Metal-Free Visible-Light Photocatalytic Tandem Radical Addition–Cyclization Strategy for the Synthesis of Sulfonyl-Containing Isoquinolinediones

Article abstract of DOI:10.1002/ejoc.201801519

A mild radical cascade reaction for the synthesis of sulfonyl-containing isoquinolinediones has been developed, in which sulfonyl radicals can be accessed from simple sodium sulfinates under visible light and eosin Y catalysis. This tandem approach features a broad range of substrates and functional group tolerance. With this strategy, trifluoromethylated isoquinolinedione was also obtained.

Full text of DOI:10.1002/ejoc.201801519

A Journal of
Accepted Article
Title: Metal-free visible-light photocatalytic tandem radical addition-
cyclization strategy for the synthesis of sulfonyl-containing
isoquinolinediones
Authors: Kai-Li Zuo, Yan-Hong He, and Zhi Guan
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201801519
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10.1002/ejoc.201801519
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Metal-free visible-light photocatalytic tandem radical addition-
cyclization strategy for the synthesis of sulfonyl-containing
isoquinolinediones
Kai-Li Zuo,[a] Yan-Hong He*[a] and Zhi Guan*[a]
Abstract: A mild radical cascade reaction for the synthesis of
sulfonyl-containing isoquinolinediones has been developed, in which
sulfonyl radicals can be accessed from simple sodium sulfinates
under visible light and eosin Y catalysis. This tandem approach
features a broad range of substrates and functional group tolerance.
With this strategy, trifluoromethylated isoquinolinedione was also
obtained.
sulfonyl radicals in photoredox reactions, which has attracted
our interest.
As a class of important skeleton, isoquinolinediones have been
the focus of research.[12] Given their unique chemical, biological
and pharmaceutical activities, a series of isoquinolinedione
derivatives[13] including sulfonyl-containing isoquinolinediones
have been synthesized. A general, concise strategy that enables
direct synthesis of sulfonyl-containing isoquinolinedione
derivatives by addition of sulfonyl radicals to N-methyl-N-
methacryloylbenzamides followed by cyclization has attracted
great interest. Several research groups used different methods
to obtain sulfonyl radicals to successfully apply this strategy. In
2015, Zhou’s group[14] and Xu’s group[15] used ArSO2NHNH2 as
the precursors and tert-butyl hydroperoxide (TBHP) as an
oxidant in the presence of tetrabutylammonium bromide (TBAB)
Introduction
Visible-light, as an abundant and sustainable clean energy
source, has attracted wide attention from synthetic organic
chemists in the past few years.[1] Visible-light photoredox
catalysis provides a green and environmentally benign synthetic
platform for the formation of C-C or C-heteroatom bonds.[2]
Photocatalysts, as a kind of medium, play an important role in
photoredox reaction since most organic molecules cannot
directly utilize visible light. Organic dyes, such as eosin Y and
rose Bengal, as a class of organic photocatalysts, are relatively
inexpensive and non-toxic. They have a wider range of
absorption compared to metal complex photocatalysts that
contain ruthenium (II) and iridium (III), and have been widely
used in photoredox transformations.[3]
o
o
+ NaI at 90 C or tetrabutylammonium iodide (TBAI) at 80 C to
generate sulfonyl radicals, respectively. In 2016, Xia’s group[16]
and Sun’s group[17] employed ArSO2Cl as the sulfonyl sources to
produce sulfonyl radicals through visible light photoredox
catalysis using Ru(bpy)3Cl2 or [Ir(ppy)2dtbbpy]PF6 as the
photocatalyst under blue LEDs, respectively. In 2017, Zhou’s
group[18] utilized ArSO2Na as the sulfonyl sources to generate
sulfonyl radicals with a combined catalyst system composed of
Co(OAc)2•4H2O and KI at 140 oC. (Scheme 1) These efforts
have greatly improved and enriched this reaction. However, the
existing methods still have some drawbacks, such as the use of
excessive amounts of oxidants, irritating reagents, noble metals,
high temperatures, etc. Therefore, it is still necessary to develop
mild, environmentally friendly and simple methods for this useful
reaction.
Many
sulfonyl-containing
compounds
display
various
bioactivities and are therefore of great significance in the
development of agrochemicals and pharmaceuticals.[4]
Accordingly, the methods of forming sulfonyl radicals are also
greatly expanded. Visible-light photoredox catalysis provides a
powerful and versatile tool for the formation of free radical
species.[5] The precursors which are currently capable of
producing sulfonyl radicals include sulfinic acids[6], sodium
Scheme 1. Methods for constructing sulfonyl-containing isoquinolinediones
[10]
sulfinates[7], sulfonyl chlorides[8], sulfonyl hydrazides[9], SO2
and so on[11]. Sodium sulfinates are stable, non-irritating and
commercially available at low cost when used as a source of
[a]
Key Laboratory of Applied Chemistry of Chongqing Municipality,
School of Chemistry and Chemical Engineering, Southwest
University
Chongqing 400715, China
Prof. Dr. Y.-H. He, Prof. Dr. Z. Guan
E-mail: heyh@swu.edu.cn
guanzhi@swu.edu.cn
http://222.198.118.160/s/chemistry/szxx/20151222/180919.html
http://222.198.118.160/s/chemistry/szxx/20151222/180909.html
Supporting information for this article is given via a link at the end of
the document.
Herein, we report a mild and metal-free method for the
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10.1002/ejoc.201801519
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synthesis of sulfonyl-containing isoquinolinediones from N-alkyl-
N-methacryloyl benzamides in which sulfonyl radicals can be
easily accessed from stable, low cost and non-irritating sodium
sulfinates by visible light photoredox catalysis using an
inexpensive organic dye, eosin Y, as a photocatalyst.
Results and Discussion
In our initial investigation, the reaction of N-methyl-N-
methacryloylbenzamide (1a) and sodium benzenesulfinate (2a)
was chosen as a model reaction. Rose Bengal was first used as
a photocatalyst for the model reaction in DMF under irradiation
of 7 W blue light-emitting diodes (LEDs) in an argon atmosphere.
