Ruthenium-catalyzed addition reaction of alcohols across olefins

Article abstract of DOI:10.1055/s-2004-836058

2-Phenylethanol was added to olefins catalyzed by ruthenium catalytic system Cp*RuCl₂(PPh₃)/2AgOTf in toluene. This reaction proceeded without β-hydride elimination, giving saturated ethers in good yields.

Full text of DOI:10.1055/s-2004-836058

LETTER
179
Ruthenium-Catalyzed Addition Reaction of Alcohols across Olefins
R
uthenium-Cataly
o
zedAddition
h
Reactionof
e
Alcohols
a
i
c
ross
O
lefinsOe, Tetsuo Ohta,* Yoshihiko Ito
Department of Molecular Science and Technology, Faculty of Engineering, Doshisha University, Kyotanabe, Kyoto, 610-6394, Japan
Fax +81(774)656789; E-mail: tota@mail.doshisha.ac.jp
Received 14 September 2004
Abstract: 2-Phenylethanol was added to olefins catalyzed by ruthe-
nium catalytic system Cp*RuCl2(PPh3)/2AgOTf in toluene. This
reaction proceeded without b-hydride elimination, giving saturated
ethers in good yields.
Ru-Cat.
O
OH
OH
O
O
R
Key words: addition reactions, ruthenium, alcohols, alkenes,
ethers
Ru-Cat.
+
R
Ar
Ar
O
Scheme 1
Synthetic organic reactions catalyzed by transition metal
complexes have enormously progressed for the last 2 de-
cades. Highly regio- and stereoselective synthetic meth-
odologies thus developed have been made possible
syntheses of complicated natural products and pharma-
ceutical active compound as well as functional molecules.
Addition reactions, which include the transition metal-
catalyzed hydrosilylation,1 hydroboration,2 hydroalumi-
nation, hydroamination3 and so on, have found wide syn-
thetic applications. Furthermore, addition reactions of
oxygen nucleophiles to olefins by use of Brønsted acids,
stoichiometric amount of Lewis acid4 and mercuric salts5
have been known and utilized.
OH
+
Ph
Ph
1
2a
Catalyst
O
Ph
Ph
3a
Scheme 2
catalyst increased the catalytic activities (entry 4). How-
ever, the activities of the cationic ruthenium complexes
were improved significantly by use of neither electron
poor phosphine ligand (2-Fur3P) nor electron rich
phosphine ligand (CyPh2P) (entries 6, 7). Employment of
bidentate phosphine ligand (dppb) also did not cause im-
provement of chemical yield (entry 5). So far, PPh3 was
the best choice of a ligand in this reaction. When
Cp*RuCl2(Ph3P), prepared independently,9 was used as a
catalyst precursor, the yield was slightly increased with a
saving of AgOTf (entry 9).
With the best catalyst Cp*RuCl2(Ph3P)/AgOTf in hand,
the ‘hydroalkoxylation’ reactions were optimized (entries
8–12). When the hydroalkoxylation reaction was carried
out by stirring a mixture of an excess of 2-phenylethanol
substrate with styrene in the presence of 2 mol% of the ru-
thenium complex catalyst at reaction temperature of
85 °C, the hydroalkoxylation reaction afforded the corre-
sponding ether product in 49% yield (entry 8). The higher
reaction temperature may have resulted in competitive
oligomerization of styrene. On the other hand, use of an
excess of styrene at reaction temperature as high as 70 °C
provided a satisfactory product yield (83% yield, entry
12).
Wacker reaction catalyzed by palladium salt also involves
the addition of oxygen nucleophiles to olefins, ending up
with accompanying b-elimination to give unsaturated
compounds.6 Herein, we wish to report new ruthenium-
catalyzed addition reactions of oxygen nucleophiles to
olefins affording saturated adducts. Two examples of ru-
thenium-catalyzed intramolecular7 and intermolecular8
addition reactions of 2-allylphenol and benzoic acid de-
rivatives produced selectively 2-methyl benzofuran and
benzoate derivatives, respectively, in moderate to good
yields (Scheme 1). It is noted that no unsaturated product,
which may be derived from accompanying b-hydride
elimination, was detected. It is also remarked that the
present addition reactions proceed with complete regio-
selectivity according to Markovnikov’s rule. Some results
of intermolecular ‘hydroalkoxylation’ of styrene with 2-
phenylethanol catalyzed by Ru(III) complexes are sum-
marized (Scheme 2, Table 1).
When (Cp*RuCl2)2 was used as a catalyst precursor in the
absence of AgOTf, no reaction took place (entry 1). Cat-
ionic ruthenium complex activated by AgOTf promoted
the addition reaction of 1 with 2a (entry 2), and addition
of triphenylphosphine (PPh3) on the ruthenium complex
Hydroalkoxylation of 1 with some other olefins in the
presence of cationic ruthenium catalyst Cp*RuCl2(Ph3P)/
2AgOTf are shown in Table 2.
SYNLETT 2005, No. 1, pp 0179–0181
Advanced online publication: 02.12.2004
DOI: 10.1055/s-2004-836058; Art ID: U26204ST
© Georg Thieme Verlag Stuttgart · New York
0
5.
0
1.
2
0
0
5
A simple terminal olefin, 1-octene (2b) was reacted with
1 in the presence of 10 mol% of ruthenium catalyst at
100 °C to give the corresponding ether 3b in 66% yield.

