Nondirected C-H alkenylation of arenes with alkenes under rhodium catalysis

Article abstract of DOI:10.1246/cl.180907

A nondirected dehydrogenative direct alkenylation of simple aromatic compounds with alkenes under rhodium catalysis is described. The site-selectivity is dominantly dictated by the steric bulkiness around the targeted CH bond. The reaction efficiency was

Full text of DOI:10.1246/cl.180907

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Nondirected C-H Alkenylation of Arenes with Alkenes under Rhodium Catalysis
Koushik Ghosh, Gen Mihara, Yuji Nishii,* and Masahiro Miura*
Advance Publication on the web December 1, 2018
doi:10.1246/cl.180907
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2018 The Chemical Society of Japan
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1
Nondirected C-HAlkenylation ofArenes with Alkenes under Rhodium Catalysis
1
1
2
1
Koushik Ghosh, Gen Mihara, Yuji Nishii,* and Masahiro Miura*
1
2
Department of Applied Chemistry and Frontier Research Base for Global Young Researchers,
Graduate School of Engineering, Osaka University, Suita, Osaka 565-0871
E-mail: y_nishii@chem.eng.osaka-u.ac.jp (Y. Nishii), miura@chem.eng.osaka-u.ac.jp (M. Miura)
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A nondirected dehydrogenative direct alkenylation of
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0
1
2
1b).9d In this context, further development of efficient
catalytic systems and better understanding of the reaction
mechanism are in high demand for the Rh catalysis. As part
simple aromatic compounds with alkenes under rhodium
catalysis is described. The site-selectivity is dominantly
dictated by the steric bulkiness around the targeting C–H
bond. The reaction efficiency was largely contingent on the
identity of copper(II) carboxylate as oxidant, and
considerable improvement of the productivity was achieved
by the addition of a sulfate salt.
1
0
53 of our continuous work in this field, we report a new Rh-
54 catalyzed dehydrogenative alkenylation that is enhanced by
5
5
5
5
6
7
the addition of a sulfate salt together with a copper
carboxylate oxidant (Figure 1c). Characteristic feature of
the reaction is described herein.
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0
Keywords:
alkenylation,
aromatic
compounds,
1
rhodium catalyst
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Vinylarenes and their derivatives are fundamental
motifs in natural products as well as various manufactured
chemicals, and thus, tremendous efforts have gone into
developing new synthetic methods for preparing them. The
palladium-catalyzed coupling reaction of aryl halides with
alkenes, which is well-known as the Mizoroki–Heck
1
,2
reaction, has often been applied for the construction of
vinylarene scaffolds. Meanwhile, significant research
interests have been focused on the aromatic C–H
alkenylation protocols under oxidative conditions because
of their atom/step economic nature and operational
simplicity. After the leading work reported by Fujiwara and
58
5
9
Figure 1. Rh-catalyzed dehydrogenative alkenylation.
3
,4
Moritani, various catalytic systems using palladium and
other transition metals have been developed for the direct
alkenylation of aromatic compounds. The efficient site-
selective C–H coupling reactions developed to date
commonly rely on chelation assistance with directing groups
6
6
6
6
0
1
2
3
We first examined the direct alkenylation using
naphthalene (1a, 0.5 mmol) and cyclohexyl acrylate (2a, 0.1
mmol) as model substrates in the presence of
5
64 [RhCl(C
2
H
2
)
2
]
2
(2.5 mol%) and a number of oxidants (0.2
mmol) (Table 1). The use of metal acetate oxidants such as
Cu(OAc) and AgOAc did not provide any coupling
on aromatic substrates. Besides, for the direct reactions on
6
6
6
6
5
6
7
8
simple arenes without the aid of any directing functions, the
main challenges have been associated with (i) reducing the
amount of the aromatic substrates with a reasonable catalyst
loading and (ii) achieving the site-selectivity of the
2
products (entries 1 and 2). On the other hand, the formation
of a small amount of product 3aa was detected with
6
2
69 Cu(OPiv) , and a significant improvement was achieved by
coupling.
1
1
7
7
7
0
1
2
using Cu(eh)
yield of 3aa (entries 3 and 4). We also examined another
copper carboxylate bearing a long alkyl chain, Cu(str) (str
2
(eh = 2-ethylhexanoate) to afford a 33%
The nondirected C-H alkenylation reactions have
traditionally been explored using Pd catalysts. Recently,
substantial progress has been achieved by employing well-
2
7
73 = stearate), but it was ineffective for the present reaction
74 (entry 5). It should be noted that Rh(II) carboxylate
designed ligand systems, where arenes may be employed as
7
e
limiting substrates.
Despite the remarkable success, a
7
7
7
5
6
7
complexes such as [Rh
2
4 2 4
(OAc) ] and [Rh (OPiv) ] in
major drawback of the Pd catalysis is the low site-selectivity
of the coupling because both steric and electronic factors are
combination with Cu(eh)
2
were totally inactive even at an
elevated temperature of 160 °C (entries 6 and 7). We
surmise that the 2-ethylhexanoate anion improves the
solubility of metal complexes present in the non-polar
medium, and at the same time, prevents the formation of
catalytically inactive Rh(II) dimeric species.
Afterward, cyclohexane was found to work remarkably
well as the solvent to produce 3aa in 59% yield (entry 8).
To enhance the productivity further, we tested the effect of
several additives (0.2 mmol) on the present catalytic system.
responsible for the selectivity. In contrast, the product
distribution in the Rh catalysis8,9 is largely dictated by steric
78
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8
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0
1
factors so that the reaction outcome is rather predictable. As
a
seminal example, Glorious reported
a Cp*Rh(III)-
catalyzed dehydrogenative alkenylation of solvent arenes
9
a
82
(Figure 1a). Recently, Yu group described the reaction of
arenes as limiting reagents with the combination of PCy
ligand and Cu(TFA) /V oxidant system; however, the
role of these additives was not fully established (Figure
8
8
8
3
4
5
3
2
2 5
O