To our delight, the desired product 3a was obtained in 45% yield
(Table 1, entry 1). On this basis, we investigated the effect of
adding water on the reaction and found that adding a small
amount of water to the reaction system can increase the
reaction yield (see Supporting Information (SI), Table S1),
possibly due to the addition of water that promotes dissolution of
2a. A yield of 56% was obtained in a mixed solvent of of DMF (2
mL)/H2O (50 μL) (Table 1, entry 2). We then investigated the
effect of substrate molar ratio on the reaction and found that
when 3.0 equivalents of 2a were used, a yield of 60% was
obtained (Table 1, entry 3; for details, see SI, Table S2). Thus,
reaction conditions of a mixed solvent of DMF (2 mL)/H2O (50
μL) and 3.0 equivalents of 2a were used for further
investigations. Next, other photocatalysts such as eosin Y, Na2-
eosin Y, eosin B and Ru(bpy)3Cl2·6H2O were examined for the
reaction (Table 1, entries 4-7). The reaction with eosin Y gave
the best yield of 70% (Table 1, entry 4). Therefore, eosin Y was
selected as the photocatalyst for the reaction. After screening
the eosin Y loading, 5 mol % of eosin Y was selected as the
optimal condition (SI, Table S3). Evaluation of different solvents
revealed that DMF was the best choice for this process (Table 1,
entries 4 and 8-11). In order to test the effect of oxygen on the
reaction, the model reaction was carried out under O2 and air
atmosphere respectively; the desired product was not obtained,
indicating that oxygen is harmful to this reaction (Table 1,
entries 12 and 13). Using green LEDs or compact fluorescent
lamp (CFL) instead of blue LEDs in the presence of eosin Y did
not give better results (Table 1, entries 14 and 15). Moreover,
control experiments proved that both photocatalyst and visible
light were required for this conversion because no reaction was
observed in the absence of visible-light or photocatalyst (Table 1,
entries 16 and 17). Therefore, based on the experimental results,
it was found that the optimized reaction conditions (for a 0.2
mmol scale of 1a) consisted of 5 mol% of eosin Y, 1a/2a = 1 : 3
(molar ratio), 7 W blue LEDs, DMF (2 mL)/H2O (50 μL) and
argon atmosphere.
Entry
1
Photocatalyst
rose Bengal
Solvent
DMF
Note
Yield (%)b
45
2a (2.0 equiv),
without H2O
2a (2.0 equiv)
2
3
rose Bengal
rose Bengal
eosin Y
DMF
DMF
DMF
DMF
DMF
DMF
DMSO
THF
56
60
--
4
--
70
5
Na2- eosin Y
eosin B
--
50
6
--
53
7
Ru(bpy)3Cl2·6H2O
eosin Y
--
56
8
--
--
60
9
eosin Y
51
10
11
eosin Y
MeCN
EtOH
--
42
eosin Y
--
trace
under air
atmosphere
under O2
atmosphere
7 W green LEDs
32 W CFL
in the dark
--
12
13
eosin Y
eosin Y
DMF
DMF
trace
NRc
14
15
16
17
eosin Y
eosin Y
eosin Y
--
DMF
DMF
DMF
DMF
40
59
NR
NR
a Unless otherwise noted, reaction conditions: 1a (0.2 mmol, 1.0 equiv), 2a
(0.6 mmol, 3.0 equiv), photocatalyst (5 mol %), H2O (50 μL) and solvent (2
mL) stirred under irradiation of 7 W blue LEDs in argon atmosphere at RT
(25-30 oC) for 24 h. b Yield of isolated product. c No reaction.
Using the optimized conditions (Table 1, entry 4), we
investigated substrate scope of the reaction (Table 2). The
transformation was first extended to various substituted N-
methyl-N-methacryloylbenzamides. Several groups such as
methyl, tertiary butyl, methoxyl, fluoro, chloro, bromo,
trifluoromethyl and ester group at different position of benzene
ring were able to survive under the optimized conditions to
produce corresponding products (3b-3l). The presence of an
electron-donating group and an electron-withdrawing group on
the benzene ring of compounds 1 had no significant effect on
the reaction. 3,4-Dichlorobenzamide and naphthamide also
could participate in the reaction delivering desired
isoquinolinediones 3m and 3n. However, to our disappointment,
when the aromatic ring of compound 1 is thiophene, the
transformation failed. The methacryloyl benzamides 1 with
different N-substituents were also examined and the
corresponding products were obtained in moderate yields (3o-
3t). A series of sodium sulfinates were then investigated in this
reaction and the desired products were obtained in good yields
(3u-3y).
Table 1. Selected optimization experiments and control experiments.[a]
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10.1002/ejoc.201801519
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Table 2. Substrate scope.[a,b]
aReaction conditions: 1 (0.2 mmol, 1.0 equiv), 2 (0.6 mmol, 3.0 equiv), eosin Y (5 mol %), H2O (50 μL) and DMF (2 mL) stirred under irradiation of 7 W blue
LEDs in argon atmosphere at RT (25-30 oC) for 24 h. bYield of the isolated product after chromatography on silica gel.
Interestingly, when a bromo substituted substrate 1 was used, it
not only gave the desired product (3z), but also produced a yield
of 30% of compound 3a in which the bromine atom was
removed (Scheme 2, a). When a meta-fluoro substituted
substrate 1 was used, two regioisomers 3aa (37%) and 3aa’
(29%) were obtained, which were formed by cyclization at the
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10.1002/ejoc.201801519
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para and ortho positions, respectively (Scheme 2, b). However,
the above-mentioned examples of meta-CH3 or CF3 substituted
substrate 1 only gave a single product (Table 2, 3j and 3l) which
was formed by cyclization at the para position, probably because
CH3 and CF3 are bulkier than F. Additionally, when sodium
trifluoromethanesulfinate
was
used,
the
trifluoromethylsulfonylation product was not formed, but
trifluoromethylated isoquinolinedione 3ab was obtained in a yield
of 37% (Scheme 2, c).[19] When R2 is hydrogen atom, the
desired cyclized product cannot be achieved, but the radical
addition product 4 was obtained (Scheme 2, d). When R2 is a
sulfonyl
group
or
the
nitrogen
atom
of
N-
methacryloylbenzamides is replaced with O, the starting material
was decomposed, and no desired product was detected.
In order to understand the effect of photo-irradiation, the reaction
with the light on/off over time was carried out (Figure 1(a)). The
results indicated that continuous irradiation of visible light is
essential, and radical-chain propagation is not a critical pathway
in this reaction. Further, to verify which substrate can quench the
excited photocatalyst, a series of fluorescence quenching
experiments of eosin Y with substrates were performed (see SI,
Figure S2-S4), and the Stern-Volmer plot is shown in Figure
1(b). The experiments showed that sodium benzenesulfinate 2a
caused a strong fluorescence quenching of excited eosin Y,
while almost no any quenching effect was observed for N-
methyl-N-methacryloylbenzamide 1a. Additionally, we tested the
reaction system with pH test paper before and after the reaction,
and the results showed that a base was generated during the
reaction (see SI, Figure S6).
