Hydration of terminal alkynes catalyzed by water-soluble cobalt porphyrin complexes

Article abstract of DOI:10.1021/ja310282t

Water-soluble cobalt(III) porphyrin complexes were found to promote the hydration of terminal alkynes to give methyl ketones. The alkyne hydration proceeded in good to excellent yield with 0.1 to 2 mol % cobalt catalyst 1 and was compatible with the presence of acid/base- or redox-sensitive functional groups such as alkyl silyl ethers; allyl ethers; trityl ethers; benzyl ethers; carboxylic esters; boronic esters; carboxamides; nitriles; and nitro, iodo, and acetal groups. Some of the alkyne substrates tested here are otherwise difficult to hydrate. The alkyne hydration can be performed on a gram scale, and the catalyst can be recovered by aqueous workup.

Full text of DOI:10.1021/ja310282t

Communication
pubs.acs.org/JACS
Hydration of Terminal Alkynes Catalyzed by Water-Soluble Cobalt
Porphyrin Complexes
Tadashi Tachinami,† Takuho Nishimura,† Richiro Ushimaru,† Ryoji Noyori,†,‡ and Hiroshi Naka*,†,‡
†Department of Chemistry, Graduate School of Science, Nagoya University, Chikusa, Nagoya 464-8602, Japan
‡Research Center for Materials Science, Nagoya University, Chikusa, Nagoya 464-8602, Japan
S
* Supporting Information
Scheme 1. Hydration of Terminal Alkynes Bearing
Functional Groups
ABSTRACT: Water-soluble cobalt(III) porphyrin com-
plexes were found to promote the hydration of terminal
alkynes to give methyl ketones. The alkyne hydration
proceeded in good to excellent yield with 0.1 to 2 mol %
cobalt catalyst 1 and was compatible with the presence of
acid/base- or redox-sensitive functional groups such as
alkyl silyl ethers; allyl ethers; trityl ethers; benzyl ethers;
carboxylic esters; boronic esters; carboxamides; nitriles;
and nitro, iodo, and acetal groups. Some of the alkyne
substrates tested here are otherwise difficult to hydrate.
The alkyne hydration can be performed on a gram scale,
and the catalyst can be recovered by aqueous workup.
atalytic hydration of C−C triple bonds is of particular
Cinterest in organic synthetic chemistry, as it provides
important carbonyl compounds for both the bulk and fine
chemical industries. In this respect, Markovnikov hydration of
alkynes is an ideal method for the synthesis of ketones; the
alkyne hydration should proceed using water as a reagent with
100% atom economy if a suitable catalyst is available.1 Terminal
alkynes are frequently used as substrates because Markovnikov
hydration of terminal alkynes generally gives the methyl
ketones exclusively.1a,2−10 Mercury(II) salts combined with
acids, such as HgO/H2SO4 and HgO/BF3, are reliable catalysts
for the hydration of alkynes and were widely used until the
discovery of the potential toxicity of mercury compounds.2
Alternative metallic catalysts have been sought over the years,
mainly among transition metals, such as Pt,3 Fe,4 Pd,5 Ir,6 Ag,7
Sn−W,8 and Au.9 Whereas most of these metals have lower
reactivity and selectivity than mercury, gold complexes can
efficiently catalyze the hydration of alkynes. For example,
(Ph3P)AuCH3/H2SO4 mediates the hydration of 1-octyne with
a high turnover frequency.9d Alkyne hydration using the
(IPr)AuCl/AgSbF6 [IPr = 1,3-bis(2,6-diisopropylphenyl)-
imidazol-2-ylidene] or (IPr)AuOH/HSbF6 system affords a
high turnover number.9g,k These systems are efficient for the
hydration of simple alkynes.11 A single-component catalyst,
AuSPhosNTf2, [SPhos = dicyclohexyl(2′,6′-dimethoxybiphen-
2-yl)phosphine] catalyzes the hydration of alkynes bearing
various functional groups at room temperature.9h Nevertheless,
the development of more chemoselective hydration of
functionalized terminal alkynes remains a challenge for fine
organic synthesis, as certain acid-labile functional groups are
not well tolerated under the conditions typically used for
mercury- or gold-catalyzed alkyne hydration (Scheme 1). To
overcome these deficiencies, we have developed a method for
hydration of terminal alkynes in the presence of the water-
soluble cobalt(III) porphyrin complex 1.12 This complex
catalyzes the hydration of various terminal alkynes, including
acid-sensitive substrates that are otherwise difficult to hydrate
(Scheme 1).
