Palladium-catalyzed decarboxylative coupling of potassium nitrophenyl acetates with aryl halides

Article abstract of DOI:10.1021/ol201750s

A palladium-catalyzed decarboxylative cross-coupling of potassium 2- and 4-nitrophenyl acetates with aryl chlorides and bromides has been developed. Because the nitro group can be readily converted to many other functional groups, the new reaction provides a useful method for the preparation of diverse 1,1-diaryl methanes and their derivatives.

Full text of DOI:10.1021/ol201750s

ORGANIC
LETTERS
2011
Vol. 13, No. 16
4240–4243
Palladium-Catalyzed Decarboxylative
Coupling of Potassium Nitrophenyl
Acetates with Aryl Halides
Rui Shang,†,‡ Zheng Huang,† Ling Chu,† Yao Fu,† and Lei Liu*,†,‡
Department of Chemistry, Joint Laboratory of Green Synthetic Chemistry, University of
Science and Technology of China, Hefei 230026, China, and Department of Chemistry,
Tsinghua University, Beijing 100084, China
lliu@mail.tsinghua.edu.cn
Received June 13, 2011
ABSTRACT
A palladium-catalyzed decarboxylative cross-coupling of potassium 2- and 4-nitrophenyl acetates with aryl chlorides and bromides has been
developed. Because the nitro group can be readily converted to many other functional groups, the new reaction provides a useful method for the
preparation of diverse 1,1-diaryl methanes and their derivatives.
Transition-metal-catalyzed decarboxylative cross-coupling
has emerged recently as a useful method for CÀC
bond formation.1 By using carboxylic acids as alternative
reagents over organometal compounds, this type of
transformation avoids highly basic reaction conditions
and produces nontoxic CO2 instead of stoichiometric
metal waste. Pioneering studies by Myers,2 Forgione,3
and Goossen4 focused on the intermolecular decarboxy-
lative coupling reactions of aromatic, alkenyl, and alkynyl
acids,5 whereas Tunge,6 Trost,7 Stoltz,8 and others9 studied
† University of Science and Technology of China.
‡ Tsinghua University.
(1) (a) Baudoin, O. Angew. Chem., Int. Ed. 2007, 46, 1373. (b)
Goossen, L. J.; Rodriguez, N.; Goossen, K. Angew. Chem., Int. Ed.
2008, 47, 3100. (c) Weaver, J. D.; Recio, A., III; Grenning, A. J.; Tunge,
J. A. Chem. Rev. 2011, 111, 1846.
(2) (a) Myers, A. G.; Tanaka, D.; Mannion, M. R. J. Am. Chem. Soc.
2002, 124, 11250. (b) Tanaka, D.; Myers, A. G. Org. Lett. 2004, 6, 433.
(c) Tanaka, D.; Romeril, S. P.; Myers, A. G. J. Am. Chem. Soc. 2005,
127, 10323.
(3) (a) Forgione, P.; Brochu, M. C.; St-Onge, M.; Thesen, K. H.;
Bailey, M. D.; Bilodeau, F. J. Am. Chem. Soc. 2006, 128, 11350. (b)
Bilodeau, F.; Brochu, M. C.; Guimond, N.; Thesen, K. H.; Forgione, P.
J. Org. Chem. 2010, 75, 1550.
(4) (a) Goossen, L. J.; Deng, G.; Levy, L. M. Science 2006, 313, 662.
(b) Goossen, L. J.; Rodriguez, N.; Melzer, B.; Linder, C.; Deng, G.;
Levy, L. M. J. Am. Chem. Soc. 2007, 129, 4824. (c) Goossen, L. J.;
Zimmermann, B.; Knauber, T. Angew. Chem., Int. Ed. 2008, 47, 7103.
(d) Goossen, L. J.; Zimmermann, B.; Knauber, T. Angew. Chem., Int.
Ed. 2008, 47, 7103. (e) Goossen, L. J.; Rodriguez, N.; Linder, C. J. Am.
Chem. Soc. 2008, 130, 15248. (f) Goossen, L. J.; Rudolphi, F.; Oppel, C.;
Rodriguez, N. Angew. Chem., Int. Ed. 2008, 47, 3043. (g) Goossen, L. J.;
Rodriguez, N.; Lange, P.; Linder, C. Angew. Chem., Int. Ed. 2010
49, 1111.
