Palladium-catalyzed direct ortho-acylation through an oxidative coupling of 2-arylbenzothiazoles with benzylic alcohols

Article abstract of DOI:10.1016/j.tet.2013.08.005

An efficient protocol was developed for Pd-catalyzed direct C-H bond acylation by cross-dehydrogenative-coupling of arylbenzothiazoles and benzylic alcohols using tert-butyl hydroperoxide (TBHP) as the oxidant. The acylation reactions exhibit good reactiv

Full text of DOI:10.1016/j.tet.2013.08.005

Accepted Manuscript
Palladium-catalyzed direct ortho-acylation through an oxidative coupling of 2-
arylbenzothiazoles with benzylic alcohols
Qiuping Ding, Huafang Ji, Changqing Ye, Jiajia Wang, Junyan Wang, Liyun Zhou,
Yiyuan Peng
PII:
S0040-4020(13)01243-X
10.1016/j.tet.2013.08.005
TET 24691
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 20 March 2013
Revised Date: 16 July 2013
Accepted Date: 6 August 2013
Please cite this article as: Ding Q, Ji H, Ye C, Wang J, Wang J, Zhou L, Peng Y, Palladium-catalyzed
direct ortho-acylation through an oxidative coupling of 2-arylbenzothiazoles with benzylic alcohols,
Tetrahedron (2013), doi: 10.1016/j.tet.2013.08.005.
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ACCEPTED MANUSCRIPT
Palladium-catalyzed direct ortho-acylation
through an oxidative coupling of 2-
arylbenzothiazoles with benzylic alcohols
*
Qiuping Ding, Huafang Ji, Changqing Ye, Jiajia Wang, Junyan Wang, Liyun Zhou
and 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
Abstract: An efficient protocol was developed for Pd-catalyzed direct C−H bond
acylation by cross-dehydrogenative-coupling of arylbenzothiazoles and benzylic alcohols
using tert-butyl hydroperoxide (TBHP) as the oxidant. The acylation reactions exhibit
good reactivities and excellent regioselectivity.
Keywords: ortho-acylation; 2-arylbenzothiazoles; benzylic alcohols; tert-butyl
hydroperoxide
Introduction
Transition-metal-catalyzed intermolecular cross-dehydrogenative-coupling (CDC) of
inert C−H bonds has recently emerged as a powerful method for the construction of new
*
Corresponding author� Tel.: +86 791 88120396; fax: +86 791 88120396; E-mail: dqpjxnu@gmail.com (Q. Ding);
yiyuanpeng@yahoo.com (Y. Peng).

ACCEPTED MANUSCRIPT
1
C−C bonds and C-X (X = N, O, S, X) bonds. The combination of transition-metal-
catalysts and directing groups is very important to success in this context. Various
2
transition metals such as Pd, Rh, Ru, Fe, Co, and Cu have been widely employed.
Recently, the direct C−H bond acylation of aromatic compounds containing various
directing groups has been described. In 2009, Cheng firstly reported Pd-catalyzed
2
3
oxidative sp C–H acylation reactions of 2-arylpyridines from aldehydes. Subsequently,
2
other groups (such as Li, Ge, and Wang) also developed many 2-arylpyridine-directed sp
4
C–H acylation by different carbonyl sources. In addition, Yu and Kim described
separately the Pd-catalyzed direct C−H bond acylation using O-methyl oximes as a
5
directing group. Anilide was also employed as a directing group for direct C−H bond
6
acylation with aldehydes. Rh-catalyzed benzamide-directed oxidative acylation and Pd-
2
catalyzed ortho-acylation of N-benzyltriflamides with aldehydes via sp C–H bonds
7
activation were described by Kim. Cyclic enamides participated intermolecular C−H
8
bond acylation reactions was reported by Duan. Most recently, Wu and co-workers
reported Pd-catalyzed ortho-acylation of 2-arylbenzoxazole in moderate to good yields
9
a
using aldehydes as acyl source. Patel also developed an efficient protocol for the ortho-
acylation of 2-arylbenzoxazoles and 2-arylbenzothiazoles with aldehydes via Pd(II)-
9
b
catalyzed C-H activation/C-C bond formation. Decarboxylative cross-coupling reaction
1
0
of benzoic acids with α-oxocarboxylic acids was reported by Ge group.
In most cases, aldehyde was employed as carbonyl source in transition-metal-catalyzed
4
b,5b,8,11
C−H bond acylation reaction. In addition, α-oxocarboxylic acids,
benzylic
α-diketones, toluene derivatives, and carboxylic acids are also very
useful carbonyl sources in the presence of transition-metal catalyst and oxidant.
4
c,12
4d
13
14
alcohols,

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As a privileged fragment, the benzothiazole core is a ubiquitous subunit in many natural
15
products and pharmaceuticals with remarkable biological activities. For example,
compounds I or their salts (Figure 1) containing a benzothiazole core are useful for
1
6
treatment of parkinsonism, hypertension, depression, etc. Thus, it is highly desired to
develop efficient and general synthetic methods for access to functionalized
benzothiazoles in order to explore their potential applications. More recently, we has
2
17
developed the Pd-catalyzed direct ortho sp C−H arylation of 2-arylbenzothiazoles.
Inspired by the above-mentioned direct acylation protocols and our interest in 2-
arylbenzothiazoles, herein we would like to report the acylation reaction of 2-
arylbenzothiazoles and benzylic alcohols using tert-butyl hydroperoxide (TBHP) as the
oxidant in the presence of catalytic palladium acetate via oxidative CDC reaction.
Figure 1 Compounds I
Results and discussions
We initially used 2-(o-tolyl)benzo[d]thiazole 1a and phenylmethanol 2a as model
substrates to optimize the reaction conditions, and selected results are summarized in
Table 1. To our delight, the combination of Pd(OAc) and TBHP (65 wt.% aqueous
2
o
solution) in PhCl solvent at 110 C can catalyze the CDC reaction and provide the
acylated product 3a in 31% yield (Table 1, entry 1). A screening of catalysts
demonstrated that other Pd catalysts, such as PdCl , Pd (dba) , Pd(CH CN) Cl ,
2
2
3
3
2
2
Pd(PhCN) Cl , and Pd(PPh ) Cl were inferior to Pd(OAc) (Table 1, entries 1-6). Then,
2
2
3 2
2
2

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the use of other oxidants, such as ditert-butyl peroxide (DTBP), O , oxone, and K S O ,
2
2
2
8
was also ineffective in this transformation (Table 1, entries 7-10). Further optimization
showed the coupling yield could be raised to 61% in the presence of 7.0 equiv of TBHP
(Table 1, entries 11-13). Subsequently, the effects of several ligands were investigated,
and the results showed that the presence of ligand affected the reaction to some extent.
Among them, benzoquinone (BQ) increased the yield to 68%, some other generally used
ligands, such as TMEDA, DMEDA, PPh , L-proline, DDQ, and 1,10-phen showed
3
ineffective (Table 1, entries 14-20). The effect of solvents on this reaction was also
examined. PhCl was found to be the best choice, and other solvents such as toluene,
AcOH, DMAc, DMF, DMSO, NMP, and CH CN failed to yield better results (Table 1,
3
entries 21-27).
a
Table 1. Optimization of the reaction conditions
Entry [Pd]
Pd(OAc)2
Solvent Oxidant Ligand
Yield
b
(
%)
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
toluene
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
DTBP
O2
-
-
-
-
-
-
-
-
-
-
-
-
31
15
27
24
13
11
18
-
PdCl2
Pd (dba)3
2
PdCl (CH CN)
2
3
2
PdCl (PhCN)2
2
PdCl (PPh )
2
3 2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Oxone
K S O
8
-
-
0
1
2
3
4
5
6
7
8
9
0
1
2
2
c
d
e
e
e
e
e
e
e
e
e
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
45
52
61
37
32
28
-
TMEDA
DMEDA
PPh3
L-proline 42
BQ
DDQ
1,10-phen
BQ
68
trace
-
50