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0
1
Interestingly, addition of KH
reaction to give 3aa in 69% and 79% yields, respectively
(entries 9 and 10). To exclude the possibility that the
2 4
Ag SO acts as an extra oxidant, we conducted some control
experiments. Addition of Ag(eh) significantly retarded the
reaction and the yield was reduced to 34% (entry 11),
whereas a bit of improvement was found with a doubled
2
PO
4
and Ag
2
SO
4
enhanced the
33 and the results are showcased in Scheme 1. The reaction
34 of toluene (1b) with 2a gave 3ba in 62% isolated yield
35 with a para/meta ratio of 3:7. Di-substituted benzene
3
3
3
3
4
4
4
4
4
4
4
6
derivatives 1c-1e were selectively converted into 3ca–
7 3ea in good yields where the reaction took place at the
8
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0
1
sterically more accessible positions. It is of interest to
compare with the fact that haloarenes such as 1d and 1e
usually suffer from low yields and poor selectivity under
amount of Cu(eh)
Cu(eh) with Ag(eh) resulted in the negligible outcome
(entry 13). From these observations, we concluded that the
2
(entry 11). Furthermore, replacement of
2
6,7
Pd catalysis. Moreover, 4-phenyltoluene (1f) afforded
1
1
1
1
1
1
1
1
1
1
2
2
2
2 3fa in 53% yield with a para/meta ratio of 1:2 ratio,
2
-
-
counter anion [SO
some influence in the catalytic cycle (see below). Indeed,
other sulfate salts involving Na SO and K SO improved
the yield of 3aa, while they were less effective than Ag SO
(entries 14 and 15). After investigating various
4
]
2 4
as well as [H PO ] apparently has
3
4
5
6
keeping the p-tolyl moiety untouched. This clearly
indicates that the selectivity of the present protocol is
mainly influenced by steric environment rather than
electronic effect. The current reaction conditions were
2
4
2
4
2
4
1
2
47 suitable for the selective -functionalization of
naphthalene derivatives as expected.
parameters, the conditions in entry 10 were found to be
optimal and employed for the following experiments.
4
8
1
49
Analysis of the isolated product 3aa (entry 10, 76%) by H
NMR indicated that it formed as the single /E isomer as
shown.
2 Table 1. Optimization studya
2
3
entry oxidant
additive
solvent
yieldb
1
Cu(OAc)
2



octane
n.d.
2
AgOAc
octane
n.d.
3
Cu(OPiv)
Cu(eh)
Cu(str)
2
octane
<5%
33%
n.d.
4
2

octane
5
2


octane
6c
7d
8
Cu(eh)
Cu(eh)
Cu(eh)
Cu(eh)
octane
n.d.
2
2
2
2




octane
n.d.
cyclohexane
cyclohexane
cyclohexane
cyclohexane
cyclohexane
cyclohexane
cyclohexane
cyclohexane
59%
69%
79%
34%
69%
<5%
64%
74%
9
KH
2
PO
4
1
1
1
1
1
0
Cu(eh)
2
Ag
2
SO
4
1
2e
Cu(eh)
2

