Efficient hydration of alkynes through acid-assisted Bronsted acid catalysis

Article abstract of DOI:10.1039/c4cc08938c

The combined acid catalyzed hydration of alkynes is an efficient one-step synthesis of carbonyl compounds. This atom-economical method is effective with a wide range of substrates, and the products are obtained in very good yields with low catalyst loading (0.2%). Furthermore, solid acids like Nafion were also efficient and could be easily recycled multiple times without loss of reactivity.

Full text of DOI:10.1039/c4cc08938c

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Efficient Hydration of Alkynes through Acid-
Assisted Brønsted Acid Catalysis
Cite this: DOI: 10.1039/x0xx00000x
Shengzong Liang, Gerald B. Hammond,* Bo Xu*
Received 00th January 2012,
Accepted 00th January 2012
DOI: 10.1039/x0xx00000x
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The combined acid catalyzed hydration of alkynes is an
efficient one-step synthesis of carbonyl compounds. This
atom-economical method is effective with a wide range of
substrates, and the products are obtained in very good yields
with low catalyst loading (0.2%). Furthermore, solid acids
like Nafion were also efficient and could be easily recycled
multiple times without loss of reactivity.
The hydration of alkynes is a straightforward and atom
economical method for the preparation of carbonyl
compounds.1, 2 Indeed, the mercury (II)ꢀcatalyzed hydration of
alkynes has been known for more than a century.3, 4 To avoid
the use of toxic mercury(II) salts, many metal catalysts, such as
Scheme 1 Notable examples of alkyne hydration.
22
Fe,5ꢀ7 Ru,8ꢀ11 Pd,12ꢀ15 Ir,16 Pt,17ꢀ20 Ag,21,
Au23ꢀ27 as well as
other metals28ꢀ34 have been developed. Notable examples
include the [(NHC)AuI] catalyzed alkyne hydration at ppm gold
catalyst loadings by Nolan and coworkers (Scheme 1a)23 and
the cobalt porphyrin complex catalyzed alkyne hydration by
Naka and coworkers, which exhibited good functional group
tolerance (Scheme 1b).35
Compared to metal Lewis acid catalysts, the Brønsted acid
catalysts are generally inexpensive, and, in some cases,
environmentally friendly. Not surprisingly, the metalꢀfree
Brønsted acid (e.g. TfOH, HNTf2) catalyzed alkyne hydrations
are known (Scheme 1c),36ꢀ38 but most of them need very high
Brønsted acid loading (e.g. 20%), long reaction times and high
temperatures. These disadvantages hinder them for wide
synthetic applications. Herein, we are glad to report an acidꢀ
assisted Brønsted acid catalyzed alkyne hydration with very
low catalyst loading (Scheme 2).
The concept of combined acid catalysis was first proposed by
Yamamoto and coworkers, which included Brønsted acidꢀ
assisted Brønsted acid (BBA) catalysis and Lewis acidꢀassisted
Brønsted acid (LBA) catalysis.39 Based on this concept, we
proposed that the acidity of a weak Brønsted acid like acetic
acid can be enhanced significantly by combining it with a
Brønsted acid or Lewis acid (Scheme 2). This enhanced acidity
may speed up the hydration of alkynes. What’s more, there are
many readily available Brønsted acids and Lewis acids to
choose from and each of them has different acid strength and
counterions, so we can fine tune the reactivity of the combined
acid system to achieve the best efficiency.
Department of Chemistry, University of Louisville, Louisville, Kentucky 40292, USA
E-mail: bo.xu@louisville.edu and gb.hammond@louisville.edu, Fax: (+) 1-502-852-
5998
Scheme 2 Concept of combined acid catalysis.
†
Electronic supplementary information (ESI) available: Detailed experimental
We used the hydration of phenyl acetylene 1a as our model
reaction (Table 1). As expected, the weak Brønsted acid acetic
procedures and 1HꢀNMR of compounds. See DOI: 10.1039/c000000x/
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acid itself did not promote the hydration of 1a (Table 1, entry quantitative yields of hydration products 2 (Table 2, entries 2ꢀ4).
