Rhodium-catalyzed selective olefination of arene esters via C-H bond activation

Article abstract of DOI:10.1021/ol200600p

Chemical equations presented. A new catalytic procedure of ortho-olefination of benzoates and benzaldehydes has been developed. Ester and carboxaldehyde units were revealed to be effective chelating groups in focusing the activation of aryl C-H bonds orth

Full text of DOI:10.1021/ol200600p

ORGANIC
LETTERS
2011
Vol. 13, No. 9
2372–2375
Rhodium-Catalyzed Selective Olefination
of Arene Esters via CꢀH Bond Activation
Sae Hume Park, Ji Young Kim, and Sukbok Chang*
Department of Chemistry and Molecular-Level Interface Research Center,
Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Korea
sbchang@kaist.ac.kr
Received March 7, 2011
ABSTRACT
A new catalytic procedure of ortho-olefination of benzoates and benzaldehydes has been developed. Ester and carboxaldehyde units were
revealed to be effective chelating groups in focusing the activation of aryl CꢀH bonds ortho to the directing moieties under the Rh-catalyzed
oxidative conditions. The reaction is highly regioselective with a range of benzoates and benzaldehydes enabling the efficient olefination with
acrylates, acrylic acid, and styrenes.
Transition-metal-catalyzed CꢀH bond activation has
attracted much attention, and its synthetic applications
have been elegantly demonstrated in organic synthesis,
medicinal chemistry, and materials science.1 Selectivity in
the activation process can be controlled by suitably posi-
tioned directing groups. As a result, a wide range of
coordinating moieties have been utilized for the efficient
activation of CꢀH bonds. Among those, carbonyl groups
are especiallynoteworthybecause they are widely available
and readily interconvertible with other functional groups.
For this purpose, carboxylic acids, amides, or acetyls are
frequently employed as chelating groups. In fact, there are
elegant examples revealing that carboxylic acids are uti-
lized as an effective controlling group in the CꢀH bond
functionalization.2
Furthermore, arene or alkane amides can be arylated
selectively under catalytic conditions.3 Alkyl and aryl
ketones are also used in the Ru- or Pd-catalyzed arylation
to react with aryl boronates or halides, respectively.4
Rhodium catalytic systems have been extensively investi-
gated in the chelation-assisted CꢀH bond activation of
carbonyl group containing compounds or their equi-
valents.5 In particular, rhodium(III) catalysts bearing a
cyclopentadienyl (Cp) ligand have been recently employed
for the CꢀH bond functionalization.6,7
Scheme 1. Rh-Catalyzed Olefination of Carbonyl Compounds
(1) For recent reviews on the CꢀH bond activation and its synthetic
applications, 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, 5094. (c) Lyons, T. W.;
Sanford, M. S. Chem. Rev. 2010, 110, 1147.
(2) Carboxylic acids as a directing group: (a) Miura, M.; Tsuda, T.;
Satoh, T.; Pivsa-Art, S.; Nomura, M. J. Org. Chem. 1998, 63, 5211.
(b) Giri, R.; Maugel, N.; Li, J.-J.; Wang, D.-H.; Breazzano, S. P.;
Saunders, L. B.; Yu, J.-Q. J. Am. Chem. Soc. 2007, 129, 3510. (c) Chiong,
H. A.; Pham, Q.-N.; Daugulis, O. J. Am. Chem. Soc. 2007, 129, 9879.
(d) Wang, D.-H.; Mei, T.-S.; Yu, J.-Q. J. Am. Chem. Soc. 2008, 130,
17676.
