Selective Construction of 2-Substituted Benzothiazoles from o-Iodoaniline Derivatives S8 and N-Tosylhydrazones

Article abstract of DOI:10.1021/acs.joc.7b03118

Selective construction of 2-substituted benzothiazoles from o-iodoaniline derivatives S₈ and N-tosylhydrazone via a copper-promoted [3 + 1 + 1]-type cyclization reaction has been realized. In the protocol, the carbon atom on N-tosylhydrazone could be regulated to construct benzothiazole by changing the reaction system. Furthermore, the transformation has achieved the construction of multiple carbon-heteroatom bonds.

Full text of DOI:10.1021/acs.joc.7b03118

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Note
Selective Construction of 2-Substituted Benzothiazoles
from o-Iodoaniline Derivatives, S8 and N-Tosylhydrazones
Yubing Huang, Peiqi Zhou, Wanqing Wu, and Huanfeng Jiang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b03118 • Publication Date (Web): 16 Jan 2018
Downloaded from http://pubs.acs.org on January 17, 2018
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Selective Construction of 2-Substituted
Benzothiazoles from o-Iodoaniline Derivatives, S8
and N-Tosylhydrazones
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Yubing Huang, Peiqi Zhou, Wanqing Wu*, Huanfeng Jiang*
Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of
Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640,
P. R. China
Fax: (+86) 20ꢀ87112906; Eꢀmail: cewuwq@scut.edu.cn, jianghf@scut.edu.cn
Abstract: A selective construction of 2ꢀsubstituted benzothiazoles from oꢀiodoaniline
derivatives, S8 and Nꢀtosylhydrazone via copperꢀpromoted [3+1+1]ꢀtype cyclization
reaction has been realized. In the protocol, the carbon atom on Nꢀtosylhydrazone
could be regulated to construct benzothiazole by changing the reaction system.
Furthermore, the transformation has achieved the construction of multiple
carbonꢀheteroatom bonds.
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Carbonꢀheteroatom bonds such as CꢀS, CꢀO and CꢀN bonds are basic fragments of
functional heterocyclic molecules. The development of novel and effective protocols
to construct these chemical bonds is a significant issue in organic synthesis,1
especially in the research of biologically active molecules, drugs and agrochemicals.
NꢀTosylhydrazones, as readily available and stable substrates, can be used as metal
carbene precursors after generating diazo compounds in situ under basic conditions.
As a result of the high concern, using metal carbene species to construct
carbonꢀheteroatom bonds has received considerable attention. In the respect, the
insertions of metal carbenes into XꢀH (X = B, N, O, S, Si, etc.) bonds,2 cyclization
reactions,3 difunctionalization4 and multicomponent reactions of metalꢀcarbene5 have
displayed versatile applications in the constructions of carbonꢀheteroatom bonds. In
recent years, our group has successfully achieved a series of conversion reactions of
Nꢀtosylhydrazones to build carbonꢀheteroatom bonds in transition metalꢀcatalyzed
systems.4a,6 For example, the cyanothiolation of copperꢀcarbene to incorporate a
sulfurꢀsubstituted quaternary carbon center,4a and the synthesis of oxiranes through
the construction of carbonyl ylides from palladium carbenes.6a Similarly, two different
bonds was built on the carbon atom of metal carbene (C1) (Scheme 1a). Furthermore,
copperꢀcatalyzed oxidative transformations of Nꢀtosylhydrazones as alkyne precusors
have been applied in the crossꢀcoupling reactions,6e where C2 was the bonding site
(Scheme 1b). Based on previous studies, we intend to construct diverse heterocyclic
molecules by using different bonding sites of Nꢀtosylhydrazones.
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Scheme 1. Transition Metal-Catalyzed Conversions of N-Tosylhydrazones
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As an important class of heterocyclic scaffold, benzothiazoles are widely found
in biologically active molecules, clinically drugs, and application materials. The
common approaches for the assembly of 2ꢀsubstituted benzothiazoles are based on the
condensations of 2ꢀaminothiophenols with carboxylic acids, aldehydes, nitriles and
etc,7 where the preparation of readily oxidized 2ꢀaminothiophenols is a major problem.
The other accesses to synthesize 2ꢀsubstituted benzothiazoles include CꢀH
functionalization/CꢀS bond formation,8 cyclization of orthoꢀhalobenzoꢀthiourea,9 and
etc.10 Normally, the benzothioureas used in such methods require further conversion
of the corresponding amides. Despite the diversification of synthetic methods, we are
still eager to develop a novel method to synthesize benzothiazoles with
readilyꢀavailable raw materials. Hence, we propose
a
copperꢀpromoted
multiꢀcomponent tandem cyclization for the selective construction of 2ꢀsubstituted
benzothiazoles from oꢀiodoaniline derivatives, S8 and Nꢀtosylhydrazones (Scheme 1c).
In the protocol, by changing the reaction system, C1 or C2 is used selectively as a
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binding site to achieve the construction of carbonꢀheteroatom bonds.
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In order to increase the yield and selectivity of products 3a and 4a, the reaction
conditions for each product were optimized individually. As shown in Table 1, the
reaction was initially carried out in the presence of CuTC (5 mol %), DBU (2 equiv)
and DMSO (1.5 mL) at 110 °C under air for 10 h to produce 3a in 40% yield (entry 1).
Then, differ copper catalysts (CuI, CuCl, CuSCN, Cu(OAc)2, etc.), as well as the
amount of copper catalyst and DBU were investigated, and the use of 10 mol % of
CuSCN and 3 equiv of DBU was found to be suitable to form 3a (entry 7). The
reaction proceeded better when conducted under N2, which delivered 3a in 72%
isolated yield (entry 8). Notably, the reaction did not occur without a copper salt
(entry 9).
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Table 1. Optimization of the Reaction Conditions to Construct 3a a
NNHTs
I
S
[Cu], DBU
S8
+
H2
+
N
N
DMSO, 110 C
3a
1a
2a
Entry
[Cu]
Base
Yield b(%) of 3a
1
2
3
4
5
6
7
CuTC (5)
CuI (5)
DBU (2)
DBU (2)
DBU (2)
DBU (2)
DBU (2)
DBU (2)
DBU (3)
40
36
CuSCN (5)
Cu(OAc)2 (5)
CuSCN (10)
CuSCN (20)
CuSCN (10)
49
n.d.
58
56
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8 c
CuSCN (10)
DBU (3)
76 (72)
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9
ꢀ
DBU (3)
n.d.
7
8
a Reaction conditions: 1a (0.1 mmol), S8 (0.12 mmol), 2a (0.12 mmol), [Cu] (mol %), DBU (equiv)
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b
in DMSO (1.5 mL) at 110 °C under air for 10 h unless otherwise noted. GC yield with
nꢀdodecane as internal standard. n.d. = not detected. The number in the parentheses is isolated
yield. c Under N2.
