-Scale Synthesis of 3a. A round bottomed flask
equipped with a magnetic stirrer bar was charged with olefinic
(
3
+
amide 1 (5.0 mmol), fac-Ir(ppy)
3
(0.15 mmol), KOAc (7.5
64.1, 48.9, 36.8, 29.7, 14.7, 13.6; HRMS (ESI) m/z: [M+H]
Calcd for C H N O 346.1550; Found 346.1550.
mmol) and bromoacetonitrile 2a (10.0 mmol). The flask was
evacuated and backfilled with Ar (three times). Then degassed
dry CH CN (20 mL) was injected under Ar. The resultant
3
mixture was stirred at room temperature under irradiation of
two 9 W blue LEDs. The reaction was monitored by thin-layer
chromatography (TLC). After completion of the reaction, water
20 mL) was added into the reaction mixture. The resulting
mixture was extracted with ethyl acetate (40 mL × 3). The
2
1
20
3
2
3
-(1,5-dimethyl-6-oxo-5,6-dihydrobenzo[4,5]imidazo[2,1-
a]isoquinolin-5-yl)propanenitrile (3e): Isolated yield (49.8 mg,
1
7
9%), White liquid, H NMR (600 MHz, CDCl
m, 1H), 7.84-7.84 (m, 1H), 7.49-7.42 (m, 3H), 7.37-7.33 (m,
H), 3.05 (s, 3H), 2.90-2.85 (m, 1H), 2.40-2.35 (m, 1H), 2.09-
2.04 (m, 1H), 2.00-1.95 (m, 1H), 1.74 (s, 3H); C{ H} NMR
(150 MHz, CDCl ): δ 171.7, 149.3, 144.1, 140.6, 140.1, 131.9,
131.0, 130.3, 126.0, 126.0, 123.5, 121.7, 120.3, 118.2, 115.7,
8.7, 36.9, 30.1, 24.6, 13.6; HRMS (ESI) m/z: [M+H] Calcd
O 316.1444; Found 316.1444.
-(3-fluoro-5-methyl-6-oxo-5,6-
3
): δ 8.36-8.34
(
2
(
1
3
1
3
organic layers were combined, and dried with anhydrous
Na
2
SO
4
. The solvent was removed in vacuo, and the residue was
+
4
purified by flash column chromatography (petroleum
ether/EtOAc = 5:1, v/v) to give the desired product 3a (0.93 g,
2%).
18 3
for C20H N
3
6
dihydrobenzo[4,5]imidazo[2,1-a]isoquinolin-5-
Characterization of products. 3-(5-methyl-6-oxo-5,6-
dihydrobenzo[4,5]imidazo[2,1-a]isoquinolin-5-
yl)propanenitrile (3f): Isolated yield (47.2 mg, 74%), White
o
1
solid, Melting range: 165.5-170.0 C; H NMR (600 MHz,
CDCl ): δ 8.54-8.52 (m, 1H), 8.32 (d, J = 7.1 Hz, 1H), 7.81 (d,
J = 7.5 Hz, 1H), 7.48-7.43 (m, 2H), 7.28-7.27 (m, 1H) 7.18-7.16
yl)propanenitrile (3a): Isolated yield (54.8 mg, 91%), White
3
o
1
solid, Melting range: 114.2-118.8 C; H NMR (600 MHz,
CDCl ): δ 8.52 (d, J = 7.8 Hz, 1H), 8.33 (d, J = 7.5 Hz, 1H),
3
(
1
m, 1H) 2.90-2.85 (m, 1H), 2.36-2.31 (m,1H), 2.15-2.10 (m,
7.82 (d, J = 7.6 Hz, 1H), 7.65-7.62 (m, 1H), 7.56-7.54 (m, 1H),
13
1
H), 2.04-1.99 (m, 1H), 1.76 (s, 3H); C{ H} NMR (150 MHz,
): δ 170.9, 165.2 (d, J = 254.4 Hz), 148.3, 144.0, 141.9
d, J = 7.6 Hz), 131.1, 129.1 (d, J = 9.0 Hz), 126.4, 126.0, 120.0,
7.48-7.43 (m, 3H), 2.90-2.85 (m, 1H), 2.42-2.37 (m, 1H), 2.11-
CDCl
3
1
3
1
2
(
1
4
C
.06 (m,1H), 2.00-1.95 (m, 1H), 1.76 (s, 3H); C{ H} NMR
(
1
150 MHz, CDCl ): δ 171.6, 149.1, 144.0, 139.1, 132.4, 131.2,
3
19.6 (d, J = 2.9 Hz), 117.7, 116.7 (d, J = 22.4 Hz), 115.6, 112.9
(d, J = 23.3 Hz)., 48.9, 36.7, 29.5, 13.6; HRMS (ESI) m/z:
28.6, 126.5, 126.3, 126.0, 125.7, 123.1, 120.0, 118.1, 115.7,
+
8.7, 36.6, 29.7, 13.6; HRMS (ESI) m/z: [M+Na] Calcd for
+
[M+H] Calcd for C19
3
H15FN O 320.1194; Found 320.1194.
19
H
15
N
3
NaO 324.1107; Found 324.1106.
