Regio- and stereoselective addition of carboxylic acids to phenylacetylene catalyzed by cyclopentadienyl ruthenium complexes

Article abstract of DOI:10.1016/j.jorganchem.2005.11.023

The direct addition of carboxylic acids to terminal alkynes such as phenylacetylene in the presence of catalytic amount of [CpRu(CO)₂Cl] (1) or [{CpRu(CO)₂}₂] (2) affords the anti-Markovnikov adducts with high selectivity. In most instances, the E-enol esters are the major products.

Full text of DOI:10.1016/j.jorganchem.2005.11.023

Journal of Organometallic Chemistry 691 (2006) 1117–1120
www.elsevier.com/locate/jorganchem
Regio- and stereoselective addition of carboxylic acids to
phenylacetylene catalyzed by cyclopentadienyl ruthenium complexes
a
b,
*
Suming Ye , Weng Kee Leong
a
Institute of Chemical and Engineering Sciences, 1 Pesek Road, Jurong Island, Singapore 627833, Singapore
Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543, Singapore
b
Received 7 October 2005; received in revised form 8 November 2005; accepted 9 November 2005
Available online 20 December 2005
Abstract
The direct addition of carboxylic acids to terminal alkynes such as phenylacetylene in the presence of catalytic amount of [CpRu-
(CO)2Cl] (1) or [{CpRu(CO)2}2] (2) affords the anti-Markovnikov adducts with high selectivity. In most instances, the E-enol esters
are the major products.
ꢀ 2005 Elsevier B.V. All rights reserved.
Keywords: Ruthenium; Anti-Markovnikov; Carboxylic acid; Phenylacetylene; Enol esters
1. Introduction
based on simple, air-stable and easily prepared Ru com-
plexes that selectively affords the anti-Markovnikov and
cis-addition products. To the best of our knowledge, this
is also the first example of cyclopentadienyl ruthenium
complexes catalyzing the addition of carboxylic acids to
alkynes.
Enol esters are important reagents and useful intermedi-
ates for carbon–carbon and carbon–heteroatom bond for-
mation reactions [1,2]. The most straightforward and
atom-economic way to the synthesis of enol esters is the
direct addition of carboxylic acids to 1-alkynes catalyzed
by transition metal complexes which can give rise to three
products (Scheme 1). Since the first report in 1983 of the
[Ru3(CO)12]-catalyzed addition reaction under rather dras-
tic conditions and low selectivity [3], a variety of transition
metal-based catalysts have been investigated, including Ru
[2,4–6], Rh [7,8], Pd [9], Ir [10], Re [11], and even bimetallic
systems[12], many of which exhibited improved regio- and
stereoselectivity under milder conditions. Most of these
catalysts afforded selective formation of the Markovnikov
adducts and only in recent years that catalysts leading to
anti-Markovnikov adducts have been reported. Among
the latter, with some notable exceptions [6], the Z-enol
esters were often the predominant product obtained
[4,5,8,11]. In this paper, we report a new catalytic system
2. Results and discussion
The catalytic efficiency of the complexes [CpRu(CO)2Cl]
(1) and [{CpRu(CO)2}2] (2) for the addition of carboxylic
acids to phenylacetylene has been studied (Table 1). The
reactions were performed under relatively mild conditions
and without optimization, and no special precautions
against air and moisture in the handling of the complexes
were needed. The products have all been characterized
spectroscopically (Table 2), and the efficiencies and selec-
tivities of the reactions have been determined by isolation,
GC as well as NMR methods; many of the Z-isomers have
been reported earlier [5,6,10,11].
Both 1 and 2 are very active catalysts for these reactions
and they show similar activities. With the exception of
C6F5COOH (6), the regioselectivity for the anti-Markovni-
kov adducts was very high. The reaction with benzoic acid
(5) proceeded particularly well. Significant stereoselectivities
*
Corresponding author. Tel.: +65 6874 5131; fax: +65 6779 1691.
E-mail address: chmlwk@nus.edu.sg (W.K. Leong).
0022-328X/$ - see front matter ꢀ 2005 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2005.11.023

