Ligand- and Acid-Free Gold(I) Chloride Catalyzed Hydration of Terminal Alkynes

Article abstract of DOI:10.1055/s-0035-1560573

Our work shows that simple alkynes can be hydrated by the AuCl/MeOH catalyst system to afford the corresponding methyl ketones in moderate to high yields without any additive, ligand, or acid promoter. This methodology is simpler, milder, and operationally easier than those reported before. The reaction media significantly affects the reaction, and methanol is found to be the best solvent. Both aliphatic and aromatic terminal alkynes were able to undergo hydration, affording moderate to excellent yields under the reaction conditions used in the present work, and excellent functional-group tolerance was also observed. A plausible mechanism for the hydration reaction was proposed.

Full text of DOI:10.1055/s-0035-1560573

SYNLETT
0
9
3
6
-
5
2
1
4
1
4
3
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-
2
0
9
6
©
Georg Thieme Verlag Stuttgart · New York
2015, 26, 2517–2520
2517
letter
Synlett
A. K. Das et al.
Letter
Ligand- and Acid-Free Gold(I) Chloride Catalyzed Hydration of Ter-
minal Alkynes
Atanu Kumar Dasa,c
Sangseung Parka,b
Senthilkumar Muthaiahd
Soon Hyeok Hong*a,b
O
AuCl (5 mol%)
R
CH + H2O
R
MeOH, 65 °C
Me
R = aryl, alkyl
14 examples
1–98% yield
2
a
Department of Chemistry, College of Natural Sciences, Seoul National University,
Seoul 151-747, Republic of Korea
soonhong@snu.ac.kr
Center for Nanoparticle Research, Institute for Basic Science (IBS), Seoul 151-747,
b
Republic of Korea
c
Current address: Center for Molecular Electrocatalysis, Chemical and Materials
Sciences Division, Pacific Northwest National Laboratory, P.O. Box 999, K2-57,
Richland, WA 99352, USA
Department of Chemistry, NIT Kurukshetra, Haryana 136119, India
d
Received: 24.06.2015
Accepted after revision: 12.08.2015
Published online: 08.09.2015
[Au(NHCIPr)Br ].1 Gold(I) catalysts appear to exhibit a
1b
3
broader substrate scope and allow a lower catalyst loading
DOI: 10.1055/s-0035-1560573; Art ID: st-2015-u0469-l
than gold(III). In particular, Hayashi and Tanaka reported
+
the use of [(PPh )AuMe]/H catalytic system that allows
3
Abstract Our work shows that simple alkynes can be hydrated by the
AuCl/MeOH catalyst system to afford the corresponding methyl ke-
tones in moderate to high yields without any additive, ligand, or acid
promoter. This methodology is simpler, milder, and operationally easier
than those reported before. The reaction media significantly affects the
reaction, and methanol is found to be the best solvent. Both aliphatic
and aromatic terminal alkynes were able to undergo hydration, afford-
ing moderate to excellent yields under the reaction conditions used in
the present work, and excellent functional-group tolerance was also ob-
served. A plausible mechanism for the hydration reaction was pro-
posed.
10e
alkyne hydration even at 100 ppm catalyst loading. Nolan
et al. established the [Au(NHCIPr)Cl]/AgSbF6 catalytic sys-
tem,1 which can allow hydration under acid-free condi-
0c
tions, using as low as 10 ppm of catalyst loading. Corma et
10d
al. reported the use of 0.5–5 mol% [Au(SPhos)(NTf )] for
2
the hydration of mostly terminal alkynes at room tempera-
ture.
Although the reported hydration of alkynes with either
acid-generated or in situ generated gold catalysts via chlo-
ride abstraction forming gold(I) cationic complexes was ex-
cellent, no study has been conducted so far using AuCl itself
as a catalyst. We herein present a method by which a
AuCl/MeOH catalyst system can be successfully applied to
the hydration of various terminal alkynes to form ketones.