The substrate scope for the construction of benzothiazoles 3 was shown in Table
2. Various Nꢀtosylhydrazones containing different functional groups, especially
electronꢀrich groups (NMe2, OMe and SMe), at the paraꢀposition of benzene ring
worked well to afford the desired benzothiazoles 3 in moderate to good yields (3aꢀ3g).
Heterocycles derived Nꢀtosylhydrazones were good substrates and the corresponding
products were delivered in good yields (3hꢀ3j). The reaction performed with sterically
hindered substrates gave the corresponding products in the yields of 82% (3k) and
75% (3l), respectively. 2ꢀIodoanilines containing various groups including Me, Br,
CF3 and OMe at 4ꢀposition of aromatic ring also worked well, and the reactions
delivered the desired products in good yields (3mꢀ3p). In addition, when
4ꢀfluoroꢀ2ꢀiodoaniline and 3,4ꢀdimethoxyacetophenone derived Nꢀtosylhydrazones
were used as substrates, the reaction gave 3q in 75% yield.
Table 2. Synthesis of Substituted Benzothiazoles 3 a
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a Reaction conditions: 1 (0.2 mmol), S8 (0.24 mmol), 2 (0.24 mmol), CuSCN (10 mol%), DBU (3
equiv) in DMSO (2.5 mL) at 110 °C under N2 for 10 h unless otherwise noted. Yields refer to the
isolated yields.
Next，we went on optimizing the reaction conditions to promote the formation of
4a. As shown in Table 3, the reaction was carried out with DABCO as base in 1.5 mL
of MeCN at 130 °C under nitrogen atmosphere, and various types of copper catalysts
were then examined. When using 10 mol% of CuI, the better selectivity and higher
yield for 4a were observed (entry 2). Reducing the amount of DABCO to 1 equivalent,
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the yield was maintained (entry 5). Subsequently, we conducted the reaction by
adding different fluoride ionꢀcontaining additives. It is found that the addition of 2
equivalent of CsF was effective and the yield of 4a increased to 53% (entry 6). The
reaction appeared to proceed more smoothly when increasing CuI loading (entries
9ꢀ10), whereas the reaction was hindered when 1 equivalent of CuI was used (entry
11). Notably, the presence of oxygen could inhibit the production of 4a (entry 12).
Similarly, the reaction did not occur without a copper salt (entry 13).
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Table 3. Optimization of Reaction Conditions to Construct 4a a
Entry
[Cu]
CuTC (10)
CuI (10)
CuCl (10)
CuSCN (10)
CuI (10)
CuI (10)
CuI (10)
CuI (10)
CuI (30)
CuI (50)
CuI (100)
Base
Additive Yield b(%) of 4a
1
DABCO (2)
DABCO (2)
DABCO (2)
DABCO (2)
DABCO (1)
DABCO (1)
DABCO (1)
DABCO (1)
DABCO (1)
DABCO (1)
DABCO (1)
-
30
41
2
ꢀ
-
3
27
4
-
13
5
-
42
6
CsF (2)
TBAF (2)
KF (2)
CsF (2)
CsF (2)
CsF (2)
53
7
50
8
43
9
65
10
11
69 (67)
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12 c
13
CuI (50)
DABCO (1)
DABCO (1)
CsF (2)
CsF (2)
trace
n.d
-
7
8
a
Reaction conditions: 1a (0.1 mmol), S8 (0.12 mmol), 2a (0.12 mmol), [Cu] (mol %), DABCO
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(equiv), additive (equiv) in MeCN (1.5 mL) at 130 °C under N2 for 10 h unless otherwise noted. b
GC yield with nꢀdodecane as internal standard. n.d = not detected. The number in the parentheses
is isolated yield. c 1 atm of O2.
The substrate scope for the synthesis of benzothiazoles 4 was shown in Table 4.
Different substituents on the aromatic ring of Nꢀtosylhydrazones have little effect on
the reaction, and the corresponding products were obtained in moderate yields (4a-4e).
Altering the position of the substituent on the aromatic ring had little effect on the
yield (4e-4f). Sterically hindered acetylnaphthalene derived Nꢀtosylhydrazones also
reacted smoothly, and the desired product was obtained in 57% yield (4g).
Additionally, various substituted 2ꢀiodoanilines worked well under the optimal
conditions, and afforded the corresponding products in moderate to good yields
(4hꢀ4k).
Table 4. Synthesis of Substituted Benzothiazoles 4 a
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CuI (0.5 equiv)
DABCO (1 equiv)
CsF (2 equiv)
NNHTs
I
S
N
R3
R3
S8
+
H2
+
R4
N
MeCN, 130 C
6
R4
7
4
1
2
8
9
S
N
S
S
N
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N
4b, 65%
S
4c
, 60%
4a, 67%
F
S
N
S
N
OMe
N
4d, 61%
4e, 66%
4f, 69%
Cl
OMe
S
N
F
S
S
N
N
4g
, 57%
4h
4i
, 66%
, 64%
F3C
S
S
N
N
4j
4k
, 68%
, 70%
a
Reaction conditions: 1 (0.2 mmol), S8 (0.24 mmol), 2 (0.24 mmol), CuI (0.5 equiv), DABCO (1
equiv), CsF (2 equiv) in MeCN (2.5 mL) at 130 °C under N2 for 10 h unless otherwise noted.
Yields refer to the isolated yields.
To further clarify the mechanism, some control experiments were conducted
(Scheme 2). Initially, in order to determine whether the reactions were initiated by the
formation of oꢀaminobenzenethiol,7aꢀ7c we mixed oꢀiodoaniline and elemental sulfur
under condition A and condition B, respectively. After the reaction, oꢀiodoaniline in
each reaction system was completely recovered (Eqn. a). Subsequently, we performed
the reactions using oꢀaminobenzenethiol and 2a as substrates (Eqn. b), and the results
further indicated that oꢀaminobenzenethiol should not be an intermediate in both
reaction systems. Because acetophenone was detected as a byꢀproduct, we next used
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acetophenone as a substrate to react with oꢀiodoaniline and S8 under two different
conditions (Eqn. c). We could infer from the results that acetophenone was not a
possible intermediate, and the reactions might be achieved via the formation of active
copper carbene intermediates. Under Condition A, benzoylformic acid could be well
converted, which required the release of CO2, and the reaction gave 3a in 92% yield
(Eqn. d). Moreover, the cyclization of imine and S8 went smoothly to give 3a in 94%
yield (Eqn. e), where imine was considered to be a probable reaction intermediate.
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Scheme 2. Control Experiments a,b
a
Condition A: Reaction conditions: CuSCN (10 mol %), DBU (3 equiv) in DMSO (1.5 mL) at
110 °C under N2 for 10 h. Condition B: CuI (0.5 equiv), DABCO (1 equiv), CsF (2 equiv) in
MeCN (1.5 mL) at 130 °C under N2 for 10 h. b GC yield with nꢀdodecane as internal standard. n.d
= not detected.