1118
S. Ye, W.K. Leong / Journal of Organometallic Chemistry 691 (2006) 1117–1120
O
yields of 13% and 19% for 1 and 2, respectively, with regi-
Markovnikov
oselectivity for the anti-Markovnikov product at 74.5%
and 77.4%, respectively, and E/Z ratios of slightly less than
unity. For the other acids, no products were formed at all.
This is again in contrast to the other ruthenium systems,
for which the yields of the 1-hexyne reactions are compara-
ble or even higher than those for phenylacetylene. The
reaction also failed to proceed when diphenylacetylene
was employed as the alkyne substrate.
R
O
R'
O
E
catalyst
R
R
+ R'COOH
O
R'
anti-Markovnikov
O
Z
O
R'
R
No catalytic intermediates were observable spectroscop-
ically when stoichiometric mixtures of phenylacetylene or
benzoic acid and 2 were heated over a period of 24 h; the
1H NMR and IR spectra showed the presence of 2 only.
In the reported [{Ru(RCOO)(CO)2(L)}2] system, it was
proposed that generation of the actual catalytic precursor
(a mononuclear intermediate) required both an alkyne
and acid [4e]; our results here therefore appear to indicate
that an intermediate having both a bound alkyne and acid
is involved in our system. Although we have yet to elucidate
the details of the catalytic cycle for this reaction, one possi-
ble cycle that we are proposing is depicted in Scheme 2.
The similar efficiencies and selectivities shown by both 1
and 2 suggest that they are precursors to the same interme-
diate. However, that no observable products were formed
when 5 was reacted with 2 suggests that this catalytically
active species is present in only very minute amounts.
The possible identity of this intermediate is [CpRu-
(CO)2(O2CR)] (A), which may be formed from 1 via nucle-
ophilic displacement of the Clꢀ ion by the carboxylate; this
would be consistent with the reaction working better with a
weaker acid (and hence stronger conjugate base). This
intermediate may also be formed from 2 via oxidative addi-
tion across the metal–metal bond. In either case, the equi-
librium probably lies to the left-hand side, and it is the
binding of the alkyne that drives the reaction forward.
Indeed, we have verified that [CpRu(CO)2(O2CPh)] does
Scheme 1.
were observed for acetic acid, butyric acid and benzoic
acid, and it appears that 1 afforded marginally better stere-
oselectivity than 2 although they showed similar regioselec-
tivity. Although the addition reaction for 6 did proceed,
regio- and stereoselectivities were low, with either 1 or 2;
separation was fairly easy, however, as the (E)-isomer pre-
cipitated out as a white solid from the reaction mixture
upon cooling to room temperature while the (Z)-isomer
and the Markovnikov adduct remained in solution. It has
been observed that strong acids may afford products in
higher regio- and stereoselectivities if the reaction temper-
ature was kept lower [5]. However, we have found that
the reaction of 6 at 70 ꢁC did not show any improvement
in selectivity. We have also found that the reaction of
CF3COOH at various temperatures ranging from 0 to
110 ꢁC did not give any addition products; the in situ
NMR spectra were always very complicated. These obser-
vations indicate that very strong carboxylic acids were not
suitable substrates for this catalytic system.
In contrast to phenylacetylene, the analogous reactions
using 1-hexyne proceeded with very low yields, and poorer
regio- and stereoselectivities; variations in the temperature
did not result in any improvement either. Thus the reaction
of 5 and 1-hexyne under the same conditions gave total
Table 1
Enol ester formation catalyzed by complexes 1 and 2
Entry
Catalyst
Alkyne
Acid
%Conversiona
%Yield of adductsb
Selectivityc
E/Z ratio
1
2
3
4
5
6
7
8
9
1
2
1
2
1
2
1
2
1
2
1
2
Phenylacetylene
CH3COOH (3)
84
92
80
79
98.5
100
78 (66)
86 (71)
78 (77)
77 (76)
90 (80)
96 (90)
(92)
97
97
97
97
96
96
47
61
93
95
98
97
6.0
2.9
4.1
3.0
3.2
2.7
0.8
1.0
1.1
1.2
5.1
5.1
CH3(CH2)2COOH (4)
C6H5COOH (5)
C6F5COOH (6)
(90)
CH3CH(Br)COOH (7)
E-CH3CH@CHCOOH (8)
88
95
94
70
48 (40)
75 (69)
91 (80)
68 (67)
10
11
12
13
14
1
2
1-Hexyne
C6H5COOH
(13)
(19)
74
77
0.8
0.9
Reaction condition: toluene, 110 ꢁC, [alkyne] = 2 M, alkyne/acid/catalyst = 100:100:1, 24 h.
a
Based on the consumption of alkyne, determined by GC.
GC yields (isolated yields).
Selectivity = anti-Markovnikov adducts/total enol esters; determined by 1H NMR and GC.
b
c

