Pd(II)-catalyzed ortho arylation of 2-arylbenzothiazoles with aryl iodides via benzothiazole-directed C-H activation

Article abstract of DOI:10.1016/j.jorganchem.2012.03.030

A novel and efficient method for the arylation of 2-arylbenzothiazoles is described via C-H activation. The desired C_Ar-C_Ar bond formation proceeded efficiently with good functional-group tolerance and high regioselectivity. Proposed

Full text of DOI:10.1016/j.jorganchem.2012.03.030

Journal of Organometallic Chemistry 711 (2012) 62e67
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Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Pd(II)-catalyzed ortho arylation of 2-arylbenzothiazoles with aryl iodides
via benzothiazole-directed CeH activation
*
*
Qiuping Ding , Huafang Ji, Dan Wang, Yuqing Lin, Weihua Yu, Yiyuan Peng
Key Laboratory of Functional Small Organic Molecules, Ministry of Education and College of Chemistry & Chemical Engineering, Jiangxi Normal University, Nanchang, Jiangxi 330022,
China
a r t i c l e i n f o
a b s t r a c t
Article history:
A novel and efficient method for the arylation of 2-arylbenzothiazoles is described via CeH activation.
The desired CAreCAr bond formation proceeded efficiently with good functional-group tolerance and high
regioselectivity. Proposed mechanism for the arylation of 2-arylbenzothiazole is depicted.
Ó 2012 Elsevier B.V. All rights reserved.
Received 20 February 2012
Received in revised form
26 March 2012
Accepted 26 March 2012
Keywords:
Arylbenzothiazoles
CeH activation
Arylation
Aryl iodide
1. Introduction
reaction through cleavage of CeH bond is an alternative to the
traditional strategy. The CeH activation [10e17] progress involves
Construction of carbonecarbon bond is fundamental to all of
organic chemistry. Arylearyl bonds are founded in diverse natural
products, medicinal agents, and organic materials. Metal
complexes-catalyzed reactions for the formation of CAreCAr bonds
are widely used in organic synthesis. Transition metal-catalyzed
cross-couplings are among the most traditional synthetic
methods [1e9], such as the SuzukieMiyaura reaction, Stille reac-
tion, Kumada reaction, and Negishi reaction. However, the forma-
tion of these bonds involved nucleophilic aromatic substitution
reactions between electron-deficient organic halides and stoi-
chiometric amounts of organometallic reagents, both coupling
components must be functionalized. The required organometallic
nucleophilic reagents are often not commercially available or are
relatively expensive. Their preparation process usually involves
many synthetic steps, during which undesired byproducts are
formed. Therefore, transition metal-catalyzed direct arylation
just one or no functionalized coupling components, which repre-
sent an environmentally and economically more attractive method.
The most widely studied area in this field is transitional metal-
catalyzed ligand-directed CeH activation followed by cross-
coupling to form C(sp2)eC(sp2), C(sp2)eC(sp3), and C(sp3)e
C(sp3) bonds. For example, amide [18], oxime ether [19], pyridine
[20e22], oxazoline [23,24], and carboxylic acid [25,26] serve as
directing groups for Pd-catalyzed ortho-arylation have been
extensively studied.
As a privileged fragment, 2-arylbenzothiazole core is found in
many natural products and pharmaceuticals that exhibit remark-
able biological activities [27e30]. Typical examples include [11C]PIB
(an agent in clinical trials for early diagnosis of Alzheimer’s disease)
[31,32] GW610 (antitumor agent) [30], and 5F203 (antitumor
agent) [33] (Fig. 1). Many efforts continue to be given to the
development of new 2-arylbenzothiazole structures and new
methods for their constructions [34e38]. As
a part of our
continuing efforts for the expeditious synthesis of biologically
relevant heterocyclic compounds [39e46], herein we would like to
report our recent efforts towards the synthesis of diverse 2-
arylbenzothiazoles via Pd-catalyzed CeH activation reactions.
* Corresponding authors. Tel./fax: þ86 791 88120380.
E-mail addresses: dqpjxnu@gmail.com (Q. Ding), yiyuanpeng@yahoo.com
(Y. Peng).
0022-328X/$ e see front matter Ó 2012 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2012.03.030

Q. Ding et al. / Journal of Organometallic Chemistry 711 (2012) 62e67
63
Me
OMe
11CH3
F
N
S
F
N
N
NH
NH2
OMe
S
HO
S
[11C]PIB
5F203
GW 610
Fig. 1. Potential therapeutic/diagnostic 2-arylbenzothiazoles.
2. Experimental
2.1. General remarks
(m, 1H), 7.64 (d, J ¼ 8.0 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d
21.1,
21.5, 121.0, 122.8, 127.1, 128.6, 129.2, 129.4, 129.5, 131.6, 134.7, 136.5,
136.8, 137.9, 142.9, 150.8, 166.1; HRMS (ESI): m/z [M þ H]þ calcd for
C28H24NS: 406.1629; found: 406.1630.