We initially found that the combination of cobalt dichloride
and a porphyrin ligand promotes the hydration of terminal
alkynes (Table 1). When a methanol solution of 1-decyne (2a,
0.50 mmol), water (0.4 mL, 22 mmol), cobalt dichloride (2 mol
%), and tetrakis(p-sulfonatophenyl)porphyrin tetrasodium salt
(Na4H2TPPS, 2 mol %) was heated at 100 °C for 12 h under an
aerobic atmosphere in a closed glass vessel, 2a was completely
consumed, giving 2-decanone (3a) in 92% yield (entry 1). Use
of other metal chlorides or HCl instead of CoCl2 resulted in
decreased conversion of 2a (entries 2−9). The reaction was not
promoted in the absence of CoCl2 or Na4H2TPPS (entries 10
and 11). The use of an argon atmosphere instead of and aerobic
atmosphere resulted in a decrease in conversion (entry 12).13
The use of salen ligands instead of Na4H2TPPS was less
effective, and other ligands such as dipyrromethenes,
bipyridines, terpyridines, salans, and salalens gave no desired
product. Other substituted porphyrins were also effective
(Table S1 in the Supporting Information), but we chose
Na4H2TPPS because it can easily be separated from the
product. At a catalyst loading of 0.1 mol %, CoCl2/Na4H2TPPS
promoted the hydration of 2a but with decreased conversion
Received: October 17, 2012
© XXXX American Chemical Society
A
dx.doi.org/10.1021/ja310282t | J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
Communication
Table 1. Screening of Precatalysts for the Hydration of 1-
Decyne (2a) to 2-Decanone (3a)
Table 2. Hydration of Terminal Alkynes 2b−n Using 1 To
a
a
Give Ketones 3b−n
b
entry
precatalyst (mol %)
conv. (%)
c
1
CoCl2 (2), Na4H2TPPS (2)
CrCl2 (2), Na4H2TPPS (2)
MnCl2 (2), Na4H2TPPS (2)
FeCl2 (2), Na4H2TPPS (2)
FeCl3 (2), Na4H2TPPS (2)
NiCl2 (2), Na4H2TPPS (2)
CuCl2 (2), Na4H2TPPS (2)
ZnCl2 (2), Na4H2TPPS (2)
HCl (200), Na4H2TPPS (2)
Na4H2TPPS (2)
>99 (92 )
2
<5
50
17
21
56
<1
<1
<1
<1
<1
34
59
24
96
25
3
4
5
6
7
8
9
10
11
CoCl2 (2)
d
12
CoCl2 (2), Na4H2TPPS (2)
CoCl2 (0.1), Na4H2TPPS (0.1)
1 (0.1)
e
13
e
14
e
15
1 (0.1), HNTf2 (0.3)
de
,
16
17
1 (0.1), HNTf2 (0.3)
ef
,
c
1 (0.3), HNTf2 (0.3)
>99 (96 )
a
Conditions: [2a]0 = 0.20 M, precatalyst (2 mol %), H2O (44 equiv).
Reactions were carried out at 100 °C for 12 h under aerobic conditions
in closed glass vessels, unless otherwise noted. Na4H2TPPS denotes
b
tetrakis(p-sulfonatophenyl)porphyrin tetrasodium salt. Of alkyne 2a,
c
determined by GC using tridecane as an internal standard. Isolated
d
yield of 3a. The reaction was carried out under an argon atmosphere.
e
f
[2a]0 = 0.80 M, H2O (4.4 equiv). 80 °C.
