Aryl-aryl coupling via palladium-catalyzed C-P/C-H bond cleavage

Article abstract of DOI:10.1016/j.tet.2013.02.001

The first example of aryl-aryl coupling through palladium-catalyzed C-P/C-H bond cleavage with good functional group tolerance is disclosed. This work demonstrates the phosphines could be used as coupling partners in palladium-catalyzed aryl-aryl coupling

Full text of DOI:10.1016/j.tet.2013.02.001

Tetrahedron 69 (2013) 3281e3286
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Arylearyl coupling via palladium-catalyzed CeP/CeH bond cleavage
*
Ziyuan Li, Haipin Zhou, Jinyi Xu, Xiaoming Wu, Hequan Yao
State Key Laboratory of Natural Medicines and Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
The first example of arylearyl coupling through palladium-catalyzed CeP/CeH bond cleavage with good
functional group tolerance is disclosed. This work demonstrates the phosphines could be used as cou-
pling partners in palladium-catalyzed arylearyl coupling.
Received 26 December 2012
Received in revised form 22 January 2013
Accepted 1 February 2013
Ó 2013 Elsevier Ltd. All rights reserved.
Available online 8 February 2013
Keywords:
CeP cleavage
Arylearyl coupling
Palladium-catalyzed
Azole
Triphenylphosphine
1. Introduction
In the past several decades, transitional metal catalyzed1 carbon
(sp2)-carbon (sp2) cross-coupling reactions for building arylearyl
scaffolds have been massively developed. In these reactions,
phosphines have been commonly used as potent ligands,2 due to
their ability to accelerate the oxidative addition step and may also
favor the transmetalation step.3 In addition to their utilization as
ligands, several reports suggested that phosphines could also be
used as coupling partners providing aryl groups to substrates
through CeP bond cleavage. For instance, it has been reported that
ruthenium4 or irinium5 could cleave the CeP bond in triar-
ylphosphines, which were used as aryl donors (Scheme 1a). Other
than these expensive metals, the more cost-effective and
commonly-used palladium has been reported to cleave the CeP
bond in tetraphenylphosphonium salt giving alkenylated benzene
in a Heck-type reaction (Scheme 1b).6 Moreover, triarylphosphines
has also been used as the phosphinating reagents in palladium-
catalyzed phosphination for the preparation of various phosphine
ligands (Scheme 1b).7 Up to date,8 few example of arylation of
unpreactivated arenes or heteroarenes via palladium-catalyzed
CeP bond cleavage, however, has been reported to the best of our
knowledge (Scheme 1c).9
Scheme 1. Discovery of CeC coupling of heteroarenes with triarylphosphine as aryl
donor.
originally focusing on the decarboxylative arylation.3a,12 However,
when we treated methyl oxazole-4-carboxylate (1a) with different
benzoic acids under reaction conditions for decarboxylative aryla-
tion, only 5-phenyloxazole (2a) was obtained. We speculated that
the phenyl group of 2a was donated from triphenylphosphine
(Ph3P) rather than benzoic acids, suggesting this arylearyl coupling
is realized via CeP bond cleavage. Recognizing the novelty of this
process, here we report our findings about a new Pd-catalyzed
arylearyl coupling reaction via CeP/CeH bond cleavage.
As a continuation of our previously works10 on Pd(II)-catalyzed
C(5)-H bond activation of azole-4-carboxylic derivatives,11 we were
* Corresponding author. Tel.: þ86 25 83271042; fax: þ86 25 83301606; e-mail
address: hyao@cpu.edu.cn (H. Yao).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.02.001

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Z. Li et al. / Tetrahedron 69 (2013) 3281e3286
Table 2
2. Results and discussion
Scope of azolesa
Our initial investigation focused on the coupling of 1a with Ph3P
as summarized in Table 1.13 A preliminary trial using 1 equiv of Ph3P
without benzoic acid still afforded the C5-phenyl product 2a, albeit
in very low yield and most of 1a was converted to homocoupling
byproduct 3a (entry 1). Subsequent screening on the additive
revealed that the use of PivOH could remarkably increase the yield
of the desired product 2a to 42% (entry 2). Changing the reaction
temperature, and the loading of Ag(I) and PivOH could generate 2a
in only moderate yield.13 To our delight, screening on acidic addi-
tives indicated that the yield of 2a could further rise to 70% while 3a
was not produced, when 2 equiv of TFA was used (entry 3). We then
explored the reaction in various solvents, and found that NMP was
the best choice (entry 4). Other palladium catalysts or other com-
monly used oxidants were shown to be less effective.13 Changing
loading of PPh3 from 0.33 equiv to 1.5 equiv revealed that
0.66 equiv of PPh3 showed no difference in the yield of 2a but
reacted faster, comparing to 1.5 equiv of PPh3 (entries 5e10). This
also suggested that at least two phenyl groups in one phosphine
compound could be provided to the substrate, showing the
promising efficiency of the triphenylphosphines as aryl donors.
Replacing the PPh3 with triphenylphosphine oxide provided no
arylated product, which excluded the possibility that the CeP bond
cleavage occurs on the phosphine oxide (entry 11). A control ex-
periment without palladium catalyst showed that the palladium
catalyst played an important role in this reaction (entry 12). Finally,
the reaction conditions in entries 7 and 10 were selected for further
investigation on the reaction scope.
a
Reaction conditions: azole (0.5 mmol), Ph3P (0.33 mmol), Pd(OAc)2
(0.05mmol), AgOAc (3 mmol) and TFA (1 mmol) in NMP (2 mL) at 120 oC
for 24 h. Isolated yields. b1.5 equiv of Ph3P was used, and reacted for 48 h.
