Chemo-, regio-, and stereoselective synthesis of syn -aryl glycol monoesters from aryl olefins with hydrogen peroxide catalyzed by RuCl 3

Article abstract of DOI:10.1055/s-0029-1219553

Chemo-, regio-, and stereoselectivity have been achieved in the oxidations of aryl olefins. The aryl olefins were oxidized by 2 equivalents of H ₂O₂ in acetic acid, catalyzed by 0.02 equivalent of RuCl₃, leading to the formations of syn-aryl glycol monoesters. As the reaction is concerted, both the regio- and stereoselectivity are excellent. In the presence of aliphatic C=C bonds, the aryl C=C bonds were selectively dioxygenated. This represents the first example of chemoselective dioxygenation of aryl C=C bonds. Georg Thieme Verlag Stuttgart - New York.

Full text of DOI:10.1055/s-0029-1219553

1118
LETTER
Chemo-, Regio-, and Stereoselective Synthesis of syn-Aryl Glycol Monoesters
from Aryl Olefins with Hydrogen Peroxide Catalyzed by RuCl3
S
ynthesis of syn-A
a
ryl
G
lycol
nMonoesters qiao Zhang, Guobiao Chu, Xiaoxue Cui, Zhijie Han, Daoke Dou, Yuanli Chen, Xiaosong Yu, Chunbao Li*
Department of Chemistry, College of Science, Tianjin University, Tianjin 300072, P. R. of China
Fax +86(22)27403475; E-mail: lichunbao@tju.edu.cn
Received 22 December 2009
RuCl3 (0.02 equiv)
H2O2 (2 equiv)
Abstract: Chemo-, regio-, and stereoselectivity have been
achieved in the oxidations of aryl olefins. The aryl olefins were ox-
idized by 2 equivalents of H2O2 in acetic acid, catalyzed by 0.02
equivalent of RuCl3, leading to the formations of syn-aryl glycol
monoesters. As the reaction is concerted, both the regio- and stereo-
selectivity are excellent. In the presence of aliphatic C=C bonds, the
aryl C=C bonds were selectively dioxygenated. This represents the
first example of chemoselective dioxygenation of aryl C=C bonds.
Ph
AcO
Ph
Ph
Ph
AcOH, r.t.,15 min
51%
OH
Scheme 1
Initially, trans-stilbene and catalytic amounts of PdCl2,
Pd(OAc)2, IrCl3, RhCl3, RuCl3 were dissolved in acetic
acid and treated with H2O2. No catalytic reactions oc-
curred with PdCl2, Pd(OAc)2, RhCl3, or IrCl3. As soon as
the addition of H2O2 was completed in 15 minutes, the
reaction catalyzed by RuCl3 was completed, yielding the
syn-glycol monoester in 51% yield (Scheme 1). However,
the oxidation did not occur when solvent AcOH was re-
placed with 5 equivalents of AcOH and MeCN, THF,
MeOH, or DMF.
Key words: synthetic methods, oxidation, glycol monoesters, ole-
fins, hydrogen peroxide
Aryl glycol monoester moieties are important architec-
tures in bioactive natural products such as the
styryllatones1 and the dibenzocyclooctadiene lignans.2
The Chemical Abstracts database documents over 3000
such monoesters. Only two reactions3 are known to trans-
form olefins into glycol monoesters. Unfortunately, these
two reactions are not chemo- or regioselectivity. The
dihydroxylations4 of olefins followed by selective esteri-
fication seems to be a reasonable synthetic approach to
these architectures. However, the diol esterification has
been shown to be problematic.5 Therefore, the develop-
ment of efficient direct synthesis of glycol monoesters has
become pressingly demanded.