All reactions were performed in reaction tubes under nitrogen
atmosphere. Flash column chromatography was performed using
silica gel (60-Å pore size, 32e63 mm, standard grade). Analytical
2.2.4. 2-(4,400-Dimethoxy-[1,10:30,100-terphenyl]-20-yl)-6-
methylbenzo[d]thiazole, 3d
thin-layer chromatography was performed using glass plates pre-
coated with 0.25 mm 230e400 mesh silica gel impregnated with
a fluorescent indicator (254 nm). Thin layer chromatography plates
were visualized by exposure to ultraviolet light. Organic solutions
were concentrated on rotary evaporators at w20 Torr (house
vacuum) at 25e35 ꢀC. Commercial reagents and solvents were used
as received. 1H NMR (400 MHz) and 13C NMR (100 MHz) spectra
were recorded in CDCl3 using a Bruker Avance (AV400) spectrom-
eter in parts per million from internal tetramethylsilane on the
Yellow powder; yield: 69.5 mg (53%); mp 163e165 ꢀC; 1H NMR
(400 MHz, CDCl3)
d
2.39 (s, 3H), 3.68 (s, 6H), 6.68 (d, J ¼ 7.2 Hz, 4H),
7.14e7.18 (m, 5H), 7.39e7.43 (m, 3H), 7.51 (t, J ¼ 8.0 Hz, 1H), 7.73 (d,
J ¼ 8.4 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d 21.5, 55.1, 113.3, 121.0,
122.8,127.1,129.3,129.6,130.4,131.6,133.2,134.8,136.8,142.6,150.8,
158.5, 166.2; HRMS (ESI): m/z [M þ H]þ calcd for C28H24NO2S:
438.1528; found: 438.1522.
2.2.5. 2-(4,400-Dichloro-[1,10:30,100-terphenyl]-20-yl)-6-methylbenzo
[d]thiazole, 3e
d
scale. HRMS were obtained using a Nova NanoSEM 200 (FEI)
instrument with ESI ionization.
Yellow powder; yield: 80.1 mg (60%); mp 176e178 ꢀC; 1H NMR
(400 MHz, CDCl3)
d
2.31 (s, 3H), 7.03 (d, J ¼ 8.4 Hz, 4H), 7.08e7.12 (m,
2.2. General procedure for CeH bond activation/arylation of 2-
arylbenzothiazoles 1 with aryl iodides 2
5H), 7.32e7.37 (m, 3H), 7.47 (t, J¼ 7.6 Hz,1H), 7.65 (d, J¼ 8.4 Hz,1H); 13C
NMR (100 MHz, CDCl3)
d 21.5, 121.1, 122.9, 127.6, 128.2, 129.7, 129.8,
130.6,131.7,133.2,135.3,136.6,139.0,141.9,150.7,164.9; HRMS (ESI): m/
In a 20 mL Teflon tube, a mixture of 2-phenylbenzothiazole 1
(0.3 mmol, 1.0 equiv), aryl iodides 2 (1.2 mmol, 4.0 equiv), AgOAc
(1.5 mmol, 5.0 equiv), and Pd(OAc)2 (10 mol%) in dried TFA (2.0 mL)
was stirred at 90 ꢀC for 12e72 h. After completion of the reaction as
indicated by TLC, the mixture was cooled to room temperature, the
resulting mixture was extracted with ethyl acetate (3 ꢁ 20 mL), The
organic layer was evaporated under vacuum, and then the residue
was purified by flash column chromatography on silica gel to
provide the corresponding pure product 3 and (or) 4.
z [M þ H]þ calcd for C26H18Cl2NS: 446.0537; found: 446.0540.
2.2.6. 6-Chloro-2-(4,400-dimethyl-[1,10:30,100-terphenyl]-20-yl)benzo
[d]thiazole, 3f
Yellow powder; yield: 105.8 mg (83%); mp 82e83 ꢀC; 1H NMR
(400 MHz, CDCl3)
d
2.12 (s, 6H), 6.86 (d, J ¼ 8.0 Hz, 4H), 7.04 (d,
J ¼ 8.0 Hz, 4H), 7.17 (dd, J ¼ 2.0, 8.8 Hz, 1H), 7.33 (d, J ¼ 7.6 Hz, 2H),
7.42e7.47 (m, 2H), 7.64 (d, J ¼ 8.8 Hz,1H); 13C NMR (100 MHz, CDCl3)
d
21.1,120.9,124.0,126.4,128.7,129.2,129.4,129.8,130.7,131.1,136.7,
137.7, 137.8, 142.9, 151.2, 167.8; HRMS (ESI): m/z [M þ H]þ calcd for
2.2.1. 2-(4,400-Dimethyl-[1,10:30,100-terphenyl]-20-yl)benzo[d]
thiazole, 3a
C27H21ClNS: 426.1083; found: 426.1078.
