Ruthenium-catalyzed oxidative vinylation of heteroarene carboxylic acids with alkenes via regioselective C-H bond cleavage

Article abstract of DOI:10.1021/ol102942w

The ruthenium-catalyzed oxidative vinylation of thiophene-2-carboxylic acids with alkenes efficiently proceeds through directed C-H bond cleavage to give the corresponding 3-vinylated products. Similarly, benzothiophene-, benzofuran-, pyrrole-, and indole

Full text of DOI:10.1021/ol102942w

ORGANIC
LETTERS
2011
Vol. 13, No. 4
706–708
Ruthenium-Catalyzed Oxidative Vinylation
of Heteroarene Carboxylic Acids with
Alkenes via Regioselective C-H
Bond Cleavage
Takumi Ueyama, Satoshi Mochida, Tatsuya Fukutani, Koji Hirano, Tetsuya Satoh,*
and Masahiro Miura*
Department of Applied Chemistry, Faculty of Engineering, Osaka University, Suita,
Osaka 565-0871, Japan
satoh@chem.eng.osaka-u.ac.jp; miura@chem.eng.osaka-u.ac.jp
Received December 6, 2010
ABSTRACT
The ruthenium-catalyzed oxidative vinylation of thiophene-2-carboxylic acids with alkenes efficiently proceeds through directed C-H bond
cleavage to give the corresponding 3-vinylated products. Similarly, benzothiophene-, benzofuran-, pyrrole-, and indolecarboxylic acids also
undergo regioselective vinylation.
Transition-metal-catalyzed C-C bond formation reac-
tions via C-H bond cleavage have attracted much atten-
tion from the atom- and step-economic points of view, and
various catalytic processes involving different modes to
activate the ubiquitously available bond have been devel-
oped.1 Among the most promising strategies is the chelation-
assisted version with the aid of directing groups, which allows
regioselective functionalization. In particular, a carboxyl
group is highly useful in organic synthesis because it can be
readily removed and further transformed after its use as a
directing group.2 As such an example, we have demonstrated
that heteroarene carboxylic acids undergo directed vinylation
and decarboxylation upon treatment with alkenes and an
oxidant under palladium catalysis.2b Thus, the reaction of
indole-3-carboxylic acids gave 3-unsubstituted 2-vinylindole
derivatives exclusively. Since the Pd-catalyzed oxidative
direct vinylation (Fujiwara reaction) usually occurs at the
electron-rich C3-position of parent indoles,3 this reaction
provides a rare vinylation method at the unusual C2-
position. Its application to thiophene and benzothiophe-
necarboxylic acids was, however, problematic, in which
mixtures of 2- and 3-vinylated products were formed
(Scheme 1).2b These acids were found to undergo decar-
boxylation more readily under the Pd-catalyzed oxidative
Scheme 1
r
10.1021/ol102942w
Published on Web 01/18/2011
2011 American Chemical Society

coupling conditions. Therefore, at least parts of the 2-
vinylated products seem to arise from the sequence of the
initial decarboxylation and subsequent nondirected viny-
lation of the resulting thiophene and benzothiophene. In
the context of our study of catalytic coupling of carboxylic
acids,4 we have succeeded in finding that the regioselective
vinylaition of a wide range of heteroarene carboxylic acids
including thiophenecarboxylic acids can be realized by
using Ru in place of Pd as the principal catalyst
component.5-7 Since decarboxylation is sluggish under
Ru catalysis, the carboxyl function remains in the viny-
lated products and therefore, is utilizable for further
catalytic transformations.8,9 The results obtained for the
coupling are described herein.
Table 1. Reaction of Thiophene-2-carboxylic Acid (1a) with
Alkenes 2a-ha
entry
2
R
LiOAcb
product, % yieldc
1
2
2a
2a
2b
2c
2c
2d
2d
2e
2e
2f
CO2Bu
þ
-
þ
þ
-
þ
-
þ
-
þ
-
þ
-
3a, 79 (74)
3a, 72
CO2Bu
3
CO2(i-Bu)
CO2(t-Bu)
CO2(t-Bu)
CO2Cyd
CO2Cyd
CO2Et
3b,(72)
4
3c,(65)
5
3c, 76 (72)
3d, 94 (79)
3d, 92
6
7
(1) Selected recent reviews for C-H functionalization: (a) Satoh, T.;
Miura, M. Chem.;Eur. J. 2010, 16, 11212. (b) Satoh, T.; Miura, M.