Scheme 2. Exceptional examples
y
=
a
+
b*x
No Weightin
8.81515 6.98901E-4
Equation
Weight
Eosin Y+1a
Eosin Y+2a
Residual Sum
of Squares
60
50
40
30
20
10
0
0.98954
0.96832
0.84413
0.99989
Pearson's
r
14
12
10
8
Adj. R-Square
Value
Standard Erro
Intercept
1
1638.3516
1
--
127.06285
--
B
B
C
C
Slope
Intercept
Slope
10.10989
1.13139
6
4
2
0
0
2
4
6
8
10
12
0.000
0.001
0.002
0.003
0.004
0.005
0.006
Next, to gain more mechanistic insight, we performed some
control experiments (Scheme 3). 2,2,6,6-Tetramethyl-1-
piperidinyloxy (TEMPO) and 2,6-di-tert-butyl-4-methylphenol
(BHT) are a class of radical scavengers. When 3.0 equivalents
of TEMPO or BHT was added to the model reaction system
under optimized reaction conditions, no desired product was
obtained (Scheme 3, a and b). In addition, 1,1-diphenylethylene
has been widely used in photochemistry due to its ability to trap
radicals. When 3.0 equivalents of 1,1-diphenylethylene were
present in the reaction system, the yield of product 3a was
lowered to 12% and the product 5 which captured the sulfonyl
radical was obtained in a yield of 35% (Scheme 3, c). All of the
results revealed that this reaction should involve a radical
process, and sulfonyl radical is a key intermediate.
Time (h)
Concentration(mol/L)
(a)
(b)
Figure 1. a) Light ON/OFF experiment; b) Sterm-Volmer profile of eosin Y by
various concentrations of 1a and 2a
On the basis of above mechanistic studies and related
literature[20], we proposed a plausible process for the current
photocatalytic radical addition/cyclization reaction (Scheme 4).
First, the excited state of photocatalyst, eosin Y*, which is
formed reversibly upon visible light irradiation, is reductively
quenched by the sulfinate 2a (E1/2 = 0.47 V vs.SCE, see SI,
Figure S5) to afford [eosin Y]·- (E1/2
[eosin Y*/eosin Y·-] =
red
+0.83 V vs.SCE)[21] and sulfonate radical A. There is a
resonance between the oxygen-centered sulfonyl radical A and
the corresponding sulfur-centered sulfonyl radical B. Next,
radical B undergoes a radical addition to alkene 1a generating
new radical C, which can be intramolecularly cyclized to form
intermediate D. Product 3a and eosin Y-H hydride[20b] are then
given from intermediate D and eosin Y radical anion by single
electron transfer (SET) and proton transfer (PT). Finally, the
Scheme 3. Control experiments
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10.1002/ejoc.201801519
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eosin Y-H hydride reacts with proton to release H2 and
regenerate eosin Y to complete the photocatalytic cycle.
by using ESI ionization sources. Melting points were taken on a WPX-4
apparatus and were uncorrected (Yice instrument equipment Co Ltd,
Shanghai). Cyclic voltammetry was performed using electrochemical
workstation (CHI700E, Shanghai Chenhua Instrument Co., Ltd. Shanghai).
Scheme 4. Proposed Reaction Mechanism
General procedure for the synthesis of products 3: A round bottom flask
was charged with eosin Y (5 mol %), N-alkyl-N-methacryloyl benzamide 1 (0.2
mmol) and sodium sulfinate 2 (0.6 mmol). The flask was evacuated and
backfilled with Ar (three times). Then DMF (2 mL) and H2O (50 μL) were added
under Ar. The resultant mixture was stirred at room temperature under
irradiation of 7 W blue LEDs. After completion of the reaction, as monitored by
TLC, brine (5 mL) was added. The resulting mixture was extracted with ethyl
acetate (5 mL × 3). The organic layer was combined, and dried over
anhydrous Na2SO4. The solvent was removed in vacuo, and the residue was
purified by flash column chromatography (petroleum ether/EtOAc 3/1-1/2, v/v)
to afford the desired product 3.
2,4-dimethyl-4-((phenylsulfonyl)methyl)isoquinoline-1,3(2H,4H)-dione
(3a):[16] White solid (48.0 mg, 70%), m.p. 175.2-176.8 oC. 1H NMR (600 MHz,
CDCl3) δ 8.29 (d, J = 7.1 Hz, 1H), 7.53 (t, J = 7.3 Hz, 1H), 7.49 (d, J = 7.5 Hz,
2H), 7.42-7.36 (m, 4H), 7.17 (d, J = 7.4 Hz, 1H), 4.46 (d, J = 14.7 Hz, 1H),
3.90 (d, J = 14.7 Hz, 1H), 3.40 (s, 3H), 1.59 (s, 3H) ppm. 13C NMR (150 MHz,
CDCl3) δ 174.3, 163.7, 140.3, 139.1, 133.4, 129.3, 129.1, 128.1, 127.6, 125.8,
124.9, 64.8, 45.4, 31.6, 27.5 ppm.
2,4,6-trimethyl-4-((phenylsulfonyl)methyl)isoquinoline-1,3(2H,4H)-dione
(3b): White solid (52.5 mg, 74%), m.p. 178.1-179.5 oC. 1H NMR (600 MHz,
CDCl3) δ 8.15 (d, J = 8.0 Hz, 1H), 7.50 (t, J = 7.4 Hz, 1H), 7.42 (d, J = 7.3 Hz,
2H), 7.34 (t, J = 7.8 Hz, 2H), 7.17 (d, J = 8.0 Hz, 1H), 6.82 (s, 1H), 4.47 (d, J =
14.8 Hz, 1H), 3.89 (d, J = 14.8 Hz, 1H), 3.40 (s, 3H), 2.17 (s, 3H), 1.57 (s, 3H)
ppm. 13C NMR (150 MHz, CDCl3) δ 174.4, 163.8, 144.4, 140.4, 138.9, 133.3,
129.3, 129.2, 128.9, 127.5, 126.3, 122.5, 64.8, 45.3, 31.5, 27.4, 21.6 ppm.
HRMS (ESI) calc. for C19H19NO4S (M+Na)+: 380.0927, found: 380.0929.
Conclusions
In summary, a general visible-light photocatalytic protocol for the
synthesis of sulfonyl-containing isoquinolinediones via radical
tandem C-S/C-C bond formation has been developed. In this
strategy, stable, non-irritating and cheap sodium sulfinates were
used as radical precursors, and a relatively inexpensive and
non-toxic organic dye eosin Y was used as a photocatalyst. This
tandem approach features a broad range of substrates and
functional
group
tolerances.