(5) (a) Maehara, A.; Tsurugi, H.; Satoh, T.; Miura, M. Org. Lett.
2008, 10, 1159. (b) Moon, J.; Jeong, M.; Nam, H.; Ju, J.; Moon, J. H.;
Jung, H. M.; Lee, S. Org. Lett. 2008, 10, 945. (c) Yamashita, M.; Hirano,
K.; Satoh, T.; Miura, M. Org. Lett. 2009, 11, 2337. (d) Miyasaka, M.;
Fukushima, A.; Satoh, T.; Hirano, K.; Miura, M. Chem.;Eur. J. 2009,
15, 3674. (e) Hu, P.; Kan, J.; Su, W.; Hong, M. Org. Lett. 2009, 11, 2341.
(f) Cornella, J.; Lu, P.; Larrosa, I. Org. Lett. 2009, 11, 5506. (g) Shang,
R.; Fu, Y.; Li, J. B.; Zhang, S. L.; Guo, Q. X.; Liu, L. J. Am. Chem. Soc.
2009, 131, 5738. (h) Shang, R.; Fu, Y.; Wang, Y.; Xu, Q.; Yu, H.-Z.; Liu,
L. Angew. Chem., Int. Ed. 2009, 48, 9350. (i) Yamashita, M.; Hirano, K.;
Satoh, T.; Miura, M. Org. Lett. 2010, 12, 592. (j) Zhang, F.; Greaney,
M. F. Angew. Chem., Int. Ed. 2010, 49, 2768. (k) Arroyave, F. A.;
Reynolds, J. R. Org. Lett. 2010, 12, 1328. (l) Yu, M.; Pan, D.; Jia, W.;
Chen, W.; Jiao, N. Tetrahedron Lett. 2010, 51, 1287. (m) Shang, R.; Xu,
Q.; Jiang, Y.-Y.; Wang, Y.; Liu, L. Org. Lett. 2010, 12, 1000. (n) Dai,
J.-J.; Liu, J.-H.; Luo, D.-F.; Liu, L. Chem. Commun. 2011, 47, 677. (o)
Park, A.; Park, K.; Kim, Y.; Lee, S. Org. Lett. 2011, 13, 944. (p) Li, M.;
Wang, C.; Ge, H. Org. Lett. 2011, 13, 2062. (q) Yeung, P. Y.; Chung,
K. H.; Kwong, F. Y. Org. Lett. 2011, 13, 2912. (r) Hu, J.; Zhao, N.;
Yang, B.; Wang, G.; Guo, L.-N.; Liang, Y.-M.; Yang, S.-D. Chem.;
Eur. J. 2011, 17, 5516.
r
10.1021/ol201750s
Published on Web 07/26/2011
2011 American Chemical Society

intramolecular decarboxylative allylation and benzylation
reactions. Despite these achievements, relatively less has
been examined on the intermolecular decarboxylative cou-
pling of aliphatic carboxylic acids.10
Table 1. Pd-Catalyzed Decarboxylative Coupling of Potassium
Nitrophenyl Acetates with Phenyl Halidesa
In our previous studies we described Pd-catalyzed dec-
arboxylative couplings of the alkali salts of 2-(2-azaaryl)-
acetates11 and cyanoacetates12 with aryl halides. These
reactions not only provide conceptually alternative meth-
ods for the preparation of functionalized azaarenes and
R-aryl nitriles but also are practically favored in terms of both
reagent accessibility and reaction scope. Here we report a
new example of this family of reactions, namely, the de-
carboxylative cross-coupling of potassium 2- and 4-nitro-
phenylacetates. Due tothe versatile conversion of the nitro
group to many other functional groups,13 the new reaction
provides a useful methodfor the preparation of diverse1,1-
diaryl methanes and their derivatives.14,15 Note that Waet-
zig and Tunge previously described the Pd-catalyzed dec-