Synthesis 2010, 3395. (c) Karimi, B.; Behzadnia, H.; Elhamifar, D.;
Akhavan, P. F.; Esfahani, F. K. Synthesis 2010, 1399. (d) Colby, D. A.;
Bergman, R. G.; Ellman, J. A. Chem. Rev. 2010, 110, 624. (e) Sun, C.-L.;
Li, B.-J.; Shi, Z.-J. Chem. Commun. 2010, 46, 677. (f) Ackermann, L.;
Vicente, R.; Kapdi, A. R. Angew. Chem., Int. Ed. 2009, 48, 9792. (g)
Chen, X.; Engle, K. M.; Wang, D.-H.; Yu, J.-Q. Angew. Chem., Int. Ed.
2009, 48, 5094. (h) Daugulis, O.; Do, H.-Q.; Shabashov, D. Acc. Chem.
Res. 2009, 42, 1074. (i) McGlacken, G. P.; Bateman, L. M. Chem. Soc.
Rev. 2009, 38, 2447. (j) Kakiuchi, F.; Kochi, T. Synthesis 2008, 3013. (k)
Lewis, J. C.; Bergman, R. G.; Ellman, J. A. Acc. Chem. Res. 2008, 41,
1013. (l) Ferreira, E. M.; Zhang, H.; Stoltz, B. M. Tetrahedron 2008, 64,
5987. (m) Park, Y. J.; Park, J.-W.; Jun, C.-H. Acc. Chem. Res. 2008, 41,
222. (n) Beccalli, E. M.; Broggini, G.; Martinelli, M.; Sottocornola, S.
Chem. Rev. 2007, 107, 5318. (o) Herrerias, C. I.; Yao, X.; Li, Z.; Li, C.-J.
Chem. Rev. 2007, 107, 2546. (p) Alberico, D.; Scott, M. E.; Lautens, M.
Chem. Rev. 2007, 107, 174. (q) Godula, K.; Sames, D. Science 2006, 312,
67. (r) Conley, B. L.; Tenn, W. J., III; Young, K. J. H.; Ganesh, S. K.;
Meier, S. K.; Ziatdinov, V. R.; Mironov, O.; Oxgaard, J; Gonzales, J.;
Goddard, W. A., III; Periana, R. A. J. Mol. Catal. A 2006, 251, 8. (s)
Kakiuchi, F.; Chatani, N. Adv. Synth. Catal. 2003, 345, 1077. (t) Ritleng,
V.; Sirlin, C.; Pfeffer, M. Chem. Rev. 2002, 102, 1731. (u) Kakiuchi, F.;
Murai, S. Acc. Chem. Res. 2002, 35, 826. (v) Dyker, G. Angew. Chem., Int.
Ed. 1999,38, 1698. (w) Kakiuchi, F.; Murai, S. Top. Organomet. Chem. 1999,
3, 47. (x) Shilov, A. E.; Shul’pin, G. B. Chem. Rev. 1997, 97, 2879.
(2) Directed vinylation/decarboxylation: (a) Mochida, S.; Hirano,
K.; Satoh, T.; Miura, M. Org. Lett. 2010, 12, 5776. (b) Maehara, A.;
Tsurugi, H.; Satoh, T.; Miura, M. Org. Lett. 2008, 10, 1159. Directed
arylation/decarboxylation:(c) Miyasaka, M.; Fukushima, A.; Satoh, T.;
Hirano, K.; Miura, M. Chem.;Eur. J. 2009, 15, 3674. (d) Nakano, M.;
Tsurugi, H.; Satoh, T.; Miura, M. Org. Lett. 2008, 10, 1851. (e) Chiong,
H. A.; Pham, Q.-N.; Daugulis, O. J. Am. Chem. Soc. 2007, 129, 9879.
For reviews, see ref 1b as well as the following: (f) Goossen, L. J.;
Rodriguez, N.; Goossen, K. Angew. Chem., Int. Ed. 2008, 47, 3100. (g)
Baudoin, O. Angew. Chem., Int. Ed. 2007, 46, 1373.
