Ruthenium-catalyzed alkenylation of azoxybenzenes with alkenes through ortho-selective C-H activation

Article abstract of DOI:10.1039/c4cc00449c

A highly selective alkenylation of azoxybenzenes catalyzed by the Ru ^III-complex was developed. It provides a direct access to a series of olefinated azoxy compounds in good yields. the Partner Organisations 2014.

Full text of DOI:10.1039/c4cc00449c

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Ruthenium-catalyzed alkenylation of
azoxybenzenes with alkenes through
ortho-selective C–H activation†
Hongji Li,a Xiaoyu Xiea and Lei Wang*ab
Cite this: Chem. Commun., 2014,
50, 4218
Received 18th January 2014,
Accepted 4th March 2014
DOI: 10.1039/c4cc00449c
www.rsc.org/chemcomm
A highly selective alkenylation of azoxybenzenes catalyzed by the
RuIII-complex was developed. It provides a direct access to a series
of olefinated azoxy compounds in good yields.
Recently, transition metal-catalyzed alkenylation of C–H bonds has
been one of the most practical, atom- and step-economical method in
synthetic organic chemistry.1 Especially noteworthy is that Fujiwara’s
group has made the initial work on the catalytic alkenylation of
electron-rich aromatic C–H bonds with alkenes by a palladium
Scheme 1 RuIII-catalyzed ortho-selective alkenylation.
complex.2 After that, the palladium catalyst was broadly employed As part of our ongoing interest in C–H activation,11 herein we
in the catalytic alkenylation of functionalized substrates.3 In addition, wish to report the first RuIII-catalyzed ortho-selective alkenylation
rhodium-catalyzed alkenylations of amides, esters and ketones were of azoxybenzenes, which provided a simple approach to a variety
also developed in recent years.4 Most recently, ruthenium complexes of olefinated azoxy compounds (Scheme 1).
have been exploited as alternative catalysts for the direct C–H bond
The initial reaction of azoxybenzene (1a) with ethyl acrylate (2a)
alkenylations.5 For example, Ackerman,5a,b Wang,5c,d and others5e–h was carried out in the presence of 2.5 mol% of [{RuCl2(p-cymene)}2]
have done excellent work on the Ru-catalyzed alkenylations. and Cu(OAc)2ÁH2O (1.0 equiv.) in 1,2-dichloroethane (DCE) at 110 1C
However, more substrates with new directing groups and the regio- for 12 h, which only generated the mono-substituted alkenylation
selective reactions at their ortho-positions were necessary to be product 3a in 17% yield (Table 1, entry 1). The structure of 3a was
explored. As far as we know, the useful azoxybenzenes with indirectly confirmed by the hydrolysis of 3a into its carboxylic acid 4a
two kinds of C–H bonds at the ortho-position of the nitrogen atom in NaOH–CH3OH,12 and the structure of 4a was further determined
have been rarely studied in group-directed C–H activation and by X-ray single crystal analysis, as described in Scheme 2 (details in
functionalizations.6
ESI†). After that, the use of anhydrous Cu(OAc)2 was investigated in
Azoxy compounds are important materials and useful intermediates the model reaction under a nitrogen atmosphere, and 29% of 3a was
in electronic devices due to their liquid crystalline properties,7 and they isolated (Table 1, entry 2). To our delight, an enhanced yield of 3a
have also been used as dyes, polymer inhibitors and stabilizers.8 In light was observed in the presence 5.0 mol% of [Cp*RuCl2]n as the catalyst
of their importance, numerous methods for the preparation of azoxy (Table 1, entry 3). Some other common additives, such as KPF6 and
compounds have been developed.9 However, there is no report on the AgSbF6, were also examined and results showed that the employ-
synthesis of ortho-alkenyl azoxybenzenes. Very recently, RuII-catalyzed ment of AgSbF6 (20 mol%) obviously accelerated this transformation
C–H bond activation and functionalizations have been (Table 1, entries 4–7).
reported,5,10 and which promoted us to explore the possibility
Subsequently, the optimization of reaction time and temperature
of RuIII-catalyzed alkenylation of azoxybenzenes with alkenes. did not improve the yield of product 3a (Table 1, entries 8–11). When
the molar ratio of 1a/2a (1 : 2) was controlled, a lower yield of 3a was
a Department of Chemistry, Huaibei Normal University, Huaibei, Anhui 235000,
P. R. China. E-mail: leiwang@chnu.edu.cnp; Fax: +86-561-309-0518;
Tel: +86-561-380-2069
b State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic
Chemistry, Chinese Academy of Sciences, Shanghai 200032, P. R. China
† Electronic supplementary information (ESI) available. CCDC 975924. For ESI and
achieved (41%), and the formation of disubstituted product may
account for this result (Table 1, entry 12).13 It was found that the use
of silver salt as an additive resulted in lower yields of 3a (Table 1,
entries 13 and 14). Additionally, it was found that the Ru-catalyzed
alkenylation reaction could not proceed in the absence of Cu(OAc)2
crystallographic data in CIF or other electronic format see DOI: 10.1039/c4cc00449c (Table 1, entries 15 and 16). Finally, some typical reaction media
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Table 1 Optimization of Ru source and additivesa
Additive 1
(1.0 equiv.)
Additive 2
(mol%)
Yieldb
(%)
Entry
Ru source
1
2
3
4
5
6
7
8
[RuCl2L]2
[RuCl2L]2
Cu(OAc)2ÁH2O
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
AgOAc
/
/
/
17
29
35
33
56