White powder; yield: 97 mg (83%); mp 159e161 ꢀC; 1H NMR
2.2.7. 2-([1,10:30,100-Terphenyl]-20-yl)-6-chlorobenzo[d]thiazole, 3g
(400 MHz, CDCl3)
d
2.23 (s, 6H), 6.96 (d, J¼ 7.6 Hz, 4H), 7.14 (d, J¼ 7.6 Hz,
Yellow oil; yield: 89.3 mg (75%); 1H NMR (400 MHz, CDCl3)
4H), 7.26 (t, J ¼ 7.6 Hz, 1H), 7.36 (t, J ¼ 7.6 Hz, 1H), 7.44 (d, J ¼ 7.6 Hz, 2H),
d
7.04e7.05 (m, 6H), 7.13e7.17 (m, 5H), 7.36 (d, J ¼ 7.6 Hz, 2H), 7.46
7.55 (d, J ¼ 8.0 Hz,1H), 7.65 (d, J ¼ 8.0 Hz,1H), 7.87 (d, J ¼ 8.0 Hz,1H); 13C
(d, J ¼ 8.0 Hz, 2H), 7.60 (d, J ¼ 8.8 Hz, 1H); 13C NMR (100 MHz,
NMR (100 MHz, CDCl3)
d
21.1, 121.3, 123.3, 124.7, 125.5, 128.7, 129.2,
CDCl3) d 120.9, 124.0, 126.5, 127.1, 128.0, 129.3, 129.6, 129.9, 130.8,
129.4,129.6,131.4,136.5,136.6,137.8,142.9,152.6,167.2; HRMS (ESI): m/
131.2, 137.7, 140.6, 143.0, 151.2, 167.5; HRMS (ESI): m/z [M þ H]þ
z [M þ H]þ calcd for C27H22NS: 392.1473; found: 392.1468.
calcd for C25H17ClNS: 398.077; found: 398.0765.
2.2.2. 2-([1,10:30,100-Terphenyl]-20-yl)benzo[d]thiazole, 3b
2.2.8. 6-Chloro-2-(4,400-dichloro-[1,10:30,100-terphenyl]-20-yl)benzo
[d]thiazole, 3h
Colorless oil; yield: 67.7 mg (63%); 1H NMR (400 MHz, CDCl3)
d
7.14e7.17 (m, 7H), 7.24e7.27 (m, 4H), 7.33 (d, J ¼ 7.6 Hz, 1H), 7.48
Yellow powder; yield: 86.3 mg (62%); mp 82e83 ꢀC; 1H NMR
(d, J ¼ 7.6 Hz, 2H), 7.59 (t, J ¼ 8.0 Hz,1H), 7.62 (d, J ¼ 8.0 Hz,1H), 7.82
(400 MHz, CDCl3)
d
7.12e7.18 (m, 8H), 7.33 (dd, J ¼ 2.0, 8.8 Hz, 1H),
(d, J ¼ 8.0 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d
121.3, 123.3, 124.8,
7.43 (d, J ¼ 7.6 Hz, 2H), 7.58 (d, J ¼ 7.6 Hz,1H), 7.62 (d, J ¼ 2.0 Hz,1H),
125.6, 127.0, 127.9, 129.3, 129.6, 129.8, 131.5, 136.5, 140.7, 142.9,
152.5, 167.0; HRMS (ESI): m/z [M þ H]þ calcd for C25H18NS: 364.116;
found: 364.1156.
7.76 (d, J ¼ 8.8 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d 121.0, 124.2,
126.8, 128.3, 129.8, 130.1, 130.6, 131.1, 131.2, 133.4, 137.6, 138.8, 141.9,
151.1, 166.7; HRMS (ESI): m/z [M þ H]þ calcd for C25H15Cl3NS:
465.9991; found: 465.9985.