8
3e, 69
9
CO2Et
3e, 84 (75)
3f, 78 (67)
3f, 66
10
11
12
13
CO2Ph
2f
CO2Ph
2g
2h
CONH(t-Bu)
CN
3g, 48 (36)
3h, 34 (26)e
a Reaction conditions: (1) [1a]/[2]/[{Ru(p-cymene)Cl2}2]:[Cu(OAc)2-
H2O]/[LiOAc] = 0.25:1:0.005:0.5:0.75 (in mmol), in DMF (3 mL) at
80 °C for 6 h under N2. (2) With the addition of MeI (1.25 mmol) and
K2CO3 (1 mmol) at rt for 12 h. b Plus sign indicates that LiOAc was
added. c GC yield based on the amount of 1a used. Value in parentheses
indicates yield after purification. d Cy = cyclohexyl. e A minor amount
of separable Z-isomer was also obtained (9%).
3
In an initial attempt, the reaction of thiophene-2-
carboxylic acid (1a) with butyl acrylate (2a) (4 equiv) was
conducted in the presence of [Ru(p-cymene)Cl2]2 (2 mol
%), Cu(OAc)2 H2O (2 equiv),10,11 and LiOAc (3 equiv) as
3
catalyst, oxidant, and additive, respectively, in DMF at 80 °C
for 6 h under N2. After the subsequent methyl esterification
using iodomethane and K2CO3 for quantification, the 3-
vinylated product 3a was obtained in 79% yield (entry 1 in
Table 1). The product yield slightly decreased under the
conditions without LiOAc (entry 2). The reactions of 1a with
a variety of acrylates 2b-f proceeded efficiently to produce
the corresponding products 3b-f in good yields (entries
2-11). In some cases, depending on the identities of alkenes
employed, the product yields became somewhat higher in the
absence of LiOAc (entries 5 versus 4 and 9 versus 8). N-(tert-
Butyl)acrylamide (2g) also underwent the coupling with 1a to
afford product 3g (entry 12). The reaction with acrylonitrile
(2h) gave regioselectively vinylated product 3h as a separ-
able mixture of geometrical isomers (entry 13).
(3) (a) Jia, C.; Kitamura, T.; Fujiwara, Y. Acc. Chem. Res. 2001, 34,
633. (b) Beccalli, E. M.; Broggini, G.; Martinelli, M.; Sottocornola, S.
Chem. Rev. 2007, 107, 5318. (c) Tsuji, J. Palladium Reagents and
Catalysts, 2nd ed.; John Wiley & Sons: Chichester, UK, 2004.
(4) (a) Yamashita, M.; Hirano, K.; Satoh, T.; Miura, M. Org. Lett.
2010, 12, 592. (b) Yamashita, M.; Hirano, K.; Satoh, T.; Miura, M.
Chem. Lett. 2010, 39, 68. (c) Yamashita, M.; Horiguchi, H.; Hirano, K.;
Satoh, T.; Miura, M. J. Org. Chem. 2009, 74, 7481. (d) Yamashita, M.;
Hirano, K.; Satoh, T.; Miura, M. Org. Lett. 2009, 11, 2337. (e) Shimizu,
M.; Hirano, K.; Satoh, T.; Miura, M. J. Org. Chem. 2009, 74, 3478. (f)
Ueura, K.; Satoh, T.; Miura, M. J. Org. Chem. 2007, 72, 5362. (g) Ueura,
K.; Satoh, T.; Miura, M. Org. Lett. 2007, 9, 1407.
Next, the vinylation of other various heteroarene car-
boxylic acids was examined under similar reaction conditions
in the presence of LiOAc. 5-Bromothiophene-2-carboxylic
(5) Nondirected oxidative vinylation on aromatic C-H bond under
Ru catalysis has been reported: Weissman, H.; Song, X.; Milstein, D.