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e
e
e
e
e
e
2
2
2
2
2
2
3
4
5
6
7
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
AcOH
DMAc
DMF
DMSO
NMP
TBHP
TBHP
TBHP
TBHP
TBHP
BQ
BQ
BQ
BQ
BQ
BQ
30
trace
-
trace
20
35
2
CH CN TBHP
3
a
Conditions: 1a (0.2 mmol), 2a (0.6 mmol), [Pd] catalyst (5 mol %), oxidant (3.0 equiv),
o
b
c
ligand (10 mol%) 110 C, 2 h; Isolated yield based on 1a; 4.0 equiv of TBHP were
d
e
used; 6.0 equiv of TBHP were used; 7.0 equiv of TBHP were used.
Under the optimized reaction conditions [Pd(OAc) (5 mol%), TBHP (7.0 equiv), BQ (10
2
o
2
mol%), PhCl, 110 C], the scope of the sp C−H acylation reactions between the 2-
arylbenzo[d]thiazoles 1 with phenylmethanol 2a was investigated. The coupling of 2-
arylbenzo[d]thiazoles 1b-1i with middle electron-withdrawing groups (Cl, F) at the
ortho-position of 2-phenyl ring underwent smoothly the CDC acylation reaction to afford
the corresponding products 3b-3i in good to excellent yields (Table 2, entries 2-9). For
instance, 2-(2-chlorophenyl)benzo[d]thiazole 1b reacted with phenylmethanol 2a leading
to the formation of acylation product 3b in 95% yield (Table 2, entry 2). The reaction of
2
-(2-fluorophenyl)benzo[d]thiazole 1f under the standard conditions gave 3f in 82% yield
(Table 2, entry 6). Generally, the benzothiazole parts with electron-neutral substituents or
electron-withdrawing groups were relatively more reactive than those with electron-
donating ones, and afforded relatively higher yields (Table 2, entries 2, 4-6, 8 and 9 vs
entries 3 and 7). Regrettably, 2-(2-nitrophenyl)benzo[d]thiazole 1j containing strongly
electron-withdrawing group (NO ) reacted with phenylmethanol 2a under the present
2
reaction conditions no desired products was obtained. If the substituents at the
benzothiazole parts and the ortho-position of 2-phenyl ring parts both were electron-
donating groups, gave the acylation product in poor yield. For example, when 6-methyl-

ACCEPTED MANUSCRIPT
2
-(o-tolyl)benzo[d]thiazole 1k was used as substrate, only a 22% yield was obtained
(Table 2, entry 11). At the same time, substituted benzo[d]thiazole with a strong electron-
donating methoxy group at the ortho position of the benzene ring showed poor reactivity.
To those 2-arylbenzo[d]thiazoles 1n-1r with electron-donating or -withdrawing group at
the meta-position of 2-phenyl ring provided ortho-acylation products 3m-3q exclusively
at the less sterically hindered position in good yields (Table 2, entries 14-18).
Fortunately, unsubstituted 2-phenylbenzo[d]thiazole 1s, also reacted with
phenylmethanol 2a smoothly under standard reaction conditions and moderate isolated
yield (62%) of the monoacylated product 3r was obtained, and only trace amount of bis-
acylated product was observed by TLC (Table 2, entry 19). On the other hand, para-
position substituted 2-arylbenzo[d]thiazole 1t afforded in moderate yield (67%) and an
inferior selectivity with mono- and bis-acylated products in almost the same amount
(Table 2, entry 20).
a
Table 2. Reaction of phenylmethanol with 2-arylbenzo[d]thiazoles
Entry
1
1
1
Product 3
Yield Entry
1
1
Product 3
Yield
(%)
b
b
(
%)
68
95
85
11
12
13
22
70
83
k
a
b
c
3j
3
a
Cl
2
3
N
S
O
1l
1
1
Ph
Cl
3
k
3
b
N
S
O
1m
3l
Ph
3
c

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4
5
6
7
8
9
92
83
82
75
80
92
-
14
15
16
17
18
19
20
N
S
65
65
81
72
67
62
32
1
1
n
o
1
1
1
1
d
e
f
3m
3
d
3
n
3
e
1p
1q
3
o
3
f
Cl
N
S
g
3
p
3
g
1
1
r
s
1
1
h
i
3
q
3
h
3
r
3
-
i
c
1
0
1
t
1
j
3
s
a
Conditions: 2-arylbenzo[d]thiazole 1 (0.2 mmol), phenylmethanol 2a (0.6 mmol),
o
b
Pd(OAc) (5 mol%), TBHP (7.0 equiv), BQ (10 mol%), PhCl, 110 C, 2h; Isolated yield
2
c
based on 1; With 35% yield of bis-acylated product.
The substituent effects of various primary alcohols on this reaction were then studied
under the optimized reaction conditions (Table 3). It was noticed that benzylic alcohols
bearing electron-donating groups (CH ) (entry 2) and electron-withdrawing substituents
3
(
NO , Cl) at the aromatic ring (entries 3 and 4) provided good to high yields. However,
2
the reaction yield decreased dramatically when 4-bromobenzyl alcohol 2e was used as the
substrate, and the desired product 3w was achieved in 35% yield. Unfortunately, to
n
aliphatic alcohol such as BuOH 2f the reaction could not occur under the recommended

ACCEPTED MANUSCRIPT
reaction conditions.
Table 3. Acylation of 2-arylbenzo[d]thiazole with primary alcohols
a
Entry
1
2
2
Product 3
Yield Entry
2
2
Product 3
Yield
(%)
b
b
(
%)
92
74
85
4
5
6
87
35
-
a
3i
d
3
v
2
2
2
b
c
2e
3
3
t
3w
3
n
BuOH
2
f
3
x
u
a
Conditions: 2-arylbenzo[d]thiazole 1i (0.2 mmol), primary alcohols 2 (0.6 mmol),
o
b
Pd(OAc) (5 mol%), TBHP (7.0 equiv), BQ (10 mol%), PhCl, 110 C, 2h; Isolated yield
2
based on 1i.
To understand the reaction mechanism, we test some other experiments. First, using
PhCHO as the alternative of PhCH OH, the desired coupling product 3a was obtained in
2
7
0% yield under the standard conditions. Subsequently, 2.0 equiv. TEMPO as a radical-
trapping reagent was used in our model reaction, and only trace of desired product 3a was
observed, suggesting that free radical intermediate was involved in the reaction.
5
a,6-9,12,13
17
Based on the previous research
and our results , a plausible reaction pathway of
the palladium-catalyzed ortho-acylation of 2-arylbenzo[d]thiazole with phenylmethanol
2
through direct C−H bond activation was suggested in Scheme 1. First, sp C−H bond
activation of 2-arylbenzo[d]thiazole occurs in the presence of the palladium catalyst to

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form a five-membered palladacycle intermediate A (was observed by NMR). Second, the
palladacycle A reacted with the acyl radical which was produced in situ from the
III
IV
5a,6,12,13
oxidation of alcohol by TBHP to form either reactive Pd or Pd intermediate B.
Finally, the reductive elimination of intermediate B afforded coupling product 3 and
II
regenerates Pd for the next catalytic cycle.
Scheme 1 Plausible mechanism for the Pd-catalyzed ortho-acylation reaction.
In summary, we have developed an efficient method for the synthesis of aromatic ketones
2
via a Pd-catalyzed direct sp C−H bond acylation of 2-arylbenzo[d]thiazoles. The cheap
and readily available benzylic alcohols were used as acylation sources in the presence of
TBHP. The reaction exhibited good functional group tolerance with good to excellent
yield and high selectivity.
Experimental Section
General experimental procedures and characterizations: 2-Arylbenzo[d]thiazole (0.2
mmol), benzylic alcohol (0.6 mmol), Pd(OAc) (0.01 mmol), TBHP (1.4 mmol, 196 ꢀL,
2
6
5% aq), BQ (0.02 mmol), and PhCl (2.0 mL) were added in a 25 mL sealed tube with a