S. Ye, W.K. Leong / Journal of Organometallic Chemistry 691 (2006) 1117–1120
1119
Table 2
Characterization of reaction products
Acid Product Appearance
IR/cmꢀ1
1H NMR, d
EI-MS, m/z
3
3
b-Styryl acetate
Colorless liquid 1761 (mC@O
)
E-isomer: 7.84 (d, 1H, Jtrans = 12.8 Hz, @CH), 7.37–7.20
(m, 5H, Ph), 6.39 (d, 1H, @CH), 2.19 (s, 3H, Me)
162 (M+)
3
1661 (mC@C
)
Z-isomer: d 7.58 (d, 1H, Jcis = 7.4 Hz, @CH), 7.37–7.20
(m, 5H, Ph), 5.70 (d, 1H, @CH), 2.27 (s, 3H, Me)
3
4
b-Styryl butyrate
b-Styryl benzoate
Colorless liquid 1756 (mC@O
)
E-isomer: 7.87 (d, 1H, Jtrans = 412.8 Hz, @CH), 7.38–7.26
190 (M+)
(m, 5H, Ph), 6.39 (d, 1H, @CH), 2.43 (t, 2H, 3J = 7.4 Hz, CCH2),
1.73 (m, 2H, CH2), 1.01 (t, 3H, 3J = 7.2 Hz, Me)
3
1655 (mC@C
)
Z-isomer: 7.58 (d, 1H, Jcis = 7.7 Hz, @CH), 7.38–7.26
(m, 5H, Ph), 5.70 (d, 1H, @CH), 2.52 (t, 2H, 3J = 7.4 Hz, CCH2),
1.78 (m, 2H, CH2), 1.03 (t, 3H, 3J = 7.6 Hz, Me)
3
5
6
White solid
White solid
1726 (mC@O
)
E-isomer: 8.09 (d, 1H, Jtrans = 12.8 Hz, @CH),
224 (M+)
314 (M+)
8.16–7.20 (m, 10H, Ph), 6.59 (d, 1H, @CH)
Z-isomer: 8.16–7.20 (m, 11H, Ph and @CH), 5.86
(d, 1H, Jcis = 7.2 Hz, @CH)
1656 (mC@C
)
3
3
b-Styryl
1754 (mC@O
)
E-isomer: 7.99 (d, 1H, Jtrans = 13.3 Hz, @CH), 7.4–7.2
pentafluorobenzoate
(m, 5H, Ph), 6.60 (d, 1H, @CH)
Z:isomer: 7.47 (d, 1H, Jcis = 7.2 Hz, @CH), 7.26–7.59
3
1651 (mC@C
)
(m, 5H, Ph), 5.93(d, 1H, @CH), M-adduct: 7.26–7.59
2
(m, 5H, Ph), 5.59 (d, 1H, Jgem = 1.2 Hz, @CH2),
5.23 (d, 1H, @CH2)
3
7
8
5
b-Styryl
2-bromopropanoate
Colorless liquid 1750 (mC@O
)
E-isomer: 7.82 (d, 1H, Jtrans = 12.8 Hz, @CH), 7.39–7.26
255 (M+)
188 (M+)
184 (M+)
(m, 5H, Ph), 6.50 (d, 1H, @CH), 4.47
(q, 1H, 3J = 6.8 Hz, CH), 1.92 (d, 3H, Me)
3
1662 (mC@C
)
Z-isomer: 7.61 (d, 1H, Jcis = 6.8Hz, @CH),
7.39–7.26 (m, 5H, Ph), 5.81 (d, 1H, @CH), 4.55
(q, 1H, 3J = 6.8 Hz), 1.92 (d, 3H, Me)
3
b-Styryl crotonate
Colorless liquid 1735 (mC@O
)
E-isomer: 7.98 (d, 1H, Jtrans = 12.8 Hz, @CH),
7.62–7.10 (m, 6H, Ph and @CH), 6.44 (d, 1H, @CH),
5.92 (dq, 1H, 3J = 15.7 and 1.6 Hz, CHMe), 1.95 (dd, 3H, Me)
3
1651 (mC@C
)
Z-isomer: 7.62 (d, 1H, Jcis = 7.2 Hz, @CH),
7.62–7.10 (m, 6H, Ph and @CH), 6.02 (dq,
1H, J = 15.7 and 1.6 Hz, CHMe), 5.74 (d, 1H, @CH), 1.99 (dd, 3H, Me)
3
Hex-1-en-1-yl benzoate Colorless liquid 1735 (mC@O
)
E-isomer: 8.2–7.2 (m, 6H, Ph and @CH), 5.60
(dt, 1H, Jtrans = 12.4 Hz, @CH), 2.09 (m, 2H, CH2),
3
1.38 (m, 4H, 2 · CH2), 0.90 (t, 3H, Me)
1665 (mC@C
)
Z-isomer: 8.2–7.2 (m, 6H, Ph and @CH), 5.01
3
(dt, 1H, Jcis = 7.2 Hz, @CH), 2.30 (m, 2H, CH2),
1.38 (m, 4H, 2 · CH2), 0.90 (t, 3H, Me)
1
2
+
+
RCOOH
RCOOH
CpRu(CO)2(O2CR) A
catalyze the reaction of 5 with phenylacetylene at a similar
efficiency (95% yield of the adducts under the same condi-
tions) [13]. The possibility of a vinylidene intermediate can-
not be completely ruled out although it is unlikely as the
predicted region- and stereoselectivities would be reversed
[4g,4h,4j,5].
The possibilities for the binding of the alkyne (step a)
include loss of a carbonyl or an g5 ! g3 ring slippage
[14], although the latter has been shown to be unlikely in
the closely related case of the cycloaddition of cyclooctadi-
ene with alkyne by [CpRu(COD)Cl], which is also believed
to proceed through initial loss of the Clꢀ ligand [14b]. The
subsequent migratory insertion (step b) is probably the crit-
ical step that dictates the regio- and stereoselectivity; the
carboxylate ligand is probably aligned as shown with
respect to the alkyne to avoid steric interaction between
them, which leads to the anti-Markovnikov product. This
CpRu(CO)2H +
CpRu(CO)2(O2CR) A
H
C
OCOR
Ph
Ph
C
[Ru]
O
H
R
a
d
O
A
OCOR
[Ru]
[Ru]
O
O
R
H
C
C
Ph
H
C
OCOR
C
[Ru]
H
b
c
C
OCOR
Ph
C
RCOOH
H
Scheme 2.