(3) Amides as a directing group: (a) Kametani, Y.; Satoh, T.; Miura,
M.; Nomura, M. Tetrahedron Lett. 2000, 41, 2655. (b) Shabashov, D.;
Daugulis, O. Org. Lett. 2006, 8, 4947. (c) Wang, D.-H.; Wasa, M.; Giri,
R.; Yu, J.-Q. J. Am. Chem. Soc. 2008, 130, 7190.
r
10.1021/ol200600p
Published on Web 04/06/2011
2011 American Chemical Society

For instance, a range of substrates having carboxylic acid,
carboxamide, or acetyl groups are readily olefinated under
Rh-catalyzed oxidative conditions (Scheme 1).8 It was
demonstrated that acetophenones or benzamides are suita-
ble substrates for the ortho-olefination using the Rh(III)
catalytic system.6g In addition, oxime has been revealed as
excellent directing group in the Rh-catalyzed oxidative aryl
coupling with unactivated alkenes.6h Despite these signifi-
cant contributions, there is still room for further improve-
ment with regard to substrate scope and reaction
conditions. For example, esters or carboxaldehydes are
seldom used as directing groups in catalytic CꢀH bond
functionalization.9 This aspect is noteworthy since those
functional groups are not only readily available but also
easily converted to others such as alcohols, amides, or other
carbonyl compounds.10 During the course of our studies,11
we found that an ester or carboxaldehyde moiety works as an
efficient directing group in the Rh(III)-catalyzed olefination
of benzoates or benzaldehydes.12
Table 1. Optimization of Reaction Conditionsa
(4) Acetyl moieties as a directing group: (a) Satoh, T.; Kametani, Y.;
Terao, Y.; Miura, M.; Nomura, M. Tetrahedron Lett. 1999, 40, 5345.
(b)Terao, Y.;Kametani, Y.;Wakui, H.;Satoh, T.;Miura, M.;Nomura, M.
Tetrahedron 2001, 57, 5967. (c) Kakiuchi, F.; Kan, S.; Igi, K.; Chatani, N.;
Murai, S. J. Am. Chem. Soc. 2003, 125, 1698. (d) Gandeepan,
P.; Parthasarathy, K.; Cheng, C.-H. J. Am. Chem. Soc. 2010, 132, 8569.
For a recent report on the Pd-catalyzed ortho-amidation of aromatic
ketones, see:(e) Sun, C.-L.; Li, B.-J.; Shi, Z.-J. Chem. Commun. 2010, 46,
677. (f) Xiao, B.; Gong, T.-J.; Xu, J.; Liu, Z.-J.; Liu, L. J. Am. Chem. Soc.
2011, 133, 1466.
(5) (a) Colby, D. A.; Bergman, R. G.; Ellman, J. A. Chem. Rev. 2010,
110, 624. (b) Tsuchikama, K.; Kuwata, Y.; Tahara, Y.-k.; Yoshinami,
Y.; Shibata, T. Org. Lett. 2007, 9, 3097. (c) Tanaka, K.; Otake, Y.;
Wada, A.; Noguchi, K.; Hirano, M. Org. Lett. 2007, 9, 2203. (d) Tanaka,
K.; Otake, Y.; Sagae, H.; Noguchi, K.; Hirano, M. Angew. Chem., Int.
Ed. 2008, 47, 1312.
(6) (a) Satoh, T.; Miura, M. Chem.;Eur. J. 2010, 16, 11212.
(b) Lenges, C. P.; Brookhart, M. J. Am. Chem. Soc. 1999, 121, 6616.
(c) Umeda, N.; Hirano, K.; Satoh, T.; Miura, M. J. Org. Chem. 2009, 74,
7094. (d) Mochida, S.; Hirano, K.; Satoh, T.; Miura, M. Org. Lett. 2010,
12, 5776. (e) Wang, F.; Song, G.; Li, X. Org. Lett. 2010, 12, 5430.
(f) Patureau, F. W.; Glorius, F. J. Am. Chem. Soc. 2010, 132, 9982.
(g) Patureau, F. W.; Besset, T.; Glorius, F. Angew. Chem., Int. Ed. 2011,
50, 1064. (h) Tsai, A. S.; Brasse, M.; Bergman, R. G.; Ellman, J. A. Org.
Lett. 2011, 13, 540. (i) Rakshit, S.; Grohmann, C.; Besset, T.; Glorius, F.