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Based on our previous research and the results of control experiments above, we
proposed the possible mechanisms for the formation of 3 and 4 (Scheme 3). Initially,
the Nꢀtosylhydrazone isomerized, followed by the release of N2H2 and Ts to provide
vinyl copper(II) complex,11 which subsequently might undergo the reaction with S8
and the migratory insertion process to form intermediate B. The product 3 could be
constructed through Mechanism A and the product 4 could be constructed through
Mechanism B. In Mechanism A, intermediate B might be oxidized under the action of
S812 and DMSO13 to form intermediate C, which could subsequently convert to imine
intermediate D after releasing H2S and CO2.14 Imine intermediate D underwent an
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15
attack of S8 and a copperꢀcatalyzed intramolecular cyclization process16 to finally
generate product 3. In Mechanism B, αꢀaminovinyl intermediate D’ might be formed
via the process of amine migration,17 which subsequently underwent the
copperꢀcatalyzed intramolecular cyclization and the electron rearrangement to
generate the desired product 4.
Scheme 3. Proposed Reaction Mechanisms
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In conclusion, a copperꢀpromoted [3+1+1]ꢀtype cyclization reaction to construct
2ꢀsubstituted benzothiazoles selectively from oꢀiodoaniline derivative, S8 and
Nꢀtosylhydrazone has been realized. In the protocol, by changing the reaction system,
the carbon atom on Nꢀtosylhydrazone was used selectively as a binding site to achieve
the construction of multiple carbonꢀheteroatom bonds. Remarkably, simple operations,
inexpensive metal catalyst and readily available substrates made this reaction more
valuable. Further applications of the synthesis are currently undergoing in our
laboratory.
EXPERIMENTAL SECTION
General Information.
Melting points were determined with a Buchi Melting Point Bꢀ545 instrument. 1H and
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13C NMR spectra were recorded using a Bruker DRXꢀ400 spectrometer using CDCl3
as solvent. The chemical shifts are referenced to signals at 7.26 and 77.0 ppm,
respectively, and chloroform is solvent with TMS as the internal standard. IR spectra
were obtained either as potassium bromide pellets or as liquid films between two
potassium bromide pellets with a Bruker TENSOR 27 spectrometer. Mass spectra
were recorded on a Thermo Scientific ISQ gas chromatographꢀmass spectrometer. The
data of HRMS was carried out on a highꢀresolution mass spectrometer
(LCMSꢀITꢀTOF). TLC was performed by using commercially prepared 100ꢀ400 mesh
silica gel plates and visualization was effected at 254 nm. Unless otherwise noted, all
reagents and solvents were obtained from commercial suppliers and used without
further purification.
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General procedures for the synthesis of reaction substrates: (I) The preparation of
Nꢀtosylhydrazones 2: A mixture of ketone compounds (5.0 mmol) and
pꢀtoluenesulfonhydrazide (5.0 mmol) in 7.5 mL MeOH was stirred at 70 oC for 0.5ꢀ3
h to afford the corresponding Nꢀtosylhydrazone 1 as white precipitate. After that, the
precipitate was washed and filtered with petroleum ether twice and dried under
vacuum to provide the pure compounds. (II) The preparation of oꢀiodoaniline
derivatives 1 could be carried out according to the literature procedure.18
General procedure A: the synthesis of benzo[d]thiazole products 3: A 25 mL
Schlenk tube equipped with a magnetic stirring bar was added oꢀiodoaniline 1 (0.2
mmol), S8 (0.24 mmol), Nꢀtosylhydrazone 2 (0.24 mmol), CuSCN (10 mol %), DBU
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(3 equiv), DMSO (2.0 mL) under argon atmosphere. The resulting mixture was
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vigorously stirred at 90 C in an oil bath. After 10 h, water was added and extracted
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with ethyl acetate twice. The combined organic phase was dried over Na2SO4 and
concentrated. The residue was purified by flash column chromatography on silica gel
with petroleum ether/ethyl acetate (PE/EA = 10:1–30:1) as the eluent to afford the
desired product.
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General procedure B: the synthesis of benzo[d]thiazole products 4: A 25 mL
Schlenk tube equipped with a magnetic stirring bar was added oꢀiodoaniline 1 (0.2
mmol), S8 (0.24 mmol), Nꢀtosylhydrazone 2 (0.24 mmol), CuI (0.5 equiv), DABCO
(1 equiv), CsF (2 equiv), MeCN (2.5 mL) under argon atmosphere. The resulting
o
mixture was vigorously stirred at 90 C in an oil bath. After 10 h, water was added
and extracted with ethyl acetate twice. The combined organic phase was dried over
Na2SO4 and concentrated. The residue was purified by flash column chromatography
on silica gel with petroleum ether/ethyl acetate (PE/EA = 10:1–30:1) as the eluent to
afford the desired product.
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2-Phenylbenzo[d]thiazole (3a). White solid, yield 30 mg (72%), mp 112ꢀ113 ºC. H
NMR (400 MHz, CDCl3): δ 8.11 (m, 3H), 7.88 (d, J = 8.0 Hz, 1H), 7.49 (m, 4H), 7.38
(t, J = 7.2 Hz, 1H). 13C NMR (101 MHz, CDCl3): δ 168.1, 154.2, 135.1, 133.7, 131.0,
129.0, 127.6, 126.4, 125.2, 123.3, 121.6. IR (KBr, cmꢀ1): 3066, 2925, 1475, 961, 761.
HRMS (ESI) (m/z): calcd for C13H10NS [M+H]+: 212.0528, found: 212.0534.
2-(4-Chlorophenyl)benzo[d]thiazole (3b). White solid, yield 34 mg (70%), mp
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114ꢀ115 ºC. H NMR (400 MHz, CDCl3) δ 8.05 (d, J = 8.2 Hz, 1H), 8.00 (d, J = 8.5
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Hz, 2H), 7.87 (d, J = 8.0 Hz, 1H), 7.48 (m, 1H), 7.43 (d, J = 8.5 Hz, 2H), 7.37 (m,
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1H). C NMR (101 MHz, CDCl3) δ 166.6, 154.0, 137.1, 135.0, 132.1, 129.3, 128.7,
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126.5, 125.4, 123.3, 121.7. IR (KBr, cmꢀ1): 3055, 2920, 1472, 967, 826, 756. HRMS
(ESI) (m/z): calcd for C13H9ClNS [M+H]+: 246.0139, found: 246.0148.
4-(Benzo[d]thiazol-2-yl)benzonitrile (3c). White solid, yield 34 mg (71%), mp
1
172ꢀ173 ºC. H NMR (400 MHz, CDCl3) δ 8.19 (d, J = 8.3 Hz, 2H), 8.11 (d, J = 8.2
Hz, 1H), 7.93 (d, J = 8.0 Hz, 1H), 7.77 (d, J = 8.2 Hz, 2H), 7.54 (m, 1H), 7.44 (m,
13
1H). C NMR (101 MHz, CDCl3) δ 165.3, 154.0, 137.5, 135.3, 132.8, 127.9, 126.8,
126.1, 123.8, 121.8, 118.3, 114.2. IR (KBr, cmꢀ1): 2920, 2854, 1636, 834, 761. HRMS
(ESI) (m/z): calcd for C14H9N2S [M+H]+: 237.0481, found: 237.0472.
