Control over C-O and C-C bond formation: ruthenium catalyzed regiospecific addition of carboxylic acid to alkyne and stereoselective dimerization of alkyne

Article abstract of DOI:10.1016/j.tetlet.2009.06.039

A cationic ruthenium(II) complex, [Ru(PPh₃)₂(CH₃CN)₃Cl][BPh₄] (1), has been found to be an effective catalyst for stereoselective dimerization of alkynes in the presence of a base, and for regiospecific addition of carboxylic acids to alkynes in presence of the Lewis acid, BF₃·Et₂O.

Full text of DOI:10.1016/j.tetlet.2009.06.039

Tetrahedron Letters 50 (2009) 4863–4865
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Tetrahedron Letters
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Control over C–O and C–C bond formation: ruthenium catalyzed
regiospecific addition of carboxylic acid to alkyne and stereoselective dimer-
ization of alkyne
*
Jyotsna Tripathy, Manish Bhattacharjee
Department of Chemistry, Indian Institute of Technology, Kharagpur 721 302, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 28 January 2009
Revised 4 June 2009
Accepted 8 June 2009
Available online 11 June 2009
A cationic ruthenium(II) complex, [Ru(PPh3)2(CH3CN)3Cl][BPh4] (1), has been found to be an effective cat-
alyst for stereoselective dimerization of alkynes in the presence of a base, and for regiospecific addition of
carboxylic acids to alkynes in presence of the Lewis acid, BF3ꢀEt2O.
Ó 2009 Elsevier Ltd. All rights reserved.
Enol esters are important intermediates in synthetic organic
chemistry.1 They are used in acylation of carbonyl compounds,2
in the synthesis of
cationic vinylidene ruthenium complex14c catalyzed enol forma-
tion and dimerization of alkyne, and the nature of the product
was found to be dependent on the type of acid. Here again, a mix-
ture of products was obtained.
Only recently, Le Paih et al. have reported ruthenium-catalyzed
condensation of two molecules of alkynes and one molecule of car-
boxylic acid.13
a
-halo ketones,3 kinetic resolution of chiral
alcohols4 and in cyclopropanation5 and cycloaddition reactions.6
In addition, these are important monomers in polymerization reac-
tions.7 Similarly, enynes are important substrates for the synthesis
of organic materials,8 and metal-catalyzed carbon–carbon bond
formation by coupling of alkynes offers a large number of such
products.9 Ruthenium compounds have been used as catalysts for
the synthesis of enol esters1,10 as well as for enynes.11
Recently, we have reported the synthesis, structure and catalytic
properties of a cationic ruthenium complex, [Ru(PPh3)2(CH3CN)3Cl]
[BPh4] (1).15 This complex catalyzes transfer hydrogenation of alde-
hydes and ketones15a and selective reduction of carbonyl group of
The first report on ruthenium-catalyzed addition of carboxylic
acid to alkyne involves Ru3(CO)12 as a catalyst.12 However, the reac-
tion conditions were harsh and the products obtained were Mark-
ovnikov products.12 This was followed by a large number of
reports on ruthenium-catalyzed addition of carboxylic acid to al-
kynes.1,10 Addition of carboxylic acid to alkynes affords three possi-
ble isomers (Scheme 1) and most of the reported reactions afford
more than one isomer. Recently regio-controlled ruthenium-cata-
lyzed addition of carboxylic acid to alkynes was reported by Goossen
et al.1c
Ruthenium-catalyzed dimerization of terminal alkynes to E and
Z 1,4-substituted enynes (A0 or B0, Scheme 2) and 2,4-disubstituted
enynes (C0 Scheme 2) and butatrienes (D0, Scheme 2) was
reported.13
Although, for both the reactions ruthenium complexes have
been used as catalysts, there are only a few reports on controlled
C–O and C–C bond formation using the same catalyst.14 In a recent
report it has been shown that, RuClx(p-cymene)(triazol-5-ylidene)
compounds can catalyze both the addition of carboxylic acid to al-
kynes and dimerization of alkynes.14a However, the regio- and ste-
reoselectivity in both the reactions were found to be very poor.14a
Another couple of reports deal with [Cl2(PCy3)2Ru@CHPh]14b and
a
,b-unsaturated carbonyl compounds.15b The complex was also
found to be an effective catalyst for monoalkylation of anilines by
alcohols.15c In continuation of our investigations on the catalytic
properties of 1, herein we report a controlled regiospecific addition
of carboxylic acid to alkynes and stereoselective dimerization of al-
kynes catalyzed by 1. We have chosen the reaction of phenylacety-
lene with benzoic acid as the model reaction. Thus, a reaction of
phenylacetylene and benzoic acid in the presence of 1 mol % of 1 in
toluene at 80 °C afforded both enol ester and dimerization products
(Scheme 3). Thus, it is clear that, complex 1 can catalyze addition of
carboxylic acid to alkyne as well as dimerization of alkynes.
We were interested in controlling the catalytic properties of 1. It
has been reported that, in ruthenium-catalyzed dimerization of al-
kynes, addition of base promotes formation of alkenylruthenium
species of the type [LnRu-C„CR], which is the key intermediate
in the dimer formation.11c,d Accordingly, a reaction of phenylacet-
ylene with carboxylic acid in the presence of a base, Na2CO3 and 1
{1:1:1:0.01} was carried out and as expected, the tail to tail Z-
dimerization product was found to be the major product (Table
1). The HPLC trace of the crude product confirms the formation
of a small amount of unsaturated ester and E-dimerization product
along with the Z-dimerization product.
Having established the reaction conditions for the dimerization
reaction, we were interested in investigating the reaction condition
* Corresponding author. Tel.: +91 3222 283302; fax: +91 3222 282252.
E-mail address: mxb@iitkgp.ac.in (M. Bhattacharjee).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.06.039

