Ruthenium-catalyzed highly regio- and stereoselective hydroarylation of aryl carbamates with alkynes via C-H bond activation

Article abstract of DOI:10.1039/c2cc37758f

Chelation-assisted alkenylation of ortho C-H bond of aryl carbamates with alkynes in the presence of a ruthenium catalyst, AgSbF₆ and pivalic acid gives highly substituted alkene derivatives in good to excellent yields in a highly regio- and stereoselective manner.

Full text of DOI:10.1039/c2cc37758f

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Ruthenium-catalyzed highly regio- and stereoselective
hydroarylation of aryl carbamates with alkynes via
C–H bond activation†
Cite this: Chem. Commun., 2013,
49, 481
Received 1st October 2012,
Accepted 7th November 2012
Mallu Chenna Reddy and Masilamani Jeganmohan*
DOI: 10.1039/c2cc37758f
www.rsc.org/chemcomm
Chelation-assisted alkenylation of ortho C–H bond of aryl carbamates products. This reaction is also not completely regioselective
with alkynes in the presence of a ruthenium catalyst, AgSbF6 and pivalic and mostly gives mixture of regioisomers.
acid gives highly substituted alkene derivatives in good to excellent
yields in a highly regio- and stereoselective manner.
These kinds of regio- and stereoisomeric issue can be easily
overcome by doing a similar type of hydroarylation reaction via
a concerted deprotonation–metalation pathway instead of an
Transition metal-catalyzed chelation-assisted C–H bond hydro- oxidative addition pathway.7–9 In 2010, Fagnou’s group
arylation of heteroatom group substituted aromatics with reported a strongly directing amide group-assisted rhodium-
alkynes is a convenient method to synthesize highly substituted catalyzed hydroarylation of substituted indoles with alkynes.9a
alkene derivatives in a highly atom-economical and environ- Very recently, Miura’s group reported a strongly directing
mentally friendly manner.1,2 Alkene structural units are present amide group-assisted ruthenium-catalyzed hydroarylation of
in various organic materials, natural products and drug mole- benzamides with alkynes.9b The catalytic reaction proceeds
cules.1,2 In 1995, Murai’s group reported alkenylation at the via chelation-assisted acetate accelerated deprotonation at the
C–H bond of carbonyl group substituted aromatics with alkynes ortho C–H bond of the heteroatom group substituted aromatic
in the presence of a ruthenium catalyst.3a,b Since then, various compound by the metal complex (Rh or Ru), providing metalla-
metal complexes, including rhodium, palladium, iridium and cycle intermediate C (eqn (1b)). Coordinative insertion of the
nickel complexes have been successfully used as catalysts aromatic group substituted alkyne into the metal–carbon bond
for hydroarylation of various heteroatom group substituted of metallacycle C provides metallacycle intermediate D. Subse-
aromatics with alkynes.4–6 It is believed that this coupling quent protonation by an organic acid gives the corresponding
reaction proceeds mechanistically via chelation-assisted oxida- alkene derivative in a highly regio- and stereoselective manner
tive addition of the ortho C–H bond of a heteroatom-substituted (eqn (1b)). The regiochemistry of the product of this reaction is
aromatic to the metal complex, yielding a five-membered completely reversed when compared with the regiochemistry of
hydrometallacycle intermediate A (eqn (1a)). Then, an aromatic product obtained via the oxidative addition pathway (eqn (1a)).
group substituted alkyne undergoes coordinative insertion into A possible explanation for the reversed regiochemistry of the
metal hydride intermediate species A, followed by reductive product is that it is probably due to intramolecular coordina-
elimination, providing the corresponding alkene derivative. tion of the phenyl group of the alkyne to the metal species
Usually, Ph groups from both the alkyne and the heteroatom which stabilizes the corresponding intermediate (eqn (1b)).