(entry 13). Because the UV−vis spectra of the reaction media
indicated the presence of cobalt(III) porphyrin complexes, we
prepared tetrakis(p-sulfonatophenyl)porphyrin cobalt(III) tri-
sodium salt hexahydrate (1).12,13 Cobalt complex 1 is a bench-
stable, purple solid, and its aqueous solution (5 mM) is near-
neutral (pH 6.9−7.0). Precatalyst 1 was found to promote the
hydration of 2a to give 3a under near-neutral pH conditions
(entry 14). The alkyne hydration was even faster in the
presence of acid [triflimide (HNTf2), 0.3 mol %] (96%; entry
15). Again, the use of an aerobic atmosphere was necessary to
maintain high catalytic activity. When the reaction was carried
out under argon under otherwise identical conditions, 3a was
obtained in low yield and a reduced cobalt(II) porphyrin
complex was detected in the reaction mixture (entry 16). Thus,
2a (5.0 mmol) was hydrated at 80 °C under aerobic, acidic
conditions, giving ketone 3a in 96% isolated yield (entry 17).
As listed in Table 2, cobalt complex 1 allowed hydration of
various terminal alkynes 2, affording the methyl ketones 3.
Hydration of 1,8-nonadiyne (2b) gave diketone 3b in 90% yield
with an increased amount of 1 (entry 1).11,14 Alkyne 2c
containing an alkyl tert-butyldiphenylsilyl (TBDPS) ether
group was tested, as the alkyl silyl ether functionality is
frequently used in organic synthesis15 but is often cleaved
under the conditions typically used for alkyne hydration using
mercury or gold catalysis.16 To our delight, cobalt porphyrin 1
served as an excellent precatalyst for the hydration of alkyne 2c
to give ketone 3c. When a methanol solution of 2c, water, and
1 was heated at 80 °C for 5 h under an aerobic atmosphere
with no acidic additive, the corresponding methyl ketone 3c
was obtained in 93% yield (entry 2). The more challenging tert-
butyldimethylsilyl (TBDMS) and trityl (Tr) ethers showed
a
Reactions were run in methanol with [2]0 = 0.80 M and H2O (4.4
equiv) at 80 °C under aerobic conditions in a closed reaction vessel,
unless otherwise noted. TBDPS = tert-butyldiphenylsilyl [t-
C4H9(C6H5)2Si]. TBDMS
C4H9(CH3)2Si]. Tr = trityl [(C6H5)3C]. Isolated yields. H2O (8.9
equiv). Without HNTf2, [2]0 = 0.10 M, H2O (22 equiv). The rest of
the material was deprotected.
= tert-butyldimethylsilyl [t-
b c
d
e
good stability under the same reaction conditions, providing
ketones 3d and 3e in 75 and 91% yield, respectively (entries 3
and 4). Hydration of alkyne 2f bearing a benzoic ester
functionality gave the corresponding ketone 3f satisfactorily
(entry 5). The terminal alkene in the allylic ether of 2g
remained intact under the slightly acidic reaction conditions,
and 3g was obtained in 92% yield (entry 6). Thus, this
hydration method is complementary to the palladium-catalyzed
Wacker reaction of terminal alkenes.17
The present catalytic system is also applicable to aromatic
alkynes (Table 2, entries 7−13). For instance, phenylacetylene
(2h) was smoothly hydrated under typical conditions, affording
acetophenone (3h) in 92% yield (entry 7). Aromatic alkynes
2i−l were hydrated to give substituted acetophenones 3i−l in
good to excellent yields without loss of the respective tert-butyl,
B
dx.doi.org/10.1021/ja310282t | J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
Communication
amide, iodo, and boronic ester functionalities (entries 8−11).
The tolerance of the iodo and boronic ester groups indicates
the immediate utility of the product for cross-coupling
chemistry. Hydration of electron-deficient aromatic alkynes
has been considered difficult to achieve because of the
decreased π-basicity of such alkynes toward soft Lewis acid
catalysts.1a The present cobalt catalysis is effective for these
substrates. The use of 2 mol % 1 and 0.30 mol % HNTf2
allowed complete hydration of p-cyanophenylacetylene (2m)
and p-nitrophenylacetylene (2n) to give the ketones 3m and
3n, respectively (entries 12 and 13). Interestingly, the tolerance
of the cyano group in 2m under the cobalt-catalyzed alkyne
hydration conditions contrasts with the case of the catalytic
activity of cobalt-containing nitrile hydratases18 and artificial
cobalt complexes19 for hydration of nitriles to amides. No
reaction took place with simple internal alkynes such as 3-
hexyne or diphenylacetylene.
the corresponding diketone 3b in 92% yield. Because the cobalt
porphyrin catalyst 1 is highly water-soluble, the catalyst could
be separated by extraction using water and ethyl acetate, and
analytically pure product 3b was obtained by recrystallization.