J. Am. Chem. Soc. 2011, 133, 2350. For an additional example of using
[RhCp*Cl2]2 catalyst in the oxidative addition of aryl or alkyl groups to
imine, see: (j) Tsai, A. S.; Tauchert, M. E.; Bergman, R. G.; Ellman, J. A.
J. Am. Chem. Soc. 2011, 133, 1248. (k) Li, Y.; Li, B.-J.; Wang, W.-H.;
Huang, W.-P.; Zhang, X.-S.; Chen, K.; Shi, Z.-J. Angew. Chem., Int. Ed.
2011, 50, 2115.
(7) For additional examples of using [RhCp*Cl2]2 catalyst in the
oxidative addition of aryl or alkyl groups to alkynes, see: (a) Hyster,
T. K.; Rovis, T. J. Am. Chem. Soc. 2010, 132, 10565. (b) Rakshit, S.;
Patureau, F. W.; Glorius, F. J. Am. Chem. Soc. 2010, 132, 9585. (c) Too,
P. C.; Wang, Y.-F.; Chiba, S. Org. Lett. 2010, 12, 5688. (d) Guimond, N.;
Gouliaras, C.; Fagnou, K. J. Am. Chem. Soc. 2010, 132, 6908.
(e) Patureau, F. W.; Besset, T.; Kuhl, N.; Glorius, F. J. Am. Chem.
Soc. 2011, 133, 2154.
(8) For recent examples of the oxidative olefination or olefin hydro-
arylation of electron-deficient arenes, see: (a) Zhang, Y.-H.; Shi, B.-F.;
Yu, J.-Q. J. Am. Chem. Soc. 2009, 131, 5072. (b) Sun, Z.-M.; Zhang, J.;
Manan, R. S.; Zhao, P. J. Am. Chem. Soc. 2010, 132, 6935. (c) Zhang, X.;
Fan, S.; He, C.-Y.; Wan, X.; Min, Q.-Q.; Yang, J.; Jiang, Z.-X. J. Am.
Chem. Soc. 2010, 132, 4506.
(9) Ester groups were used as a directing group with catalysts other
than Rh species: Ru-catalyzed addition of aromatic esters to olefins: (a)
Sonoda, M.; Kakiuchi, F.; Kamatani, A.; Chatani, N.; Murai, S. Chem.
Lett. 1996, 109. (b) Kakiuchi, F.; Ohtaki, H.; Sonoda, M.; Chatani, N.;
Murai, S. Chem. Lett. 2001, 918. Ru-catalyzed hydrovinylation of
alkynes with acrylates. (c) Neisius, N. M.; Plietker, B. Angew. Chem.,
Int. Ed. 2009, 48, 5752.
(10) (a) Esters, Organic. Ullmann’s Encyclopedia of Industrial Chem-
istry; Riemenschneider, W., Bolt, H. M., Eds.; Wiley-VCH: Weinheim, 2005.
(b) Veitch, G. E.; Bridgwood, K. L.; Ley, S. V. Org. Lett. 2008, 10, 3623.
(c) Cao, P.; Raleigh, D. P. J. Am. Chem. Soc. 2010, 132, 4052.
(11) (a) Cho, S. H.; Hwang, S. J.; Chang, S. J. Am. Chem. Soc. 2008,
130, 9254. (b) Hwang, S. J.; Cho, S. H.; Chang, S. J. Am. Chem. Soc.
2008, 130, 16158. (c) Cho, S. H.; Kim, J. Y.; Lee, S. Y.; Chang, S. Angew.
Chem., Int. Ed. 2009, 48, 9127. (d) Kim, M.; Kwak, J.; Chang, S. Angew.
Chem., Int. Ed. 2009, 48, 8935. (e) Kim, J. Y.; Cho, S. H.; Joseph, J.;
Chang, S. Angew. Chem., Int. Ed. 2010, 49, 9899. (f) Kim, J.; Chang, S.
