Ruthenium-catalyzed regioselective oxidative coupling of aromatic and heteroaromatic esters with alkenes under an open atmosphere

Article abstract of DOI:10.1039/c2cc33339b

A ruthenium-catalyzed oxidative coupling of substituted aromatic and heteroaromatic esters with alkenes in the presence of catalytic amounts of AgSbF₆ and Cu(OAc)₂ to provide highly substituted alkene derivatives in good to excellent yields under an open atmosphere is described.

Full text of DOI:10.1039/c2cc33339b

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COMMUNICATION
Ruthenium-catalyzed regioselective oxidative coupling of aromatic and
heteroaromatic esters with alkenes under an open atmospherew
Kishor Padala, Sandeep Pimparkar, Padmaja Madasamy and Masilamani Jeganmohan*
Received 9th May 2012, Accepted 31st May 2012
DOI: 10.1039/c2cc33339b
A ruthenium-catalyzed oxidative coupling of substituted aromatic
and heteroaromatic esters with alkenes in the presence of catalytic
amounts of AgSbF6 and Cu(OAc)2 to provide highly substituted
alkene derivatives in good to excellent yields under an open atmo-
sphere is described.
But, activation in the presence of weak directing groups such
as aldehydes, esters, cyano and ketones are still a challenging
task.10 Herein, we would like to report ortho-alkenylation of
aromatic esters with alkenes in the presence of catalytic
amounts of [{RuCl2(p-cymene)}2], AgSbF6 and Cu(OAc)2,
affording highly substituted alkene derivatives in a highly
regio- and stereoselective manner. The catalytic reaction is also
compatible with various heteroaromatic esters. Interestingly,
the present ruthenium-catalyzed alkenylation reaction is carried
out under an open atmosphere and only a catalytic amount of
Cu(OAc)2 has been used as a terminal oxidant, the reduced
copper source being reoxidized by air.9f,10
Chelation-assisted ortho C–H bond activation of directing
group substituted aromatics and subsequent alkenylation with
alkenes catalyzed by transition metal complexes is an efficient
method for synthesizing substituted olefins in a highly regio- and
stereoselective manner.1 These reactions are environmentally
friendly and highly atom-economical when compared with the
other conventional methods such as carbon-halide functionaliza-
tion.2 In 1968, Fujiwara et al. demonstrated a palladium-catalyzed
alkenylation of electron-rich aromatics with alkenes by C–H bond
activation.3 In 1986, Lewis’s group showed a ruthenium-catalyzed
ortho ethylation of phenol with ethylene.4a In 1993, Murai’s group
described a ruthenium-catalyzed heteroatom-directed ortho C–H
bond activation of substituted aromatics and subsequent addition
with alkenes leading to substituted alkane derivatives.4b,c Later,
palladium-catalyzed heteroatom-directed ortho-alkenylation of
substituted aromatics with alkenes via C–H bond activation has
Treatment of methyl benzoate (1a) with ethyl acrylate (2a)
in the presence of catalytic amounts of [{RuCl2(p-cymene)}2]
(3 mol%), AgSbF6 (20 mol%) and Cu(OAc)2 (2.20 mmol) in
THF at 100 1C for 12 h gave an alkene derivative 3a in 41%
isolated yield (Scheme 1). To improve the yield of the reaction,
in addition to an ester directing group, a very weak directing
group such as 1,3-dioxol (–O–CH2–O–) was introduced at 3
and 4 positions of methyl benzoate 1a in order to further
activate the aromatic C–H bond efficiently. Interestingly, in
the reaction of methyl piperonate (1b) with ethyl acrylate (2a)
under similar reaction conditions, the corresponding alkenylated
compound 3b was obtained in excellent 85% isolated yield with a
high E-stereoselectivity. The catalytic reaction is also regioselective
and alkenylation takes place selectively at the sterically hindered
C–H bond of 1b whereby both ester and 1,3-dioxol substituents act
as directing groups. Thus, C–H bond activation takes place
selectively at the sterically hindered C–H bond. Next, the same
been demonstrated by the groups of Yu, Miura and others.5,6
A
meta-selective alkenylation of aromatics with alkenes catalyzed by
a palladium pyridine complex has been illustrated by Yu and
Sanford et al.7 Subsequently, this type of heteroatom-directed
ortho-alkenylation of substituted aromatics with alkenes in the
presence of a rhodium catalyst has been successfully extended by
the groups of Miura, Glorius and others.8 Recently, a less
expensive ruthenium complex has gained much attention in this
type of reaction.9,10 In this reaction, Cu(OAc)2 has been used as an
internal oxidant. This oxidant provides the acetate source to
the ruthenium species which facilitates ortho-metalation by a
concerted deprotonation metalation pathway.1f
Various directing groups such as amines, oximes, amides,
pyridyl, COOH, phenol, OH and carbonyl can be used in the
metal-catalyzed ortho alkenylation reactions. In the presence of
strong directing groups, C–H bond activation reactions are facile.