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Teflon-lined cap. The mixture was heated at 110 °C for 2 h. After being cooled to room
temperature, 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 corresponding pure coupling product 3.
(2-(benzo[d]thiazol-2-yl)-3-methylphenyl)(phenyl)methanone 3a. Isolated as a
o
1
yellow solid (68% yield, 44.7 mg), mp: 135-136 C; H NMR (400 MHz, CDCl ) δ 2.43
3
(s, 3H), 7.27 (t, J = 7.6 Hz, 2H), 7.33 (d, J = 8.0 Hz, 1H), 7.37-7.42 (m, 3H), 7.46-7.48
1
3
(
m, 2H), 7.69 (d, J = 7.6 Hz, 2H), 7.78 (d, J = 7.6 Hz, 1H), 7.93 (d, J = 8.0 Hz, 1H); C
NMR (100 MHz, CDCl ) δ 20.5, 121.3, 123.4, 125.2, 126.0, 126.6, 128.0, 129.3, 129.9,
3
−
1
1
32.5, 132.7, 132.8, 136.2, 137.4, 138.2, 140.7, 152.9, 165.2, 197.3; IR (KBr) ν/cm :
+
1
735, 1458, 1087, 775; HRMS (ESI): m/z [M + H] calcd for C H NOS: 330.0953;
2
1
16
found: 330.0950.
(2-(benzo[d]thiazol-2-yl)-3-chlorophenyl)(phenyl)methanone 3b. Isolated as a yellow
o
1
solid (95% yield, 66.3 mg), mp: 178-179 C; H NMR (400 MHz, CDCl ) δ 7.26 (t, J =
3
7
7
.6 Hz, 2H), 7.31-7.41 (m, 3H), 7.49-7.56 (m, 2H), 7.65 (d, J = 7.6 Hz, 2H), 7.69 (d, J =
1
3
.6 Hz, 1H), 7.80 (d, J = 7.6 Hz, 1H), 7.88 (d, J = 8.0 Hz, 1H); C NMR (100 MHz,
CDCl ) δ 121.3, 123.6, 125.6, 126.1, 127.5, 128.1, 129.4, 130.6, 131.8, 132.0, 132.9,
3
−
1
1
34.2, 136.3, 137.0, 142.9, 152.2, 162.1, 195.8; IR (KBr) ν/cm : 1669, 1317, 758;
+
HRMS (ESI): m/z [M + H] calcd for C H ClNOS: 350.0406, found: 350.0400.
2
0
13
(3-chloro-2-(6-methylbenzo[d]thiazol-2-yl)phenyl)(phenyl)methanone 3c. Isolated as a
o
1
yellow solid (85% yield, 61.7 mg), mp: 134-135 C; H NMR (400 MHz, CDCl ) δ 2.43
3
(s, 3H), 7.19 (d, J = 8.4 Hz, 1H), 7.25 (t, J = 7.2 Hz, 2H), 7.36 (t, J = 7.2 Hz, 1H), 7.47-
7
.52 (m, 2H), 7.57 (s, 1H), 7.64 (d, J = 7.6 Hz, 2H), 7.68 (d, J = 7.6 Hz, 1H), 7.74 (d, J =

ACCEPTED MANUSCRIPT
1
3
8
1
.4 Hz, 1H); C NMR (100 MHz, CDCl ) δ 21.6, 120.9, 123.0, 127.4, 127.7, 128.1,
3
29.4, 130.5, 131.8, 131.9, 132.8, 134.1, 135.8, 136.5, 137.0, 142.9, 150.4, 160.9, 195.8;
−
1
+
IR (KBr) ν/cm : 1670, 1276, 707; HRMS (ESI): m/z [M + H] calcd for C H ClNOS:
2
1
15
3
64.0563, found: 364.0568.
(3-chloro-2-(6-chlorobenzo[d]thiazol-2-yl)phenyl)(phenyl)methanone 3d. Isolated as a
o
1
yellow solid (92% yield, 70.5 mg), mp:147-148 C; H NMR (400 MHz, CDCl ) δ 7.26
3
(t, J = 7.6 Hz, 2H), 7.34 (d, J = 8.8 Hz, 1H), 7.38 (t, J = 7.6 Hz, 1H), 7.49 (d, J = 7.6 Hz,
1
H), 7.54 (t, J = 7.6 Hz, 1H), 7.64 (d, J = 7.6 Hz, 2H), 7.69 (d, J = 7.6 Hz, 1H), 7.76 (t, J
1
3
=
4.0 Hz, 2H); C NMR (100 MHz, CDCl ) δ 120.9, 124.3, 127.0, 127.6, 128.2, 129.4,
3
1
30.9, 131.3, 131.6, 132.1, 133.0, 134.1, 136.9, 137.5, 142.9, 150.7, 162.7, 195.6; IR
−
1
+
(
KBr) ν/cm : 1672, 1303, 826; HRMS (ESI): m/z [M + H] calcd for C H Cl NOS:
20 12 2
3
84.0017, found: 384.0021.
(3-chloro-2-(6-fluorobenzo[d]thiazol-2-yl)phenyl)(phenyl)methanone 3e. Isolated as a
o
1
yellow solid (83% yield, 60.9 mg), mp: 152-153 C; H NMR (400 MHz, CDCl ) δ 7.13
3
(t, J = 8.8 Hz, 1H), 7.26 (t, J = 7.6 Hz, 2H), 7.38 (t, J = 7.2 Hz, 1H), 7.46-7.51 (m, 2H),
7
4
=
.54 (d, J = 8.0 Hz, 1H), 7.64 (d, J = 7.6 Hz, 2H), 7.69 (d, J = 7.6 Hz, 1H), 7.81 (dd, J =
1
3
2
2
.8, 8.8 Hz, 1H); C NMR (100 MHz, CDCl ) δ 107.4 (d, J = 27.0 Hz), 114.9 (d, J
C-F
3
C-F
3
25.0 Hz), 124.6 (d, J = 10.0 Hz), 127.6, 128.2, 129.4, 130.8, 131.4, 132.0, 132.9,
C-F
3
1
1
34.1, 136.9, 137.3 (d, J = 11.0 Hz), 142.9, 148.8, 160.6 (d, J = 245.0 Hz), 195.7;
C-F C-F
−
1
+
IR (KBr) ν/cm : 1667, 1321, 750; HRMS (ESI): m/z [M + H] calcd for C H ClFNOS:
2
0
12
3
68.0312, found: 368.0310.
(2-(benzo[d]thiazol-2-yl)-3-fluorophenyl)(phenyl)methanone 3f. Isolated as a yellow
o
1
solid (82% yield, 54.6 mg), mp: 108-109 C; H NMR (400 MHz, CDCl ) δ 7.25-7.40
3