2.2.3. 2-(4,400-Dimethyl-[1,10:30,100-terphenyl]-20-yl)-6-methylbenzo
[d]thiazole, 3c
2.2.9. 2-(4,400-Dimethyl-[1,10:30,100-terphenyl]-20-yl)-6-fluorobenzo
[d]thiazole, 3i
Yellow powder; yield: 82.6 mg (68%); mp 153e155 ꢀC; 1H NMR
(400 MHz, CDCl3)
7.06 (d, J ¼ 8.0 Hz, 5H), 7.31 (s, 1H), 7.33 (d, J ¼ 7.6 Hz, 2H), 7.43e7.47
d
2.13 (s, 6H), 2.29 (s, 3H), 6.86 (d, J ¼ 8.0 Hz, 4H),
Yellow oil; yield: 92.0 mg (75%); 1H NMR (400 MHz, CDCl3)
d
2.11 (s, 6H), 6.85 (d, J ¼ 8.0 Hz, 4H), 6.93 (dt, J ¼ 2.4, 8.8 Hz, 1H),

64
Q. Ding et al. / Journal of Organometallic Chemistry 711 (2012) 62e67
7.04 (d, J ¼ 8.0 Hz, 4H), 7.15 (dd, J ¼ 2.4, 8.0 Hz, 1H), 7.32 (d,
J ¼ 7.6 Hz, 2H), 7.43 (d, J ¼ 7.2 Hz, 1H), 7.67 (dd, J ¼ 9.2, 9.2 Hz, 1H);
2.2.16. 2-([1,10-Biphenyl]-2-yl)benzo[d]thiazole [47], 4b
Colorless oil; yield: 8.6 mg (10%); 1H NMR (400 MHz, CDCl3)
13C NMR (100 MHz, CDCl3)
d
21.1, 107.4 (d, 2JCeF ¼ 27.0 Hz), 114.2 (d,
d
7.30e7.39 (m, 6H), 7.42e7.57 (m, 4H), 7.71 (d, J ¼ 7.6 Hz, 1H), 8.05
2JCeF ¼ 24.0 Hz), 124.1 (d, 3JCeF ¼ 9.0 Hz), 128.7, 129.2, 129.4, 129.8,
(d, J ¼ 8.8 Hz,1H), 8.08 (d, J ¼ 7.2 Hz,1H); 13C NMR (100 MHz, CDCl3)
3
131.2, 136.7, 137.6 (d, JCeF ¼ 11.0 Hz), 137.8, 143.0, 149.3, 160.1 (d,
d 121.3, 123.2, 124.9, 125.9, 127.8, 128.3, 130.0, 130.1, 130.5, 130.9,
4
1JCeF ¼ 244.0 Hz), 166.9 (d, JCeF ¼ 4.0 Hz); HRMS (ESI): m/z
132.6, 136.6, 140.2, 141.7, 152.7, 167.9; HRMS (ESI): m/z [M þ H]þ
[M þ H]þ calcd for C27H21FNS: 410.1379; found: 410.1373.
calcd for C19H14NS: 288.0847; found: 288.0840.
2.2.10. 2-([1,10:30,100-Terphenyl]-20-yl)-6-fluorobenzo[d]thiazole, 3j
2.2.17. 6-Chloro-2-(5-methoxy-40-methyl-[1,10-biphenyl]-2-yl)
benzo[d]thiazole, 4k
Yellow oil; yield: 83.4 mg (73%); 1H NMR (400 MHz, CDCl3)
d
6.91e6.96 (m, 2H), 7.04e7.08 (m, 6H), 7.11e7.16 (m, 4H), 7.37 (d,
Yellow powder; yield: 10.9 mg (10%); mp 147e148 ꢀC; 1H NMR
J ¼ 7.6 Hz, 2H), 7.47 (t, J ¼ 7.2 Hz, 1H), 7.62e7.65 (m, 1H); 13C NMR
(400 MHz, CDCl3)
d
2.33 (s, 3H), 3.81 (s, 3H), 6.81 (d, J ¼ 2.4 Hz, 1H),
2
(100 MHz, CDCl3)
d
107.3 (d, JCeF
¼
27.0 Hz), 114.3 (d,
6.94 (dd, J ¼ 2.4, 8.4 Hz, 1H), 7.08e7.20 (m, 4H), 7.29 (dd, J ¼ 2.0,
8.8 Hz, 1H), 7.57 (d, J ¼ 2.0 Hz, 1H), 7.82 (d, J ¼ 8.8 Hz, 1H), 8.01 (d,
2JCeF ¼ 24.0 Hz), 124.1 (d, JCeF ¼ 9.0 Hz), 127.1, 127.9, 129.3, 129.6,
3
3
129.8, 131.3, 137.5 (d, JCeF ¼ 12 Hz), 140.6, 143.0, 149.2, 161.2 (d,
J ¼ 8.8 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d 21.3, 55.5, 113.6, 116.0,
1JCeF ¼ 244.0 Hz), 166.6; HRMS (ESI): m/z [M þ H]þ calcd for
120.8, 123.5, 125.1, 126.5, 129.2, 129.8, 130.4, 131.9, 137.0, 137.7,138.1,
143.5, 151.3, 160.9, 168.3; HRMS (ESI): m/z [M þ H]þ calcd for
C21H17ClNOS: 366.0719; found: 366.0715.
C25H17FNS: 382.1066; found: 382.1060.