Department of Chemistry, Indian Institute of Science Education and
Research, Pune 411021, India. E-mail: mjeganmohan@iiserpune.ac.in
w Electronic supplementary information (ESI) available: Detailed
experimental procedures and spectroscopic data. See DOI: 10.1039/
c2cc33339b
Scheme 1 Scope of alkenes 2a–f with piperonates 1b–d.
c
7140 Chem. Commun., 2012, 48, 7140–7142
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coupling reaction was carried out under an open atmosphere in the
presence of Cu(OAc)2 (0.30 mmol, 30 mol%) under similar reaction
conditions. Interestingly, the corresponding alkene derivative 3b
was observed in 86% yield. The catalytic reaction was also tested
with various solvents such as CH3CN, toluene, MeOH, tert-BuOH,
DMF, DME, DMA and DMSO. Among them, DCE
(1,2-dichloroethane) solvent was equally effective for the reaction
similar to that with THF, giving the coupling product 3b in 87%
yield under an open atmosphere in the presence of Cu(OAc)2
(0.30 mmol, 30 mol%). Remaining solvents were totally ineffective
for the reaction. However, the catalytic reaction did not proceed in
the absence of either a copper source or silver salt.
Scheme 3 Scope of aromatic esters.
3,4-dimethoxybenzoate (1f) and isopropyl 3,4-dimethoxy-
benzoate (1g) also regioselectively coupled with cyclohexyl
acrylate (2d) providing coupling products 3m and 3n in 66%
and 62% yields, respectively, in a highly regio- and stereo-
selective manner. In this case also, C–H bond activation takes
place at the sterically less hindered C–H bond of 1f and 1g.
A similar type of regioselective product 3o in moderate 40% yield
was observed in the reaction of methyl 2-naphthoate (1h) with
ethyl acrylate (2a) under similar reaction conditions. Interestingly,
isopropyl 2-naphthoate (1i) reacted efficiently with 2a yielding the
corresponding alkene derivative 3p in good 65% yield.
Under similar reaction conditions, various acrylates 2b–e
were effectively coupled with substituted piperonates 1b–d
(Scheme 1). Thus, the reaction of methyl piperonate (1b) with
methyl acrylate (2b), n-butyl acrylate (2c) and cyclohexyl acrylate
(2d) afforded the corresponding alkenylated products 3c–e in 89%,
82% and 78% yields, respectively. Very interestingly, 2-hydroxy-
ethyl acrylate (2e) is also efficiently involved in the coupling
reaction giving product 3f in 72% yield. The catalytic reaction
was also tested with styrenes. Thus, 4-bromostyrene (2f) reacted
smoothly with 1b yielding an alkenylated product 3g in 62% yield.
Next, the effect of replacing the methyl group in methyl piperonate
(1b) by other substituents such as ethyl and isopropyl groups was
investigated. Thus, ethyl piperonate (1c) reacted nicely with methyl
acrylate (2b) affording compound 3h in 85% yield. Similarly,
isopropyl piperonate (1d) underwent coupling with ethyl and
methyl acrylates 2a and 2b yielding coupling products 3i and 3j
in 89% and 86% yields, respectively. These reactions were also
highly regio- and stereoselective similar to that with 3b.