ACCEPTED MANUSCRIPT
1
3
(
m, 8H), 7.53-7.59 (m, 1H), 7.73 (d, J = 8.4 Hz, 2H), 7.87 (dd, J = 4.0, 8.4 Hz, 1H); C
2
3
NMR (100 MHz, CDCl ) δ 117.6 (d, J = 23.0 Hz), 120.4 (d, J = 13.0 Hz), 121.3,
3
C-F
C-F
3
1
1
1
3
23.4, 124.7, 125.5, 126.1, 128.2, 129.0, 131.7 (d, J = 9.0 Hz), 132.6, 135.8, 137.6,
C-F
1
−1
42.4, 152.0, 158.3, 160.1 (d, J = 252.0 Hz), 196.0; IR (KBr) ν/cm : 1668, 1299,
C-F
+
273, 757; HRMS (ESI): m/z [M + H] calcd for C H FNOS: 334.0702, found:
2
0
13
34.0700.
3-fluoro-2-(6-methylbenzo[d]thiazol-2-yl)phenyl)(phenyl)methanone 3g. Isolated as a
(
o
1
yellow solid (75% yield, 52.0 mg), mp:131-132 C; H NMR (400 MHz, CDCl ) δ 2.41
3
(
s, 3H), 7.15 (d, J = 8.4 Hz, 1H), 7.26 (t, J = 7.6 Hz, 2H), 7.34 (d, J = 6.8 Hz, 2H), 7.37
t, J = 9.2 Hz, 1H), 7.55 (t, J = 7.6 Hz, 1H), 7.57 (s, 1H), 7.63 (d, J = 8.0 Hz, 1H), 7.71
(
1
3
2
(
d, J = 7.6 Hz, 2H); C NMR (100 MHz, CDCl ) δ 21.6, 117.6 (d, J = 22.0 Hz), 120.5
3 C-F
2
3
(
d, J = 14.0 Hz), 120.9, 122.9, 124.7, 127.8, 128.2, 128.9, 131.5 (d, J = 9.0 Hz),
C-F C-F
1
1
32.6, 135.8, 136.0, 137.6, 142.3, 150.2, 157.1, 160.0 (d, J = 253.0 Hz), 196.1; IR
C-F
−
1
+
(
KBr) ν/cm : 1671, 1299, 745; HRMS (ESI): m/z [M + H] calcd for C H FNOS:
21 15
3
48.0858, found: 348.0859.
(2-(6-chlorobenzo[d]thiazol-2-yl)-3-fluorophenyl)(phenyl)methanone 3h. Isolated as a
o
1
yellow solid (80% yield, 58.7 mg), mp: 170-171 C; H NMR (400 MHz, CDCl ) δ 7.27-
3
7
.42 (m, 6H), 7.57-7.62 (m, 1H), 7.65 (d, J = 8.8 Hz, 1H), 7.71 (d, J = 7.6 Hz, 2H), 7.78
1
3
2
2
(
s, 1H); C NMR (100 MHz, CDCl ) δ 117.7 (d, J = 22.0 Hz), 120.0 (d, J = 13.0
3 C-F C-F
3
Hz), 120.8, 124.1, 124.8, 127.0, 128.3, 128.9, 131.5, 132.0 (d, J = 9.0 Hz), 132.7,
C-F
3
1
1
36.9 (d, J = 6.0 Hz), 137.5, 142.3, 150.5, 158.8, 160.1 (d, J = 253.0 Hz), 195.8;
C-F C-F
−
1
+
IR (KBr) ν/cm : 1671, 1309, 722; HRMS (ESI): m/z [M + H] calcd for C H ClFNOS:
2
0
12
3
68.0312, found: 368.0315.

ACCEPTED MANUSCRIPT
(3-fluoro-2-(6-fluorobenzo[d]thiazol-2-yl)phenyl)(phenyl)methanone 3i. Isolated as a
o
1
colorless solid (92% yield, 64.6 mg), mp:124-125 C; H NMR (400 MHz, CDCl ) δ 7.08
3
(t, J = 8.8 Hz, 1H), 7.28 (t, J = 7.6 Hz, 2H), 7.34-7.41 (m, 3H), 7.47 (d, J = 8.0 Hz, 1H),
1
3
2
7
2
1
1
.56-7.61 (m, 1H), 7.67-7.73 (m, 3H); C NMR (100 MHz, CDCl ) δ 107.3 (d, J
=
3
C-F
2
2
3
7.0 Hz), 114.9 (d, J = 25.0 Hz), 117.6 (d, J = 22.0 Hz), 120.1 (d, J = 13.0 Hz),
C-F
C-F
C-F
3
3
24.4 (d, J = 9.0 Hz), 124.8, 128.3, 128.9, 131.8 (d, J = 9.0 Hz), 132.7, 136.9,
C-F
C-F
1
1
37.5, 142.3, 148.6, 158.1, 160.0 (d, J = 252.0 Hz), 160.6 (d, J = 245.0 Hz), 195.9;
C-F
C-F
−
1
+
IR (KBr) ν/cm : 1665, 1279, 7788; HRMS (ESI): m/z [M + H] calcd for C H F NOS:
20
12 2
3
52.0608, found: 352.0612.
(3-methyl-2-(6-methylbenzo[d]thiazol-2-yl)phenyl)(phenyl)methanone 3j. Isolated as a
o
1
brown solid (22% yield, 15.1 mg), mp: 70-71 C; H NMR (400 MHz, CDCl ) δ 2.43 (s,
3
3
7
H), 2.45 (s, 3H), 7.22 (d, J = 8.4 Hz, 1H), 7.28 (t, J = 7.6 Hz, 2H), 7.38-7.44 (m, 2H),
1
3
.46-7.49 (m, 2H), 7.57 (s, 1H), 7.69 (d, J = 7.2 Hz, 2H), 7.80 (d, J = 8.0 Hz, 1H); C
NMR (100 MHz, CDCl ) δ 20.5, 21.5, 121.0, 122.8, 126.5, 127.6, 128.0, 129.2, 129.9,
3
1
32.6, 132.7, 132.8, 135.3, 136.4, 137.4, 138.2, 140.7, 151.1, 164.0, 197.4; IR (KBr)
−
1
+
ν/cm : 1668, 1275, 774; HRMS (ESI): m/z [M + H] calcd for C H NOS: 344.1109,
2
2
18
found: 344.1111.
2-(6-chlorobenzo[d]thiazol-2-yl)-3-methylphenyl)(phenyl)methanone 3k. Isolated as a
(
o
1
White solid (70% yield, 50.8 mg); mp:122-123 C; H NMR (400 MHz, CDCl ) δ 2.43
3
(s, 3H), 7.30 (t, J = 7.6 Hz, 2H), 7.37 (d, J = 8.8 Hz,1H), 7.39-7.44 (m, 2H), 7.49 (d, J =
1
3
3
.6 Hz, 2H), 7.69 (d, J = 7.6 Hz, 2H), 7.76 (s, 1H), 7.83 (d, J = 8.8 Hz, 1H); C NMR
(
100 MHz, CDCl ) δ 20.5, 120.9, 124.1, 126.8, 126.9, 128.1, 129.5, 129.9, 131.2, 132.1,
3
−
1
1
32.8, 132.9, 137.3, 137.4, 138.2, 140.6, 151.4, 165.8, 197.2; IR (KBr) ν/cm : 1668,

ACCEPTED MANUSCRIPT
+
1
3
279, 719; HRMS (ESI): m/z [M + H] calcd for C H ClNOS: 364.0563, found:
2
1
15
64.0568.
(2-(6-fluorobenzo[d]thiazol-2-yl)-3-methylphenyl)(phenyl)methanone 3l. Isolated as a
o
1
yellow solid (83% yield, 57.6 mg), mp:132-133 C; H NMR (400 MHz, CDCl ) δ 2.43
3
(s, 3H), 7.14 (t, J = 7.6 Hz, 1H), 7.29 (t, J = 7.6 Hz, 2H), 7.38-7.48 (m, 5H), 6.68 (d, J =
13
7
.6 Hz, 2H), 7.85 (dd, J = 4.8, 8.4 Hz,1H); C NMR (100 MHz, CDCl ) δ 20.5, 107.5 (d,
3
2
2
3
JC-F = 26.0 Hz), 114.7 (d, J = 25.0 Hz), 124.3 (d, J = 10.0 Hz), 126.7, 128.1,
C-F
C-F
3
1
1
29.4, 129.9, 132.2, 132.8, 132.9, 137.2 (d, J = 11.0 Hz), 137.4, 138.2, 140.6, 149.5,
C-F
1
−1
60.4 (d, J = 245.0 Hz), 165.0, 197.2; IR (KBr) ν/cm : 1668, 1282, 849; HRMS
C-F
+
(
ESI): m/z [M + H] calcd for C H FNOS: 348.0858, found: 348.0862.
2
1
15
(2-(benzo[d]thiazol-2-yl)-4-methylphenyl)(phenyl)methanone 3m. Isolated as a white
o
1
solid (65% yield, 42.8 mg), mp: 129-130 C; H NMR (400 MHz, CDCl ) δ 2.52 (s, 3H),
3
7
.25-7.30 (m, 3H), 7.32-7.39 (m, 2H), 7.41 (s, 7.41), 7.45 (d, J = 7.6 Hz, 1H), 7.73-7.81
1
3
(
m, 5H); C NMR (100 MHz, CDCl ) δ 21.4, 121.4, 123.4, 125.2, 126.1, 128.2, 129.1,
3
1
29.3, 130.3, 131.0, 132.3, 132.6, 135.4, 137.0, 138.0, 140.6, 153.5, 165.6, 197.7; IR
−
1
+
(
KBr) ν/cm : 1663, 1281, 732; HRMS (ESI): m/z [M + H] calcd for C H NOS:
21 16
3
30.0953, found: 330.0949.
(2-(6-chlorobenzo[d]thiazol-2-yl)-4-methylphenyl)(phenyl)methanone 3n. Isolated as a
o
1
yellow solid (65% yield, 47.2 mg), mp:125-126 C; H NMR (400 MHz, CDCl ) δ 2.52
3
(s, 3H), 7.25-7.32 (m, 3H), 7.35-7.46 (m, 3H), 7.68 (d, J = 8.4 Hz, 1H), 7.69 (s, 1H),
1
3
7
1
.71-7.76 (m, 3H); C NMR (100 MHz, CDCl ) δ 21.4, 121.0, 124.1, 127.0, 128.2,
3
29.2, 130.2, 131.1, 131.2 131.9, 132.7, 136.5, 137.0, 137.9, 140.8, 152.0, 166.1, 197.5;

