Pd(PPh3)4-catalyzed direct ortho-fluorination of 2-arylbenzothiazoles with an electrophilic fluoride N-fluorobenzenesulfonimide (NFSI)

Article abstract of DOI:10.1016/j.tet.2013.11.034

An efficient protocol was developed for regio-selective Pd-catalyzed direct ortho-fluorination of 2-arylbenzo[d]thiazoles using N-fluorobenzenesulfonimide (NFSI) as the F⁺ source, and l-proline as the crucial promoter. The present method offered a practical route to synthesize valuable fluorinated products, which are of potential importance in the pharmaceutical and agrochemical industries.

Full text of DOI:10.1016/j.tet.2013.11.034

Tetrahedron 70 (2014) 409e416
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Tetrahedron
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Pd(PPh3)4-catalyzed direct ortho-fluorination of
2-arylbenzothiazoles with an electrophilic fluoride
N-fluorobenzenesulfonimide (NFSI)
,
,
a
Qiuping Ding a b, Changqing Ye b, Shouzhi Pu a , Banpeng Cao
*
a Jiangxi Key Laboratory of Organic Chemistry, Jiangxi Science & Technology, Normal University, Nanchang, Jiangxi 330013, PR China
b Key Laboratory of Functional Small Organic Molecules, Ministry of Education and College of Chemistry & Chemical Engineering, Jiangxi Normal
University, Nanchang, Jiangxi 330022, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient protocol was developed for regio-selective Pd-catalyzed direct ortho-fluorination of 2-
arylbenzo[d]thiazoles using N-fluorobenzenesulfonimide (NFSI) as the Fþ source, and
L-proline as the
Received 21 September 2013
Received in revised form 8 November 2013
Accepted 14 November 2013
Available online 20 November 2013
crucial promoter. The present method offered a practical route to synthesize valuable fluorinated
products, which are of potential importance in the pharmaceutical and agrochemical industries.
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
2-Arylbenzo[d]thiazole
Fluorination
N-Fluorobenzenesulfonimide
L-Proline
1. Introduction
are only a few protocols have been reported to access fluoro-
substituted-1,3-benzo[d]thiazoles.5 In addition, no examples have
2-Arylbenzo[d]thiazoles as privileged motifs are present in
many natural products and pharmaceuticals that exhibit remark-
able biological and therapeutic activities, such as antitumor, anti-
viral, and antimicrobial activities.1 Substitution of hydrogen with
fluorine can dramatically improve the physical, chemical, and bi-
ological activity of organic molecules. Recently, there are more than
20% newly registered pharmaceuticals and 40% agrochemicals
containing one or more fluorine atoms. In particular, fluoro-
substituted-1,3-benzo[d]thiazoles are versatile building blocks
found in a broad range of pharmaceutically active molecules.2 For
instance, benzo[d]thiazoles A and B are found to be potent S1P1
been reported for the synthesis of these important compounds via
direct CeH bond fluorination of 2-arylbenzo[d]thiazoles. It seems
to be a more practical approach to obtain the highly desired fluoro-
substituted-1,3-benzo[d]thiazoles if these functionalized 2-
arylbenzo[d]thiazoles can undergo directed CeH fluorination.
Recently, transition metal-catalyzed CeF bond formation has
become an attractive approach to fluorine containing pharmaceu-
ticals and agrochemicals. Although much remarkable achievements
have been made in CeF bond formation in the last few years,6
development of more efficient methods via ligand-directed CeH
bond activation/fluorination for the synthesis of fluorine containing
arenes is still full of challenge.7 In 2006, Sanford group reported the
pioneering work of pyridine-directed Pd(II)-catalyzed CeH bond
fluorination using electrophilic fluorinating reagent (N-fluoro-
2,4,6-trimethylpyridinium tetrafluoroborate) as Fþ source upon
microwave irradiation.7a Subsequently, Yu et al. reported two
Pd(II)-catalyzed ortho-fluorinations of CeH bond using N-fluoro-
2,4,6-trimethylpyridinium triflate as the Fþ source and NMP as
agonist (EC50¼0.042 and 0.017
m
M, respectively, Fig. 1).2a,b Benzo[d]
thiazole C could potently inhibit the growth of trypanosomes (Fig.
1).2c Benzo[d]thiazole D has an excellent inhibitory effect on the
inflammatory cytokine production (Fig. 1).2d In addition, fluoro-
substituted-1,3-benzo[d]thiazoles have been used as phosphores-
cent material.3 Practical methods for the synthesis of functionalized
2-arylbenzo[d]thiazoles are well-documented.4 In contrast, there
a
crucial promoter directed by triflamide and N-arylamide
groups.7b,c Very recently, when we were preparing this manuscript,
Xu et al. reported the Pd(OAc)2-catalyzed regio-selective aromatic
CeH bond fluorination of quinoxaline, pyrazole, benzo[d]oxazole,
and pyrazine derivatives promoted by trifluoroacetic acid (TFA).7d
* Corresponding author. Tel./fax: þ86 791 83831996; e-mail address: pushouzhi@
tsinghua.org.cn (S. Pu).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.11.034

410
Q. Ding et al. / Tetrahedron 70 (2014) 409e416
Fig. 1. Potential therapeutic/diagnostic fluoro-substituted-1,3-benzothiazoles.
We and others have previously reported the Pd-catalyzed ortho-
functionalization of 2-arylbenzo[d]thiazole to construct various
CeC8 and CeO9 bonds from CeH bond. Therefore, benzo[d]thiazole
might be a feasible directing group for CeH bond fluorination.
Herein, we reported the simple Pd-catalyzed direct CeH bond
fluorination to synthesize fluoro-substituted-1,3-benzothiazoles
Table 1
Optimization of the reaction conditionsa
using an electrophilic fluoride (NFSI) promoted by L-proline.
Entry
Solvent
[Pd] (x mol %)
L-proline (y mol %)
Yieldb (%)
1
2
3
4
5
6
7
8
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
PhCl
CH3CN
Dioxane
DMF
DMA
DMSO
Toluene
DCM
Cyclohexane
Pd(OAc)2 (30)
PdCl2 (30)
20
20
20
20
20
20
0
33
2. Results and discussions
Trace
N.R.