Thus, chromatographic purification was not required in this
case.
In addition, reuse of 1 was tested with 2c as an alkyne
substrate. After the hydration reaction, the water-soluble cobalt
complex 1 was recovered by concentration of the water layer
after extraction with n-hexane and then reused for further
reactions to generate ketone 3c from 2c (first run, 8 h, 91%
yield; second run, 10 h, 90% yield; third run, 14 h, 91% yield;
see entry 2 of Table 2 for the reaction conditions).
Preliminary mechanistic studies using alkyne 2h indicated the
following: (1) The hydration essentially involves hydro-
alkoxylation of the alkyne with methanol followed by hydrolysis
of the methyl vinyl ether and/or dimethyl acetal (Table S2).
(2) The rate of the hydroalkoxylation reaction is first order in
precatalyst, first order in 2h, and second order in CH3OH
(Figures S1 and S2). (3) The Hammett ρ value of −2.1 for
hydroalkoxylation of p-substituted phenylacetylenes using
methanol indicated the formation of a cationic transition state
in the rate-determining step (Figure S3). (4) The primary
kinetic isotope effect of 2.6 obtained using methanol-d1 implied
that proton transfer is involved in the rate-determining step
(Figure S4). (5) The catalysis is better promoted when
electron-deficient porphyrin ligands are used (Table S1).
Overall, these results are consistent with a mechanism in
which the cobalt porphyrin complex promotes hydroalkox-
ylation/hydration of the alkyne by activating the alkyne as a
monomeric soft Lewis acid.20 Further experimental and
theoretical studies to elucidate the mechanistic details are
underway in our laboratory.
To determine the potential for using the cobalt-catalyzed
alkyne hydration in late-stage transformations of complex
molecules, the hydration of terminal alkynes attached to
biomolecular scaffolds was tested (Scheme 2). Alkyne 2o
Scheme 2. Hydration of Terminal Alkynes on Sugar and
Amino Acid Scaffolds
In summary, hydration of terminal alkynes to methyl ketones
was achieved using water-soluble cobalt porphyrin complex 1.
To our knowledge, this is the first example of cobalt-catalyzed
hydration of alkynes. The catalysis is best performed under
slightly acidic, aerobic conditions and can be performed under
near-neutral conditions that are compatible with the presence
of acid-labile functional groups.
conjugated with a benzyl-protected sugar was smoothly
hydrated to give ketone 3o in 97% yield without loss of the
glycosyl linkage. The stereochemistry at the anomeric center
remained unchanged (α/β = 99:1). Similarly, selective
hydration of alkyne 2p linked with a protected amino acid
gave the corresponding ketone 3p in 91% yield under our
standard conditions. Benzyl ether, acetal, alkyl ester, and
carboxamide moieties also tolerated the reaction conditions.
The results listed in Table 2 and Scheme 2 indicate the
potential applicability of the present method to hydration of
terminal alkynes in the presence of acid/base- or redox-
sensitive functional groups.
ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental procedures, spectroscopic data, and supporting
figures and tables. This material is available free of charge via
the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
h_naka@nagoya-u.jp
■
Notes
To check the scalability of the present method, a gram-scale
hydration of 1,8-nonadiyne (2b) was carried out (Scheme 3).
Hydration of 2b (5.1 g, 42 mmol) proceeded smoothly, giving
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Scheme 3. Gram-Scale Double Hydration of Terminal
Alkyne 2b
This work was partly supported by the Nagoya University
Science Foundation and a Grant-in-Aid for Young Scientists
(B) from the Ministry of Education, Culture, