Copper-catalyzed oxidative decarboxylative arylation of benzothiazoles with phenylacetic acids and α-hydroxyphenylacetic acids with O2 as the sole oxidant

Article abstract of DOI:10.1021/ol402871f

A Cu(II)-catalyzed oxidative decarboxylative synthesis of 2-aryl benzothiazole from phenylacetic acids and α-hydroxyphenylacetic acids has been developed. This reaction proceeds via Cu(II)-catalyzed decarboxylation, C-H bond oxidation, ring-opening, and condensation steps in a one-pot protocol with dioxygen as the sole terminal oxidant. Various functional groups were tolerated under standard conditions, and isolated yields were as high as 95%.

Full text of DOI:10.1021/ol402871f

ORGANIC
LETTERS
2
013
Vol. 15, No. 23
990–5993
Copper-Catalyzed Oxidative
Decarboxylative Arylation of
5
Benzothiazoles with Phenylacetic Acids
and r‑Hydroxyphenylacetic Acids with
O as the Sole Oxidant
2
Qiuling Song,* Qiang Feng, and Mingxin Zhou
School of Biomedical Sciences at Huaqiao Univeristy, Xiamen, Fujian, 361021, China
qsong@hqu.edu.cn
Received October 5, 2013
ABSTRACT
A Cu(II)-catalyzed oxidative decarboxylative synthesis of 2-aryl benzothiazole from phenylacetic acids and R-hydroxyphenylacetic acids has been
developed. This reaction proceeds via Cu(II)-catalyzed decarboxylation, CÀH bond oxidation, ring-opening, and condensation steps in a one-pot protocol
with dioxygen as the sole terminal oxidant. Various functional groups were tolerated under standard conditions, and isolated yields were as high as 95%.
1
The use of decarboxylation to activate reactions has
2
Since the pioneering work of Myers and Goossen, cata-
3
2
lytic decarboxylation of C(sp ) (aromatic and alkenyl )
4
5
attracted great attention due to the ready access of starting
materials, the use of neutral conditions, and the relative
cleanliness of a pathway with CO as the only byproduct.
6
and C(sp) (alkynyl ) acids has been extensively studied, yet
3
decarboxylation atansp -hybridizedcarbon forfunctional
2
7
introduction is relatively rare and remains a significant
3
challenge. The most common decarboxylation of an sp -
hybridized carbon is the Pd-catalyzed decarboxylative
(
1) For recent decarboxylation reviews, see: (a) Dzik, W. I.; Lange,
P. P.; Goo Chem. Sci. 2012, 3, 2671–2678. (b) Shang, R.; Liu, L. Science
China Chemistry 2011, 54, 1670–1687.
8
allylation reaction, yet the decarboxylative allylation
reaction required presynthesis of allylic carboxylates from
(
2) (a) Myers, A. G.; Tanaka, D.; Mannion, M. R. J. Am. Chem. Soc.
002, 124, 11250–11251. (b) Tanaka, D.; Romeril, S. P.; Myers, A. G.
J. Am. Chem. Soc. 2005, 127, 10323–10333.
3) (a) Goossen, L. J.; Rodrıguez, N.; Goossen, K. Angew. Chem.,
Int. Ed. 2008, 47, 3100–3120. (b) Goossen, L. J.; Rodrıguez, N.; Melzer,
B.; Linder, C.; Deng, G.; Levy, L. M. J. Am. Chem. Soc. 2007, 129, 4824–
833.
4) (a) Shang, R.; Fu, Y.; Li, J.-B.; Zhang, S.-L.; Guo, Q.-X.; Liu, L.
2
3
sp -hybridized carboxylic acids. In 2009, Li reported a
(
´
´
novel Cu(I)- and FeSO -catalyzed decarboxylative cou-
4
3
9
pling of the sp -hybridized carbon of R-amino acids, but
4
(
J. Am. Chem. Soc. 2009, 131, 5738–5739. (b) Zhang, F.; Greaney, M. F.
Angew. Chem., Int. Ed. 2010, 49, 2768–2771. (c) Cornella, J.; Righi, M.;
Larrosa, I. Angew. Chem., Int. Ed. 2011, 50, 9429–9432. (d) Hu, P.;
Zhang, M.; Jie, X.; Su, W. Angew. Chem., Int. Ed. 2012, 51, 227–231.