Trace
20
47
16
20
35
54
30
10
54
54
24
22
33
16
25
Pd(PhCN)2Cl2 (30)
Pd(PPh3)2Cl2 (30)
Pd2(dba)3 (30)
Pd(PPh3)4 (30)
Pd(PPh3)4 (30)
Pd(PPh3)4 (30)
Pd(PPh3)4 (30)
Pd(PPh3)4 (30)
Pd(PPh3)4 (30)
Pd(PPh3)4 (30)
Pd(PPh3)4 (20)
Pd(PPh3)4 (15)
Pd(PPh3)4 (10)
Pd(PPh3)4 (15)
Pd(PPh3)4 (15)
Pd(PPh3)4 (15)
Pd(PPh3)4 (15)
Pd(PPh3)4 (15)
Pd(PPh3)4 (15)
Pd(PPh3)4 (15)
Pd(PPh3)4 (15)
Pd(PPh3)4 (15)
Based on the Yu’s work for the CeH bond fluorination of
triflamide-protected benzylamines, we started our research by
treating the model substrate 2-(o-tolyl)benzo[d]thiazole 1a with
NFSI (2.0 equiv) under the NMP/DCE reaction system [NMP
(0.5 equiv), DCE (2 mL), Pd(OAc)2 (10 mol %), 120 ꢀC]. However, no
desired product was observed under the conditions. In view of the
structural similarities between NMP and proline, we retried the
reaction in the presence of L-proline (20 mol %) instead of NMP. To
our delight, the monofluorinated product 2a was obtained in 25%
yield, with a trace amount of acetoxylated by-product, which in-
dicated that L-proline as an additive can promote the fluorination
reaction. Then, we investigated the effects of fluorinating agents,
and several commonly used fluorinating agents were utilized in the
present work. Unfortunately, when the substrate 1a was treated
with N-fluoro-2,4,6-trimethylpyridiniums (F1 and F2) or Select-
fluor F3, no fluorinated product was observed (Scheme 1). How-
ever, the desired fluorinated product 2a was obtained in 33%
isolated yield by using NFSI as the fluorine source catalyzed by
Pd(OAc)2 (30 mol %) (Scheme 1). Subsequently, various palladium
catalysts including Pd(II) and Pd(0), such as PdCl2, Pd(PhCN)2Cl2,
Pd(PPh3)2Cl2, Pd2(dba)3, and Pd(PPh3)4 were also screened, and the
results indicated that Pd(PPh3)4 was the best efficient catalyst
5
9
10
40
50
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
100
40
40
40
40
40
40
40
40
40
40
40
40
19
N.R.
48
53
74
a
Reaction conditions: 0.3 mmol of 2-arylbenzothiazole 1a, NFSI (3.0 equiv), 2 mL
of solvent, 5 h.
b
Isolated yield based on 1a.
(Table 1, entries 2e6). The control experiment also showed that
proline was important for the reaction to proceed (Table 1, entry 7).
The reaction was also sensitive to the loading of -proline, with
0.4 equiv being optimal (Table 1, entries 8e12). The use of 0.05 or
1.0 equiv of -proline reduced the yield to 20% and 10%, respectively.
L-
L
L
The reaction still showed high efficiency when the loading of
Pd(PPh3)4 was decreased to 15 mol % (Table 1, entry 14). Finally,
a range of solvents were screened, which identified that reactions
in polar and aprotic solvents, such as DMF, DMA, or DMSO occurred
in low yields (Table 1, entries 16e21), while reaction in the non-
polar solvent cyclohexane gave the desired product in good yield
(Table 1, entry 24).
Scheme 1. Palladium-catalyzed fluorination of 2-(o-tolyl)benzo[d]thiazole with Fþ
With the optimized reaction conditions in hand, we next sur-
veyed the substrate scope of benzothiazole-directed ortho-CeH
bond fluorination. As summarized in Table 2, the protocol can be
utilized for the synthesis of diverse fluoro-substituted-1,3-
benzothiazoles and is tolerant of many common functional
groups, including halogen (F, Cl), methyl, and methyl ether. Sub-
strates containing electron-donating or moderate electron-
source.
withdrawing substituents on the ortho-position of 2-phenyl ring
undergo the fluorination process smoothly under standard condi-
tions to afford the corresponding products in good yields (Table 2,
entries 1e4). For instance, substrates 1b (R2¼o-OCH3) and 1d

Q. Ding et al. / Tetrahedron 70 (2014) 409e416
411
Table 2
Substrate scope of Pd-catalyzed CeH bond fluorinationa
Entry
1
Substrate 1
Product 2
Yieldb (%)
74
1a
2a
2
68
1b
2b
3
68
1c
1d
1e
2c
2d
2e
4
69
5
Trace
6
54
1f
2f
7
71
1g
2g
8
82
1h
1i
2h
2i
9
35
10
63
1j
2j
11
12
68
65
1k
1l
2k
2l
(continued on next page)

412
Q. Ding et al. / Tetrahedron 70 (2014) 409e416
Table 2 (continued )
Entry
Substrate 1
Product 2
Yieldb (%)
13
14
15
16
17
73
1m
2m
60/17c
44/16c
47/15c
63/tracec
1n
2n
1o
1p
2o
2p
1q
2q
18
34/8c
1r
2r
19
20
79/4 (35/40c)
1s
2s
56/33c
1t
2t
21
22
53/37c
Trace
1u
2u
1v
2v
a
Reaction conditions: 0.3 mmol of 2-arylbenzothiazole 1, Pd(PPh3)4 (15 mol %), NFSI (3.0 equiv, unless otherwise noted), 2 mL of cyclohexane, 120 ꢀC, 5 h.
Isolated yield of 2 based on 2-arylbenzothiazole 1.
Isolated yield of difluorinated product 3 (4.0 equiv of NFSI was used).
b
c
(R2¼o-F) gave the fluorinated products 2b and 2d in 68% and 69%
meta-position of 2-phenyl ring were examined under standard
conditions. The results showed that monofluorinated products
2ner were predominant at the less sterically hindered position in
moderate yields with a small amount of difluorinated products
(Table 2, entries 14e18). For example, a mixture of monofluorinated
product 2n (60%) and difluorinated product 3n (17%) is obtained,
when the fluorination reaction of 2-(m-tolyl)benzo[d]thiazole 1n
was performed using 4.0 equiv of NFSI (Table 2, entry 14). To those
substrates without substituents at the 2-phenyl ring can also un-
dergo the fluorination reaction efficiently to give a mixture of
mono- and difluorinated products. The fluorination of 2-
phenylbenzo[d]thiazole 1s indicated that monofluorinated prod-
uct 2s is obtained predominantly in 79% yield with 4% difluorinated
product 3s when 3.0 equiv of NFSI was utilized, while the similar
yields, respectively (Table 2, entries 2 and 4). Unfortunately, only
a trace amount of desired product was detected for the reaction of
substrate 1e bearing a strong electron-withdrawing substituent
(R2¼o-NO2) (Table 2, entry 5). Then, effects of substituents on
the benzothiazole side were investigated under the present
method. Generally, the benzothiazole parts with electron-
withdrawing groups were relatively more favorable in this
transformation (Table 2, entries 7,8, and 10e13 vs entries 6 and 9).
Substrate 1f bearing a methyl group afforded the product 2f in 54%
yield (Table 2, entry 6). Substrates 1g, 1h, and 1jem bearing
electron-withdrawing halogen gave the desired products in yields
ranging from 63% to 82% (Table 2, entries 7,8 and 10e13). Fur-
thermore, 2-arylbenzo[d]thiazoles 1ner with substituents at the

Q. Ding et al. / Tetrahedron 70 (2014) 409e416
413
amount of mono- and difluorinated products are obtained when
(400 MHz, CDCl3)
d
2.32 (s, 3H), 6.96 (t, J¼8.8 Hz, 1H), 7.04 (d,
4.0 equiv of NFSI was used (Table 2, entry 19). Unfortunately, 2-
position heterocyclic ring substituted benzo[d]thiazole 1v failed
to afford the corresponding fluorinated product 2v (Table 2, entry
22).