Table 1
Optimization of reaction conditionsa
provide an opportunity for further synthetic functionalization.
Similar patterns were observed on 2-phenyl substituted thiazoles
(2he2o). In addition, 2-alkyl or 2-carbonylsubstituted substrates
could be phenylated in good yields (2pe2s) and the arylation of 2-
phenylthiazole occurred selectively at C5-position (2t). Notably, 2-
phenyl-4-methoxymethyl thiazole could also be phenylated to af-
ford the corresponding product (2u) in moderate yield under the
optimized conditions, while it was not efficiently arylated with
unpreactivated benzene via double CeH cleavage.10a
Entry
Ph3P (equiv)
Additive (equiv)
Solvent
Yields (%) (2a/3a/1a)b
1
1
d
DMF
DMF
DMF
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
17/66/8
42/36/23
70/trace/23
78/7/7
52/40/0
65/28/0
81/8/4
2
1
1
1
PivOH (2)
TFA (2)
TFA (2)
TFA (2)
TFA (2)
TFA (2)
TFA (2)
TFA (2)
TFA (2)
TFA (2)
TFA (2)
3c
4
Next, the effective conditions were extended to a variety of
substituted triarylphosphines as illustrated in Table 3.15 To our
5
6
7
8
0.33
0.5
0.66
1.2
1.5
1.5
1.5
1.5
Table 3
Scope of triarylphosphinesa
82/6/6
9
72/6/17
86/trace/7
0/92/trace
0/0/95
10d
11e
12d,f
a
Reaction conditions: methyl 2-phenylthiazole-4-carboxylate 1a (0.5 mmol),
Ph3P (1.5 mmol), Pd(OAc)2 (0.05 mmol), AgOAc (3 mmol) and additive in DMF or
NMP (2 mL) at 120 ꢀC for 24 h.
b
Isolated yields.
c
Reacted at 140 ꢀC.
d
Reacted for 48 h.
Ph3P was replaced with triphenylphosphine oxide(Ph3P]O).
No palladium catalyst.
e
f
With the optimized conditions established, we first evaluated
the coupling reactions of various azoles with PPh3 as illustrated in
Table 2, 2ae2u.14 Generally, both oxazole and thiazole substrates
could afford the desired products in good to excellent yields. A wide
range of substituents on azoles at C2 position were tolerated under
these conditions. For 2-phenyloxazole substrates, electron-
donating substitutions on phenyl group gave the corresponding
products in excellent yields (2b, 2c), while trifluoromethyl and
halogen groups slightly declined the yields (2de2g). It is note-
worthy that the tolerance of chloro and bromo substituents might
a
Reaction conditions: azole (0.5 mmol), Ar3P (0.33 mmol), Pd(OAc)2
(0.05mmol), AgOAc (3 mmol) and TFA (1 mmol) in NMP (2 mL) at 120
oC for 24 h. Isolated yields. b1.5 equiv of Ar3P was used, reacted for 48 h.

Z. Li et al. / Tetrahedron 69 (2013) 3281e3286
3283
delight, most substituted triarylphosphines were well tolerated
under the optimized conditions, leading to the desired products in
moderate to good yields (4a, 4b, 4de4f, 4he4l). For example, tri(m-
methylphenyl)phosphine or tri(p-methylphenyl) phosphine affor-
ded the corresponding products in good yields (4a, 4b, 4h, 4i).
When halogen or methoxyl substitutions were introduced on tri-
arylphosphine, the desired products were achieved in moderate
yields (4de4f, 4je4l). Electron-withdrawing substitution on the
benzene group of triarylphosphines, such as CF3, led to the decrease
in the yield of the phenylated product (4g). To our disappointed, the
use of the sterically hindered triarylphosphine with ortho-methyl
substitution failed to give the corresponding product (4c).
In addition, our protocol could be applied to other heteroarenes
(Scheme 2). Benzothiazole (5) reacted smoothly to afford 2-
phenylbenzothiazole (6) in 79% yield. Moreover, free indole (7)
could be phenylated at C2 position to give the desired product 8 in
53% yield. Very interestingly, acetanilide (9), a typical model sub-
strate for palladium catalyzed CeH bond activation, did not provide
the desired arylated product (10).
electron spray ionization (ESI) as the ion source. All substrates were
synthesized from corresponding aldehydes or nitriles by our re-
cently disclosed methods.16 Unless otherwise indicated, all re-
agents and solvents were obtained from commercial suppliers and
used as received.
4.2. General experimental procedure
A suspension of Pd(OAc)2 (10 mol %), Ar3P (0.33 mmol or
0.75 mmol), AgOAc (3.0 mmol), TFA (1.0 mmol) and azole-4-
carboxylates (0.5 mmol) in NMP (2 mL) was introduced to
a Schlenk tube. After stirring at 120 ꢀC under argon for 24 h (re-
actions with 0.33 mmol of Ph3P), or 48 h (reactions with 0.75 mmol
of Ph3P), the reaction mixture was diluted with ethyl acetate, and
then filtered through a pad of Celite. Volatiles were removed in
vacuo to give the crude products, which was purified by flash col-
umn chromatography on silica gel to afford pure arylated products.