Ag(eh)
Cu(eh)
2


3
Ag(eh)
4
Cu(eh)
2

Na
2
SO
4
1
5
Cu(eh)
2
K
2
SO
4
a
2
2
2
2
2
2
4
5
6
7
8
9
Reaction conditions: 1 (0.5 mmol), 2 (0.1 mmol),
(2.5 mol %), oxidant (0.2 mmol), and
additive (0.2 mmol) in cyclohexane (0.5 mL) at 140 °C for
2 4 2 2
[RhCl(C H ) ]
50
b
c
12 h. Determined by GC analysis. [Rh
as catalyst at 160 ˚C. [Rh (OPiv)
2 4
160 ˚C. Cu(eh)
2
(OAc)
] is used as catalyst at
2
(0.4 mmol) was used.
4
] is used
5
5
5
5
5
5
1 Scheme 1. Substrate scope of the direct alkenylation.
d
2
3
4
5
6
Reaction conditions: 1 (1.25 mmol), 2 (0.25 mmol),
[RhCl(C (2.5 mol %), Cu(eh) (0.5 mmol), and
Ag SO (0.5 mmol), in cyclohexane (3.0 mL) at 140 °C
for 24 h. Isolated yields are shown.
e
2
H
4
)
2
]
2
2
3
3
3
0
1
2
2
4
We next examined the electronic and steric
effects of aromatic substrates on the reaction outcome,

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2,3-Dimethylnaphthalene (1g) and 2,3-bis(ethoxycarbonyl)-
naphthalene (1h) respectively produced the corresponding
alkenylated products 3ga and 3hb in 76% and 62% yields.
With the mono-substituted naphthalenes 1i and 1j, the
corresponding mixtures of -alkenylated products were
obtained. Importantly, no reaction at the neighbouring
positions of the carbonyl functionalities in 1h, 1j, and 1k13
was observed, despite directed C–H coupling would be
feasible with ester and ketone directing groups.5,14 9,10-
Dibromoanthracene (1l) was also applicable to give the -
alkenylated product 5la. Additionally, we were interested in
checking the reactivity of electronically biased heterocyclic
compounds. High yields were obtained with complete C2
selectivity when benzo[b]thiophene (1m), benzo[b]furan
(1n), and thieno[3,2-b]thiophene (1o) were employed under
the optimized reaction conditions. On the other hand,
dibenzo[b,d]furan (1p) provided the mixture of two isomers
with 70% isolated yield where the C2 and C3 were
preferably alkenylated.
44
45
After the exploration of substrate scope in the present
46 protocol, we turned our attention to the possible mechanism
47 of the current catalytic system. A significant difference of
48 3aa yield between the independent reactions of 1a with 2b
49 (31%) and 1a-d with 2b (14%) was observed after 1 h (eqs.
8
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
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3
3
50 2 and 3). This may imply that the aromatic C–H bond
51 cleavage step is involved in the rate-limiting stage, while the
52 accurate kinetic constants could not be determined due to
9
a
53 the presence of initial incubation time (see below).
To
54 provide some information concerning the oxidation state of
55 the catalytically active Rh species, we examined the direct
56 alkenylation of 1a with 2a using a stoichiometric amount of
57 either [RhCl(C H ) ] or RhCl in the presence of K(eh)
58 (potassium 2-ethylhexanoate) and Ag SO (eq. 4).
59 Interestingly, 3aa was not formed at all with [RhCl(C H ) ]
2
2 2
2
3
2
4
2
2 2 2,
Subsequently, the reaction of some polycyclic aromatic
hydrocarbons with various alkenes were tested (Scheme 2).
Treatment of naphthalene with a series of acrylate esters 2a–
2d afforded 3aa–3ad with synthetically appreciable
chemical yields. The reaction of 1a with 2a could be
conducted in 1.0 mmol scale without any difficulty (eq. 1).
In addition, styrene (2e) and other Michael acceptors 2f–2h
were well-tolerated. However, no productive result was
obtained with an aliphatic alkene, 1-octene (not shown).
Pyrene (1r) was exclusively transformed into the
corresponding C2-alkenylated products 3ra, 3rb, and 3rd in
good yields. Such unique selectivity towards the C2
position of pyrene again advocates that the current
methodology is driven by steric factor. Likewise,
phenanthrene (1q) gave 3qa as a mixture of the C2- and C3-
alkenylated isomers in 60% yield, and the most olefinic K-
60 whereas RhCl allowed to give the product in 24% yield.
3
61 According to these observations, we concluded that the C–H
62 activation is only initiated by a Rh(III) species with the aid
63 of 2-ethylhexanoate anion as the internal base.
6
4
1
5
region remained intact.
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In order to gain additional insight into the role of
SO in the catalytic system, we monitored the reaction
progress in detail (Figure 2). In the presence of Ag SO
there was an induction period and a considerable rate
acceleration was observed after 30 min. This period is not
for the initial generation of the catalytically active Rh
complex, because the use of pre-heated mixture,
[RhCl(C H ) ] , Cu(eh) , and Ag SO at 120 °C for 30 min
2 2 2 2 2 2 4
in cyclohexane before the addition of 1a and 2a, exhibited a
similar time course at the initial stage. Additionally, a
Ag
2
4
2
4
,
considerable rate acceleration was observed when Ag
was introduced to the reaction mixture after 1 h. From these
observations, Ag SO does not likely participate in the
2 4
SO
3
8
2
4
initial C–H activation stage of the reaction, but it might
3
4
4
4
4
9 Scheme 2. Alkenylation using various alkene coupling
assist the reoxidation of Rh(I) species to generate the
0
1
2
3
partners. Reaction conditions: 1 (1.25 mmol), 2 (0.25
mmol), [RhCl(C (2.5 mol%), Cu(eh) (0.5 mmol),
and Ag SO (0.5 mmol) in cyclohexane (3.0 mL) at
140 °C for 24 h. Isolated yields are shown.
9d,11,16
catalytically active Rh(III) complex.
While the detail
2
H
4
)
2
]
2
2
is not clear at this stage, the additive would help the electron
transfer from Rh(I) to Cu(II) by ligation. We are still
working to find more the specific role of the additive and
the proper reaction mechanism.
2
4