2.2.11. 6-Chloro-2-(50-methoxy-4,400-dimethyl-[1,10:30,100-
terphenyl]-20-yl)benzo[d]thiazole, 3k
2.2.18. 6-Fluoro-2-(4-methyl-[1,10-biphenyl]-2-yl)benzo[d]thiazole,
Yellow powder; yield: 71 mg (52%); mp 158e160 ꢀC; 1H NMR
4o
(400 MHz, CDCl3)
d
2.23 (s, 6H), 3.88 (s, 3H), 6.92e7.00 (m 6H), 7.13
Colorless powder; yield: 59.3 mg (62%); mp 105e107 ꢀC; 1H
(d, J ¼ 8.0 Hz, 4H), 7.27 (dd, J ¼ 2.0, 8.8 Hz, 1H), 7.56 (s, 1H), 7.72 (d,
NMR (400 MHz, CDCl3) d 2.47 (s, 3H), 7.16e7.20 (m, 1H),
J ¼ 8.8 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d
21.1, 55.5, 114.9, 120.8,
7.24e7.40(m, 8H), 7.88 (s, 1H), 7.97 (dd, J ¼ 4.8, 8.8 Hz,1H); 13C NMR
2
123.8, 123.9, 126.3, 128.7, 129.1, 130.5, 136.8, 137.8, 137.9, 144.5,
(100 MHz, CDCl3)
d
20.0, 106.3 (d, JCeF ¼ 27.0 Hz), 113.5 (d,
151.2, 160.1, 168.0; HRMS (ESI): m/z [M
C28H23ClNOS: 456.1189; found: 456.1183.
þ
H]þ calcd for
2JCeF ¼ 24.0 Hz), 122.9 (d, 3JCeF ¼ 9.0 Hz), 126.7, 127.3, 129.0, 129.6,
129.8,130.0,131.0,136.5 (d, 3JCeF ¼ 11.0 Hz),136.7,137.9,139.0, 148.3
4
1
(d, JCeF
¼
1.0 Hz), 159.2 (d, JCeF
¼
244.0 Hz), 166.8 (d,
2.2.12. 6-Chloro-2-(50-methoxy-[1,10:30,100-terphenyl]-20-yl)benzo
[d]thiazole, 3l
4JCeF ¼ 3.0 Hz); HRMS (ESI): m/z [M þ H]þ calcd for C20H15FNS:
320.0909; found: 320.0903.
Yellow powder; yield: 76.8 mg (60%); mp 143e145 ꢀC; 1H NMR
(400 MHz, CDCl3)
d
3.79 (s, 3H), 6.91 (s, 2H), 7.01e7.11 (m, 6H),
2.2.19. 2-(40-Chloro-4-methyl-[1,10-biphenyl]-2-yl)-6-fluorobenzo
[d]thiazole, 4p
7.12e7.20 (m, 5H), 7.45 (d, J ¼ 1.6 Hz,1H), 7.58 (d, J ¼ 8.4 Hz,1H); 13C
NMR (100 MHz, CDCl3)
d
55.6, 115.1, 120.8, 123.9, 124.0, 126.4, 127.2,
Colorless powder; yield: 62.5 mg (59%); mp 113e114 ꢀC; 1H
128.0,129.2,130.6,137.9,140.7,144.6,151.2,160.2,167.7; HRMS (ESI):
NMR (400 MHz, CDCl3) d 2.46 (s, 3H), 7.16e7.34 (m, 7H), 7.40 (dd,
m/z [M þ H]þ calcd for C26H19ClNOS: 428.0876; found: 428.0870.
J ¼ 2.4, 8.0 Hz, 1H), 7.84 (s, 1H), 7.98 (dd, J ¼ 4.8, 8.8 Hz, 1H); 13C
2
NMR (100 MHz, CDCl3)
d
20.0, 106.5 (d, JCeF ¼ 26.0 Hz), 113.6 (d,
2.2.13. 6-Chloro-2-(4,400,50-trimethoxy-[1,10:30,100-terphenyl]-20-yl)
benzo[d]thiazole, 3m
2JCeF ¼ 24.0 Hz), 123.1 (d, 3JCeF ¼ 9.0 Hz), 127.5, 129.7, 129.8, 130.0,
3
130.2, 131.0, 132.8, 136.4 (d, JCeF ¼ 11.0 Hz), 136.5, 137.0, 137.5,
Yellow oil; yield: 96.4 mg (66%); 1H NMR (400 MHz, CDCl3)
148.3, 159.2 (d, 1JCeF ¼ 244.0 Hz), 166.3; HRMS (ESI): m/z [M þ H]þ
d
3.72 (s, 6H), 3.90 (s, 3H), 6.70 (d, J ¼ 8.4 Hz, 4H), 6.95 (s, 2H), 7.16
calcd for C20H14ClFNS: 354.052; found: 354.0515.
(d, J ¼ 8.4 Hz, 4H), 7.29 (dd, J ¼ 2.0, 8.8 Hz, 1H), 7.60 (s, 1H), 7.43 (d,
J ¼ 8.4 Hz, 1H); 13C NMR (400 MHz, CDCl3)
d
55.1, 55.5, 113.4, 114.8,
2.2.20. 2-(4-Chloro-[1,10-biphenyl]-2-yl)benzo[d]thiazole, 4q
Yellow powder; yield: 84.7 mg (88%); mp 134e135 ꢀC; 1H NMR
120.8, 123.9,126.3,130.3,130.5, 133.1,137.9, 144.2,151.2, 158.7, 160.1,
168.0; HRMS (ESI): m/z [M þ H]þ calcd for C28H23ClNO3S: 488.1087;
found: 488.1082.