4864
J. Tripathy, M. Bhattacharjee / Tetrahedron Letters 50 (2009) 4863–4865
Scheme 1. Addition products of carboxylic acid to alkynes.
Table 1
Effect of additive on the nature of product in the 1 catalyzed reaction between
phenylacetylene and benzoic acida
d
d
d
Additive
None
Conv. (%)
Sel. A00 (%)
Sel. B00 (%)
Sel. C00 (%)
90
95
85
98
47
5
8
31
90
56
0
22
5
36
4
b
Na2CO3
Et3Nb
BF3ꢀEt2Oc
96
Scheme 2. Products of dimerization of alkynes.
a
Conditions: 2.5 mmol phenylacetylene, 2.5 mmol benzoic acid, 0.025 mmol 1,
toluene 80 °C.
b
c
2.5 mmol of Na2CO3.
0.025 mmol of BF3ꢀEt2O.
From HPLC.
for the addition of carboxylic acid to alkynes. It has been suggested
that, coordination of both the reactants, that is, carboxylic acid as
well as alkyne is necessary for the catalytic reaction.12,14
d
Recently, [RuCl{C(@CHPh)OC(@O)CH2CH3}(CO) (PPh3)] has
been isolated and structurally characterized as an intermediate
in the ruthenium-catalyzed Z-enol ester formation.16 However,
Bruneau and Dixneuf have suggested that, formation of enol esters
takes place through the attack of the external nucleophilic acid to
the coordinated electrophilic alkyne. Also, it has been shown that,
the presence of a coordinated monophosphine is necessary for the
catalytic activity.1a
In case of 1, two triphenylphosphines are coordinated to the
ruthenium centre and it was thought that, removal of one triphen-
ylphosphine may generate catalytically active species for the addi-
tion reaction. Boron trifluoride is known to form adduct with
phosphines. We thought to use BF3 as a phosphine scavenger.
The efficacy of BF3 as phosphine scavenger was established from
in situ 31P (external standard: H3PO4) and 11B NMR (external stan-
dard: BF3ꢀEt2O) spectra of the reaction between complex 1 and
BF3ꢀEt2O. The 31P{1H} NMR spectrum of 1 in CD3CN shows only
one peak at 32.8 ppm. The 11B{1H} spectrum of the compound
shows one broad peak at ꢁ6.3 ppm, due to [BPh4]ꢁ anion. When
BF3ꢀEt2O is added to this solution and heated to about 60 °C for
15 min, the peak at 32.8 ppm disappears and three new peaks ap-
pear at 53.2, 34.9 and 8.7 ppm in the 31P{1H} NMR spectrum. The
broad nature of the peak at 8.7 ppm suggests that, this signal is
due to Ph3PꢀBF3 adduct. Even at higher temperature (60 °C) the
peak could not be resolved. The signal at 34.9 ppm has been as-
signed to 31P signal of the ruthenium-coordinated Ph3PꢀBF3. Also,
with time this signal disappears. The signal at 53.2 ppm has been
assigned to a monophosphine complex of ruthenium of the type
[Ru(PPh3)(CD3CN)4Cl][BPh4]. The conclusive evidence of phosphine
abstraction comes from the 11B{1H} spectrum of the solution. The
Scheme 4. Reaction of alkynes with carboxylic acid in the presence of 1 and
BF3ꢀEt2O.
resolved at higher temperature. The peak due to [BPh4]ꢁ could
not be observed, as it is merged along with the ꢁ0.5 ppm signal.
Having established the efficacy of BF3 as phosphine scavenger,
we have carried out a reaction between benzoic acid and phenyl-
acetylene in the presence of 1 mol % of
1
and BF3ꢀEt2O
{1:1:0.01:0.01} in toluene at 80 °C. The major product is the Mark-
ovnikov addition product (Table 1). It may be noted that, only a few
catalysts are known to afford selectively Markovnikov addition
product.1c,10
The reaction is quite effective in the cases of aromatic and ali-
phatic carboxylic acids (Scheme 4) (Table 2, entries 1–7) and af-
fords the corresponding addition product in good yields. Only in
the case of acetic acid, formation of small amounts of Z-1,4 diphe-
nyl-1-buten-3-yne and 2,4-diphenyl-1-buten-3-yne could be ob-
11B{1H} spectrum of the solution shows
a broad signal at
ꢁ0.5 ppm. This is due to the Ph3PꢀBF3 species.17 The 11B{1H} spec-
trum of Ph3PꢀBF3 in CDCl3 shows a peak at ꢁ0.4 ppm.17 The slight
shift observed is due to the solvent effect. The peak could not be
Scheme 3. Reaction of phenylacetylene with benzoic acid in the presence of 1.

