A Four-Component Reaction for the Synthesis of β-Quinoline Allylic Sulfones under Iron Catalysis

Article abstract of DOI:10.1021/acs.joc.8b01486

An efficient strategy for the preparation of allylic sulfones has been developed. In this protocol, readily available 2-methylquinolines or 2-methylbenzothiazoles, sodium sulfinates, and dimethylacetamide (DMA) were successfully assembled under user-friendly iron catalysis, and DMA provided two carbons as a dual synthon. A broad range of functionalized heterocyclic allylic sulfones were accessed with a wide functional group tolerance.

Full text of DOI:10.1021/acs.joc.8b01486

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Article
A Four-Component Reaction for the Synthesis of #-
Quinoline Allylic Sulfones under Iron Catalysis
Fuhong Xiao, Chao Liu, Shanshan Yuan, Huawen Huang, and Guo-Jun Deng
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b01486 • Publication Date (Web): 03 Aug 2018
Downloaded from http://pubs.acs.org on August 3, 2018
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A Four-Component Reaction for the Synthesis of β-Quinoline Allylic
Sulfones under Iron Catalysis
Fuhong Xiao,* Chao Liu, Shanshan Yuan, Huawen Huang, GuoꢀJun Deng*
Key Laboratory for Green Organic Synthesis and Application of Hunan Province, Key Laboratory
of Environmentally Friendly Chemistry and Application of Ministry of Education, College of
Chemistry, Xiangtan University, Xiangtan 411105, China.
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Fax: (+86)ꢀ731ꢀ58292251
ABSTRACT: An efficient strategy for the preparation of allylic sulfones has been developed. In
this protocol, readily available 2ꢀmethylquinolines or 2ꢀmethylbenzothiazoles, sodium sulfinates
and dimethylacetamide (DMA) were successfully assembled under userꢀfriendly iron catalysis.
And DMA provided two carbons as a dual synthon. A broad range of functionalized heterocyclic
allylic sulfones were accessed with a wide functional group tolerance.
■ INTRODUCTION
Quinoline derivatives widely exist in natural products, bioactive pharmaceutical drugs, and
1
functional materials. Among them, 2ꢀalkenylquinoline regards as one of the typical molecular
2
skeletons possessing significant bioactivities. Moreover, quinoline compounds were also
used as significant and versatile structural skeletal frameworks in molecular synthesis. As a
result, direct quinoline functionalization has attracted considerable interest in organic
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transformations. Alternatively, 2ꢀmethylquinolines frequently serve as a versatile nucleophilic
coupling partner (via enamine intermediate), which undergoes nucleophilic addition reaction
3
4
5
6
to construct the new C−C, C−N, C−O bonds and among others. For example, Huang and
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coꢀworkers described an nucleophilic addition reaction between 2ꢀalkyl azaarenes and the
7
C=N double bonds of Nꢀsulfonyl aldimines. Very recently, significant progress has been
3
made on the C(sp )−H bond functionalization of 2ꢀalkyl azaarenes through oxidative cross
8
dehydrogenative coupling (CDC). Given the highly pharmaceutical and synthetic importance
of quinolines and other azaarenes in chemistry, the development of environmentally friendly
strategies for their direct functionalization is still highly desirable.
Multicomponent reactions (MCRs) have been established as a powerful methodology in
9
molecular synthesis to show overall considerable atomꢀ and stepꢀeconomy. Speciffically,
many concise multicomponent approaches have been developed to construct C−S bond via the
3
10
direct C(sp )−H bond functionalization. In 2017, Wen and coworkers disclosed the
chemoselective formation of allylic sulfones and allylic sulfides from methylketones with
DMSO as multiꢀfunctional synthons, in which three molecules of DMSO were incorperated
1
1
into the final products (Scheme 1a).
Recently, we reported on an ironꢀcatalyzed
threeꢀcomponent reaction with N,Nꢀdimethylacetamide (DMA) as the dual carbon source and
1
2
sodium sulfinates as the sulfone precursor to afford allylic sulfones (Scheme 1b). As our
continuing interest in C−H bond functionalization of methylquinolins including oxidative
1
3
sulfonylation (Scheme 1c), herein, we developed a simple and efficient threeꢀcomponent
fourꢀmolecular approach for the synthesis of allylic sulfones bearing quinoline and
benzothiazole motifs from readily available 2ꢀmethylheterocycles, sodium sulfinates, and
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DMA (Scheme 1d). In this protocol, earthꢀabundant, cheap and lowꢀtoxic iron(III) chloride
2 2
was used as the most effective catalyst and DMA provides two carbons (ꢀCH ꢀ and =CH ) as a
dual synthon. Most importantly, this work provides a viable and sustainable access to highly
functionalized quinolines and benzothiazoles.
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Scheme 1. C-S Bond Formation via C(sp )−H Bond Functionalization.
■
RESULTS AND DISCUSSION
Synthesis of β-Quinoline Allylic Sulfones. For the optimization of reaction conditions, we
chosen 2ꢀmethylquinoline (1a) and sodium benzenesulfinate (2a) as starting materials (Table
). To our pleasure, the corresponding product 3aa was obtained in 52% yield when the
reaction was carried out with FeCl (10 mol%) and K (3.5 equiv) in DMA at 110 °C for
1
3
2 2 8
S O
1
4 h, while other metal salts such as NiCl2 and CuCl did not give the product (entries 1−3).
2
Then, elevated or reduced reaction temperature could not enhance the transformation (entries
−5). We also tried to modify the amount of the oxidant, in which 3.5 equiv of K proved
4
2 2 8
S O
to be optimal (entries 6−8). To our delight, the reaction yield was significantly increased when
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a mixture of DMA/H O (v/v = 10:1) was used as the solvent (entry 9). With this coꢀsolvent
2
3 3 3 4 2 2 2
system, some other iron catalysts such as Fe(NO ) , Fe(acac) , Fe(SO ) •7H O and FeCl
•
4H
2
O provided lower yields (entries 10−13). The variation of the oxidant showed that
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K S O was superior to Na S O , oxone and K S O (entries 14−16). The addition of other
2
2
8
2
2
8
2
2
5
3 2
protic solvents such as alcohol and CH COOH showed that H O gave the best result (entries
1
7−18). Decreasing or increasing the amount of H
2
O did not enhance the reaction yields
(
entries 19−20). Moreover, the desired product was not observed when the reaction was
carried out in the absence of the oxidant or iron catalyst (entries 21−22). Finally, air
atmosphere found to be superior to oxygen and argon.
a
Table 1. Screening reaction Conditions
o
b
entry
catalyst
oxidant
solvent
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA:H
temperature ( C)
yield (%)
1
2
3
4
5
NiCl
2
K
K
2
2
S
2
2
O
8
8
8
8
8
8
8
8
8
110
110
110
100
120
110
110
110
110
0
CuCl
2
S
O
trace
52
24
36
42
35
43
90
FeCl3
K S O
2
2
2
2
2
2
2
2
2
2
FeCl
FeCl
FeCl
FeCl
3
3
3
3
K
K
K
K
S
S
S
S
O
O
O
O
c
6
d
7
e
8
FeCl3
K S O
2
2
9
FeCl
3
K
2
S
2
O
2
O = 10:1
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1
0
Fe(NO
3
)
3
K
K
2
2
S
2
2
O
8
8
8
8
DMA:H
DMA:H
2
2
O = 10:1
O = 10:1
110
110
110
110
110
110
110
110
110
110
110
110
110
110
110
21
29
5
11
Fe(acac)
3
S
O
1
2
FeSO ·7H O K S O
DMA:H O = 10:1
2
4
2
2
2
1
1
1
1
1
1
1
1
1
1
2
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2
2
2
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5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
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7
8
9
0
1
2
3
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9
0
1
2
3
4
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9
0
1
2
3
4
5
6
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8
9
0
13
FeCl
FeCl
FeCl
FeCl
2
3
3
3
·4H
2
O
K
2
S
2
O
DMA:H
DMA:H
DMA:H
DMA:H
2
2
2
2
O = 10:1
O = 10:1
O = 10:1
O = 10:1
84
66
24
8
1
1
1
1
4
5
6
7
Na
2
S
2
O
8
Oxone
K
2
S
2
O
5
8
8
8
8
FeCl3
K S O
DMA:EtOH = 10:1
DMA:AcOH = 10:1
54
45
85
77
0
2
2
2
2
2
2
2
2
18
FeCl
FeCl
FeCl
FeCl
ꢀ
3
3
3
3
K
K
K
ꢀ
S
S
S
O
O
O
1
9
DMA:H
DMA:H
DMA:H
2
2
2
O = 5:1
20
O = 20:1
O = 10:1
2
2
2
2
1
2
3
4
K S O
DMA:H O = 10:1
0
2
2
2
2
2
2
8
8
8
2
f
FeCl
FeCl
3
3
K
K
S
S
O
O
DMA:H
DMA:H
2
2
O = 10:1
O = 10:1
54
60
g
a
Conditions: 1a (0.2 mmol), 2a (0.5 mmol), catalyst (10 mol %), oxidant (3.5 equiv), DMA (2.0 mL), 110
o
b
c
d
e
C, 14 h, under air atmosphere. Isolated yield based on 1a.
2 2 8 2 2 8
K S O (3.0 equiv). K S O (2.5 equiv). 2a
f
g
(
1.5 equiv). O atmosphere. Ar atmosphere.
2
Besides the established DMA as the one carbon synthon, we screened other small molecular
compounds which can provide carbon sources for the present fourꢀcomponent reaction
(
Scheme 2). When N,Nꢀdimethylpropionamide (DMPA) was used, moderate yield of 3aa was
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observed, while other candidates of carbon sources such as N,Nꢀdimethylformamide (DMF),
N,Nꢀdiethylformamide (DEF), dimethyl sulfoxide (DMSO), Nꢀmethylpyrrolidone (NMP) and
tetramethylethylenediamine (TMEDA) did not afford the desired products. These results show
the unique feature of DMA in the reaction system.