(7) (a) Torregrosa, R. R. P.; Ariyarathna, Y.; Chattopadhyay, K.;
Tunge, J. A. J. Am. Chem. Soc. 2010, 132, 9280–9282. (b) Shang, R.;
Yang, Z.-W.; Wang, Y.; Zhang, S.-L.; Liu, L. J. Am. Chem. Soc. 2010,
132, 14391–14393. (c) Shang, R.; Ji, D.-S.; Chu, L.; Fu, Y.; Liu, L.
Angew. Chem., Int. Ed. 2011, 50, 4470–4474. (d) Zhang, C.; Seidel, D.
J. Am. Chem. Soc. 2010, 132, 1798–1799. (e) Shang, R.; Huang, Z.; Chu,
L.; Fu, Y.; Liu, L. Org. Lett. 2011, 13, 4240–4243.
(
5) (a) Yamashita, M.; Hirano, K.; Satoh, T.; Miura, M. Org. Lett.
009, 12, 592–595. (b) Hu, J.; Zhao, N.; Yang, B.; Wang, G.; Guo, L.-N.;
Liang, Y.-M.; Yang, S.-D. Chem.;Eur. J. 2011, 17, 5516–5521.
6) (a) Moon, J.; Jeong, M.; Nam, H.; Ju, J.; Moon, J. H.; Jung,
2
(
H. M.; Lee, S. Org. Lett. 2008, 10, 945–948. (b) Feng, C.; Loh, T.-P.
Chem. Commun. 2010, 46, 4779–4781. (c) Zhao, D.; Gao, C.; Su, X.; He,
Y.; You, J.; Xue, Y. Chem. Commun. 2010, 46, 9049–9051. (d) Park, A.;
Park, K.; Kim, Y.; Lee, S. Org. Lett. 2011, 13, 944–947. (e) Chen, Z.-S.;
Duan, X.-H.; Zhou, P.-X.; Ali, S.; Luo, J.-Y.; Liang, Y.-M. Angew.
Chem., Int. Ed. 2012, 51, 1370–1374.
(8) (a) Waetzig, S. R.; Tunge, J. A. J. Am. Chem. Soc. 2007, 129,
14860–14861. (b) Weaver, J. D.; Recio, A.; Grenning, A. J.; Tunge, J. A.
Chem. Rev. 2011, 111, 1846–1913.
(9) (a) Bi, H.-P.; Zhao, L.; Liang, Y.-M.; Li, C.-J. Angew. Chem., Int.
Ed. 2009, 48, 792–795. (b) Bi, H.-P.; Chen, W.-W.; Liang, Y.-M.; Li,
C.-J. Org. Lett. 2009, 11, 3246–3249.
1
0.1021/ol402871f r 2013 American Chemical Society
Published on Web 11/19/2013

the reactions work well chiefly with prolines and require
excess peroxides as oxidants under an inert atmosphere.
Recently, Liu et al. developed Pd-catalyzed decarboxyla-
a
Table 1. Investigation of the Reaction Parameters
7
b,c,e,10
tion of aliphatic carboxylate salts;
these are the first
examples of intermolecular decarboxylative coupling of
various types of aliphatic carboxylates, but these reactions
require carboxylate salts, not free carboxylic acids. Thus
3
the direct oxidative decarboxylation of sp -hybridized
carboxylic acids with the formation of new CÀC or
temp time yield
b
entry
catalyst
solvent (°C)
(h)
(%)
CÀheteroatom bonds remains a challenge, especially with
c
1
Cu(OAc)
2
(10 mol %)
O
2
DMSO
120
100
100
130
130
130
130
130
130
130
130
130
24
24
26
26
26
24
24
24
24
24
24
24
66
O as the terminal oxidant.
2
2
2
Cu(OAc) (10 mol %) O2 DMSO
18
45
2
-Substituted benzothiazoles are important heterocyclic
3
Cu(OAc)
Cu(OAc)
Cu(OAc)
2
2
2
(20 mol %)
(20 mol %)
(20 mol %)
(20 mol %)
(20 mol %)
O
2
O
2
O
2
O
2
O
2
O
2
O
2
DMSO
DMSO
DMF
c
4
77
scaffolds in pharmaceuticals, organic electronic materials,
and biologically active natural products. Conventional
methods for the synthesis of 2-substituted benzothiazoles
typically involve the condensation of 2-amino thiophenols
5
52
40
32
trace
36
20
6
6
Cu(OTf)
Cu(TFA)
2
DMSO
DMSO
DMSO
DMSO
7
2
8
CuBr
2
(20 mol %)
4
(20 mol %)
1
1
and aldehydes. Very recently condensations between
1
9
CuSO
2
benzothiazoles and aldehydes were also developed.