J¼7.6 Hz, 1H), 7.23e7.30 (m, 1H), 7.37 (t, J¼7.6 Hz, 1H), 7.44 (t,
J¼7.6 Hz, 1H), 7.87 (d, J¼8.0 Hz, 1H), 8.06 (d, J¼8.4 Hz, 1H); 13C NMR
2
(100 MHz, CDCl3)
d
19.3, 112.1 (d, JCeF¼22 Hz), 120.4, 120.6 (d,
2JCeF¼15 Hz), 122.5, 124.4, 125.0, 125.2, 130.0 (d, 3JCeF¼9 Hz), 135.1,
1
Though the detailed role of
L-proline remains ambiguous,
139.3, 152.1, 159.5 (d, JCeF¼248 Hz), 160.2; 19F NMR (376 MHz,
a plausible reaction mechanism has been proposed in Scheme 2. A
Pd(II/IV) catalytic cycle (path a) was proposed based on the pre-
vious literature involving high-valent palladium fluoride.7b,10 The
reaction is initiated through oxidation of Pd(0) by NFSI to give Pd(II)
fluoride complex I,10d,f and subsequent CeH activation of 1 offers
intermediate II, and then oxidation addition of intermediate II by
NFSI yields the Pd(IV) intermediate III promoted by catalytic
CDCl3)
d
ꢁ111.84; HRMS-ESI (m/z): calcd for C14H11FNS (MþH):
244.0596, found 244.0591.
3.1.2. 2-(2-Fluoro-6-methoxyphenyl)benzo[d]thiazole 2b. Isolated
as a yellow oil (52.8 mg, 68% yield); 1H NMR (400 MHz, CDCl3)
d
3.89 (s, 3H), 6.82e6.89 (m, 2H), 7.36e7.43 (m, 2H), 7.51 (t,
J¼7.6 Hz, 1H), 7.93 (d, J¼7.6 Hz, 1H), 8.16 (d, J¼8.0 Hz, 1H); 13C NMR
2
amount of
L-proline, which undergoes reductive elimination to
(100 MHz, CDCl3)
d
56.4, 107.0, 108.7 (d, JCeF¼25 Hz), 112.0 (d,
generate the fluorination product 2. Another possible pathway for
this transformation is the reductive elimination of intermediate II
to give product 2 and Pd(0), which involving a Pd(0)/Pd(II) mech-
anism (path b).
2JCeF¼15 Hz), 121.2, 123.6, 125.2, 125.9, 131.8 (d, 3JCeF¼11 Hz), 136.1,
153.0, 158.6, 158.7, 161.0 (d, JCeF¼251 Hz); 19F NMR (376 MHz,
1
CDCl3)
d
ꢁ110.99; HRMS-ESI (m/z): calcd for C14H11FNOS (MþH):
260.0545, found 260.0540.
3.1.3. 2-(2-Chloro-6-fluorophenyl)benzo[d]thiazole 2c.5c Isolated as
a yellow oil (53.6 mg, 68%); 1H NMR (400 MHz, CDCl3)
d 7.16 (t,
J¼8.4 Hz, 1H), 7.35 (d, J¼7.6 Hz, 2H), 7.41 (t, J¼7.2 Hz, 1H), 7.47 (t,
J¼8.0 Hz, 1H), 7.55 (t, J¼7.6 Hz, 1H), 7.97 (d, J¼8.0 Hz, 1H), 8.18 (d,
J¼8.0 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d
114.6 (d, 2JCeF¼22 Hz),
2
121.6, 122.1 (d, JCeF¼18 Hz), 123.9, 125.8, 125.9, 126.3, 131.9 (d,
3JCeF¼9 Hz), 135.0, 136.3, 153.1, 158.5, 160.9 (d, 1JCeF¼252 Hz); 19F
NMR (376 MHz, CDCl3)
d
ꢁ109.12; HRMS-ESI (m/z): calcd for
C13H8ClFNS (MþH): 264.0050, found 264.0045.
3.1.4. 2-(2,6-Difluorophenyl)benzo[d]thiazole 2d. Isolated as a yel-
low oil (51.1 mg, 69%); 1H NMR (400 MHz, CDCl3)
7.06 (t, J¼8.4 Hz,
d
2H), 7.39e7.46 (m, 2H), 7.53 (t, J¼8.0 Hz, 1H), 7.95 (d, J¼7.6 Hz, 1H),
8.19 (d, J¼8.0 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d 112.1 (t,
2JCeF¼16 Hz), 112.2 (d, 2JCeF¼26 Hz), 121.3, 123.9, 125.7, 126.3, 131.8
2
3
3
(t, JCeF¼10 Hz), 135.7 (t, JCeF¼2 Hz), 153.0, 155.8 (t, JCeF¼4 Hz),
160.5 (dd, JCeF¼6, 254 Hz); 19F NMR (376 MHz, CDCl3)
d
ꢁ109.56;
HRMS-ESI (m/z): calcd for C13H8F2NS (MþH): 248.0346, found
248.0341.
Scheme 2. Proposed mechanism.
3.1.5. 2-(2-Chloro-6-fluorophenyl)-6-methylbenzo[d]thiazole
2f. Isolated as a yellow oil (44.9 mg, 54% yield); 1H NMR
In summary, we have developed a regio-selective Pd-catalyzed
(400 MHz, CDCl3)
d
2.53 (s, 3H), 7.15 (t, J¼8.4 Hz, 1H), 7.34e7.42
direct ortho-fluorination of 2-arylbenzo[d]thiazoles using NFSI as
(m, 3H), 7.76 (s, 1H), 8.05 (d, J¼8.0 Hz, 1H); 13C NMR (100 MHz,
the Fþ source, and
L-proline as the crucial promoter. The reaction
2
2
CDCl3)
d
21.6, 114.5 (d, JCeF¼22 Hz), 121.1, 122.3 (d, JCeF¼18 Hz),
tolerated a range of different substrates with a variety of functional
groups. The present protocol offered an efficient route to synthesize
valuable fluorinated products, which are of potential importance in
the pharmaceutical and agrochemical industries. Further research
will focus on the mechanistic studies and synthetic applications of
the present transformations.
3
123.4, 125.8, 127.9, 131.7 (d, JCeF¼9 Hz), 135.1, 136.0, 136.6, 151.3,
157.3, 160.9 (d, JCeF¼252 Hz); 19F NMR (376 MHz, CDCl3)
1
d
ꢁ109.15; HRMS-ESI (m/z): calcd for C14H10ClFNS (MþH):
278.0207, found 278.0201.
3.1.6. 6-Chloro-2-(2-chloro-6-fluorophenyl)benzo[d]thiazole
2g. Isolated as a colorless solid (63.0 mg, 71% yield); mp: 80e81 ꢀC.