4.3. Characterization data of title compounds
4.3.1. Methyl
113 mg (81%). 1H NMR (300 MHz, CDCl3)
2,5-diphenyloxazole-4-carboxylate10a
(2a). Yield
d
3.97 (s, 3H), 7.47e7.49 (m,
6H), 8.13e8.16 (m, 4H) ppm; 13C NMR (75 MHz, CDCl3)
d 162.7,159.8,
155.3, 131.1, 130.4, 128.8, 128.5, 128.0, 127.0, 126.8, 126.3, 52.4 ppm.
4.3.2. Methyl 2-(p-methylphenyl)-5-phenyloxazole-4-carboxylate
(2b). Yield 131 mg (90%). White solid, mp 109e100.5 ꢀC; 1H NMR
(300 MHz, CDCl3)
7.45e7.51 (m, 3H), 8.03 (d, J¼7.9 Hz, 2H), 8.14 (d, J¼7.3 Hz, 2H)
ppm; 13C NMR (75 MHz, CDCl3)
162.3, 159.5, 154.5, 141.1, 129.8,
d
2.39 (s, 3H), 3.97 (s, 3H), 7.27 (d, J¼7.9 Hz, 2H),
d
129.0, 127.9, 127.3, 126.6, 126.3, 123.1, 51.9, 21.1 ppm; IR (KBr) 2944,
1721, 1562, 1502, 1216, 1097, 1011, 828, 769, 731, 690 cmꢁ1; HRMS
(ESI) calcd for [C18H15NO3þH]þ 294.1125, found 294.1128.
4.3.3. Methyl 2-(p-methoxylphenyl)-5-phenyloxazole-4-carboxy-
late10a (2c). Yield 129 mg (84%). 1H NMR (300 MHz, CDCl3)
d
3.82
(s, 3H), 3.95 (s, 3H), 6.96 (d, J¼8.8 Hz, 2H), 7.40e7.50 (m, 3H),
8.05e8.13 (m, 4H) ppm; 13C NMR (75 MHz, CDCl3)
162.8, 162.0,
Scheme 2. Phenylation of other heteroarenes via CeP cleavage.
d
3. Conclusion
159.9, 154.8, 130.2, 128.6, 128.4, 128.3, 127.8, 127.2, 119.0, 114.3, 55.4,
52.3 ppm.
In summary, we have discovered a novel palladium-catalyzed
arylearyl cross-coupling reaction between triphenylphosphines
and unpreactivated simple arenes through C(sp2)-P/C(sp2)-H bond
cleavage. This is the first report that arylearyl coupling via CeP
bond cleavage of phosphines could be catalyzed by a cost-effective
palladium catalyst, rather than more expensive Ru or Ir catalysts.
Further studies on the mechanism of this reaction are currently
undergoing in our laboratory.
4.3.4. Methyl 2-(p-trifluoromethylphenyl)-5-phenyloxazole-4-carbo-
xylate10a (2d). Yield 126 mg (73%). 1H NMR (300 MHz, CDCl3)
d
3.94 (s, 3H), 7.45e7.48 (m, 3H), 7.70 (d, J¼8.2 Hz, 2H), 8.09e8.12
(m, 2H), 8.21 (d, J¼8.2 Hz, 2H) ppm; 13C NMR (75 MHz, CDCl3)
d
162.3, 158.2, 155.8, 132.8, 132.4, 130.6, 129.4, 128.2, 127.0, 126.6,
125.9, 125.8, 125.7, 125.5, 121.9, 52.4 ppm.
4.3.5. Methyl 2-(p-fluorophenyl)-5-phenyloxazole-4-carboxylate
(2e). Yield 121 mg (82%). White solid, mp 142e144 ꢀC; 1H NMR
4. Experimental section
4.1. General information
(300 MHz, CDCl3)
d
3.94 (s, 3H), 7.14 (t, J¼8.6 Hz, 2H), 7.42e7.48
(m, 3H), 8.01e8.14 (m, 4H) ppm; 13C NMR (75 MHz, CDCl3)
d
165.1,
161.8, 161.5, 157.9, 154.2, 129.4, 128.0, 127.9, 127.4, 126.9, 125.8,
121.6, 115.2, 114.9, 51.3 ppm; IR (KBr) 3062, 2950, 1726, 1612, 1500,
1363, 1222, 1107, 1012, 849, 734, 686 cmꢁ1; HRMS (ESI) calcd for
[C17H12FNO3þH]þ 298.0880, found 298.0881.
Melting point (mp) was measured on a microscopic melting
point apparatus. 1H and 13C NMR spectra were collected using
CDCl3 as solvent. Chemical shifts of 1H NMR were recorded in parts
per million (ppm,
with the solvent resonance as an internal standard (CDCl3:
¼7.26 ppm). Data are reported as follows: chemical shift in ppm
d
) relative to tetramethylsilane (
d
¼0.00 ppm)
4.3.6. Methyl 2-(p-chlorophenyl)-5-phenyloxazole-4-carboxylate10a
d
(2f). Yield 125 mg (80%). 1H NMR (300 MHz, CDCl3)
d
3.95 (s,
3H), 7.40e7.47 (m, 5H), 8.02e8.11 (m, 4H) ppm; 13C NMR (75 MHz,
CDCl3) 162.5, 158.8, 155.4, 137.3, 130.5, 129.2, 128.5, 128.4, 128.1,
(
d
), multiplicity (s¼singlet, d¼doublet, t¼triplet, q¼quartet, br
s¼broad singlet, m¼multiplet), coupling constant (Hertz, Hz), and
d
integration. Chemical shifts of 13C NMR were reported in ppm with
126.8, 124.8, 52.4 ppm.