This methodology is extremely simple, inexpensive, and en-
vironment-friendly; moreover, the hydration of terminal
alkynes produces respective Markovnikov ketones, without
any acid promoters or additives.
Key words hydration, alkynes, ketones, gold, homogeneous catalysis
Hydration is one of the most useful functionalizations of
1
simple unactivated alkynes. Although acids can mediate
the hydration of alkynes, it generally requires a large excess
2
of acidic reagent. In the past, widely employed catalytic
systems were made of toxic mercury(II) salts in acidic me-
3
dia. To avoid the use of toxic mercury(II) salts, applications
of various transition-metal catalysts containing rutheni-
Hydration of phenylacetylene catalyzed by 5 mol% AuCl
was chosen as the standard reaction. In a MeOH solution,
hydration of phenylacetylene afforded acetophenone as the
sole Markovnikov product in 98% yield. The use of 2 mol%
AuCl also gave acetophenone in a good yield (Table 1, entry
4). The nature of the reaction medium significantly affected
the reaction. The use of other solvents, such as EtOH (88%)
and 2-PrOH (72%) resulted in lower yields, and only a trace
amount of the product was obtained in both THF and
MeCN. However, no product was obtained in CH Cl .
4
5
5b,6
palladium(II),7 cop-
um(II), ruthenium(III), rhodium,
per(II) or silver(I), platinum,9 gold(I),10 gold(III),
8
8
1b,11
and
other metal centers were examined. Gold compounds form
an important class of catalysts, favorably replacing toxic
mercury(II) salts. Gold(I) has attracted attention because it
requires mild reaction conditions for product formation.10
Gold(III)-mediated alkyne hydration has also been report-
ed, with emphasis on terminal alkynes. Gold(III) catalysts
1
b
facilitating this transformation include salts such as NaAuCl
4
2
2
and complexes such as BzPPh [Au(NHC )Cl3]1
1a
and
3
mes
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A. K. Das et al.
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Table 1 Optimization of Reaction Conditions
Table 2 (continued)
Entry Alkyne
Ketone
Time Yield
O
AuCl
CH + H2O
a,b
(
h) (%)
solvent, 65 °C
Me
O
7
8
MeO
F
CH MeO
3
97
Entry Catalyst loading Solvent
Time
(h)
Water
GC yield
Me
(
mol%)
(equiv) (%)a
O
1
2
3
4
5
6
7
8
9
5
5
5
2
5
5
5
5
5
5
5
MeOH
3
3
3
3
3
3
3
3
3
3
3
4
98
98
93
82
0
3
81
98
CH
F
24
MeOH–CH
MeOH–CH
MeOH–CH
2
2
2
Cl
Cl
Cl
2
2
2
4
Me
O
1
4
9
Cl
CH
Cl
Br
24 70
24 67
MeOH–H
EtOH
2
O (1:1)
excess
Me
4
4
4
4
4
4
88
72
trace
trace
0
O
2-PrOH
MeCN
THF
10
Br
CH
Me
Me
N
Me
Me
O
11
CH
N
3
3
3
97
82
87
10
2 2
CH Cl
Me
Me
11
H
2
O
0
a
O
O
O
GC yields are the average of at least two runs using dodecane as an internal
Me
Me
HO
3
standard.
12
13
Me
Me
HO
3
CH
CH
CH
Me
Me
Me
Table 2 Hydration of Alkynes12
5
2
5
2
AuCl (5 mol%)
MeOH, 65 °C
O
R
CH + H2O
R
14
24 21
Me
a
Determined by GC using dodecane as an internal standard.
H NMR yields against 1,3,5-trimethoxybenzene as an internal standard.
