Highly efficient Au1-catalyzed hydration of alkynes

Article abstract of DOI:10.1002/1521-3773(20021202)41:23<4563::AID-ANIE4563>3.0.CO;2-U

As good as gold: Hydration of alkynes by using gold - acid catalyst systems with high turnover frequencies provides a greener synthetic route to carbonyl compounds in high yields, as shown.

Full text of DOI:10.1002/1521-3773(20021202)41:23<4563::AID-ANIE4563>3.0.CO;2-U

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Highly Efficient AuI-Catalyzed Hydration of
Alkynes**
The following aspects about the catalytic system are worth
noting. First, the nature of the reaction medium significantly
affects the reaction. The reaction run without using solvent (in
otherwise the same conditions as the preliminary experiment)
did not furnish 2-octanone. On the other hand, the use of 2-
propanol (71%), dioxane (56%), acetonitrile (53%), or THF
(11%) resulted in a low yield, and the yield obtained with
dichloromethane, DMF, or toluene was even lower. Thus
methanol was the solvent of choice for this particular trans-
formation.[16]
Second, the efficiency of the catalyst was significantly
enhanced by addition of appropriate ligands, which enabled
the quantity of the precious catalyst used to be minimized. For
instance, the control experiment run without ligand addition
under the conditions shown in Table 1 (only 0.01 mol%
Eiichiro Mizushima, Kazuhiko Sato,
Teruyuki Hayashi,* and Masato Tanaka*
Hydration of unsaturated carbon compounds is one of the
most straightforward and environmentally benign methods to
form the carbon oxygen bond. Synthesis of carbonyl com-
pounds by the hydration of alkynes is an important variation
in this category, which has been extensively studied.[1] Acid-
catalyzed hydration of alkynes is long known.[2,3] However,
only electron-rich acetylene compounds, such as alkynyl
ethers, alkynyl thioethers and ynamines react satisfactori-
ly.[1d,4] The reaction of simple alkynes is usually sluggish and
needs cocatalysts, typically toxic mercury(ii) salts, to enhance
the reactivity.[5] More recent interest lies in the use of
transition-metal-complex catalysts containing RuII,[6] RuIII,[7]
Rh,[8] Pt,[9] AuIII,[10] and other metal centers.[11] However, the
process catalyzed by these complexes is not efficient either.
The highest turnover frequency (TOF) is 550 hꢀ1 claimed as
the initial TOF for the hydration of 3-pentyn-1-ol catalyzed by
[cis-PtCl2(tppts)2] (tppts ¼ P(m-C6H4SO3Na)3), but its overall
TOF is no more than approximately 100 hꢀ1.[9c] Recently Teles
and co-workers reported the addition of methanol to alkynes
catalyzed by AuI species in conjunction with acidic cocata-
lysts.[12] Hydration of propargyl alcohol was also briefly
mentioned in their patent application,[13] although the yield
was quite low.[14] Herein we report that the AuI acid systems
in aqueous methanol serve as powerful catalysts,[15] which
promote the hydration of alkynes [Eq. (1)] and have turnover
frequencies of at least two orders of magnitude higher than
[cis-PtCl2(tppts)2].
Table 1. Hydration of 1-octyne in methanol.[a]
Entry
Acid
Additive
Yield[b]
1
2
3
4
5
6
H2SO4
H2SO4
H2SO4
CF3SO3H
CH3SO3H
H3PW12O40
35%
CO (1 atm)
(PhO)3P (0.004 mmol)
99%
77%
80%
99%
90%
[a] Reaction conditions: [(Ph3P)AuCH3] 0.002 mmol, acid 0.5 mmol, 1-
octyne 20 mmol, water 1 mL, methanol 10 mL, 708C, 1 h. [b] GC yield of 2-
octanone.
catalyst) gave 2-octanone in only 35% yield (TOF ¼ 3500 hꢀ1,
entry 1), while the yield dramatically increased to 99% when
the reaction was carried out under an atmosphere of carbon
monoxide (TOF ¼ 9900 hꢀ1, entry 2). Addition of triphenyl
phosphite (2 equiv relative to Au) also boosted the yield, to
90% (TOF ¼ 9000 hꢀ1, entry 3). The reaction of phenylace-
tylene under the standard conditions of Table 1 gave a 14%
yield of acetophenone (TOF ¼ 1400 hꢀ1), while the same
reaction carried out under an atmosphere of carbon mon-
oxide resulted in a 33% yield (TOF ¼ 3300 hꢀ1). Although
the provenance of the ligand effect is ambiguous at this time,
it is envisaged to be associated with the stability of the
catalyst. The reactions without the addition of ligand occa-
sionally proceeded with catalyst deterioration, which could be
observed as metallic particle precipitation. However, when
these reactions were run in the presence of CO, phosphites, or
ethyl diphenylphosphinite, particle formation was not evi-
dent. On the other hand, addition of triphenylphosphane
resulted in a total loss of catalytic activity.