arboxylative allylation of nitrophenyl acetates.6e
GC yield (%)
entry
X
position
[Pd]
ligand
1
2
1
2
3
4
5
6
7
8
9
Cl 2-NO2 [PdCl(allyl)]2
Cl 2-NO2 [PdCl(allyl)]2
Cl 2-NO2 [PdCl(allyl)]2
Cl 2-NO2 [PdCl(allyl)]2
Cl 2-NO2 [PdCl(allyl)]2
Cl 2-NO2 [PdCl(allyl)]2
Cl 2-NO2 [PdCl(allyl)]2
P(Ad)2nBu
P(tBu)3
83
<5
18
61
74
16
17
43
36
16
21
73
16
<5
18
19
t-BuX-Phos <5
S-Phos
85
83
51
56
91
87
7
Dave-Phos
DCyPF
Brett-Phos
Our work started with the decarboxylative coupling
of potassium 2-nitrophenyl acetate with chlorobenzene
n
(Table 1). When [PdCl(allyl)]2 and P(Ad)2 Bu were used
as the catalyst and ligand, the desired transformation took
place readily to give a good yield (83%) of the coupling
product 1 (entry 1), whereas decarboxylative protonation
Cl 2-NO2 [PdCl(allyl)]2 X-Phos
Cl 2-NO2 Pd2(dba)3
X-Phos
X-Phos
X-Phos
X-Phos
X-Phos
X-Phos
10b Cl 2-NO2 Pd(OAc)2
11
12
13
14
Cl 4-NO2 [PdCl(allyl)]2
Cl 3-NO2 [PdCl(allyl)]2
Br 2-NO2 [PdCl(allyl)]2
Br 4-NO2 [PdCl(allyl)]2
89
n.r.
85
87
a All the reactions were carried out at a 0.25 mmol scale in 0.5 mL of
mesitylene. GC yields are measured as an average of two runs, using
benzophenone as internal standard. b 4% mol [Pd].
(6) (a) Rayabarapu, D. K.; Tunge, J. A. J. Am. Chem. Soc. 2005, 127,
13510. (b) Burger, E. C.; Tunge, J. A. J. Am. Chem. Soc. 2006, 128,
10002. (c) Waetzig, S. R.; Rayabarapu, D. K.; Weaver, J. D.; Tunge,
J. A. Angew. Chem., Int. Ed. 2006, 45, 4977. (d) Waetzig, S. R.; Tunge,
J. A. J. Am. Chem. Soc. 2007, 129, 4138. (e) Waetzig, S. R.; Tunge, J. A.
J. Am. Chem. Soc. 2007, 129, 14860. (f) Weaver, J. D.; Tunge, J. A. Org.
Lett. 2008, 10, 4657. (g) Torregrosa, R. R. P.; Ariyarathna, Y.;
Chattopadhyay, K.; Tunge, J. A. J. Am. Chem. Soc. 2010, 132, 9280.
(h) Weaver, J. D.; Ka, B. J.; Morris, D. K.; Thompson, W.; Tunge, J. A.
J. Am. Chem. Soc. 2010, 132, 12179. (i) Grenning, A. J.; Tunge, J. A. Org.
Lett. 2010, 12, 740. (j) Jana, R.; Partridge, J. J.; Tunge, J. A. Angew.
Chem., Int. Ed. 2011, 50, 5157.
(7) (a) Trost, B. M.; Xu, J.; Schmidt, T. J. Am. Chem. Soc. 2008, 130,
11852. (b) Trost, B. M.; Xu, J.; Schmidt, T. J. Am. Chem. Soc. 2009, 131,
18343.
(8) Mohr, J. T.; Nishimata, T.; Behenna, D. C.; Stoltz, B. M. J. Am.
Chem. Soc. 2006, 128, 11348.
(9) (a) Nakamura, M.; Hajra, A.; Endo, A. H.; Nakamura, E. Angew.
Chem., Int. Ed. 2005, 44, 7248. (b) He, H.; Zheng, X.-J.; Li, Y.; Dai
L.-X.; You, S.-L. Org. Lett. 2007, 9, 4339. (c) Fields, W. H.; Chruma,
J. J. Org. Lett. 2010, 12, 316. (d) Yeagley, A. A.; Lowder, M. A.;
Chruma, J. J. Org. Lett. 2009, 11, 4022. (f) Fields, W. H.; Khan, A. K.;
Sabat, M.; Chruma, J. J. Org. Lett. 2008, 10, 5131. (g) Yeagley, A. A.;
Chruma, J. J. Org. Lett. 2007, 9, 2879.