substituted aromatic attach to the same carbon of the alkene,
providing a mixtures of cis and trans stereoisomeric addition
ð1bÞ
ð1aÞ
Department of Chemistry, Indian Institute of Science Education and Research, Pune,
Until now, for this type of hydroarylation reaction, only
strongly directing amide group directed hydroarylation reac-
tions have been studied. Herein, we wish to report an unpre-
411021, India. E-mail: mjeganmohan@iiserpune.ac.in
† Electronic supplementary information (ESI) available: Detailed experimental
procedures and spectroscopic data. CCDC 907975 and 907976. For ESI and
cedented weakly directing carbamate group assisted
hydroarylation of aryl carbamates with alkynes in the presence
crystallographic data in CIF or other electronic format see DOI: 10.1039/
c2cc37758f
c
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Chem. Commun., 2013, 49, 481--483 481

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of [{RuCl2(p-cymene)}2], AgSbF6 and pivalic acid, which affords
To explore the scope of the present hydroarylation reaction, the
highly substituted alkene derivatives in good to excellent yields reactions of various substituted aryl carbamates 1b–k with 2a–b
in a highly regio- and stereoselective manner. The alkyne were examined (Table 1). 3-Methoxyphenyl carbamate 1b underwent
substituents determine the regiochemistry of the coupling hydroarylation with ethyl but-2-ynoate (2a) under the optimized
product. In the alkene products, Ph or ester groups from the reaction conditions, providing coupling product 3b in 79% yield in a
alkyne are trans to the aromatic carbamate.
highly regio- and stereoselective manner (entry 2). In substrate 1b,
Treatment of 4-methoxyphenyl diethylcarbamate (1a) with there are two C–H bonds which could undergo hydroarylation with
ethyl but-2-ynoate (2a) in the presence of [{RuCl2(p-cymene)}2] 2a. The coupling reaction was very selective for the less hindered
(5 mol%), AgSbF6 (20 mol%) and pivalic acid (5.0 equiv.) in C–H bond of 1b. Similarly, 3,4-dimethoxyphenyl carbamate 1c and
1,4-dioxane at 100 1C for 24 h gave hydroarylation product 3a 3,4-dimethylphenyl carbamate 1d afforded alkene derivatives 3c
in 77% isolated yield (Table 1, entry 1) (for detailed optimiza- and 3d in 83% and 80% yields, respectively, in a highly regio- and
tion studies see ESI†). The catalytic reaction is highly regioselec- stereoselective manner (entries 3 and 4). As for 1b, in this reaction,
tive and the ortho C–H bond of 1a very selectively inserts at alkenylation takes place selectively at the less hindered C–H bond of
the methyl-substituted carbon of alkyne 2a. The catalytic reac- 1c and 1d. In contrast, sesamol carbamate 1e reacted with 2a at the
tion is also highly stereoselective, giving only the E-stereoisomer more sterically hindered C–H bond, yielding 3e as the product of the
of 3a.
E-stereoselective coupling in 82% yield in a highly regioselective
manner (entry 5). Next, the hydroarylation reaction was tested with
halogen group substituted carbamates 1f–i. Thus, 4-iodo 1f,
4-bromo 1g, 4-chloro 1h and 4-fluoro 1i phenyl carbamates
efficiently reacted with methyl oct-2-ynoate (2b) giving E-stereo-
selective alkene derivatives 3f–i in 80%, 75%, 73% and 64% yields,
respectively (entries 6–9). Similarly, 1-naphthalenyl diethylcarba-
mate (1j) reacted with ethyl but-2-ynoate (2a) affording coupling
product 3j in 65% yield in a highly stereoselective manner (entry 10).
Interestingly, 2-naphthalenyl diethylcarbamate (1k) reacted with
ethyl but-2-ynoate (2a) at the less sterically hindered ortho C–H
bond of the naphthyl moiety, providing coupling product 3k in 69%
yield, in a highly regio- and stereoselective manner (entry 11).
