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Gold(I)-Catalyzed Addition of Carboxylic Acids to acids to alkynes catalyzed by transition metals is an efficient
Alkynes way to prepare enol esters4 and has been extensively studied
by ruthenium complexes.5 The electrophilic activation of
terminal alkynes by suitable ruthenium complexes together
Bathoju Chandra Chary and Sunggak Kim*
with carboxylic acids has provided an easy access to alk-1-en-
Division of Chemistry and Biological Chemistry, School of 2-yl esters 1 and (Z)-alk-1-enyl esters 2 derived from the
Physical and Mathematical Sciences, Nanyang Technological Markovnikov6 and the anti-Markovnikov addition, respec-
University, Singapore 637371, Singapore tively (Scheme 1).7

[email protected] SCHEME 1. Ru-Catalyzed Addition of Acids to Alkynes

Received August 6, 2010

The gold(I)-catalyzed intramolecular addition of car-

boxylic acids and esters to terminal alkynes, which results
in lactones, was reported previously by several groups,8 but
somewhat surprisingly, only one example of the intermolec-
ular version was reported to date.9 Reaction of acetic acid
with 3-hexyne in tetrahydrofuran at 60 °C using (triphenyl-
phosphine)gold(I) pentafluoropropionate and boron tri-
fluoride etherate as a cocatalyst afforded 3-hexene 3-acetate
in a very low yield (6.2%) along with 3-hexanone (12.3%).9
Au(I)-catalyzed hydroacyloxylation of alkynes with car- To improve this unsatisfactory result and to determine the
boxylic acids is described. PPh3AuCl/AgPF6 catalyst scope and limitations of hydroacyloxylation, we have inves-
affords the Markonikov addition products, whereas tigated the addition of carboxylic acids to alkynes using
PPh3AuCl/AgOTf catalyst gives the more stable isomer- gold(I) catalysts along with our recent interest in the func-
ized products via the Markonikov products. tionalization of alkynes.10
We initially studied the effectiveness of gold(I) catalysts
using 1-hexyne and benzoic acid in toluene (Scheme 2). When
1-hexyne was treated with benzoic acid in toluene in the pre-
Gold catalysis has attracted a great deal of recent attention sence of Ph3PAuCl/AgOTf catalyst (5 mol %) at room tem-
due to its extraordinary versatility in functional group perature for 15 h, somewhat surprisingly, an E- and Z-mixture
transformations associated with carbon-carbon multiple of a more stable enol benzoate 4 was isolated in 87% yield
bonds.1 Among various useful functionalizations of alkynes, (entry 1). Apparently, the initially formed Markovnikov addi-
Au(I)-catalyzed nucleophilic additions to alkynes proved to tion product 3 was isomerized completely to the thermodynami-
be synthetically useful and include hydroamination,2 hydro- cally more stable enol benzoate 4. Ph3PAuCl/AgBF 4 was
xylation, and hydroalkoxylation.3 Addition of carboxylic
(5) For reviews, see: (a) Bruneau, C.; Dixneuf, P. H. Chem. Commun.
(1) For reviews on gold catalysis, see: (a) Hashmi, A. S. K. Chem. Soc. 1997, 507. (b) Bruneau, C.; Neveux, M.; Kabouche, Z.; Ruppin, C.; Dixneuf,
