Gold(I)-catalyzed addition of carboxylic acids to alkynes

Article abstract of DOI:10.1021/jo101543q

Au(I)-catalyzed hydroacyloxylation of alkynes with carboxylic acids is described. PPh₃AuCl/AgPF₆ catalyst affords the Markonikov addition products, whereas PPh₃AuCl/AgOTf catalyst gives the more stable isomerized products

Full text of DOI:10.1021/jo101543q

pubs.acs.org/joc
acids to alkynes catalyzed by transition metals is an efficient
Gold(I)-Catalyzed Addition of Carboxylic Acids to
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
with carboxylic acids has provided an easy access to alk-1-en-
2-yl esters 1 and (Z)-alk-1-enyl esters 2 derived from the
Markovnikov6 and the anti-Markovnikov addition, respec-
tively (Scheme 1).7
Bathoju Chandra Chary and Sunggak Kim*
Division of Chemistry and Biological Chemistry, School of
Physical and Mathematical Sciences, Nanyang Technological
University, Singapore 637371, Singapore
sgkim@ntu.edu.sg
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
To improve this unsatisfactory result and to determine the
scope and limitations of hydroacyloxylation, we have inves-
tigated the addition of carboxylic acids to alkynes using
gold(I) catalysts along with our recent interest in the func-
tionalization of alkynes.10
Au(I)-catalyzed hydroacyloxylation of alkynes with car-
boxylic acids is described. PPh3AuCl/AgPF6 catalyst
affords the Markonikov addition products, whereas
PPh3AuCl/AgOTf catalyst gives the more stable isomer-
ized products via the Markonikov products.
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-
sence of Ph3PAuCl/AgOTf catalyst (5 mol %) at room tem-
perature for 15 h, somewhat surprisingly, an E- and Z-mixture
of a more stable enol benzoate 4 was isolated in 87% yield
(entry 1). Apparently, the initially formed Markovnikov addi-
tion product 3was isomerized completely to the thermodynami-
cally more stable enol benzoate 4. Ph3PAuCl/AgBF4 was
Gold catalysis has attracted a great deal of recent attention
due to its extraordinary versatility in functional group
transformations associated with carbon-carbon multiple
bonds.1 Among various useful functionalizations of alkynes,
Au(I)-catalyzed nucleophilic additions to alkynes proved to
be synthetically useful and include hydroamination,2 hydro-
xylation, and hydroalkoxylation.3 Addition of carboxylic
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3239. (c) Arcadi, A. Chem. Rev. 2008, 108, 3266. (d) Patil, N.; Yamamoto, Y.
Chem. Rev. 2008, 108, 3395. (e) Li, Z.; Brouwer, C.; He, C. Chem. Rev. 2008,
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M.; Herdtweck, E.; Pleier, A. K.; Walter, E.; Yan, Y. K. Organometallics
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Fukuda, Y.; Utimoto, K. Bull. Chem. Soc. Jpn. 1991, 64, 2013. (c) Arcadi,
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Beletskaya, I. P.; Yus, M. Chem. Rev. 2004, 104, 3079. (c) Bruneau, C.;
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Chem. Commun. 1993, 850. (b) Tokunaga, M.; Suzuki, T.; Koga, N.;
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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
JOCNote
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
5 mol % of Ph3P-AuCl/AgPF6. As shown in Table 2,
several noteworthy features have been found. First, alkyl-
substituted terminal alkynes afforded the Markovnikov
products exclusively without any anti-Markovnikov pro-
ducts (entries 1-11), but phenylacetylene led to a signifi-
cant amount of the anti-Markovnikov products 2 together
with 1 (entries 12 and 13) Second, diaryl- and arylalkyl-
substituted alkynes were slower than terminal alkynes
(entries 16-18). In particular, in the case of diphenylacet-
ylene, the reaction was not complete under prolonged
reflux (entry 16). Third, the addition of carboxylic acids
to conjugated alkyne esters proceeded regio- and stereo-
selectively via conjugative trans-addition (entries 14 and
15). Fourth, aromatic and aliphatic carboxylic acids
worked equally well. R,β-Unsaturated carboxylic acids
such as acrylic acid and trans-cinnamic acid could be
successfully employed (entries 10 and 11). Finally, it is
noteworthy that the acidity of carboxylic acids influenced
the reaction rate considerably. When 4-nitrobenzoic acid
was employed, the reaction was complete within 12 h at
60 °C, whereas the reaction using 4-methoxybenzoic acid
was required 24 h for completion of the reaction (entries 4
and 6). The reaction using formic acid was complete
within 3 h under the same conditions (entry 3). The most
notable observation was realized with trifluoroacetic acid.
The reaction was much faster and occurred at room
temperature within 6 h (entry 7). Furthermore, it is note-
worthy that vinyl trifluoroacetate was not further isomer-
ized to the more stable thermodynamic isomer under the
present strong acidic conditions.
much less reactive than Ph3PAuCl/AgOTf, and the reaction
was very slow at room temperature, yielding a small
amount of the product (<10%) after 15 h. As shown in
Table 1, the reaction required heating at 80 °C for 15 h and
a 2:1 mixture of 3 and 4 was obtained (entry 2). Interest-
ingly, Ph3PAuCl/AgPF6 catalyst required heating at 60 °C
and afforded only the Markovnikov addition product 3 in
82% yield without any isomerization to 4 (entry 3). In
addition, when the reaction was repeated in the presence
of allyltrimethylsilane (10 mol %) as an acid scavenger, 3
was isolated in 76% yield (entry 4). Ph3PAuCl/AgSbF6
and Ph3PAuCl/AgNO3 catalyst were totally ineffective,
and no reaction occurred in refluxing toluene after 15 h
(entries 5 and 6). Similarly, Ph3PAuCl and AgPF6 were
also unsuccessful (entries 7 and 8). In addition, to check
the possibility of a protic acid catalysis, when the reaction
was carried out in the presence of 5 mol % of triflic acid in
toluene at 60 °C for 15 h, no reaction took place (entry 9).
In addition, in the presence of a trace amount (0.5 mol %)
of triflic acid, the reaction did not occur. Furthermore, the
reaction did not proceed in the presence of 5 mol % of
benzenesulfonic acid (entry 10).
TABLE 1. Optimization of Reactiona
entry
cat.
temp (°C)
3 (%)
4 (%)
1
2
3
4
5
6
7
8
9
10
PPh3AuCl/AgOTf
PPh3AuCl/AgBF4
PPh3AuCl/AgPF6b
PPh3AuCl/AgPF6
PPh3AuCl/AgSbF6
PPh3AuCl/AgNO3
PPh3AuCl
AgPF6
TfOH
PhSO2OH
rt
80
60
60
110
110
110
110
60
0
50
82
76
0
0
0
0
0
87
25
0
0
0
0
0
0
0
We briefly studied the hydroacyloxylation using Ph3PAu-
Cl/AgOTf catalyst (Scheme 3). When the reaction of 1-hex-
yne with benzoic acid in the presence of 5 mol % catalyst in
toluene at room temperature was monitored by 1H NMR,
somewhat surprisingly, the formation of the Markovnikov
product 7 was not observed after 2 h, although the reac-
tion was incomplete. Thus, to prove the isomerization
of kinetic enol esters to thermodynamic enol esters by
Ph3PAuCl/AgOTf and to determine its efficiency, the
isomerization of enol benzoate 3 was initially attempted
using 5 mol % of Ph3PAuCl/AgOTf in deuteriochloro-
form at room temperature for 6 h, but no reaction took
place. However, when the reaction was carried out in
60
0
0
aThe reaction was carried out in toluene for 15 h using 5 mol % of
catalyst. bIn the presence of 10 mol % of allyltrimethylsilane.
The influence of solvent was briefly investigated using
5 mol % of Ph3PAuCl/AgPF6. It was found that the present
reaction was very sensitive to solvent, and toluene gave the
best result. When the reaction was carried out in dichloro-
methane, 1,2-dichloroethane, acetonitrile, ethanol, and tri-
fluoroethanol using Ph3PAuCl/AgPF6 catalyst at 60 °C for
15 h, the reaction did not proceed smoothly to give an
observable amount of the desired product. The effectiveness
of toluene could be due to stabilization of the cationic
complex by the formation of an arene-gold complex.11
SCHEME 3. Au-Catalyzed Addition of Acids to Alkynes
(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