4-(Benzo[d]thiazol-2-yl)-N,N-dimethylaniline (3d). Yellow solid, yield 41 mg
(81%), mp 171ꢀ172 ºC. 1H NMR (400 MHz, CDCl3) δ 7.97 (m, 3H), 7.84 (dd, J = 7.9,
13
0.5 Hz, 1H), 7.44 (m, 1H), 7.30 (m, 1H), 6.75 (d, J = 8.9 Hz, 2H), 3.05 (s, 6H). C
NMR (101 MHz, CDCl3) δ 168.8, 154.4, 152.2, 134.6, 128.9, 126.0, 124.2, 122.3,
121.4, 121.4, 111.7, 40.2. IR (KBr, cmꢀ1): 2919, 2854, 1608, 815, 754. HRMS (ESI)
(m/z): calcd for C15H15N2S [M+H]+: 255.0950, found: 255.0951.
2-(4-Methoxyphenyl)benzo[d]thiazole (3e). White solid, yield 39 mg (80%), mp
1
120ꢀ121 ºC. H NMR (400 MHz, CDCl3) δ 8.03 (d, J = 8.6 Hz, 3H), 7.86 (d, J = 7.9
Hz, 1H), 7.46 (t, J = 7.7 Hz, 1H), 7.34 (t, J = 7.6 Hz, 1H), 6.99 (d, J = 8.7 Hz, 2H),
3.87 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 167.9, 162.0, 154.1, 134.8, 129.2, 126.4,
126.2, 124.8, 122.8, 121.5, 114.4, 55.5. IR (KBr, cmꢀ1): 2918, 2847, 1598, 830, 756.
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HRMS (ESI) (m/z): calcd for C14H12NOS [M+H]+: 242.0634, found: 242.0639.
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2-(4-(Methylthio)phenyl)benzo[d]thiazole (3f). White solid, yield 43 mg (84%), mp
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142ꢀ143 ºC. H NMR (400 MHz, CDCl3) δ 8.06 (d, J = 8.1 Hz, 1H), 8.00 (d, J = 8.4
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Hz, 2H), 7.88 (d, J = 8.0 Hz, 1H), 7.48 (t, J = 7.7 Hz, 1H), 7.37 (t, J = 7.6 Hz, 1H),
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7.33 (d, J = 8.4 Hz, 2H), 2.54 (s, 3H). C NMR (101 MHz, CDCl3) δ 167.7, 154.0,
142.9, 134.8, 130.0, 127.8, 126.4, 126.0, 125.1, 123.0, 121.6, 15.2. IR (KBr, cmꢀ1):
2919, 2850, 1427, 812, 755. HRMS (ESI) (m/z): calcd for C14H12NS2 [M+H]+:
258.0406, found: 258.0399.
2-([1,1'-Biphenyl]-4-yl)benzo[d]thiazole (3g). Yellow solid, yield 38 mg (67%), mp
190ꢀ191 ºC. 1H NMR (400 MHz, CDCl3) δ 8.18 (d, J = 8.2 Hz, 2H), 8.10 (d, J = 8.1
Hz, 1H), 7.92 (d, J = 7.9 Hz, 1H), 7.73 (d, J = 8.3 Hz, 2H), 7.66 (d, J = 7.5 Hz, 2H),
13
7.49 (m, 3H), 7.40 (t, J = 7.4 Hz, 2H). C NMR (101 MHz, CDCl3) δ 167.8, 154.1,
143.8, 140.1, 135.0, 132.4, 129.0, 128.0, 128.0, 127.7, 127.1, 126.4, 125.2, 123.2,
121.6. IR (KBr, cmꢀ1): 2920, 2852, 965, 757. HRMS (ESI) (m/z): calcd for C19H14NS
[M+H]+: 288.0841, found: 288.0846.
2-(Furan-2-yl)benzo[d]thiazole (3h). Brown solid, yield 30 mg (74%), mp 101ꢀ102
1
ºC. H NMR (400 MHz, CDCl3) δ 8.04 (d, J = 8.2 Hz, 1H), 7.86 (d, J = 8.0 Hz, 1H),
7.58 (s, 1H), 7.47 (t, J = 7.7 Hz, 1H), 7.35 (t, J = 7.6 Hz, 1H), 7.18 (d, J = 3.3 Hz, 1H),
6.57 (m, 1H); 13C NMR (101 MHz, CDCl3) δ 157.6, 153.7, 148.7, 144.7, 134.3, 126.5,
125.2, 123.1, 121.6, 112.6, 111.5. IR (KBr, cmꢀ1): ν = 3123, 2921, 1500, 746. HRMS
(ESI) calcd for C11H8NOS [M+H]+: 202.0321, found: 202.0313.
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2-(Thiophen-2-yl)benzo[d]thiazole (3i). White solid, yield 33 mg (77%), mp 99ꢀ100
ºC. 1H NMR (400 MHz, CDCl3) δ 8.06 (d, J = 8.2 Hz, 1H), 7.87 (dd, J = 8.0, 0.5 Hz,
1H), 7.68 (dd, J = 3.7, 1.0 Hz, 1H), 7.51 (m, 2H), 7.39 (m, 1H), 7.16 (dd, J = 5.0, 3.8
Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 161.4, 153.7, 137.3, 134.7, 129.3, 128.7,
128.1, 126.5, 125.2, 123.0, 121.5. IR (KBr, cmꢀ1): 3061, 2922, 1421, 908, 706. HRMS
(ESI) (m/z): calcd for C11H8NS2 [M+H]+: 218.0093, found: 218.0099.
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2-(Pyridin-4-yl)benzo[d]thiazole (3j). White solid, yield 31 mg (72%), mp 123ꢀ124
ºC. 1H NMR (400 MHz, CDCl3) δ 8.78 (s, 2H), 8.12 (d, J = 8.1 Hz, 1H), 7.93 (m, 3H),
7.53 (m, 1H), 7.44 (m, 1H). 13C NMR (101 MHz, CDCl3, ppm) δ 165.0, 154.0, 150.7,
140.5, 135.2, 126.8, 126.2, 123.9, 121.9, 121.3. IR (KBr, cmꢀ1): 3658, 3038, 2920,
1408, 758. HRMS (ESI) (m/z): calcd for C12H9N2S [M+H]+: 213.0481, found:
213.0486.