-(3,5-dimethyl-6-oxo-5,6-dihydrobenzo[4,5]imidazo[2,1-
a]isoquinolin-5-yl)propanenitrile (3b): Isolated yield (53.0 mg,
3
-(3-chloro-5-methyl-6-oxo-5,6-
3
dihydrobenzo[4,5]imidazo[2,1-a]isoquinolin-5-
yl)propanenitrile (3g): Isolated yield (42.3 mg, 63%), White
o
1
8
(
4%), White solid, Melting range: 148.1-149.5 C; H NMR
600 MHz, CDCl ): δ 8.39 (d, J = 8.0 Hz, 1H), 8.32 (d, J = 7.4
Hz, 1H), 7.80 (d, J = 7.6 Hz, 1H), 7.46-7.41 (m, 2H), 7.36 (d, J
o
1
solid, Melting range: 164.0-169.4 C; H NMR (600 MHz,
CDCl ): δ 8.46 (d, J = 8.4 Hz, 1H), 8.32 (d, J = 8.3 Hz, 1H),
.82 (d, J = 8.0 Hz, 1H), 7.54 (d, J = 8.3 Hz, 1H), 7.48-7.46 (m,
3
3
7
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 9
+
3
H), 2.90-2.85 (m, 1H), 2.38-2.33 (m, 1H), 2.15-2.09 (m, 1H),
36.7, 29.6, 20.6, 20.5, 13.7; HRMS (ESI) m/z: [M+H] Calcd
3
for C21H19ClN O 364.1211; Found 364.1211.
1
3
1
1
2
3
4
5
6
7
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
2.05-2.00 (m, 1H), 1.77 (s, 3H); C{ H} NMR (150 MHz,
CDCl ): δ 170.8, 148.2, 143.9, 140.8, 138.7, 131.1, 129.3,
127.9, 126.5, 126.2, 126.0, 121.7, 120.1, 117.7, 115.7, 48.7,
6.6, 29.5, 13.6; HRMS (ESI) m/z: [M+H]+ Calcd for
O 336.0898; Found 336.0897.
3-(3-bromo-5-methyl-6-oxo-5,6-
3
ethyl-2,2-difluoro-3-(5-methyl-6-oxo-5,6-
dihydrobenzo[4,5]imidazo[2,1-a]isoquinolin-5-yl)propanoate
4a): Isolated yield (66.9 mg, 87%), White solid, Melting range:
16.7-119.0 C; H NMR (600 MHz, CDCl ): δ 8.52 (d, J = 7.6
3
Hz, 1H), 8.36 (d, J = 7.2 Hz, 1H), 7.84 (d, J = 7.8 Hz, 1H), 7.58-
7.55 (m, 1H), 7.52-7.50 (m, 1H), 7.48-7.42 (m, 3H), 3.97-3.85
(m, 2H), 3.45-3.38 (m, 1H), 3.09-3.01 (m, 1H), 1.76 (s, 3H),
3
1.13 (t, J = 7.1 Hz, 3H); C{ H} NMR (150 MHz, CDCl ): δ
171.4, 163.3 (t, J = 31.8 Hz), 149.3, 144.0, 138.7, 131.5, 131.3,
128.3, 126.8, 126.2, 126.0, 125.7, 122.7, 119.9, 115.7, 114.4
1 2
= 251.2 Hz, J = 255.8 Hz), 63.1, 45.3 (d, J = 4.6 Hz),
44.5 (t, J = 23.6 Hz), 31.3, 13.6; F NMR (565 MHz, CDCl ):
δ -98.8, -99.3, -103.8, -104.2; HRMS (ESI) m/z: [M+Na]
Calcd for C21 NaO 407.1177; Found 407.1175.
3
(
1
19 3
C H15ClN
o
1
dihydrobenzo[4,5]imidazo[2,1-a]isoquinolin-5-
yl)propanenitrile (3h): Isolated yield (52.5 mg, 69%), White
o
1
13
1
solid, Melting range: 168.5-170.4 C; H NMR (600 MHz,
CDCl ): δ 8.41-8.38 (m, 1H), 8.33-8.32 (m, 1H), 7.84-7.81 (m,
H), 7.70-7.68 (m, 1H), 7.62 (s, 1H) 7.47-7.46 (m, 2H), 2.90-
.85 (m, 1H), 2.38-2.33 (m, 1H), 2.14-2.09 (m, 1H), 2.06-2.01
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
1
2
(
(dd, J
m, 1H), 1.77 (s, 3H); 13C{ H} NMR (150 MHz, CDCl
1
): δ
19
3
3
+
1
1
70.8, 148.2, 143.8, 141.0, 132.2, 131.1, 129.0, 128.1, 127.1,
26.5, 126.3, 122.1, 120.1, 117.8, 115.7, 48.7, 36.7, 29.5, 13.6;
H
18
F
2
N
2
3
+
HRMS (ESI) m/z: [M+H] Calcd for C19
Found 380.0393.