With
this
method,
6-(tert-butyl)-2,4-dimethyl-4-((phenylsulfonyl)methyl)isoquinoline-
1,3(2H,4H)-dione (3c): White solid (36.4 mg, 46%), m.p. 183.8-184.5 oC. 1H
NMR (600 MHz, CDCl3) δ 8.20 (d, J = 8.3 Hz, 1H), 7.51-7.44 (m, 4H), 7.37-
7.35 (m, 2H), 7.19 (d, J = 3.8 Hz, 1H), 4.49 (d, J = 14.7 Hz, 1H), 3.94 (d, J =
14.7 Hz, 1H), 3.38 (s, 3H), 1.59 (s, 3H), 1.24-1.23 (m, 9H) ppm. 13C NMR (150
MHz, CDCl3) δ 174.6, 163.8, 157.4, 140.4, 138.9, 133.5, 129.1, 129.0, 127.7,
125.6, 122.4, 122.3, 65.0, 45.7, 35.2, 31.8, 30.9, 27.4 ppm. HRMS (ESI) calc.
for C22H25NO4S (M+Na)+: 422.1397, found: 422.1395.
trifluoromethylated isoquinolinedione was also obtained.
Compared to previously reported methods, this protocol is more
environmentally friendly, milder and more economical, avoiding
the use of excessive amounts of oxidants, additives, irritating
reagents, noble metals and high temperatures. Therefore, we
believe that this work is a useful complement to existing
methods.
6-methoxy-2,4-dimethyl-4-((phenylsulfonyl)methyl)isoquinoline-
1,3(2H,4H)-dione (3d): White solid (45.4 mg, 61%), m.p. 159.7-160.7 oC. 1H
NMR (600 MHz, CDCl3) δ 8.22 (d, J = 8.8 Hz, 1H), 7.52 (t, J = 7.4 Hz, 1H),
7.48 (d, J = 7.5 Hz, 2H), 7.36 (t, J = 7.8 Hz, 2H), 6.89 (dd, J = 8.8, 2.2 Hz, 1H),
6.51 (d, J = 2.2 Hz, 1H), 4.47 (d, J = 14.8 Hz, 1H), 3.86 (d, J = 14.7 Hz, 1H),
3.71 (s, 3H), 3.38 (s, 3H), 1.57 (s, 3H) ppm. 13C NMR (150 MHz, CDCl3) δ
174.4, 163.7, 163.4, 141.2, 140.4, 133.3, 131.6, 129.0, 127.6, 117.9, 114.1,
111.1, 64.8, 55.4, 45.7, 31.7, 27.4 ppm. HRMS (ESI) calc. for C19H19NO5S
(M+Na)+: 396.0876, found: 396.0875.
Experimental Section
General information: N-Alkyl-N-methacryloyl benzamides 1 were prepared
according to the literature[22]. Eosin Y was purchased from J&K Scientific Ltd.
L520P26-5g. DMF was dried over 3A molecular sieves. Unless otherwise
noted, all reagents were purchased from commercial suppliers and used
without further purification. Reactions were monitored by thin-layer
chromatography (TLC) with Haiyang GF 254 silica gel plates (Qingdao
Haiyang chemical industry Co Ltd, Qingdao, China) using UV light and vanillic
aldehyde as visualizing agents. Flash column chromatography was performed
using 200-300 mesh silica gel at increased pressure. 1H NMR spectra and 13
C
6-fluoro-2,4-dimethyl-4-((phenylsulfonyl)methyl)isoquinoline-1,3(2H,4H)-
dione (3e): White solid (48.3 mg, 67%), m.p. 241.3-242.0 oC. 1H NMR (600
MHz, CDCl3) δ 8.31 (dd, J = 8.5, 5.9 Hz, 1H), 7.57 (t, J = 7.4 Hz, 1H), 7.53 (d,
J = 7.6 Hz, 2H), 7.41 (t, J = 7.7 Hz, 2H), 7.10 (t, J = 7.9 Hz, 1H), 6.83 (d, J =
9.1 Hz, 1H), 4.46 (d, J = 14.7 Hz, 1H), 3.82 (d, J = 14.7 Hz, 1H), 3.40 (s, 3H),
NMR spectra were respectively recorded on 600 MHz and 150 MHz NMR
spectrometers. Chemical shifts (δ) were expressed in ppm with TMS as the
internal standard, and coupling constants (J) were reported in Hz.
Fluorescence emission was determined by fluorescence spectrophotometer
(F-2500 Hitachi, Tokyo, Japan). High-resolution mass spectra were obtained
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1.59 (s, 3H) ppm. 13C NMR (150 MHz, CDCl3) δ 173.8, 166.7, 165.0, 162.8,
142.1 (d, J = 8.6 Hz), 133.7, 132.3 (d, J = 9.7 Hz), 129.2, 127.5, 121.3, 116.2,
116.1, 113.0, 112.8, 64.7, 45.6, 31.4, 27.6 ppm. HRMS (ESI) calc. for
C18H16FNO4S (M+Na)+: 384.0676, found: 384.0679.
NMR (150 MHz, CDCl3) δ 173.5, 162.7 (d, J = 266.2 Hz), 160.6, 141.7, 140.3,
134.5 (d, J = 10.5 Hz), 133.6, 129.2, 127.6, 121.9 (d, J = 4.2 Hz), 116.7 (d, J =
22. 2Hz), 113.9 (d, J = 4.2 Hz), 64.8, 45.4, 31.8, 27.4. HRMS (ESI) calc. for
C18H16FNO4S (M+Na)+: 384.0676, found: 384.0677.
6-chloro-2,4-dimethyl-4-((phenylsulfonyl)methyl)isoquinoline-1,3(2H,4H)-
dione (3f): White solid (50.7 mg, 67%), m.p. 218.5-219.7 oC. 1H NMR (600
MHz, CDCl3) δ 8.22 (d, J = 8.5 Hz, 1H), 7.56 (t, J = 7.4 Hz, 1H), 7.47 (d, J =
7.5 Hz, 2H), 7.39 (t, J = 7.8 Hz, 2H), 7.35 (dd, J = 8.4, 1.5 Hz, 1H), 7.06 (d, J =
1.1 Hz, 1H), 4.46 (d, J = 14.8 Hz, 1H), 3.85 (d, J = 14.8 Hz, 1H), 3.42 (s, 3H),
1.58 (s, 3H) ppm. 13C NMR (150 MHz, CDCl3) δ 173.7, 162.9, 140.7, 140.2,
140.1, 133.8, 130.8, 129.1, 128.8, 127.4, 126.2, 123.4, 64.6, 45.4, 31.3, 27.6
ppm. HRMS (ESI) calc. for C18H16ClNO4S (M+Na)+: 400.0381, found:
400.0380.
