addition of carboxylic acids to alkynes.6À15 However,
most of the examples are limited to the reaction of
terminal alkynes or symmetrical internal alkynes. To
the best of our knowledge, there is only one example of
the ruthenium-catalyzed addition of carboxylic acid to
an unsymmetrical internal alkyne: Shvo and co-workers
examined the addition reaction of benzoic acid to 1-phe-
nyl-1-heptyne, but the reaction yielded a mixture of
more than four stereoisomers.3b During the course of
our research on the ruthenium-catalyzed trimerization
of trifluoromethyl group-substituted internal alkynes,16
we observed the formation of enol esters when car-
boxylic acid was added to the reaction mixture. The
result strongly encouraged us to investigate the ruthe-
nium-catalyzed stereoselective addition of carboxylic
acid to aryl and trifluoromethyl group substituted un-
symmetrical internal alkynes; we succeeded in obtaining
the trifluoromethyl group substituted enol esters with
high regio- and stereoselectivities.
Table 1. Ruthenium-Catalyzed Addition of Acetic Acids 2a
to 1aa
entry
L
solvent
temp (°C)
yieldb (%)
1
2
3
4
5
6
7
8
9
2-DPPBN
CH3CN
CH3CN
CH3CN
CH3CN
dioxane
dioxane
dioxane
dioxane
toluene
80
80
32
28
DPPB
80
60
PPh3
80
67
2-DPPBN
100
100
100
100
100
63
67
DPPB
PPh3
PPh3
67
80 (73)c
71
We examined the addition reaction of acetic acid (2a)
to p-tolyl and trifluoromethyl group substituted inter-
nal alkyne 1a using ruthenium catalysts (Table 1).
Based on the observation of our previous ruthenium-
catalyzed trimerization of 1a, we tested the addition of
2a to 1a by Ru3(CO)12 with 2-(diphenylphosphino)
benzonitrile (2-DPPBN). The reaction at 80 °C in
CH3CN gave the expected trifluoromethyl group-sub-
stituted enol esters 3aa, but the yield was miserable
(entry 1). To our delight, optimization of the catalysts
afforded desired enol ester: the PPh3- or DPPB-ligated
ruthenium catalysts exhibit good catalyst activity
against the desired reaction (entries 3 and 4). The yields
were improved by raising the reaction temperature to
100 °C (entries 5À9). In particular, the PPh3-ligated
ruthenium catalyst gave the best results, and 80% of the
desired product was then obtained as a single stereo-
isomer (entry 8).17 Toluene also worked as a good
solvent for this reaction, but the dioxane solvent system
gave a better result than did toluene (entries 8 and 9).
We further observed that the reaction proceeded with
high regio- and E-selectivities.18,19
a Reaction conditions: 1a (1.0 mmol), 2a (1.0 mmol), 3.3 mol % of
Ru3(CO)12, ligand (10 mol % for PPh3, 5 mol % for 2-DPPBN and
DPPB), 0.5 mL of solvent, 12 h. b The yields were determined by 1H
NMR using an internal standard (trioxane). c Isolated yield is shown in
parentheses.
We next demonstrated the Ru3(CO)12/3PPh3-cata-
lyzed addition of several carboxylic acids 2bÀo to aryl
and trifluoromethyl group substituted unsymmetrical
internal alkynes 1aÀe, and the results are summarized
in Table 2. Typically, the reaction was carried out as
follows: 3.3 mol % of Ru3(CO)12, 10 mol % of PPh3,
alkyne 1, and carboxylic acid 2 (1.0 equiv) were mixed in
dioxane at 100 °C for 12 h. The addition of benzoic acid
(2b) to 1a under optimized conditions formed the desired
enol ester 3ab in 89% isolated yield without formation of
byproduct (entry 1). We also confirmed that the amount of
ruthenium catalyst could be reduced to 1.1 mol % of
Ru3(CO)12 and 3.3 mol % of PPh3 without decreasing
the yield (entry 2). Benzoic acid analogues, which have the
electron-donating group on the aromatic ring, provided
the desired products 3acÀaf (entries 3À6) (Figure 1). On
the other hand, an electron-withdrawing group also did
not influence the result, and the desired enol esters were
obtained in good yields (entries 7À9). The sterically hin-
dered aromatic carboxylic acids, such as 1-naphthoic acid
(2j) and ortho-substituted benzoic acid analogues 2kÀm,
gave trifluoromethyl group substituted internal enol esters
3ajÀam in good yield (entries 10À14), and even the reac-
tion with 2,6-dimethylbenzoic acid (2n) formed the pro-
duct 3an in 70% isolated yield (entry 14). To our delight,
we confirmed that the ruthenium catalyst systems exhibit
good catalyst activity for the reaction of aliphatic car-
boxylic acid (entries 15 and 16). We further succeeded in
obtaining the desired product in the addition of benzoic
acid to several aryl and trifluoromethyl group containing
internal alkynes (1bÀe) with good to high yields (entries
17À20). Those results clearly indicate that the reaction is
applicable to reactions using various combinations of
carboxylic acid and 1-aryl-3,3,3-trifluoropropynes.
(10) Ye, S.; Leong, W. K. J. Organomet. Chem. 2006, 691, 1117–1120.
~
(11) Pelagatti, P.; Bacchi, A.; Balordi, M.; Bolano, S.; Calbiani, F.;
Elviri, L.; Gonsalvi, L.; Pelizzi, C.; Peruzzini, M.; Rogolino, D. Eur. J.
Inorg. Chem. 2006, 2422–2436.
(12) (a) Yi, C. S.; Gao, R. Organometallics 2009, 28, 6585–6592. (b)
Yi, C. S. J. Organomet. Chem. 2011, 696, 76–80.
(13) Tripathy, J.; Bhattacharjee, M. Tetrahedron Lett. 2009, 50,
4863–4865.
(14) Tan, S. T.; Fan, W. Y. Eur. J. Inorg. Chem. 2010, 4631–4635.
(15) Cadierno, V.; Francos, J.; Gimeno, J. Organometallics 2011, 30,
852–862.
(16) Kawatsura, M.; Yamamoto, M.; Namioka, J.; Kajita, K.;
Hirakawa, T.; Itoh, T. Org. Lett. 2011, 13, 1001–1003.
(17) We confirmed the formation of 3,3,3-trifluoro-1-tolylpropan-1-
one as a byproduct (<10%), and the structure of it was determined by
comparison with reported NMR data; see: (a) Kamitoi, Y.; Hojo, Y.;
Masuda, R.; Ohara, S.; Kawamura, Y.; Ebisu, T. Synthesis 1989, 43–45.
(b) Laurent, A. J.; Lesniak, S. Tetrahedron Lett. 1992, 33, 3311–3314.
(18) Regioselectivity (>20:1) and E-selectivity (>20:1) were deter-
mined by 1H and 19F NMR of the crude materials.
(19) The stereochemistry of 3aa was determined by comparison of the
X-ray crystallographic analysis of the product 3ad.
3286
Org. Lett., Vol. 13, No. 12, 2011
Kawatsura, Motoi
