Addition reaction of 2-phenylbenzoic acid onto unactivated olefins catalyzed by Ru(II)-xantphos catalysis

Article abstract of DOI:10.1016/j.tetlet.2010.03.052

Ru(II)-xantphos catalysis is found to be effective for the addition reaction of 2-phenylbenzoic acid onto unactivated olefins. Thus, the reactions of 2-phenylbenzoic acid and unactivated olefins are carried out in the presence of 5 mol % of Ru(II)-xantpho

Full text of DOI:10.1016/j.tetlet.2010.03.052

Tetrahedron Letters 51 (2010) 2806–2809
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Tetrahedron Letters
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Addition reaction of 2-phenylbenzoic acid onto unactivated olefins catalyzed
by Ru(II)–xantphos catalysis
a
Yohei Oe b, Tetsuo Ohta b, , Yoshihiko Ito
*
a Department of the Molecular Science and Technology, Faculty of Engineering, Doshisha University, Kyotanabe, Kyoto 610-0394, Japan
b Department of Biomedical Information, Faculty of Life and Medical Sciences, Doshisha University Kyotanabe, Kyoto 610-0394, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Ru(II)–xantphos catalysis is found to be effective for the addition reaction of 2-phenylbenzoic acid onto
unactivated olefins. Thus, the reactions of 2-phenylbenzoic acid and unactivated olefins are carried out in
the presence of 5 mol % of Ru(II)–xantphos catalysis in refluxing CHCl3 for 48 h to afford the correspond-
ing esters in 40–95% yield. The control experiments indicate that the influence of TfOH for Brønsted acid
catalyst was vanishingly small in our new catalytic system.
Received 29 January 2010
Revised 9 March 2010
Accepted 15 March 2010
Available online 17 March 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Esters are one of the most important compounds for pharmaceu-
tics, perfume chemistry and fine chemicals. Esters are also well-
known for being converted into the corresponding alcohols and
carboxylic acids by saponification and then acidification. The transi-
tion metal-catalyzed addition of carboxylic acids onto olefins is one
of the most attractive methodologies for ester formations because of
its almost perfect atom economy, and therefore, several metal com-
plexes1–6 were recently reported as efficient catalysts, including our
Ru(III) and Ru(II) catalyses.7 Combining the nature of esters with
these catalytic addition reactions of carboxylic acids onto olefin
might be considered to be an efficient methodology for the prepara-
tion of alcohols from olefins in two steps with recovery of the start-
ing carboxylic acids. Brown’s hydroboration–oxidation method8 is
well-known as the most common method for the preparation of
alcohols from olefins in two steps, and its asymmetric version9 has
been developed by Knochel and co-workers. However, obtained bor-
on-derived wastes are hardly reusable and not applicable from the
view-point of atom efficiency. Thus, if the catalytic addition of car-
boxylic acids onto olefins becomes more versatile, a new environ-
mentally benign synthetic pathway of alcohols from olefins could
be proposed. We have already reported that the ester formations
using carboxylic acids and olefins proceeded in the presence of
Ru(III) catalyses, though the narrow scope of olefin substrates was
problematic.7a More recently, we found that the Ru(II) catalyses gen-
erated in situ by mixing [(p-cymene)RuCl2]2, AgOTf, and DppX
showed good catalytic activity for the addition of carboxylic acids,
alcohols, and sulfonamides onto styrene in CHCl3, and that [(p-cym-
ene)Ru(OTf)(DppX)]OTf were formed as catalytically active com-
plexes for the reaction by NMR experiments, FAB MS spectra, and
X-ray analysis.7c Furthermore, under these catalytic conditions
(DppX = Dppe), the reaction of 2-phenylbenzoic acid (1) with 2-
allylanisole (2a) in the presence of 5 mol % Ru of the catalyst gave
2-{1-(20-methoxyphenyl)}propyl 2-phenylbenzoate (3a) in 60%
yield (Eq. 1), though the yield was not satisfied and long reaction
time was required. To the best of our knowledge, the reaction tem-
perature(at61 °C)isthelowestoneof thepreliminaryreportedtran-
sition metal-catalyzed addition reactions of carboxylic acids onto
unactivatedolefin describedabove. Theresultencouragedustoopti-
mizethereactionconditionstoexpandthescopeofolefinsubstrates.
Herein, we report the recent modification of our Ru-catalyzed addi-
tion of carboxylic acid onto various unactivated olefins using xant-
phos as a ligand, which dramatically increased the catalytic activity.
The bite angle of the bisphosphine ligands is known to be a crit-
ical trigger for laying down catalytic activity and reactivity in var-
[(p-cymene)RuCl2]2 (2.5 mol%)
O
O
AgOTf (10 mol%)
Dppe (5 mol%)
OH
O
+
ð1Þ
CHCl3, reflux, 60 h
Ph
OMe
2b
(2.5 mmol)
OMe
Ph
3a
1
(60% Yield)
(1 mmol)
* Corresponding author. Fax: +81 774 65 6789.
E-mail address: tota@mail.doshisha.ac.jp (T. Ohta).
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.03.052