Rev. 2008, 37, 1766. (b) Li, Z.; Brouwer, C.; He, C. Chem. Rev. 2008, 108, P. H. Synlett 1991, 755. (c) Bruneau, C.; Dixneuf, P. H. Acc. Chem. Res. 1999,
3239. (c) Arcadi, A. Chem. Rev. 2008, 108, 3266. (d) Patil, N.; Yamamoto, Y. 32, 311. (d) Bruneau, C.; Dixneuf, P. H. Angew. Chem., Int. Ed. 2005, 45,
Chem. Rev. 2008, 108, 3395. (e) Li, Z.; Brouwer, C.; He, C. Chem. Rev. 2008, 2176.
108, 3239. (f ) Shen, H. C. Tetrahedron 2008, 64, 3885. (g) Muzart, J. (6) (a) Rotem, M.; Shvo, Y. Organometallics 1983, 2, 1689. (b) Mitsudo,
Tetrahedron 2008, 64, 5815. (h) Skouta, R.; Li, C. J. Tetrahedron 2008, 64, T.; Hori, Y.; Yamakawa, Y.; Watanabe, Y. J. Org. Chem. 1987, 52, 2230.
4917. (i) Furstner, A. Chem. Soc. Rev. 2009, 38, 3208. ( j) Shapiro, N. D.; (c) Ruppin, C.; Dixneuf, P. H. Tetrahedron Lett. 1986, 27, 6323. (d) Ruppin,
Toste, F. D. Synlett 2010, 675. C.; Dixneuf, P. H.; Lecolier, S. Tetrahedron Lett. 1988, 29, 5365. (e) Philippot,
(2) (a) Fukuda, Y.; Utimoto, K.; Nozaki, H. Synthesis 1991, 975. K.; Devanne, D.; Dixneuf, P. H J. Chem. Soc., Chem. Commun. 1990, 119.
(b) Muller, T. E. Tetrahedron Lett. 1998, 39, 5961. (c) Muller, T. E.; Grosche, (f ) Opstal, T.; Verpoort, F. Tetrahedron Lett. 2002, 43, 9259.
M.; Herdtweck, E.; Pleier, A. K.; Walter, E.; Yan, Y. K. Organometallics (7) (a) Doucet, H.; Hofer, J.; Bruneau, C.; Dixneuf, P. H. J. Chem. Soc.,
2000, 19, 170. (d) Mizushima, E.; Hayashi, T.; Tanaka, M. Org. Lett. 2003, 5, Chem. Commun. 1993, 850. (b) Tokunaga, M.; Suzuki, T.; Koga, N.;
3349. (e) Luo, Y.; Li, Z.; Li, C. J. Org. Lett. 2005, 7, 2675. Fukushima, T.; Horiuchi, A.; Wakatsuki, Y. J. Am. Chem. Soc. 2001, 123,
(3) (a) Fukuda, Y.; Utimoto, K. J. Org. Chem. 1991, 56, 3729. (b) 11917. (c) Doucet, H.; MartinVaca, B.; Bruneau, C.; Dixneuf, P. H. J. Org.
Fukuda, Y.; Utimoto, K. Bull. Chem. Soc. Jpn. 1991, 64, 2013. (c) Arcadi, Chem. 1995, 60, 7247. (d) Melis, K.; Samulkiewiecz, P.; Rynkowski, J.;
A.; Cerichelli, G.; Chiarini, M.; Giuseppe, S.; Marinelli, F. Tetrahedron Lett. Verpoort, F. Tetrahedron Lett. 2002, 43, 2713. (e) Gossen, L. J.; Paetzold, J.;
2000, 41, 9195. (d) Teles, J. H.; Brode, S.; Chabanas, M. Angew. Chem., Int. Koley, D. Chem. Commun. 2003, 706.
Ed. 1998, 37, 1415. (e) Hashmi, A. S. K.; Schwarz, L.; Choi, J. H.; Frost, M. (8) (a) Genin, E.; Toullec, P. Y.; Antoniotti, S.; Brancour, C.; Genet, J. P.;
Angew. Chem., Int. Ed. 2000, 39, 2285. (f ) Antoniotti, S.; Genin, E.; Michelet, Michelet, V. J. Am. Chem. Soc. 2006, 128, 3112. (b) Harkat, H.; Weibel,
V.; Genet, J. P. J. Am. Chem. Soc. 2005, 127, 9976. J. M.; Pale, P. Tetrahedron Lett. 2006, 47, 6273. (c) Kang, J.-E.; Shin, S.
(4) For reviews on transition-metal-catalyzed reactions of alkynes, see: Synlett 2006, 717.
(a) Muller, T. E.; Beller, M. Chem. Rev. 1998, 98, 675. (b) Alonso, F.; (9) Roembke, P.; Schmidbaur, H.; Cronje, S.; Raubenheimer, H. J. Mol.
Beletskaya, I. P.; Yus, M. Chem. Rev. 2004, 104, 3079. (c) Bruneau, C.; Catal. A 2004, 212, 35.
Dixneuf, P. H. Angew. Chem., Int. Ed. 2006, 45, 2176. (d) Yamamoto, Y. J. (10) Lee, P. H.; Kim, S.; Park, A. R.; Chary, B. C.; Kim, S. Angew. Chem.,
Org. Chem. 2007, 72, 7817. Int. Ed. 2010, 49, 6806.