J. Am. Chem. Soc. 2010, 132, 10272. (g) Kim, S. H.; Chang, S. Org. Lett.
2010, 12, 1868. (h) Kim, S. H.; Yoon, J.; Chang, S. Org. Lett. 2011, 13,
1474.(i) Kwak, J.; Kim, M.; Chang, S. J. Am. Chem. Soc. 2011, 133, 3780.
additive
(mol %)
oxidant
(equiv)
entry
solvent
yield (%)b
1c
2c
3c
4
5d
6
None
Cu(OAc)2 (1.5)
None
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
tAmylOH
DMF
<1
15
84
80
60
82
12
44
<1
<1
10
80
<1
78
AgSbF6(20)
AgSbF6(20)
AgSbF6(10)
AgSbF6(4)
AgSbF6(10)
AgSbF6(10)
AgSbF6(10)
AgSbF6(10)
AgSbF6(10)
AgBF4(10)
AgSbF6(10)
AgSbF6(10)
None
Cu(OAc)2 (1.5)
Cu(OAc)2 (1.5)
Cu(OAc)2 (1.5)
Cu(OAc) (1.5)
Ag2CO3 (1.5)
Cu(OAc)2 (1.5)
Cu(OAc)2 (1.5)
Cu(OAc)2 (1.5)
Cu(OAc)2 (1.5)
Cu(OAc)2 (0.2)
O2
7
8
9
10
11
12
13e
14f
o-Xylene
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
Cu(OAc)2 (0.2)
a Conditions: 1d (0.2 mmol), 2a (0.4 mmol), [RhCp*Cl2]2 (2.5 mol
%), additive, and oxidant with solvent (0.7 mL) for 12 h at 110 °C in a
screw-capped vial. b NMR yield. c 5 Mol % of [RhCp*Cl2]2 was used. d
1
Mol % of [RhCp*Cl2]2 was used. e Carried out in a pressure tube.
f Carried out with [RhCp*(MeCN)3][SbF6]2 (5 mol %).
Ethyl 2-methylbenzoate was chosen as a test substrate to
react with ethyl acrylate using a rhodium(III) catalyst under
various conditions (Table 1). We were pleased to observe
that the [RhCp*Cl2]2 species (5 mol %) exhibited notable
catalytic activity to afford the desired product in high NMR
yield in the presence of AgSbF6 (20 mol %) and 1.5 equiv of
Cu(OAc)2 (entry 3), whereas poor results were obtained in
the absence of either additives (entries 1ꢀ2). The generated
double bond was in an E-form almost exclusively. The
olefination proceeded smoothly even with lower amounts
of Rh catalyst (1 mol %, entry 5). While a similar catalytic
activity of the rhodium catalyst was maintained with the use
of a Cu(I) oxidant (entry 6), the same equivalent of silver
carbonate resulted in a decreased yield (entry 7).
1,2-Dichloroethane was the solvent of choice; other
media provided a sluggish olefination (entries 8ꢀ10).
(12) During the preparation of this manuscript, Glorius et al. re-
ported the Rh-catalyzed olefination of acetophenones (ref 6g). In this
work, it was briefly shown as a footnote (ref 19) that an ester group
directed olefination of ethyl benzoate with styrene took place using the
same Rh catalyst (2.5 mol %, dioxane, 140 °C, 16 h) in 33% yield.
Org. Lett., Vol. 13, No. 9, 2011
2373

Silver additives other than AgSbF6 were inferior (e.g.,
entry 11). The olefination proceeded smoothly even with
a catalytic copper oxidant (entry 12).6f,13 However, reac-
tion under atmospheric oxygen did not give the desired
product in the absence of a copper species (entry 13).14 The
use of a pregenerated cationic rhodium species as a catalyst
afforded a similar product yield in the absence of a silver
additive (entry 14),15 thus indicating that the silver additive
generates a cationic rhodium species in situ.
counterpart (Scheme 2). It was observed that alteration of
an alkoxy part of benzoates did not change the reaction
efficiency, and a similar level of product yields was ob-
tained in the olefination of ethyl, isopropyl, and benzyl
benzoates (3a, 3b, and 3c, respectively).