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M. S. Sanford, Org. Lett. 2012, 14, 1760. c) C.-H. Ying, S.-B.
Yan, W.-L. Duan, Org. Lett. 2014, 16, 500. d) K. Naksomboon,
C. Valderas, M. Gꢀmez-Martınez, Y. ꢁlvarez-Casao, M. ꢁ.
́
Fernꢂndez-Ibꢂꢃez, ACS Catal. 2017, 7, 6342. e) P. Wang, P.
Verma, G. Xia, J. Shi, J. X. Qiao, S. Tao, P. T. W. Cheng, M. A.
Poss, M. E. Farmer, K.-S. Yeung, J.-Q. Yu, Nature, 2017, 551,
489. f) H. Chen, P. Wedi, T. Meyer, G. Tavakoli, M. van
Gemmeren, Angew. Chem. Int. Ed. 2018, 57, 2497.
For pioneering reports on the Rh-catalyzed nondirected C–H
functionalization, see: a) P. Hong, H. Yamazaki, K. Sonogashira,
N. Hagihara, Chem. Lett. 1978, 535. b) P. Hong, B-R. Cho, H.
Yamazaki, Chem. Lett. 1979, 339. c) T. Mise, P. Hong, H.
Yamazaki, Chem. Lett. 1980, 439. d) T. Matsumoto, H. Yoshida,
Chem. Lett. 2000, 1064. e) T. Matsumoto, R. A. Periana, D. J.
Taube, H. Yoshida, J. Catal. 2002, 206, 272.
For recent examples, see: a) F. W. Patureau, C. Nimphius, F.
Glorius, Org. Lett. 2011, 13, 6346. b) L. Zheng, J. Wang, Chem.
Eur. J. 2012, 18, 9699. (c) J. Wencel-Delord, C. Nimphius, F. W.
Patureau, F. Glorius, Chem. Asian J. 2012, 7, 1208. d) H. U.
Vora, A. P. Silvestri, C. J. Engelin, J.-Q. Yu, Angew. Chem., Int.
Ed. 2014, 53, 2683. e) B. A. Vaughan, M. S. Webster-Gardiner,
T. R. Cundari, T. B. Gunnoe, Science 2015, 348, 421. f) M. S.
Webster-Gardiner, J. Chen, B. A. Vaughan, B. A. McKeown, W.
Schinski, T. B. Gunnoe, J. Am. Chem. Soc. 2017, 139, 15. g) B.
A. Vaughan, S. K. Khani, J. B. Gary, J. D. Kammert, M. S.
Webster-Gardiner, B. A. McKeown, R. J. Davis, T. R. Cundari,
T. B. Gunnoe, J. Am. Chem. Soc. 2017, 139, 1485.
8
9
1
2
3
4
5
6
65
66
Figure 2. Time course of the direct alkenylation of
naphthalene (1a) with alkene 2a: (i) ○ standard condition,
6
6
6
7
7
8
9
0
(ii) ● without Ag
2
SO
4
2 2 2 2 2
, (iii) ■ [RhCl(C H ) ] , Cu(eh) , and
Ag
Ag
2
SO
SO
4
were pre-heated at 120 °C for 30 min, (iv)
was added at 60 min.
▲
2
4
71
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4
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5
In summary, we have found that the combination of
Cu(eh) and Ag SO is an effective oxidant system for the
2
2
4
75
76
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
Rh-catalyzed nondirected C–H alkenylation of aromatic
compounds without using any precious phosphine and
cyclopentadienyl ligands. The reaction system exhibits
relatively broad scope for the preparation of alkenylated
arenes in good yields. Control experiments suggested the
occurrence of Rh(III) species in the C–H activation stage,