3. Experimental section
1H NMR (400 MHz, CDCl3)
d
7.16 (t, J¼8.4 Hz, 1H), 7.35 (d, J¼8.0 Hz,
1H), 7.40e7.46 (m, 1H), 7.51 (d, J¼8.0 Hz, 1H), 7.94 (s, 1H), 8.08 (d,
3.1. General experimental procedures and characterizations
J¼8.8 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d
114.6 (d, 2JCeF¼22 Hz),
2
121.1, 121.7 (d, JCeF¼17 Hz), 124.7, 125.9, 127.2, 131.9, 132.0 (d,
2-Arylbenzo[d]thiazole (0.3 mmol), NFSI (3 or
4 equiv),
3JCeF¼9 Hz), 135.0, 137.5, 151.6, 158.9, 160.8 (d, 1JCeF¼252 Hz); 19F
Pd(PPh3)4 (15 mol %), -proline (40 mol %), cyclohexane (2 mL) were
L
NMR (376 MHz, CDCl3)
d
ꢁ109.02; HRMS-ESI (m/z): calcd for
added in a 25 mL sealed tube with a Teflon-lined cap. The mixture
was heated at 120 ꢀC for 5 h. After being cooled to room temper-
ature, the volatiles were removed under reduced pressure, and the
residue was purified by a flash column chromatography on silica gel
using petroleum ether/ethyl acetate as eluent to give the corre-
sponding pure coupling product 2 and 3.
C13H7Cl2FNS (MþH): 297.9660, found 297.9655.
3.1.7. 2-(2-Chloro-6-fluorophenyl)-6-fluorobenzo[d]thiazole
2h. Isolated as colorless solid (69.1 mg, 82% yield), mp:
a
120e121 ꢀC; 1H NMR (400 MHz, CDCl3)
d
7.16 (t, J¼8.4 Hz, 1H), 7.29
(d, J¼8.8 Hz, 1H), 7.36 (d, J¼8.4 Hz, 1H), 7.40e7.46 (m, 1H), 7.65 (d,
J¼8.0 Hz, 1H), 8.10e8.14 (m, 1H); 13C NMR (100 MHz, CDCl3)
d 107.6
3.1.1. 2-(2-Fluoro-6-methylphenyl)benzo[d]thiazole 2a. Isolated as
a yellow solid (53.9 mg, 74% yield), mp: 52e53 ꢀC; 1H NMR
(d, 2JCeF¼27 Hz), 114.6 (d, 2JCeF¼22 Hz), 115.2 (d, 2JCeF¼25 Hz), 121.7
(d, 2JCeF¼17 Hz), 125.0 (d, 3JCeF¼9 Hz), 125.9, 132.0 (d, 3JCeF¼10 Hz),

414
Q. Ding et al. / Tetrahedron 70 (2014) 409e416
135.0,137.4 (d, 3JCeF¼11 Hz), 158.2,160.8 (d, 1JCeF¼245 Hz), 160.9 (d,
(376 MHz, CDCl3)
(MþH): 244.0596, found 244.0591.
d
ꢁ116.92; HRMS-ESI (m/z): calcd for C14H1FNS
1JCeF¼253 Hz); 19F NMR (376 MHz, CDCl3)
d
ꢁ109.11, ꢁ114.77;
HRMS-ESI (m/z): calcd for C13H7ClF2NS (MþH): 281.9956, found
281.9950.
3.1.14. 2-(2,6-Difluoro-3-methylphenyl)benzo[d]thiazole
3n. Isolated as a yellow oil (13.3 mg, 17% yield); 1H NMR (400 MHz,
3.1.8. 2-(2-Chloro-6-fluorophenyl)-6-methylbenzo[d]thiazole
2i. Isolated as a colorless solid (27.4 mg, 35% yield), mp: 71e72 ꢀC;
CDCl3)
d
2.34 (s, 3H), 6.98 (t, J¼8.8 Hz, 1H), 7.27e7.32 (m, 1H), 7.45
(t, J¼8.0 Hz, 1H), 7.54 (t, J¼8.4 Hz, 1H), 7.96 (d, J¼8.0 Hz, 1H), 8.19 (d,
3
1H NMR (400 MHz, CDCl3)
d
2.53 (s, 3H), 7.08 (t, J¼8.4 Hz, 2H), 7.35
J¼8.0 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d
2
14.3 (d, JCeF¼4 Hz),
2
(d, J¼8.4 Hz, 1H), 7.39e7.47 (m, 1H), 7.75 (s, 1H), 8.06 (d, J¼8.0 Hz,
111.4 (dd, JCeF¼4, 22 Hz), 121.3, 121.6 (dd, JCeF¼2, 18 Hz), 123.8,
125.6, 126.2, 128.8,130.9,133.0 (dd, 3JCeF¼7, 10 Hz), 153.0,158.4 (dd,
1JCeF¼6, 254 Hz), 158.7 (dd, 1JCeF¼6, 252 Hz), 167.7 (d, 3JCeF¼4 Hz);
1H); 13C NMR (100 MHz, CDCl3)
d
21.6, 112.2 (d, 2JCeF¼26 Hz), 120.9,
123.3, 128.0, 131.59, 131.6 (d, 2JCeF¼21 Hz), 135.9, 136.0, 151.2, 154.6,
161.8 (d, JCeF¼254 Hz); 19F NMR (376 MHz, CDCl3)
d
ꢁ111.86;
19F NMR (376 MHz, CDCl3)
d
ꢁ112.44, ꢁ113.77; HRMS-ESI (m/z):
1
HRMS-ESI (m/z): calcd for C14H10F2NS (MþH): 262.0502, found
calcd for C14H10F2NS (MþH): 262.0502, found 262.0506.
262.0497.
3.1.15. 6-Fluoro-2-(2-fluoro-5-methylphenyl)benzo[d]thiazole
3.1.9. 6-Chloro-2-(2,6-difluorophenyl)benzo[d]thiazole 2j. Isolated
as a colorless solid (53.1 mg, 63% yield), mp: 127e128 ꢀC; 1H NMR
2o. Isolated as
a
colorless solid (34.4 mg, 44% yield), mp:
2.34 (s, 3H), 7.02 (t,
122e123 ꢀC; 1H NMR (400 MHz, CDCl3)
d
(400 MHz, CDCl3)
d
7.09 (t, J¼8.4 Hz, 2H), 7.42e7.51 (m, 2H), 7.93 (s,
J¼9.6 Hz, 1H), 7.11e7.22 (m, 2H), 7.51 (d, J¼6.4 Hz, 1H), 7.94e7.98
1H), 8.09 (d, J¼8.8 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d
111.6 (t,
(m, 1H), 8.08 (d, J¼6.4 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d 20.6,
2JCeF¼15 Hz), 112.3 (d, 2JCeF¼26 Hz), 120.8, 124.6, 127.2, 131.8, 132.1
107.5 (d, 2JCeF¼27 Hz), 115.1 (d, 2JCeF¼24 Hz), 116.1 (d, 2JCeF¼22 Hz),
(t, 3JCeF¼11 Hz),136.8,151.5,156.3,160.5 (d, 1JCeF¼254 Hz); 19F NMR
120.6 (d, JCeF¼11 Hz), 124.2 (d, JCeF¼9 Hz), 129.5, 132.8 (d,
2
3
1
(376 MHz, CDCl3)
d
ꢁ109.24; HRMS-ESI (m/z): calcd for
3JCeF¼8 Hz), 134.4, 136.8, 149.2, 158.8 (d, JCeF¼249 Hz), 160.5 (d,
C
13H7ClF2NS (MþH): 281.9956, found 281.9950.