68
70c
62d
69e
51f
70g
41h
24
11
0
[Cp*RuCl2]n
[Cp*RuCl2]n
[Cp*RuCl2]n
[Cp*RuCl2]n
[Cp*RuCl2]n
[Cp*RuCl2]n
[Cp*RuCl2]n
[Cp*RuCl2]n
[Cp*RuCl2]n
[Cp*RuCl2]n
[Cp*RuCl2]n
[Cp*RuCl2]n
[Cp*RuCl2]n
[Cp*RuCl2]n
KPF6 (10)
AgSbF6 (10)
AgSbF6 (20)
AgSbF6 (30)
AgSbF6 (20)
AgSbF6 (20)
AgSbF6 (20)
AgSbF6 (20)
AgSbF6 (20)
AgSbF6 (20)
AgSbF6 (20)
AgSbF6 (20)
AgSbF6 (20)
9
10
11
12
13
14
15
16
Ag2CO3
/
/
0i
a
Reaction conditions: azoxybenzene (1a, 0.20 mmol), ethyl acrylate (2a,
0.30 mmol), Ru complex (containing 5.0 mol% Ru), additive 1 (0.20 mmol),
additive 2 amount indicated in this Table in DCE (1.0 mL) at 110 1C under
c
N2 for 12 h. b Isolated yields. 30 mol% of AgSbF6. d 90 1C. e 130 1C. f 8 h.
g 15 h. h Molar ratio of 1a with 2a = 1:2. i 2a (0.60 mmol) was used. Cp* =
pentamethylcyclopentadienyl, L = p-cymene.
Scheme 3 The alkenylation of azoxybenzenes with alkenes. a Reaction
conditions: azoxybenzene (1, 0.20 mmol), alkene (2, 0.30 mmol),
[Cp*RuCl2]n (5.0 mol%), AgSbF6 (0.04 mmol), Cu(OAc)2 (0.20 mmol),
DCE (1.0 mL), 110 1C, N2, 12 h; isolated yields. b 130 1C.
azoxybenzenes was also examined using ethyl acrylate as one of the
coupling partner. Electron-withdrawing groups (F, Cl, and CO2Et)
and electron-donating groups (Me, and MeO) at the para-
positions of the nitrogen on the benzene rings were all tolerated
under the optimized reaction conditions. In the most cases,
electron-rich azoxybenzenes seemed to be more active than that
electron-deficient one, and the former gave slightly high yields
of the corresponding products (3q vs. 3u). Moreover, the
Scheme 2 Hydrolysis of 3a into 4a, and the structure of 4a determined
by X-ray single crystal analysis.
were investigated and experimental results indicated that DCE was steric effect was distinctively observed when methyl-substituted
the most suitable solvent for this reaction (Table S1 in ESI†). azoxybenzenes at their para-, meta- and ortho-positions were
With the optimized reaction conditions in hand, we next explored used to react with ethyl acrylate, giving products 3r–t in 67%,
the substrate scope in Ru-catalyzed alkenylation of azoxybenzenes 1 60% and 33% yields, respectively.
with alkenes 2, as shown in Scheme 3. Under a nitrogen atmosphere,
Next, we focused on the intermolecular competition experi-
a variety of alkyl acrylates reacted with azoxybenzene 1a smoothly ments,5a,14 which were performed using differently substituted
under present reaction conditions, and the corresponding products azoxybenzenes and ethyl acrylate under standard reaction con-
3a–h were isolated in 57–81% yields. Generally, alkyl acrylates with ditions, as shown in Scheme 4. The experimental results
low boiling point would lead to much lower yields of the desired revealed that electron-rich azoxybenzene was preferentially
products (3a–c vs. 3d–h). When 2-hydroxyethyl acrylate 2i was used to functionalized in C–H activation, and high yields of the corres-
couple with 1a, the corresponding olefinated product 3i was isolated ponding products were obtained (Scheme 4).
only in 29% yield, even at elevated temperature. On the other hand,
In addition, we continued our investigation into selective H–D
aryl acrylates (2j–l) were used as the coupling partners in the exchange15 at the ortho-positions of the azoxy group on the benzene
alkenylation of 1a, providing the anticipated products (3j–l) in ring, which was performed in the mixture of DCE–D2O (1:1) at
satisfactory yields. Interestingly, the reactions of diethyl and dimethyl 110 1C under a nitrogen atmosphere for 12 h (Scheme 5). A
vinylphosphonates with 1a generated the coupling products 3m in significant D–H exchange (87.5%) provided the solid evidence for
65% yield, and 3n in 59% yield, respectively. Next, the scope of a reversible C–H bond ruthenation process.
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the CuII salt was not clear, we proposed that the acetate anion may
be coordinated to the ruthenium species and accelerate the ortho-
metalation.14b
In conclusion, we have developed a highly selective RuIII-
complex-catalyzed ortho-alkenylation of azoxybenzenes with
activated alkenes in the presence of AgSbF6 and Cu(OAc)2 to
afford a variety of olefinated azoxy derivatives in good yields.
Further application of these useful azoxy compounds and
detailed mechanistic investigation are in progress.
This work was financially supported by the National Science
Foundation of China (No. 21372095 and 21172092) and the
Department of Education, Anhui Province (No. KJ2013B246).
Notes and references
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Scheme 5 RuIII-catalyzed ortho-selective alkenylation.
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[Cp*RuCl2]n generated RuIII species I, which reacted with 1a to form
a five-membered metallacycle II by Ru-catalyzed ortho-selective C–H
bond activation of 1a and its coordination. Then, the coordinative
insertion of alkene 2 into intermediate II afforded a seven-
membered intermediate III. Finally, the b-hydrogen elimination
from intermediate III gave the final product 3 and regenerated the
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Scheme 6 The proposed reaction mechanism.
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products was obtained in the reaction of 1a (0.20 mmol) with ethyl
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