Mild chemo-selective hydration of terminal alkynes catalysed by AgSbF 6

Article abstract of DOI:10.1039/c1cc12928g

The chemo-selective hydration of a wide range of non-activated terminal alkynes catalysed by AgSbF₆ under mild conditions is reported.

Full text of DOI:10.1039/c1cc12928g

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Mild chemo-selective hydration of terminal alkynes catalysed by
AgSbF6w
b
c
Mathieu Bui The Thuong,ab Andre Mann* and Alain Wagner*
´
Received 18th May 2011, Accepted 10th October 2011
DOI: 10.1039/c1cc12928g
The chemo-selective hydration of a wide range of non-activated
terminal alkynes catalysed by AgSbF6 under mild conditions is
reported.
trigger the hydration of unactivated alkynes. In 1993, Marsella
and colleagues reported in a table summarising their catalyst
screen that AgOTf could hydrate 2-methylbut-3yn-2ol with
44% conversion after 70 hours.11 In 1965, Dillard and colleagues
reported that N-propargylamides could be hydrated by
AgNO3.12 Also as previously mentioned, silver salts were used
in the alkyne hydration reaction as co-catalysts to enhance the
reactivity of gold metal species.3b The co-catalyst role played by
silver in the hydration process was not clearly determined, but in
control experiments authors stated ‘‘It should be noted that,
unlike in 1,4-dioxane, silver salts alone catalyze the hydration
reaction in MeOH, but only to a minor extent’’.3b
Hydration of alkynes is a simple and efficient method for the
preparation of valuable carbonyl compounds.1 A variety of metal
based catalysts such as Hg,2 Au,3 Pt,4 Pd,5 Ir,6 and Fe7 have been
employed. These transition metals are prone to catalyse the
addition of water to alkynes following Markovnikov’s rule.
Conversely, the anti-Markovnikov hydration of alkynes forming
aldehydes can be achieved with Ru complexes.8 Although, the
addition of water to the C–C triple bond is a well known chemical
transformation, this reaction has increased in importance during
the past decade, notably with the development of atom economical
reactions.9 Recently, gold catalysts have shown promising results
in terms of efficacy. As an example, Nolan and co-workers
reported the [(NHC)AuI]-catalysed hydration of a wide range of
alkynes at part-per-million loadings using silver as a co-catalyst.3b
Although very effective, the above-mentioned catalytic systems are
not very selective for the hydration of terminal alkynes in the
presence of internal alkynes.
Here, we report that silver salts can efficiently and chemo-
selectively hydrate a wide range of terminal alkynes under mild
conditions. The reaction is very easy to perform, since co-catalysts,
catalyst activators, acids or ligands are not required. 4-Phenyl-
butyne was used as a model system to explore the reaction.
Different silver catalysts were tested using 10 mol% of metal
in a methanol/water mixture: 10/1 at 75 1C for 24 hours. We
found that both the silver source and the counteranion had a
dramatic effect on reaction efficiency. Indeed Ag2O, Ag2CO3,
AgNO2, and AgOAc gave less than 10% conversion. Ag2SO4
gave 40% conversion and AgNO3, AgBF4, and AgOTf gave
around 80% conversion. Finally, AgSbF6 and AgPF6 afforded
complete conversion. From the different silver catalysts tested,
we found that the hydration of 4-phenylbutyne could be
efficiently achieved with 10 mol% of AgSbF6 in a methanol/
water mixture: 10/1 at 75 1C (Table 1, entry 1).
Indeed following our literature review, we were surprised to
find that selective hydration reaction was only observed when
either mercury oxide-boron trifluoride2b or p-methoxybenze-
netellurinic acid anhydride was used as catalyst, which are
toxic and not readily available respectively.10
In the course of our study, we determined that terminal
alkynes could be selectively hydrated by simple silver metal
species (Scheme 1). To the best of our knowledge, only very
few studies could lead one to suspect that Ag is inclined to
Table 1 Optimisation studies
Scheme 1 Silver catalysed hydration of terminal alkynes.
Entry
Catalyst/mol%
T/1C
Yielda (%)
a
´
Novalix Pharma, Bioparc, Bld Sebastien Brant, BP 30170, F-67405
Illkirch CEDEX, France
Laboratoire d’Innovation Therapeutique, Faculte de Pharmacie,
1
2
3
4
5
6
10
5
1
5
5
75
75
75
50
rt
495a
495a
57a
b
c
´
67000 Strasbourg, France. E-mail: andre.mann@pharma.u-strasbg.fr
´
44b
´
Laboratory of Functional ChemoSystems, Faculte de Pharmacie,
0b
67000 Strasbourg, France. E-mail: wagner@bioorga.u-strasbg.fr;