Direct CÀH activation by transition metal catalyzed
10
11
2
Cu(OAc) (20 mol %) air DMSO
Cu(OAc)
Cu(OAc)
2
2
(20 mol %)
(20 mol %)
N
2
DMSO
DMSO
1
cross-coupling of benzothiazoles and aryl halides or
3
d
0
12
O
2
1
4
aromatic boronic acids was another attractive method.
In term of decarboxylative coupling, Tan et al. reported
elegant work on the synthesis of 2-arylbenzothiazole from
coupling benzothiazole with benzoic acid. Yet this reac-
tion used an expensive Pd salt as the catalyst, phosphine
ligands and silver salts were necessary for the success of the
reactions, and benzoic acids were only limited to ortho-
substituted ones, thus limiting the substrate scope.
a
Reaction conditions: phenyl acetic acid (1.0 mmol), benzothiazole
0.5 mmol), cat. in solvent (0.75 mL) in a sealed tube under correspond-
b c d
ing atomsphere. GC yield. Isolated yield. 2 equiv of TEMPO was
added.
(
1
5
CÀH bond functionalization, ring-opening, and conden-
sation steps in a one-pot reaction in DMSO with dioxygen
as the sole terminal oxidant. This transformation repre-
sents a novel protocol for preparation of 2-aryl benzothia-
zoles. Furthermore, the easy availability of phenylacetic
acids, R-hydroxyphenylacetic acids, and copper(II) salts
makes this reaction highly practical and broad in scope.
Very recently, the Cu-catalyzed decarboxylative cou-
b,16
1
pling reaction has attracted much attention
due to
the readily availability, low cost, and low toxicity of copper
salts. To the best of our knowledge, there is no oxidative
3
decarboxylation of an sp -hybridized carbon using Cu(II)
salts as the catalyst without added ligands and using
dioxygen as the terminal oxidant. Herein we report the
first Cu(II)-catalyzed oxidative decarboxylative synthesis
of 2-aryl benzothiazole from phenylacetic acids and
R-hydroxyphenylacetic acids. This reaction proceeds via
Cu(II)-catalyzed decarboxylation, dioxygen activation,
(
10) Shang, R.; Huang, Z.; Xiao, X.; Lu, X.; Fu, Y.; Liu, L. Adv.
Synth. Catal. 2012, 354, 2465–2472.
11) (a) Riadi, Y.; Mamouni, R.; Azzalou, R.; Haddad, M. E.;
Routier, S.; Guillaumet, G.; Lazar, S. Tetrahedron Lett. 2011, 52,
492–3495. (b) Chen, Y.-X.; Qian, L.-F.; Zhang, W.; Han, B. Angew.
Chem., Int. Ed. 2008, 47, 9330–9333.
12) (a) Liu, S.; Chen, R.; Guo, X.; Yang, H.; Deng, G.; Li, C.-J.
(
3
We commenced our study with phenylacetic acid (1a)
and benzothiazole (2a) under Cu(OAc) /O as a model
(
Green Chem. 2012, 14, 1577. (b) Yang, Z.; Chen, X.; Wang, S.; Liu, J.;
Xie, K.; Wang, A.; Tan, Z. J. Org. Chem. 2012, 77, 7086–7091.
2
2
reaction (Table 1). To our delight, the desired product
was formed in 66% isolated yield (Table 1, entry 1)
with 10 mol % Cu(OAc) at 120 °C under 1 atm of O .
(13) (a) Kondo, Y.; Komine, T.; Sakamoto, T. Org. Lett. 2000, 2,
3111–3113. (b) Do, H.-Q.; Daugulis, O. J. Am. Chem. Soc. 2007, 129,
12404–12405. (c) Lewis, J. C.; Berman, A. M.; Bergman, R. G.; Ellman,
2
2
J. A. J. Am. Chem. Soc. 2008, 130, 2493–2500. (d) Huang, J.; Chan, J.;
Chen, Y.; Borths, C. J.; Baucom, K. D.; Larsen, R. D.; Faul, M. M.