A series of aryl olefins were smoothly oxidized into the
monoesters by RuCl3 (0.02 equiv) and H2O2 (2 equiv) in
AcOH at room temperature. Table 1 summarizes the re-
sults of the reactions. Terminal (entries 5 and 6), internal
(entries 1–4 and 7-9), monosubstituted (entry 6), disubsti-
tuted (entries 1, 3, and 5), and trisubstituted (entries 2, 4,
and 7–9) olefins were all transformed into the aryl glycol
monoesters. The olefins of entries 1–4 afforded only syn-
aryl glycol monoesters. The syn stereochemistry of the
monoester (entry 3) was confirmed by NOE experiments
Metal oxides such as OsO4, RuO4, Cp*ReO3, and KMnO4
are known to syn-dihydroxylate olefins via a concerted
mechanism.6 Both RuO4 and RuO4 generated in situ from
RuCl3 and NaIO4 have been employed in the syn dihy-
droxylation of olefins. Middle-valent Ru=O species gen-
erated from catalytic amounts of RuCl3 and 2,6-
dichloropyridine N-oxide transform olefins into the corre-
sponding epoxides,7 while those generated from catalytic
amounts of RuCl3 and peracetic acid transform olefins
into the corresponding hydroxyketones via a nonconcert-
ed mechanism.8 We speculated that certain acetoxy-coor-
dinated Ru=O species could be generated from RuCl3 in
the presence of H2O2 and AcOH, and could then be possi-
ble to react with olefins via a concerted mechanism, and
our protocol was supported by experimental facts. Herein
we would like to report our chemo-, regio-, and stereo-
selective synthesis of aryl glycol monoesters from aryl
olefins with hydrogen peroxide catalyzed by ruthenium
trichloride.
1
of H NMR (see Supporting Information). Other syn-
monoesters (entries 1–3) are known compounds.9 For
monosubstituted (entry 6) and symmetrically disubtituted
olefins (entry 3), the acetoxy group of the oxidation prod-
uct is located at the benzylic position. For trisubstituted
olefins (entries 2, 4, and 7–9), the acetoxy group of the ox-
idation product is located at the monosubstituted end of
the C=C bond. Analyzing the crude products from the ox-
idation did not indicate any signals corresponding to the
regio- and stereoisomers. This compares well with the
known dioxygenation methods of olefins in terms of
regio- and stereoselectivity.3 In the literature, the mo-
noester regioisomer products had to be peracetylated to
simplify their purifications. A phenyl diene (entry 16) and
a phenyl triene (entries 17) were similarly converted to the
corresponding monoesters. These two monoester prod-
ucts were not stable and the yields were low. In the major
products, hydroxy groups were attached to the nonsubsti-
tuted end of the terminal double bonds and the acetoxy
group to the monosubstituted end of the terminal double
bonds. This is similar to the reported [3+2] dipolar cy-
SYNLETT 2010, No. 7, pp 1118–1122
x
x.
x
x.
2
0
1
0
Advanced online publication: 26.02.2010
DOI: 10.1055/s-0029-1219553; Art ID: W20309ST
© Georg Thieme Verlag Stuttgart · New York

LETTER
Synthesis of syn-Aryl Glycol Monoesters
1119
cloaddition, where only the terminal C=C bond of an aryl products were obtained, which were peracetylated for pu-
diene reacts concertedly with a nitrone.10
rification. The same results were obtained by treating in-
dole derivatives with H2O2 and AcOH in the absence of
RuCl3. This reaction possibly proceeds via epoxidation
followed by ring opening by acetate, which is mechanisti-
cally different from the oxidation of other olefins (entries
1–9).
However, subjecting aliphatic (entries 10 and 11), elec-
tron-rich (entries 12 and 13), electron-deficient (entry 14),
and strained (entry 15) olefins to the oxidation led to the
recovery of the starting materials. Under the same oxida-
tion conditions, it took one day to oxidize indole deri-
vatives (acetyl, benzoyl, benzenesulfonyl, and p-
toluenesulfonyl indoles). However, the trans monoester
a
Table 1 Oxidation of Aryl Olefins into syn-Aryl Glycol Monoesters Using H2O2 in AcOH Catalyzed by RuCl3
Entry
1
Substrate
Product
Yield (%)b
51
AcO
Ph
Ph
Ph
Ph
OH
AcO
2
3
4
67
51
52
HO
Ph
Ph
OAc
OH
O
N
O
N
O
NH2
Ph
O
NH2
Ph
Ph
OH
Ph
OAc
OH
5
6
56
30
OAc
Ph
Ph
Ph
OAc
OH
Ph
Ph
OAc
HO
Ph
7
8
9
68
63
75
OAc
OH
OAc
HO
10
11
12
cyclohexene
cholesterol
n.r.
n.r.
n.r.