Fax: +33 0368854306; Tel: +33 0368854297
1
120
498b
a
b
w Electronic supplementary information (ESI) available: Experimental
details and the characterization data for all compounds. See DOI:
10.1039/c1cc12928g
Measured by NMR after 24 h reaction. Measured by GC after 24 h
reaction.
c
434 Chem. Commun., 2012, 48, 434–436
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Table 2 AgSbF6 catalysed hydration of terminal alkynesa
To confirm that silver was the true catalyst of the reaction, a
series of control experiments were performed. No hydration
product was detected when the reaction was carried out under
similar conditions without AgSbF6. Similarly, when AgSbF6
was replaced by either NaSbF6 or KPF6, no hydrated product
was detected. Finally, we confirmed that hydration was not
caused by an acid catalysed process: the reaction was performed
in the presence of HBF4 and no ketone could be detected by GC
analysis, moreover the starting material remained unchanged.
Using the same model system, we then varied the temperature
and the catalyst loading. The reaction was complete after
24 hours with 5 mol% catalyst loading (entry 2). Under the
same conditions, use of 1 mol% of catalyst afforded 57% of
hydrated alkyne (entry 2). Notably, a complete conversion was
obtained with 1 mol% of AgSbF6, after 24 hours (entry 6)
under the reaction conditions previously described by Nolan for
the AuI/AgI catalyzed alkyne hydration (MeOH/H2O (2: 1),
120 1C). When the reaction was performed with 5 mol% catalyst
loading, but at the reduced temperature of 50 1C, the percentage
of hydration dropped to 44%. At room temperature, no traces of
hydrated alkyne could be detected by GC analysis of the crude
mixture, and the starting material remained unchanged.
Yieldb
(%)
Entry Alkyne
1
Product
93
2
3
4
5
6
7
8
82
90c
90d,e
78
—
0
89
93f
Considering the reaction conditions, two mechanisms could
be proposed: the direct addition of water to the triple bond
activated by the metal or a two step process, involving the
addition of methanol to the triple bond, forming a transient
enol that could be then hydrolyzed in situ. Therefore, we
performed additional experiments to elucidate the mechanism
of the reaction. We ran the experiment in pure water without
methanol, and while the reaction did occur, the conversion
was very low (10%), however this could be due to the low
solubility of the alkyne. The reaction was then repeated in a
THF/water mixture (10/1) at 75 1C. 4-Phenylbutanone was
obtained with a yield of 55%. It therefore appears that
methanol is not essential in the hydration process, although
the presence of methanol increases the rate of reaction. In light
of these results, the most plausible mechanism is that methanol
attacks the triple bond and undergoes a subsequent hydration
to afford the ketone. This is similar to the mechanism proposed
by Leyva and Corma, who observed that hydration of alkynes
with gold catalysts was faster in the presence of methanol in the
case of terminal alkynes.3c However, we were unable to detect
any of the proposed vinylether or diketal intermediates, by
NMR analysis in the crude mixture or GC analysis.
9
80;0;0g
92d
10
11
80
12
88
13
14
94
82
15
16
92
91
Then we explored the scope of this selective AgSbF6 catalysed
alkyne hydration (Table 2). A number of substrates were tested
under standard conditions. To determine the selectivity of the
Ag catalyst we decided to keep the reaction conditions constant:
10 mol% AgSbF6 catalyst loading in MeOH/H2O (10/1) at
75 1C for 24 hours. Simple aliphatic alkynes, such as 1-decyne
and 1-tetradecyne, were efficiently converted into 2-decanone
and 2-tetradecanone respectively (entries 2 and 3). Arylalkynes
were also hydrated in good yield. Noteworthy, 36 hours were
required for the total conversion of phenylacetylene (entry 4).
Several functionalized aliphatic terminal alkynes were tolerated
as substrates for the hydration reactions: unprotected alcohol
(entry 7), nitrile (entry 10), alkene (entry 11), phthalimide
(entry 12), amide (entry 13). When an alkyne bearing a carboxylic
acid group was hydrated, it was also esterificated during the same
17
18
—
—
0
0
19
89h
a
Reaction conditions: alkyne (1 mmol), AgSbF6 (0.1 mmol), MeOH
d
b
c
(1.5 mL), H2O (0.15 mL), 75 1C. Isolated yield. 20 mol%. GC
conversion. 36 hours. 48 hours. 80% is for X = Cl. Mixture of
keto-enol/diketone (9/1).
e
f
g
h
c
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Chem. Commun., 2012, 48, 434–436 435