The present alkenylation reaction was tested with various
substituted aromatic esters 1 and ethyl or methyl acrylates
(2a and 2b) under the optimized reaction conditions (Scheme 3).
The reaction of methyl 2,3-dimethoxybenzoate (1j) with methyl
acrylate (2b) afforded coupling product 3q in 65% yield. Methyl
4-hydroxybenzoate (1k) reacted with 2b providing 3r albeit in
moderate 45% yield. Whereas, methyl 4-methoxybenzoate (1l)
reacted with 2b affording 3s in 61% yield. Methyl 4-iodobenzoate
(1m) also efficiently participated in the reaction giving the corre-
sponding alkene derivative 3t in 59% yield. Whereas, methyl
2-iodobenzoate (1n) reacted with 2a providing coupling product
3a in 75% yield, in which the ortho I group of 1n participates in the
coupling reaction via oxidative addition.2 Methyl 1-napthoate (1o)
reacted with 2b affording the corresponding alkenylated derivative
3u only in 52% yield. The yield of coupling product 3v can be
improved up to 75% by replacing the methyl group by an
isopropyl group in 1-naphthoate (1p). The catalytic reaction was
also tested with various electron-withdrawing group substituted
aromatic esters such as methyl 4-nitrobenzoate and methyl
4-trifluorobenzoate under similar reaction conditions. However, in
the reaction, no coupling product was observed and only starting
material was recovered. It seems that electron-withdrawing group
substituted aromatic ester was not a compatible substrate for the
present coupling reaction.
In addition to 1b–d, the regioselectivities of other unsymmetrical
aromatic esters 1e–i were also examined under the same reaction
conditions (Scheme 2). The reaction of methyl 1,4-benzodioxane-
6-carboxylate (1e) with methyl acrylate (2b) provided substituted
alkene derivative 3k in 87% yield in a highly regio- and stereo-
selective manner. Similar to that of 1b–d, coupling reaction takes
place at the sterically hindered C–H bond of 1e. In contrast, 1e
reacted with styrene (2g) giving substituted E-stilbene derivative 3l,
albeit in only 30% yield in an opposite regiochemistry. In the
reaction, the remaining amount of 70% of starting material 1e
was recovered. In the reaction, C–H bond activation takes place
at the sterically less hindered C–H bond of 1e. Similarly, methyl
The present catalytic reaction was also examined with various
heterocyclic esters (Scheme 4). Thus, methyl thiophene-3-carboxy-
late (1q) underwent coupling reaction with methyl acrylate (2b)
providing an alkene derivative 3w in 81% yield. Substituted indole
(1r) and isopropyl furan-3-carboxylate (1s) also efficiently reacted
with methyl acrylate (2b) giving the corresponding alkenylated
products 3x and 3y in 47% and 64% yields, respectively. In the
substrate 1r, C–H bond activation takes place nicely at electron-
rich C3–H carbon.
Next, the selective de-esterification of aromatic group
substituted ester of compounds 3c and 3j was tried in the
presence of LiOHꢀH2O (1.0 equiv.) in THF : H2O : MeOH
Scheme 2 Regioselective studies of substituted aromatic esters.
c
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Notes and references
1 Selected reviews: (a) X. Chen, K. M. Engle, D.-H. Wang and
J.-Q. Yu, Angew. Chem., Int. Ed., 2009, 48, 5094; (b) T. W. Lyons
and M. S. Sanford, Chem. Rev., 2010, 110, 1147; (c) J. L. Bras and
J. Muzart, Chem. Rev., 2011, 111, 1170; (d) C. S. Yeung and
V. M. Dong, Chem. Rev., 2011, 111, 1215; (e) H. M. L. Davies,
J. D. Bois and J.-Q. Yu, Chem. Soc. Rev., 2011, 40, 1855, references
therein; (f) L. Ackermann, Chem. Rev., 2011, 111, 1351.
2 Selected papers: (a) S. A. Shahzad and T. Wirth, Angew. Chem.,
Int. Ed., 2009, 48, 2588; (b) S. A. Shahzad, C. Venin and T. Wirth,
Eur. J. Org. Chem., 2010, 3465.
Scheme 4 Scope of heteroaromatic esters.