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S. Ye, W.K. Leong / Journal of Organometallic Chemistry 691 (2006) 1117–1120
intramolecular nature of step b would also account for the
stereoselectivity; indeed it is expected to lead to only the E-
isomers. That the Z-isomers are also observed may be
attributed to either of two possibilities: alkene isomeriza-
tion, or the presence of another reaction pathway for step
b. We have confirmed that alkene isomerization did not
occur in our system; no isomerization product was found
when the pure E-b-styryl pentafluorobenzoate and
3 mol% of 2 was refluxed in toluene for 24 h. It is therefore
likely that step b involved two alternative pathways, the
other being an intermolecular attack by carboxylate. This
would seem to be consistent with the observation that ste-
reoselectivities are poorest for the strongest acids 6 and 7,
since they would be expected to form more carboxylates
in solution and hence favor the intermolecular pathway.
The final two steps of the proposed cycle involve oxidative
addition of the carboxylic acid (step c) followed by reduc-
tive elimination of the product and regeneration of the cat-
alytically active species (step d).
by silica gel column chromatography (eluant: hexane–
diethyl ether, 10:1, v/v) to afford first a mixture of the Z-
and E-enol esters (0.42 g) as a colorless oil, followed by
the Markovnikov adduct.
Acknowledgment
This work was supported by an A*STAR Grant (Re-
search Grant No. 012 101 0035).
Appendix A. Supplementary data
1H NMR spectra of the anti-Markovnikov products.
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.jorganchem.
2005.11.023.
References
In conclusion we have uncovered a highly efficient and
selective catalytic method for the synthesis of b-styryl type
enol esters by the addition of carboxylic acids to 1-alkynes
using two readily available half-sandwich ruthenium com-
plexes. In particular, they are the first examples for which
high selectivity for the anti-Markovnikov, cis-addition
products is obtained.
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3. Experimental
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3.1. General procedures
All manipulations were carried out under an inert atmo-
sphere using Schlenk techniques. Catalytic reactions were
performed in a thick-walled glass Carius tube equipped
1
with a Teflon valve. H NMR spectra were recorded as
CDCl3 solutions on a Bruker ACF300 NMR spectrometer;
chemical shifts were referenced to the residual solvent res-
onance. IR spectra were recorded as CH2Cl2 solutions in a
solution cell with NaCl windows and 0.1 mm pathlength,
on a BioRad FTS-165 FTIR instrument. Mass spectra
were obtained on a Finnigan Mat 95XL-T spectrometer.
GC analyses were performed on a Perkin–Elmer Autosys-
tem XL with an HP-1 column. Toluene was dried and dis-
tilled under nitrogen before use. The complexes
[CpRu(CO)2Cl] (1) and [{CpRu(CO)2}2] (2) were prepared
according to the literature methods [15,16]. All the other
chemicals were of commercial reagent grade and used as
received without further purification.
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3.2. A typical procedure for the catalytic runs
Acetic acid (115 lL, 2 mmol), phenylacetylene (0.22 mL,
2 mmol) and the catalyst (0.02 mmol) in toluene (1 mL)
were stirred at 110 ꢁC for 24 h. After cooling, the reaction
mixture was diluted with toluene to 4 mL and n-nonane
(70 lL) was added as internal standard. The resulting mix-
ture was then analyzed by GC. The product was purified
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