It is noted that the moderate yields observed in the
olefination of unsubstituted benzoates can be ascribed to
the formation of bisolefinated compounds albeit as minor
side products (<5%).16 The position of an additional
substituent on substrates had little effect on the reaction
efficiencyasshownin thecases of ethyl benzoatesbearing a
methyl substituent at the 2-, 3-, or 4-position (3d, 3e, and
3f, respectively).
Scheme 2. Ortho-olefination of Arene Estersa
High regioselectivity was observed in the reaction of
ethyl 3-methylbenzoate leading to olefination only at the
CꢀH bond para to the methyl substituent presumably due
to steric reasons (3e). Functional group tolerance was high
as demonstrated in the reaction of ethyl benzoates bearing
chloro, bromo, and iodo groups, albeit product yields were
rather modest (3gꢀ3i). While ethyl 4-methoxybenzoate
underwent the olefination moderately (3j), reaction of an
unprotected hydroxy-containing substrate provided the
desired product (3k) with an acceptable yield, again show-
ing high functional group tolerance. A substrate bearing
two esteric moieties such as diethyl terephthalate under-
went the olefination to give a mono-olefinic product (3l) as
the major product in addition to a mixture of isomeric
double olefinic compounds as minor products. A range of
heterocyclic esters were next examined. For example, ethyl
thiophene-3-carboxylate and ethyl furan-3-carboxy-
late underwent the olefination exclusively at the 2-position
albeit in moderate yields (3m and 3n).
Scheme 3. Ortho-olefination of Ethyl Benzoatesa
a Conditions: 1 (0.2 mmol), 2a (0.4 mmol), [RhCp*Cl2]2 (2.5 mol %),
AgSbF6 (10 mol %), and Cu(OAc)2 (0.2 equiv) with 1,2-dichloroethane
(0.7 mL) for 12 h at 110 °C in a screw-capped vial; yields of isolated
products. b 1.5 equiv of Cu(OAc)2 was used. c Double olefinated com-
pounds were also produced in 9% yield as a mixture of 2,6- and 2,
5-isomeric bis-olefins.
a Conditions: 1d (0.2 mmol), 2 (0.4 mmol), [RhCp*Cl2]2 (2.5 mol %),
AgSbF6 (10 mol %), and Cu(OAc)2 (0.2 equiv) with 1,2-dichloroethane
(0.7 mL) for 12 h at 110 °C in a screw-capped vial; yield of isolated
products.
To explore the substrate scope, we examined various
types of arene esters in the reaction with ethyl acrylate as a
(13) (a) Ueura, K.; Satoh, T.; Miura, M. Org. Lett. 2007, 9, 1407.
(b) Stuart, D. R.; Alsabeh, P.; Kuhn, M.; Fagnou, K. J. Am. Chem. Soc.
2010, 132, 18326.
(14) Product yields were obtained from reactions under either O2 or
air atmosphere when catalytic amounts of copper additives were used.
(15) White, C.; Thompson, S. J.; Maitlis, P. M. J. Chem. Soc., Dalton
Trans. 1977, 1654.
However, poor reactivity was observed in the reaction of
heterocyclics bearing anester moietyat the 2-position (e.g.,
(16) When two reactants (1a and 2a) were employed with the same
ratio (1:1), 3a was obtained in 26%.
2374
Org. Lett., Vol. 13, No. 9, 2011

3o). When ethyl 1-naphthoate was subjected to the optimal
conditions, a single regioisomer (3p) was obtained. In
addition, the regioselectivity still remained high in the case
of ethyl 2-naphthoate leading to 3q olefinated only at the
3-position of the naphthyl ring.
On the basis of the above data and precedent litera-
ture,7a,13b,20 a plausible pathway is proposed in Scheme 4.