3
H15BrN O 380.0393;
ethyl-3-(3,5-dimethyl-6-oxo-5,6-
dihydrobenzo[4,5]imidazo[2,1-a]isoquinolin-5-yl)-2,2-
difluoropropanoate (4b): Isolated yield (64.5 mg, 81%), White
solid, Melting range: 123.9-126.6 C; H NMR (600 MHz,
CDCl ): δ 8.41 (d, J = 8.0 Hz, 1H), 8.35 (d, J = 7.3 Hz, 1H),
7.82 (d, J = 7.8 Hz, 1H), 7.45-7.40 (m, 2H), 7.32 (d, J = 8.0 Hz,
3
-(1,2-dichloro-5-methyl-6-oxo-5,6-
dihydrobenzo[4,5]imidazo[2,1-a]isoquinolin-5-
yl)propanenitrile (3i): Isolated yield (42.9 mg, 58%), White
o
1
3
o
1
solid, Melting range: 231.5-233.8 C; H NMR (600 MHz,
CDCl ): δ 8.37-8.35 (m, 1H), 7.95-7.93 (m, 1H), 7.71 (d, J =
8.5 Hz, 1H), 7.50-7.49 (m, 2H), 7.37 (d, J = 8.5 Hz, 1H), 2.91-
.86 (m, 1H), 2.38-2.33 (m,1H), 2.16-2.10 (m, 1H), 2.04-1.99
3
1H), 7.25 (s, 1H), 3.96-3.84 (m, 2H), 3.43-3.36 (m, 1H), 3.08-
3.00 (m, 1H), 2.46 (s, 3H), 1.74 (s, 3H), 1.12 (t, J = 7.1 Hz, 3H);
1
3
1
2
C{ H} NMR (150 MHz, CDCl
Hz), 149.5, 143.9, 142.0, 138.7, 131.4, 129.3, 127.3, 126.2,
126.0, 125.5, 120.0, 119.7, 115.6, 114.4 (dd, J = 249.3 Hz, J
254.2 Hz), 63.0, 45.2 (d, J = 4.7 Hz), 44.4 (t, J = 22.3 Hz), 31.3,
3
): δ 171.5, 163.3 (t, J = 31.9
1
3
1
(
1
1
m, 1H), 1.76 (s, 3H); C{ H} NMR (150 MHz, CDCl
3
): δ
70.3, 145.8, 143.8, 140.0, 135.9, 132.5, 130.4, 128.0, 127.1,
26.5, 124.9, 123.3, 121.1, 117.8, 115.7, 48.8, 36.7, 29.8, 13.6;
1
2
=
+
19
HRMS (ESI) m/z: [M+H] Calcd for C19
Found 370.0506.
H
14Cl
2
N
3
O 370.0508;
21.8, 13.6; F NMR (565 MHz, CDCl
3
): δ -98.6, -99.1, -103.9,
-104.4; HRMS (ESI) m/z: [M+H] Calcd for C22
99.1515; Found 399.1514.
ethyl-2,2-difluoro-3-(3-methoxy-5-methyl-6-oxo-5,6-
dihydrobenzo[4,5]imidazo[2,1-a]isoquinolin-5-yl)propanoate
(4c): Isolated yield (70.4 mg, 85%), White solid, Melting range:
+
21 2 2 3
H F N O
3
3
-(5,9,10-trimethyl-6-oxo-5,6-
dihydrobenzo[4,5]imidazo[2,1-a]isoquinolin-5-
yl)propanenitrile (3j): Isolated yield (52.7 mg, 80%), White
1
liquid, H NMR (600 MHz, CDCl
s, 1H), 7.62-7.58 (m, 2H), 7.54-7.51 (m, 1H), 7.46 (d, J = 7.9
Hz, 1H), 2.90-2.85 (m, 1H), 2.43-2.36 (m, 1H), 2.09-2.04 (m,
3
): δ 8.49-8.47 (m, 1H), 8.11
o
1
(
148.3-156.4 C; H NMR (600 MHz, CDCl
Hz, 1H), 8.34 (d, J = 7.7 Hz, 1H), 7.82 (d, J = 7.7 Hz, 1H), 7.46-
7.40 (m, 2H), 7.07 (dd, J = 8.7, J = 2.0 Hz, 1H), 6.93 (d, J
=2.0 Hz, 1H), 4.00-3.90 (m, 5H), 3.45-3.38 (m, 1H), 3.06-2.98
3
): δ 8.52 (d, J = 7.9
13
1
1
H), 1.99-1.94 (m, 1H), 1.75 (s, 3H); C{ H} NMR (150 MHz,
1
2
CDCl ): δ 171.5, 148.3, 142.5, 138.9, 135.4, 135.3, 132.0,
129.5, 128.6, 126.3, 125.7, 123.5, 120.3, 118.1, 116.0, 48.6,
36.8, 29.6, 20.5, 20.4, 13.6; HRMS (ESI) m/z: [M+H] Calcd
20 3
for C21H N O 330.1601; Found 330.1597.
3
1
3
1
(m, 1H), 1.75 (s, 3H), 1.15 (t, J = 7.1 Hz, 3H); C{ H} NMR
(150 MHz, CDCl ): δ 171.4, 163.3 (t, J = 32.0 Hz), 162.3, 149.5,
140.8, 131.3, 128.8, 128.2, 125.9, 125.3, 124.7, 119.4, 115.6,
+
3
1
5
14.3 (dd, J
5.6, 45.5 (d, J = 5.2 Hz), 44.4 (t, J = 23.5 Hz), 31.4, 13.6;
): δ -98.5, -98.9, -103.9, -104.4; HRMS
ESI) m/z: [M+H] Calcd for C22 415.1464; Found
15.1463.