1) even at 120oC, but the combination of acetic acid with only a Terminal aliphatic alkyne also worked well (Table 2, entry 5). The
very mild Lewis acid (KCl) gave a 16% conversion under the hydration of internal alkynes was slower than that of terminal
same conditions (Table 1, entry 2). The combination of acetic alkynes, and a slightly higher catalyst loading (1 mol %) was needed
acid with a slightly stronger Lewis acid (LiNTf2) gave a good to achieve good yields (Table 2, entries 6ꢀ8). Alkenes and carboxylic
yield of the hydration product 2a (Table 1, entry 3). We also acids were well tolerated (Table 2, entries 9 and 11), but the ꢀOH
tried to lower the loading of the acid coꢀcatalyst and reduce the group in 1ꢀethynylcyclohexanol (1j) did not survive the hydration
temperature: the combination of AcOH with a strong Brønsted condition (Table 2, entry 10). Hydration of ethyl phenylpropiolate
o
acid TfOH (0.5%) was very efficient at 100 C (Table 1, entry (1l) gave the decarboxylation product 2a in 70% yield (Table 2,
4). TsOH, HBF4·Et2O, and Tf2NH were less efficient (Table 1, entry 12). An antiꢀMarkovnikov product cinnamaldehyde (2m) was
entries 5ꢀ7). Super acid Tf3CH40 also gave a very good yield of
Table 2 Scope of the LBA alkyne hydration
product (Table 1, entry 8). These results indicated that a
Brønsted acidꢀassisted Brønsted acid (BBA) combination was
able to catalyze the hydration of 1a at low catalyst loadings (0.5
mol %). Then, we explored the viability of using a Lewis acidꢀ
assisted Brønsted acid (LBA) system because there are more
choices of available Lewis acids. Most of the AcOH/Lewis acid
combinations tested were effective (Table 1, entries 9ꢀ12).
Among them, Ga(OTf)3 (Table 1, entry 12) gave the best
reactivity. We could further lower the catalyst loading down to
0.2% by increasing the concentration of 1a (Table 1, entry 13).
The combination of AcOH and Ga(OTf)3 is important; without
AcOH Ga(OTf)3 is not a good catalyst for the hydration
reaction (Table 1, entry 14).
Table 1 Screening for the best conditions of alkyne hydration.
entry
co-catalyst
(mol %)
condition
Yieldb
(%)
1
-
Mw,a 120 oC, 1 h
Mw,a 120 oC, 1 h
Mw,a 120 oC, 1 h
100 oC, 10 h
100 oC, 24 h
100 oC, 24 h
100 oC, 24 h
100 oC, 10 h
100 oC, 14 h
100 oC, 12 h
100 oC, 10 h
100 oC, 8 h
trace
16
2
KCl (4%)
3
LiNTf2 (4%)
93
4
TfOH (0.5%)
TsOH (0.5%)
HBF4·Et2O (0.5%)
Tf2NH (0.5%)
Tf3CH (0.5%)
Yb(OTf)3 (0.5%)
Sc(OTf)3 (0.5%)
In(OTf)3 (0.5%)
Ga(OTf)3 (0.5%)
Ga(OTf)3 (0.2%)
Ga(OTf)3 (0.5%)
99
5
Trace
4
6
7
56
8
99
9
99
10
11
12
13c
14d
99
99
99
100 oC, 6 h
120 oC, 1 h
99
trace
a Mw = Microwave. b 1H NMR Yield. c [1a] = 2.5 M. d The reaction was
conducted in dioxane.
1
b
aYields were determined by H NMR. Condition A: [1] = 2.5 M in HOAc,
o
c
H2O (1 equiv), Ga(OTf)3 (0.2 mol %), 100 C using oil bath. Condition B:
With the optimized conditions in hand (AcOH/TfOH or
AcOH/Ga(OTf)3), we explored the substrate scope of this new
methodology (Table 2). Substituted phenyl acetylenes with either
electronꢀdonating or electron–withdrawing groups all gave close to
o
[1] = 2.5 M in HOAc, H2O (1 equiv), Ga(OTf)3 (1 mol %), 100 C using
microwave. dCondition A with Ga(OTf)3 (1 mol %). eCondition B with
Ga(OTf)3 (1 mol %) at 90oC. fCondition A with H2O (2 equiv) and a
microwave was used.
2 | Chem. Commun., 2014, 00, 1-4
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formed in the hydration of propargyl acetate (1m) (Table 2, entry 13).
Finally, hydration of diyne (1n) also gave the expected diꢀhydration
product 2n in good yield (Table 2, entry 14).
Considering the use of relative inconvenient solvent (HOAc), we
furthermore tested the hydration reaction in dioxane in the presence
of catalytic amount of combined acid (eq 1). It turned out that 90%
of the hydrolysis product was obtained with 10% of unreacted 1a left
after 70 minutes in a microwave. Therefore, compared to two control
experiments (Table 1, entries 1 and 14), this result clearly showed
that the LBA system is very efficient for hydration of alkyne.
Scheme 4 Examples of BBA alkyne hydration using Nafion NR50.