(10) Decarboxylative coupling of amino acids has been reported: (a)
Bi, H.-P.; Zhao, L.; Liang, Y.-M.; Li, C.-J. Angew. Chem., Int. Ed. 2009,
48, 792. (b) Bi, H.-P.; Chen, W.-W.; Liang, Y.-M.; Li, C.-J. Org. Lett.
2009, 11, 3246. (c) Zhang, C.; Seidel, D. J. Am. Chem. Soc. 2010, 132,
1798.
(11) Shang, R.; Yang, Z. W.; Wang, Y.; Zhang, S.-L.; Liu, L. J. Am.
Chem. Soc. 2010, 132, 14391.
(12) Shang, R.; Ji, D. S.; Chu, L.; Fu, Y.; Liu, L. Angew. Chem., Int.
Ed. 2011, 50, 4470.
(13) The Nitro Group in Organic Synthesis; Ono, N., Ed.; Wiley-VCH:
New York, 2001.
(14) Miura et al. previously reported Pd-catalyzed coupling of 4-al-
kylnitrobenzenes with aryl bromides to produce mono- and diarylated
products at the benzylic position: Inoh, J.-I.; Satoh, T.; Pivsa-Art, S.;
Miura, M.; Nomura, M. Tetrahedron Lett. 1998, 39, 4673. The present
method has advantages over the direct arylation of nitrotoluenes, where
diarylation can be a problem.
(15) Base-mediated decarboxylation of nitrophenyl acetic acids can
take place to produce alkylnitrobenzenes; see: Bull, D. J.; Fray, M. J.;
Mackenny, M. C.; Malloy, K. A. Synlett 1996, 647. However, the
potassium salt of 4-nitrophenyl acetic acid does not decarboxylate at
140 °C in the absence of Pd.
also occurred to produce byproduct 2. To improve the
yield of decarboxylative coupling we tested a number of
different phosphine ligands. It is interesting to find that
P(tBu)3 and t-BuX-Phos completely inhibited the coupling
process (entries 2À3), while S-Phos, Dave-Phos, DCyPF,
and Brett-Phos promoted the coupling to various extents
(entries 4À7). The optimal ligand turned out to be X-Phos,
and the corresponding yield was 91% (entry 8). Note that
X-Phos can also be used with Pd2(dba)3 as the catalyst in
the decarboxylative coupling reaction (entry 9), but when
Pd(OAc)2 was used the major reaction turned again to
decarboxylative protonation (entry 10). Extension of the
optimized reaction conditions to potassium 4-nitrophenyl
acetate was successful, and the yield was 89% (entry 11).
However, potassium 3-nitrophenyl acetate was completely
unreactive in the present transformation (entry 12). Further-
more, bromobenzene can be used in the decarboxylative
coupling with the potassium salts of both 2- and 4-nitro-
phenyl acetates (entries 13À14). Note that radical trap
experiments were performed and the results indicated no
involvement of radical intermediates (Supporting Infor-
mation).
To explore the substrate scope, we examined a variety of
arylhalidesinthe decarboxylativecoupling (Table2). Both
electron-rich and -poor aryl chlorides as well as bromides
can be successfully converted across a wide range of func-
tional groups including ether (3e, 4g, 4i), ester (3c, 3r), tosyl
(3a), fluoro (3d), trifluoromethyl (3f), thioether (3p), silyl
Org. Lett., Vol. 13, No. 16, 2011
4241

Inthe abovereactionsthe carboxylate reagents are easily
generated from commerically available 2- and 4-nitrophe-
nyl acetic acids. According to the previous studies,16 the
potassium salts of R-alkylated 2- and 4-nitrophenyl acet-
ates can also be readily prepared through the simple
alkylation reactions of 2- and 4-nitrophenyl acetate esters
(Supporting Information). Gratifyingly, we found that
these substituted potassium carboxylates can also react
with various aryl halides through decarboxylative cross-
coupling (Table 3). These reactions again tolerate diverse
functional groups including ether, ester, fluoro, trifluor-
omethyl, nitrile, acetal, and amine and heterocycles such
as pyridine and benzothiazole. It is significant to notice
Table 2. Aryl Halide Scopea
Table 3. Coupling of R-Alkylated Substratesa
a All the reactions were carried out at a 0.50 mmol scale in 1.0 mL of
mesitylene. The yield (average of two runs) of the isolated product was
calculated based on the quantity of the aryl halide. More details can be
found in the Supporting Information. b S-Phos was used as a ligand.