J. Tripathy, M. Bhattacharjee / Tetrahedron Letters 50 (2009) 4863–4865
4865
Table 2
In summary, we have demonstrated that the same catalyst can
be used for C–C and C–O bond formation when reaction conditions
are changed. In addition, the catalyst can be synthesized very eas-
ily from a reaction of commercially available [Ru(PPh3)3Cl2] with
NaBPh4 in acetonitrile.15a In contrast to the catalytic system re-
ported earlier1c the present catalyst does not require any expensive
phosphine additives such as, P(p-Cl–C6H4)3 or P(Fur)3. We are now
investigating the details of the dimerization reactions of alkynes.
Addition of carboxylic acid to alkynes catalyzed by 1a
Entry
Alkyne
Acid
Product
Yieldb (%)
1
2
3
4
5
6
7
8
9
2a
2b
2c
2d
2e
2f
3a
3b
3c
3d
3e
3f
4a
4b
4c
4d
4e
4f
4g
4h
4i
78
82
73
73
70
72
70
74
70
62
65
71
2g
2h
2i
2j
2k
2l
3g
3a
3a
3a
3a
3a
Acknowledgements
10
11
12
4j
4k
4l
We thank the Department of Science and Technology, Govern-
ment of India, New Delhi for NMR facility and Professor A. Basak,
Department of Chemistry, Indian Institute of Technology, Kharag-
pur, India for HPLC. We also thank the reviewers for their helpful
comments.
a
Conditions: 10 mmol alkynes, 10 mmol carboxylic acid, 0.1 mmol 1, 0.1 mmol
BF3ꢀEt2O, toluene 80 °C.
b
Isolated yield.
Supplementary data
served. The reaction fails in the cases of amino acids, oxalic acid
and cinnamic acid. This may be due to the chelation of the metal
centre by the acid, thus preventing coordination of phenylacety-
lene to the ruthenium centre. The reaction is also, effective in the
case of substituted phenylacetylenes such as 1-ethynyl-4-fluoro-
benzene, or 1-ethynyl-4-methoxybenzene (Table 2, entries 8 and
9) and other substituted aromatic and heteroaromatic alkynes such
as 2-ethynyl-6-methoxynaphthalene and 2-ethynylpyridine (Table
2entries 10 and 11) and aliphatic alkyne, 1-hexyne (Table 2, entry
12).
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2009.06.039.
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Effect of base on the 1 catalyzed dimerization of phenylacety-
lene has also been studied. In the presence of Et3N, Z-dimerization
product is obtained as a major product (56%). Along with the Z-
dimerization product, E-dimerization product (36%) and addition
product (8%) are also obtained (Table 1). Thus it is clear that,
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