Y. Oe et al. / Tetrahedron Letters 51 (2010) 2806–2809
2807
Table 1
Effects of bisphosphine ligandsa
[(p-cymene)RuCl2]2 (2.5 mol%)
AgOTf (10 mol%)
O
O
Ligand (5 mol%)
OH
O
+
OMe
2a
CHCl3, reflux, under Ar
OMe
Ph
1
Ph
3a
Entry
Ligand
Bite anglee (°)
Time (h)
Yieldb (%)
1
2
3
4
Dppe
Dppp
85
95
—
60
60
60
60
24
42
42
60
80
85
82
95
32
64
Dpppent
Dpph
Xantphos
Xantphos
Xantphos
—
5
111
111
111
6c
7d
a
Reaction conditions: mixture of 2-phenylbenzoic acid (1) (1 mmol) and 2-allylanisole (2a) (2.5 mmol) was stirred in refluxing CHCl3 (3 mL) for given reaction time in the
presence of 5 mol % Ru Catalysis.
b
Isolated yield after purification by silica gel column chromatography.
Benzoic acid was used instead of 1.
2-Phenylpropionic acid was used instead of 1.
Ref. 13.
c
d
e
ious transition metal-catalyzed reactions.10 Therefore, the effects
of several bisphosphine ligands with different bite angles on the
reaction between 1 and 2a were investigated, and the selected re-
sults are summarized in Table 1. When the reaction of 1 with 2a
was performed with Dppe as a ligand at reflux for 60 h, ester 3a
was obtained in 60% yield (entry 1). Changing the ligand to Dppp,
which has larger bite angle than Dppe, increases the yield of 3a to
80% (entry 2), although the reaction time could not be shortened
while maintaining good yields. Using Dpppent showed a similar
tendency (85% yield, entry 3); however, little decrease in the prod-
uct yield was observed by using Dpph (82% yield, entry 4). It was
expected that the hexane linker was too flexible to maintain a large
bite angle on the ruthenium center. On the basis of this hypothesis,
xantphos, which has rigid heterocyclic xanthenes promising a large
bite angle, was chosen as a ligand.11 As expected, we were pleased
to find that using xantphos increases the product yield up to 95%
and that the reaction time could be shortened to 24 h (entry 5).
Hartwig and co-workers reported the exchange of the hydroamin-
substrate, the product yield was slightly decreased to afford 2-(1-
phenyl)propyl 2-phenylbenzoate (3c) in 40% yield (entry 3).
Allylbenzene bearing acid-labile acetal substituent (2d) can be
subjected to the present catalytic system to give a 67% yield of
the corresponding ester (3d) (entry 4). 4-Phenyl-1-butene (2e)
was also reacted with 1 to give 2-(4-phenyl)butyl 2-phenylbenzo-
ate (3e) in 56% yield (entry 5). Aliphatic olefin, 1-octene (2f), gave
the desired ester (3f) in 89% yield without concomitant of its regio
isomers (entry 6). Cyclic olefin, cyclohexene (2g) was also applied
to the present catalytic reaction with 1 to obtain cyclohexyl
2-phenylbenzoate (3g) in excellent yield (89%, entry 7). (S)-(ꢀ)-
Limonene (2h) bearing one gem-substituted olefin site and one
three-substituted cyclic olefin site was not reacted with 1 at the
both positions under the present catalytic conditions (entry 8).
Methyl cis-jasmonate (2i), which has an internal (Z)-alkene group,
also did not afford the corresponding adduct (entry 9). As de-
scribed above, the present Ru–xantphos catalytic system showed
a broad scope of unactivated terminal olefin substrates in the
esterification with 2-phenylbenzoic acid.
ation product, which was coordinated as an
g
6-arene ligand, with
the next vinylarene substrate in their anti-Markovnikov hydroam-
ination of vinylarenes.12 They used Dpppent as a ligand for highly
efficient reaction, where Dpppent behaves as a P–C–P tridentate
ligand to accelerate the exchange reaction. We speculated that
With the efficient Ru–xantphos catalytic system, we investigated
some mechanistic studies. Hartwig and co-workers reported that
the reaction of 4-methoxybenzoic acid with 2-norbornene was car-
ried out in the presence of 1 mol % of TfOH in 1,4-dioxane at 80 °C for
22 h to give 2-norbornyl 4-methoxybenzoate in 83% yield.14 Inde-
pendently, He and co-workers reported that phenylacetic acid was
reacted with 4-allylanisole (2b) in the presence of 2 mol % of TfOH
in toluene at 50 °C to give the corresponding ester in 60% conver-
sion.15 Hii and co-workers proposed that their copper-catalyzed
hydroamination proceeded by TfOH generated through the ligand
exchange reaction of tosylamide with Cu(OTf)2.16 To confirm the dif-
ference between our Ru catalysis and TfOH catalyst, we examined
control experiments using TfOH (Eq. 2). Thus, the reaction of 1 with
2b was conducted in the presence of 1 mol % of TfOH in CHCl3 at
reflux or room temperature for 48 h to give the trace amount of
similar dissociation or slippage of
g
6-p-cymene ligand occurred
by chelate coordination of xantphos to Ru center to increase the
catalytic activity. Benzoic acid and 2-phenylpropionic acid were
also reacted with 2a to afford the corresponding adducts in 32%
yield and 64% yield, respectively (entries 6 and 7).
With the effective Ru–xantphos catalytic system in hand, we
investigated the scope of olefins by using 1 as a nucleophile, and
the selected results are summarized in Table 2. 4-Allylanisole
(2b) was a good substrate for the present reaction to give 2-{1-
(40-methoxyphenyl)}propyl 2-phenylbenzoate (3b) in 95% yield
after 48 h (entry 2). When allylbenzene (2c) was used as an olefin
O
OMe
O
TfOH (1 mol%)
CHCl3, 48 h
OH
O
+
ð2Þ
MeO
Ph
Ph
Trace at Rt or Reflux
2b
1
3b
(1 mmol)
(2.5 mmol)