0
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a
Scheme 2. One Carbon Synthons.
a
o
3 2 2 8
Conditions: 1a (0.2 mmol), 2a (0.5 mmol), FeCl (10 mol %), K S O (3.5 equiv), ‘C1’ (2.0 mL), 110 C,
1
4 h, air atmosphere.
We also investigated other frequently employed sulfone sources for the formation of
quinolinyl allylic sulfones (Scheme 3). Unexpectedly, the desired reaction did not occur with
sulfonohydrazide and sulfonyl chloride, while modest yield of 3aa was obtained when we use
sulfonothioate instead of sodium benzenesulfinate. Notably, allylicthioether 3a was formed
when 4ꢀmethylbenzenethiol was subjected to the standard reaction conditions, while
1,2ꢀdiꢀpꢀtolyldisulfane could not afford the allylicthioether product.
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Scheme 3. Other Sulfone Sources.
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
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3
3
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0
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0
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0
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9
0
With the optimized reaction conditions established, a variety of sodium sulfinates were
examined for the multiꢀcomponent transformation (Scheme 4). Generally, a range of
paraꢀsubstituted phenyl sodium sulfinates reacted smoothly with 1a to provide βꢀquinoline
allylic sulfones (3ab−3ai) in moderate to high yields. A variety of functional groups on the
benzene ring such as alkyl (2b−2c), methoxy (2d), nitro (2e), halo (2f−2h) and
trifluoromethyl (2i) were all well tolerated. Notably, carbon−halogen bond cleavage of the
substrates was not observed in the present system. The reaction yield decreased dramatically
when sodium 4ꢀnitrobenzenesulfinate (2e) was used as the substrate, probably because of the
highly electronꢀwithdrawing effect. Naphthylsulfinic acid sodium salts furnished the
corresponding product 3aj and 3ak in 71% and 69% yield, respectively. To our delight, in
addition to aromatic sodium sulfinates, relatively lower reactive cyclopropanesulfinate (2l)
could also react with 2ꢀmethylquinoline, providing the desired products 3al in 41% yield,
while other aliphatic sodium sulfinates including sodium trifluoromethanesulfinate did not
afford the corresponding products.
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1
1
1
1
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1
1
1
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2
2
2
2
2
2
3
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4
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4
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6
Scheme 4. Substrate Scope with Respect to Sodium Sulfinates.
0
1
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8
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0
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3
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5
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7
8
9
0
3 2 2 8
Reaction conditions: 1a (0.2 mmol), 2 (0.5 mmol), FeCl (10 mol %), K S O (3.5 equiv), DMA (2.0 mL),
o
H O (0.2 mL), 14 h, 110 C, under air. Isolated yield based on 1a.
2
To further explore the generality and limitations of the multiꢀcomponent sulfonylation,
other 2ꢀmethylazaarenes were treated with sodium benzenesulfinate 2a (Scheme 5). Moderate
yields were obtained for 2ꢀmethylquinolines with electronꢀdonating groups such as methyl
(
1b), alkoxy (1c, 1l and 1m) and phenyl (1d) were presented at the C6 or C8ꢀposition. The
quinolins bearing electronꢀwithdrawing acetyl (1e), nitro (1f) and trifluoromethyl (1g) groups
afforded the desired products in slightly lower yields. Notably, halogen substituted substrates
reacted well under the optimized reaction conditions (3ha−3ka). The bulky
3ꢀmethylbenzo[f]quinoline (1n) also showed excellent reactivity. Apart from
2
ꢀmethylquinolines, other methyl substituted quinolines such as 1ꢀmethylisoquinoline (1o),
4ꢀmethylquinoline (1p) and 2ꢀmethylquinoxaline (1q) could also be applied in this reaction
system to provide the corresponding products in moderate to good yields. However, very low
yield was obtained when using 2ꢀmethylpyridine (1r) as the substrate. Unexpectedly,
2
ꢀmethylꢀ1,4ꢀnaphthyridine bearing a 3ꢀphenyl group could not convert to the corresponding
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product, and instead sulfonylmethylation product 3sa was obtained.
Scheme 5. Substrate Scope with Respect to Methyl aza-Heterocycles.
X
X
FeCl3, K2S2O8
R
R
PhSO2Na
Ph
+
N
S
DMA:H2O = 10:1
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
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0
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2
3
4
5
6
7
8
9
0
O O
3
1
2a
R = 6-CH3, 3ba, 61%
R = 6-Ph, 3da, 45%
R = 6-NO2, 3fa, 28%
R = 6-Cl, 3ha, 73%
R = 6-I, 3ja, 55%
R = 6-OCH3, 3ca, 75%
R = 6-CO2CH3, 3ea, 24%
R = 6-CF3, 3ga, 47%
R = 6-Br, 3ia, 76%
R
Ph
N
S
O
O
R = 7-Cl, 3ka, 54%
R = 8-OCH3, 3la, 71% R = 8-OEt, 3ma, 79%
Ph
S
N
O
O
Ph
S
Ph
N
S
O
O
N
O
O
3
na, 76%
3oa, 58%
3pa, 81%
N
N
Ph
Ph
Ph
S
O
O
N
S
N
N
S
O
O
O
Ph
O
3qa, 47%
3ra, 17%
3sa, 50%
Reaction conditions: 1 (0.2 mmol), 2a (0.5 mmol), FeCl
3
(10 mol %), K
2
S
2
O
8
(3.5 equiv), DMA (2.0 mL),
o
H O (0.2 mL), 14 h, 110 C, under air. Isolated yield based on 1.
2
Benzothiazole and its derivatives are widespread in pharmaceuticals, functional materials
1
4
and biological systems. To our delight, 2ꢀmethylbenzothiazoles could also convert to the
corresponding products with sodium sulfinates and DMA under the optimized reaction
conditions (Scheme 6). The reaction of 2ꢀmethylbenzothiazole (4a) and sodium
benzenesulfinate
(2a)
generated
the
corresponding
2
ꢀ[3ꢀ(phenylsulfonyl)propꢀ1ꢀenꢀ2ꢀyl]benzo[d]thiazole 5aa in 68% isolated yield. The haloꢀ
and methoxylꢀ2ꢀmethylbenzothiazoles (5ba−5ea) were also smoothly reacted sodium
benzenesulfinate (2a), affording the target products in moderate yields. The desired product
5
fa was obtained in 50% yield when 2ꢀmethylnaphtho[2,1ꢀd]thiazole (4f) was used as the
substrate. Furthermore, The reactions with sodium benzenesulfinates bearing
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2
2
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2
2
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5
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5
5
5
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electronꢀdonating groups substituents at the paraꢀposition proceeded smoothly to give the
desired
products
(5ab−5ad).
Lower
yields
were
obtained
when
sodium
4
ꢀnitrobenzenesulfinate (2e) and sodium 4ꢀ(trifluoromethyl)benzenesulfinate (2i) were used as
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
the substrates, probably because of the highly electronꢀwithdrawing effect. Under the
optimized conditions, halogen substituents were all well tolerated and afforded the desired
products (5af−5ah) in good yields.
Scheme 6. Substrate Scope with Respect to 2-Methylbenzothiazoles.
3 2 2 8
Reaction conditions: 4 (0.2 mmol), 2 (0.5 mmol), FeCl (10 mol %), K S O (3.5 equiv), DMA (2.0 mL),
o
H O (0.2 mL), 14 h, 110 C, under air. Isolated yield based on 4.
2
The reaction convergence was reflected by the substrate limitations to above methyl
azaꢀheterocycles. range of other methylheterocycles such as 8ꢀmethylquinoline,
ꢀmethylbenzo[d]imidazole, 2ꢀmethylbenzo[d]oxazole, 2ꢀmethylpyrazine, and so forth, failed
A
2
to react with sodium sulfinates and DMA under the standard reaction conditions (Scheme 7a).
When 2ꢀmethylindole was used, the sulfonylmethylation product 7 at C3ꢀposition of indole
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was obtained in 35% yield (Scheme 7b). When the intramolecular competition reaction of
1ꢀ(3ꢀmethylquinoxalinꢀ2ꢀyl)ethanone 8 with 2a was carried out under the standard reaction
conditions, only the benzyl C−H sulfonylmethylation product 9 was obtained in 21% yield,
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
2
while the αꢀmethyl group to carbonyl did not participated (Scheme 7c). Unexpectedly, the
disulfonylmethylation product 11 was obtained when using 2,3ꢀdimethylquinoxaline 10 as the
substrate. To our delight, the reaction yield was significantly increased to 81% when 7.0 equiv.
sodium benzenesulfinate (2a) was used. (Scheme 7d).
Scheme 7. Other Methylheterocycles.
a) failed methylheterocycles:
N
N
O
N
H
N
N
H
N
N
N
O
N
S
N
H
b) 2-methylindole:
O
S
O
FeCl3, K2S2O8
DMA:H2O = 10:1
N
+ PhSO2Na
H
N
H
6
7, 35%
2a
c) intramolecular competition reaction:
O
O
N
N
N
FeCl3, K2S2O8
DMA:H2O = 10:1
+
PhSO2Na
O
N
S
O
Ph
8
2a
9, 21%
d) disulfonylmethylation reaction:
N
O
S
O
FeCl3, K2S2O8
N
Ph
Ph
+
PhSO2Na
DMA:H2O = 10:1
N
N
S
O
O
1
0
2a
11, 30%
2
a (7.0 equiv), 81%
The 2ꢀ(3ꢀ(phenylsulfonyl)propꢀ1ꢀenꢀ2ꢀyl)quinoline product 3aa was obtained in 72% yield
in a gramꢀscale reaction. We further evaluated the ozonolysis reaction of 3aa. When 3aa was
o
dissolved in CH
2
Cl
2
and cooled to ꢀ78 C, O
3
gas was bubbled into the mixture for 20 min.