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process and gave the corresponding methyl ester (entry 8). With
terminal halides (Cl, Br, I) the hydration operates only with
chlorine, not with Br or I, an evidence for interesting chemo-
selective behaviour of the AgSbF6 catalyst (entry 9). No conver-
sion was obtained with 2-ethynylpyridine (entry 6). Here the lack
of reactivity was attributed to the deactivation of the silver salt by
chelation with the pyridine’s nitrogen. Indeed, we confirmed that
the hydration of 4-phenylbutyne was completely inhibited by
performing the reaction in the presence of one equivalent of
pyridine. Interestingly, propargyl alcohol did not afford the
expected methyl ketone, but underwent the Meyer–Schuster
rearrangement instead (entry 14).13
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We then examined the reactivity of diynes. 1,9-Decadiyne was
dihydrated and gave 2,9-decanedione in 92% yield (entry 15). On
the other hand, the addition of water to 1,5-decadiyne occurred
selectively at the terminal triple bond giving the corresponding
methyl ketone (entry 16).
Next, the hydration of internal alkynes was evaluated. No
reaction occurred with 5-decyne or diphenylacetylene (entries 17
and 18). Interestingly, non-activated internal alkyne remained intact
although most catalytic systems do hydrate them. Conversely,
activated internal alkynes underwent hydration, but probably
through Lewis acid promoted 1–4 nucleophilic addition of water
(entry 19).
In conclusion, we propose a simple and efficient method for
the selective hydration of terminal alkynes. AgSbF6, in aqueous
methanol at 75 1C, enables the reactions to proceed smoothly
and to afford excellent yields, without the need of co-catalysts,
ligands or catalyst activators.14 Furthermore, non-activated
internal alkynes are inert under these reaction conditions,
enabling the selective hydration of terminal alkynes. It has to
be emphasized that silver salts alone are effective catalysts for
alkyne hydration, and that the role of silver as a co-catalyst has
been undervalued in Au promoted hydration. This is currently
being investigated in our laboratory.
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12 N. R. Easton, D. R. Cassad and R. D. Dillard, J. Org. Chem.,
1965, 30, 3084.
This work was supported by Novalix and ANRT. We thank
Dr J. Suffert for the use of the GC mass spectrometer.
Notes and references
13 For
a review on the Meyer-Schuster rearrangement see:
D. A. Engel and G. B. Dudley, Org. Biomol. Chem., 2009, 7, 4149.
14 Caution: dry silver acetylide may decompose violently: see
P. B. Davis and D. H. Scheiber, J. Am. Chem. Soc., 1956, 78, 1675.
1 L. Hintermann and A. Labonne, Synthesis, 2007, 1121.
2 (a) H. Yamamoto and H. Imagawa, Synlett, 2009, 1175;
(b) I. D. Campbell, N. A. Dobson and G. Eglinton, J. Chem.
c
436 Chem. Commun., 2012, 48, 434–436
This journal is The Royal Society of Chemistry 2012