0
0
0
triacetylglucal
13
n.r.
0
O
O
Synlett 2010, No. 7, 1118–1122 © Thieme Stuttgart · New York

1120
Y. Zhang et al.
LETTER
a
Table 1 Oxidation of Aryl Olefins into syn-Aryl Glycol Monoesters Using H2O2 in AcOH Catalyzed by RuCl3 (continued)
Entry
14
Substrate
Product
n.r.
Yield (%)b
0
O
N
H
OMe
O
15
n.r.
0
N
Ph
O
OAc
16
17
24
10
Ph
OH
Ph
Ph
OAc
Ph
OH
OAc
18
19
74
71
HO
O
O
OAc
MeO
O
MeO
O
HO
OAc
20
21
22
73
68
65
HO
O
O
OAc
MeO
O
MeO
O
HO
OAc
OAc
OH
OH
O
O
23
24
63
73
O
O
OAc
MeO
MeO
HO
O
O
OAc
MeO
MeO
HO
O
O
O
O
O
25
40
O
H
H
N
N
O
H
O
H
Synlett 2010, No. 7, 1118–1122 © Thieme Stuttgart · New York

LETTER
Synthesis of syn-Aryl Glycol Monoesters
1121
a
Table 1 Oxidation of Aryl Olefins into syn-Aryl Glycol Monoesters Using H2O2 in AcOH Catalyzed by RuCl3 (continued)
Entry
Substrate
Product
Yield (%)b
OAc
HO
O
O
O
O
O
26
49
O
H
H
N
N
O
O
H
H
OAc
OH
N
Tol
27
5012
N
O
O
Tol
O
H
O
H
N
N
O
H
O
H
a Olefin (1 equiv), H2O2 (2 equiv), RuCl3·nH2O (0.02 equiv), and AcOH (solvent), r.t., 15 min.
b Isolated yield.
A series of dienes (entries 18–27) containing both aliphat- cycloaddition between 2-metalla-1,4-diene and alkenes
ic and aryl C=C bonds was subjected to the oxidation, has never been reported.
leading to syn-glycol monoesters with intact aliphatic
C=C bonds as expected. The oxidation of the olefin (entry
To support the concerted mechanism, we have analyzed
by MS (ES) a solution of RuCl3 in AcOH treated with ex-
27, Scheme 2) was chemo-, regio-, and stereoselective,
cess H2O2. The peaks corresponding to O=Ru(OAc)mCln
while in the literature methods,3,4 aliphatic olefins and aryl
(when m + n = 2, m, n = 0, 1, 2; when m + n = 3, m, n = 1,
olefins were found to be equally oxidized. To the best of
2) cannot be detected from MS (ES) analysis. However,
our knowledge, chemoselective dioxygenations of aryl
O=Ru(OAc)3 is detected to exist as [O=Ru(OAc)3 + Na]+
C=C bonds in the presence of aliphatic C=C bonds have
{[M + Na]+}, which, after MS/MS analysis, exhibits the
never been previously reported.
peaks corresponding to [M+] {[O=Ru(OAc)3]+}, [M –
The mechanism of the reaction is proposed as follows AcO]+ and [M + Na – H2O]+ (see Supporting Informa-
(Figure 1). After exchanging with acetate, RuCl3 becomes
Ru(OAc)3, which is oxidized by H2O2 into O=Ru(OAc)3
Ph
O Ru(OAc)3
Ph
(triacetoxyruthenium oxo). This intermediate serves as a
2-ruthena-1, 4-diene (the right part of transition state I of
AcOH
RuCl3
Ru(OAc)3
– H2O
Ph
Figure 1) and undergoes a concerted [5+2] reaction with
C=C bond, leading to intermediate II via transition state I.