The substrate scope of the hydroarylation reaction was
extended successfully to include various substituted alkynes
2b–k (Table 2 and eqn (2)). Thus, 1-phenyl-1-propyne (2c),
1-phenyl-1-butyne (2d) and 1-phenyl-1-hexyne (2e) reacted very
selectively at the sterically hindered C–H bond of sesamol
carbamate 1e, providing the corresponding alkene derivatives
3l–n in 86%, 84% and 81% yields, respectively, in a highly
stereoselective manner (Table 2, entries 1–3). The catalytic
reaction is highly regioselective and the C–H bond of 1e added
at the Me, n-Pr or n-pentyl group-substituted carbon of alkynes
2c–e. Similarly, methoxy ether 2f and methyl ester 2g substi-
tuted alkynes also successfully participated in the reaction,
affording coupling products 3o and 3p in 83% and 75% yields,
respectively (entries 4 and 5). Methyl hex-2-ynoate (2h) and
methyl oct-2-ynoate (2b) provided the corresponding E-stereo-
selective alkene derivatives 3q and 3r in 79% and 76%
yields, respectively (entries 6 and 7). Similarly, trimethyl-
(phenylethynyl)silane (2i) also efficiently participated in the
reaction with 1e affording alkene derivative 3s in 72% yield
(entry 8). However, in product 3s, the TMS moiety of the alkyne
was cleaved under the reaction conditions. 4-Iodophenyl carbamate
1f efficiently reacted with 1-phenyl-1-propyne (2c) under similar
reaction conditions providing the corresponding alkene derivative
3t in 75% yield (entry 9). Diphenylacetylene (2j) also reacted
Table 1 The reaction of aryl carbamates 1a–k with alkynes 2a–ba
Entry Carbamates 1a–k Alkynes 2a–b Product 3
Yieldb (%)
77
1
2
2a
2a
79
3
4
1c: R1 = R1 = OMe 2a
1d: R1 = R1 = Me 2a
3c: R1 = R1 = OMe 83
3d: R1 = R1 = Me 80
5
2a
82c
6
1f: R1 = I
1g: R1 = Br
1h: R1 = Cl
1i: R1 = F
2b
3f: R1 = I
3g: R1 = Br
3h: R1 = Cl
3i: R1 = F
80
7
8
9
2b
2b
2b
75
73
64
10
65
69
11
2a
a
All reactions were carried out under the following reaction conditions:
1a–k (1.0 mmol), 2a–b (1.5 mmol), [{RuCl2(p-cymene)}2] (5 mol%),
AgSbF6 (20 mol%) and pivalic acid (5.0 mmol) in 1,4-dioxane at 100 1C
ð2Þ
b
c
for 24 h under a N2 atmosphere. Isolated yield. The reaction was
carried out at 100 1C for 16 h.
c
482 Chem. Commun., 2013, 49, 481--483
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Table 2 The reaction of carbamates 1e or 1f with alkynes 2b–ja
confirmed by single crystal X-ray diffraction (see ESI†). For
detailed mechanistic studies of this, see the ESI.†
Entry
1
Alkynes 2b–j
Product 3l–u
Yieldb (%)
ð3aÞ
1
1e
2c: R2 = Me
3l: R2 = Me
86
2
3
1e
1e
2d: R2 = Et
3m: R2 = Et
84
81
2e: R2 = n-Bu
3n: R2 = n-Bu
ð3bÞ
We thank the DST (SR/S1/OC-26/2011), India, for their
support of this research. M. C. R. thanks the CSIR for a
fellowship.
4
5
1e
1e
2f: R3 = OMe
2g: R3 = CO2Me
3o: R3 = OMe
3p: R3 = CO2Me
83
75
Notes and references
1 A. B. Flynn and W. W. Ogilvie, Chem. Rev., 2007, 107, 4698.
2 Selected reviews: (a) V. Ritleng, C. Sirlin and M. Pfeffer, Chem. Rev.,
2002, 102, 1731; (b) T. W. Lyons and M. S. Sanford, Chem. Rev., 2010,
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Soc. Rev., 2011, 40, 1992; ( f ) S. H. Cho, J. Y. Kim, J. Kwak and
S. Chang, Chem. Soc. Rev., 2011, 40, 5068.
6
7
1e
1e
2h: R4 = n-Pr
2b: R4 = n-Pentyl
3q: R4 = n-Pr
3r: R4 = n-Pentyl
79
76
3 Ruthenium selected papers: (a) N. J. Clegg, S. Paruthiyil,
D. C. Leitman, F. Kakiuchi, Y. Yamamoto, N. Chatani and S. Murai,
Chem. Lett., 1995, 681; (b) F. Kakiuchi, T. Uetsuhara, Y. Tanaka,
N. Chatani and S. Murai, J. Mol. Catal. A: Chem., 2002, 182 and 511;
from other groups: (c) T. Mitsudo, S.-W. Zhang, M. Nagao and
Y. Watanabe, J. Chem. Soc., Chem. Commun., 1991, 598;
(d) N. M. Neisius and B. Plietker, Angew. Chem., Int. Ed., 2009,
48, 5752.