2808
Y. Oe et al. / Tetrahedron Letters 51 (2010) 2806–2809
Table 2
Scope of olefin substratesa
[(p-cymene)RuCl2]2 (2.5 mol%)
O
O
R
AgOTf (10 mol%)
R'
Xantphos (5 mol%)
OH
R'
O
+
R
CHCl3, reflux, under Ar
Ph
1
Ph
3a-g
2a-g
Entry
1
Olefin
Productb
Yieldc (%)
95
O
Ar
O
MeO
2a
3a
3c
OMe
OMe
O
O
2
3
4
94
40
56
OMe
Ar
Ar
O
O
2b
3b
2c
O
O
O
O
O
O
Ar
Ar
O
O
2d
3d
5
6
67
89
2e
3e
O
O
2f
Ar
O
3f
7
8
89
0
Ar
O
3g
2g
—
2h
O
9
—
0
CO2Me
2h
a
Reaction conditions: mixture of 2-phenylbenzoic acid (1) (1 mmol) and given olefin (2) (2.5 mmol) was stirred in refluxing CHCl3 (3 mL) for 48 h in the presence of
5 mol % of Ru catalysis.
b
Ar = 2-biphenyl.
c
Isolated yield after purification by silica gel column chromatography.
esterification product 3b in both cases. We cannot fully rule out the
in situ generated acid-catalyzed reaction pathway from these data;
however, this apparent difference of reactivity between TfOH and
our Ru–xantphos catalysis indicated that Ru presumably works as
lytic conditions. After the removal of solvent, treatment of the
crude product with saturated KOH methanol solution at room tem-
perature for 6 h afforded the desired alcohol 4b in 64% yield.18 As
expected, starting acid 1 can be recovered in quantitative yield
by acidification followed by simple extraction with ethyl acetate.
In summary, Ru(II)–xantphos catalysis-catalyzed esterification
of unactivated olefins using 2-phenylbenzoic acid as a coupling
partner was achieved. We also demonstrated an example of one-
pot alcohol preparations from olefins by means of the present
ruthenium catalytic reaction and followed by hydrolysis, where
a Lewis acid that activates the olefin substrate by forming
p–olefin
complex like Wacker-type reactions.17
Finally, we demonstrated the alcohol preparation process from
carboxylic acids and olefins in one-pot using our Ru-catalyzed
addition reaction and hydrolysis of the obtained ester (Eq. 3). Thus,
the reaction of 1 with 2b was performed under the present cata-