J. Am. Chem. Soc. 2001, 123, 337.
(6) Ru-catalyzed directed vinylation using vinyl halides, vinyl bor-
onates, and vinyl and allyl acetates: (a) Ueno, S.; Kochi, T.; Chatani, N.;
Kakiuchi, F. Org. Lett. 2009, 11, 855. (b) Matsuura, Y.; Tamura, M.;
Kochi, T.; Sato, M.; Chatani, N.; Kakiuchi, F. J. Am. Chem. Soc. 2007,
129, 9858. (c) Ueno, S.; Chatani, N.; Kakiuchi, F. J. Org. Chem. 2007,
72, 3600. (d) Oi, S.; Tanaka, Y.; Inoue, Y. Organometallics 2006, 25,
4773. (e) Oi, S.; Aizawa, E.; Ogino, Y.; Inoue, Y. J. Org. Chem. 2005, 70,
3113. (f) Oi, S.; Ogino, Y.; Fukita, S.; Inoue, Y. Org. Lett. 2002, 4, 1783.
(g) Oi, S.; Fukita, S.; Hirata, N.; Watanuki, N.; Miyano, S.; Inoue, Y.
Org. Lett. 2001, 3, 2579.
(7) Ru-catalyzed directed oxidative arylation and alkylation: (a)
Hiroshima, S.; Matsumura, D.; Kochi, T.; Kakiuchi, F. Org. Lett.
2010, 12, 5318. (b) Guo, X.; Deng, G.; Li, C.-J. Adv. Synth. Catal.
2009, 351, 2071. (c) Kitazawa, K.; Kochi, T.; Sato, M.; Kakiuchi, F. Org.
Lett. 2009, 11, 1951. (d) Oi, S.; Sato, H.; Sugawara, S.; Inoue, Y. Org.
Lett. 2008, 10, 1823. (e) Deng, G.; Zhao, L.; Li, C.-J. Angew. Chem., Int.
Ed. 2008, 47, 6278. (f) Pastine, S. J.; Gribkov, D. V.; Sames, D. J. Am.
Chem. Soc. 2006, 128, 14220. (g) Kakiuchi, F.; Matsuura, Y.; Kan, S.;
Chatani, N. J. Am. Chem. Soc. 2005, 127, 5936. (h) Kakiuchi, F.; Kan,
S.; Igi, K.; Chatani, N.; Murai, S. J. Am. Chem. Soc. 2003, 125, 1698.
Org. Lett., Vol. 13, No. 4, 2011
707

(1d) (entry 3). The reactions of benzofuran- and pyrrole-2-
carboxylic acids 1e and 1f with 2a also gave the corresponding
3-vinylated products 3l and 3m, respectively, maintaining
their carboxylic group (entries 4 and 5). Expectedly, 1-methy-
lindole-2-carboxylic acid (1g) underwent the vinylation to
afford 3-vinylated product 3n in 84% yield (entry 6). It
should be noted that such 3-vinylindole-2-carboxylic acid
derivatives have attracted much attention due to their neu-
roprotective activities.13 The present procedure provides a
significant shortcut for the target.
Table 2. Reaction of Heteroarenecarboxylic Acids 1b-g with
2aa
Scheme 2a
a GC yield based on the amount of 1 used. Value in parentheses
indicates yield after purification.
As shown in Scheme 2, 1-methylindole-3-carboxylic acid
(1h) also underwent the regioselective vinylation at the C2-
position to produce 3o. Meanwhile, thiophene-3-carbox-
ylic acid (1i) reacted with 2a in a 1:2 manner to afford 2,4-
divinylated product 3p in 84% yield.
In summary, we have demonstrated that the ruthenium-
catalyzed oxidative vinylation of heteroarene carboxylic
acids with alkenes takes place efficiently through regiose-
lective C-H bond cleavage without loss of the carboxyl
function. Ru catalyst systems for oxidative C-C coupling
reactions have been less explored thanthose with Pd or Rh.