the solvent as the internal standard (CDCl3:
d
¼77.0 ppm). Infrared
spectra (IR) were recorded on an FT-IR spectrometer; absorptions
are reported in reciprocal centimeters. High Resolution Mass
measurement was performed on a Q-TOF mass spectrometer with
4.3.7. Methyl 2-(p-bromophenyl)-5-phenyloxazole-4-carboxylate
(2g). Yield 135 mg (76%). White solid, mp 138e139 ꢀC; 1H NMR
(300 MHz, CDCl3)
d
3.96 (s, 3H), 7.42e7.50 (m, 3H), 7.61 (d, J¼8.5 Hz,

3284
Z. Li et al. / Tetrahedron 69 (2013) 3281e3286
2H), 8.00 (d, J¼8.5 Hz, 2H), 8.09e8.13 (m, 2H) ppm; 13C NMR
145.7, 139.5, 130.1, 129.4, 128.5, 127.6, 60.7, 18.7, 13.6 ppm; IR (KBr)
2967, 2925, 1716, 1477, 1325, 1202, 1037, 745, 688 cmꢁ1; HRMS (ESI)
calcd for [C13H13NO2SþH]þ 248.0745, found 248.0747.
(75 MHz, CDCl3) d 162.0, 158.4, 155.0, 131.6, 130.0, 128.0, 127.9, 127.7,
126.2, 125.3, 124.7, 52.0 ppm; IR (KBr) 2997, 2950, 1724, 1483, 1462,
1211, 1072, 1010, 827, 750, 689 cmꢁ1; HRMS (ESI) calcd for
[C17H12BrNO3þH]þ 358.0073, found 358.0069.
4.3.17. Ethyl 2-ethyl-5-phenylthiazole-4-carboxylate (2q). Yield
100 mg (81%). Colorless oil; 1H NMR (300 MHz, CDCl3)
d 1.21 (t,
4.3.8. Methyl 2,5-diphenylthiazole-4-carboxylate10a (2h). Yield
J¼7.1 Hz, 3H), 1.41 (t, J¼7.6 Hz, 3H), 3.07 (q, J¼7.6 Hz, 2H), 4.27 (q,
126 mg (86%). 1H NMR (300 MHz, CDCl3)
d
3.86 (s, 3H), 7.41e7.46
(m, 6H), 7.53e7.57 (m, 2H), 7.96e8.00 (m, 2H) ppm; 13C NMR
(75 MHz, CDCl3) 164.3, 160.8, 144.5, 139.0, 130.9, 128.8, 128.4,
J¼7.1 Hz, 2H), 7.37e7.40 (m, 3H), 7.44e7.47 (m, 2H) ppm; 13C NMR
(75 MHz, CDCl3) d 170.8, 161.6, 145.1, 139.5, 130.3, 129.4, 128.4, 127.5,
d
60.6, 26.6, 13.8, 13.5 ppm; IR (KBr) 3003, 2979, 1720, 1476, 1276,
128.0, 127.4, 127.2, 126.4, 124.9, 50.4 ppm.
1260, 1190, 1025, 722, 739 cmꢁ1
; HRMS (ESI) calcd for
[C14H15NO2SþH]þ 262.0896, found 262.0896.
4.3.9. Methyl 2-(p-methylphenyl)-5-phenylthiazole-4-carboxylate10a
(2i). Yield 139 mg (90%). 1H NMR (300 MHz, CDCl3)
d
2.38 (s, 3H),
4.3.18. Ethyl 2-propyl-5-phenylthiazole-4-carboxylate (2r). Yield
3.84 (s, 3H), 7.24 (d, J¼8.2 Hz, 2H), 7.40e7.42 (m, 3H), 7.51e7.53 (m,
108 mg (79%). Colorless oil; 1H NMR (300 MHz, CDCl3)
d 1.04 (t,
2H), 7.86 (d, J¼8.2 Hz, 2H) ppm; 13C NMR (75 MHz, CDCl3)
d
166.3,
J¼7.5 Hz, 3H), 1.20 (t, J¼7.1 Hz, 3H), 1.79e1.89 (m, 2H), 3.00 (q,
162.7,146.0,141.0,140.7,130.4,130.1,129.9,129.7,129.2,128.3,126.7,
52.3, 21.5 ppm.
J¼7.5 Hz, 2H), 4.27 (q, J¼7.1 Hz, 2H), 7.36e7.49 (m, 3H), 7.43e7.46
(m, 2H) ppm; 13C NMR (75 MHz, CDCl3)
d 169.2, 161.6, 145.1, 139.5,
130.3, 129.4, 128.4, 127.5, 60.6, 35.0, 23.0, 13.5, 13.2 ppm; IR (KBr)
2963, 2932, 1725, 1478, 1324, 1191, 1026, 754, 696 cmꢁ1; HRMS (ESI)
calcd for [C15H17NO2SþH]þ 276.1053, found 276.1055.