(400 MHz, CDCl3)
d 7.16e7.29 (m, 7H), 7.31e7.38 (m, 2H), 7.57 (d,
J ¼ 8.0 Hz, 1H), 7.94 (d, J ¼ 8.4 Hz, 1H), 8.04 (d, J ¼ 1.6 Hz, 1H); 13C
NMR (100 MHz, CDCl3)
d 120.3, 122.4, 124.2, 125.0, 127.1, 127.5,
2.2.14. 2-(50-Methoxy-[1,10:30,100-terphenyl]-20-yl)benzo[d]
thiazole, 3n
128.8, 128.9, 129.1, 131.1, 132.9, 133.1, 135.7, 138.2, 139.2, 151.7, 165.0;
HRMS (ESI): m/z [M þ H]þ calcd for C19H13ClNS: 322.0457; found:
322.0452.
Colorless oil; yield: 62.5 mg (53%); 1H NMR (400 MHz, CDCl3)
d
3.88 (s, 3H), 6.99 (s, 2H), 7.05e7.18 (m, 6H), 7.19e28 (s, 5H), 7.32 (t,
J ¼ 7.6 Hz, 1H), 7.71(d, J ¼ 7.6 Hz, 1H), 7.76 (d, J ¼ 8.0 Hz, 1H); 13C
2.2.21. 2-(4-Chloro-40-methoxy-[1,10-biphenyl]-2-yl)benzo[d]
thiazole, 4r
NMR (100 MHz, CDCl3) d 53.6, 112.9, 119.5, 120.9, 121.8, 122.9, 123.7,
125.2, 125.9, 126.6, 127.1, 134.4, 138.5, 142.1, 150.4, 157.9, 164.4;
HRMS (ESI): m/z [M þ H]þ calcd for C26H20NOS: 394.1266; found:
394.1260.
Yellow powder; yield: 50.5 mg (48%); mp 91e92 ꢀC; 1H NMR
(400 MHz, CDCl3)
d
3.72 (s, 3H), 6.78 (d, J ¼ 8.8 Hz, 2H), 7.10 (d,
J ¼ 8.8 Hz, 2H), 7.20e7.26 (m, 2H), 7.33e7.36 (m, 2H), 7.61 (d,
J ¼ 8.0 Hz, 1H), 7.96 (d, J ¼ 8.4 Hz, 1H), 8.04 (s, 1H); 13C NMR
2.2.15. 2-(40-Methyl-[1,10-biphenyl]-2-yl)benzo[d]thiazole, 4a
(400 MHz, CDCl3) d 54.3, 113.0, 120.3, 122.4, 124.1, 125.0, 128.9,
Colorless oil; yield: 11.7 mg (13%); 1H NMR (400 MHz, CDCl3)
2.39 (s, 3H), 7.16 (d, J ¼ 7.6 Hz, 2H), 7.23 (d, J ¼ 8.0 Hz, 2H), 7.32 (t,
129.0, 130.1, 130.4, 131.3, 132.6, 133.2, 135.7, 138.9, 151.6, 158.8,
165.3; HRMS (ESI): m/z [M þ H]þ calcd for C20H15ClNOS: 352.0563;
found: 352.0057.
d
J ¼ 8.0 Hz, 1H), 7.41e7.52 (m, 4H), 7.72 (d, J ¼ 7.6 Hz, 1H), 8.08 (d,
J ¼ 7.6 Hz, 2H); 13C NMR (100 MHz, CDCl3)
d 20.2, 120.3, 121.1, 123.8,
124.8, 126.5, 128.0, 128.8, 129.0, 129.3, 129.9, 131.5, 135.6, 136.1,
136.5, 140.6, 151.6, 167.0; HRMS (ESI): m/z [M þ H]þ calcd for
C20H16NS: 302.1003; found: 302.0998.
2.2.22. 2-(4,40-Dichloro-[1,10-biphenyl]-2-yl)benzo[d]thiazole, 4s
Yellow powder; yield: 59.6 mg (56%); mp 89e91 ꢀC; 1H NMR
(400 MHz, CDCl3)
d
7.12 (d, J ¼ 8.4 Hz, 2H), 7.20e7.27 (m, 4H),

Q. Ding et al. / Journal of Organometallic Chemistry 711 (2012) 62e67
65
7.35e7.39 (m, 2H), 7.64 (d, J ¼ 8.0 Hz, 1H), 7.95 (d, J ¼ 8.4 Hz, 1H),
(Table 1, entry 11). When trifluoroacetic acid (TFA) was changed to
HOAc or 1,4-dioxane, only trace desired product was observed
(Table 1, entries 12 and 13). Thus, under optimized conditions
[Pd(OAc)2 (10 mol %), AgOAc (5.0 equiv), TFA, 90 ꢀC], the ortho-
diarylated product 3a, was obtained in 83% isolated yield, with 13%
yield of ortho-monoarylated product 4a.