Entry Alkyne
Ketone
Time Yield
b 1
a,b
(
h) (%)
O
The preliminary screening experiments were carried
1
2
CH
3
3
98
Me
out using a stock solution of phenylacetylene by using do-
decane as the internal standard in MeOH–CH Cl (9:1). The
2
2
Me
Me
amount of CH Cl was kept low to make the solution homo-
2
2
O
98
geneous. However the reaction in only MeOH, afforded a
similar yield (Table 1, entry 1). The result indicates that
CH Cl does not affect the reaction rate in any way. The hy-
CH
Me
2
2
Me
Me
dration did not proceed in the presence of a large excess of
H O (Table 1, entry 5). However, four equivalents of H O (vs.
O
3
3
3
3
98
98
99
2
2
CH
phenylacetylene) gave the best result (Table 1, entries 1 and
).
Me
3
O
The applicability of this catalyst system to other types
4
5
Me
CH
Me
of alkynes is summarized in Table 2. Besides phenylacety-
lene, other terminal alkynes (both aliphatic and aromatic),
including those bearing functional groups such as alkoxy,
chloro, bromo, fluoro, hydroxy, and tertiary amine, also un-
derwent hydration, affording moderate to excellent yields.
Substituted phenylacetylenes, such as 2-, 3-, and 4-ethynyl-
toluene, reacted smoothly, forming the corresponding
methyl ketones in excellent yields (Table 2, entries 2–4).
Similarly, 2-, 3-, and 4-methoxyphenylacetylene gave the
corresponding ketones in excellent yields. The above results
Me
OMe
OMe
O
CH
Me
MeO
MeO
O
6
3
95
CH
Me
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A. K. Das et al.
Letter
are in contrast with the results obtained for the [(PPh )Au-
Me]/H -catalyzed hydration of 3- and 4-methoxyphenyl-
ple bond, and they claimed that the reaction is not only cat-
alyzed by gold(III) but also catalyzed by water at the same
time.13
3
+
acetylene in which 4-methoxyphenylacetylene showed
higher reactivity than 3-methoxyphenylacetylene.10e The
same reaction conditions were applied to halo-substituted
phenylacetylenes such as 4-fluoro-, 4-chloro-, and 4-bro-
mophenylacetylene, and moderate to excellent yields were
obtained (Table 2, entries 8–10), but longer time was need-
ed to complete the reaction. 4-Ethynyl-N,N-dimethylaniline
showed excellent reactivity, forming the corresponding ke-
tone in 97% yield (Table 2, entry 11). Aliphatic alkynes such
as 1-octyne and 1-hexyne gave the corresponding methyl
ketones in good yields; when the substituents such as hy-
droxy groups are attached, the yield is dramatically de-
creased even after conducting the reaction for 24 hours (Ta-
ble 2, entry 14).
The mechanism of this reaction is presumably similar to
that of the reaction that forms with enol ether as a plausible
intermediate.1 We excluded the possibility of a direct at-
tack by water to the alkyne moiety, because no product was
obtained when the reaction was carried out in large excess
0f
of water [MeOH–H O (1:1)] or in pure water (Table 1, en-
2
tries 5 and 11). Only alcoholic solvents gave the respective
ketone whereas no product was obtained in THF, MeCN, or
CH Cl . Among the alcoholic solvents, MeOH afforded the
2
2
best result (98%); the yields decreased when EtOH (88%) or
2-PrOH (72%) was used as the solvent medium. We ob-
served that treatment of AuCl with methanol at room tem-
perature for 15 minutes could form an active catalyst, pro-
1
Different hypotheses for the mechanism of gold(I)-cata-
lyzed hydration of alkynes have been proposed. Tales and
posed to be a [MeO–Au] species. The observation of a H
NMR peak (δ = 3.74 ppm) of the gold-coordinated methyl
group (methyl group of uncoordinated MeOH showed a
peak at δ = 3.37 ppm) in CD Cl supported the formation of
10f
co-workers explained enol ethers and ketals as plausible
intermediates in the hydration of alkynes, based on the iso-
lation of these complexes when the reaction was carried
out in the absence of water. Hayashi, Tanaka, and co-work-
2
2
the [MeO–Au] complex.14 We proposed that the [MeO–Au]
complex activated the alkyne to form gold–alkyne-π com-
plex 2 (Scheme 1). Complex 2 was then attacked by one
molecule of methanol to form intermediate 3 which formed
10e
ers claimed that the reaction proceeded through the di-
rect attack of water to the alkyne, based on the observation
that the reaction occurred in a nonalcoholic medium. How-
ever, they cannot completely exclude the formation of di-
methyl ketals as intermediates under the conditions they
used. In addition, platinum-catalyzed hydration has been
reported to work without forming methanol adducts.9
Laguna and co-workers proposed that the gold(III)-cata-
lyzed hydration of alkynes occurred by the direct attack of
intermediate 4 after immediate rearrangement. A similar
+
rearrangement was observed for the [(Me PAu)]/H -cata-
3
lyzed addition of alcohols to alkynes, where the calculated
–1
activation energy for the rearrangement was 43 kJ mol ,
10f
and the overall process was exothermic. In recent theo-
retical studies, it is suggested that proton-transfer from 4 to
5 by alcoholic solvents or by water decrease activation en-
11a
15
water.