4.3.10. Methyl 2-(p-methoxylphenyl)-5-phenylthiazole-4-carboxy-
late10a (2j). Yield 141 mg (87%). 1H NMR (300 MHz, CDCl3)
d 3.83
(s, 3H), 3.84 (s, 3H), 6.95 (d, J¼8.8 Hz, 2H), 7.40e7.43 (m, 3H),
7.51e7.54 (m, 2H), 7.91 (d, J¼8.8 Hz, 2H) ppm; 13C NMR (75 MHz,
4.3.19. Ethyl 2-benzoyl-5-phenylthiazole-4-carboxylate (2s). Yield
134 mg (80%). White solid, mp 93e94 ꢀC; 1H NMR (300 MHz, CDCl3)
CDCl3)
d 166.0, 162.8, 161.7, 145.5, 140.5, 130.5, 129.9, 129.2, 128.3,
128.2, 125.6, 114.3, 55.4, 52.2 ppm.
d
1.23 (t, J¼7.1 Hz, 3H), 4.31 (q, J¼7.1 Hz, 2H), 7.43e7.47 (m, 3H),
7.49e7.56 (m, 4H), 7.65 (t, J¼7.2 Hz, 1H), 8.58 (d, J¼7.3 Hz, 2H) ppm;
13C NMR (75 MHz, CDCl3)
183.5, 165.2, 161.9, 152.0, 142.4, 134.5,
4.3.11. Methyl 2-(p-nitrophenyl)-5-phenylthiazole-4-carboxylate
d
(2k). Yield 121 mg (71%). Yellow solid, mp 173e174 ꢀC; 1H NMR
134.0, 131.4, 129.9, 129.8, 128.6, 128.4, 61.5, 13.9 ppm; IR (KBr) 3050,
2979, 2968, 1722, 1664, 1458, 1331, 1295, 1200, 1140, 1031, 876, 750,
686 cmꢁ1; HRMS (ESI) calcd for [C19H15NO3SþH]þ 338.0851, found
338.0854.
(300 MHz, CDCl3)
d
3.87 (s, 3H), 7.47e7.56 (m, 5H), 8.15 (d, J¼8.7 Hz,
2H), 8.31 (d, J¼8.7 Hz, 2H) ppm; 13C NMR (75 MHz, CDCl3)
d 161.9,
161.3, 147.8, 147.2, 137.1, 128.9, 128.8, 128.6, 127.4, 126.4, 123.4,
51.5 ppm; IR (KBr) 2943,1726,1596,1513,1345,1209,1018, 856, 751,
690 cmꢁ1; HRMS (ESI) calcd for [C17H12N2O4SþH]þ 341.0596, found
341.0598.
4.3.20. 2,5-Diphenylthiazole (2t). Yield 89 mg (75%). Light yellow
solid, mp 106e107 ꢀC; 1H NMR (300 MHz, CDCl3)
d 7.32e7.47 (m, 6H),
7.62 (d, J¼7.7 Hz, 2H), 7.96e8.00 (m, 2H), 8.03 (s, 1H) ppm; 13C NMR
4.3.12. Methyl 2-(p-trifluoromethylphenyl)-5-phenylthiazole-4-
carboxylate10a (2l). Yield 145 mg (80%). 1H NMR (300 MHz,
(75 MHz, CDCl3) d 167.2, 139.2, 133.7, 131.4, 130.0, 129.1, 129.0, 128.3,
126.7, 126.4 ppm; IR (KBr) 1450, 1400, 1072, 754, 690, 631 cmꢁ1
;
CDCl3)
d
3.86 (s, 3H), 7.44e7.46 (m, 3H), 7.52e7.56 (m, 2H), 7.71 (d,
HRMS (ESI) calcd for [C15H11NSþH]þ 238.0685, found 238.0691.
J¼8.2 Hz, 2H), 8.09 (d, J¼8.2 Hz, 2H) ppm; 13C NMR (75 MHz, CDCl3)
d
164.1, 162.5, 147.4, 141.3, 135.8, 132.5, 132.0, 129.9, 129.6, 128.3,
4.3.21. 2,5-Diphenylthiazol-4-ylmethyl ether (2u). Yield 92 mg
(66%). Colorless oil; 1H NMR (300 MHz, CDCl3)
3.49 (s, 3H), 4.54 (s,
2H), 7.36e7.45 (m, 6H), 7.57 (d, J¼7.1 Hz, 2H), 7.95e7.98 (m, 2H)
ppm; 13C NMR (75 MHz, CDCl3)
164.8, 147.9, 136.7, 132.6, 130.4,
129.0, 128.4, 127.9, 127.8, 127.5, 125.6, 67.2, 57.4 ppm; IR (KBr) 2923,
2885, 1593, 1485, 1460, 1095, 763, 690 cmꢁ1; HRMS (ESI) calcd for
[C17H15NOSþH]þ 282.0947, found 282.0952.
127.0, 126.1, 126.0, 125.6, 122.0, 52.4 ppm.
d
4.3.13. Methyl 2-(p-fluorophenyl)-5-phenylthiazole-4-carboxylate10a
d
(2m). Yield 133 mg (85%). 1H NMR (300 MHz, CDCl3)
d
3.85 (s,
3H), 7.13 (t, J¼8.6 Hz, 2H), 7.42e7.44 (m, 3H), 7.52e7.55 (m, 2H),
7.94e7.98 (m, 2H) ppm; 13C NMR (75 MHz, CDCl3)
165.9, 164.9,
d
162.6, 146.4, 140.8, 130.1, 129.9, 129.3, 129.1, 128.8, 128.7, 128.3,
116.3, 116.0, 52.3 ppm.