ethyl-3-(3-ethoxy-5-methyl-6-oxo-5,6-
1 2
= 251.3 Hz, J = 256.0 Hz), 114.2, 112.5, 63.1,
3-(3,5,9,10-tetramethyl-6-oxo-5,6-
1
9
F
dihydrobenzo[4,5]imidazo[2,1-a]isoquinolin-5-
yl)propanenitrile (3k): Isolated yield (67.3 mg, 98%), White
NMR (565 MHz, CDCl
(
4
3
+
21 2 2 4
H F N O
o
1
solid, Melting range: 180.5-181.8 C; H NMR (600 MHz,
CDCl ): δ 8.53 (d, J = 7.2 Hz, 1H), 8.12 (s, 1H), 7.63 (s, 1H),
.38 (d, J = 7.8 Hz, 1H), 7.25 (s, 1H), 2.90-2.85 (m, 1H), 2.51-
.30 (m, 10H), 2.09-2.03 (m, 1H), 2.02-1.97 (m, 1H), 1.75 (s,
3
7
2
3
1
1
dihydrobenzo[4,5]imidazo[2,1-a]isoquinolin-5-yl)-2,2-
difluoropropanoate (4d): Isolated yield (78.0 mg, 91%), White
1
3
1
H); C{ H} NMR (150 MHz, CDCl
3
): δ 171.6, 148.2, 143.8,
o
1
39.3, 136.0, 135.9, 130.0, 128.9, 127.1, 126.2, 119.3, 118.1,
solid, Melting range: 128.7-129.9 C; H NMR (600 MHz,
CDCl ): δ 8.44 (d, J = 8.7 Hz, 1H), 8.32 (d, J = 7.9 Hz, 1H),
7.78 (d, J = 7.6 Hz, 1H), 7.43-7.38 (m, 2H), 7.03 (d, J = 8.7 Hz,
H), 6.92 (s, 1H), 4.15-4.12 (m, 2H), 4.00-3.90 (m, 2H), 3.44-
3.37 (m, 1H), 3.04-2.96 (m, 1H), 1.74 (s, 3H), 1.47 (t, J = 6.5
16.0, 48.7, 36.7, 29.8, 22.1, 20.6, 20.4, 13.7; HRMS (ESI) m/z:
3
+
[
M+H] Calcd for C22
H
22
N
3
O 344.1757; Found 344.1757.
1
3
-(3-chloro-5,9,10-trimethyl-6-oxo-5,6-
dihydrobenzo[4,5]imidazo[2,1-a]isoquinolin-5-
1
3
1
Hz, 3H), 1.15 (t, J = 7.1 Hz, 3H); C{ H} NMR (150 MHz,
CDCl ): δ 171.4, 163.3 (t, J = 31.9 Hz), 161.7, 149.6, 144.0,
40.8, 131.4, 130.0, 128.2, 125.9, 125.2, 119.4, 115.6, 115.3,
14.6, 113.0, 114.4 (dd, J = 249.5 Hz, J = 253.8 Hz), 63.3, 45.5
yl)propanenitrile (3l): Isolated yield (45.8 mg, 63%), White
o
1
3
solid, Melting range: 194.1-195.4 C; H NMR (600 MHz,
CDCl ): δ 8.55 (d, J = 8.0 Hz, 1H), 8.12 (s, 1H), 7.62 (s, 1H),
.53 (d, J = 7.7 Hz, 1H), 7.44 (s, 1H), 2.90-2.85 (m, 1H), 2.43-
1
1
3
1
2
7
1
9
(
(
d, J = 4.1 Hz), 44.5 (t, J = 22.4 Hz), 31.4, 14.7, 13.6; F NMR
565 MHz, CDCl ): δ -98.6, -99.0, -103.9, -104.4; HRMS (ESI)
1
3
1
2.30 (m,7H), 2.13-2.01 (m, 2H), 1.77 (s, 3H); C{ H} NMR
(150 MHz, CDCl ): δ 170.7, 147.2, 140.8, 138.9, 136.2, 136.1,
129.4, 129.1, 128.2, 126.1, 121.2, 119.8, 117.7, 116.0, 48.7,
3
3
ACS Paragon Plus Environment

Page 7 of 9
The Journal of Organic Chemistry
23 2 2 4
H F N O 429.1620; Found
ethyl-3-(3-chloro-5,9,10-trimethyl-6-oxo-5,6-
m/z: [M+H]+ Calcd for C23
429.1622.
1
2
3
4
5
6
7
8
9
dihydrobenzo[4,5]imidazo[2,1-a]isoquinolin-5-yl)-2,2-
difluoropropanoate (4i): Isolated yield (58.1 mg, 65%), White
ethyl-2,2-difluoro-3-(3-fluoro-5-methyl-6-oxo-5,6-
dihydrobenzo[4,5]imidazo[2,1-a]isoquinolin-5-yl)propanoate
4e): Isolated yield (61.2 mg, 76%), White solid, Melting range:
3
30.0-131.5 C; H NMR (600 MHz, CDCl ): δ 8.54-8.52 (m,
o
1
solid, Melting range: 172.0-173.9 C; H NMR (600 MHz,
CDCl ): δ 8.51-8.50 (m, 1H), 8.13 (s, 1H), 7.61 (s, 1H), 7.49-
7.48 (m, 1H), 7.43 (s, 1H), 4.02 (q, J = 7.1 Hz, 2H), 3.45-3.38
(
1
3
o
1
(
1
m, 1H), 3.02-2.94 (m, 1H), 2.43-2.41 (m, 6H), 1.76 (s, 3H),
.19 (t, J = 7.1 Hz, 3H); C{ H} NMR (150 MHz, CDCl
1H), 8.34 (d, J = 8.2 Hz, 1H), 7.82 (d, J = 7.3 Hz, 1H), 7.47-
7.42 (m, 2H), 7.25-7.22 (m, 1H), 7.17-7.15 (m, 1H), 4.03 (q, J
= 7.2 Hz, 2H), 3.47-3.39 (m, 1H), 3.00-2.92 (m, 1H), 1.76 (s,
1
3
1
3
): δ
1
70.5, 163.0 (t, J =32.1 Hz), 147.5, 141.4, 140.4, 137.6, 135.7,
1
3
1
135.5, 129.5, 129.0, 127.8, 127.0, 121.1, 119.9, 116.0, 114.1
dd, J = 249.7 Hz, J = 253.5 Hz), 63.3, 45.2 (d, J = 4.3 Hz),
4.5 (t, J = 23.7 Hz), 31.2, 20.5, 20.4, 13.7; F NMR (565 MHz,
3
H), 1.19 (t, J = 7.1 Hz, 3H); C{ H} NMR (150 MHz, CDCl
3
):
(
4
1
2
δ 170.8, 164.6 (d, J = 253.2 Hz), 163.1 (t, J = 31.9 Hz), 148.6,
43.9, 141.7 (d, J = 7.8 Hz), 131.4, 128.8 (d, J = 9.1 Hz), 126.2,
25.8, 119.9, 119.1 (d, J = 2.8 Hz), 116.3 (d, J = 22.4 Hz),
= 250.5 Hz, J = 253.1 Hz), 113.8 (d, J =
1 2
3.4 Hz), 63.2, 45.5 (d, J = 3.9 Hz), 44.5 (t, J = 22.8 Hz), 31.2,
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
19
1
1
1
2
1
1
3
CDCl ): δ -99.2, -99.6, -103.5, -104.0; HRMS (ESI) m/z:
+
[
M+H] Calcd for C23
5-methyl-5-(2,2,2-trifluoroethyl)benzo[4,5]imidazo[2,1-
a]isoquinolin-6(5H)-one (5a): Isolated yield (37.0 mg, 56%),
2 2 3
H22ClF N O 447.1282; Found 447.1281.