2-(Benzo[d][1,3]dioxol-5-yl)benzo[d]thiazole (3K). Brown solid, yield 42 mg (82%),
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mp 120ꢀ121 ºC. H NMR (400 MHz, CDCl3) δ 8.02 (d, J = 8.2 Hz, 1H), 7.86 (d, J =
8.0 Hz, 1H), 7.59 (m, 2H), 7.46 (t, J = 7.7 Hz, 1H), 7.35 (t, J = 7.6 Hz, 1H), 6.89 (d, J
= 8.0 Hz, 1H), 6.04 (s, 2H). 13C NMR (101 MHz, CDCl3, ppm) δ 167.6, 154.0, 150.2,
148.4, 134.8, 128.0, 126.3, 125.0, 122.9, 122.6, 121.5, 108.6, 107.6, 101.7. IR (KBr,
cmꢀ1): 2917, 1471, 1249, 1034, 755. HRMS (ESI) (m/z): calcd for C14H10NO2S
[M+H]+: 256.0427, found: 256.0429.
2-(Naphthalen-1-yl)benzo[d]thiazole (3l). White solid, yield 39 mg (75%), mp
1
124ꢀ125 ºC. H NMR (400 MHz, CDCl3) δ 9.18 (d, J = 8.3 Hz, 1H), 8.35 (t, J = 6.8
Hz, 1H), 7.98 (m, 4H), 7.71 (dd, J = 10.6, 3.5 Hz, 1H), 7.61 (m, 3H), 7.48 (t, J = 7.6
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Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 167.8, 154.4, 135.6, 134.2, 131.2, 130.9,
130.8, 129.6, 128.6, 127.8, 126.6, 126.4, 126.2, 125.4, 125.1, 123.7, 121.6. IR (KBr,
cmꢀ1): 3054, 1503, 934, 765. HRMS (ESI) (m/z): calcd for C17H12NS [M+H]+:
262.0685, found: 262.0689.
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6-Methyl-2-phenylbenzo[d]thiazole (3m). Yellow solid, yield 33 mg (73%), mp
125ꢀ126 ºC. 1H NMR (400 MHz, CDCl3) δ 8.07 (dd, J = 6.6, 2.9 Hz, 2H), 7.95 (d, J =
8.3 Hz, 1H), 7.67 (s, 1H), 7.47 (dd, J = 4.9, 1.6 Hz, 3H), 7.29 (d, J = 8.3 Hz, 1H),
2.48 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 167.0, 152.2, 135.4, 135.2, 133.7, 130.8,
129.0, 128.0, 127.5, 122.7, 121.4, 21.6. IR (KBr, cmꢀ1): 2919, 1442, 965, 810, 759,
685. HRMS (ESI) (m/z): calcd for C14H12NS [M+H]+: 226.0685, found: 226.0687.
6-Bromo-2-phenylbenzo[d]thiazole (3n). White solid, yield 46 mg (80%), mp
1
156ꢀ157 ºC. H NMR (400 MHz, CDCl3) δ 8.07 (m, 2H), 8.03 (d, J = 1.9 Hz, 1H),
7.92 (d, J = 8.7 Hz, 1H), 7.59 (dd, J = 8.7, 1.9 Hz, 1H), 7.49 (m, 3H). 13C NMR (101
MHz, CDCl3) δ 168.6, 152.9, 136.6, 133.1, 131.4, 129.9, 129.1, 127.6, 124.3, 124.2,
118.8. IR (KBr, cmꢀ1): 3660, 2920, 1475, 964, 817, 757, 681. HRMS (ESI) (m/z):
calcd for C13H9BrNS [M+H]+: 289.9634, found: 289.9641.
2-Phenyl-6-(trifluoromethyl)benzo[d]thiazole (3o). Yellow solid, yield 35 mg
1
(63%), mp 151ꢀ152 ºC. H NMR (400 MHz, CDCl3) δ 8.20 (s, 1H), 8.16 (d, J = 8.6
13
Hz, 1H), 8.11 (dd, J = 7.4, 2.1 Hz, 2H), 7.73 (d, J = 8.6 Hz, 1H), 7.52 (m, 3H). C
NMR (101 MHz, CDCl3) δ 171.2, 156.1, 135.1, 133.1, 131.7, 129.2, 127.8, 127.3 (q,
J = 31.3 Hz), 124.2 (q, J = 270.0 Hz), 123.5, 123.3 (q, J = 3.7 Hz), 119.32 (q, J = 4.2
Hz). IR (KBr, cmꢀ1): 3658, 2921, 1318, 1115, 839. HRMS (ESI) (m/z): calcd for
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C14H9F3NS [M+H]+: 280.0402, found: 280.0410.
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6-Methoxy-2-phenylbenzo[d]thiazole (3p). White solid, yield 37 mg (76%), mp
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116ꢀ117 ºC. H NMR (400 MHz, CDCl3) δ 8.06 (m, 2H), 7.98 (d, J = 8.9 Hz, 1H),
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7.48 (dd, J = 5.3, 1.7 Hz, 3H), 7.34 (d, J = 1.9 Hz, 1H), 7.11 (dd, J = 8.9, 2.5 Hz, 1H),
3.88 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 165.6, 157.8, 148.7, 136.5, 133.8, 130.5,
129.0, 127.3, 123.7, 115.7, 104.2, 55.8. IR (KBr, cmꢀ1): 2930, 1470, 1269, 1023, 823.
HRMS (ESI) (m/z): calcd for C14H12NOS [M+H]+: 242.0634, found: 242.0637.
2-(3,4-Dimethoxyphenyl)-6-fluorobenzo[d]thiazole (3q). Yellow solid, yield 43 mg
(75%), mp 153ꢀ155 ºC. 1H NMR (400 MHz, CDCl3) δ 7.94 (dd, J = 8.9, 4.8 Hz, 1H),
7.65 (d, J = 1.4 Hz, 1H), 7.52 (dd, J = 8.2, 2.0 Hz, 2H), 7.18 (td, J = 8.9, 2.5 Hz, 1H),
13
6.91 (d, J = 8.3 Hz, 1H), 4.00 (s, 3H), 3.94 (s, 3H). C NMR (101 MHz, CDCl3) δ
167.6 (d, J = 3.1 Hz), 160.3 (d, J = 245.4 Hz), 151.7, 150.7 (d, J = 1.4 Hz), 149.4,
135.9 (d, J = 11.3 Hz), 126.4, 123.6 (d, J = 9.3 Hz), 121.1, 114.8 (d, J = 24.6 Hz),
111.1, 109.7, 107.8 (d, J = 26.8 Hz), 56.1, 56.0. IR (KBr, cmꢀ1): 2919, 1449, 1242,
1014, 802. HRMS (ESI) (m/z): calcd for C15H13FNO2S [M+H]+: 290.0646, found:
290.0652.