The present catalyst systems and related ones are expected
to be applicable to other coupling reactions. Work is
underway toward further development of the catalysis.
a Reaction conditions: (1) [1]/[2a]/[{Ru(p-cymene)Cl2}2]:[Cu(OAc)2
3
H2O]/[LiOAc] = 0.25:1:0.005:0.5:0.75 (in mmol), in DMF (3 mL) at
80 °C under N2. (2) With the addition of MeI (1.25 mmol) and K2CO3
(1 mmol) at rt for 12 h. b GC yield based on the amount of 1 used. Value
in parentheses indicates yield after purification. c [Cu(OAc)2 H2O] =
3
1 (in mmol). d At 70 °C.
acid (1b) and 2,5-thiophenedicarboxylic acid (1c) reacted
with 2a to form products 3i12 and 3j, respectively (entries 1
and 2 in Table 2). In the latter case, no divinylated product
could be detected in the reaction mixture. Similarly, 3-viny-
lated benzothiophene-2-carboxylate 3k was obtained exclu-
sively in 95% yield from benzothiophene-2-carboxylic acid
(8) Selected examples of decarboxylative arylation: (a) Bilodeau, F.;
Brochu, M.-C.; Guimond, N.; Thesen, K. H.; Forgione, P. J. Org. Chem.
2010, 75, 1550. (b) Miyasaka, M.; Hirano, K.; Satoh, T.; Miura, M. Adv.
Acknowledgment. This work was partly supported by
Grants-in-Aid from the Ministry of Education, Culture,
Sports, Science and Technology, Japan.
Synth. Catal. 2009, 351, 2683. (c) Goossen, L. J.; Rodrıguez, N.; Melzer,
´
B.; Linder, C.; Deng, G.; Levy, L. M. J. Am. Chem. Soc. 2007, 129, 4824.
(d) Goossen, L. J.; Deng, G.; Levy, L. M. Science 2006, 313, 662. (e)
Forgione, P.; Brochu, M.-C.; St-Onge, M.; Thesen, K. H.; Bailey, M.;
Bilodeau, F. J. Am. Chem. Soc. 2006, 126, 11350. (f) Okazawa, T.; Satoh,
T.; Miura, M.; Nomura, M. J. Am. Chem. Soc. 2002, 124, 5286.
(9) Decarboxylative homocoupling: Cornella, J.; Lahlali, H.; Larrosa, I.
Chem. Commun. 2010, 46, 8276.
(10) A similar Ru/Cu catalyst system was employed in the oxidative
coupling of areneboronic acids with alkenes: (a) Farrington, E. J.;
Barnard, C. F. J.; Rowsell, E.; Brown, J. M. Adv. Synth. Catal. 2005,
347, 185. (b) Farrington, E. J.; Brown, J. M.; Barnard, C. F. J.; Rowsell,
E. Angew. Chem., Int. Ed. 2002, 41, 169.
Supporting Information Available. Standard experi-
mental procedure and characterization data of products.
This material is available free of charge via the Internet at
http://pubs.acs.org.
(13) (a) Di Fabio, R.; Conti, N.; De Magistris, E.; Feriani, A.;
Provera, S.; Sabbatini, F. M.; Reggiani, A.; Rovatti, L.; Barnaby,
R. J. J. Med. Chem. 1999, 42, 3486 and references cited therein. (b) Di
Fabio, R.; Capelli, A. M.; Conti, N.; Cugola, A.; Donati, D.; Feriani, A.;
Gastaldi, P.; Gaviraghi, G.; Hewkin, C. T.; Micheli, F.; Missio, A.;
Mugnaini, M.; Pecunioso, A.; Quaglia, A. M.; Ratti, E.; Rossi, L.;
Tedesco, G.; Trist, D. G.; Reggiani, A. J. Med. Chem. 1997, 40, 841.
(11) The yield of 3a decreased to 20-40% by using Ag2CO3 or
AgOAc in place of Cu(OAc)2 H2O as an oxidant.
(12) A small amount (8%) of debrominated product 3a was also
3
formed.
708
Org. Lett., Vol. 13, No. 4, 2011