Based on theoretical calculations, Lein and co-
ergy significantly. Further MeOH addition formed the cor-
workers reported the complete mechanism of gold(III)-cat-
alyzed nucleophilic addition of water to an unactivated tri-
responding dimethyl ketal 6 and subsequent demethoxyl-
ation of this intermediate would explain the formation of
product 7.1
0d
AuCl
+
MeOH
HCl + (MeO)Au
R
[
MeO Au]
+
OMe
OMe
1
H
-
H
R
R
R
H
H
5
2
MeO
Au
MeOH
H
+
O
Me
MeOH
MeO Au
R
Me
O
H
H
OMe
OMe
R
R
H
HO+
Au
4
H
R
OMe
2
MeOH
H2O
7
6
3
Scheme 1 Plausible mechanism for the hydration of alkynes using AuCl as the catalyst
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A. K. Das et al.
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In summary, we have demonstrated the hydration of
terminal alkynes using a AuCl/MeOH catalyst system. This
methodology is both atom-economical and operationally
easier than those reported earlier and works without any
additive, ligand, or acid promoter. The catalytic system
showed good to excellent activity toward substituted phe-
nylacetylene and excellent functional-group tolerance;
however, it failed to hydrate internal alkynes. We proposed
that [MeO–Au] is an active catalyst, and the reaction pro-
ceeds through the enol ether intermediate pathway.
(5) (a) Khan, M. M. T.; Halligudi, S. B.; Shukla, S. J. Mol. Catal. 1990,
58, 299. (b) James, B. R.; Rempel, G. L. J. Am. Chem. Soc. 1969, 91,
863.
(
(
6) Blum, J.; Huminer, H.; Alper, H. J. Mol. Catal. 1992, 75, 153.
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Acknowledgment
(
1
f) Teles, J. H.; Brode, S.; Chabanas, M. Angew. Chem. Int. Ed.
998, 37, 1415.
This research was supported by the National Research Foundation of
Korea (NRF-2014R1A2A1A11050028; NRF-2014S1A2A2028156) and
the Institute for Basic Science (IBS-R006-D1), funded by the Korean
Government.
(
11) (a) Casado, R.; Contel, M.; Laguna, M.; Romero, P.; Sanz, S. J. Am.
Chem. Soc. 2003, 125, 11925. (b) de Frémont, P.; Singh, R.;
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Supporting Information
(12) General Procedure for Alkyne Hydration
In a 4 mL reaction vial equipped with a magnetic stirring bar,
AuCl (5.8 mg, 0.025 mmol, 5 mol%) was added to MeOH (1 mL)
under argon atmosphere. The reaction mixture was stirred for 5
min, and then starting material (0.5 mmol, 1.0 equiv) and inter-
nal standard dodecane (1.0 equiv) were added, followed by
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0035-1560573.
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References and Notes
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(
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(
(
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(
(
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(
+
(
Lewis acid assisted Brønsted acid system.
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Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 2517–2520