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2-Benzylbenzo[d]thiazole (4a). Brown oil, yield 30 mg (67%). H NMR (400 MHz,
CDCl3) δ 8.06 (d, J = 8.1 Hz, 1H), 7.80 (d, J = 8.0 Hz, 1H), 7.48 (m, 1H), 7.38 (m,
13
6H), 4.48 (s, 2H). C NMR (101 MHz, CDCl3) δ 171.3, 153.2, 137.2, 135.7, 129.2,
128.9, 127.4, 126.0, 124.9, 122.8, 121.6, 40.6. IR (KBr, cmꢀ1): 3063, 2923, 1648,
1490, 1284, 760, 705. HRMS (ESI) (m/z): calcd for C14H12NS [M+H]+: 226.0685,
found: 226.0676.
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2-(4-Methylbenzyl)benzo[d]thiazole (4b). Brown oil, yield 31 mg (65%). H NMR
(400 MHz, CDCl3) δ 8.06 (d, J = 8.2 Hz, 1H), 7.81 (d, J = 8.0 Hz, 1H), 7.47 (d, J =
7.5 Hz, 1H), 7.35 (d, J = 7.4 Hz, 1H), 7.31 (d, J = 7.9 Hz, 2H), 7.21 (d, J = 7.8 Hz,
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2H), 4.44 (s, 2H), 2.39 (s, 3H). C NMR (101 MHz, CDCl3) δ 171.7, 153.3, 137.0,
135.7, 134.2, 129.6, 129.1, 126.0, 124.8, 122.8, 121.6, 40.3, 21.2. IR (KBr, cmꢀ1):
3023, 2920, 1511, 1436, 756. HRMS (ESI) (m/z): calcd for C15H14NS [M+H]+:
240.0841, found: 240.0846.
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2-(4-Fluorobenzyl)benzo[d]thiazole (4c). Brown oil, yield 29 mg (60%). H NMR
(400 MHz, CDCl3) δ 8.01 (d, J = 8.2 Hz, 1H), 7.80 (d, J = 8.0 Hz, 1H), 7.46 (m, 1H),
7.34 (m, 3H), 7.04 (m, 2H), 4.41 (s, 2H). 13C NMR (101 MHz, CDCl3) δ 171.0, 162.2
(d, J = 246.0 Hz), 153.1, 135.5, 132.9 (d, J = 3.3 Hz), 130.7 (d, J = 8.1 Hz), 126.1,
125.0, 122.8, 121.6, 115.8 (d, J = 21.5 Hz), 39.7. IR (KBr, cmꢀ1): 3061, 2922, 1506,
1225, 830, 758. HRMS (ESI) (m/z): calcd for C14H11FNS [M+H]+: 244.0591, found:
244.0589.
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2-(4-Chlorobenzyl)benzo[d]thiazole (4d). Brown oil, yield 32 mg (61%). H NMR
(400 MHz, CDCl3) δ 8.00 (d, J = 8.1 Hz, 1H), 7.80 (d, J = 7.9 Hz, 1H), 7.45 (d, J =
7.8 Hz, 1H), 7.36 (d, J = 7.6 Hz, 1H), 7.31 (s, 4H), 4.41 (s, 2H). 13C NMR (101 MHz,
CDCl3) δ 170.4, 153.0, 135.6, 135.5, 133.4, 130.5, 129.0, 126.2, 125.0, 122.8, 121.6,
39.8. IR (KBr, cmꢀ1): 3067, 2921, 1491, 1091, 812, 757. HRMS (ESI) (m/z): calcd for
C14H11ClNS [M+H]+: 260.0295, found: 260.0293.
2-(4-Methoxybenzyl)benzo[d]thiazole (4e). Brown oil, yield 34 mg (66%). 1H NMR
(400 MHz, CDCl3) δ 7.98 (d, J = 8.2 Hz, 1H), 7.76 (d, J = 8.0 Hz, 1H), 7.42 (t, J = 7.7
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Hz, 1H), 7.29 (m, 3H), 6.87 (d, J = 8.5 Hz, 2H), 4.36 (s, 2H), 3.77 (s, 3H). C NMR
(101 MHz, CDCl3) δ 172.0, 159.0, 153.4, 135.7, 130.3, 129.3, 126.0, 124.8, 122.8,
121.5, 114.3, 55.3, 39.8. IR (KBr, cmꢀ1): 3063, 2931, 1511, 1249, 761. HRMS (ESI)
(m/z): calcd for C15H14NOS [M+H]+: 256.0791, found: 256.0798.
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2-(2-methoxybenzyl)benzo[d]thiazole (4f). Brown oil, yield 35 mg (69%). H NMR
(400 MHz, CDCl3) δ 7.96 (d, J = 8.2 Hz, 1H), 7.68 (d, J = 8.0 Hz, 1H), 7.36 (t, J = 7.7
Hz, 1H), 7.28 (d, J = 7.4 Hz, 1H), 7.23 (t, J = 7.6 Hz, 2H), 6.89 (t, J = 7.4 Hz, 1H),
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6.83 (d, J = 8.2 Hz, 1H), 4.42 (s, 2H), 3.75 (s, 3H). C NMR (101 MHz, CDCl3) δ
171.8, 157.4, 153.3, 135.8, 130.9, 129.0, 125.8, 125.8, 124.6, 122.65, 121.5, 120.8,
110.8, 55.4, 35.2. IR (KBr, cmꢀ1): 3064, 2938, 1595, 1501, 1247, 756. HRMS (ESI)
(m/z): calcd for C15H14NOS [M+H]+: 256.0791, found: 256.0795.
2-(Naphthalen-2-ylmethyl)benzo[d]thiazole (4g). Brown oil, yield 31 mg (57%). 1H
NMR (400 MHz, CDCl3) δ 8.04 (d, J = 8.2 Hz, 1H), 7.83 (d, J = 7.9 Hz, 4H), 7.78 (d,
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J = 8.0 Hz, 1H), 7.48 (m, 4H), 7.34 (t, J = 7.6 Hz, 1H), 4.61 (s, 2H). C NMR (101
MHz, CDCl3) δ 171.2, 153.3, 135.7, 134.6, 133.6, 132.6, 128.7, 127.9, 127.8, 127.8,
127.2, 126.3, 126.0, 126.0, 124.9, 122.8, 121.6, 40.8. IR (KBr, cmꢀ1): 3689, 2920,
1509, 966, 751. HRMS (ESI) (m/z): calcd for C18H14NS [M+H]+: 276.0841, found:
276.0846.
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2-Benzyl-6-methylbenzo[d]thiazole (4h). Brown oil, yield 31 mg (64%). H NMR
(400 MHz, CDCl3) δ 7.92 (d, J = 8.3 Hz, 1H), 7.60 (s, 1H), 7.38 (m, 4H), 7.33 (d, J =
13
3.2 Hz, 1H), 7.28 (s, 1H), 4.46 (s, 2H), 2.49 (s, 3H). C NMR (101 MHz, CDCl3) δ
170.1, 151.3, 137.3, 135.9, 134.9, 129.2, 128.9, 127.6, 127.3, 122.3, 121.3, 40.6, 21.5.