The hydrolysis of II leads to the syn-glycol monoester and
Ru(OAc)2OH; the latter reacts with AcOH to regenerate
Ru(OAc)3. The concerted approach of O=Ru(OAc)3 to-
wards the C=C bond as depicted in transition state I of
Figure 1 determines the syn stereochemistry of the dioxy-
genation reaction. Although no-metal-participated [5+2]
cycloadditions have been used in organic synthesis,11 the
– HCl
O
O
I
O
AcOH
Ru(OAc)2
Ph
Ru(OAc)2OH
OH
Ph
H
2 O
ORu(OAc)2
Ph
Ph
Ph
AcO
AcO
II
Figure 1
OAc
OH
RuCl3 (0.02 equiv)
H2O2 (2 equiv)
N
Tol
O
N
Tol
H
AcOH, r.t., 15 min
50%
O
O
N
H
O
N
O
H
O
H
Scheme 2
Synlett 2010, No. 7, 1118–1122 © Thieme Stuttgart · New York

1122
Y. Zhang et al.
LETTER
(4) (a) Kolb, H. C.; VanNiewenhze, M. S.; Sharpless, K. B.
tion). O=Ru(OAc)3 is a new compound. Its life time is less
than 1 hour according to our MS (ES) analysis. The fact
that the oxidation can be only performed in AcOH is prob-
ably due to the stability of O=Ru(OAc)3 in AcOH. Pre-
sumably, oxidative species other than O=Ru(OAc)3 exist
in a minor amount. Probably they oxidize glycol mo-
noester products further and cause the reduction in the ox-
idation yield because Ru exists in several oxidation states
and oxidize various substrates.7e
Chem. Rev. 1994, 94, 2483. (b) Shing, T. K. M.; Tai, V. W.;
Tam, E. K. W. Angew. Chem., Int. Ed. Engl. 1994, 33, 2312.
(c) Plietker, B.; Niggemann, M. Org. Lett. 2003, 5, 3353.
(d) Santoro, S.; Santi, C.; Sabatini, M.; Testaferri, L.;
Tiecco, M. Adv. Synth. Catal. 2008, 350, 2881; and
references cited therein.
(5) Yang, Z.; Zhou, W. J. Chem. Soc., Chem. Commun. 1995,
743.
(6) Deubel, D. V.; Frenking, G. Acc. Chem. Res. 2003, 36, 645.
(7) (a) Higuchi, T.; Ohtake, H.; Hirobe, M. Tetrahedron Lett.
1989, 30, 6545. (b) Ohtake, H.; Higuchi, T.; Hirobe, M.
Tetrahedron Lett. 1992, 33, 2521. (c) Groves, J. T.; Quinn,
R. J. Am. Chem. Soc. 1985, 107, 5790. (d) Groves, J. T.;
Bonchio, M.; Carofilio, T.; Shalyaev, T. J. Am. Chem. Soc.
1996, 118, 8961. (e) Murahashi, S.; Komiya, N. In Modern
Oxidation Methods; Bäckvall, J., Ed.; Wiley-VCH:
Weinheim, 2004, 165.
(8) Murahashi, S.; Saito, T.; Hanaoka, H.; Murakami, Y.; Naota,
T.; Kumobayashi, H.; Akutagawa, S. J. Org. Chem. 1993,
58, 2929.
(9) (a) Vedejs, E.; Daugulis, O.; Diver, S. T. J. Org. Chem.
1996, 61, 430. (b) Naemura, K.; Miyabe, H.; Shingai, Y.
J. Chem. Soc., Perkin Trans. 1 1991, 957. (c) Naemura, K.;
Murata, M.; Tanaka, R.; Yano, M.; Hirose, K.; Tobe, Y.
Tetrahedron: Asymmetry 1996, 7, 3285. (d) Morimoto, T.;
Hirano, M.; Koyama, T. J. Chem. Soc., Perkin Trans. 2
1985, 1109.