2,4-dimethyl-4-((phenylsulfonyl)methyl)-7-(trifluoromethyl)isoquinoline-
1,3(2H,4H)-dione (3l): White solid (47.6 mg, 58%), m.p. 151.9-152.6 oC. 1H
NMR (600 MHz, CDCl3) δ 8.56 (s, 1H), 7.58-7.54 (m, 2H), 7.48 (d, J = 7.4 Hz,
2H), 7.38 (t, J = 7.8 Hz, 2H), 7.29 (d, J = 8.2 Hz, 1H), 4.50 (d, J = 14.8 Hz, 1H),
3.92 (d, J = 14.8 Hz, 1H), 3.45 (s, 3H), 1.62 (s, 3H). 13C NMR (150 MHz,
CDCl3) δ 173.5, 162.6, 142.7, 140.0, 133.7, 130.8 (q, J = 33.7 Hz), 130.7,
129.6 (q, J = 3.4 Hz), 129.3, 127.5, 126.8, 126.6 (q, J = 3.8 Hz), 125.6, 124.2
122.4, 64.6, 45.5, 31.2, 27.8. HRMS (ESI) calc. for C19H16F3NO4S (M+Na)+:
434.0644, found: 434.0641.
methyl 2,4-dimethyl-1,3-dioxo-4-((phenylsulfonyl)methyl)-1,2,3,4-
tetrahydroisoquinoline-6-carboxylate (3g): White solid (43.0 mg, 54%), m.p.
223.2-223.9 oC. 1H NMR (600 MHz, CDCl3) δ 8.35 (d, J = 8.2 Hz, 1H), 8.00 (d,
J = 8.2 Hz, 1H), 7.73 (s, 1H), 7.47 (t, J = 7.4 Hz, 1H), 7.43 (d, J = 7.5 Hz, 2H),
7.33 (t, J = 7.8 Hz, 2H), 4.48 (d, J = 14.8 Hz, 1H), 3.98 (d, J = 14.8 Hz, 1H),
3.91 (s, 3H), 3.44 (s, 3H), 1.63 (s, 3H) ppm. 13C NMR (150 MHz, CDCl3) δ
173.9, 165.3, 163.0, 140.2, 139.08, 134.3, 133.2, 129.5, 129.1, 128.8, 128.2,
127.4, 64.8, 52.5, 45.4, 31.2, 27.7 ppm. HRMS (ESI) calc. for C20H19NO6S
(M+Na)+: 424.0825, found: 424.0825.
6,7-dichloro-2,4-dimethyl-4-((phenylsulfonyl)methyl)isoquinoline-
1,3(2H,4H)-dione (3m): White solid (33.0 mg, 40%), m.p. 237.7-238.7 oC. 1H
NMR (600 MHz, CDCl3) δ 8.33 (s, 1H), 7.59 (t, J = 7.4 Hz, 1H), 7.49 (d, J = 7.6
Hz, 2H), 7.41 (t, J = 7.7 Hz, 2H), 7.14 (s, 1H), 4.45 (d, J = 14.8 Hz, 1H), 3.81
(d, J = 14.9 Hz, 1H), 3.42 (s, 3H), 1.59 (s, 3H). 13C NMR (150 MHz, CDCl3) δ
173.3, 162.0, 139.9, 138.4, 138.3, 133.8, 133.4, 130.9, 129.2, 128.2, 127.3,
124.8, 64.9, 45.0, 31.0, 27.8. HRMS (ESI) calc. for C18H15Cl2NO4S (M+Na)+:
433.9991, found: 433.9993.
1,3-dimethyl-1-((phenylsulfonyl)methyl)benzo[f]isoquinoline-2,4(1H,3H)-
dione (3n): White solid (24.8 mg, 32%), m.p. 189.8-190.5 oC. 1H NMR (600
MHz, CDCl3) δ 8.37 (d, J = 8.6 Hz, 1H), 8.06-8.05 (m, 1H), 7.76 (d, J = 8.6 Hz,
1H), 7.69-7.67 (m, 1H), 7.45-7.43 (m, 2H), 7.08 (t, J = 7.4 Hz, 1H), 7.02 (d, J =
7.3 Hz, 2H), 6.88 (t, J = 7.8 Hz, 2H), 4.75 (d, J = 15.0 Hz, 1H), 4.68 (d, J =
15.1 Hz, 1H), 3.51 (s, 3H), 2.02 (s, 3H) ppm. 13C NMR (150 MHz, CDCl3) δ
175.6, 164.1, 136.6, 135.9, 132.6, 130.2, 130.1, 129.2, 128.1, 127.6, 126.8,
126.7, 125.1, 124.4, 124.2, 63.7, 46.6, 29.1, 27.8 ppm. HRMS (ESI) calc. for
C22H19NO4S (M+Na)+: 416.0927, found: 416.0928.
2,4-dimethyl-4-((phenylsulfonyl)methyl)-6-(trifluoromethyl)isoquinoline-
1,3(2H,4H)-dione (3h): White solid (49.1 mg, 60%), m.p. 226.3-226.7 oC. 1H
NMR (600 MHz, CDCl3) δ 8.43 (d, J = 8.2 Hz, 1H), 7.65 (d, J = 8.2 Hz, 1H),
7.53 (t, J = 7.4 Hz, 1H), 7.45 (d, J = 7.3 Hz, 2H), 7.38-7.38 (m, 3H), 4.50 (d, J
= 14.8 Hz, 1H), 3.91 (d, J = 14.8 Hz, 1H), 3.46 (s, 3H), 1.63 (s, 3H) ppm. 13
C
NMR (150 MHz, CDCl3) δ 173.6, 162.7, 140.0, 139.9, 135.0 (q, J = 32.9 Hz),
133.8, 130.2, 129.2, 127.9, 127.3, 125.0 (q, J = 32.9 Hz), 123.9, 123.0 (q, J =
3.7 Hz), 122.1, 64.8, 45.5, 31.2, 27.8 ppm. HRMS (ESI) calc. for
C19H16F3NO4S (M+Na)+: 434.0644, found: 434.0640.
2-ethyl-4-methyl-4-((phenylsulfonyl)methyl)isoquinoline-1,3(2H,4H)-dione
(3o):[14] White solid (42.8 mg, 60%), m.p. 175.8-177.1 oC. 1H NMR (600 MHz,
CDCl3) δ 8.30-8.28 (m, 1H), 7.53-7.49 (m, 3H), 7.41-7.36 (m, 4H), 7.16-7.14
(m, 1H), 4.47 (d, J = 14.6 Hz, 1H)., 4.09 (q, J = 7.0 Hz, 2H), 3.91 (d, J = 14.6
Hz, 1H), 1.57 (s, 3H), 1.30 (t, J = 7.1 Hz, 3H) ppm. 13C NMR (150 MHz,
CDCl3) δ 173.9, 163.3, 140.5, 139.2, 133.3, 133.3, 129.3, 129.1, 128.1, 127.5,
125.7, 125.0, 64.7, 45.4, 36.1, 31.5, 12.7 ppm.