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IR (KBr, cmꢀ1): 3685, 3054, 2920, 1507, 1228, 1028, 690. HRMS (ESI) (m/z): calcd
for C15H14NS [M+H]+: 240.0841, found: 240.0843.
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2-Benzyl-6-fluorobenzo[d]thiazole (4i). Brown solid, yield 32 mg (66%), mp 57ꢀ58
ºC. 1H NMR (400 MHz, CDCl3) δ 7.95 (dt, J = 8.7, 4.3 Hz, 1H), 7.46 (dd, J = 4.9, 3.0
Hz, 1H), 7.39 (d, J = 4.3 Hz, 4H), 7.33 (m, 1H), 7.20 (m, 1H), 4.43 (d, J = 3.6 Hz,
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2H). C NMR (101 MHz, CDCl3) δ 170.9 (d, J = 3.2 Hz), 160.3 (d, J = 245.0 Hz),
149.9, 137.0, 136.6 (d, J = 11.3 Hz), 129.2, 129.0, 127.5, 123.7 (d, J = 9.4 Hz), 114.6
(d, J = 24.7 Hz), 107.8 (d, J = 26.7 Hz), 40.6. IR (KBr, cmꢀ1): 3067, 2922, 1453, 1249,
817, 701. HRMS (ESI) (m/z): calcd for C14H11FNS [M+H]+: 244.0591, found:
244.0597.
2-Benzyl-6-(trifluoromethyl)benzo[d]thiazole (4j). Brown oil, yield 41 mg (70%).
1H NMR (400 MHz, CDCl3) δ 8.09 (d, J = 8.5 Hz, 2H), 7.69 (m, 1H), 7.38 (d, J = 4.4
Hz, 4H), 7.33 (m, 1H), 4.47 (s, 2H). 13C NMR (101 MHz, CDCl3) δ 174.7, 155.3,
136.6, 135.8, 129.2, 129.0, 127.6, 127.1 (q, J = 32.0 Hz), 124.2 (q, J = 273.4 Hz),
123.2, 123.0 (q, J = 3.4 Hz), 119.2 (q, J = 4.2 Hz), 40.8. IR (KBr, cmꢀ1): 3029, 2924,
1320, 1124, 650. HRMS (ESI) (m/z): calcd for C15H11F3NS [M+H]+: 294.0559, found:
294.0552.
2-Benzyl-5-methylbenzo[d]thiazole (4k). Yellow solid, yield 33 mg (68%), mp
1
79ꢀ81 ºC. H NMR (400 MHz, CDCl3) δ 7.79 (s, 1H), 7.62 (d, J = 8.2 Hz, 1H), 7.31
(m, 5H), 7.13 (m, 1H), 4.40 (s, 2H), 2.46 (s, 3H). 13C NMR (101 MHz, CDCl3) δ
171.2, 153.7, 137.3, 136.0, 132.7, 129.2, 128.9, 127.3, 126.4, 122.9, 121.0, 40.7, 21.5.
IR (KBr, cmꢀ1): 3060, 2921, 1647, 1486, 1283, 863, 703. HRMS (ESI) (m/z): calcd
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ASSOCIATED CONTENT
Supporting Information
NMR spectra of the products. The Supporting Information is available free of charge
via the Internet at http://pubs.acs.org.
ACKNOWLEDGMENTS
This work was supported by the National Program on Key Research Project
(2016YFA0602900), the National Natural Science Foundation of China
(21420102003 and 21672072), and the Fundamental Research Funds for the Central
Universities (2015ZY001 and 2017ZD062) for financial support.
REFERENCES
(1) For selected reviews, see: (a) Xia, Y.; Wang, J. Chem. Soc. Rev. 2017, 46,
2306ꢀ2362. (b) Dong, X.; Liu, Q.; Dong, Y.; Liu, H. Chem. Eur. J. 2017, 23,
2481ꢀ2511. (c) Zhu, X.; Chiba, S. Chem. Soc. Rev. 2016, 45, 4504ꢀ4523. (d) Liu, J.;
Chen, G.; Tan, Z. Adv. Synth. Catal. 2016, 358, 1174ꢀ1194. (e) Wu, W.; Jiang, H. Acc.
Chem. Res. 2014, 47, 2483ꢀ2504. (f) Sambiagio, C.; Marsden, S. P.; Blacker, A. J.;
McGowan, P. C. Chem. Soc. Rev. 2014, 43, 3525ꢀ3550. (g) Zeng, X. Chem. Rev. 2013,
113, 6864ꢀ6900.
(2) (a) Yang, J.ꢀM.; Li, Z.ꢀQ.; Li, M.ꢀL.; He, Q.; Zhu, S.ꢀF.; Zhou, Q.ꢀL. J. Am.
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Page 24 of 26
1
2
3
4
5
6
7
8
9
Chem. Soc. 2017, 139, 3784ꢀ3789. (b) Chen, D.; Zhu, D.ꢀX.; Xu, M.ꢀH. J. Am. Chem.
Soc. 2016, 138, 1498ꢀ1501. (c) Yu, Z.; Ma, B.; Chen, M.; Wu, H.ꢀH.; Liu, L.; Zhang, J.
J. Am. Chem. Soc. 2014, 136, 6904ꢀ6907. (d) Gillingham, D.; Fei, N. Chem. Soc. Rev.
2013, 42, 4918ꢀ4931. (e) Zhao, X.; Zhang, Y.; Wang, J. Chem. Commun. 2012, 48,
10162ꢀ10173.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(3) (a) Huang, F.; Liu, Z.; Wang, Q.; Lou, J.; Yu, Z. Org. Lett. 2017, 19, 3660ꢀ3663.
(b) Hyster, T. K.; Ruhl, K. E.; Rovis, T. J. Am. Chem. Soc. 2013, 135, 5364ꢀ5367.
(4) (a) Huang, Y.; Li, X.; Wang, X.; Yu, Y.; Zheng, J.; Wu, W.; Jiang, H. Chem. Sci.
2017, 8, 7047ꢀ7051. (b) Hari, D. P.; Waser, J. J. Am. Chem. Soc. 2016, 138,
2190ꢀ2193. (c) Chen, G.; Song, J.; Yu, Y.; Luo, X.; Li, C.; Huang, X. Chem. Sci. 2016,
7, 1786ꢀ1790. (d) Qin, G.; Li, L.; Li, J.; Huang, H.; J. Am. Chem. Soc. 2015, 137,
12490ꢀ12493.
(5) (a) Chen, D.ꢀF.; Zhao, F.; Hu, Y.; Gong, L.ꢀZ. Angew. Chem. Int. Ed. 2014, 53,
10763ꢀ10767. (b) Guo, X.; Hu, W. Acc. Chem. Res. 2013, 46, 2427–2440. (c) Li, W.;
Liu, X.; Tan, F.; Hao, X.; Zheng, J.; Lin, L.; Feng, X. Angew. Chem. Int. Ed. 2013, 52,
10883ꢀ10886. (d) Qiu, H.; Li, M.; Jiang, L.ꢀQ.; Lv, F.ꢀP.; Zan, L.; Zhai, C.ꢀW.; Doyle,
M. P.; Hu, W.ꢀH. Nat. Chem. 2012, 4, 733ꢀ738. (e) Zhou, C.ꢀY.; Wang, J.ꢀC.; Wei, J.;
Xu, Z.ꢀJ.; Guo, Z.; Low, K.ꢀH.; Che, C.ꢀM. Angew. Chem. Int. Ed. 2012, 51,
11376ꢀ11380.