In summary, we have, for the first time, developed an eco-
nomical and environmentally friendly selective oxidation
system of aryl olefins, and the aryl olefins have been
chemo-, regio-, and stereoselectively transformed into
syn-aryl glycol monoesters. This represents the first ex-
ample of selective synthesis of syn-aryl glycol monoesters
in the presence of aliphatic C=C bonds. The terminal oxi-
dant is H2O2, which is safe and economical and is regard-
ed as one of the two green oxidants (oxygen and H2O2).
The protocol and purification of the reaction are simple.
This procedure has provided a practical synthesis of syn-
aryl glycol monoester from aryl olefins. To synthesize
bioactive natural products such as lignans and styryllac-
tones and to shorten the routes leading to a few other
drugs, we are presently working on enantioselective syn-
thesis of aryl glycol esters as a protocol.
(10) Iida, H.; Tanaka, M.; Kibayashi, C. J. Org. Chem. 1984, 49,
1909.
(11) (a) Volkmann, R. A.; Weeks, P. D.; Kuhla, D. E.; Whipple,
E. B.; Chmurny, G. N. J. Org. Chem. 1977, 42, 3976.
(b) Wender, P. A.; McDonald, F. E. J. Am. Chem. Soc. 1990,
112, 4956. (c) Rumbo, A.; Castedo, L.; Mourino, A.;
Mascarenas, J. L. J. Org. Chem. 1993, 58, 5585.
(d) Rodríguez, J. R.; Rumbo, A.; Castedo, L.; Mascarenas,
J. L. J. Org. Chem. 1999, 64, 4560.
(12) General Procedure for the Oxidation of Aryl Olefins
To a solution of olefin (1 mmol) and RuCl3·nH2O (0.02
mmol) in AcOH (20 mL) was added H2O2 (30%, 2 mmol) in
AcOH (5 mL) dropwisely at r.t. When all H2O2 was added in
15 min, the reaction was completed as checked by TLC. The
reaction mixture was diluted with H2O (100 mL), and
extracted with EtOAc (3 × 30 mL). The organic layers were
combined, neutralized with aq NaHCO3 (3 × 30 mL),
washed with brine (3 × 30 mL), dried over anhyd Na2SO4,
and concentrated in vacuum to give the crude product which
was purified by flash chromatography on silica gel to afford
the corresponding product, the aryl glycol monoester (for
details: Table 1 and Supporting Information).
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.
Acknowledgment
We thank NSFC (20572078) for financial support.
References and Notes
(1) (a) El-Zayat, A. A. E.; Ferrigni, N. R.; McCloud, T. G.;
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(2) (a) Min, H.; Park, E.; Hong, J.; Kang, Y.; Kim, S.; Chung,
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Spectroscopic Data for a Product (Entry 27, Table 1)
White solid (mp 248–250 °C); yield 50%. IR (KBr): n =
3436, 2935, 2814, 1731, 1675, 1546, 1218, 1034 cm–1. 1H
NMR (500 MHz, DMSO-d6): d = 7.34–7.04 (m, 12 H), 6.18
(m, 2 H), 6.14 (d, J = 5.5 Hz, 1 H), 5.79 (d, J = 6.5 Hz, 1 H),
5.33 (d, J = 4.9 Hz, 1 H), 4.01 (dd, J = 7.0, 14.1 Hz, 1 H),
3.46 (m, 2 H), 3.30 (m, 2 H), 2.22 (s, 3 H), 2.00 (s, 3 H), 1.56
(m, 2 H) ppm. 13C NMR (125 MHz, DMSO-d6): d = 177.16,
177.14, 170.65, 137.57, 136.67, 136.11, 135.20, 134.26,
129.48, 129.32, 128.83, 128.54, 127.37, 127.01, 126.76,
126.14, 71.70, 62.55, 60.47, 52.41, 46.12, 45.50, 21.41,
21.25 ppm. ESI-MS: m/z = 585.2 [M + Na]+. ESI-HRMS:
m/z calcd for C34H30N2O6 + Na [M + Na]+: 585.2001; found:
585.2009.
(3) (a) Woodward, R. B.; Brutcher, F. V. J. Am. Chem. Soc.
1958, 80, 209. (b) Li, Y.; Song, D.; Dong, V. M. J. Am.
Chem. Soc. 2008, 130, 2962.
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