It should be noted that our combined acid catalysis sometimes had
higher or different regioselectivities compared to transition metals
(e.g., Au) catalyzed counterparts due to different reaction
mechanisms. For example, the hydration of phenyl substituted
internal alkyne 1h (Table 2, entry 8) produced the aryl ketone isomer
(2h), but the gold catalyzed hydration of 1h gave a mixture of two
isomers.23 In a more extreme case, the gold catalyzed hydration of
propargyl acetate gave the Markovnikov product 3m (Scheme 3b).41,
42 However, our system furnished the antiꢀMarkovnikov product 2m
exclusively (Scheme 3a). The regioselectivity of our system can be
rationalized by relative stability of the corresponding carbocation
intermediates.
process, the acidity of either Ga(OTf)3 or HOAc was not strong
enough to activate the triple bond of alkyne, but the combined
system of them (LBA) provided much stronger acidity than when
one of them was used. To capture the possible enol acetate
intermediate we conducted the hydration of 1a under anhydrous
condition. We found that even in the absence of water we can still
obtain hydration product 2a in 92% yield along with acetic acid
anhydride (Scheme 5), but no enol acetate was observed. It has been
reported that acid can catalyze the acetoxylysis of enol acetate to
give corresponding ketone and acid anhydride (Scheme 5).43 So one
plausible explanation for formation of acid anhydride is that the
reaction went through our proposed enol acetate intermediate 4.
OAc
H2O (1 equiv), Ga(OTf)3 (0.2 mol %)
(a)
HOAc, 100 o
C
CHO
1m
1m
2m, 96%
OAc
OAc
Ph3PAuCl/AgSbF6
dioxane/H2O
(b)
O
3m 97%
Scheme 3 Regioselectivity for hydration of 1m
.
Scheme 5 Hydration of 1a using anhydrous acetic acid.
We also examined the feasibility of using solid acids in our LBA
or BBA strategy for alkyne hydration because heterogeneous solid
acids can be easily recycled and are less corrosive than acids in
solution phase. We investigated common solid acids catalysts such
as Zeolite (ZSMꢀ5) and Nafion. ZSMꢀ5 showed relatively slow
reaction on the hydration of phenylacetylene 1a (71% after 24 hours).
Nafion gave a much better result, it could be easily reused and did
not lose its reactivity after 3 reaction cycles (Scheme 4a). We also
tested two other alkyne substrates 1b and 1g, both of which gave
similar results as those obtained with Ga(OTf)3 (Scheme 4b and 4c).
In summary, we have developed a highly efficient acidꢀassisted
Brønsted acid catalysis system for alkyne hydration. This
methodology worked well for various alkyne substrates using very
low catalyst loading. Furthermore, solid acids like Nafion were also
efficient and could be recycled easily multiple times without loss of
reactivity
.
Acknowledgements
We are grateful to the National Science Foundation for financial
support (CHEꢀ1111316 and CHEꢀ1401700).
Nafion
is
a
tetrafluoroethyleneꢀbased
copolymer
with
perfluroalkanesulfonic acid functionality; its excellent performance
could be due to its higher acidity (compared to Zeolite).
Notes and references
The possible reaction pathway of this transformation was also
investigated. Although acetic acid is a weak nucleophile compared to
water, due to its high concentration (as solvent) it is possible that
hydroacetoxylation reaction takes place first followed by hydrolysis
1.
2.
3.
F. Alonso, I. P. Beletskaya and M. Yus, Chem. Rev., 2004, 104,
3079ꢀ3160.
L. Hintermann and A. Labonne, Synthesis, 2007, 2007, 1121ꢀ
1150.
M. Kutscheroff, Chem. Ber., 1884, 17, 13ꢀ29.
M. Kutscheroff, Chem. Ber., 1881, 14, 1540ꢀ1542.
of the enol acetate intermediate to give ketone product 2. In this 4.
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ChemComm
Page 4 of 4
View Article Online
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DOI: 10.1039/CC4hCeCm08C93o8mCm
5.
X.ꢀF. Wu, D. Bezier and C. Darcel, Adv. Synth. Catal., 2009, 351, 43.
367ꢀ370.
H. J. Hagemeyer and D. C. Hull, Ind. Eng. Chem., 1949, 41,
2920ꢀ2924.
6.
J. R. CabreroꢀAntonino, A. LeyvaꢀPérez and A. Corma, Chem.
Eur. J., 2012, 18, 11107ꢀ11114.
7.
J. Park, J. Yeon, P. H. Lee and K. Lee, Tetrahedron Lett., 2013,
54, 4414ꢀ4417.
8.
M. Tokunaga and Y. Wakatsuki, Angew. Chem. Int. Ed., 1998, 37,
2867ꢀ2869.
9.
L. Ackermann and L. T. Kaspar, J. Org. Chem., 2007, 72, 6149ꢀ
6153.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
D. B. Grotjahn and D. A. Lev, J. Am. Chem. Soc., 2004, 126,
12232ꢀ12233.
J. Halpern, B. R. James and A. L. W. Kemp, J. Am. Chem. Soc.,
1961, 83, 4097ꢀ4098.