15.7, 114.4 (dd, J
19
3.6; F NMR (565 MHz, CDCl
03.3, -106.4; HRMS (ESI) m/z: [M+H] Calcd for
403.1264; Found 403.1264.
ethyl-3-(3-chloro-5-methyl-6-oxo-5,6-
3
): δ -99.9, -100.4, -102.9, -
+
o
1
White solid, Melting range: 127.6-130.1 C; H NMR (600
C
21
H
18
F
3
N
2
O
3
MHz, CDCl ): δ 8.54 (d, J = 7.7 Hz, 1H), 8.36 (d, J = 7.3 Hz,
3
1H), 7.84 (d, J = 8.2 Hz, 1H), 7.61-7.59 (m, 1H), 7.54-7.52 (m,
1H), 7.48-7.43 (m, 3H), 3.51-3.44 (m, 1H), 2.98-2.91 (m, 1H),
dihydrobenzo[4,5]imidazo[2,1-a]isoquinolin-5-yl)-2,2-
1
3
1
3
1.76 (s, 3H); C{ H} NMR (150 MHz, CDCl ): δ 170.9, 149.2,
difluoropropanoate (4f): Isolated yield (68.7 mg, 82%), White
o
1
143.9, 138.5, 131.6, 131.4, 128.4, 126.4, 126.4, 126.2, 125.8,
solid, Melting range: 121.0-126.3 C; H NMR (600 MHz,
CDCl ): δ 8.45 (d, J = 8.3 Hz, 1H), 8.34 (d, J = 6.9 Hz, 1H),
7.82 (d, J = 7.0 Hz, 1H), 7.49-7.42 (m, 4H), 4.02 (q, J = 7.1 Hz,
H), 3.46-3.39 (m, 1H), 3.02-2.94 (m, 1H), 1.75 (s, 3H), 1.18
1
2
25.0 (q, J = 277.0 Hz), 122.4, 119.9, 115.7, , 45.3, 44.0 (q, J =
3
1
9
3
7.8 Hz), 30.9; F NMR (565 MHz, CDCl ): δ -61.4; HRMS
+
+
(ESI) m/z: [M+H] Calcd for C18
14 3 2
H F N O 331.1053; Found
2
1
3
1
331.1051.
(
t, J = 7.1 Hz, 3H); C{ H} NMR (150 MHz, CDCl
3
): δ 170.7,
63.0 (t, J =32.0 Hz), 148.4, 143.9, 140.5, 137.6, 131.4, 128.9,
27.6, 127.0, 126.2, 126.0, 121.4, 120.0, 115.7, 114.2 (dd, J
50.3 Hz, J = 253.1 Hz), 63.3, 45.3 (d, J = 4.1 Hz), 44.4 (t, J =
3.3 Hz), 31.1, 13.7; F NMR (565 MHz, CDCl
1
1
2
2
9
3,5-dimethyl-5-(2,2,2-trifluoroethyl)benzo[4,5]imidazo[2,1-
1
=
a]isoquinolin-6(5H)-one (5b): Isolated yield (44.1 mg, 64%),
o
1
2
White solid, Melting range: 203.4-208.1 C; H NMR (600
1
9
3
+
): δ -99.3, -
MHz, CDCl ): δ 8.42 (d, J = 7.9 Hz, 1H), 8.34 (d, J = 7.4 Hz,
3
9.7, -103.3, -103.8; HRMS (ESI) m/z: [M+H] Calcd for
419.0969; Found 419.0967.
ethyl-3-(3-bromo-5-methyl-6-oxo-5,6-
1H), 7.82 (d, J = 7.8 Hz, 1H), 7.47-7.41 (m, 2H), 7.35 (d, J =
C
21
H
18ClF
2
N
2
O
3
7.9 Hz, 1H), 7.25 (s, 1H), 3.49-3.42 (m, 1H), 2.97-2.90 (m, 1H),
13
1
2
3
.48 (s, 3H), 1.75 (s, 3H); C{ H} NMR (150 MHz, CDCl ): δ
171.1, 149.4, 143.8, 142.4, 138.5, 131.3, 129.6, 129.6, 126.8,
dihydrobenzo[4,5]imidazo[2,1-a]isoquinolin-5-yl)-2,2-
126.4, 126.1, 125.6, 124.9 (q, J = 276.8 Hz), 119.7, 115.6, 45.2,
difluoropropanoate (4g): Isolated yield (79.7 mg, 86%), White
1
9
o
1
3
44.0 (q, J = 27.5 Hz), 30.9, 21.9; F NMR (565 MHz, CDCl ):
solid, Melting range: 153.8-156.3 C; H NMR (600 MHz,
CDCl ): δ 8.45 (d, J = 8.3 Hz, 1H), 8.35-8.34 (m, 1H), 7.83-
7.82 (m, 1H), 7.65 (dd, J = 8.4, J = 1.8 Hz, 1H), 7.61 (d, J =
+
16 3 2
δ -61.3; HRMS (ESI) m/z: [M+H] Calcd for C19H F N O
3
3
45.1209; Found 345.1209.