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9
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2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
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4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Then, The O was removed by bubbled in N (2 min), Me S was added dropwise. The mixture
3
2
2
o
was stirred at ꢀ78 C for about 10 min, then allowed to stir at r.t. 1 h. The product
2
ꢀ(phenylsulfonyl)ꢀ1ꢀ(quinolinꢀ2ꢀyl)ethanone (12) was obtained in 49% yield (Scheme 8).
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
Scheme 8. Ozonolysis Reaction.
o
1
) O , DCM, -78 C
3
Ph
Ph
N
S
o
N
S
2) Me S, -78 C to r.t.
2
O
O
O O
O
3
(
aa, 72%, 1.3 g
6 mmol scale)
12, 51%
Mechanistically, the model reaction was significantly inhibited by the addition of
2,2,6,6ꢀtetramethylpiperidinꢀ1ꢀoxyl (TEMPO) or butylated hydroxytoluene (BHT) as a radical
scavenger under the standard conditions (Scheme 9a). Hence, we speculate that the present
multiꢀcomponent reaction proceed through a radical process. Moreover, we employed
2
ꢀvinylquinoline as the starting material under the standard conditions, in which the
corresponding product 3aa was obtained in 30% yield (Scheme 9b).
Scheme 9. Control Experiments.
1
2,15
According to our previous work and related references,
a proposed mechanism is
proposed in Figure 1. Initially, DMA was gradually oxidized to generate the iminium species
B in the [Fe]/K
2
S
2
O
8
ꢀbased system. 2ꢀmethylquinoline 1a can be isomerized to C by the
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Brønsted acidꢀpromoted, and treatment of the iminium species B with intermediate C affords
the intermediate product 2ꢀvinylquinoline 1a’. Then sodium benzenesulfinate 2a with
2
ꢀvinylquinoline 1a’ undergoes Michaelꢀtype addition reaction to afford the anion
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
intermediate D. Finally D and B undergoes nucleophilic addition reaction, followed by
elimination methylamide to give the final product 3aa.
Figure 1. Possible reaction mechanism.
■
CONCLUSIONS
In summary, we have developed an ironꢀcatalyzed oxidative benzylic C−H functionalization
of 2ꢀmethylquinolines and 2ꢀmethylbenzothiazoles with sodium sulfinates and DMA under mild
conditions. In this system, two carbonꢀcarbon bonds and one carbonꢀsulfur bond were formed with
high chemoꢀselectivity. Moreover, the broad functional group tolerance makes this method
attractive for the synthesis of highly functionalized quinoline and benzothiazole derivatives.
■
EXPERIMENTAL SECTION
General Methods. All reactions were carried out under an atmosphere of air. Column
1
13
chromatography was performed using silica gel 48ꢀ75 ꢁm. H NMR and C NMR spectra were
recorded on BrukerꢀAV (400 and 100 MHz, respectively) instrument internally referenced to
tetramethylsilane (TMS) or chloroform signals. Mass spectra were measured on Agilent 5975
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2
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2
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3
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3
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4
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5
5
5
5
5
5
6
GCꢀMS instrument (EI). HRMS was conducted using electrospraying ionization (ESI) and was
performed on a Thermo Scientific LTQ Orbitrap XL. The structures of known compounds were
1
13
further corroborated by comparing their H NMR, C NMR data and MS data with those of
literature. Most reagents were obtained from commercial suppliers and used without further
purification.
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 Procedure for the Synthesis of 3 or 5. A 10 mL ovenꢀdried reaction vessel was
2 2 8 3
charged with K S O (189.2 mg, 0.7 mmol), FeCl (4.0 mg, 0.02 mmol), 2ꢀmethylquinoline (1a,
2
27.0 ꢁL, 0.2 mmol), sodium benzenesulfinate (2a, 82.0 mg, 0.5 mmol), DMA (2.0 mL) and H O
o
(
0.2 mL) under air. The sealed reaction vessel was stirred at 110 C for 14 h. After cooling to
room temperature, the reaction was diluted with ethyl acetate (3.0 mL) and washed with saturated
sodium chloride solution. The organic layer was separated, and the aqueous layer was extracted
with ethyl acetate for three times. The combined organic layer was dried over magnesium sulfate
and the volatiles were removed under reduced pressure. The residue was purified by column
chromatography on silica gel (petroleum ether/ethyl acetate = 4:1) to yield the desired product 3aa
o
as white solid (55.6 mg, 90% yield), mp = 92ꢀ95 C.
2ꢀ[3ꢀ(Phenylsulfonyl)propꢀ1ꢀenꢀ2ꢀyl]quinoline (3aa). White solid (55.6 mg, 90% yield), mp = 92ꢀ95
o
1
C. H NMR (400 MHz, CDCl
3
) δ 7.99 (d, J = 8.6 Hz, 1H), 7.80ꢀ7.75 (m, 3H), 7.70 (d, J = 8.1 Hz, 1H),
7.65ꢀ7.62 (m, 1H), 7.57 (d, J = 8.6 Hz, 1H), 7.49ꢀ7.45 (m, 1H), 7.23ꢀ7.17 (m, 3H), 6.18 (s, 1H), 5.88 (s,
1
3
1
3
H), 4.87 (s, 2H). C NMR (100 MHz, CDCl ) δ 154.6, 146.7, 138.9, 137.1, 136.3, 132.9, 129.4, 128.5,
+
+
128.4, 127.2, 126.9, 126.6, 124.1, 117.6, 58.9. HRMS (ESI) calcd. for: C18
found 310.0899.
2
H15NO S (M+H) 310.0896,
o
1
2ꢀ(3ꢀTosylpropꢀ1ꢀenꢀ2ꢀyl)quinoline (3ab). White solid (59.5 mg, 92% yield), mp = 149ꢀ152 C. H
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NMR (400 MHz, CDCl
3
) δ 8.00 (d, J = 8.6 Hz, 1H), 7.77 (d, J = 8.4 Hz, 1H), 7.71 (d, J = 8.1 Hz, 1H),
7.65ꢀ7.57 (t, 4H), 7.49ꢀ7.45 (m, 1H), 6.93 (d, J = 8.0 Hz, 2H), 6.16 (s, 1H), 5.86 (s, 1H), 4.83 (s, 2H),
13
2
.06 (s, 3H). C NMR (100 MHz, CDCl ) δ 154.7, 146.8, 144.0, 137.4, 136.2, 136.0, 129.5, 129.3,
3
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
+
2
129.0, 128.5, 127.1, 126.9, 126.7, 124.1, 117.9, 59.2, 21.2. HRMS (ESI) calcd. for: C19H18NO S
+
(
M+H) 324.1053, found 324.1055.
2ꢀ{3ꢀ[(4ꢀtertꢀButylphenyl)sulfonyl]propꢀ1ꢀenꢀ2ꢀyl}quinoline (3ac). White solid. (38.0 mg, 52% yield),
1
mp = 157ꢀ160 °C. H NMR (400 MHz, CDCl
3
) δ 7.93 (d, J = 8.6 Hz, 1H), 7.76 (d, J = 8.4 Hz, 1H),
7.67ꢀ7.59 (m, 4H), 7.53 (d, J = 8.7 Hz, 1H), 7.44 (t, J = 7.5 Hz, 1H), 7.08 (d, J = 8.5 Hz, 2H), 6.19 (s,
1
3
3
1H), 5.94 (s, 1H), 4.85 (s, 2H), 0.97 (s, 9H). C NMR (100 MHz, CDCl ) δ 156.7, 154.5, 146.7, 137.3,
136.19, 135.6, 129.4, 128.5, 127.1, 126.8, 126.6, 125.2, 124.2, 117.6, 58.9, 34.7, 30.6. HRMS (ESI)
+
+
2
calcd. for: C22H24NO S (M+H) 366.1522, found 366.1524.
2ꢀ{3ꢀ[(4ꢀMethoxyphenyl)sulfonyl]propꢀ1ꢀenꢀ2ꢀyl}quinoline (3ad). White solid (40.7 mg, 60% yield),
1
mp = 151ꢀ154 °C. H NMR (400 MHz, CDCl ) δ 8.00 (d, J = 8.6 Hz, 1H), 7.81 (d, J = 7.5 Hz, 1H),
3
7.72 (d, J = 8.1 Hz, 1H), 7.65ꢀ7.63 (m, 3H), 7.57 (d, J = 8.7 Hz, 1H), 7.48 (t, J = 7.5 Hz, 1H), 6.57 (d, J
1
3
=
8.7 Hz, 2H), 6.16 (s, 1H), 5.87 (s, 1H), 4.83 (s, 2H), 3.54 (d, J = 0.9 Hz, 3H). C NMR (100 MHz,
3
CDCl ) δ 163.1, 154.8, 146.7, 137.5, 136.3, 130.7, 130.4, 129.4, 127.2, 126.9, 126.6, 124.1, 117.9,
+
+
3
113.6, 59.4, 55.3. HRMS (ESI) calcd. for: C19H18NO S (M+H) 340.1002, found 340.1007.
2ꢀ{3ꢀ[(4ꢀNitrophenyl)sulfonyl]propꢀ1ꢀenꢀ2ꢀyl}quinoline (3ae). Yellow solid (18.4 mg, 26% yield), mp
1
=
200ꢀ203 °C. H NMR (400 MHz, CDCl
3
) δ 8.01 (d, J = 8.6 Hz, 1H), 7.92ꢀ7.87 (m, 4H), 7.69 (d, J =
13
8.1 Hz, 1H), 7.62ꢀ7.60 (m, 3H), 7.48ꢀ7.4 (m, 1H), 6.27 (s, 1H), 6.01 (s, 1H), 4.92 (s, 2H). C NMR
3
(100 MHz, CDCl ) δ 153.8, 149.8, 146.4, 144.7, 136.6, 130.0, 129.8, 128.9, 127.4, 127.2, 126.9, 124.8,
+
+
15 2 4
123.3, 117.5, 59.4. HRMS (ESI) calcd. for: C18H N O S (M+H) 355.0747, found 355.0751.