4.3.22. Methyl 2-phenyl-5-(4-methylphenyl)thiazole-4-
carboxylate10a (4a). Yield 116 mg (75%). 1H NMR (300 MHz,
4.3.14. Methyl 2-(p-chlorophenyl)-5-phenylthiazole-4-carboxylate10a
CDCl3)
d
2.40 (s, 3H), 3.86 (s, 3H), 7.24 (d, J¼7.9 Hz, 2H), 7.43e7.45
(2n). Yield 130 mg (79%). 1H NMR (300 MHz, CDCl3)
d
3.85 (s, 3H),
7.40e7.44 (m, 5H), 7.51e7.55 (m, 2H), 7.90 (d, J¼8.6 Hz, 2H) ppm;
13C NMR (75 MHz, CDCl3)
164.7, 162.5, 146.6, 141.0, 136.7, 131.2,
(m, 5H), 7.95e7.98 (m, 2H) ppm; 13C NMR (75 MHz, CDCl3)
d
164.8,
161.8, 145.8, 139.5, 138.5, 131.8, 129.6, 128.8, 128.0, 126.3, 125.8, 51.3,
20.4 ppm.
d
130.1, 129.9, 129.4, 129.3, 128.3, 127.9, 52.3 ppm.
4.3.23. Methyl 2-phenyl-5-(3-methylphenyl)thiazole-4-
4.3.15. Methyl 2-(p-bromophenyl)-5-phenylthiazole-4-carboxy-
carboxylate10a (4b). Yield 125 mg (81%). 1H NMR (300 MHz,
late10a (2o). Yield 136 mg (73%). 1H NMR (300 MHz, CDCl3)
d
3.85
CDCl3)
d
2.41 (s, 3H), 3.86 (s, 3H), 7.23e7.34 (m, 4H), 7.44e7.46 (m,
165.0,
(s, 3H), 7.42e7.44 (m, 3H), 7.51e7.54 (m, 2H), 7.57 (d, J¼8.5 Hz, 2H),
3H), 7.96e7.99 (m, 2H) ppm; 13C NMR (75 MHz, CDCl3)
d
7.84 (d, J¼8.5 Hz, 2H) ppm; 13C NMR (75 MHz, CDCl3)
d
164.7, 162.5,
161.7,145.6, 139.8, 137.0,131.8, 129.6, 129.5, 129.2, 129.1,128.0, 127.2,
126.0, 125.8, 51.3, 20.4 ppm.
146.6, 141.0, 132.2, 131.6, 130.1, 129.9, 129.4, 128.3, 128.1, 125.0,
52.3 ppm.
4.3.24. Methyl 2-phenyl-5-(4-methoxylphenyl)thiazole-4-
4.3.16. Ethyl 2-methyl-5-phenylthiazole-4-carboxylate (2p). Yield
carboxylate (4d). Yield 97 mg (60%). Light yellow solid, mp
96 mg (83%). Colorless oil; 1H NMR (300 MHz, CDCl3)
d
1.22 (t,
J¼7.1 Hz, 3H), 2.74 (s, 3H), 4.28 (q, J¼7.1 Hz, 2H), 7.38e7.40 (m, 3H),
7.42e7.47 (m, 2H) ppm; 13C NMR (75 MHz, CDCl3)
163.8, 161.5,
136e138 ꢀC; 1H NMR (300 MHz, CDCl3)
d
3.85 (s, 3H), 3.87 (s, 3H),
6.96 (d, J¼8.5 Hz, 2H), 7.44e7.46 (m, 3H), 7.50 (d, J¼8.5 Hz, 2H),
7.96e7.97 (m, 2H) ppm; 13C NMR (75 MHz, CDCl3)
164.9, 162.3,
d
d

Z. Li et al. / Tetrahedron 69 (2013) 3281e3286
3285
160.0, 146.3, 139.7, 132.3, 130.8, 130.0, 128.5, 126.2, 121.8, 113.2, 54.8,
(300 MHz, CDCl3)
d
3.95 (s, 3H), 7.43 (d, J¼8.7 Hz, 2H), 7.41e7.46 (m,
51.7 ppm; IR (KBr) 2950, 2832, 1720, 1603, 1485, 1333, 1250, 1177,
1005, 830, 768, 694 cmꢁ1; HRMS (ESI) calcd for [C18H15NO3SþH]þ
326.0845, found 326.0843.
3H), 8.07e8.10 (m, 4H) ppm; 13C NMR (75 MHz, CDCl3)
d 161.5,
158.7,153.0,135.3,130.2,128.6,127.8,127.7,127.2,125.8,125.1,124.3,
51.4 ppm; IR (KBr) 2950, 2844, 1719, 1488, 1358, 1222, 1094, 836,
788, 708, 683 cmꢁ1; HRMS (ESI) calcd for [C17H12ClNO3þH]þ
314.0578, found 314.0569.
4.3.25. Methyl 2-phenyl-5-(4-fluorophenyl)thiazole-4-carboxylate
(4e). Yield 118 mg (76%). White solid, mp 126e128 ꢀC; 1H NMR
(300 MHz, CDCl3)
3H), 7.50e7.56 (m, 2H), 7.94e7.99 (m, 2H) ppm; 13C NMR (75 MHz,
CDCl3) 166.1, 165.0, 162.5, 161.7, 145.3, 140.9, 132.6, 131.9, 131.8,
130.7, 129.0, 126.8, 126.3, 126.2, 115.5, 115.3, 52.3 ppm; IR (KBr)
d
3.86 (s, 3H), 7.13 (t, J¼8.6 Hz, 2H), 7.44e7.47 (m,
4.3.33. 2-Phenylbenzothiazole (6). Yield 83 mg (79%). White solid,
mp 108e110 ꢀC; 1H NMR (300 MHz, CDCl3)
d
7.39 (t, J¼7.4 Hz, 1H),
7.48e7.53 (m, 4H), 7.90 (d, J¼8.0 Hz, 1H), 8.09e8.11 (m, 3H) ppm;
13C NMR (75 MHz, CDCl3)
167.0, 153.2, 134.0, 132.6, 129.9, 128.0,
d
d
2944, 1721, 1528, 1468, 1343, 1224, 1200, 1007, 843, 762, 689 cmꢁ1
;
126.5, 125.3, 124.1, 122.2, 120.6 ppm; IR (KBr) 1479, 1433, 1222, 963,
766, 687, 621 cmꢁ1; HRMS (ESI) calcd for [C13H9NSþH]þ 212.0534,
found 212.0538.