ACCEPTED MANUSCRIPT
−
1
+
IR (KBr) ν/cm : 1683, 1292, 814; HRMS (ESI): m/z [M + H] calcd for C H ClNOS:
2
1
15
3
64.0563, found: 364.0567.
(2-(6-fluorobenzo[d]thiazol-2-yl)-4-methylphenyl)(phenyl)methanone 3o. Isolated as a
o
1
yellow solid (81% yield, 56.2 mg), mp:138-139 C; H NMR (400 MHz, CDCl ) δ 2.51
3
(s, 3H), 7.08 (t, J = 8.8 Hz, 1H), 7.28 (t, J = 7.6 Hz, 2H), 7.35-7.46 (m, 4H), 7.68 (s, 1H),
1
3
2
7
.70-7.75 (m, 3H); C NMR (100 MHz, CDCl ) δ 21.4, 107.6 (d, J = 27.0 Hz), 114.8
3 C-F
2
3
(
d, J = 24.0 Hz), 124.3 (d, J = 10.0 Hz), 128.2, 129.2, 129.3, 130.2, 131.0, 132.0,
C-F C-F
3
1
1
1
32.6, 136.3 (d, J = 12.0 Hz), 136.9, 137.9, 140.7, 150.1, 160.5 (d, J = 244.0 Hz),
C-F C-F
−
1
+
65.4, 197.6; IR (KBr) ν/cm : 1663, 1280, 929, 733; HRMS (ESI): m/z [M + H] calcd
for C H FNOS: 348.0858, found: 348.0861.
2
1
15
(2-(benzo[d]thiazol-2-yl)-4-chlorophenyl)(phenyl)methanone 3p. Isolated as a white solid
o
1
(
72% yield, 50.2 mg), mp:134-135 C; H NMR (400 MHz, CDCl ) δ 7.25-7.34 (m, 3H),
3
7
2
1
1
.35-7.41 (m, 2H), 7.48 (d, J = 8.4 Hz, 1H), 7.57 (d, J = 8.0 Hz, 1H), 7.74 (d, J = 7.6 Hz,
13
H), 7.79 (t, J = 6.8 Hz, 2H), 7.93 (s, 1H); C NMR (100 MHz, CDCl ) δ 121.5, 123.6,
3
25.7, 126.4, 128.3, 129.2, 129.5, 130.2, 130.3, 132.9, 133.9, 135.4, 136.2, 137.5, 138.0,
−
1
+
53.3, 163.7, 196.5; IR (KBr) ν/cm : 1665, 1277, 778; HRMS (ESI): m/z [M + H] calcd
for C H ClNOS: 350.0406, found: 350.0411.
2
0
13
(4-chloro-2-(6-methylbenzo[d]thiazol-2-yl)phenyl)(phenyl)methanone 3q. Isolated as a
o
1
yellow solid (67% yield, 48.6 mg), mp: 87-88 C H NMR (400 MHz, CDCl ) δ 2.41 (s,
3
3
H), 7.17 (d, J = 8.4 Hz, 1H), 7.28 (t, J = 7.2 Hz, 2H), 7.38 (t, J = 7.2 Hz, 1H), 7.47 (d, J
8.0 Hz, 1H), 7.55 (d, J = 7.6 Hz, 1H), 7.56 (s, 1H), 7.66 (d, J = 8.4 Hz, 1H), 7.73 (d, J
=
=
1
3
7.6 Hz, 2H), 7.90 (s, 1H); C NMR (100 MHz, CDCl ) δ 21.6, 121.2, 123.1, 128.0,
3
1
28.3, 129.2, 129.3, 130.1, 130.3, 132.9, 134.0, 135.6, 136.0, 136.2, 137.5, 137.9, 151.5,

ACCEPTED MANUSCRIPT
−
1
+
1
62.5, 196.6; IR (KBr) ν/cm : 1666, 1273, 738; HRMS (ESI): m/z [M + H] calcd for
C H ClNOS: 364.0563, found: 364.0559.
21
15
9
b
(
(2-(benzo[d]thiazol-2-yl)phenyl)(phenyl)methanone 3r . Isolated as a yellow solid (62%
o
1
yield, 40.8 mg), mp: 109-110 C; H NMR (400 MHz, CDCl ) δ 7.29 (t, J = 7.6 Hz, 3H),
3
7
7
1
1
.34- 7.38 (m, 2H), 7.54 (d, J = 6.8 Hz, 1H), 7.60-7.64 (m, 2H), 7.77 (t, J = 7.6 Hz, 4H),
1
3
.93 (d, J = 7.2 Hz, 1H); C NMR (100 MHz, CDCl ) δ 121.4, 123.4, 125.3, 126.2,
3
28.2, 128.9, 129.3, 129.6, 130.2, 130.3, 132.1, 132.7, 135.3, 137.8, 139.7, 153.5, 165.3,
−
1
+
97.7; IR (KBr) ν/cm : 1666, 1256, 799; HRMS (ESI): m/z [M + H] calcd for
C H NOS: 316.0796, found: 316.0791.
20
14
(2-(benzo[d]thiazol-2-yl)-5-methoxyphenyl)(phenyl)methanone 3s Isolated in 32% yield.
1
H NMR (400 MHz, CDCl ) δ 3.81 (s, 3H), 6.94 (s, 1H), 7.03 (d, J = 8.8 Hz, 1H), 7.16-
3
7
.30 (m, 5H), 7.65 (t, J = 6.4 Hz, 2H), 7.69 (d, J = 7.6 Hz, 2H), 7.78 (d, J = 8.0 Hz, 1H);
1
3
C NMR (100 MHz, CDCl ) δ 55.6, 113.9, 115.8, 121.2, 123.1, 124.6, 124.9, 125.9,
3
1
28.2, 129.2, 131.1, 132.6, 135.1, 137.7, 141.3, 153.5, 161.2, 165.0, 197.2; HRMS (ESI):
+
m/z [M + H] calcd for C H NO S: 346.0902, found: 346.0897.
2
1
16
2
(2-(benzo[d]thiazol-2-yl)-5-methoxy-1,3-phenylene)bis(phenylmethanone) 3s’ Isolated in
1
3
5% yield. H NMR (400 MHz, CDCl ) δ 3.93 (s, 3H), 7.15 (t, J = 7.2 Hz, 2H), 7.20-7.26
3
1
3
(
m, 7H), 7.34 (t, J = 7.6 Hz, 2H), 7.52 (d, J = 8.0 Hz, 1H), 7.66-7.73 (m, 5H); C NMR
(
100 MHz, CDCl ) δ 56.0, 115.7, 121.0, 123.1, 123.4, 125.0, 125.9, 128.2, 129.5, 133.1,
3
+
1
36.3, 136.7, 142.6, 152.5, 160.4, 162.7, 196.6; HRMS (ESI): m/z [M + H] calcd for
C H NO S: 450.1164, found: 450.1173.
28
20
3
(3-fluoro-2-(6-fluorobenzo[d]thiazol-2-yl)phenyl)(p-tolyl)methanone 3t. Isolated as a
o
1
yellow solid (74% yield, 54.0 mg), mp: 135-136 C; H NMR (400 MHz, CDCl ) δ 2.29
3