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2
2
2
2
2
2
2
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3
3
3
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3
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3
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5
5
6
2
ꢀ{3ꢀ[(4ꢀFluorophenyl)sulfonyl]propꢀ1ꢀenꢀ2ꢀyl}quinoline (3af). White solid (48.5 mg, 74% yield), mp
1
= 222ꢀ225 °C. H NMR (400 MHz, CDCl
3
) δ 8.01 (d, J = 8.6 Hz, 1H), 7.79ꢀ7.73 (m, 4H), 7.67ꢀ7.62 (t,
1
H), 7.58 (d, J = 8.7 Hz, 1H), 7.51ꢀ7.46 (m, 1H), 6.87ꢀ6.77 (m, 2H), 6.20 (s, 1H), 5.91 (s, 1H), 4.86 (s,
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
3
2H). C NMR (100 MHz, CDCl ) δ 165.3 (d, J = 254.16 Hz), 154.3, 146.7, 137.1, 136.4, 136.0, 135.0,
1
31.4 (d, J = 9.52 Hz), 129.4 (d, J = 37.57 Hz), 127.2, 126.9, 126.8, 124.2, 117.5, 115.5 (d, J = 22.72
+
+
2
Hz), 59.0. HRMS (ESI) calcd. for: C18H15FNO S (M+H) 328.0802, found 328.0804.
2
ꢀ{3ꢀ[(4ꢀChlorophenyl)sulfonyl]propꢀ1ꢀenꢀ2ꢀyl}quinoline (3ag). White solid. (65.3 mg, 95% yield),
1
mp = 251ꢀ254 °C. H NMR (400 MHz, CDCl ) δ 8.03 (d, J = 8.6 Hz, 1H), 7.74 (d, J = 7.5 Hz, 2H),
3
1 2
7.70ꢀ7.65 (m, 3H), 7.59 (d, J = 8.7 Hz, 1H), 7.51 (dd, J = 11.4, J = 4.5 Hz, 1H), 7.11 (d, J = 8.6 Hz,
13
2
3
H), 6.21 (s, 1H), 5.92 (s, 1H), 4.87 (s, 2H). C NMR (100 MHz, CDCl ) δ 154.3, 146.6, 139.8, 137.44,
137.42, 137.0, 136.5, 130.0, 129.7, 129.1, 128.6, 127.3, 126.9, 124.4, 117.6, 59.2. HRMS (ESI) calcd.
+
+
2
for: C18H15ClNO S (M+H) 344.0507, found 344.0508.
2ꢀ{3ꢀ[(4ꢀBromophenyl)sulfonyl]propꢀ1ꢀenꢀ2ꢀyl}quinoline (3ah). White solid. (73.0 mg, 94% yield),
1
mp = 234ꢀ237 °C. H NMR (400 MHz, CDCl
3
) δ 8.02 (d, J = 8.6 Hz, 1H), 7.73 (d, J = 8.7 Hz, 2H),
7
4
1
.69ꢀ7.67 (m, 1H), 7.58ꢀ7.55 (m, 3H), 7.51ꢀ7.47 (m, 1H), 7.27ꢀ7.25 (m, 2H), 6.20 (s, 1H), 5.91 (s, 1H),
13
3
.85 (s, 2H). C NMR (100 MHz, CDCl ) δ 154.3, 146.6, 138.0, 137.1, 136.5, 131.6, 130.0, 129.7,
+
+
2
29.2, 128.4, 127.3, 126.9, 124.4, 117.6, 59.3. HRMS (ESI) calcd. for: C18H15BrNO S (M+H)
388.0001, found 388.0004.
2
ꢀ{3ꢀ[(4ꢀ(Trifluoromethyl)phenyl)sulfonyl]propꢀ1ꢀenꢀ2ꢀyl}quinoline (3ai). White solid. (47.5 mg, 63%
1
yield), mp = 249ꢀ251 °C. H NMR (400 MHz, CDCl
3
) δ 7.97 (d, J = 8.7 Hz, 1H), 7.83 (d, J = 8.1 Hz,
2
H), 7.68 (d, J = 8.1 Hz, 1H), 7.64ꢀ7.58 (m, 2H), 7.55 (d, J = 8.7 Hz, 1H), 7.49ꢀ7.45 (m, 1H), 7.34 (d, J
1
3
3
= 8.2 Hz, 2H), 6.22 (s, 1H), 5.96 (s, 1H), 4.89 (s, 2H). C NMR (100 MHz, CDCl ) δ 154.0, 146.4,
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42.4, 136.9, 136.4, 134.4 (q, J = 3.69 Hz), 129.7, 129.2, 128.9, 127.2, 126.9, 126.8, 125.3 (q, J =
+
15 3 2
32.79 Hz), 124.5, 122.8 (q, J = 271.43 Hz), 117.4, 59.2. HRMS (ESI) calcd. for: C19H F NO S
+
(M+H) 378.0770, found 378.0773.
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
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5
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0
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7
8
9
0
1
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4
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7
8
9
0
1
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4
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7
8
9
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0
2ꢀ[3ꢀ(Naphthalenꢀ1ꢀylsulfonyl)propꢀ1ꢀenꢀ2ꢀyl]quinoline (3aj). White solid. (51.0 mg, 71% yield), mp
1
=
203ꢀ206 °C. H NMR (400 MHz, CDCl
3
) δ 8.95 (d, J = 8.7 Hz, 1H), 8.04 (dd, J
1
= 7.3, J
2
= 1.2 Hz,
1
H), 7.87 (d, J = 8.6 Hz, 1H), 7.73ꢀ7.60 (m, 4H), 7.50ꢀ7.38 (m, 4H), 7.25ꢀ7.21 (m, 2H), 6.12 (s, 1H),
1
3
5
3
.88 (s, 1H), 5.05 (s, 2H). C NMR (100 MHz, CDCl ) δ 154.5, 146.5, 137.2, 136.0, 134.6, 134.3,
1
33.8, 130.8, 129.2, 129.1, 128.7, 128.3, 127.0, 126.7, 126.6, 126.4, 124.8 124.1, 123.7, 117.7, 58.7.
+
+
2
HRMS (ESI) calcd. for: C22H18NO S (M+H) 360.1053, found 360.1057.
2ꢀ[3ꢀ(Naphthalenꢀ2ꢀylsulfonyl)propꢀ1ꢀenꢀ2ꢀyl]quinoline (3ak). White solid. (49.6 mg, 69% yield), mp
1
= 200ꢀ203 °C. H NMR (400 MHz, CDCl
3
) δ 8.27 (s, 1H), 7.84 (s, 1H), 7.84 (m, 1H), 7.75ꢀ7.72 (m,
13
2H), 7.60ꢀ7.43 (m, 7H), 7.39ꢀ7.37(m, 1H), 6.16 (s, 1H), 5.90 (s, 1H), 4.95 (s, 2H). C NMR (100 MHz,
CDCl ) δ 154.6, 146.5, 137.4, 136.1, 135.8, 134.8, 131.6, 130.3, 129.2, 129.1, 128.9, 128.7, 128.5,
3
+
1
2
27.5, 127.1, 127.0, 126.7, 126.4, 124.1, 123.2, 117.7, 59.4.HRMS (ESI) calcd. for: C22H18NO S
+
(M+H) 360.1053, found 360.1054.
2
ꢀ[3ꢀ(Cyclopropylsulfonyl)propꢀ1ꢀenꢀ2ꢀyl]quinoline (3al). White solid (22.4 mg, 41% yield). mp =
1
1
31–134 °C. H NMR (400 MHz, CDCl
3
) δ 8.17 (d, J = 8.7 Hz, 1H), 8.05 (d, J = 8.4 Hz, 1H), 7.82 (d, J
= 8.7 Hz, 2H), 7.74ꢀ7.70 (m, 1H), 7.57ꢀ7.53 (m, 1H), 6.31 (s, 1H), 6.04 (s, 1H), 4.79 (s, 2H), 2.31ꢀ2.24
13
3
(m, 1H), 1.16ꢀ1.11 (m, 2H), 0.67ꢀ0.63 (m, 2H). C NMR (100 MHz, CDCl ) δ 155.1, 147.1, 137.1,
136.7, 129.9, 129.4, 127.5, 127.3, 126.9, 124.3, 117.7, 56.7, 29.9, 4.9. HRMS (ESI) calcd. for:
+
+
15 2
C H16NO S (M+H) 274.0896, found 274.0898.
6ꢀMethylꢀ2ꢀ[3ꢀ(phenylsulfonyl)propꢀ1ꢀenꢀ2ꢀyl]quinoline (3ba). White solid (39.5 mg, 61% yield), mp
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2
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2
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3
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3
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5
5
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5
5
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5
5
5
5
6
1
=
3
153ꢀ156 °C. H NMR (400 MHz, CDCl , ppm) δ 7.89 (d, J = 8.6 Hz, 1H), 7.77ꢀ7.75 (m, 2H), 7.67 (d,
J = 8.5 Hz, 1H), 7.53 (d, J = 8.6 Hz, 1H), 7.46ꢀ7.44 (m, 2H), 7.26ꢀ7.17 (m, 3H), 6.14 (s, 1H), 5.85 (s,
13
1
H), 4.85 (s, 2H), 2.50 (s, 3H). C NMR (100 MHz, CDCl , ppm) δ 153.8, 145.3, 138.9, 137.2, 136.6,
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
135.6, 132.9, 131.7, 129.1, 128.5, 128.3, 127.0, 126.1, 123.6, 117.6, 58.9, 21.6. HRMS (ESI) calcd. for:
+
+
19 2
C H18NO S (M+H) 324.1053, found 324.1057.