3 Selected papers: (a) Y. Fujiwara, I. Moritani, M. Matsuda and
S. Teranishi, Tetrahedron Lett., 1968, 3863; (b) Y. Fujiwara,
I. Moritani, S. Danno, R. Asano and S. Teranishi, J. Am. Chem.
Soc., 1969, 91, 7166.
4 (a) L. N. Lewis and J. F. Smith, J. Am. Chem. Soc., 1986,
108, 2728; (b) S. Murai, F. Kakiuchi, S. Sekine, Y. Tanaka,
A. Kamatani, M. Sonoda and N. Chatani, Nature, 1993,
366, 529; (c) F. Kakiuchi and S. Murai, Acc. Chem. Res., 2002,
35, 826.
5 Selected references: (a) S. E. Diamond, A. Szalkiewicz and
F. Mares, J. Am. Chem. Soc., 1979, 101, 490; (b) L.-C. Kao and
A. Sen, J. Chem. Soc., Chem. Commun., 1991, 1242; (c) M. Miura,
T. Tsuda, T. Satoh, S. Pivsa-Art and M. Nomura, J. Org. Chem.,
1998, 63, 5211; (d) K. Li, L. N. Foresee and J. A. Tunge, J. Org.
Chem., 2005, 70, 2881; (e) E. M. Beck, N. P. Grimster, R. Hatley
and M. J. Gaunt, J. Am. Chem. Soc., 2006, 128, 2528;
(f) T. Nishikata and B. H. Lipshutz, Org. Lett., 2010, 12, 1972;
(g) P. Gandeepan, K. Parthasarathy and C.-H. Cheng, J. Am.
Chem. Soc., 2010, 132, 8569; (h) J. Karthikeyan and C.-H. Cheng,
Angew. Chem., Int. Ed., 2011, 50, 9880.
(4:1:1) at 80 1C for 12 h. Surprisingly, in the reaction,
de-esterification takes place very selectively at unsaturated ester
providing substituted carboxylic acids 4a and 4b in 79% and 87%
yields, respectively (eqn (1)). An ester group connected with
aromatic moieties of 3c and 3j remains intact. For selective
de-esterification of aromatic group substituted ester, the reaction
was tried with various bases such as NaOH and KOH under the
same reaction conditions. In these reactions also, de-esterification
selectively takes place at unsaturated ester. The coupling reaction of
methyl piperonate (1b) with acrylic acid (2h) was tried under the
optimized reaction conditions. However, in the reaction, coupling
product 4a was not observed and only acrylic acid dimerization was
observed. By using the present de-esterification reaction, substituted
acrylic acid derivatives can be synthesized in excellent yields.
6 (a) J.-J. Li, T.-S. Mei and J.-Q. Yu, Angew. Chem., Int. Ed., 2008,
47, 6452; (b) K. M. Engle, D.-H. Wang and J.-Q. Yu, J. Am. Chem.
Soc., 2010, 132, 14137; (c) D.-H. Wang, K. M. Engle, B.-F. Shi and
J.-Q. Yu, Science, 2010, 327, 315; (d) B.-F. Shi, Y.-H. Zhang,
J. K. Lam, D.-H. Wang and J.-Q. Yu, J. Am. Chem. Soc., 2010,
132, 460; (e) Y. Lu, D.-H. Wang, K.-M. Engle and J.-Q. Yu, J. Am.
Chem. Soc., 2010, 132, 5916; (f) M. Ye, G.-L. Gao and J.-Q. Yu,
J. Am. Chem. Soc., 2011, 133, 6964.
ð1Þ
The catalytic reaction proceeds via reaction of the
[{RuCl2(p-cymene)}2] complex with AgSbF6 giving cationic
ruthenium complex 5 (eqn (2)). Coordination of the carbonyl
oxygen of aromatic ester 1 to the ruthenium cationic species 5
followed by ortho-metalation affords ruthenacycle intermediate 6
(eqn (2)).1f Insertion of alkene 2 into the Ru–carbon bond of
intermediate 6 provides a seven-membered ruthenacycle inter-
mediate 7 (eqn (2)). b-Hydride elimination of intermediate 7
yields coupling product 3 and regenerates the active ruthenium
species for the next catalytic cycle. The remaining amount of the
active Cu(OAc)2 source is regenerated under an atmosphere from
the reduced copper source such as CuOAc.