ACCEPTED MANUSCRIPT
(s, 3H), 7.07-7.11 (m, 3H), 7.31 (d, J = 7.2 Hz, 1H), 7.37 (t, J = 9.2 Hz, 1H), 7.48 (d, J =
8
.0 Hz, 1H), 7.54-7.59 (m, 1H), 7.64 (d, J = 8.0 Hz, 2H), 7.70 (dd, J = 4.8, 8.8 Hz,1H);
1
3
2
2
C NMR (100 MHz, CDCl ) δ 21.7, 107.3 (d, J = 26.0 Hz), 114.9 (d, J = 25.0
3
C-F
C-F
2
3
3
Hz), 117.5 (d, J = 22.0 Hz), 120.0 (d, J = 14.0 Hz), 124.5 (d, J = 10.0 Hz),
C-F
C-F
C-F
3
3
1
1
24.6, 129.1, 129.3, 131.7 (d, J = 9.0 Hz), 134.9, 136.9 (d, J = 11.0 Hz), 142.5,
C-F C-F
1
1
43.7, 148.7, 158.2, 160.1 (d, J = 252.0 Hz), 160.6 (d, J = 244.0 Hz), 195.7; IR
C-F
C-F
−
1
+
(
KBr) ν/cm : 1661, 1279, 788; HRMS (ESI): m/z [M + H] calcd for C H F NOS:
21
14 2
3
66.0764, found: 366.0771.
(4-chlorophenyl)(3-fluoro-2-(6-fluorobenzo[d]thiazol-2-yl)phenyl)methanone
3u.
o
1
Isolated as a yellow solid (85% yield, 54.0 mg), mp: 107-108 C; H NMR (400 MHz,
CDCl ) δ 7.10 (dt, J = 2.4, 8.8 Hz, 1H), 7.27 (d, J = 8.4 Hz, 2H), 7.32 (d, J = 7.6 Hz, 1H),
3
7
.39 (t, J = 8.4 Hz, 1H), 7.49 (dd, J = 2.8, 8.0 Hz, 1H), 7.59 (dt, J = 5.2, 8.0 Hz, 1H), 7.67
1
3
(
d, J = 8.4 Hz, 2H), 7.68 (d, J = 8.8 Hz, 1H)� C NMR (100 MHz, CDCl ) δ 107.4 (d,
3
2
2
2
3
JC-F = 27.0 Hz), 115.2 (d, J = 25.0 Hz), 117.8 (d, J = 22.0 Hz), 119.9 (d, J =
C-F
C-F
C-F
3
3
1
1
1
4.0 Hz), 124.3 (d, J = 9.0 Hz), 124.6, 128.7, 130.2, 131.9 (d, J = 9.0 Hz), 136.0,
C-F C-F
1
1
36.7, 139.0, 141.7, 148.5, 157.9, 158.8 (d, J = 252.0 Hz), 159.4 (d, J = 245.0 Hz),
C-F
C-F
−
1
+
94.7; IR (KBr) ν/cm : 1670, 1275, 843; HRMS (ESI): m/z [M + H] calcd for
C H ClF NOS: 386.0218, found: 386.0225.
20
11
2
(3-fluoro-2-(6-fluorobenzo[d]thiazol-2-yl)phenyl)(4-nitrophenyl)methanone 3v. Isolated
o
1
as a yellow solid (87% yield, 68.9 mg), mp: 143-144 C; H NMR (400 MHz, CDCl ) δ
3
7
2
1
.11 (dt, J = 1.6, 7.2 Hz, 1H), 7.38 (d, J = 7.6 Hz, 1H), 7.44-7.50 (m, 2H), 7.60-7.66 (m,
1
3
H), 7.86 (d, J = 8.4 Hz, 2H), 8.12 (d, J = 8.4 Hz, 2H); C NMR (100 MHz, CDCl ) δ
3
2
2
2
07.6 (d, J = 26.0 Hz), 115.4 (d, J = 25.0 Hz), 118.4 (d, J = 22.0 Hz), 119.8 (d,
C-F
C-F
C-F

ACCEPTED MANUSCRIPT
3
3
3
JC-F = 13.0 Hz), 123.6, 124.1 (d, J = 10.0 Hz), 124.8, 129.3, 132.3 (d, J = 9.0 Hz),
C-F
C-F
1
1
1
2
36.7, 140.7, 142.6, 148.0, 149.7, 157.6, 158.8 (d, J = 253.0 Hz), 159.5 (d, J
=
C-F
C-F
−
1
+
46.0 Hz), 194.0; IR (KBr) ν/cm : 1673, 1255, 797; HRMS (ESI): m/z [M + H] calcd
for C H F N O S: 397.0458, found: 397.0465.
2
0
11
2
2
3
(4-bromophenyl)(3-fluoro-2-(6-fluorobenzo[d]thiazol-2-yl)phenyl)methanone
3w.
o
1
Isolated as a yellow solid (35% yield, 30.0 mg), mp: 124-125 C; H NMR (400 MHz,
CDCl ) δ 7.12 (dt, J = 2.4, 8.8 Hz, 1H), 7.32 (d, J = 7.2 Hz, 1H), 7.38-7.41 (m, 1H), 7.44
3
(d, J = 8.4 Hz, 2H), 7.51 (dd, J = 2.4, 8.0 Hz, 1H), 7.57-7.63 (m, 3H), 7.68 (dd, J = 4.8,
1
3
2
2
8
2
1
1
1
4
.8 Hz, 1H); C NMR (100 MHz, CDCl ) δ 107.5 (d, J = 27.0 Hz), 115.2 (d, J
=
3
C-F
C-F
2
3
3
5.0 Hz), 117.8 (d, J = 22.0 Hz), 119.9 (d, J = 14.0 Hz), 124.3 (d, J = 10.0 Hz),
C-F
C-F
C-F
3
24.6, 127.8, 130.3, 131.6, 131.9 (d, J = 9.0 Hz), 136.4, 136.7, 141.6, 148.5, 157.8,
C-F
1
1
−1
60.0 (d, J = 254.0 Hz), 161.7 (d, J = 245.0 Hz), 194.9; IR (KBr) ν/cm : 1671,
C-F
C-F
+
275, 795; HRMS (ESI): m/z [M + H] calcd for C H BrF NOS: 429.9713, found:
2
0
11
2
29.9708.
Acknowledgements
Financial Supported from National Natural Science Foundation of China (21002042),
Jiangxi Educational Committee (GJJ12169), and Open Project Program of Key
Laboratory of Functional Small Organic Molecule, Ministry of Education, Jiangxi
Normal University (No. KLFS-KF-201217) is gratefully acknowledged.
References and notes