6
ꢀMethoxyꢀ2ꢀ[3ꢀ(phenylsulfonyl)propꢀ1ꢀenꢀ2ꢀyl]quinolone (3ca). White solid (50.9 mg, 75% yield),
1
mp = 153ꢀ157 °C. H NMR (400 MHz, CDCl
3
) δ 7.87 (d, J = 8.6 Hz, 1H), 7.77ꢀ7.74 (m, 2H), 7.66 (d, J
=
9.1 Hz, 1H), 7.53 (d, J = 8.7 Hz, 1H), 7.28ꢀ7.17 (m, 4H), 6.96 (d, J = 2.8 Hz, 1H), 6.12 (s, 1H), 5.81
1
3
3
(s, 1H), 4.84 (s, 2H), 3.90 (s, 3H). C NMR (100 MHz, CDCl ) δ 157.9, 152.2, 142.7, 138.9, 137.0,
1
35.0, 132.9, 130.8, 128.5, 128.3, 127.9, 123.0, 122.0, 117.9, 104.8, 58.9, 55.5. HRMS (ESI) calcd. for:
+
+
C
19 3
H18NO S (M+H) 340.1002, found 340.1003.
6
ꢀPhenylꢀ2ꢀ[3ꢀ(phenylsulfonyl)propꢀ1ꢀenꢀ2ꢀyl]quinolone (3da). White solid (34.7 mg, 45% yield), mp
1
= 157ꢀ160 °C. H NMR (400 MHz, CDCl3) δ 8.03 (d, J = 8.6 Hz, 1H), 7.91ꢀ7.86 (m, 3H), 7.80ꢀ7.78
(
m, 2H), 7.72ꢀ7.70 (m, 2H), 7.60 (d, J = 8.7 Hz, 1H), 7.50 (t, J = 7.6 Hz, 2H), 7.42 (dd, J = 4.8, 3.7 Hz,
1
3
1
1
1
3
H), 7.26ꢀ7.22 (m, 3H), 6.19 (s, 1H), 5.88 (s, 1H), 4.88 (s, 2H). C NMR (100 MHz, CDCl ) δ 154.6,
46.1, 140.1, 139.3, 138.9, 137.1, 136.5, 133.0, 129.8, 129.1, 129.0, 128.6, 128.4, 127.8, 127.3, 127.1,
+
+
2
24.9, 124.1, 118.1, 58.9. HRMS (ESI) calcd. for: C24H20NO S (M+H) 386.1209, found 386.1212.
2ꢀ[3ꢀ(Phenylsulfonyl)propꢀ1ꢀenꢀ2ꢀyl]quinolineꢀ6ꢀcarboxylate (3ea). Yellow solid (17.6 mg, 24%
1
yield), mp = 173ꢀ176 °C. H NMR (400 MHz, CDCl3) δ 8.49ꢀ8.48 (m, 1H), 8.24ꢀ8.21 (m, 1H), 8.12 (d,
J = 8.6 Hz, 1H), 7.87 (d, J = 8.7 Hz, 1H), 7.78ꢀ7.76 (m, 2H), 7.67 (d, J = 8.7 Hz, 1H), 7.26ꢀ7.20 (m,
13
3
H), 6.26 (s, 1H), 5.96 (s, 1H), 4.87 (s, 2H), 4.00 (s, 3H). C NMR (100 MHz, CDCl3) δ 166.6, 156.8,
148.7, 139.0, 137.6, 137.0, 133.1, 130.3, 129.7, 129.1, 128.6, 128.5, 128.1, 126.1, 125.5, 118.5, 58.9,
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8
9
+
+
5
4
2.5. HRMS (ESI) calcd. for: C20H18NO S (M+H) 368.0951, found 368.0954.
6ꢀNitroꢀ2ꢀ[3ꢀ(phenylsulfonyl)propꢀ1ꢀenꢀ2ꢀyl]quinolone (3fa). Yellow solid (19.8 mg, 28% yield), mp
1
=
174ꢀ177 °C. H NMR (400 MHz, CDCl3) δ 8.70 (d, J = 2.5 Hz, 1H), 8.42ꢀ8.40 (m, 1H), 8.22 (d, J =
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
8.7 Hz, 1H), 7.95 (d, J = 9.2 Hz, 1H), 7.87ꢀ7.66 (m, 3H), 7.33ꢀ7.23 (m, 3H), 6.32 (s, 1H), 6.00 (s, 1H),
13
4
1
3
2
.85 (s, 2H). C NMR (100 MHz, CDCl
3
) δ 158.1, 148.9, 145.5, 138.9, 138.1, 136.6, 133.3, 131.0,
+
+
28.59, 128.55, 126.7, 125.7, 124.0, 123.1, 119.6, 58.7. HRMS (ESI) calcd. for: C18
55.0747, found 355.0749.
15 2 4
H N O S (M+H)
ꢀ[3ꢀ(Phenylsulfonyl)propꢀ1ꢀenꢀ2ꢀyl]ꢀ6ꢀ(trifluoromethyl)quinoline (3ga). White solid (35.5 mg, 47%
1
yield), mp = 135ꢀ138 °C. H NMR (400 MHz, CDCl
3
) δ 8.10 (d, J = 8.7 Hz, 1H), 8.03 (s, 1H), 7.92 (d,
J = 8.8 Hz, 1H), 7.82ꢀ7.77 (m, J = 8.3, 6.2, 1.8 Hz, 3H), 7.71 (d, J = 8.7 Hz, 1H), 7.31ꢀ7.22 (m, 3H),
1
3
3
6.26 (s, 1H), 5.95 (s, 1H), 4.85 (s, 2H). C NMR (100 MHz, CDCl ) δ 156.8 147.8, 138.9 137.1 136.8,
1
33.1, 130.6, 129.1, 128.2, 128.53, 128.49, 125.94 (q, J = 169.58 Hz), 125.90, 125.5, 125.1 (q, J = 2.78
+
+
Hz), 118.9, 58.8. HRMS (ESI) calcd. for: C H F NO S (M+H) 378.0770, found 378.0772.
1
9
15
3
2
6
ꢀChloroꢀ2ꢀ[3ꢀ(phenylsulfonyl)propꢀ1ꢀenꢀ2ꢀyl]quinoline (3ha). White solid (50.3 mg, 73% yield), mp
1
=
91ꢀ94 °C. H NMR (400 MHz, CDCl
3
) δ 7.92 (d, J = 8.7 Hz, 1H), 7.78ꢀ7.69 (m, 4H), 7.62ꢀ7.55 (m,
1
3
2
3
H), 7.28ꢀ7.20 (m, 3H), 6.19 (s, 1H), 5.89 (s, 1H), 4.83 (s, 2H). C NMR (100 MHz, CDCl ) δ 154.9,
1
45.1, 138.9, 136.8, 135.5, 133.1, 132.4, 131.0, 130.4, 128.5, 128.4, 127.5, 125.9, 124.7, 118.5, 58.8.
+
+
HRMS (ESI) calcd. for: C H ClNO S (M+H) 344.0507, found 344.0509.
1
8
15
2
6
ꢀBromoꢀ2ꢀ[3ꢀ(phenylsulfonyl)propꢀ1ꢀenꢀ2ꢀyl]quinoline (3ia). White solid (59.0 mg, 76% yield), mp
1
= 195ꢀ198 °C. H NMR (400 MHz, CDCl
3
) δ 7.91 (d, J = 8.7 Hz, 1H), 7.87 (d, J = 1.9 Hz, 1H),
7
.77ꢀ7.75 (m, 2H), 7.71ꢀ7.65 (m, 2H), 7.61 (d, J = 8.7 Hz, 1H), 7.28ꢀ7.20 (m, 3H), 6.20 (s, 1H), 5.90 (s,
1
3
3
1H), 4.83 (s, 2H). C NMR (100 MHz, CDCl ) δ 155.0, 145.3, 138.9, 136.9, 135.4, 133.1, 133.0, 131.0,
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2
2
2
2
2
2
2
2
2
3
3
3
3
3
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5
5
5
5
5
5
6
+
1
2
29.3, 128.6, 128.5, 128.0, 124.8, 120.6, 118.6, 58.8. HRMS (ESI) calcd. for: for: C18H15BrNO S
+
(M+H) 388.0001, found 388.0005.
6
ꢀIodoꢀ2ꢀ[3ꢀ(phenylsulfonyl)propꢀ1ꢀenꢀ2ꢀyl]quinoline (3ja). White solid (47.9 mg, 55% yield), mp =
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
119ꢀ121 °C. H NMR (400 MHz, CDCl
3
) δ 8.13 (d, J = 1.6 Hz, 1H), 7.95ꢀ7.87 (m, 2H), 7.79ꢀ7.77 (m,
13
2
H), 7.62 (d, J = 8.7 Hz, 2H), 7.30ꢀ7.22 (m, 3H), 6.22 (s, 1H), 5.92 (s, 1H), 4.85 (s, 2H). C NMR
(100 MHz, CDCl
3
) δ 155.1, 145.7, 138.9, 138.2, 136.9, 136.0, 135.1, 133.1, 131.1, 128.5, 128.4, 124.7,
+
+
118.3, 92.2, 58.8. HRMS (ESI) calcd. for: C18
H15INO
2
S (M+H) 435.9863, found 435.9864.
7
ꢀChloroꢀ2ꢀ[3ꢀ(phenylsulfonyl)propꢀ1ꢀenꢀ2ꢀyl]quinoline (3ka). Yellow solid (37.1 mg, 54% yield), mp
1
3
= 102ꢀ105 °C. H NMR (400 MHz, CDCl ) δ 7.97 (d, J = 8.6 Hz, 1H), 7.78ꢀ7.76 (m, 3H), 7.65ꢀ7.58 (m,
1
3
2
H), 7.43ꢀ7.40 (m, 1H), 7.30ꢀ7.22 (m, 3H), 6.20 (s, 1H), 5.89 (s, 1H), 4.82 (s, 2H). C NMR (100
3
MHz, CDCl ) δ 155.6, 147.1, 139.0, 136.9, 136.1, 135.2, 133.0, 128.47, 128.46, 128.4, 128.3, 127.6,
+
+
2
125.2, 124.8, 117.8, 58.9. HRMS (ESI) calcd. for: C18H15ClNO S (M+H) 344.0507, found 344.0508.