O
R2
[(Ph3P)AuCH3] + acid
R2
R1
R2
(1)
R1
+
H2O
+
R1
MeOH
O
In a preliminary experiment, a mixture of 1-octyne
(1 mmol), [(Ph3P)AuCH3] (0.01 mmol, 1 mol%) and concen-
trated sulfuric acid (0.5 mmol, 50 mol%) in aqueous meth-
anol (1.5 mL, methanol:H2O ¼ 2:1 v/v) was heated for 1 h at
708C affording the corresponding Markovnikov hydration
product, 2-octanone, in 95% yield without anti-Markovnikov
hydration, or possible methanol addition.[12] The reaction did
not proceed in the absence of either the Au catalyst or sulfuric
acid.
Third, other acid catalysts, such as CF3SO3H, CH3SO3H,
and H3PW12O40 (entries 4 6) also gave extremely high yields
even in the absence of the coordinative additives. The reaction
of 1-octyne in the presence of CF3SO3H using only
0.005 mol% of the gold catalyst under otherwise the same
conditions as those in entry 4 gave a 70% yield (TOF ¼
14000 hꢀ1). Since the activity was already high, the effect of
carbon monoxide was only marginal, but a distinct increase in
the yield to 78% (TOF ¼ 15600 hꢀ1) was obtained when the
reaction was run under an atmospheric pressure of carbon
monoxide. The turnover frequency reported herein is the
highest recorded.
[*] Dr. T. Hayashi, Prof. Dr. M. Tanaka, Dr. E. Mizushima, Dr. K. Sato
National Institute of Advanced Industrial Science and Technology
Tsukuba Central 5, Tsukuba, Ibaraki 305-8565 (Japan)
Fax : (þ 81)298-61-4511
E-mail: t.hayashi@aist.go.jp
m.tanaka@res.titech.ac.jp
Prof. Dr. M. Tanaka
Chemical Resources Laboratory
Tokyo Institute of Technology
4259 Nagatsuta, Midori-ku, Yokohama 226-8503 (Japan)
Fax : (þ 81)45-924-5244
[**] E.M. thanks the NEDO for a postdoctoral fellowship.
Angew. Chem. Int. Ed. 2002, 41, No. 23
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Table 2. Gold(i)-catalyzed hydration of alkynes, see Equation (1).[a]
Entry
Alkynes
Adducts
Cat. mol%
Time
Yield[b]
R1
R2
1[c]
2[d]
n-C6H13
n-C4H9
H
H
n-C6H13C(O)CH3
n-C4H9C(O)CH3
0.1
0.2
1 h
2 h
80%
99%
3
H
1.0
1 h
90 %
O
4
5[e]
NC(CH2)3
Cl(CH2)3
H
H
NC(CH2)3C(O)CH3
Cl(CH2)3C(O)CH3
0.2
1.0
1 h
4 h
83%
72 %
44 %[f]
20%[g]
17%[g]
HO
HO
O
6
H
1.0
2 h
CHO
OH
OH
7[h]
H
1.0
2 h
45 %[f]
CHO
O
8[i]
9
C6H5
H
H
H
H
H
H
H
n-C3H7
C6H5
CH3
C6H5C(O)CH3
0.2
0.2
1.0
0.2
0.2
0.2
1.0
0.2
1.0
0.2
1 h
1 h
1 h
1 h
1 h
1 h
1 h
5 h
5 h
5 h
98%
95%
77 %
93%
96%
66%
54 %
92%
53 %
42%
o-CH3OC6H4
m-CH3OC6H4
p-CH3OC6H4
p-CH3C6H4
o-ClC6H4
p-ClC6H4
n-C3H7
o-CH3OC6H4C(O)CH3
m-CH3OC6H4C(O)CH3
p-CH3OC6H4C(O)CH3
p-CH3C6H4C(O)CH3
o-ClC6H4C(O)CH3
p-ClC6H4C(O)CH3
n-C4H9C(O)(n-C3H7)
C6H5CH2C(O)C6H5
10
11
12[i]
13
14
15
16
17[d]
C6H5
n-C3H7
n-C4H9C(O)CH3 n-C3H7C(O)C2H5
34%
[a] Reaction conditions: [(Ph3P)AuCH3], H2SO4 50 mol%, alkyne 1 mmol, water 0.5 mL, methanol 1 3 mL, 708C. [b] GC yield. [c] H2SO4 25 mol%, alkyne
2 mmol. [d] 608C. [e] Run under CO (1 atm). [f] Yield of ketone. [g] Yield of aldehyde. [h] H3PW12O40 was used as acid in place of H2SO4. [i] CF3SO3H was
used as acid in place of H2SO4.
The new procedure was applied to various alkynes as
summarized in Table 2. Besides 1-octynes, other terminal
alkynes, both aliphatic and aromatic, including those bearing
functional groups such as alkoxy, cyano, chloro, and olefinic
groups were all able to undergo hydration under similar
reaction conditions. However, the reactivity significantly
depended on the nature of the substituent, and ligand addition
was occasionally required to obtain acceptable yields.