7928 J. Org. Chem. 2010, 75, 7928–7931 Published on Web 10/25/2010 DOI: 10.1021/jo101543q
r 2010 American Chemical Society
Chary and Kim
JOC Note
SCHEME 2. Au-Catalyzed Addition of Acids to Alkynes Thus, the remaining reactions were carried out in toluene
at 60 °C using 5 mol % of Ph3PAuCl/AgPF6 to afford the
Markovnikov addition product. Furthermore, to prepare
the isomerized enol esters, the reaction was carried out in
toluene at room temperature using 5 mol % of Ph3PAuCl/
AgOTf.
In order to determine the scope and limitations of the
method, structurally different alkynes and carboxylic
acids were employed under the standard conditions using
much less reactive than Ph3PAuCl/AgOTf, and the reaction 5 mol % of Ph3P-AuCl/AgPF6. As shown in Table 2,
was very slow at room temperature, yielding a small several noteworthy features have been found. First, alkyl-
amount of the product (<10%) after 15 h. As shown in substituted terminal alkynes afforded the Markovnikov
Table 1, the reaction required heating at 80 °C for 15 h and products exclusively without any anti-Markovnikov pro-
a 2:1 mixture of 3 and 4 was obtained (entry 2). Interest- ducts (entries 1-11), but phenylacetylene led to a signifi-
ingly, Ph3PAuCl/AgPF6 catalyst required heating at 60 °C cant amount of the anti-Markovnikov products 2 together
and afforded only the Markovnikov addition product 3 in with 1 (entries 12 and 13) Second, diaryl- and arylalkyl-
82% yield without any isomerization to 4 (entry 3). In substituted alkynes were slower than terminal alkynes
addition, when the reaction was repeated in the presence (entries 16-18). In particular, in the case of diphenylacet-
of allyltrimethylsilane (10 mol %) as an acid scavenger, 3 ylene, the reaction was not complete under prolonged
was isolated in 76% yield (entry 4). Ph3PAuCl/AgSbF6 reflux (entry 16). Third, the addition of carboxylic acids
and Ph3PAuCl/AgNO3 catalyst were totally ineffective, to conjugated alkyne esters proceeded regio- and stereo-
and no reaction occurred in refluxing toluene after 15 h selectively via conjugative trans-addition (entries 14 and
(entries 5 and 6). Similarly, Ph3 PAuCl and AgPF6 were 15). Fourth, aromatic and aliphatic carboxylic acids
also unsuccessful (entries 7 and 8). In addition, to check worked equally well. R,β-Unsaturated carboxylic acids
the possibility of a protic acid catalysis, when the reaction such as acrylic acid and trans-cinnamic acid could be
was carried out in the presence of 5 mol % of triflic acid in successfully employed (entries 10 and 11). Finally, it is
toluene at 60 °C for 15 h, no reaction took place (entry 9). noteworthy that the acidity of carboxylic acids influenced
In addition, in the presence of a trace amount (0.5 mol %) the reaction rate considerably. When 4-nitrobenzoic acid
of triflic acid, the reaction did not occur. Furthermore, the was employed, the reaction was complete within 12 h at
reaction did not proceed in the presence of 5 mol % of 60 °C, whereas the reaction using 4-methoxybenzoic acid
benzenesulfonic acid (entry 10). was required 24 h for completion of the reaction (entries 4
and 6). The reaction using formic acid was complete
TABLE 1. Optimization of Reactiona
within 3 h under the same conditions (entry 3). The most
entry cat. temp (°C) 3 (%) 4 (%)
notable observation was realized with trifluoroacetic acid.
1 PPh3AuCl/AgOTf rt 0 87 The reaction was much faster and occurred at room
2 PPh3AuCl/AgBF4 80 50 25
temperature within 6 h (entry 7). Furthermore, it is note-
3 PPh3AuCl/AgPF6 60 82 0
4 PPh3AuCl/AgPF6b 60 76 0 worthy that vinyl trifluoroacetate was not further isomer-
5 PPh3AuCl/AgSbF6 110 0 0 ized to the more stable thermodynamic isomer under the
6 PPh3AuCl/AgNO3 110 0 0 present strong acidic conditions.
7 PPh3AuCl 110 0 0 We briefly studied the hydroacyloxylation using Ph3PAu-
8 AgPF6 110 0 0
9 TfOH 60 0 0 Cl/AgOTf catalyst (Scheme 3). When the reaction of 1-hex-
10 PhSO2OH 60 0 0 yne with benzoic acid in the presence of 5 mol % catalyst in
a
The reaction was carried out in toluene for 15 h using 5 mol % of toluene at room temperature was monitored by 1H NMR,
catalyst. bIn the presence of 10 mol % of allyltrimethylsilane. somewhat surprisingly, the formation of the Markovnikov
product 7 was not observed after 2 h, although the reac-
The influence of solvent was briefly investigated using tion was incomplete. Thus, to prove the isomerization
5 mol % of Ph3PAuCl/AgPF6. It was found that the present of kinetic enol esters to thermodynamic enol esters by
reaction was very sensitive to solvent, and toluene gave the Ph3PAuCl/AgOTf and to determine its efficiency, the
best result. When the reaction was carried out in dichloro- isomerization of enol benzoate 3 was initially attempted
methane, 1,2-dichloroethane, acetonitrile, ethanol, and tri- using 5 mol % of Ph3PAuCl/AgOTf in deuteriochloro-
fluoroethanol using Ph3PAuCl/AgPF6 catalyst at 60 °C for form at room temperature for 6 h, but no reaction took
15 h, the reaction did not proceed smoothly to give an place. However, when the reaction was carried out in
observable amount of the desired product. The effectiveness
of toluene could be due to stabilization of the cationic SCHEME 3. Au-Catalyzed Addition of Acids to Alkynes
complex by the formation of an arene-gold complex.11

(11) (a) Herrero-Gomez, E.; Nieto-Oberhuber, G.; Lopez, S.; Benet-

Buchholz, J.; Echavarren, A. M. Angew. Chem., Int. Ed. 2006, 45, 5455.
(b) Hintermann, L.; Labonne, A. Synthesis 2007, 1121. (c) Perez-Galan,
P.; Delpont, N.; Herrero-Gomez, E.; Maseras, F.; Echavarren, A. M.
Chem.;Eur. J. 2010, 16, 5324. (d) Corma, A.; Ruiz, V. R.; Leyva-Perez,
A.; Sabater, M. J. Adv. Synth. Catal. 2010, 352, 1701. The reviewer’s
comment regarding the effectiveness of toluene solvent is acknowledged.

J. Org. Chem. Vol. 75, No. 22, 2010 7929

JOC Note Chary and Kim

TABLE 2. Addition of Carboxylic Acids to Alkynes with PPh3AuCl/AgPF6 Catalysta

a
The reaction was carried out with alkyne (1.2 equiv), carboxylic acid (1.0 equiv), and 5 mol % Ph3PAuCl/AgPF6 in toluene. bRatio of 1 and 2. cYield
of recovered diphenylacetylene.

SCHEME 4. Au(I)-Catalyzed Isomerization and occurred very rapidly in toluene. Table 3 summarizes
some experimental results obtained in the isomerization of
the kinetic enol esters to the more stable isomers using
5 mol % of Ph3PAuCl/AgOTf in toluene. The reaction
proceeded cleanly at room temperature.
In conclusion, we have developed the Au(I)-catalyzed addi-
toluene, the isomerization proceeded very fast at room tion of carboxylic acids to alkynes to afford the Markovnikov
temperature and only a small amount of 3 (<10%) was addition products. Furthermore, Ph3PAuCl/AgOTf in toluene
detected after 2 h (Scheme 4). The results obtained here is effective for the isomerization of kinetic enol esters into
indicate that the isomerization was sensitive to solvents thermodynamic isomers.
7930 J. Org. Chem. Vol. 75, No. 22, 2010
Chary and Kim
JOC Note
TABLE 3. PPh3AuCl/AgOTf-Catalyzed Addition of Acids to Alkynesa 33.2, 28.8, 22.2, 13.9; IR (film) 3019.9, 1733.5, 1667.4, 1215.6,
1170.0, 1026.6, 707.4, 665.9 cm-1; HRMS (EI) calcd for C13H16O2
Mþ 227.1048, found 227.1047.
Typical Procedure for the Hydroacyloxylation Using
Ph3PAuCl/AgOTf Catalyst. To a suspension of Ph3PAuCl
(6.1 mg, 0.01 mmol), AgOTf (3.1 mg, 0.01 mmol), and benzoic
acid (30 mg, 0.24 mmol) in toluene (1 mL) was added 1-hexyne
(34 μL, 0.29 mmol) at room temperature. After being stirred for