Scheme 4. Proposed Mechanism of Ester-Directed Olefination
With the above promising results in hand, we next
investigated the scope of alkene reactants in the olefination
of ethyl 2-methylbenzoate (1d) under the optimized con-
ditions (Scheme 3). As expected, acrylates of various
alcohols were all smoothly reacted to afford the corre-
sponding products in good yields (3r, 3s, and 3t). In
addition, it was found that acrylic acid itself was olefinated
with a similar efficiency to give an E-cinnamic acid deri-
vative (3u) in moderate yield. Moreover, it was seen that
styrenes readily underwent the olefination reaction. In-
deed, a reaction of 1d with a range of styrenes proceeded
smoothly to furnish stilbene ester derivatives in syntheti-
cally useful yields (3v and 3w).
It is postulated that [RhCp*Cl2]2 dissociates initially into
unsaturated monomeric complexes, with which AgSbF6
reacts to generate a cationic Rh species A. Because of its
highly electrophilic character, A is expected to readily
coordinate to a carbonyl oxygen of ethyl benzoate to form
B. Subsequent CꢀH bond activation at the ortho-position
is assumed to take place leading to an arylrhodium species
D presumably via a transition state C. Olefin insertion
from D may generate a rhodacycle species E and β-hydride
elimination of the intermediate provides an olefinated
product, concomitantly releasing a Rh(I) species that is
reoxidized to the þ3 oxidation state by the action of a
copper species. Reduced copper is assumed to be oxidized
by oxygen or air.
In summary, we have found that an ester or carboxal-
dehyde unit can be utilized as an efficient chelating group
to direct an olefination reaction via the regioselective CꢀH
bond activation under the oxidative Rh(III) catalytic
conditions. Although further improvements are desired
with regard to the substrate scope and reaction effi-
ciency, the present study demonstrates the directing
ability of those readily available groups in the CꢀH
bond functionalization.
It was interesting to observe that a carboxaldehyde unit
works as a directing group enabling selective olefination
albeit in moderate yield (eq 1).4b,17 This result is significant
in that no hydroacylation adduct was observed under the
conditions.18 However, a significant amount of hydrode-
carbonylation compounds were formed as the byproduct
that is responsible for the low product yields in benzalde-
hydes. When a competition experiment was performed
between ethyl benzoate and benzaldehyde, the olefination
took place only at the former substrate, implying that the
chelating ability of the formyl group is much weaker than
that of an esteric moiety (eq 2).
A significant kinetic isotope effect (KIE) was observed
(kH/kD = 2.3),19 implying that the CꢀH bond cleavage at
the 2-position of ethyl benzoate is most likely involved in
the rate-determining step (eq 3).
Acknowledgment. This research was supported by the
Korea Research Foundation (KRF-2008-C00024, Star
Faculty Program) and MIRC (NRF-2010-0001957).
Supporting Information Available. Experimental de-
tails, and 1H and 13C NMR spectra of new compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
(17) For previous examples of catalytic (Ru or Pd) ortho-functiona-
lization of benzaldehyde, see: (a) Kakiuchi, F.; Sato, T.; Igi, K.; Chatani,
€
€
€
N.; Murai, S. Chem. Lett. 2001, 386. (b) Gurbuz, N.; Ozdemir, I.;
C-etinkaya, B. Tetrahedron Lett. 2005, 46, 2273.
(18) (a) Willis, M. C.; McNally, S. J.; Beswick, P. J. Angew. Chem.,
Int. Ed. 2004, 43, 340. (b) Roy, A. H.; Lenges, C. P.; Brookhart, M.
J. Am. Chem. Soc. 2007, 129, 2082.
(19) (a) Lockley, W. J. S. Tetrahedron Lett. 1982, 23, 3819. (b)
Campbell, M. J.; Johnson, J. S. Org. Lett. 2007, 9, 1521.
(20) (a) Li, L.; Brennessel, W.; Jones, W. D. J. Am. Chem. Soc. 2008,
130, 12414. (b) Boutadla, Y.; Al-Duaij, O.; Davies, D. L.; Griffith, G. A.;
Singh, K. Organometallics 2009, 28, 433.
Org. Lett., Vol. 13, No. 9, 2011
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