J. Am. Chem. Soc. 2010, 132, 3674–3675.
Further catalysts, solvents, and temperatures were all
extensively screened, and eventually, the optimal reaction
conditions emerged as phenylacetic acid (1a) (1.0 mmol),
(14) (a) Liu, B.; Qin, X.; Li, K.; Li, X.; Guo, Q.; Lan, J.; You, J.
Chem.;Eur. J. 2010, 16, 11836–11839. (b) Kirchberg, S.; Tani, S.; Ueda,
K.; Yamaguchi, J.; Studer, A.; Itami, K. Angew. Chem., Int. Ed. 2011, 50,
benzothiazole (2a) (0.5 mmol), and Cu(OAc) (20 mol %)
2
2
387–2391.
15) Xie, K.; Yang, Z.; Zhou, X.; Li, X.; Wang, S.; Tan, Z.; An, X.;
Guo, C.-C. Org. Lett. 2010, 12, 1564–1567.
16) (a) Yang, H.; Sun, P.; Zhu, Y.; Yan, H.; Lu, L.; Qu, X.; Li, T.;
at 130 °C in DMSO (0.75 mL) under an O atomosphere
Table 1, entry 4).
With these optimized conditions in hand, the substrate
2
(
(
(
Mao, J. Chem. Commun. 2012, 48, 7847–7849. (b) Cui, Z.; Shang, X.;
Shao, X.-F.; Liu, Z.-Q. Chem. Sci 2012, 3, 2853–2858. (c) Shang, R.; Fu,
Y.; Wang, Y.; Xu, Q.; Yu, H.-Z.; Liu, L. Angew. Chem., Int. Ed. 2009, 48,
scope was investigated (Scheme 1). Phenylacetic acids
possessing electron-donating groups on the aromatic rings
gave the desired products in moderate to good yields
9350–9354.
Org. Lett., Vol. 15, No. 23, 2013
5991

Scheme 1. Copper-Catalyzed Aerobic Oxidative Decarboxylative
Arylation of Benzothiazoles with Phenylacetic Acid
Scheme 2. Copper-Catalyzed Aerobic Oxidative Decarboxylative
Arylation of Benzothiazoles with R-Hydroxyphenylacetic Acid
a
a
a
Reaction conditions: 1 (1 mmol), 2 (0.5 mmol), Cu(OAc)
; reaction was monitored by TLC
plate. All the yields are isolated yields.
2
a
4
Reaction conditions: 4 (1 mmol), 2 (0.5 mmol), CuSO (20 mol %),
(
20 mol %), DMSO (0.75 mL), O
2
b
O ; reaction were monitored by TLC plate. All the yields are isolated
yields.
b
2
(
3ab, 3af, 3anÀ3ao in Scheme 1). Phenylacetic acids bear-
products in up to 93% isolated yields (Scheme 1, 3baÀ3fa).
All in all, fluoro, chloro, bromo, methoxy, ethoxyl, methyl,
tert-butyl, nitro, and trifluoromethyl groups were well
tolerated.
ing electron-withdrawing groups on the aromatic ring were
better, with the desired 2-arylbenzothiazoles obtained in
good to excellent yields (Scheme 1, 3acÀ3ae, 3agÀ3am). It
was noteworthy that halo-substituted phenylacetic acid
survived well, leading to halo-substituted benzothiazole
derivatives, which could be used for further transforma-
tion. The position of the substituents on aromatic rings
of phenylacetic acids had little effect (Scheme 1, 3acÀ3ae,
Intrigued by the above results, we applied the same
conditions to R-hydroxyphenylacetic acids (Supporting
Information (SI), Table S1). To our delight, under the
above-mentioned standard conditions, 2-phenyl ben-
zothiazole (3aa) was obtained in 72% isolated yield from
R-hydroxyphenylacetic acid (4a) and benzothiazole (2a)
(SI, Table S1, entry 1). Solvents, catalysts, catalysts load-
ings, and temperatures were all investigated, and after con-
dition screening, it appeared that 20 mol % of CuSO4
showed the highest efficiency for this transformation with
a 92% isolated yield (SI, Table S1, entry 10).