Phenylacetylene derivatives having electron-donating
groups (entries 8, 9, 11, and 12), reacted smoothly. However,
as the results of o- and p-chlorophenylacetylenes and
m-methoxyphenylacetylene show, electronegative groups
bound to the aromatic ring appear to weaken the reactivity
towards hydration, which suggest that the hydration (en-
tries 10, 13, and 14) mechanism has an electrophilic nature.
Finally, internal alkynes displayed a low reactivity, presum-
ably because of steric hindrance. Diphenylacetylene being less
reactive (entry 16) than more electron-rich 4-octyne (en-
try 15) is in agreement with the forgoing statement on the
nature of the hydration.
In summary, the [(Ph3P)AuCH3] and acid catalyst systems
are highly efficient in the hydration of a wide range of alkynes
in aqueous methanol. The new procedure offers a valuable
alternative to the Wacker oxidation, especially in the field of
total synthesis.
Ethynylcyclohexene and hexynonitrile reacted smoothly
(entries 3 and 4) leading to the formation of the correspond-
ing methyl ketones in good yields. Interestingly, the olefinic
and cyano functional groups remained intact although these
functional groups could be potentially hydrated or hydro-
lyzed. Conversely, the reactions of 5-chloropentyne and
5-hexyn-1-ol did not give satisfactory yields (11 and ~1%
yields in 1 h, respectively) even when 1 mol% catalyst was used
(otherwise identical conditions).[17] Since metallic particle
precipitation was evident in these reactions, the low activity
was a result of the deterioration of the catalyst. When the
reaction with 5-chloropentyne was carried out under an
atmospheric pressure of carbon monoxide for 4 h, the corre-
sponding methyl ketone was obtained with a 72% yield
(entry 5). The yield of the 5-hexyn-1-ol reaction was also
improved in the presence of carbon monoxide or triphenyl
phosphite, resulting in 33 and 31% yields, respectively, over 3 h.
Propargylic alcohols, which are totally inert in the AuIII-
catalyzed hydration,[10a] also reacted smoothly in the new
procedure (entries 6 and 7). However, they afforded mixtures
of methyl ketones (Markovnikov addition) and a,b-unsatu-
rated aldehydes (anti-Markovnikov addition[6] followed by
dehydration[18]), although all the other terminal alkynes
examined formed only Markovnikov adducts.
Experimental Section
Typical procedure (entry 4, Table 1): A mixture of [(PPh3)AuMe] (1.0 mg,
0.002 mmol), CF3SO3H (75 mg, 0.5 mmol), water (1 mL), 1-octyne (2.2 g,
20 mmol) dissolved in methanol (10 mL) was stirred at 708C for 1 h.
Analysis of the resulting mixture by gas chromatography showed the
formation of 2-octanone in 99% yield.
Received: July 3, 2002 [Z19655]
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[14] The authors reported 200 400 turnovers for propynol and but-1-yn-3-
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[16] One reviewer pointed out
a possible mechanism that involves
methanol addition forming a dimethyl acetal as a transient inter-
mediate, which is rapidly hydrolyzed under the acidic conditions to
give the final ketone product. Although we are unable to rigorously
exclude this possibility when the reaction is run in methanol, the
following points strongly support the theory that the reaction involves
the direct attack of water. First, the hydration reaction reported herein
proceeds in non-alcoholic solvents. Second, the regiochemistry of the
hydration reaction is not in full agreement with the methanol addition
reaction. In addition, the [cis-PtCl2(tppts)2]-catalyzed reaction of
alkynes in aqueous methanol showed that hydration proceeds
preferentially, without forming the methanol adduct.[9a] Note that this
platinum-catalyzed hydration was run in the absence of acid
promoters.
[17] The reaction of 5-hexyn-1-ol did not form any other product and the
substrate could be recovered nearly quantitatively.
[18] Acid-catalyzed Rupe-type rearrangement of the starting propargylic
alcohols appeared to be another possibility leading to the formation of
the a,b-unasturated aldehydes. However, the following control
experiments exclude this possibility. A reaction similar to entry 7,
Table 2 run using only H3PW12O40 in the absence of the gold complex
did not furnish the a,b-unsaturated aldehyde and the 1-ethynyl-1-
cyclohexanol was recovered quantitatively. Another control experi-
ment using H3PW12O40 and PPh3 (1 mol% relative to 1-ethynyl-1-
cyclohexanol) in the absence of the gold complex did not form the a,b-
unsaturated aldehyde either. In general, Rupe rearrangement of
tertiary a-acetylenic alcohols gives a,b-unsaturated ketones as the
major product, which is not consistent with our observation. See: S.
Swaminathan, K. V. Narayanan, Chem. Rev. 1971, 71, 429.
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