ACCEPTED MANUSCRIPT
1
For some recent reviews : (a) K. M. Engle, T.-S. Mei, M. Wasa, J.-Q. Yu, Acc. Chem.
Res. 2012, 45, 788; (b) A. J. Hickman, M. S. Sanford, Nature 2012, 484, 177; (c) M. C.
White, Science 2012, 335, 807; (d) C. Zhang, C. Tang, N. Jiao, Chem. Soc. Rev. 2012, 41,
3
1
4
464; (e) A. E. Wendlandt, A. M. Suess, S. S. Stahl, Angew. Chem., Int. Ed. 2011, 50,
1062; (f) J. Wencel-Delord, T. Dröge, F. Liu, F. Glorius, Chem. Soc. Rev. 2011, 40,
740; (g) C.-L. Sun, B.-J. Li, Z.-J. Shi, Chem. Rev. 2011, 111, 1293; (h) C. S. Yeung, V.
M. Dong, Chem. Rev. 2011, 111, 1215; (i) H. Zhang, W. Shi, A. Lei, Chem. Rev. 2011,
11, 1780; (j) S. H. Cho, J. K. Kim, J. Kwak, S. Chang, Chem. Soc. Rev. 2011, 40, 5068;
k) T. W. Lyons, M. S. Sanford, Chem. Rev. 2010, 110, 1147; (l) D. A. Colby, R. G.
Bergman, J. A. Ellman, Chem. Rev. 2010, 110, 624.
For some recent examples, see: (a) H. Li, P. Li, L. Wang, Org. Lett. 2013, 15, 620; (b)
P. Xie, Y. Xie, B. Qian, H. Zhou, C. Xia, H. Huang, J. Am. Chem. Soc. 2012, 134, 9902;
c) J. Y. Kim, S. H. Park, J. Ryu, S. H. Cho, S. H. Kim, S. Chang, J. Am. Chem. Soc.
1
(
2
(
2
012, 134, 9110; (d) K. Gao, P. S. Lee, T. Fujita, N. Yoshikai, J. Am. Chem. Soc. 2010,
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Deng, D. L. Yin, J. H. Li, J. Am. Chem. Soc. 2010, 132, 8900; (f) X. Wang, L. Truesdale,
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X. Jia, S. Zhang, W. Wang, F. Luo, J. Cheng, Org. Lett. 2009, 11, 3120.
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I. S. Kim, Adv. Synth. Catal. 2013, 355, 332.
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(a) Q. Zhang, C. Li, F. Yang, J. Li, Y. Wu, Tetrahedron 2013, 69, 320; (b) A. Banerjee,
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0 J. Miao, H. Ge, Org. Lett. 2013, 10.1021/ol400919u.
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E. Callegari, K. R. Henne, A. E. Mutlib, D. K. Dalvie, J. S. Lee, Y. Nakai, J. P.

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O’Donnell, J. Boer, S. P. Harriman, Curr. Drug Metab. 2005, 6, 161; (e) I. Hutchinson,
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6 I. Takehiro, K. Satoko, S. Hiroaki, Jpn. Kokai Tokkyo Koho (2011), JP 2011021010,
Feb 3, 2011.
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7 Q. Ding, H. Ji, D. Wang, Y. Lin, W. Yu, Y. Peng, J. Organomet. Chem. 2012, 711,
2.
Graphical abstract:

ACCEPTED MANUSCRIPT
a
Table 1. Optimization of the reaction conditions
Entry [Pd]
Pd(OAc)2
Solvent Oxidant Ligand
Yield
b
(
%)
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
toluene
AcOH
DMAc
DMF
DMSO
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
DTBP
O2
-
-
-
-
-
-
-
-
-
-
-
-
31
15
27
24
13
11
18
-
PdCl2
Pd (dba)3
2
PdCl (CH CN)
2
3
2
PdCl (PhCN)2
2
PdCl (PPh )
2
3 2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Oxone
K S O
8
-
-
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
2
2
c
d
e
e
e
e
e
e
e
e
e
e
e
e
e
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
45
52
61
37
32
28
-
TMEDA
DMEDA
PPh3
L-proline 42
BQ
DDQ
1,10-phen
BQ
BQ
BQ
68
trace
-
50
30
trace
-
trace
BQ
BQ

ACCEPTED MANUSCRIPT
e
e
2
6
7
Pd(OAc)2
Pd(OAc)2
NMP
TBHP
BQ
BQ
20
35
2
CH CN TBHP
3
a
Conditions: 1a (0.2 mmol), 2a (0.6 mmol), [Pd] catalyst (5 mol %), oxidant (3.0 equiv),
o
ligand (10 mol%) 110 C, 2 h.
b
Isolated yield based on 1a.
c
4
.0 equiv of TBHP were used.
d
e
6
.0 equiv of TBHP were used.
7
.0 equiv of TBHP were used.
a
Table 2. Reaction of phenylmethanol with 2-arylbenzo[d]thiazoles
Entry
1
1
1
Product 3
Yield Entry
1
1
Product 3
Yield
(%)
b
b
(
%)
68
95
85
11
12
13
22
70
83
k
a
b
c
3j
3
a
Cl
2
3
N
S
O
1l
1
1
Ph
Cl
3
k
3
b
N
S
O
1m
3l
Ph
3
c
4
5
6
92
83
82
14
15
16
N
S
65
65
81
1
1
n
o
1
1
1
d
e
f
3m
3
d
3
n
3
e
1p
3
o
3
f

ACCEPTED MANUSCRIPT
Cl
7
8
9
1
75
80
92
-
17
18
19
20
72
67
62
32
N
S
1
g
1q
3
p
3
g
1
1
r
s
1
1
h
i
3
q
3
h
3
r
3
-
i
c
0
1
t
1
j
3
s
a
Conditions: 2-arylbenzo[d]thiazole 1 (0.2 mmol), phenylmethanol 2a (0.6 mmol),
o
Pd(OAc) (5 mol%), TBHP (7.0 equiv), BQ (10 mol%), PhCl, 110 C, 2h.
2
b
c
Isolated yield based on 1. With 35% yield of bis-acylated product.
a
Table 3. Acylation of 2-arylbenzo[d]thiazole with primary alcohols
Entry
1
2
2
Product 3
Yield Entry
2
2
Product 3
Yield
(%)
b
b
(
%)
92
74
85
4
5
6
87
35
-
a
3i
d
3
v
2
2
2
b
c
2e
3
3
t
3w
3
n
BuOH
2
f
3
x
u
a
Conditions: 2-arylbenzo[d]thiazole 1i (0.2 mmol), primary alcohols 2 (0.6 mmol),
o
Pd(OAc) (5 mol%), TBHP (7.0 equiv), BQ (10 mol%), PhCl, 110 C, 2h.
2

ACCEPTED MANUSCRIPT
b
Isolated yield based on 1i.
Scheme 1 Plausible mechanism for the Pd-catalyzed ortho-acylation reaction.

ACCEPTED MANUSCRIPT
Palladium-catalyzed direct ortho-acylation through an oxidative
coupling of 2-arylbenzothiazoles with benzylic alcohols
*
Qiuping Ding, Huafang Ji, Changqing Ye, Jiajia Wang, Junyan Wang, Liyun
Zhou and 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
Supporting Information
1
2
. Characterization data of some new substrate 1.
. NMR spectra of all new compounds 3 and 1.
S2-S6
S7-S45
*
Corresponding author：Tel.: +86 791 88120380; fax: +86 791 88120380; E-mail:
dqpjxnu@gmail.com; yiyuanpeng@yahoo.com
S1