HRMS (ESI) calcd for [C17H12FNO2SþH]þ 314.0646, found 314.0649.
4.3.26. Methyl 2-phenyl-5-(4-chlorophenyl)thiazole-4-carboxylate
(4f). Yield 97 mg (60%). White solid, mp 122e123 ꢀC; 1H NMR
4.3.34. 2-Phenylindole (8). Yield 51 mg (53%). White solid, mp
(300 MHz, CDCl3)
d
3.86 (s, 3H), 7.13 (d, J¼8.5 Hz, 2H), 7.44e7.50 (m,
188e190 ꢀC; 1H NMR (300 MHz, CDCl3)
d
6.83 (s, 1H), 7.10e7.24 (m,
2H), 7.29e7,46 (m, 4H), 7.62e7.67 (m, 3H), 8.31 (br s, 1H) ppm; 13C
NMR (75 MHz, CDCl3) 136.9, 135.8, 131.4, 128.0, 126.7, 124.1, 121.3,
5H), 7.96e7.99 (m, 2H) ppm; 13C NMR (75 MHz, CDCl3)
d
166.4,
162.5, 145.0, 141.1, 135.5, 132.6, 131.2, 130.8, 129.0, 128.7, 128.5,
126.8, 52.3 ppm; IR (KBr) 2950, 1719, 1464, 1399, 1199, 1085, 1012,
763, 686 cmꢁ1; HRMS (ESI) calcd for [C17H12ClNO2SþH]þ 330.0350,
found 330.0345.
d
119.6, 119.3, 109.9, 99.0 ppm; IR (KBr) 3440, 1400, 1092, 798, 743,
689 cmꢁ1; HRMS (ESI) calcd for [C14H11NþH]þ 194.0964, found
194.0968.
4.3.27. Methyl 2-phenyl-5-(4-trifluoromethylphenyl)thiazole-4-
carboxylate (4g). Yield 45 mg (25%). White solid, mp 147e149 ꢀC;
Acknowledgements
1H NMR (300 MHz, CDCl3)
d
3.88 (s, 3H), 7.47e7.49 (m, 5H),
7.66e7.73 (m, 4H), 7.97e8.00 (m, 2H) ppm; 13C NMR (75 MHz,
CDCl3) 165.9, 161.3, 143.2, 133.0, 131.4, 130.4, 129.9, 129.3, 129.1,
This work was supported by NSFC-20902111, NSFC-21272276,
PSCIRT1193, Fok Ying Tong Education Foundation (121040) by the
Ministry of Education of China, SKLNM (JKGZ201110), and Funda-
mental Research Funds for the Central Universities (2011BPY01 and
JKY2011028 for Z.L). We thank Miss. Ling Ma in this group for
reproducing the results of 2b, 2l in Table 2 and 4a, 4d in Table 3.
d
128.0, 125.8, 124.2, 124.1, 121.0, 51.3 ppm; IR (KBr) 2950, 2838, 1714,
1610, 1506, 1217, 1181, 1094, 835, 786, 708, 683 cmꢁ1; HRMS (ESI)
calcd for [C18H12F3NO2SþH]þ 364.0614, found 364.0615.
4.3.28. Methyl 2-phenyl-5-(4-methylphenyl)oxazole-4-carboxy-
Supplementary data
late10a (4h). Yield 104 mg (71%). 1H NMR (300 MHz, CDCl3)
d 2.41
(s, 3H), 3.97 (s, 3H), 7.29 (d, J¼8.2 Hz, 2H), 7.46e7.49 (m, 3H), 8.04
Supplementary data including detailed results of reaction con-
dition screening and reaction scope investigation, and character-
ization of all title compounds can be found online. Supplementary
data related to this article can be found at http://dx.doi.org/10.1016/
j.tet.2013.02.001.
(d, J¼8.2 Hz, 2H), 8.13e8.16 (m, 2H) ppm; 13C NMR (75 MHz, CDCl3)
d
161.8, 158.5, 154.6, 139.8, 130.0, 128.2, 127.8, 127.4, 125.8, 125.4,
123.2, 51.3, 20.6 ppm.