1
2
1.6 Hz, 1H), 7.47-7.43 (m, 2H), 4.03 (q, J = 7.2 Hz, 2H), 3.46-
3.39 (m, 1H), 3.03-2.95 (m, 1H), 1.76 (s, 3H), 1.19 (t, J = 7.2
3-methoxy-5-methyl-5-(2,2,2-
trifluoroethyl)benzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one
1
3
1
Hz, 3H); C{ H} NMR (150 MHz, CDCl
J =32.0 Hz), 148.5, 143.9, 140.6, 131.8, 131.4, 130.0, 127.7,
26.2, 126.0, 125.9, 121.8, 120.0, 115.7, 114.2 (dd, J = 250.2
Hz, J = 253.4 Hz), 64.0, 63.1, 45.3 (d, J = 4.8 Hz), 44.5 (t, J =
3
): δ 170.6, 163.0 (t,
(5c): Isolated yield (45.4 mg, 63%), White solid, Melting range:
o
1
154.2-156.4 C; H NMR (600 MHz, CDCl ): δ 8.47 (d, J = 8.7
3
1
1
Hz, 1H), 8.32 (d, J = 7.8 Hz, 1H), 7.79 (d, J = 7.6 Hz, 1H), 7.45-
2
7.39 (m, 2H), 7.08-7.07 (m, 1H), 6.94 (s, 1H), 3.92 (s, 3H),
1
9
13
1
2
9
2.5 Hz), 31.1, 13.7; F NMR (565 MHz, CDCl
3
+
): δ -99.1, -
3.50-3.43(m, 1H), 2.94-2.86 (m, 1H), 1.75 (s, 3H); C{ H}
9.6, -103.4, -103.9; HRMS (ESI) m/z: [M+H] Calcd for
463.0463; Found 463.0461.
ethyl-2,2-difluoro-3-(3,5,9,10-tetramethyl-6-oxo-5,6-
dihydrobenzo[4,5]imidazo[2,1-a]isoquinolin-5-yl)propanoate
NMR (150 MHz, CDCl ): δ 171.0, 162.5, 149.4, 144.1, 140.6,
3
C
21
H
18BrF
2
N
2
O
3
131.3, 128.4, 126.1, 125.4, 124.9 (q, J = 277.1 Hz), 119.5,
1
3
15.6, 115.2, 114.0, 112.4, 55.6, 45.4, 44.0 (q, J = 27.7 Hz),
19
1.1; F NMR (565 MHz, CDCl
3
): δ -61.3; HRMS (ESI) m/z:
+
[M+H] Calcd for C19
H
16
F
3
N
2
O
2
361.1158; Found 361.1157.
(
1
4h): Isolated yield (72.5 mg, 85%), White solid, Melting range:
o
1
51.1-152.8 C; H NMR (600 MHz, CDCl
3
): δ 8.37 (d, J = 8.0
3-bromo-5-methyl-5-(2,2,2-
Hz, 1H), 8.13 (s, 1H), 7.57 (s, 1H), 7.30 (d, J = 8.0 Hz, 1H),
.23 (s, 1H), 3.94-3.82 (m, 2H), 3.42-3.35 (m, 1H), 3.06-2.98
m, 1H), 2.45-2.40 (m, 9H), 1.73 (s, 3H), 1.11 (t, J = 7.2 Hz,
trifluoroethyl)benzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one
7
(
(5d): Isolated yield (37.6 mg, 46%), White solid, Melting range:
o
1
241.0-244.1 C; H NMR (600 MHz, CDCl ): δ 8.39 (d, J = 8.4
3
1
3
1
3H); C{ H} NMR (150 MHz, CDCl
3
): δ 171.4, 163.4 (t, J =
Hz, 1H), 8.35-8.34 (m, 1H), 7.84-7.82 (m, 1H), 7.68-7.66 (m,
31.9 Hz), 148.8, 142.2, 141.6, 138.5, 135.0, 134.8, 129.7, 129.3,
1H), 7.62 (s, 1H), 7.49-7.45 (m, 2H), 3.51-3.44 (m, 1H), 2.94-
1
3
1
1
2
2
9
27.3, 126.0, 120.2, 119.9, 116.0, 114.4 (dd, J
1
= 249.0 Hz, J
2
=
2.86 (m, 1H), 1.77 (s, 3H); C{ H} NMR (150 MHz, CDCl ):
3
54.3 Hz), 63.0, 45.1 (d, J = 5.1 Hz), 44.5 (t, J = 23.6 Hz), 31.3,
δ 171.2, 148.4, 143.9, 140.2, 132.0, 131.3, 129.7, 127.8, 126.4,
1
9
1.8, 20.5, 20.4, 13.6; F NMR (565 MHz, CDCl
3
): δ -98.4, -
126.3, 126.2, 124.8 (q, J = 277.2 Hz), 121.5, 120.1, 115.7, 45.2,
+
19
8.9, -104.2, -104.7; HRMS (ESI) m/z: [M+H] Calcd for
427.1828; Found 427.1827.