2,4,8-trimethyl-4-((phenylsulfonyl)methyl)isoquinoline-1,3(2H,4H)-dione
(3i): White solid (49.2 mg, 69%), m.p. 211.1-212.0 oC. 1H NMR (600 MHz,
CDCl3) δ 7.54-7.53 (m, 3H), 7.39 (t, J = 7.8 Hz, 2H), 7.27-7.24 (m, 1H), 7.20 (d,
J = 7.4 Hz, 1H), 7.11 (d, J = 7.7 Hz, 1H), 4.47 (d, J = 14.6 Hz, 1H), 3.90 (d, J =
14.6 Hz, 1H), 3.38 (s, 3H), 2.82 (s, 3H), 1.58 (s, 3H) ppm. 13C NMR (150 MHz,
CDCl3) δ 174.0, 164.3, 143.0, 140.4, 133.4, 132.3, 132.2, 129.0, 127.6, 124.2,
123.0, 65.0, 45.6, 32.1, 27.5, 24.1 ppm. HRMS (ESI) calc. for C19H19NO4S
(M+Na)+: 380.0927, found: 380.0931.
4-methyl-4-((phenylsulfonyl)methyl)-2-propylisoquinoline-1,3(2H,4H)-
dione (3p): White solid (46.0 mg, 62%), m.p. 116.0-116.7 oC. 1H NMR (600
MHz, CDCl3) δ 8.28 (d, J = 7.7 Hz, 1H), 7.54-7.49 (m, 3H), 7.41-7.34 (m, 4H),
7.15 (d, J = 7.7 Hz, 1H), 4.48 (d, J = 14.7 Hz, 1H), 4.03-3.97 (m, 2H), 3.92 (d,
J = 14.7 Hz, 1H), 1.78-1.70 (m, 2H), 1.57 (s, 3H), 1.00 (t, J = 7.4 Hz, 3H) ppm.
13C NMR (150 MHz, CDCl3) δ 174.1, 163.5, 140.5, 139.2, 133.4, 133.3, 129.3,
129.1, 128.1, 127.5, 125.7, 124.9, 45.5, 42.5, 31.7, 20.9, 11.4 ppm. HRMS
(ESI) calc. for C20H20NO4S (M+Na)+: 394.1083, found: 394.1086.
2,4,7-trimethyl-4-((phenylsulfonyl)methyl)isoquinoline-1,3(2H,4H)-dione
(3j): White solid (37.2 mg, 52%), m.p. 159.2-159.8 oC. 1H NMR (600 MHz,
CDCl3) δ 8.06 (s, 1H), 7.53-7.46 (m, 3H), 7.36-7.33 (m, 2H), 7.13-7.12 (m, 1H),
7.04-7.02 (m, 1H), 4.42 (d, J = 14.6 Hz, 1H), 3.88 (d, J = 14.6 Hz, 1H), 3.39 (s,
3H), 2.38 (s, 3H), 1.56 (s, 3H). 13C NMR (150 MHz, CDCl3) δ 174.4, 163.9,
140.3, 138.1, 136.2, 134.4, 133.2, 129.3, 129.0, 127.6, 125.8, 124.6, 65.0,
45.1, 31.5, 27.5, 21.0. HRMS (ESI) calc. for C19H19NO4S (M+Na)+: 380.0927,
found: 380.0930.
2-isopropyl-4-methyl-4-((phenylsulfonyl)methyl)isoquinoline-1,3(2H,4H)-
dione (3q): [14] White solid (42.5 mg, 57%), m.p. 156.2-156.6 oC. 1H NMR (600
MHz, CDCl3) δ 8.27 (d, J = 7.0 Hz, 1H), 7.53-7.48 (m, 3H), 7.39-7.35 (m, 3H),
7.33-7.29 (m, 1H), 7.10-7.09 (m, 1H), 5.30-5.23 (m, 1H), 4.46 (d, J = 14.6 Hz,
1H), 3.88 (d, J = 14.6 Hz, 1H), 1.58-1.53 (m, 9H) ppm. 13C NMR (150 MHz,
8-fluoro-2,4-dimethyl-4-((phenylsulfonyl)methyl)isoquinoline-1,3(2H,4H)-
dione (3k): White solid (47.0 mg, 65%), m.p. 213.3-214.3 oC. 1H NMR (600
MHz, CDCl3) δ 7.61-7.56 (m, 3H), 7.46-7.42 (m, 3H), 7.14-7.09 (m, 2H), 4.48
(d, J = 14.6 Hz, 1H), 3.88 (d, J = 14.6 Hz, 1H), 3.38 (s, 3H), 1.60 (s, 3H). 13C
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10.1002/ejoc.201801519
European Journal of Organic Chemistry
FULL PAPER
CDCl3) δ 174.3, 163.9, 140.8, 139.1, 133.3, 133.1, 129.3, 129.3, 129.1, 128.0,
2,4-dimethyl-4-((methylsulfonyl)methyl)isoquinoline-1,3(2H,4H)-dione
(3x):[15] White solid (42.6 mg, 76%), m.p. 123.4-124.0 oC. 1H NMR (600 MHz,
CDCl3) δ 8.32 (dd, J = 7.9, 0.8 Hz, 1H), 7.69-7.68 (m, 1H), 7.53-7.49 (m, 2H),
4.31 (d, J = 14.7 Hz, 1H), 3.82 (d, J = 14.7 Hz, 1H), 3.43 (s, 3H), 2.61 (s, 3H),
1.65 (s, 3H) ppm. 13C NMR (150 MHz, CDCl3) δ 174.6, 163.7, 140.0, 133.9,
129.8, 128.4, 125.2, 124.9, 63.5, 45.6, 43.9, 31.3, 27.5 ppm.
127.4, 125.5, 64.8, 45.9, 45.7, 31.4, 19.6, 19.2 ppm.
2-cyclopropyl-4-methyl-4-((phenylsulfonyl)methyl)isoquinoline-
1,3(2H,4H)-dione (3r): White solid (50.6 mg, 69%), m.p 177.8-180.2 oC. 1H
NMR (600 MHz, CDCl3) δ 8.27-8.25 (m, 1H), 7.54-7.50 (m, 3H), 7.40-7.34 (m,
4H), 7.15 (d, J = 7.7 Hz, 1H), 4.44 (d, J = 14.6 Hz, 1H), 3.87 (d, J = 14.6 Hz,
1H), 2.81-2.77 (m, 1H), 1.55 (s, 3H), 1.22-1.15 (m, 2H), 0.97-0.93 (m, 1H),
0.72-0.68 (m, 1H) ppm. 13C NMR (150 MHz, CDCl3) δ 175.1, 164.6, 140.5,
139.1, 133.4, 133.3, 129.2, 129.1, 128.1, 127.5, 125.8, 125.5, 64.7, 45.7, 31.3,
24.8, 8.4, 8.3 ppm. HRMS (ESI) calc. for C20H19NO4S (M+Na)+: 392.0927,
found: 392.0929.