7 (a) Y.-H. Zhang, B.-F. Shi and J.-Q. Yu, J. Am. Chem. Soc., 2009,
131, 5072; (b) A. Kubota, M. H. Emmert and M. S. Sanford, Org.
Lett., 2012, 14, 1760.
8 Selected references: (a) N. Umeda, K. Hirano, T. Satoh and
M. Miura, J. Org. Chem., 2009, 74, 7094; (b) S. Mochida,
K. Hirano, T. Satoh and M. Miura, Org. Lett., 2010, 12, 5776;
(c) S. Rakshit, C. Grohmann, T. Besset and F. Glorius, J. Am.
Chem. Soc., 2011, 133, 2350; (d) F. W. Patureau and F. Glorius,
J. Am. Chem. Soc., 2010, 132, 9982; (e) F. W. Patureau, T. Besset
and F. Glorius, Angew. Chem., Int. Ed., 2011, 50, 1064; (f) C. Feng
and T.-P. Loh, Chem. Commun., 2011, 47, 10458; (g) S. Park,
J. Y. Kim and S. Chang, Org. Lett., 2011, 13, 2372; (h) F. Wang,
G. Song and X. Li, Org. Lett., 2010, 12, 5430; (i) T.-J. Gong,
B. Xiao, Z.-J. Liu, J. Wan, J. Xu, D.-F. Luo, Y. Fu and L. Liu,
Org. Lett., 2011, 13, 3235; (j) K. Muralirajan, K. Parthasarathy
and C.-H. Cheng, Angew. Chem., Int. Ed., 2011, 50, 4169;
(k) A. S. Tsai, M. Brasse, R. G. Bergman and J. A. Ellman,
Org. Lett., 2011, 13, 540; (l) J. Jayakumar, K. Parthasarathy and
C.-H. Cheng, Angew. Chem., Int. Ed., 2012, 51, 197.
9 Alkylation: (a) M. Sonoda, F. Kakiuchi, A. Kamatani, N. Chatani
and S. Murai, Chem. Lett., 1996, 109; Alkenylation:
(b) T. Ueyama, S. Mochida, T. Fukutani, K. Hirano, T. Satoh
and M. Miura, Org. Lett., 2011, 13, 706; (c) L. Ackermann and
J. Pospech, Org. Lett., 2011, 13, 4153; (d) L. Ackermann, L. Wang,
R. Wolfram and A. V. Lygin, Org. Lett., 2012, 14, 728; (e) B. Li,
J. Ma, N. Wang, H. Feng, S. Xu and B. Wang, Org. Lett., 2012,
14, 736; (f) L. Ackermann, L. Wang and A. V. Lygin, Chem. Sci.,
2012, 3, 177; (g) L. Ackermann, A. V. Lygin and N. Hofmann,
Angew. Chem., Int. Ed., 2011, 50, 6379.
10 (a) P. Kishor and M. Jeganmohan, Org. Lett., 2012, 14, 1134;
(b) P. Kishor and M. Jeganmohan, Org. Lett., 2011, 13, 6144;
(c) C. G. Ravi Kiran and M. Jeganmohan, Eur. J. Org. Chem.,
2012, 417; (d) C. G. Ravi Kiran and M. Jeganmohan, Chem.
Commun., 2012, 48, 2030.
ð2Þ
In conclusion, we have developed a ruthenium-catalyzed
highly regioselective ortho-alkenylation of aromatic and hetero-
aromatic esters with alkenes giving substituted alkene derivatives
in a highly stereoselective manner. Further extension of the C–H
bond activation of other directing group substituted aromatics
and functionalization with other p-components and the detailed
mechanistic investigation are in progress.
We thank the BRNS (2011/20/37C/07/BRNS), India, for
the support of this research. K. P. thanks the CSIR for a
fellowship.
c
7142 Chem. Commun., 2012, 48, 7140–7142
This journal is The Royal Society of Chemistry 2012