1JCeF¼244 Hz), 161.2; 19F NMR (376 MHz, CDCl3)
ꢁ115.62, ꢁ117.15;
d
HRMS-ESI (m/z): calcd for C14H10F2NS (MþH): 262.0502, found
3.1.10. 2-(2,6-Difluorophenyl)-6-fluorobenzo[d]thiazole 2k. Isolated
as a colorless solid (54.0 mg, 68% yield), mp: 91e92 ꢀC; 1H NMR
262.0499.
(400 MHz, CDCl3)
d
7.09 (t, J¼8.8 Hz, 2H), 7.27 (t, J¼8.8 Hz, 1H),
3.1.16. 2-(2,6-Difluoro-3-methylphenyl)-6-fluorobenzo[d]thiazole
7.41e7.49 (m,1H), 7.63 (d, J¼8.0 Hz,1H), 8.11e8.15 (m,1H); 13C NMR
3o. Isolated as
a
colorless solid (13.4 mg, 16% yield), mp:
2.33 (s, 3H), 6.98 (t,
2
2
(100 MHz, CDCl3)
d
107.4 (d, JCeF¼27 Hz), 111.7 (t, JCeF¼16 Hz),
176e177 ꢀC; 1H NMR (400 MHz, CDCl3)
d
112.3 (d, 2JCeF¼26 Hz), 115.2 (d, 2JCeF¼25 Hz), 124.9 (d, 3JCeF¼9 Hz),
132.0 (t, 3JCeF¼11 Hz), 136.7 (d, 3JCeF¼14 Hz), 149.7, 155.5, 160.5 (d,
1JCeF¼254 Hz), 160.8 (d, 2JCeF¼245 Hz); 19F NMR (376 MHz, CDCl3)
J¼8.8 Hz, 1H), 7.26e7.32 (m, 2H), 7.63 (d, J¼7.6 Hz, 1H), 8.11e8.14
(m, 1H); 13C NMR (100 MHz, CDCl3)
d
14.3 (d, 3JCeF¼4 Hz), 107.4 (d,
2JCeF¼26 Hz), 111.5 (d, 2JCeF¼22 Hz), 115.1 (d, 2JCeF¼25 Hz), 121.6 (d,
3
3
d
ꢁ109.54, ꢁ114.78; HRMS-ESI (m/z): calcd for C13H7F3NS (MþH):
2JCeF¼19 Hz), 124.8 (d, JCeF¼10 Hz), 128.8 (d, JCeF¼4 Hz), 130.9,
3
3
266.0251, found 266.0255.
133.1 (d, JCeF¼9 Hz), 136.8 (d, JCeF¼11 Hz), 149.7, 156.0 (d,
3JCeF¼4 Hz), 158.3 (d, 1JCeF¼247 Hz), 158.6 (d, 1JCeF¼253 Hz), 160.8
3.1.11. 6-Chloro-2-(2-fluoro-6-methylphenyl)benzo[d]thiazole
(d, 1JCeF¼245 Hz); 19F NMR (376 MHz, CDCl3)
d
ꢁ112.40, ꢁ113.72,
2l. Isolated as
a
colorless solid (54.0 mg, 65% yield), mp:
2.41 (s, 3H), 7.04 (t,
ꢁ114.99; HRMS-ESI (m/z): calcd for C14H9F3NS (MþH): 280.0408,
103e104 ꢀC; 1H NMR (400 MHz, CDCl3)
d
found 280.0405.
J¼8.8 Hz, 1H), 7.13 (d, J¼7.6 Hz, 1H), 7.32e7.38 (m, 1H), 7.48 (d,
J¼8.8 Hz,1H), 7.92 (s,1H), 8.03 (d, J¼7.6 Hz,1H); 13C NMR (100 MHz,
3.1.17. 6-Chloro-2-(2-fluoro-5-methylphenyl)benzo[d]thiazole
2
2
CDCl3)
d
20.4, 113.3 (d, JCeF¼22 Hz), 121.0, 121.3 (d, JCeF¼14 Hz),
2p. Isolated as
a
colorless solid (39.1 mg, 47% yield), mp:
2.41 (s, 3H), 7.10 (dd,
3
124.3, 126.4, 127.0, 131.3 (d, JCeF¼9 Hz), 131.4, 137.4, 140.3, 151.7,
152e153 ꢀC; 1H NMR (400 MHz, CDCl3)
d
160.6 (d, JCeF¼246 Hz); 19F NMR (376 MHz, CDCl3)
d
ꢁ112.80;
J¼8.4, 11.2 Hz, 1H), 7.21e7.27 (m, 1H), 7.45 (d, J¼10.4 Hz, 1H), 7.88 (s,
1
HRMS-ESI (m/z): calcd for C14H10ClFNS (MþH): 278.0207, found
1H), 7.99 (d, J¼8.8 Hz, 1H), 8.17 (d, J¼6.8 Hz, 1H); 13C NMR
2
278.0203.
(100 MHz, CDCl3)
d
19.6, 115.0 (d, JCeF¼22 Hz), 119.4 (d,
2JCeF¼11 Hz), 119.9, 122.8, 126.1, 128.5, 130.1, 132.0 (d, JCeF¼8 Hz),
3
3.1.12. 6-Fluoro-2-(2-fluoro-6-methylphenyl)benzo[d]thiazole
2m. Isolated as a colorless solid (57.1 mg, 73% yield), mp: 70e71 ꢀC;
133.3, 135.9 (d, 3JCeF¼8 Hz), 150.0, 157.9 (d, 1JCeF¼250 Hz), 160.8 (d,
3JCeF¼6 Hz); 19F NMR (376 MHz, CDCl3)
ꢁ116.64; HRMS-ESI (m/z):
d
1H NMR (400 MHz, CDCl3)
d
2.41 (s, 3H), 7.04 (t, J¼8.8 Hz, 1H), 7.13
calcd for C14H10ClFNS (MþH): 278.0207, found 278.0205.