Chary and Kim
JOCNote
TABLE 2. Addition of Carboxylic Acids to Alkynes with PPh3AuCl/AgPF6 Catalysta
aThe 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-
tion of carboxylic acids to alkynes to afford the Markovnikov
addition products. Furthermore, Ph3PAuCl/AgOTf in toluene
is effective for the isomerization of kinetic enol esters into
thermodynamic isomers.
toluene, the isomerization proceeded very fast at room
temperature and only a small amount of 3 (<10%) was
detected after 2 h (Scheme 4). The results obtained here
indicate that the isomerization was sensitive to solvents
7930 J. Org. Chem. Vol. 75, No. 22, 2010

Chary and Kim
JOCNote
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, 665.9cm-1; HRMS (EI)calcdfor 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
1
oil: H NMR (CDCl3, 400 MHz) δ 8.05-8.12(m, 2H), 7.56-
7.59 (m, 1H), 7.25-7.46(m, 2H), 5.23 (t, J = 7.8 Hz, 1H), 5.09
(t, J = 7.3 Hz, 1H), 1.96-1.99(m, 5H), 1.34-1.40 (m, 2H), 0.91
(t, J = 6.2 Hz, 3H); 13C NMR (CDCl3, 100 MHz) δ 165.5, 164.6,
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,
1215.6, 1170.0, 1026.6,707.4, 665.9 cm-1; HRMS (EI) calcd for
C13H16O2Mþ 205.1229, found 205.1225.
aThe reaction was carried out using 5 mol % of PPh3AuCl/AgOTf in
toluene at room temperature for 15 h. bIsolated yields. cDiastereomeric
ratio.
Experimental Section
Typical Procedure for Ph3PAuCl/AgPF6-Catalyzed Addition
of Carboxylic Acids to Alkynes. To a suspension of Ph3PAuCl
(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
(56 μL 0.49 mmol) at room temperature. After being stirred at
60 °C for 15 h, the solvent was removed under reduced pressure,
and the reaction mixture was purified by silica gel column
chromatography (EtOAc/hexane = 1:10) to give hex-1-en-2-yl
benzoate (69 mg, 82%) as a colorless oil: 1H NMR (CDCl3, 400
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
(m, 2H), 1.42-1.33 (m, 2H), 0.91 (t, J = 7.4 Hz, 3H); 13C NMR
(CDCl3, 100 MHz) 164.9, 156.9, 133.4, 130.0, 128.5, 128.4, 101.4,
Acknowledgment. We gratefully acknowledge Nanyang
Technological University for financial support.
Supporting Information Available: Spectral data for all
compounds including copies of 1H NMR and 13C NMR spectra.
This material is available free of charge via the Internet at http://
pubs.acs.org.
Note Added after ASAP Publication. A text correction was
made to the paragraph above Scheme 3; the new version
reposted October 27, 2010.
J. Org. Chem. Vol. 75, No. 22, 2010 7931