3
ahÀ3aj, 3akÀ3am, 3anÀ3ao), with only o-substitution
giving slightly inferior yields to m- and p-substitution,
probably as a result of steric hindrance. Both 1- and
2
-naphthylacetic acid reacted well and gave the corre-
sponding benzothiazole derivatives in 75% and 86% yields
Scheme 1, 3ap and 3aq). Heteroaromatic acetic acid,
-pyridylacetic acid, also worked well under standard con-
(
3
Under the optimized conditions, various R-hydroxyphe-
nylacetic acids and benzothiazoles were explored to check
the tolerance of the reaction. As shown in Scheme 2, the
reaction worked very well with diverse benzothiazoles and
various R-hydroxyphenylacetic acids to give 2-arylben-
zothiazoles in 44À95% isolated yields.
ditions to give a moderate isolated yield (Scheme 1, 3ar).
Benzothiazoles bearing substituents with diverse electronic
properties on the benzo group were also explored for
the reactions. Both electron-withdrawing groups (such as
chloro and nitro groups) and electron-donating groups
(such as methyl, methoxy, and ethoxy groups) reacted
smoothly with phenyacetic acid to afford the desired
In order to elucidate the reaction mechanism, several
control experiments were carried out (Schemes 3 and S1).
5
992
Org. Lett., Vol. 15, No. 23, 2013

Scheme 3. Control Experiments
Scheme 4. Plausible Reaction Mechanism
opened in the presence of acid. The resulting 2-aminothio-
phenol reacts with the aldehyde, and after oxidative con-
densation, the desired 2-substituted benzothiazole is
obtained (Scheme 4).
In the case of the reaction between benzothiazoles and
R-hydroxyphenylacetic acid, control experiments were
performed and a proposed mechanism is given in the SI
Sincethe reaction involvesoxygen, radical trapping experi-
mentswereconductedby employing2,2,6,6-tetramethyl-1-
piperidinyloxy (TEMPO) with phenylacetic acid and ben-
zothiazole under standard conditions. The result showed
that the reactions were inhibited by TEMPO (Table 1,
entry 12, Scheme 3, eq 1). The reaction of benzyl alcohol
with both benzothiazole and 2-aminothiophenol gave just
a trace of desired products, showing that benzyl alcohol is
not an intermediate for this reaction (SI, Scheme S1, eqs S1
and S2). Toluene was also treated under standard condi-
tions, and no desired product was formed (SI, Scheme S1,
eq S3). Interestingly, if only phenylacetic acid was applied
under the standard conditions, 88% of benzaldehyde
was obtained (Scheme 3, eq 2). When benzaldehyde re-
acted with benzothiazole and 2-aminothiophenol respec-
tively, only the latter gave the desired product in 91%
yield (Scheme 3, eq 3); the former gave no product (SI,
Scheme S1, eq S4), suggesting that 2-aminothiophenol is a
key intermediate. This result demonstrated that a ring-
opening pathway was taken in the reaction. However, if
only benzothiazole was treated under the standard condi-
tions, no ring-opened product, 2-aminothiophenol, was
detected (SI, Scheme S1, eq S5). Significantly, when 2-oxo-
(
Schemes S2 and S3).
In summary, Cu(II)/O systems that catalyzed the oxi-
2
dative decarboxylative synthesis of 2-aryl benzothiazole
from phenylacetic acids and R-hydroxyphenylacetic acids
has been developed. These reactions are the first decarbox-
3
ylations of an sp -hybridized carbon catalyzed by Cu(II)
followed by oxidation of the R-methylene group with
dioxygen as the oxidant and reagent, thus expanding the
utility of decarboxylation in organic synthesis and also
providing a sustainable synthesis for 2-aryl benzothiazole
derivatives. Further studies on the scope, mechanistic
elucidation, and synthetic application of this reaction are
in progress in our laboratory.
Acknowledgment. We are grateful for financial support
from the National Science Foundation of China (21202049),
the Recruitment Program of Global Experts, and Research
Funds of Huaqiao University.
2
-phenylacetic acid was treated under the standard condi-
tions, only 13% of the desired product was obtained along
with 37% benzaldehyde (SI, Scheme S1, eq S6). At this
point point, even though the exact reaction mechanism is
not clear for 2-substituted benzothiazole formation, we
may give a plausible reaction mechanism (Scheme 4):
Phenylacetic acid is decarboxylated and oxidized to the
aldehyde, and at the same time the benzothiazole ring is
Supporting Information Available. Experimental pro-
cedures and full spectroscopic data for all compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
The authors declare no competing financial interest.
Org. Lett., Vol. 15, No. 23, 2013
5993