8ꢀMethoxyꢀ2ꢀ[3ꢀ(phenylsulfonyl)propꢀ1ꢀenꢀ2ꢀyl]quinoline (3la). White solid (48.2 mg, 71% yield),
1
mp = 138ꢀ141 °C. H NMR (400 MHz, CDCl
3
) δ 7.95 (d, J = 8.6 Hz, 1H), 7.78ꢀ7.76 (m, 2H), 7.56 (d, J
=
8.6 Hz, 1H), 7.42ꢀ7.38 (m, 1H), 7.29ꢀ7.27 (m, 1H), 7.20ꢀ7.13 (m, 3H), 6.99 (d, J = 7.7 Hz, 1H), 6.12
1
3
(
3
s, 1H), 5.82 (s, 1H), 4.92 (s, 2H), 4.05 (s, 3H). C NMR (100 MHz, CDCl ) δ 155.3, 153.6, 138.72,
1
38.69, 137.3, 136.2, 132.7, 128.6, 128.11, 128.06, 126.9, 123.7, 119.1, 118.4, 108.1, 59.1, 55.9.
+
+
HRMS (ESI) calcd. for: C H NO S (M+H) 340.1002, found 340.1003.
1
9
18
3
8
ꢀEthoxyꢀ2ꢀ[3ꢀ(phenylsulfonyl)propꢀ1ꢀenꢀ2ꢀyl]quinoline (3ma). White solid (55.8 mg, 79% yield), mp
1
= 105ꢀ108 °C. H NMR (400 MHz, CDCl
3
) δ 7.84 (d, J = 8.7 Hz, 1H), 7.76ꢀ7.74 (m, 2H), 7.65 (d, J =
9
.2 Hz, 1H), 7.51 (d, J = 8.7 Hz, 1H), 7.27ꢀ7.26 (m, 4H), 6.94 (d, J = 2.7 Hz, 1H), 6.10 (s, 1H), 5.80 (s,
13
3
1H), 4.84 (s, 2H), 4.11 (q, J = 7.0 Hz, 2H), 1.47 (t, J = 7.0 Hz, 3H). C NMR (100 MHz, CDCl ) δ
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57.2, 152.1, 142.6, 138.9, 137.0, 135.0, 132.9, 130.7, 128.5, 128.3, 128.0, 122.9, 122.2, 117.8, 105. 5,
+
+
3
63.7, 58.9, 14.7. HRMS (ESI) calcd. for: C20H20NO S (M+H) 354.1158, found 354.1158.
3
ꢀ[3ꢀ(Phenylsulfonyl)propꢀ1ꢀenꢀ2ꢀyl]benzo[f]quinoline (3na). Yellow solid (54.6 mg, 76% yield), mp
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
= 124ꢀ127 °C. H NMR (400 MHz, CDCl ) δ 8.72 (d, J = 8.7 Hz, 1H), 8.49 (d, J = 7.8 Hz, 1H),
7
4
1
.88ꢀ7.86 (m, 2H), 7.79ꢀ7.75 (m, 2H), 7.70ꢀ7.60 (m, 4H), 7.18ꢀ7.16 (m, 3H), 6.19 (s, 1H), 5.85 (s, 1H),
1
3
3
.87 (s, 2H). C NMR (100 MHz, CDCl ) δ 154.1, 146.6, 138.8, 136.8, 133.0, 131.6, 131.0, 130.7,
29.2, 128.6, 128.5, 128.3, 128.0, 127.2, 127.0, 124.0, 123.8, 122.6, 117.7, 58.9. HRMS (ESI) calcd.
+
+
for: C H NO S (M+H) 360.1053, found 360.1055.
2
2
18
2
1ꢀ[3ꢀ(Phenylsulfonyl)propꢀ1ꢀenꢀ2ꢀyl]isoquinoline (3oa). White solid (35.9 mg, 58% yield), mp =
1
92ꢀ95 °C. H NMR (400 MHz, CDCl
3
) δ 8.32ꢀ8.30 (m, 2H), 7.76 (d, J = 8.2 Hz, 1H), 7.68ꢀ7.61 (m,
3H), 7.59ꢀ7.55 (m, 1H), 7.44 (d, J = 5.6 Hz, 1H), 7.31ꢀ7.27 (m, 1H), 7.15 (t, J = 7.8 Hz, 2H), 5.97 (s,
13
1
H), 5.72 (s, 1H), 4.75 (s, 2H). C NMR (100 MHz, CDCl
3
) δ 157.8, 140.9, 138.6, 136.8, 134.4, 133.1,
130.1, 128.4, 128.0, 127.4, 127.3, 126.90, 126.87, 126.2, 120.2, 62.7. HRMS (ESI) calcd. for:
+
+
18 2
C H16NO S (M+H) 310.0896, found 310.0899.
1
4
ꢀ[3ꢀ(Phenylsulfonyl)propꢀ1ꢀenꢀ2ꢀyl]quinoline (3pa). Yellow oli (50.0 mg, 81% yield). H NMR (400
3
MHz, CDCl ) δ 8.73 (d, J = 4.4 Hz, 1H), 8.09 (d, J = 8.4 Hz, 1H), 7.87 (d, J = 7.8 Hz, 1H), 7.73ꢀ7.64
(m, 3H), 7.54ꢀ7.49 (m, 2H), 7.34 (t, J = 7.9 Hz, 2H), 7.07 (d, J = 4.4 Hz, 1H), 5.84 (s, 1H), 5.62 (s, 1H),
1
3
4.35 (s, 2H). C NMR (100 MHz, CDCl ) δ 149.6, 148.3, 146.3, 138.4, 133.7, 133.2, 130.0, 129.4,
3
+
+
1
2
28.9, 128.1, 127.2, 126.9, 125.5, 124.7, 119.9, 63.0. HRMS (ESI) calcd. for: C18H16NO S (M+H)
310.0896, found 310.0897.
2
ꢀ[3ꢀ(Phenylsulfonyl)propꢀ1ꢀenꢀ2ꢀyl]quinoxaline (3qa). White solid (29.2 mg, 47% yield), mp =
1
164ꢀ167 °C. H NMR (400 MHz, CDCl
3
) δ 9.02 (s, 1H), 8.02ꢀ8.00 (m, 1H), 7.83ꢀ7.77 (m, 3H),
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3
7
.73ꢀ7.69 (m, 2H), 7.28ꢀ7.23 (m, 3H), 6.33 (s, 1H), 5.98 (s, 1H), 4.78 (s, 2H). C NMR (100 MHz,
3
CDCl ) δ 149.5, 142.2, 141.0, 140.7, 138.6, 135.1, 133.3, 130.2, 130.0, 129.3, 128.8, 128.6, 128.5,
+
+
1
25.8, 58.5. HRMS (ESI) calcd. for: C H N O S (M+H) 311.0849, found 311.0850.
17 15 2 2
0
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4
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6
7
8
9
0
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7
8
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0
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7
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8
9
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2ꢀ[3ꢀ(Phenylsulfonyl)propꢀ1ꢀenꢀ2ꢀyl]pyridine (3ra). White solid (8.9 mg, 17% yield), mp =
1
1
7
33ꢀ135 °C. H NMR (400 MHz, CDCl
3
) δ 8.37 (d, J = 3.8 Hz, 1H), 7.81ꢀ7.76 (m, 2H), 7.64 (m, 1H),
1
3
.52ꢀ7.48 (m, 2H), 7.39 (t, J = 7.7 Hz, 2H), 7.14 (m, 1H), 6.03 (s, 1H), 5.63 (s, 1H), 4.66 (s, 2H).
C
3
NMR (100 MHz, CDCl ) δ 155.4, 148.4, 138.8, 136.6, 136.5, 133.3, 128.6, 123.3, 122.5, 120.3, 59.1.
+
+
HRMS (ESI) calcd. for: C H NO S (M+H) 262.0896, found 262.0899.
1
4
16
2
2ꢀPhenylꢀ3ꢀ[2ꢀ(phenylsulfonyl)ethyl]quinoxaline (3sa). Yellow solid (37.4 mg, 50% yield), mp =
1
1
22ꢀ124 °C. H NMR (400 MHz, CDCl
3
) δ 8.11ꢀ8.09 (m, 1H), 7.97ꢀ7.95 (m, 1H), 7.80 (d, J = 7.4 Hz,
2H), 7.75ꢀ7.72 (m, 2H), 7.68ꢀ7.52 (m, 6H), 7.44 (t, J = 7.6 Hz, 2H), 3.83ꢀ3.80 (m, 2H), 3.53ꢀ3.49 (m,
13
2H). C NMR (100 MHz, CDCl
3
) δ 154.4, 150.7, 140.8, 140.7, 139.0, 137.8, 133.5, 129.90, 129.85,
+
129.3, 129.2, 129.1, 128.82, 128.78, 128.4, 128.0, 53.8, 28.9. HRMS (ESI) calcd. for: C H N O S
2
2
19
2
2
+
(M+H) 375.1162, found 375.1165.
2
1
5
ꢀ[3ꢀ(phenylsulfonyl)propꢀ1ꢀenꢀ2ꢀyl]benzo[d]thiazole (5aa). White solid (42.9 mg, 68% yield), mp =
1
25ꢀ128 °C. H NMR (400 MHz, CDCl
3
) δ 7.86ꢀ7.84 (m, 2H), 7.76 (d, J = 8.4 Hz, 2H), 7.42ꢀ7.30 (m,
13
3
H), 6.20 (s, 1H), 5.93 (s, 1H), 4.64 (s, 2H). C NMR (100 MHz, CDCl ) δ 167.9, 154.1, 138.5, 133.6,
133.5, 131.8, 128.9, 128.73, 128.69, 127.6, 126.2, 122.4, 119.7, 58.9. HRMS (ESI) calcd. for:
+
+
16 2 2
C H14NO S (M+H) 316.0461, found 316.0466.