(6) (a) Zhu, C.; Zhu, R.; Chen, P.; Chen, F.; Wu, W.; Jiang, H. Adv. Synth. Catal.
2017, 359, 3154ꢀ3159. (b) Peng, J.; Gao, Y.; Zhu, C.; Liu, B.; Gao, Y.; Hu, M.; Wu,
W.; Jiang, H. J. Org. Chem. 2017, 82, 3581ꢀ3588. (c) Huang, Y.; Yu, Y.; Zhu, Z.; Zhu,
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The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
C.; Cen, J.; Li, X.; Wu, W.; Jiang, H. J. Org. Chem. 2017, 82, 7621ꢀ7627. (d) Huang,
Y.; Li, X.; Yu, Y.; Zhu, C.; Wu, W.; Jiang, H. J. Org. Chem. 2016, 81, 5014ꢀ5020. (e)
Li, X.; Liu, X.; Chen, H.; Wu, W.; Qi, C.; Jiang, H. Angew. Chem. 2014, 53,
14485ꢀ14489.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(7) (a) Dev, D.; Chandra, J.; Palakurthy, N. B.; Thalluri, K.; Kalita, T.; Mandal, B.;
Asian J. Org. Chem. 2016, 5, 663ꢀ675. (b) Sun, Y.; Jiang, H.; Wu, W.; Zeng, W.; Wu,
X. Org. Lett. 2013, 15, 1598ꢀ1601. (c) Liao, Y.; Qi, H.; Chen, S.; Jiang, P.; Zhou, W.;
Deng, G.ꢀJ. Org. Lett. 2012, 14, 6004ꢀ6007.
(8) (a) Zhu, X.; Yang, Y.; Xiao, G.; Song, J.; Liang, Y.; Deng, G. Chem. Commun.
2017, 53, 11917ꢀ1920. (b) Zhang, G.; Liu, C.; Yi, H.; Meng, Q.; Bian, C.; Chen, H.;
Jian, J.ꢀX.; Wu, L.ꢀZ.; Lei, A. J. Am. Chem. Soc. 2015, 137, 9273ꢀ9280. (c) Joyce, L.
L.; Batey, R. A.; Org. Lett. 2009, 11, 2792ꢀ2795.
(9) (a) Urzúa, J. I.; Contreras, R.; Salas, C. O.; Tapia, R. A. RSC Adv. 2016, 6,
82401ꢀ82408. (b) Cheng, Y.; Peng, Q.; Fan, W.; Li, P. J. Org. Chem. 2014, 79,
5812ꢀ5819. (c) Feng, E.; Huang, H.; Zhou, Y.; Ye, D.; Jiang, H.; Liu, H. J. Comb.
Chem. 2010, 12, 422ꢀ429.
(10) (a) Nguyen, L. A.; Ngo, Q. A.; Retailleau, P.; Nguyen, T. B. Green Chem. 2017,
19, 4289ꢀ4293. (b) Wang, X.; Miao, D.; Li, X.; Hu, R.; Yang, Z.; Gu, R.; Han, S.
Tetrahedron 2017, 73, 5194ꢀ5199. (c) Nguyen, T. B.; Ermolenko, L.; Retailleau, P.;
AlꢀMourabit, A. Angew. Chem. Int. Ed. 2014, 53, 13808ꢀ13812. (d) Zhang, X.; Zeng,
W.; Yang, Y.; Huang, H.; Liang, Y. Org. Lett. 2014, 16, 876ꢀ879. (e) Tong, Y.; Pan, Q.;
Jiang, Z.; Miao, D.; Shi, X.; Han, S. Tetrahedron Lett. 2014, 55, 5499ꢀ5503. (f) Ma,
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1
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3
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5
6
D.; Xie, S.; Xue, P.; Zhang, X.; Dong, J.; Jiang, Y. Angew. Chem. 2009, 48,
4222ꢀ4225.
7
8
9
(11) Mao, S.; Gao, Y.ꢀR.; Zhu, X.ꢀQ.; Guo, D.ꢀD.; Wang, Y.ꢀQ.; Org. Lett. 2015, 17,
1692ꢀ1695.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
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40
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42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(12) (a) Nguyen, T. B.; Retailleau, P. Org. Lett. 2017, 19, 4858ꢀ4860. (b) Zhu, X.;
Yang, Y.; Xiao, G.; Song, J.; Liang Y.; Deng, G. Chem. Commun. 2017, 53,
11917ꢀ11920. (c) Nguyen, T. B.; Ermolenko, L.; AlꢀMourabit, A. Org. Lett. 2012, 14,
4274–4277.
(13) Che, X.; Jiang, J.; Xiao, F.; Huang, H.; Deng, G.ꢀJ. Org. Lett. 2017, 19,
4576ꢀ4579.
(14) (a) Guntreddi, T.; Vanjari, R.; Singh, K. N. Org. Lett. 2014, 16, 3624ꢀ3627. (b)
Aly, M. F.; Grigg, R. Tetrahedron 1988, 44, 7271ꢀ7282.
(15) (a) Wei, J.; Li, Y.; Jiang, X. Org. Lett. 2016, 18, 340ꢀ343. (b) Xu, H.; Deng, H.;
Li, Z.; Xiang, H.; Zhou, X. Eur. J. Org. Chem. 2013, 7054ꢀ7057.
(16) (a) Yan, K.; Yang, D.; Wei, W.; Lu, S.; Li, G.; Zhao, C.; Zhang, Q.; Wang, H.
Org. Chem. Front. 2016, 3, 66ꢀ70. (b) Sun, L.ꢀL.; Deng, C.ꢀL.; Tang, R.ꢀY.; Zhang,
X.ꢀG. J. Org. Chem. 2011, 76, 7546ꢀ7550.
(17) Priebbenow, D. L.; Bolm, C. Chem. Soc. Rev. 2013, 42, 7870ꢀ7880.
(18) (a) Åkerbladh, L.; Odell, L. R. J. Org. Chem. 2016, 81, 2966ꢀ2973. (b) Ahmed,
A.; Dhara, S.; Singha, R.; Nuree, Y.; Sarkar, P.; Ray, J. K. RSC Adv. 2014, 4,
53137ꢀ53141. (c) Kajigaeshi, S.; Kakinami, T.; Yamasaki, H.; Fujisaki, S.; Okamoto,
T. Bull. Chem. Soc. Jpn. 1988, 61, 600ꢀ602.
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