Y. Oe et al. / Tetrahedron Letters 51 (2010) 2806–2809
2809
O
O
Ru-Xantphos
sat. KOH
in MeOH
rt, 6 h
Catalysis (5 mol%)
OH
OH
+
+
CHCl3, reflux, 42 h
OH
ð3Þ
MeO
MeO
Ph
1
then
Ph
2b
removal of solvent
1
4b
(quant.)
(64% yield)
2. Fe: (a) Komeyama, K.; Mieno, Y.; Yukawa, S.; Morimoto, T.; Takaki, K. Chem.
Lett. 2007, 36, 752; (b) Choi, J.-C.; Kohno, K.; Matsuda, D.; Yasuda, H.; Sakakura,
T. Chem. Commun. 2008, 777.
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Raubenheimer, H. J. Mol. Catal. A: Chem. 2004, 212, 35.
the starting carboxylic acid was quantitatively recovered. The
investigations of the addition of optically active carboxylic acids
and asymmetric addition using optically active catalysts are under
way in our laboratory.
4. Ag: Yang, C.-G.; Reich, N. W.; Shi, Z.; He, C. Org. Lett. 2005, 7, 4553.
5. In: Chen, W. Y.; Lu, J. Catal. Commun. 2007, 8, 1298.
Acknowledgments
6. Pd: Hosokawa, T.; Shinohara, T.; Ooka, Y.; Murahashi, S.-I. Chem. Lett. 1989,
2001.
We would like to dedicate this Letter to the memory of our
mentor, late Professor Yoshihiko Ito. This work was partially sup-
ported by Doshisha University’s Research Promotion Fund, and a
Grant to RCAST at Doshisha University from the Ministry of Educa-
tion, Culture, Sports, Science and Technology, Japan. This work was
supported by a Grant-in-Aid for Young Scientists (Start-up: No.
20850034) from JSPS.
7. Ru: (a) Oe, Y.; Ohta, T.; Ito, Y. Chem. Commun. 2004, 1620; (b) Ohta, T.; Kataoka,
Y.; Miyoshi, A.; Oe, Y.; Furukawa, I.; Ito, Y. J. Organomet. Chem. 2007, 692, 671;
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Supplementary data
Supplementary data (typical experimental procedures and cop-
ies of 1H and 13C NMR spectra and HRMS of all the products) asso-
ciated with this article can be found, in the online version, at
doi:10.1016/j.tetlet.2010.03.052.
References and notes
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1. Cu: Taylor, J. G.; Whitall, N.; Hii, K. K. M. Chem. Commun. 2005, 5103.