44.0 (q, J = 27.9 Hz), 30.8; F NMR (565 MHz, CDCl ): δ -
3
24 25 2 2 3
C H F N O
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 9
6
1.4; HRMS (ESI) m/z: [M+H]+ Calcd for C18
409.0158; Found 409.0156.
,9,10-trimethyl-5-(2,2,2-
trifluoroethyl)benzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one
H
13BrF
3
N
2
O
ACKNOWLEDGMENT
1
2
3
4
5
6
7
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
This work was financially supported by the National Natural
Science Foundation of China (No 21672174 and No 21977084),
and the Natural Science Foundation of Chongqing (No.
cstc2019jcyj-msxmX0297).
5
(
1
5e): Isolated yield (40.9 mg, 57%), White solid, Melting range:
70.1-172.9 C; H NMR (600 MHz, CDCl ): δ 8.50 (d, J = 8.5
3
o
1
REFERENCES
Hz, 1H), 8.14 (s, 1H), 7.59 (s, 1H), 7.58-7.55 (m, 1H), 7.52-
7.49 (m, 1H), 7.45 (d, J = 7.9 Hz, 1H), 3.50-3.42 (m, 1H), 2.96-
(1) (a) Patil, N. T.; Yamamoto, Y. Coinage Metal-Assisted Synthesis
of Heterocycles. Chem. Rev. 2008, 108, 3395-3442. (b) Guo, X. X.; Gu,
D. W.; Wu, Z. X.; Zhang, W. B. Copper-Catalyzed C–H
Functionalization Reactions: Efficient Synthesis of Heterocycles.
Chem. Rev. 2015, 115, 1622-1651. (c) Pan, F.; Shu, C.; Ye, L.-W.
Recent progress towards gold-catalyzed synthesis of N-containing
tricyclic compounds based on ynamides. Org. Biomol. Chem. 2016, 14,
2.89 (m, 1H), 2.43-2.41 (m, 6H), 1.75 (s, 3H); 1 C{ H} NMR
3
1
(
1
1
150 MHz, CDCl
3
): δ 170.9, 148.5, 142.4, 138.3, 135.2, 135.2,
31.3, 129.7, 128.4, 126.4, 126.2, 125.0 (q, J = 277.2 Hz),
22.7, 120.1, 116.0, 45.2, 44.0 (q, J = 27.6 Hz), 30.9, 20.5, 20.4;
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
9
F NMR (565 MHz, CDCl
3
): δ -61.4; HRMS (ESI) m/z:
O 359.1366; Found 359.1365.
,5,9,10-tetramethyl-5-(2,2,2-
trifluoroethyl)benzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one
+
[
18 3 2
M+H] Calcd for C20H F N
9
456-9465. (d) Wu, B.; Yoshikai, N. Recent developments in synthetic
methods for benzo[b]heteroles. Org. Biomol. Chem. 2016, 14, 5402-
416. (e) Xie, L.-Y.; Qu, J.; Peng, S.; Liu, K.-J.; Wang, Z.; Ding, M.-
3
5
H.; Wang, Y.; Cao, Z.; He, W.-M. Coinage Metal-Assisted Synthesis
of Heterocycles. Green Chem. 2018, 20, 760-764.
(5f): Isolated yield (49.9 mg, 67%), White solid, Melting range:
o
1
1
3
96.2-198.5 C; H NMR (600 MHz, CDCl ): δ 8.37 (d, J = 8.0
(2) Fulp, A. B.; Wang, X. WO2005002503 A2, 2005.
Hz, 1H), 8.12 (s, 1H), 7.57 (s, 1H), 7.32 (d, J = 8.0 Hz, 1H),
(3) Deady, L. W.; Rodemann, T. Reduced Benzimidazo[2,1-
a]isoquinolines. Synthesis and Cytotoxicity Studies. Aust. J. Chem.
2002, 54, 529-534.
7
2
.23 (s, 1H), 3.48-3.40 (m, 1H), 2.95-2.88 (m, 1H), 2.47 (s, 3H),
13
1
.42-2.40 (m, 6H), 1.73 (s, 3H); C{ H} NMR (150 MHz,
): δ 171.0, 148.8, 142.5, 141.9, 138.3, 135.0, 134.9,
129.7, 129.4, 126.8, 126.1, 125.0 (q, J = 277.2 Hz), 120.0,
(4) Shun, C. K. J.; Chou, Y. C. WO2005002503 A2, 2005.
CDCl
3
(5) Taublaender, M. J.; Glöcklhofer, F.; Marchetti-Deschmann, M.;
1
9
Unterlass, M. Green and Rapid Hydrothermal Crystallization and
Synthesis of Fully Conjugated Aromatic Compounds. Angew. Chem.,
Int. Ed. 2018, 57, 12270-12274.
(6) Meng, G.; Niu, H.-Y.; Qu, G.-R.; Fossey, J. S.; Li, J.-P.; Guo,
H.-M. Synthesis of fused N-heterocycles via tandem C–H activation.
Chem. Commun. 2012, 48, 9601-9603.
116.0, 45.1, 44.0 (q, J = 27.6 Hz), 30.9, 21.9, 20.5, 20.4;
NMR (565 MHz, CDCl ): δ -61.4; HRMS (ESI) m/z: [M+H]
O 373.1522; Found 373.1522.