4-((ethylsulfonyl)methyl)-2,4-dimethylisoquinoline-1,3(2H,4H)-dione (3y):
White solid (34.0 mg, 58%), m.p. 153.0-154.5 oC. 1H NMR (600 MHz, CDCl3) δ
8.31 (dd, J = 7.8, 0.9 Hz, 1H), 7.69-7.69 (m, 1H), 7.52-7.48 (m, 2H), 4.27 (d, J
= 14.4 Hz, 1H), 3.74 (d, J = 14.5 Hz, 1H), 3.42 (s, 3H), 2.78-2.67(m, 2H), 1.64
(s, 3H), 1.28 (t, J = 7.4 Hz, 3H) ppm. 13C NMR (150 MHz, CDCl3) δ 174.7,
163.8, 140.1, 133.8, 129.7, 128.3, 125.2, 124.8, 60.5, 50.2, 45.5, 31.5, 27.5,
6.3 ppm. HRMS (ESI) calc. for C14H17NO4S (M+Na)+: 318.0770, found:
318.0773.
4-methyl-2-phenyl-4-((phenylsulfonyl)methyl)isoquinoline-1,3(2H,4H)-
dione (3s): White solid (41.4 mg, 51%), m.p. 246.2-247.7 oC. 1H NMR (600
MHz, CDCl3) δ 8.32 (dd, J = 7.6, 1.5 Hz, 1H), 7.55-7.51 (m, 5H), 7.48-7.35 (m,
7H), 7.22 (d, J = 7.5 Hz, 1H), 4.47 (d, J = 14.6 Hz, 1H), 3.97 (d, J = 14.6 Hz,
1H), 1.70 (s, 3H) ppm. 13C NMR (150 MHz, CDCl3) δ 174.4, 163.8, 140.6,
139.3, 135.6, 133.7, 133.4, 129.7, 129.3, 129.2, 128.7, 128.5, 128.3, 127.5,
126.0, 125.1, 65.2, 45.9, 31.4 ppm. HRMS (ESI) calc. for C23H19NO4S
(M+Na)+: 428.0927, found: 428.0928.
6-bromo-2,4-dimethyl-4-((phenylsulfonyl)methyl)isoquinoline-1,3(2H,4H)-
dione (3z): White solid (26.4 mg, 31%), m.p. 244.3-245.0 oC. 1H NMR (600
MHz, CDCl3) δ 8.14 (d, J = 8.4 Hz, 1H), 7.56 (t, J = 7.2 Hz, 1H), 7.51 (dd, J =
8.4, 1.7 Hz, 1H), 7.47 (d, J = 7.9 Hz, 2H), 7.40 (t, J = 7.7 Hz, 2H), 7.20 (d, J =
1.6 Hz, 1H), 4.46 (d, J = 14.8 Hz, 1H), 3.83 (d, J = 14.8 Hz, 1H), 3.42 (s, 3H),
1.58 (s, 3H) ppm. 13C NMR (150 MHz, CDCl3) δ 173.6, 163.1, 140.7, 140.1,
133.9, 131.7, 130.8, 129.2, 129.1, 128.8, 127.3, 123.9, 64.7, 45.3, 31.3, 27.7
ppm. HRMS (ESI) calc. for C18H16BrNO4S (M+Na)+: 443.9876, found:
443.9873.
2-benzyl-4-methyl-4-((phenylsulfonyl)methyl)isoquinoline-1,3(2H,4H)-
dione (3t): White solid (48.2 mg, 57%), m.p. 149.8-151.4 oC. 1H NMR (600
MHz, CDCl3) δ 8.29 (d, J = 4.0 Hz, 1H), 7.52-7.46 (m, 5H), 7.40-7.36 (m, 4H),
7.30 (m, 2H), 7.25-7.20 (m, 2H), 5.23 (q, J = 14.0 Hz, 2H), 4.48 (d, J = 14.6 Hz,
1H), 3.94 (d, J = 14.4 Hz, 1H), 1.53 (s, 3H) ppm. 13C NMR (150 MHz, CDCl3) δ
174.2, 163.5, 140.6, 139.4, 137.0, 133.6, 133.4, 129.6, 129.1, 128.5, 128.4,
128.1, 127.6, 127.6, 125.8, 124.8, 64.4, 45.9, 44.1, 31.7 ppm. HRMS (ESI)
calc. for C24H21NO4S (M+Na)+: 442.1083, found: 442.1088.
5-fluoro-2,4-dimethyl-4-((phenylsulfonyl)methyl)isoquinoline-1,3(2H,4H)-
dione (3aa): White solid (26.4 mg, 37%), m.p. 171.6-172.5 oC. 1H NMR (600
MHz, CDCl3) δ 7.95 (dd, J = 8.8, 2.8 Hz, 1H), 7.58-7.56 (m, 1H), 7.53-7.51 (m,
2H), 7.43-7.40 (m, 2H), 7.17 (dd, J = 8.7, 4.8 Hz, 1H), 7.10-7.06 (m, 1H), 4.45
(d, J = 14.7 Hz, 1H), 3.86 (d, J = 14.7 Hz, 1H), 3.41 (s, 3H), 1.58 (s, 3H) ppm.
13C NMR (150 MHz, CDCl3) δ 174.0, 162.7 (d, J = 2.5 Hz), 162.0 (d, J = 247.9
Hz) 140.14, 134.9 (d, J = 3.3 Hz), 133.6, 129.2, 128.1 (d, J = 7.9 Hz), 127.6,
127.0 (d, J = 7.8 Hz), 121.0 (d, J = 22.6 Hz), 115.4 (d, J = 23.4 Hz), 64.9, 45.1,
31.5, 27.7 ppm. HRMS (ESI) calc. for C18H16FNO4S (M+Na)+: 384.0676,
found: 384.0679.
2,4-dimethyl-4-(tosylmethyl)isoquinoline-1,3(2H,4H)-dione (3u):[16] White
solid (46.5 mg, 65%), m.p. 140.7-141.0 oC. 1H NMR (600 MHz, CDCl3) δ 8.29-
8.27 (m, 1H), 7.42-7.40 (m, 2H), 7.36 (d, J = 8.2 Hz, 2H), 7.21-7.19 (m, 1H),
7.16 (d, J = 8.0 Hz, 2H), 4.44 (d, J = 14.6 Hz, 1H), 3.87 (d, J = 14.6 Hz, 1H),
3.39 (s, 3H), 2.39 (s, 3H), 1.58 (s, 3H) ppm. 13C NMR (150 MHz, CDCl3) δ
174.3 163.8, 144.5, 139.2, 137.3, 133.4, 129.6, 129.3, 128.0, 127.7, 125.9,
124.8, 64.9, 45.4, 31.6, 27.5, 21.5 ppm.