4.3.29. Methyl 2-phenyl-5-(3-methylphenyl)oxazole-4-carboxy-
late10a (4i). Yield 117 mg (80%). 1H NMR (300 MHz, CDCl3)
d 2.44
References and notes
(s, 3H), 3.97 (s, 3H), 7.27 (d, J¼7.7 Hz, 1H), 7.38 (t, J¼7.7 Hz, 1H),
7.46e7.49 (m, 3H), 7.93e7.96 (m, 2H), 8.13e8.17 (m, 2H) ppm; 13C
1. For recent reviews on transition-metal-catalyzed arylearyl formation, see: (a)
Ackermann, L.; Vicente, R.; Kapdi, A. R. Angew. Chem., Int. Ed. 2009, 48, 9792; (b)
Chen, X.; Engle, K. M.; Wang, D.-H.; Yu, J.-Q. Angew. Chem., Int. Ed. 2009, 48,
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Perez, H.; Etayo, P.; Panossian, A.; Vidal-Ferran, A. Chem. Rev. 2011, 111, 2119; (b)
Grushin, V. V. Chem. Rev. 2004, 104, 1629; (c) Kosolapoff, G. M.; Maier, L.; Or-
ganic Phosphorous Compounds, 2nd ed.; Wiley-Interscience: New York, NY,
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London, United Kingdom, 1969e1983; Vols. 1e15.
NMR (75 MHz, CDCl3)
d 161.7, 158.7, 154.5, 137.2, 130.2, 130.1, 127.9,
127.8, 127.4, 126.9, 125.9, 125.4, 124.8, 51.4, 20.6 ppm.
4.3.30. Methyl 2-phenyl-5-(4-methoxylphenyl)oxazole-4-carboxy-
late (4j). Yield 72 mg (47%). White solid, mp 131e132.5 ꢀC; 1H
NMR (300 MHz, CDCl3)
2H), 7.46e7.48 (m, 3H), 8.12e8.15 (m, 4H) ppm; 13C NMR (75 MHz,
CDCl3) 162.4, 160.7, 158.6, 155.1, 130.4, 129.7, 128.3, 126.2, 126.0,
d
3.87 (s, 3H), 3.97 (s, 3H), 7.01 (d, J¼8.9 Hz,
d
119.0, 113.4, 54.9, 51.8 ppm; IR (KBr) 2962, 2926, 2855, 1729, 1465,
1330, 1261, 1108, 1069, 1020, 802, 761, 686 cmꢁ1; HRMS (ESI) calcd
for [C18H15NO4þH]þ 310.1074, found 310.1066.
3. (a) Hu, P.; Zhang, M.; Jie, X.; Su, W. Angew. Chem., Int. Ed. 2012, 51, 227; (b)
Amatore, C.; Bahsoun, A. A.; Jutand, A.; Meyer, G.; Ntepe, A. N.; Ricard, L. J. Am.
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4. For selected recent examples on the Ru-mediated CeP cleavage of triar-
ylphosphines, see: (a) Tan, X.; Li, B.; Xu, S.; Song, H.; Wang, B. Organometallics
2011, 30, 2308; (b) Cabeza, J. A.; Damonte, M.; García-Alvarez, P.; Kennedy, A. R.;
Perez-Carreno, E. Organometallics 2011, 30, 826.
5. Blum, O.; Frolow, F.; Milstein, D. J. Chem. Soc., Chem. Commun. 1991, 258.
6. For palladium catalyzed CeP cleavage of triarylphosphines or tetraar-
ylphosphonium halides in Heck reaction, see: (a) Reetz, M. T.; Lohmer, G.;
Schwickardi, R. Angew. Chem., Int. Ed. 1998, 37, 481; (b) Garrou, P. E. Chem. Rev.
1985, 85, 171.
4.3.31. Methyl 2-phenyl-5-(4-fluorophenyl)oxazole-4-carboxylate
(4k). Yield 89 mg (60%). White solid, mp 140e142 ꢀC; 1H NMR
(300 MHz, CDCl3)
d
3.95 (s, 3H), 7.16 (t, J¼8.7 Hz, 2H), 7.44e7.47 (m,
3H), 7.09e7.18 (m, 4H) ppm; 13C NMR (75 MHz, CDCl3)
d
164.4,
161.6, 161.0,158.6, 153.3, 130.1, 129.6, 129.5, 127.8, 126.6, 125.7, 125.1,
122.2, 122.1, 114.7, 114.4, 51.3 ppm; IR (KBr) 2950, 2844, 1715, 1505,
1434, 1355, 1235, 1094, 1009, 844, 708 cmꢁ1; HRMS (ESI) calcd for
[C17H12FNO3þH]þ 298.0874, found 298.0876.
4.3.32. Methyl 2-phenyl-5-(4-chlorophenyl)thiazole-4-carboxylate
7. For selected examples on palladium-catalyzed phosphination using triar-
ylphosphines as the phosphinating reagents for the synthesis of new
(4l). Yield 89 mg (57%). White solid, mp 131e132 ꢀC; 1H NMR

3286
Z. Li et al. / Tetrahedron 69 (2013) 3281e3286
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(b) Kwong, F. Y.; Chan, K. S. Organometallics 2000, 19, 2058; (c) Kwong, F. Y.;
Chan, K. S. Organometallics 2001, 20, 2570.
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positions, see: (a) Roger, J.; Gottumukkala, A. L.; Doucet, H. ChemCatChem 2010,
2, 20; (b) Zhao, D.; You, J.; Hu, C. Chem.dEur. J. 2011, 20, 5466.
12. For selected reviews on palladium catalyzed decarboxylative cross coupling,
see: (a) Rodriguez, N.; Goossen, L. J. Chem. Soc. Rev. 2011, 40, 5030; (b) Weaver,
J. D.; Recio, A., III; Grenning, A. J.; Tunge, J. A. Chem. Rev 2011, 111, 1846; (c) Hu,
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13. See the Supplementary data (Table S1) for the detailed results of reaction
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14. See the Supplementary data (Table S2) for the detailed results of azole scope
investigation with different loadings of Ph3P.
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