2-((5-methyl-6-oxo-5,6-
F
+
3
20 3 2
Calcd for C21H F N
diethyl
dihydrobenzo[4,5]imidazo[2,1-a]isoquinolin-5-
yl)methyl)malonate (6a): Isolated yield (53 mg, 63%), White
liquid; H NMR (600 MHz, CDCl
8
(7) Sun, X.; Hu, Y.; Nie, S.-Z.; Yan, Y.-Y.; Zhang, X.-J.; Yan, M.
Efficient Construction of C=N Double Bonds via Acceptorless
Dehydrogenative Coupling. Adv. Synth. Catal. 2013, 355, 2179-2184.
(8) Xue, D.; Long, Y.-Q. Metal-Free TEMPO-Promoted C(sp )–H
Amination To Afford Multisubstituted Benzimidazoles. J. Org. Chem.
2014, 79, 4727-4734.
(9) Mai, S.; Luo, Y.; Huang, X.; Shu, Z.; Li, B.; Lan, Y.; Song, Q.
Diversity-oriented synthesis of imidazo[2,1-a]isoquinolines. Chem.
Commun. 2018, 54, 10240-10243.
1
3
): δ 8.52-8.50 (m, 1H), 8.35-
.33 (m, 1H), 7.84-7.83 (m, 1H), 7.60-7.57 (m, 1H), 7.52-7.49
3
(m, 2H), 7.46-7.43 (m, 2H), 3.97-3.93 (m, 1H), 3.88-3.83 (m,
1
1
H), 3.77-3.69 (m, 2H), 3.10-3.05 (m, 2H), 2.80-2.75 (m, 1H),
.77 (s, 3H), 1.03 (t, J = 7.1 Hz, 3H), 0.98 (t, J = 7.1 Hz, 3H);
1
3
1
C{ H} NMR (150 MHz, CDCl
3
): δ 172.0, 168.5, 168.4, 149.5,
1
1
43.9, 139.9, 131.9, 131.3, 128.2, 126.5, 126.1, 126.0, 125.7,
(10) Sun, K.; Li, S.-J.; Chen, X.-L.; Liu, Y.; Huang, X.-Q.; Wei, D.-
23.0, 119.8, 115.7, 61.7, 61.6, 48.7, 48.0, 39.3, 30.2, 13.7,
H.; Qu, L.-B.; Zhao, Y.-F.; Yu, B. Silver-catalyzed decarboxylative
radical cascade cyclization toward benzimidazo[2,1-a]isoquinolin-
+
13.6; HRMS (ESI) m/z: [M+H] Calcd for C24
421.1758; Found 421.1768.
25 2 5
H N O
6
(5H)-ones. Chem. Commun. 2019, 55, 2861-2864.
(11) Sun, K.; Li, G.; Li, Y.; Yu, J.; Zhao, Q.; Zhang, Z.; Zhang, G.
Oxidative Radical Relay Functionalization for the Synthesis of
Benzimidazo[2,1-a ]iso-quinolin-6(5H)-ones. Adv. Synth. Catal. 2020,
362, 1947-1954.
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the ACS
Publications website.
(12) (a) Shaw, M. H.; Twilton, J.; MacMillan, D. W. C. Photoredox
Catalysis in Organic Chemistry. J. Org. Chem. 2016, 81, 6898-6926.
(b) Welin, E. R.; Le, C.; Arias-Rotondo, D. M.; McCusker, J. K.;
MacMillan, D. W. C. Photosensitized, energy transfer-mediated
organometallic catalysis through electronically excited nickel(II).
Science. 2017, 355, 380-385. (c) Liang, Y.; Zhang, X.; MacMillan, D.
Experimental
characterization data; spectral data (PDF)
procedures;
mechanistic
investigation;
3
W. C. Decarboxylative sp C–N coupling via dual copper and
photoredox catalysis. Nature. 2018, 559, 83-88. (d) Kornfilt, D. J. P.;
MacMillan, D. W. C. Copper-Catalyzed Trifluoromethylation of Alkyl
Bromides. J. Am. Chem. Soc. 2019, 141, 6853-6858.
AUTHOR INFORMATION
Corresponding Author
*E-mail: heyh@swu.edu.cn (for Y.-H. He).
*E-mail: guanzhi@swu.edu.cn (for Z. Guan)
(13) (a) Staveness, D.; Bosque, I.; Stephenson, C. R. J. Free Radical
Chemistry Enabled by Visible Light-Induced Electron Transfer. Acc.
Chem. Res. 2016, 49, 2295-2306. (b) Karkӓs, M. D.; Porco, J. A.;
Stephenson, C. R. J. Photochemical Approaches to Complex
Chemotypes: Applications in Natural Product Synthesis. Chem. Rev.
2016, 116, 9683-9747. (c) Monos, T. M.; McAtee, R. C.; Stephenson,
C. R. J. Arylsulfonylacetamides as bifunctional reagents for alkene
aminoarylation. Science. 2018, 361, 1369-1373.
(14) (a) Blum, T. R.; Miller, Z. D.; Bates, D. M.; Guzei, I. A.; Yoon,
T. P. Enantioselective photochemistry through Lewis acid–catalyzed
triplet energy transfer. Science. 2016, 354, 1391-1395. (b) Yoon, T. P.
ORICD
Yan-Hong He: 0000-0002-6405-285X
Zhi Guan: 0000-0002-0369-6141
Notes
The authors declare no competing financial interest.
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The Journal of Organic Chemistry
Photochemical Stereocontrol Using Tandem Photoredox–Chiral Lewis
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Visible-Light Promoted Radical Cyclization to Access Perfluoroa-kyl-
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Acid Catalysis. Acc. Chem. Res. 2016, 49, 2307-2315. (c) Skubi, K. L.;
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Benzimidazo[2,1-a]isoquinolin-6(5H)-ones
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5
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5
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