(d, J¼7.6 Hz, 1H), 7.26 (t, J¼8.8 Hz, 1H), 7.32e7.37 (m, 1H), 7.63 (d,
J¼8.0 Hz, 1H), 8.05e8.09 (m, 1H); 13C NMR (100 MHz, CDCl3)
d
20.4,
3.1.18. 6-Chloro-2-(2,6-difluoro-3-methylphenyl)benzo[d]thiazole
107.6 (d, 2JCeF¼27 Hz),113.3 (d, 2JCeF¼22 Hz),114.9 (d, 2JCeF¼24 Hz),
3p. Isolated as
a
colorless solid (13.3 mg, 15% yield), mp:
2.36 (s, 3H), 6.99 (t,
2
3
121.4 (d, JCeF¼14 Hz), 124.6 (d, JCeF¼10 Hz), 126.4, 131.2 (d,
132e133 ꢀC; 1H NMR (400 MHz, CDCl3)
d
3
3JCeF¼9 Hz), 137.2 (d, JCeF¼11 Hz), 140.3, 149.8, 160.6 (d,
J¼9.2 Hz, 1H), 7.31 (t, J¼8.0 Hz, 1H), 7.50 (d, J¼8.8 Hz, 1H), 7.94 (s,
1JCeF¼260 Hz), 160.7 (d, 1JCeF¼259 Hz), 161.8; 19F NMR (376 MHz,
1H), 8.08 (d, J¼8.8 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d 14.3 (d,
3
CDCl3)
d
ꢁ113.02, ꢁ115.51; HRMS-ESI (m/z): calcd for C14H10F2NS
3JCeF¼4 Hz), 111.1 (t, JCeF¼6 Hz), 111.6 (dd, JCeF¼4, 22 Hz), 120.9,
(MþH): 262.0502, found 262.0497.
121.7 (dd, JCeF¼4,18 Hz),124.5,127.1,131.7,133.3 (dd, JCeF¼8,10 Hz),
3
136.8 (t, JCeF¼4 Hz), 151.5, 156.9 (t, JCeF¼4 Hz), 158.3 (dd, JCeF¼6,
3.1.13. 2-(2-Fluoro-5-methylphenyl)benzo[d]thiazole 2n. Isolated as
a yellow solid (43.7 mg, 60% yield), mp: 61e62 ꢀC; 1H NMR
253 Hz), 158.6 (dd, JCeF¼4, 256 Hz); 19F NMR (376 MHz, CDCl3)
d
ꢁ112.05, ꢁ113.36; HRMS-ESI (m/z): calcd for C14H9ClF2NS (MþH):
(400 MHz, CDCl3)
d
2.42 (s, 3H), 7.11 (t, J¼9.2 Hz, 1H), 7.23e7.26 (m,
296.0112, found 296.0116.
1H), 7.40 (t, J¼8.0 Hz, 1H), 7.51 (t, J¼8.4 Hz, 1H), 7.93 (d, J¼8.0 Hz,
1H), 8.12 (d, J¼8.0 Hz, 1H), 8.21 (d, J¼6.8 Hz, 1H); 13C NMR
3.1.19. 2-(5-Chloro-2-fluorophenyl)benzo[d]thiazole 2q. Isolated as
a colorless solid (49.7 mg, 63% yield), mp: 97e97 ꢀC; 1H NMR
2
(100 MHz, CDCl3)
d
20.6, 116.1 (d, JCeF¼22 Hz), 120.9 (d,
2JCeF¼11 Hz), 121.5, 123.2, 125.2, 126.3, 129.7, 132.8 (d, 3JCeF¼9 Hz),
(400 MHz, CDCl3)
(t, J¼7.2 Hz, 1H), 7.95 (d, J¼7.6 Hz, 1H), 8.13 (d, J¼8.0 Hz, 1H), 8.44
d
7.19 (t, J¼10.0 Hz, 1H), 7.39e7.46 (m, 2H), 7.54
134.3, 135.8, 152.5, 158.9 (d, JCeF¼250 Hz), 161.4; 19F NMR
1

Q. Ding et al. / Tetrahedron 70 (2014) 409e416
415
(dd, J¼2.8, 6.4 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d
117.7 (d,
1JCeF¼254 Hz); 19F NMR (376 MHz, CDCl3)
d
ꢁ109.24; HRMS-ESI (m/
3
2JCeF¼24 Hz), 121.5, 122.8 (d, JCeF¼11 Hz), 123.5, 125.7, 126.5,
z): calcd for C13H7ClF2NS (MþH): 281.9956, found 281.9950.
3
129.2, 130.2, 131.7 (d, JCeF¼9 Hz), 135.9, 152.4, 159.0 (d,
1JCeF¼252 Hz), 159.5; 19F NMR (376 MHz, CDCl3)
d
ꢁ114.65;
Acknowledgements
HRMS-ESI (m/z): calcd for C13H8ClFNS (MþH): 264.0050, found
264.0045.
Financial Supported from National Natural Science Foundation
of China (21262016), Jiangxi Educational Committee (GJJ12169), the
Project of Jiangxi Youth Scientist (20122BCB23012), and Open
Project Program of Key Laboratory of Functional Small Organic
Molecule, Ministry of Education, Jiangxi Normal University (No.
KLFS-KF-201204 and KLFS-KF-201217) is gratefully acknowledged.
3.1.20. 2-(5-Chloro-2-fluorophenyl)-6-methylbenzo[d]thiazole
2r. Isolated as
a
colorless solid (28.2 mg, 34% yield), mp:
2.51 (s, 3H), 7.16 (t,
165e166 ꢀC; 1H NMR (400 MHz, CDCl3)
d
J¼9.6 Hz, 1H), 7.33 (d, J¼8.4 Hz, 1H), 7.35e7.39 (m, 1H), 7.71 (s, 1H),
7.99 (d, J¼8.0 Hz, 1H), 8.39e8.42 (m, 1H); 13C NMR (100 MHz,
CDCl3)
d
21.6, 117.7 (d, 2JCeF¼24 Hz), 121.1, 122.8, 123.0, 128.2, 129.1,
3
3
Supplementary data
130.2, 131.5 (d, JCeF¼9 Hz), 136.0 (d, JCeF¼8 Hz), 136.1 (d,
3JCeF¼8 Hz), 150.5, 158.4, 158.9 (d, JCeF¼252 Hz); 19F NMR
1
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2013.11.034.
(376 MHz, CDCl3)
d
ꢁ114.86; HRMS-ESI (m/z): calcd for C14H10ClFNS
(MþH): 278.0207, found 278.0209.
3.1.21. 2-(3-Chloro-2,6-difluorophenyl)-6-methylbenzo[d]thiazole
3r. Isolated as a colorless solid (7.0 mg, 8% yield), mp: 108e109 ꢀC;
References and notes
1H NMR (400 MHz, CDCl3)
d
2.44 (s, 3H), 7.05 (t, J¼8.8 Hz, 1H), 7.37
(d, J¼7.6 Hz, 1H), 7.47e7.53 (m, 1H), 7.76 (s, 1H), 8.07 (d, J¼7.6 Hz,
1H); 13C NMR (100 MHz, CDCl3)
1. (a) Mortimer, C. G.; Wells, G.; Crochard, J. P.; Stone, E. L.; Bradshaw, T. D.; Ste-
vens, M. F. G.; Westwell, A. D. J. Med. Chem. 2006, 49, 179; (b) McKee, M. L.;
Kerwin, S. M. Bioorg. Med. Chem. 2008, 16, 1775; (c) Kiumars, K.; Khodaei, M. M.;
Naali, F. J. Org. Chem. 2008, 73, 6835; (d) Sun, Q.; Wu, R.; Cai, S.; Lin, Y.; Sellers,
L.; Sakamoto, K.; He, B.; Peterson, B. R. J. Med. Chem. 2011, 54, 1126; (e) Lim, C. S.;
Masanta, G.; Kim, H. J.; Han, J. H.; Kim, H. M.; Cho, B. R. J. Am. Chem. Soc. 2011,
133, 11132; (f) Konig, J.; Wyllie, S.; Wells, G.; Stevens, M. F.; Wyatt, P. G.; Fair-
lamb, A. H. J. Biol. Chem. 2011, 286, 8523; (g) Cellier, M.; Fabrega, O. J.; Fa-
zackerley, E.; James, A. L.; Orenga, S.; Perry, J. D.; Salwatura, V. L.; Stanforth, S. P.