5ꢀFluoroꢀ2ꢀ[3ꢀ(phenylsulfonyl)propꢀ1ꢀenꢀ2ꢀyl]benzo[d]thiazole (5ba). White solid (44.0 mg, 66%
1
yield), mp = 131ꢀ134 °C. H NMR (400 MHz, CDCl
3
) δ 7.86ꢀ7.83 (m, 2H), 7.70ꢀ7.66 (m, 1H),
1
3
7.46ꢀ7.33 (m, 4H), 7.14ꢀ7.10 (m, 1H), 6.21 (s, 1H), 5.93 (s, 1H), 4.61 (s, 2H). C NMR (100 MHz,
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CDCl
3
) δ 168.6, 162.8, 160.4, 153.8 (J = 12.0 Hz), 138.4, 133.5, 131.8, 130.08 (d, J = 1.9 Hz), 128.7,
127.3, 122.1(d, J = 8.89 Hz), 114.5 (d, J = 24.9 Hz), 109.4 (d, J = 23.4 Hz), 58.9. HRMS (ESI) calcd.
+
+
for: C H FNO S (M+H) 334.0366, found 334.0368.
1
6
13
2 2
1
1
1
1
1
1
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1
1
1
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5
5
5
5
6
0
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8
9
0
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7
8
9
0
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9
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8
9
0
5ꢀChloroꢀ2ꢀ[3ꢀ(phenylsulfonyl)propꢀ1ꢀenꢀ2ꢀyl]benzo[d]thiazole (5ca). Yellow solid (44.0 mg, 63%
1
yield), mp = 150ꢀ153 °C. H NMR (400 MHz, CDCl
3
) δ 7.85 (d, J = 7.7 Hz, 2H), 7.76 (s, 1H), 7.68 (d,
1
3
J = 8.6 Hz, 1H), 7.46ꢀ7.29 (m, 4H), 6.23 (s, 1H), 5.97 (s, 1H), 4.62 (s, 2H). C NMR (100 MHz,
3
CDCl ) δ 168.1, 153.7, 138.4, 133.6, 133.0, 132.2, 131.7, 128.7, 127.6, 126.3, 123.1, 122.1, 58.9.
+
+
HRMS (ESI) calcd. for: C H ClNO S (M+H) 350.0071, found 350.0073.
1
6
13
2 2
5ꢀBromoꢀ2ꢀ[3ꢀ(phenylsulfonyl)propꢀ1ꢀenꢀ2ꢀyl]benzo[d]thiazole (5da). Yellow solid (39.4 mg, 50%
1
yield), mp = 146ꢀ149 °C. H NMR (400 MHz, CDCl
3
) δ 7.93 (s, 1H), 7.85 (d, J = 7.6 Hz, 2H), 7.62 (d,
1
3
J = 8.4 Hz, 1H), 7.46ꢀ7.35 (m, 4H), 6.22 (s, 1H), 5.97 (s, 1H), 4.61 (s, 2H). C NMR (100 MHz,
3
CDCl ) δ 167.9, 154.0, 138.4, 133.6, 133.5, 131.7, 128.9, 128.73, 128.68, 127.6, 126.2, 122.4, 119.7,
+
+
58.8. HRMS (ESI) calcd. for: C H BrNO S (M+H) 393.9566, found 393.9561.
1
6
13
2 2
5ꢀMethoxyꢀ2ꢀ[3ꢀ(phenylsulfonyl)propꢀ1ꢀenꢀ2ꢀyl]benzo[d]thiazole(5ea). Yellow oil (38.0 mg, 55%
1
yield). H NMR (400 MHz, CDCl
3
) δ 7.87ꢀ7.85 (m, 2H), 7.61 (d, J = 8.8 Hz, 1H), 7.41ꢀ7.34 (m, 3H),
1
3
7.27 (m, 1H), 7.02ꢀ7.00 (m, 1H), 6.20 (s, 1H), 5.88 (s, 1H), 4.63 (s, 2H), 3.87 (s, 3H). C NMR (100
3
MHz, CDCl ) δ 167.4, 158.9, 154.0, 138.4, 133.5, 131.8, 128.73, 128.66, 126.6, 126.5, 121.6, 116.2,
+
+
105.5, 59.0, 55.6. HRMS (ESI) calcd. for: C H NO S (M+H) 346.0566, found 346.0569.
1
7
16
3 2
2ꢀ[3ꢀ(Phenylsulfonyl)propꢀ1ꢀenꢀ2ꢀyl]naphtho[2,1ꢀd]thiazole (5fa). White solid (36.5 mg, 50% yield),
1
mp = 155ꢀ158 °C. H NMR (400 MHz, CDCl
3
) δ 8.48 (d, J = 8.1 Hz, 1H), 7.91 (d, J = 8.1 Hz, 1H),
7.86 (d, J = 7.6 Hz, 2H), 7.76 (s, 2H), 7.66 (t, J = 7.5 Hz, 1H), 7.58 (t, J = 7.5 Hz, 1H), 7.18 (t, J = 7.5
13
3
Hz, 2H), 7.11ꢀ7.10 (m, 1H), 6.24 (s, 1H), 5.96 (s, 1H), 4.77 (s, 2H). C NMR (100 MHz, CDCl ) δ
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65.1, 149.1, 138.5, 133.3, 132.2, 131.8, 131.5, 128.7, 128.5, 128.4, 128.0, 126.9, 126.7, 126.2, 125.7,
+
+
2 2
123.8, 118.6, 59.3. HRMS (ESI) calcd. for: C20H16NO S (M+H) 366.0617, found 366.0618.
2
ꢀ(3ꢀTosylpropꢀ1ꢀenꢀ2ꢀyl)benzo[d]thiazole (5ab). White solid (55.9 mg, 86% yield), mp = 133ꢀ136 °C.
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
H NMR (400 MHz, CDCl ) δ 7.76 (t, J = 6.2 Hz, 2H), 7.70 (d, J = 7.2 Hz, 2H), 7.41 (t, J = 7.5 Hz, 1H),
7
2
1
.34 (t, J = 7.6 Hz, 1H), 7.07 (d, J = 7.6 Hz, 2H), 6.19 (d, J = 3.5 Hz, 1H), 5.93 (s, 1H), 4.60 (s, 2H),
1
3
.13 (s, 3H). C NMR (100 MHz, CDCl3) δ 166.3, 152.9, 144.6, 135.5, 134.7, 132.2, 129.3, 128.7,
+
+
2 2
26.8, 126.1, 125.7, 123.3, 121.4, 59.3, 21.3. HRMS (ESI) calcd. for: C17H16NO S (M+H) 330.0617,
found 330.0623.
2ꢀ(3ꢀ((4ꢀ(tertꢀButyl)phenyl)sulfonyl)propꢀ1ꢀenꢀ2ꢀyl)benzo[d]thiazole (5ac). Yellow solid (31.1 mg,
1
5
3% yield), mp = 128ꢀ131 °C. H NMR (400 MHz, CDCl
3
) δ 7.74ꢀ7.71 (m, 4H), 7.38ꢀ7.29 (m, 2H),
1
3
7.23 (d, J = 8.5 Hz, 2H), 6.19 (s, 1H), 5.99 (s, 1H), 4.62 (s, 2H), 1.02 (s, 9H). C NMR (100 MHz,
CDCl3) δ 166.2, 157.3, 152.8, 135.1 134.6, 132.2, 128.7, 126. 9, 126.1, 125.7, 125.5, 123.3, 121.3, 59.1,
+
+
34.8, 30.6. HRMS (ESI) calcd. for: C H NO S (M+H) 372.1087, found 372.1090.
2
0
22
2 2
2
ꢀ{3ꢀ[(4ꢀMethoxyphenyl)sulfonyl]propꢀ1ꢀenꢀ2ꢀyl}benzo[d]thiazole (5ad). Yellow solid (41.0 mg, 59%
1
yield), mp = 152ꢀ155 °C. H NMR (400 MHz, CDCl
3
) δ 7.77ꢀ7.42 (m, 4H), 7.42ꢀ7.32 (m, 2H),
1
3
6
.72ꢀ6.70 (m, 2H), 6.19 (s, 1H), 5.92 (s, 1H), 4.59 (s, 2H), 3.58 (s, 3H). C NMR (100 MHz, CDCl3) δ
1
66.3, 163.5, 153.0, 134.7, 132.3, 130.9, 130.0, 126.8, 126.1, 125.7, 123.4, 121.3, 113.8, 59.5, 55.4.
+
+
HRMS (ESI) calcd. for: C H NO S (M+H) 346.0566, found 346.0570.
1
7
16
3 2
2
ꢀ{3ꢀ[(4ꢀNitrophenyl)sulfonyl]propꢀ1ꢀenꢀ2ꢀyl}benzo[d]thiazole (5ae). Yellow solid (16.4 mg, 22%
1
yield), mp = 181ꢀ184 °C. H NMR (400 MHz, CDCl
3
) δ 8.09ꢀ8.06 (m, 2H), 8.02ꢀ8.00 (m, 2H),
13
7
.76ꢀ7.74 (m, 1H), 7.62ꢀ7.60 (m, 1H), 7.40ꢀ7.32 (m, 1H), 6.25 (s, 1H), 6.05 (s, 1H), 4.70 (s, 2H).
C
NMR (100 MHz, CDCl3) δ 165.6, 152.5, 150.5, 144.2, 134.4, 131.5, 130.3, 127.7, 126.6, 126.3, 123.6,
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+
+
1
13 2 4 2
23.0, 121.6, 59.4. HRMS (ESI) calcd. for: C16H N O S (M+H) 361.0307, found 361.0311.