(3l, 4h), nitrile (3b, 3h, 3n), olefin (3k), acetal (3q), and
amine (3g, 3i). The isolated yields range from modest to
excellent (55À96%). Note that, for some electron-poor
aryl halides, S-Phos has to be used to replace X-Phos to
improve the reaction yields. Substitution at the ortho-
position (4d) can be tolerated. Halogenated heterocycles
such as benzothiazole (3m), thiophene (3o), indole (4c),
pyridine (4k), and quinoline (4f, 4j) are also good sub-
strates. Finally, the aryl-Br bond can be selectively cross-
coupled in the presence of the aryl-Cl bond (4e).
a All the reactions were carried out at a 0.50 mmol scale in 1.0 mL of
mesitylene. The yield (average of two runs) of the isolated product was
calculated based on the quantity of the aryl halide. More details can be
found in the Supporting Information. b Xant-Phos was used as a ligand.
c S-Phos was used as a ligand.
(16) Prasad, G.; Hanna, P. E.; Noland, W. E.; Venkatraman, S. J.
Org. Chem. 1991, 56, 7188.
4242
Org. Lett., Vol. 13, No. 16, 2011

that R-dialkylated substrates (5i, 5j, 5k) can undergo the
decarboxylative coupling to generate quaternary carbon
centers. The reactions of these particularsubstrates suggest
that decarboxylation takes place prior to cross-coupling.
the above decarboxylative coupling reactions can be used
to prepare a variety of 1,1-diaryl methanes. Scheme 2
shows that a 2-benzylated phenol can be synthesized by
using the decarboxylative cross-coupling. Furthermore, by
converting NH2 to I we synthesized a substituted fluorene.17
Scheme 1. New Synthesis of 4-Aryl Quinolines and Dihydro-
quinolinones
Scheme 2. Further Transformations by Using Sandmeyer Reaction
In summary, we report a practical protocol for the palla-
dium-catalyzed decarboxylative cross-coupling of potassium
2- and 4-nitrophenyl acetates with aryl chlorides and bro-
mides. This reaction adds a new example to the repertoire of
catalytic decarboxylative cross-coupling of activated alipha-
tic carboxylic acids.18 Because the nitro group can be readily
converted to many other functional groups, the new reaction
provides a useful method for the preparation of diverse
1,1-diaryl methanes and their derivatives.
By using the above decarboxylative coupling reactions
we can now synthesize a variety of nitro-substituted 1,
1-diaryl methanes. The synthetic utility ofthis method may
be substantially increased when the NO2 substituent is
converted to other groups.13 Scheme 1 shows a new
synthesis of 4-aryl quinolines and dihydroquinolinones
starting from the products of the decarboxylative coupling
reactions. The reduction of NO2 to NH2 by either SnCl2 or
Zn/HCl constitutes the critical step of the synthesis. In the
previous catalytic allylation of nitrophenyl acetates, Tunge
et al. also showed that decarboxylative coupling can be
followed by reductive cyclization to afford dihydroquino-
lones or quinolines.6e
Acknowledgment. The authors are grateful to the
National Science Foundation of China (No. 20832004,
20972148), the National Basic Research Program of China,
Knowledge Innovation Program of Chinese Academy of
Science, the Fundamental Research Funds for the Central
Universities and NECT (08-0519) for the financial support.
Importantly, NH2 can be further converted to many
other groups through the Sandmeyer reaction. Therefore,
(17) Parisien, M.; Valette, D.; Fagnou, K. J. Org. Chem. 2005, 70,
7578.
(18) We also tested the potassium salts of 4-cyanophenyl acetate,
4-trifluoromethylphenyl acetate, and pentafluorophenyl acetate. These
substrates do not provide the cross-coupling products.
Supporting Information Available. Experimental de-
tails. This material is available free of charge via the
Internet at http://pubs.acs.org.
Org. Lett., Vol. 13, No. 16, 2011
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