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Klang, I. M.; Lithgow, G. J. Nature 2011, 472, 226.
d
21.6, 112.7 (dd, JCeF¼4, 23 Hz),
3
117.8 (dd, JCeF¼4, 7 Hz), 121.0, 123.5, 128.2, 128.8 (d, JCeF¼4 Hz),
130.9,131.8 (d, 3JCeF¼10 Hz), 136.3, 151.2, 152.4 (dd, JCeF¼4, 252 Hz),
155.8 (dd, JCeF¼4, 256 Hz),167.7 (d, 3JCeF¼4 Hz); 19F NMR (376 MHz,
CDCl3)
d
ꢁ109.27, ꢁ110.62; HRMS-ESI (m/z): calcd for C14H9ClF2NS
(MþH): 296.0112, found 296.0109.
2. (a) Lanman, B. A.; Cee, V. J.; Cheruku, S. R.; Frohn, M.; Golden, J.; Lin, J.; Lobera,
M.; Marantz, Y.; Muller, K. M.; Neira, S. C.; Pickrell, A. J.; Rivenzon-Segal, D.;
Schutz, N.; Sharadendu, A.; Yu, X.; Zhang, Z.; Buys, J.; Fiorino, M.; Gore, A.;
Horner, M.; Itano, A.; McElvain, M.; Middleton, S.; Schrag, M.; Vargas, H. M.; Xu,
3.1.22. 2-(2-Fluorophenyl)benzo[d]thiazole 2s.5e,9 Isolated as a col-
orless solid (54.2 mg, 79% yield), mp: 97e97 ꢀC; 1H NMR
(400 MHz, CDCl3)
d
7.19 (t, J¼9.6 Hz, 1H), 7.26 (t, J¼7.6 Hz, 1H),
€
H.; Xu, Y.; Zhang, X.; Siu, J.; Burli, R. W. ACS Med. Chem. Lett. 2011, 2, 102; (b)
7.35e7.44 (m, 2H), 7.48 (t, J¼7.6 Hz, 1H), 7.89 (d, J¼7.6 Hz, 1H),
Frohn, M.; Cee, V. J.; Lanma, B. A.; Pickrell, A. J.; Rivenzon-Segal, J. G. D.; Mid-
dleton, S.; Fiorino, M.; Xu, H.; Schrag, M.; Xu, Y.; McElvain, M.; Muller, K.; Siu, J.;
8.11 (d, J¼8.0 Hz, 1H), 8.39 (t, J¼7.6 Hz, 1H); 13C NMR (100 MHz,
2
€
Burli, R. Bioorg. Med. Chem. Lett. 2012, 22, 628; (c) Hwang, J. Y.; Smithson, D. C.;
CDCl3)
d
116.4 (d, JCeF¼22 Hz), 121.4, 121.5, 123.3, 124.7, 125.3,
Holbrook, G.; Zhu, F.; Connelly, M. C.; Kaiser, M.; Brun, R.; Guy, R. K. Bioorg. Med.
Chem. Lett. 2013, 23, 4127; (d) Kiyoshi, N.; Masamichi, T.; Makoto, A. PCT Int.
Appl., 2007, WO 2007091313 A1 20070816.
3
3
126.3, 129.8, 132.1 (d, JCeF¼7 Hz), 135.8 (d, JCeF¼7 Hz), 152.6,
160.6 (d, JCeF¼252 Hz), 161.1; 19F NMR (376 MHz, CDCl3)
1
3. (a) Li, Y. J. Lumin. 2011, 131, 1821; (b) Zhang, J.; Li, Y.; Hui, C.; Zhu, J. Synth. Met.
2011, 161, 1166; (c) Chang, W.; Yang, P.-Y. J. Lumin. 2012, 132, 403; (d) Cui, X.;
Zhang, H. M.; Wu, T. F.; Li, M. Spectrochim. Acta, Part A 2011, 82, 126.
4. For selected examples, see: (a) Benedi, C.; Bravo, F.; Uriz, P.; Fernandez, E.;
Claver, C.; Castillon, S. Tetrahedron Lett. 2003, 44, 6073; (b) Evindar, G.; Batey, R.
A. J. Org. Chem. 2006, 71, 1802; (c) Itoh, T.; Mase, T. Org. Lett. 2007, 9, 3687; (d)
Do, H.; Daugulis, O. J. Am. Chem. Soc. 2007, 129, 12404; (e) Zhao, D.; Wang, W.;
Yang, F.; Lan, J.; Yang, L.; Gao, G.; You, J. Angew. Chem., Int. Ed. 2009, 48, 3296; (f)
Huang, J.; Chan, J.; Chen, Y.; Borths, C.; Kyle, K.; Larsen, R.; Margaret, M. J. Am.
Chem. Soc. 2010, 132, 3674; (g) Ranjit, S.; Liu, X. Chem.dEur. J. 2011, 17, 1105; (h)
Wang, Z.; Li, K.; Zhao, D.; Lan, J.; You, J. Angew. Chem., Int. Ed. 2011, 50, 5365; (i)
Zhu, M.; Fujita, K.; Yamaguchi, R. Chem. Commun. 2011, 12876; (j) Nishino, M.;
Hirano, K.; Satoh, T.; Miura, M. Angew. Chem., Int. Ed. 2012, 51, 6993; (k) Liao, Y.;
Qi, H.; Chen, S.; Jiang, P.; Zhou, W.; Deng, G.-J. Org. Lett. 2012, 14, 6004; (l) Yu, D.;
Lu, L.; Shen, Q. Org. Lett. 2013, 15, 940.
5. (a) Mettey, Y.; Michaud, S.; Vierfond, J. M. Heterocycles 1994, 38, 1001; (b)
Sharghi, H.; Asemani, O. Synth. Commun. 2009, 39, 860; (c) Xie, K.; Yang, Z.;
Zhou, X.; Li, X.; Wang, S.; Tan, Z.; An, X.; Guo, C.-C. Org. Lett. 2010, 12, 1564; (d)
Kalkhambkar, R. G.; Laali, K. K. Tetrahedron Lett. 2012, 53, 4212; (e) Yang, Z.;
Chen, X.; Wang, S.; Liu, J.; Xie, K.; Wang, A.; Tan, Z. J. Org. Chem. 2012, 77, 7086.