2ꢀ{3ꢀ[(4ꢀFluorophenyl)sulfonyl]propꢀ1ꢀenꢀ2ꢀyl}benzo[d]thiazole (5af). Yellow solid (47.6 mg, 71%
1
yield), mp = 140ꢀ143 °C. H NMR (400 MHz, CDCl ) δ 7.87ꢀ7.83 (m, 4H), 7.76 (t, J = 8.0 Hz, 2H),
3
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
13
7.44ꢀ7.34 (m, 4H), 6.97 (t, J = 8.5 Hz, 2H), 6.22 (s, 1H), 5.97 (s, 1H), 4.64 (s, 2H). C NMR (100
MHz, CDCl3) δ 166.1, 165.7 (J = 255 Hz), 152.9, 134.7, 132.0, 131.8, 131.7, 127.1, 126.4, 126.1, 123.3,
+
+
1
3
2
21.5, 116.0 (J = 22 Hz), 59.2. HRMS (ESI) calcd. for: C16
2 2
H13FNO S (M+H) 334.0366, found
34.0369.
ꢀ{3ꢀ[(4ꢀChlorophenyl)sulfonyl]propꢀ1ꢀenꢀ2ꢀyl}benzo[d]thiazole (5ag). Yellow solid (60.4 mg, 87%
1
yield), mp = 158ꢀ161 °C. H NMR (400 MHz, CDCl
3
) δ 7.76 (q, J = 8.3 Hz, 4H), 7.43 (t, J = 7.7 Hz,
1
3
1
H), 7.36 (t, J = 7.5 Hz, 1H), 7.26 (d, J = 8.3 Hz, 2H), 6.22 (s, 1H), 5.97 (s, 1H), 4.63 (s, 2H).
C
NMR (100 MHz, CDCl3) δ 165.9, 152. 8, 140.4, 137.0, 134.6, 131.9, 130.2, 128.9, 127.1, 126.4, 126.1,
+
+
1
2 2
23.3, 121.4, 59.3. HRMS (ESI) calcd. for: C16H13ClNO S (M+H) 350.0071, found 350.0074.
2ꢀ{3ꢀ[(4ꢀBromophenyl)sulfonyl]propꢀ1ꢀenꢀ2ꢀyl}benzo[d]thiazole (5ah). Yellow solid (63.1 mg, 80%
1
yield), mp = 139ꢀ142 °C. H NMR (400 MHz, CDCl
3
) δ 7.78 (d, J = 7.9 Hz, 1H), 7.73 (d, J = 8.1 Hz,
1
4
1
H), 7.68 (d, J = 8.4 Hz, 2H), 7.46ꢀ7.41 (m, 3H),, 7.37 (d, J = 7.7 Hz, 1H), 6.21 (s, 1H), 5.96 (s, 1H),
1
3
.63 (s, 2H). C NMR (100 MHz, CDCl3) δ 165.9, 152.8, 137.5, 134.6, 131.9, 130.3, 129.1, 127.1,
+
+
2 2
26.4, 126.0, 123.3, 121.4, 59.3. HRMS (ESI) calcd. for: C16H13BrNO S (M+H) 393.9566, found
3
93.9569.
2
ꢀ(3ꢀ((4ꢀ(Trifluoromethyl)phenyl)sulfonyl)propꢀ1ꢀenꢀ2ꢀyl)benzo[d]thiazole (5ai). White solid (27.5
1
mg, 36% yield), mp = 163ꢀ166 °C. H NMR (400 MHz, CDCl
3
) δ 7.95 (d, J = 8.1 Hz, 2H), 7.75ꢀ7.73
(
m, 1H), 7.65ꢀ7.63 (m, 1H), 7.51 (d, J = 8.2 Hz, 2H), 7.41ꢀ7.32 (m, 2H), 6.23 (s, 1H), 6.01 (s, 1H),
1
3
4.67 (s, 2H). C NMR (100 MHz, CDCl3) δ 165.7, 152.6, 142.0, 135.0 (q, J = 33.0 Hz), 134.4, 131.7,
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2
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29.4, 127.4, 126.4, 126.1, 125.6 (q, J = 3.3 Hz), 123.1, 122.8 (q, J = 270.2 Hz), 121.4, 59.3. HRMS
+
+
13 3 2 2
(ESI) calcd. for: C17H F NO S (M+H) 384.0334, found 384.0337.
1
2ꢀ[3ꢀ(pꢀtolylthio)propꢀ1ꢀenꢀ2ꢀyl]quinoline (3a). Yellow oil (21.0 mg, 36% yield). H NMR (400 MHz,
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
CDCl
3
) δ 8.13ꢀ8.08 (m, 2H), 7.79 (d, J = 8.0 Hz, 1H), 7.72ꢀ7.67 (m, 2H), 7.51 (t, J = 7.2 Hz, 1H), 7.29
13
(d, J = 8.1 Hz, 2H), 7.07 (d, J = 8.0 Hz, 2H), 5.88 (s, 1H), 5.51 (s, 1H), 4.31 (s, 2H), 2.30 (s, 3H). C
3
NMR (100 MHz, CDCl ) δ 156.7, 147.6, 144.5, 136.4, 136.1, 132.8, 131.0, 129.8, 129.5, 129.4, 127.3,
+
+
1
26.4, 118.8, 118.4, 38.0, 21.0. HRMS (ESI) calcd. for: C18
H
16NS (M+H) 278.0998, found 278.1000.
1
2
ꢀMethylꢀ3ꢀ[(phenylsulfonyl)methyl]ꢀ1Hꢀindole (7). Yellow oil (19.9 mg, 35% yield). H NMR (400
3
MHz, CDCl ) δ 8.01 (s, 1H), 7.65ꢀ7.63 (m, 2H), 7.54 (t, J = 7.5 Hz, 1H), 7.37 (t, J = 7.8 Hz, 2H), 7.22
(d, J = 8.1 Hz, 1H), 7.15 (d, J = 7.9 Hz, 1H), 7.10ꢀ7.06 (m, 1H), 6.99ꢀ6.94 (m, 1H), 4.47 (s, 2H), 2.10
13
3
(s, 3H). C NMR (100 MHz, CDCl ) δ 138.3, 135.9, 134.8, 133.4, 128.8, 128.7, 128.1, 121.6, 120.1,
+
+
117.9, 110.3, 99.2, 53.9, 11.4. HRMS (ESI) calcd. for: C16
H15NO
2
SNa (M+Na) 308.0716 found
308.0718.
1
1
ꢀ{3ꢀ[2ꢀ(Phenylsulfonyl)ethyl]quinoxalinꢀ2ꢀyl}ethanone (9). White solid (14.3 mg, 21% yield). H
3
NMR (400 MHz, CDCl ) δ 8.11 (d, J = 8.2 Hz, 1H), 7.98 (d, J = 7.6 Hz, 3H), 7.86ꢀ7.77 (m, 2H),
1
3
7
3
.63ꢀ7.53 (m, 3H), 3.88ꢀ3.85 (m, 2H), 3.77ꢀ3.73 (m, 2H), 2.83 (s, 3H). C NMR (100 MHz, CDCl ) δ
2
01.2, 151.5, 146.4, 142.2, 139.7, 139.1, 133.6, 132.3, 130.2, 129.8, 129.2, 128.6, 128.2, 53.9, 29.6,
+
+
27.6. HRMS (ESI) calcd. for: C H N O S (M+H) 341.0954, found 341.0958.
1
8
17
2
3
1
2
,3ꢀBis[2ꢀ(phenylsulfonyl)ethyl]quinoxaline (11). Yellow oil (28.0 mg, 30% yield). H NMR (400
MHz, CDCl
3
) δ 7.96 (d, J = 7.3 Hz, 4H), 7.87ꢀ7.84 (m, 2H), 7.67ꢀ7.60 (m, 4H), 7.55 (t, J = 7.5 Hz, 4H),
13
3
.91ꢀ3.87 (m, 4H), 3.44ꢀ3.40 (m, 4H). C NMR (100 MHz, CDCl
3
) δ 150.8, 140.4, 139.1, 133. 8,
+
+
129.6, 129.4, 128.5, 128.0, 53.0, 27.1. HRMS (ESI) calcd. for: C24
H
23
N
2
O
4
S
2
(M+H) 467.1094,
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found 467.1094.
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2ꢀ(Phenylsulfonyl)ꢀ1ꢀ(quinolinꢀ2ꢀyl)ethanone (12). White solid (15.8 mg, 49% yield). H NMR (400
MHz, CDCl ) δ 8.26 (d, J = 8.5 Hz, 1H), 8.06 (dd, J = 8.4, 6.7 Hz, 2H), 8.08ꢀ8.04 (m, 2H), 7.96ꢀ7.94
3
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
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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, 2H),7.86 (d, J = 8.2 Hz, 1H), 7.79 (td, J = 7.0, 3.5 Hz, 1H), 7.69ꢀ7.65 (m, 1H), 7.56ꢀ7.52 (m, 1H),
13
7.49ꢀ7.45 (m, 2H), 5.36 (s, 2H). C NMR (100 MHz, CDCl
3
) δ 189.8, 151.3, 146.8, 139.6, 137.4,
133.8, 130.6, 130.3, 129.8, 129.4, 129.0, 128.5, 127.6, 118.1, 61.0. HRMS (ESI) calcd. for:
+
+
C
17 3
H13NO S (M+Na) 334.0508, found 334.0511.
■
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the ACS Publications website at DOI:
10.1020/acs.joc.0000000
1
13
Copies of H and C NMR spectra of the products (PDF)
■
AUTHOR INFORMATION
Corresponding Author
Eꢀmail: fhxiao@xtu.edu.cn.
*
*Eꢀmail: gjdeng@xtu.edu.cn.
ORCID
Fuhong Xiao: 0000ꢀ0003ꢀ0862ꢀ0557
GuoꢀJun Deng: 0000ꢀ0003ꢀ2759ꢀ0314
Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENT
This work was supported by the National Natural Science Foundation of China (21502160,
1572194), Hunan Provincial Natural Science Foundation of China (16JJ3112), the Scientific
Research Fund of Hunan Provincial Education Department (YB2016B024),
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