and that the ethylhexanoate and sulfate could jointly
suppress the catalyst deactivation.
7
7
7
8
7
8
9
0
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11
M. Miura, T. Satoh, K. Hirano, Bull. Chem. Soc. Jpn. 2014, 87,
751.
M. V. Pham, N. Cramer, Angew. Chem., Int. Ed. 2014, 53, 3484.
81 12 For detail, see the Supporting Information.
82 13 The connectivity of 3ka was confirmed by X-ray diffraction
8
8
8
8
3
4
5
6
measurement where the two regioisomers were co-crystallized.
For detail, see the Supporting Information.
Z. Huang, H, N. Lim, F. Mo, M. C. Young, G. Dong, Chem. Soc.
Rev. 2015, 44, 7764.
14
This work was supported by JSPS KAKENHI Grant No. JP
17H06092 (Grant-in-Aid for Specially Promoted Research)
to M.M.
The authors declare no competing financial interest.
Supporting Information (detailed experimental procedures,
spectra, and X-ray crystallographic data) is available on
http://dx.doi.org/10.1246/cl.******.
87 15 R. G. Harvey, Polycyclic Aromatic Hydrocarbons (Wiley-VCH,
88
8
9
1997.
9
0
16
J. Wencel-Delord, C. Nimphius, H. Wang, F. Glorius, Angew.
Chem., Int. Ed. 2012, 51, 13001.
2
6 References and Notes
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4
4
4
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9
0
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1
a) The Mizoroki-Heak Reaction, ed. by M. Oestreich, Wiley,
Chichester, 2009. b) New Trends in Cross-Coupling: Theory and
Applications, ed. by T. Colacot, Royal Society of Chemistry,
Cambridge, 2014.
a) T. Mizoroki, K. Mori, A. Ozaki, Bull. Chem. Soc. Jpn. 1971,
44, 581. b) R. F. Heck, J. P. Nolley, Jr., J. Org. Chem. 1972, 37,
2320.
a) I. Moritani, Y. Fujiwara, Tetrahedron Lett. 1967, 8, 1119. b) Y.
Fujiwara, I. Moritani, M. Matsuda, S. Teranishi, Tetrahedron
Lett. 1968, 9, 633. c) Y. Fujiwara, I. Moritani, S. Danno, R.
Asano, S. Teranishi, J. Am. Chem. Soc. 1969, 91, 7166. d) Y.
Fujiwara, R. Aasano, I. Moritani, S. Teranishi, J. Org. Chem.
1976, 41, 1681.
2
3
4
5
L. Zohu, W. Lu, Chem. Eur. J. 2014, 20, 634.
C. Sambiagio, D. Schöbauer, R. Blieck, T. Dao-Huy, G.
Pototschnig, P. Schaaf, T. Wiesinger, M. F. Zia, J. Wencel-
Delord, T. Besset, B. U. W. Maes, M. Schnürch, Chem. Soc. Rev.
2018, 47, 6603.
For recent reviews, see; a) N. Kuhl, M. N. Hopkinson, J. Wencel-
Delord, F. Glorius, Angew. Chem., Int. Ed. 2012, 51, 10236. b) P.
Wedi, M. van Gemmeren, Angew. Chem., Int. Ed. 2018, 57,
13016.
6
7
For selected examples, see: a) Y.-H. Zhang, B.-F. Shi, J. -Q. Yu,
J. Am. Chem. Soc. 2009, 131, 5072. b) A. Ubota, M. H. Emmert,