ACCEPTED MANUSCRIPT
o
2
-(2-chlorophenyl)benzo[d]thiazole (1b) mp: 86-87 C;
1
H NMR (400 MHz, CDCl ) δ 7.27-7.34 (m, 3H), 7.41-7.46 (m, 2H), 7.83 (d, J = 8.0 Hz,
3
1
H), 8.10 (d, J = 8.0 Hz, 1H), 8.17 (dd, J = 2.4, 7.2 Hz, 1H);
1
3
C NMR (100 MHz, CDCl ) δ 121.4, 123.5, 125.5, 126.3, 127.1, 130.8, 131.1, 131.8,
3
1
32.3, 132.7, 136.2, 152.6, 164.1;
o
2
-(2-chlorophenyl)-6-methylbenzo[d]thiazole (1c) mp: 101-102 C;
1
H NMR (400 MHz, CDCl ) δ 2.45 (s, 3H), 7.28 (d, J = 8.0 Hz, 1H), 7.30-7.35 (m, 2H),
3
7
.46 (d, J = 6.4 Hz, 1H), 7.65 (s, 1H), 7.98 (d, J = 8.4 Hz, 1H), 8.17 (d, J = 6.4 Hz, 1H);
1
3
C NMR (100 MHz, CDCl ) δ 21.6, 121.0, 123.0, 127.1, 128.0, 130.8, 130.9, 131.7,
3
1
32.4, 132.6, 135.6, 136.4, 150.7, 163.0;
o
6
-chloro-2-(2-chlorophenyl)benzo[d]thiazole (1d) mp: 136-137 C;
1
H NMR (400 MHz, CDCl ) δ 7.36-7.42 (m, 2H), 7.47 (d, J = 8.4 Hz, 1H), 7.50-7.54 (m,
3
1
H), 7.90 (s, 1H), 8.02 (d, J = 8.8 Hz, 1H), 8.20-8.24 (m, 1H);
1
3
C NMR (100 MHz, CDCl ) δ 120.9, 124.2, 127.2, 130.9, 131.4, 131.7, 131.8, 132.7,
3
1
37.3, 151.0, 164.6;
o
2
-(2-chlorophenyl)-6-fluorobenzo[d]thiazole (1e) mp: 127-128 C;
1
H NMR (400 MHz, CDCl ) δ 7.22 (t, J = 8.8 Hz, 1H), 7.35-7.37 (m, 2H), 7.46-7.52
3
(m,1H), 7.57 (d, J = 8.0 Hz, 1H), 8.01-8.05 (m, 1H), 8.17-8.21 (m, 1H);
S2

ACCEPTED MANUSCRIPT
1
3
2
2
C NMR (100 MHz, CDCl ) δ 107.4 (d, J = 26.5 Hz), 115.1 (d, J = 24.7 Hz),
3
C-F
C-F
3
3
1
24.5 (d, J = 9.3 Hz), 127.1, 130.8, 131.2, 131.6, 131.9, 132.6, 137.1 (d, J = 11.1
C-F C-F
1
Hz), 149.1, 160.6 (d, J = 244.8 Hz), 163.8;
C-F
o
2
-(2-fluorophenyl)benzo[d]thiazole (1f) mp: 97-98 C;
1
H NMR (400 MHz, CDCl ) δ 7.19 (t, J = 9.6 Hz, 1H), 7.26 (t, J = 7.6 Hz, 1H), 7.35-7.44
3
(m, 2H), 7.48 (t, J = 7.6 Hz, 1H), 7.89 (d, J = 7.6 Hz, 1H), 8.11 (d, J = 8.0 Hz, 1H), 8.39
1
3
2
(
t, J = 7.6 Hz, 1H); C NMR (100 MHz, CDCl ) δ 116.4 (d, J = 21.8 Hz), 121.4,
3 C-F
3
3
1
21.5, 123.3, 124.7, 125.3, 126.3, 129.8, 132.1 (d, J = 6.8 Hz), 135.8 (d, J = 6.8
C-F C-F
1
Hz), 152.6, 160.6 (d, J = 252.0 Hz), 161.0;
C-F
o
2
-(2-fluorophenyl)-6-methylbenzo[d]thiazole (1g) mp: 111-112 C;
1
H NMR (400 MHz, CDCl ) δ 2.46 (s, 3H), 7.15-7.29 (m, 3H), 7.37-7.42 (m, 1H), 7.65
3
(s, 1H), 7.97 (d, J = 8.4 Hz, 1H), 8.37 (dt, J = 1.6, 8.0 Hz, 1H);
1
3
2
3
C NMR (100 MHz, CDCl ) δ 21.6, 116.3 (d, J = 21.9 Hz), 121.1, 121.6 (d, J
=
=
3
C-F
C-F
3
3
1
1.0 Hz), 122.8, 124.6, 128.0, 129.7, 131.9 (d, J = 8.7 Hz), 135.5, 136.0 (d, J
C-F
C-F
1
7
.8 Hz), 150.7, 160.0, 160.5 (d, J = 251.8 Hz);
C-F
o
6
-chloro-2-(2-fluorophenyl)benzo[d]thiazole (1h) mp: 149-149 C;
1
H NMR (400 MHz, CDCl ) δ 7.22 (t, J = 9.2 Hz, 1H), 7.30 (t, J = 6.8 Hz, 1H), 7.45 (d, J
3
=
8.0 Hz, 2H), 7.88 (s, 1H), 7.99 (d, J = 8.0 Hz, 1H), 8.35-8.43 (m, 1H);
1
3
2
C NMR (100 MHz, CDCl ) δ 116.4 (d, J = 21.8 Hz), 121.0, 121.1, 124.0, 124.7,
3
C-F
3
3
1
27.2, 129.7, 131.2, 132.4 (d, J = 8.7 Hz), 136.9 (d, J = 8.4 Hz), 151.1, 160.6 (d,
C-F C-F
1
3
JC-F = 252.1 Hz), 161.5 (d, J = 5.9 Hz);
C-F
S3

ACCEPTED MANUSCRIPT
o
6
-fluoro-2-(2-fluorophenyl)benzo[d]thiazole (1i) mp: 124-125 C;
1
H NMR (400 MHz, CDCl ) δ 7.19-7.31 (m, 3H), 7.43-7.46 (m, 1H), 7.59 (dd, J = 2.4,
3
8
.0 Hz, 1H), 8.03 (dd, J = 4.8, 9.2 Hz, 1H), 8.36 (dt, J = 1.6, 8.0 Hz, 1H);
1
3
2
2
C NMR (100 MHz, CDCl ) δ 107.5 (d, J = 26.5 Hz), 115.1 (d, J = 24.7 Hz),
3
C-F
C-F
2
3
3
1
16.4 (d, J = 21.8 Hz), 121.2 (d, J = 11.2 Hz), 124.3 (d, J = 9.4 Hz), 124.7,
C-F C-F C-F
3
3
3
1
1
29.6, 132.2 (d, J = 8.7 Hz), 136.7 (d, J = 8.5 Hz), 136.8 (d, J = 8.4 Hz),
C-F C-F C-F
1
3
49.2, 160.4 (d, J = 251.9 Hz), 160.5 (d, J = 244.3 Hz), 160.8;
C-F
C-F
o
6
-methyl-2-(o-tolyl)benzo[d]thiazole (1k) mp: 97-98 C;
1
H NMR (400 MHz, CDCl ) δ 2.56 (s, 3H), 2.71 (s, 3H), 7.39-7.44 (m, 2H), 7.50-7.53
3
(m, 2H), 7.80 (s, 1H), 8.01 (d, J = 7.6 Hz, 1H), 8.51 (d, J = 8.4 Hz, 1H);
1
3
C NMR (100 MHz, CDCl ) δ 21.6, 21.8, 120.8, 121.5, 127.0, 127.9, 130.2, 131.2,
3
1
32.1, 132.4, 132.6, 137.7, 138.2, 143.5, 169.6;
o
6
-chloro-2-(o-tolyl)benzo[d]thiazole (1l) mp: 94-95 C;
1
H NMR (400 MHz, CDCl ) δ 2.64 (s, 3H), 7.28-7.36 (m, 3H), 7.43 (dd, J = 2.0, 8.8 Hz,
3
1
H), 7.72 (d, J = 7.6 Hz, 1H), 7.85 (d, J = 6.0 Hz,1H), 7.97 (d, J = 8.8 Hz, 1H);
1
3
C NMR (100 MHz, CDCl ) δ 21.5, 121.0, 124.1, 126.2, 127.0, 130.3, 130.5, 131.0,
3
1
31.7, 132.6, 136.7, 137.4, 152.4, 168.5;
o
6
-fluoro-2-(o-tolyl)benzo[d]thiazole (1m) mp: 64-65 C;
S4