4 Rhodium selected papers: (a) Y. Shibata, M. Hirano and K. Tanaka,
Org. Lett., 2008, 10, 2829; (b) P. Hong and H. Yamazaki, J. Mol. Catal.,
1983, 21, 133; (c) S. G. Lim, J. H. Lee, C. W. Moon, J. B. Hong and
C. H. Jun, Org. Lett., 2003, 5, 2759; (d) K. Parthasarathy and
C. H. Cheng, Org. Lett., 2008, 10, 325.
8
1e
72
9
1f
75c
89
10
1e
5 Iridium selected paper: (a) T. Satoh, Y. Nishinaka, M. Miura and
M. Nomura, Chem. Lett., 1999, 615; Palladium selected paper:
(b) N. Tsukada, T. Mitsuboshi, H. Setoguchi and Y. Inoue, J. Am.
Chem. Soc., 2003, 125, 12102.
6 Nickel selected papers: (a) Y. Nakao, K. S. Kanyiva and T. Hiyama,
J. Am. Chem. Soc., 2008, 130, 2448; (b) Y. Nakao, Chem. Rec., 2011,
11, 242.
7 Alkenylation by alkenes selected papers: (a) J.-J. Li, T.-S. Mei and
J.-Q. Yu, Angew. Chem., Int. Ed., 2008, 47, 6452; (b) P. Gandeepan and
C.-H. Cheng, J. Am. Chem. Soc., 2012, 134, 5738; (c) T. Ueyama,
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Lett., 2011, 13, 706; (d) L. Ackermann, A. V. Lygin and N. Hofmann,
Angew. Chem., Int. Ed., 2011, 50, 6379.
8 (a) P. Kishor and M. Jeganmohan, Org. Lett., 2012, 14, 1134;
(b) P. Kishor and M. Jeganmohan, Org. Lett., 2011, 13, 6144;
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a
All reactions were carried out under the following reaction conditions:
1e or 1f (1.0 mmol), 2b–j (1.5 mmol), [{RuCl2(p-cymene)}2] (5 mol%),
AgSbF6 (20 mol%) and pivalic acid (5.0 mmol) in 1,4-dioxane at 100 1C
b
c
for 16 h under a N2 atmosphere. Isolated yield. The reaction was
done at 100 1C for 24 h.
efficiently with 1e yielding alkenylated product 3u in excellent
89% yield (entry 10). Subsequently, the reaction of 1e with
methyl 3-phenylpropiolate (2k) was also tested under similar
reaction conditions (eqn (2)). In this reaction, a mixture of
regioisomeric products 3v and 3v0 were observed in 89% yield
in approximately a 1 : 1 ratio.
It was found that ester 3r was converted into carboxylic acid
derivative 4a in the presence of LiOH (2.0 equiv.) (eqn (3a)),
whereas 10.0 equiv. of LiOH cleaved both ester and carbamate
moieties of compound 3k, giving phenol derivative 4b in 87%
yield (eqn (3b)). The structures of compounds 4a and 4b were
9 (a) D. J. Schipper, M. Hutchinson and K. Fagnou, J. Am. Chem. Soc.,
2010, 132, 6910; (b) Y. Hashimoto, K. Hirano, T. Satoh, F. Kakiuchi
and M. Miura, Org. Lett., 2012, 14, 2058; (c) P. Zhao, R. Niu, F. Wang,
K. Han and X. Li, Org. Lett., 2012, 14, 4166.
c
This journal is The Royal Society of Chemistry 2013
Chem. Commun., 2013, 49, 481--483 483