With this promising result in hand, we started to investigate the
scope of this reaction under the optimized conditions. As summa-
rized in Table 2, benzothiazole-directed CeH activation can be
8.00 (d, J ¼ 2.0 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d 120.4, 122.4,
124.4, 125.2, 127.7, 129.0, 129.3, 130.1, 131.0, 133.0, 133.2, 133.4,
135.4, 136.6, 137.7, 151.6, 164.6; HRMS (ESI): m/z [M þ H]þ calcd for
C19H12Cl2NS: 356.0068; found: 356.0062.
2.2.23. 2-(3-Methoxy-[1,10-biphenyl]-2-yl)-6-methylbenzo[d]
thiazole, 4t
Colorless oil; yield: 67.5 mg (68%); 1H NMR (400 MHz, CDCl3)
d
2.41 (s, 3H), 3.77 (s, 3H), 6.97 (d, J ¼ 8.4 Hz, 1H), 7.05 (d, J ¼ 7.6 Hz,
extended to a wide variety of substrates. A range of 2-
1H), 7.10e7.17 (m, 3H), 7.21 (d, J ¼ 9.2 Hz 1H), 7.23e7.27 (m, 2H),
arylbenzothiazoles coupled with aryl iodides to give the corre-
sponding arylated products in moderate to good yields. Electron
factors determined the reactivity of the substrates. Substrates aryl
iodides or 2-arylbenzothiazoles could tolerate various functional
groups such as CH3, OCH3, and Cl. Better results were obtained
when aryl iodide containing a moderately electron-donating group
(CH3) 2a or electron-neutral group (H) 2b was employed. To strong
electron-withdrawing group such as NO2, the desired product was
not observed (Table 2, entry 9). For example, 6-chloro-2-
phenylbenzo[d]thiazole 1c reacted with 1-iodo-4-methylbenzene
2a led to the desired product 3f in 83% yield (Table 2, entry 6),
while 62% yield of 3h was afforded when 1-chloro-4-iodobenzene
2d was utilized in the reaction (Table 2, entry 8). Good results were
observed when 6-fluoro-2- phenylbenzo[d]thiazole 1d reacted
with 2a and 2b (Table 2, entries 10 and 11). When R2 was a strong
electron-donating group (OCH3), the reactions also occurred
smoothly to afford the corresponding products, just in relatively
low yield. For instance, reaction of 6-chloro-2-(4-methoxyphenyl)
benzo[d]thiazole 1e with 2a gave rise to the diarylated cross-
coupling product 3k in 52% yield (Table 2, entry 12). The position
of substituent R2 had a critical effect on the arylation reaction. The
arylation showed high regioselectivity for cross-coupling at the less
hindered ortho-position for 2-arylbenzothiazoles containing
a meta-substituent (Table 2, entries 16e20). In case of ortho-
substituted 2-arylbenzothiazole, the arylation occurred at the other
ortho-position in good yield (Table 2, entry 21).
7.45 (t, J ¼ 8.0 Hz, 1H), 7.51 (s, 1H), 7.89 (d, J ¼ 8.4 Hz, 1H); 13C NMR
(100 MHz, CDCl3)
d 21.5, 56.1, 110.1, 121.0, 122.1, 122.6, 122.9, 127.0,
127.2, 127.9, 129.3, 130.8, 134.8, 136.9, 140.3, 143.9, 151.2, 158.0,
163.3; HRMS (ESI): m/z [M þ H]þ calcd for C21H18NOS: 332.1109;
found: 332.1105.