15 h, the solvent was evaporated under reduced pressure, and
the resulting crude product was separated by silica gel column
chromatography (EtOAc/hexane = 1:10) to give hex-2-en-2-yl
benzoate (diastereomeric ratio 1:3.1, 44 mg, 87%) as a colorless
oil: 1H NMR (CDCl3, 400 MHz) δ 8.05-8.12(m, 2H), 7.56-
a
7.59 (m, 1H), 7.25-7.46(m, 2H), 5.23 (t, J = 7.8 Hz, 1H), 5.09
The reaction was carried out using 5 mol % of PPh3AuCl/AgOTf in (t, J = 7.3 Hz, 1H), 1.96-1.99(m, 5H), 1.34-1.40 (m, 2H), 0.91
toluene at room temperature for 15 h. bIsolated yields. cDiastereomeric (t, J = 6.2 Hz, 3H); 13C NMR (CDCl3, 100 MHz) δ 165.5, 164.6,
ratio.
145.8, 145.2, 133.3, 130.1, 128.6, 128.6, 117.8, 117.4, 28.8, 27.7,
22.9, 22.5, 19.8, 15.5, 13.9; IR (film) 3019.9, 1733.5, 1667.4,
Experimental Section 1215.6, 1170.0, 1026.6,707.4, 665.9 cm-1; HRMS (EI) calcd for
C13H16O2Mþ 205.1229, found 205.1225.
Typical Procedure for Ph3PAuCl/AgPF6-Catalyzed Addition
of Carboxylic Acids to Alkynes. To a suspension of Ph3PAuCl
Acknowledgment. We gratefully acknowledge Nanyang
(10 mg, 0.02 mmol), AgPF6 (5.1 mg, 0.02 mmol), and benzoic
acid (50 mg, 0.41 mmol) in toluene (1 mL) was added 1-hexyne Technological University for financial support.
(56 μL 0.49 mmol) at room temperature. After being stirred at
60 °C for 15 h, the solvent was removed under reduced pressure, Supporting Information Available: Spectral data for all
and the reaction mixture was purified by silica gel column compounds including copies of 1H NMR and 13C NMR spectra.
chromatography (EtOAc/hexane = 1:10) to give hex-1-en-2-yl This material is available free of charge via the Internet at http://
benzoate (69 mg, 82%) as a colorless oil: 1H NMR (CDCl3, 400 pubs.acs.org.
MHz) δ 8.11-8.03 (m, 2H), 7.59-7.53 (m, 1H), 7.47-7.41 (m,
2H), 4.83 (s, 1H), 4.82 (s, 1H), 2.33 (t, J = 7.6 Hz, 2H), 1.55-1.48 Note Added after ASAP Publication. A text correction was
(m, 2H), 1.42-1.33 (m, 2H), 0.91 (t, J = 7.4 Hz, 3H); 13C NMR made to the paragraph above Scheme 3; the new version
(CDCl3, 100 MHz) 164.9, 156.9, 133.4, 130.0, 128.5, 128.4, 101.4, reposted October 27, 2010.

J. Org. Chem. Vol. 75, No. 22, 2010 7931