7-fluoro-2,4-dimethyl-4-((phenylsulfonyl)methyl)isoquinoline-1,3(2H,4H)-
dione (3aa’):White solid (21.0 mg, 29%), m.p. 166.4-168.0 oC. 1H NMR (600
MHz, CDCl3) δ 8.16 (d, J = 7.9 Hz, 1H), 7.55-7.50 (m, 3H), 7.42-7.36 (m, 3H),
7.03-7.00 (m, 1H), 4.39 (d, J = 14.6 Hz, 1H), 4.24 (d, J = 14.6 Hz, 1H), 3.41 (s,
3H), 1.68 (s, 3H) ppm. 13C NMR (150 MHz, CDCl3) δ 173.9, 162.8 (d, J = 3.2
Hz), 159.7 (d, J = 248.7 Hz), 139.6, 133.5, 129.9 (d, J = 9.3 Hz), 129.0, 127.6,
126.9 (d, J = 3.5 Hz), 126.0 (d, J = 12.1 Hz), 125.5 (d, J = 2.9 Hz), 120.9,
120.7, 62.3 (d, J = 6.1 Hz), 43.4 (d, J = 3.1 Hz), 27.9 (d, J = 2.9 Hz), 27. 8 ppm.
HRMS (ESI) calc. for C18H16FNO4S (M+Na)+: 384.0676, found: 384.0679.
4-(((4-fluorophenyl)sulfonyl)methyl)-2,4-dimethylisoquinoline-1,3(2H,4H)-
dione (3v):[16] White solid (36.7 mg, 51%), m.p. 176.9-177.6 oC. 1H NMR (600
MHz, CDCl3) δ 8.31-8.29 (m, 1H), 7.51-7.49 (m, 2H), 7.44-7.42(m, 2H), 7.19-
7.17 (m, 1H), 7.04 (t, J = 8.5 Hz, 2H), 4.47 (d, J = 14.7 Hz, 1H), 3.90 (d, J =
14.7 Hz, 1H), 3.42 (s, 3H), 1.59 (s, 3H) ppm. 13C NMR (150 MHz, CDCl3) δ
174.3, 165.59 (d, J = 256.7 Hz), 163.7, 139.1, 136.4, 133.5, 130.5 (d, J = 9.6
Hz), 129.4, 128.2, 125.7, 124.9, 116.34 (d, J = 22.7 Hz), 65.0, 45.5, 31.5, 27.6
ppm.
2,4-dimethyl-4-(2,2,2-trifluoroethyl)isoquinoline-1,3(2H,4H)-dione (3ab):[16]
Colorless liquid (20.0 mg, 37%). 1H NMR (600 MHz, CDCl3) δ 8.30-8.28 (m,
1H), 7.66 (d, J = 0.9 Hz, 1H), 7.50-7.47 (m, 1H), 7.43 (d, J = 7.9 Hz, 1H), 3.41
(s, 3H), 3.40-3.32 (m, 1H), 2.84-2.77 (m, 1H), 1.66 (s, 3H) ppm. 13C NMR (150
MHz, CDCl3) δ 174.5, 163.7, 140.4, 133.8, 129.3, 128.7, 128.5, 128.0, 127.7,
125.6, 125.0 (q, J = 277.0 Hz), 124.3, 44.41 (q, J = 27.5 Hz), 43.6, 31.1, 27.4
ppm.
4-(((4-chlorophenyl)sulfonyl)methyl)-2,4-dimethylisoquinoline-1,3(2H,4H)-
dione (3w):[16] White solid (61.9 mg, 82%), m.p. 156.7-158.5 oC. 1H NMR (600
MHz, CDCl3) δ 8.29-8.29 (m, 1H), 7.44-7.40 (m, 4H), 7.33-7.32 (m, 2H), 7.16
(d, J = 7.5 Hz, 1H), 4.46 (d, J = 14.7 Hz, 1H), 3.89 (d, J = 14.7 Hz, 1H), 3.41 (s,
3H), 1.58 (s, 3H) ppm. 13C NMR (150 MHz, CDCl3) δ 174.2, 163.7, 140.3,
139.0, 138.7, 133.5, 129.4, 129.4, 129.1, 128.2, 125.7, 124.9, 64.9, 45.4, 31.5,
27.6 ppm.
N-(2-methyl-3-(phenylsulfonyl)propanoyl)benzamide (4): White solid (31.0
mg, 47%), m.p. 137.4-138.2 oC. 1H NMR (600 MHz, CDCl3) δ 8.92 (s, 1H),
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10.1002/ejoc.201801519
European Journal of Organic Chemistry
FULL PAPER
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7.92-7,87 (m, 4H), 7.66-7.61 (m, 2H), 7.55-7.50 (m, 4H), 4.23 (s, 1H), 3.97 (dd,
J = 14.3, 9.0 Hz, 1H), 3.13 (dd, J = 14.3, 3.3 Hz, 1H), 1.36 (d, J = 7.0 Hz, 3H)
ppm. 13C NMR (150 MHz, CDCl3) δ 176.1, 165.3, 139.3, 133.9, 133.4, 132.6,
129.3, 129.0, 128.2, 127.9, 58.7, 35.5, 18.1 ppm. HRMS (ESI) calc. for
C17H17NO4S (M+Na)+: 354.0770, found: 354.0773.
(2-(phenylsulfonyl)ethene-1,1-diyl)dibenzene (5):[23] White solid (67.0 mg,
35%), m.p. 114.8-115.9 oC. 1H NMR (600 MHz, CDCl3) δ 7.58 (d, J = 7.3 Hz,
2H), 7.48 (t, J = 7.4 Hz, 1H), 7.38-7.33 (m, 4H), 7.31-7.27 (m, 4H), 7.22-7.20
(m, 2H), 7.08-7.07 (m, 2H), 7.02 (s, 1H) ppm. 13C NMR (150 MHz, CDCl3) δ
155.2, 141.6, 139.2, 135.5, 132.8, 130.3, 129.8, 128.9, 128.8, 128.7, 128.6
128.2, 127.9, 127.7 ppm.
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Acknowledgments
This work was financially supported by the National Natural Science
Foundation of China (Nos 21472152 and 21672174) and the Basic and
Frontier Research Project of Chongqing (cstc2015jcyjBX0106).
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Keywords: photocatalysis • eosin Y • cycloaddition • radical
reaction • sodium sulfinate
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Entry for the Table of Contents
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Key Topic: Photochemistry
Kai-Li Zuo, Yan-Hong He* and Zhi
Guan*
Page No. – Page No.
Metal-free visible-light photocatalytic
tandem radical addition-cyclization
strategy for the synthesis of sulfonyl-
containing isoquinolinediones
A mild visible-light photocatalytic C-S/C-C bond forming radical tandem reaction for the synthesis of sulfonyl-containing
isoquinolinediones has been developed using sodium sulfinates as a sulfonyl radical source and eosin Y as an organic
photocatalyst without any additives.
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