C. Xu, W. Du, Y. Zeng, B. Dai and H. Guo, Org. Lett., 2014, 16,
948ꢀ951.
X. Li, G. Hu, P. Luo, G. Tang, Y. Gao, P. Xu and Y. Zhao, Adv.
Synth. Catal., 2012, 354, 2427ꢀ2432.
Y. Fukuda, H. Shiragami, K. Utimoto and H. Nozaki, J. Org.
Chem., 1991, 56, 5816ꢀ5819.
A. LeyvaꢀPérez, J. R. CabreroꢀAntonino, P. RubioꢀMarqués, S. I.
AlꢀResayes and A. Corma, ACS Catal., 2014, 4, 722ꢀ731.
S. y. Kim, C. S. Chin and M.ꢀS. Eum, J. Mol. Catal. A: Chem.,
2006, 253, 245ꢀ248.
D. W. Lucey and J. D. Atwood, Organometallics, 2002, 21, 2481ꢀ
2490.
W. Baidossi, M. Lahav and J. Blum, J. Org. Chem., 1997, 62,
669ꢀ672.
J. W. Hartman, W. C. Hiscox and P. W. Jennings, J. Org. Chem.,
1993, 58, 7613ꢀ7614.
W. Hiscox and P. W. Jennings, Organometallics, 1990, 9, 1997ꢀ
1999.
M. B. T. Thuong, A. Mann and A. Wagner, Chem. Commun.,
2012, 48, 434ꢀ436.
Z.ꢀW. Chen, D.ꢀN. Ye, Y.ꢀP. Qian, M. Ye and L.ꢀX. Liu,
Tetrahedron, 2013, 69, 6116ꢀ6120.
N. Marion, R. S. Ramon and S. P. Nolan, J. Am. Chem. Soc.,
2009, 131, 448ꢀ449.
E. Mizushima, D.ꢀM. Cui, D. C. D. Nath, T. Hayashi and M.
Tanaka, Organic Syntheses, 2006, 83, 55ꢀ60.
E. Mizushima, K. Sato, T. Hayashi and M. Tanaka, Angew.
Chem., Int. Ed., 2002, 41, 4563ꢀ4565.
26.
27.
Y. Fukuda and K. Utimoto, J. Org. Chem., 1991, 56, 3729ꢀ3731.
R. Casado, M. Contel, M. Laguna, P. Romero and S. Sanz, J. Am.
Chem. Soc., 2003, 125, 11925ꢀ11935.
28.
D. B. Grotjahn and D. A. Lev, J. Am. Chem. Soc., 2004, 126,
12232ꢀ12233.
29.
30.
W.ꢀJ. Liu and J.ꢀH. Li, Youji Huaxue, 2006, 26, 1073ꢀ1078.
A. Vasudevan and M. K. Verzal, Synlett, 2004, DOI: 10.1055/sꢀ
2004ꢀ817749, 631ꢀ634.
31.
32.
I. K. Meier and J. A. Marsella, J. Mol. Catal., 1993, 78, 31ꢀ42.
A. Finiels, P. Geneste, M. Lasperas, F. Marichez and P. Moreau,
Stud. Surf. Sci. Catal., 1991, 59, 565ꢀ571.
33.
34.
35.
36.
A. Finiels, P. Geneste, F. Marichez and P. Moreau, Catal. Lett.,
1989, 2, 181ꢀ184.
G. A. Olah and D. Meidar, Synthesis, 1978, DOI: 10.1055/sꢀ1978ꢀ
24845, 671ꢀ672.
T. Tachinami, T. Nishimura, R. Ushimaru, R. Noyori and H.
Naka, J. Am. Chem. Soc., 2013, 135, 50ꢀ53.
S. Kamiguchi, I. Takahashi, K. Kondo, S. Nagashima, H.
Kurokawa, H. Miura and T. Chihara, J. Cluster Sci., 2007, 18,
845ꢀ853.
37.
T. Tsuchimoto, T. Joya, E. Shirakawa and Y. Kawakami, Synlett,
2000, 1777ꢀ1778.
38.
39.
N. Menashe and Y. Shvo, J. Org. Chem., 1993, 58, 7434ꢀ7439.
H. Yamamoto and K. Futatsugi, Angew. Chem. Int. Ed., 2005, 44,
1924ꢀ1942.
40.
41.
T. Akiyama, Chem. Rev., 2007, 107, 5744ꢀ5758.
N. Ghosh, S. Nayak and A. K. Sahoo, J. Org. Chem., 2011, 76,
500ꢀ511.
42.
D. Wang, R. Cai, S. Sharma, J. Jirak, S. K. Thummanapelli, N. G.
Akhmedov, H. Zhang, X. Liu, J. L. Petersen and X. Shi, J. Am.
Chem. Soc., 2012, 134, 9012ꢀ9019.
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