6. For selected examples, see: (a) Furuya, T.; Kaiser, H. M.; Ritter, T. Angew. Chem.,
Int. Ed. 2008, 47, 5993; (b) Furuya, T.; Ritter, T. Org. Lett. 2009, 11, 2860; (c)
Watson, D. A.; Su, M.; Teverovskiy, G.; Zhang, Y.; García-Fortanet, J.; Kinzel, T.;
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Chem. Soc. 2010, 132, 12150; (e) Furuya, T.; Strom, A. E.; Ritter, T. J. Am. Chem.
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S.; Hartwig, J. F. J. Am. Chem. Soc. 2012, 134, 10795; (h) Lee, E.; Hooker, J. M.;
Ritter, T. J. Am. Chem. Soc. 2012, 134, 17456; (i) Fier, P. S.; Luo, J.; Hartwig, J. F. J.
Am. Chem. Soc. 2013, 135, 2552; (j) Ye, Y.; Sanford, M. S. J. Am. Chem. Soc. 2013,
135, 4648.
d
ꢁ111.65; HRMS-ESI (m/z): calcd for C13H9FNS (MþH): 230.0440,
found 230.0434.
3.1.23. 2-(2-Fluorophenyl)-6-methylbenzo[d]thiazole 2t.9 Isolated
as a colorless solid (40.8 mg, 56% yield), mp: 111e112 ꢀC; 1H NMR
(400 MHz, CDCl3)
d 2.46 (s, 3H), 7.15e7.29 (m, 3H), 7.37e7.42 (m,
1H), 7.65 (s, 1H), 7.97 (d, J¼8.4 Hz, 1H), 8.37 (dt, J¼1.6, 8.0 Hz, 1H);
13C NMR (100 MHz, CDCl3)
d
21.6, 116.3 (d, 2JCeF¼22 Hz), 121.1, 121.6
3
3
(d, JCeF¼11 Hz), 122.8, 124.6, 128.0, 129.7, 131.9 (d, JCeF¼9 Hz),
135.5, 136.0 (d, 3JCeF¼8 Hz),150.7,160.0,160.5 (d, 1JCeF¼252 Hz); 19
F
NMR (376 MHz, CDCl3)
d
ꢁ112.01; HRMS-ESI (m/z): calcd for
C
14H11FNS (MþH): 244.0596, found 244.0591.
3.1.24. 6-Chloro-2-(2-fluorophenyl)benzo[d]thiazole 2u.9 Isolated as
a colorless solid (41.8 mg, 53% yield), mp: 148e149 ꢀC; 1H NMR
(400 MHz, CDCl3)
d
7.22 (t, J¼9.2 Hz, 1H), 7.30 (t, J¼6.8 Hz, 1H),
7.43e7.46 (m, 1H), 7.88 (s, 1H), 7.99 (d, J¼8.0 Hz, 1H), 8.35e8.43 (m,
1H); 13C NMR (100 MHz, CDCl3)
d
116.4 (d, 2JCeF¼22 Hz),121.0,121.1,
3
124.0, 124.8, 127.2, 129.7, 131.2, 132.4 (d, JCeF¼9 Hz), 136.9 (d,
3JCeF¼8 Hz),151.1,160.6 (d, 1JCeF¼252 Hz),161.5; 19F NMR (376 MHz,
CDCl3)
d
ꢁ111.65; HRMS-ESI (m/z): calcd for C13H8ClFNS (MþH):
264.0050, found 264.0047.
7. (a) Hull, K. L.; Anani, W. Q.; Sanford, M. S. J. Am. Chem. Soc. 2006, 128, 7134; (b)
Wang, X.; Mei, T.-S.; Yu, J.-Q. J. Am. Chem. Soc. 2009, 131, 7520; (c) Chan, K. S. L.;
Wasa, M.; Wang, X.; Yu, J.-Q. Angew. Chem., Int. Ed. 2011, 50, 9081; (d) Lou, S.-J.;
Xu, D.-Q.; Xia, A.-B.; Wang, Y.-F.; Liu, Y.-K.; Du, X.-H.; Xu, Z.-Y. Chem. Commun.
2013, 6218.
8. (a) Ding, Q.; Ji, H.; Wang, D.; Lin, Y.; Yu, W.; Peng, Y. J. Organomet. Chem. 2012,
711, 62; (b) Hashimoto, Y.; Ortloff, T.; Hirano, K.; Satoh, T.; Bolm, C.; Miura, M.
Chem. Lett. 2012, 41, 151; (c) Zhang, Q.; Li, C.; Yang, F.; Li, J.; Wu, Y. Tetrahedron
3.1.25. 6-Chloro-2-(2,6-difluorophenyl)benzo[d]thiazole 3u. Isolated
as a colorless solid (31.2 mg, 37% yield), mp: 127e128 ꢀC; 1H NMR
(400 MHz, CDCl3)
d
7.09 (t, J¼8.4 Hz, 2H), 7.42e7.51 (m, 2H), 7.93 (s,
1H), 8.09 (d, J¼8.8 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d 111.6 (t,
2JCeF¼15 Hz), 112.3 (d, 2JCeF¼26 Hz), 120.8, 124.6, 127.2, 131.8, 132.1
3
3
(t, JCeF¼11 Hz), 136.8, 151.5, 156.3, 160.5 (dd, JCeF¼6 Hz,

416
Q. Ding et al. / Tetrahedron 70 (2014) 409e416
2013, 69, 320; (d) Zhang, Q.; Yang, F.; Wu, Y. Tetrahedron 2013, 69, 4908; (e)
Reddy, V. P.; Qiu, R.; Iwasaki, T.; Kambe, N. Org. Lett. 2013, 15, 1290.
9. Ding, Q.; Ji, H.; Nie, Z.; Yang, Q.; Peng, Y. J. Organomet. Chem. 2013, 739, 33.
10. For mechanistic studies on CeF reductive elimination from high-valent palla-
dium fluoride, see: (a) Furuya, T.; Ritter, T. J. Am. Chem. Soc. 2008, 130, 10060; (b)
Ball, N. D.; Sanford, M. S. J. Am. Chem. Soc. 2009, 131, 3796; (c) Furuya, T.;
Benitez, D.; Tkatchouk, E.; Strom, A. E.; Tang, P.; Goddard, W. A., III; Ritter, T. J.
Am. Chem. Soc. 2010, 132, 3793; (d) Qiu, S.; Xu, T.; Zhou, J.; Guo, Y.; Liu, G. J. Am.
Chem. Soc. 2010, 132, 2856; (e) Engle, K. M.; Mei, T.-S.; Wang, X.; Yu, J.-Q. Angew.
Chem., Int. Ed. 2011, 50, 1478; (f) Peng, H.; Yuan, Z.; Wang, H.-Y.; Guo, Y.-L.; Liu,
G. Chem. Sci. 2013, 4, 3172.