180
Y. Oe et al.
LETTER
Table 1 Effects of Catalyst, Temperature and Molecular Ratio on the Hydroalkoxylation Reaction of 2-Phenylethanol (1) with Styrene (2a)a
Entry
1
Ruthenium complex (mol%)
(Cp*RuCl2)2 (1)
Ligand
None
Silver salt (mol%) Temp (°C)
Ratio 1:2a
1:1
Yield (%)b
None
85
85
85
85
85
85
85
85
85
85
100
70
0
33
16
54
44
41
47
49
56
72
38
83
2
(Cp*RuCl2)2 (1)
None
AgOTf (6)
AgBF4 (6)
AgOTf (6)
AgOTf (6)
AgOTf (6)
AgOTf (6)
AgOTf (4)
AgOTf (4)
AgOTf (4)
AgOTf (4)
AgOTf (4)
1:1
3
(Cp*RuCl2)2 (1)
Ph3P
1:1
4
(Cp*RuCl2)2 (1)
Ph3P
1:1
5
(Cp*RuCl2)2 (1)
DPPB
(2-Fur)3P
CyPh2P
None
1:1
6
(Cp*RuCl2)2 (1)
1:1
7
(Cp*RuCl2)2 (1)
1:1
8
Cp*RuCl2(Ph3P) (2)
Cp*RuCl2(Ph3P) (2)
Cp*RuCl2(Ph3P) (2)
Cp*RuCl2(Ph3P) (2)
Cp*RuCl2(Ph3P) (2)
2:1
9
None
1:1
10
11
12
None
1:2.5
1:2.5
1:2.5
None
None
a Reaction conditions: 2-Phenylethanol (1 mmol), styrene and Ru/Ag/Ligand were stirred in toluene (2 mL).
b Isolated yield after the purification by silica gel column chromatography. Yields were based on 2-phenylethanol except entry 7.
Strained 2-norbornene (2c) was subjected to the hy- Presumably, the hydroalkoxylation reaction starts with
droalkoxylation with 2-phenylethanol in a 1:1 molar ratio the coordination of olefin substrate to the ruthenium com-
at 85 °C to afford 2-phenylethyl exo-2-norbornyl ether plex, followed by nucleophilic attack of the alcohol for the
(3c) in an excellent yield. Attempts for hydroalkoxylation resultant activated olefin. Accordingly, the hydroalkoxyl-
reactions with secondary and tertiary alcohols all failed.
ation remarkably depended upon a molar ratio of olefin
and alcohol, i.e., an excess amount of olefin substrate fa-
vored the hydroalkoxylation, while an excess of alcohol
retarded the reaction. The regioselectivite Markovnikov
addition of the hydroalkoxylation reaction may suggest a
carbonium ion character of the intermediate generated
from olefin coordination on ruthenium complex.
Table 2 Ruthenium-Catalyzed Hydroalkoxylation Reactions of 2-
Phenylethanol with Olefins (2a–c)a
OH
+
Ph
R
1
2a–c
Cp*RuCl2(Ph3P)
AgOTf
O
R
In conclusion, we found that cationic ruthenium catalyst
CpRuCl2(Ph3P)/2AgOTf promoted the addition reaction
of primary alcohol to olefins. Further studies including to
clarifying the mechanistic aspects on hydroalkoxylation
are now going.
Ph
toluene
3a–c
Entry
1
Olefin (equiv)
Product
Yield (%)b
83
Styrene (2a)
(2.5)
O
Ph
Ph
Acknowledgment
3a
This work was partially supported by Doshisha University’s Re-
search Promotion Fund, and a grant to RCAST at Doshisha Univer-
sity from the Ministry of Education, Japan. This work was
supported by Grant-in-Aid for Scientific Research on Priority Areas
(No.16033259, ‘Reaction Control of Dynamic Complexes’) from
Ministry of Education, Culture, Sports, Science and Technology,
Japan.
2c
3
1-Octene (2b)
(10)
66
89
O
O
C6H13
Ph
3b
2-Norbornene (2c)
(1)
Ph
3c
a Reaction conditions: 2-phenylethanol (1 mmol), olefin and
Cp*RuCl2(Ph3P)/2AgOTf (0.2 mmol) were stirred in toluene, at
70 °C, for 48 h.
References
(1) For review, see: Burgess, K.; Ohlmeyer, M. J. Chem. Rev.
1991, 91, 1179.
(2) For example: Glaser, P. B.; Tilley, T. D. J. Am. Chem. Soc.
b Isolated yield after the purification by silica gel column chromato-
graphy.
c Reaction was carried in the presence of 10 mol% Ru at 100 °C.
2003, 125, 13640.
Synlett 2005, No. 1, 179–181 © Thieme Stuttgart · New York

LETTER
Ruthenium-Catalyzed Addition Reaction of Alcohols across Olefins
(8) Oe, Y.; Ohta, T.; Ito, Y. Chem. Commun. 2004, 1162.
181
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(10) Typical Procedure of Ruthenium-Catalyzed
Hydroalkoxylation Reaction of 2-Phenylethanol(1) with
Styrene (2a) Described in Table 2, Entry 1.
Cp*RuCl2 (Ph3P) (11 mg, 0.02 mmol) was dissolved in
toluene (2 mL) and the solution was heated to 85 °C. After
15 min, AgOTf (11.5 mg, 0.045 mmol) was added and
stirred at 85 °C for 3 h. The reaction mixture was cooled to
r.t. 2-Phenylethanol (1, 122 mg, 1.0 mmol) and styrene (2a,
260 mg, 2.5 mmol) were added. The reaction mixture was
heated to 70 °C and stirred for 48 h. The crude product was
purified by silica gel chromatography (hexane–EtOAc =
10:1), yielding product 3a (187 mg, 83%).
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Synlett 2005, No. 1, 179–181 © Thieme Stuttgart · New York