3. Results and discussion
Initially, we studied the coupling of 2-phenylbenzo[d]thiazole
1a with 1-iodo-4-methylbenzene 2a in the presence of Pd(OAc)2 to
afford 3a (Table 1). The effects of different oxidants, temperatures,
and solvents were systematically investigated. Unfortunately, it
failed to provide the desired arylated product when Cu(OAc)2, BQ
(1,4-benzoquinone), and oxone were used as oxidant (Table 1,
entries 1e3). The use of PhI(OAc)2 as oxidant delivered the desired
ortho-diarylated product 3a in 5% yield, and trace of monoarylated
product 4a (Table 1, entry 4), while AgOAc afforded the 3a in an
encouraged 31% yield (Table 1, entry 5). Further study showed that
elevated amount of Pd(OAc)2 led to higher 41% yield (Table 1, entry
5). Examination of the loading of oxidant revealed that the yield
was found to grow with increasing oxidant amount (Table 1, entries
6 and 7). Lower yield was obtained when combination of AgOAc
and Cu(OAc)2 as oxidant (Table 1, entry 8). No reaction occurred
without catalysts or oxidants. Examination of the temperature
effect showed that the best results being obtained at relatively high
temperature 90 ꢀC (Table 1, entry 9), while inferior results were
obtained when the reaction temperature was more than 100 ꢀC
Based on known metal-catalyzed directing-group-assisted CeH
bond activation reaction and an analogy for the reaction of 2-
Table 1
Optimization of reaction conditions.a
p-tol
CH3
S
S
S
Pd(OAc)2 (x mol %)
+
I
+
Oxidant, CF3COOH, T
N
N
N
p-tol
p-tol
4a
1a
2a
3a
Entry
x
Oxidant (equiv)
T/ꢀC
Yield (%)b/3
Yield (%)b/4
1
2
3
4
5
6
7
8
5
5
5
5
5
10
10
10
10
10
10
10
10
Cu(OAc)2 (2.5)
BQ (2.5)
Oxone (2.5)
80
80
80
80
80
80
80
80
90
90
100
90
90
e
e
e
e
e
e
PhI(OAc)2 (2.5)
AgOAc (2.5)
AgOAc (2.5)
AgOAc (5.0)
AgOAc/Cu(OAc)2(5.0/2.5)
AgOAc (2.5)
AgOAc (5.0)
AgOAc (5.0)
AgOAc (5.0)
AgOAc (5.0)
5
Trace
3
5
8
6
11
13
9
31
41
49
44
73
83
60
Trace
Trace
9
10
11
12c
13d
e
e
a
Reaction conditions: 2-phenylbenzo[d]thiazole 1a (0.3 mmol), 1-iodo-4-methylbenzene 2a (1.2 mmol, 4.0 equiv), solvent (2 mL), 48 h.
Isolated yield based on 2-phenylbenzo[d]thiazole 1a.
HOAc as solvent.
b
c
d
1,4-Dioxane as solvent.

66
Q. Ding et al. / Journal of Organometallic Chemistry 711 (2012) 62e67
Table 2
CeH bond activation/arylation of 2-arylbenzothiazoles 1 with aryl iodides 2.a
Ar
Ar
ArI (2, 4.0 equiv)
Pd(OAc)2 (10 mol%)
S
S
S
R1
R1
R1
or
R2
R2
N
R2
AgOAc (5.0 equiv)
CF3COOH, 90 oC
N
N
Ar
1
3
4
OCH3
Cl
NO2
CH3
I
I
I
I
I
2a
2b
2c
2d
2e
Entry
Substrate 1
2
t [h]
Yield (%)b/3
Yield (%)b/4
1
2
3
2a
2b
2a
48
72
48
83/3a
62/3b
68/3c
13/4a
10/4b
Trace
1a
1a
1b
4
5
1b
1b
2c
2d
24
72
53/3d
60/3e
Trace
Trace
6
2a
48
83/3f
Trace
1c
7
8
9
1c
1c
1c
2b
2d
2e
72
72
72
75/3g
62/3h
e
Trace
Trace
Trace
10
11
2a
2b
48
72
75/3i
73/3j
Trace
Trace
1d
1d
Cl
S
OCH3
12
2a
72
52/3k
10/4k
N
1e
13
14
1e
2b
2c
72
72
60/3l
Trace
Trace
1e
66/3m
15
2b
72
53/3n
Trace
1f
16
17
18
2b
2d
2b
36
48
36
e
e
e
62/4o
59/4p
88/4q
1g
1g
1h
19
20
1h
1h
2c
2d
36
48
e
e
48/4r
56/4s
21
2b
12
e
68/4t
1i
a
Reaction conditions: 2-arylbenzothiazole 1 (0.3 mmol), aryl iodide 2 (1.2 mmol, 4.0 equiv), CF3COOH (2 mL), 90 ꢀC, 12e72 h.
Isolated yield based on 2-arylbenzothiazole 1.
b

Q. Ding et al. / Journal of Organometallic Chemistry 711 (2012) 62e67
67
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Scheme 1. Proposed mechanism for Pd-catalyzed directed arylation with AgI/AreI.
arylbenzoxazole [18e24], a possible reaction mechanism for the
arylation of 2-arylbenzothiazole is depicted in Scheme 1. The
proposed catalytic cycle involves the following steps: (ⅰ) cyclo-
palladation of 2-arylbenzothiazole via CeH activation, (ii) oxidation
addition of Pd(II) to Pd(IV), (iii) reductive elimination affording
monoarylated product 4 and Pd(II). The monoarylated product 4
could re-enter the catalytic cycle to ultimately yield the corre-
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4. Conclusion
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desired CAreCAr bond formation proceeded efficiently with good
functional-group tolerance and high regioselectivity. Proposed
mechanism for the arylation of 2-arylbenzothiazole is depicted. The
application of benzothiazole as a directing group to construct a C-
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Acknowledgments
Financial Supported from National Natural Science Foundation
of China (No. 21002042 and 21162012), Jiangxi Educational
Committee (GJJ12169), and Natural Science Foundation of Jiangxi
Province of China (2009GQH0054) is gratefully acknowledged.
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Appendix A. Supporting information
Supplementary data related to this article can be found online at
doi:10.1016/j.jorganchem.2012.03.030.
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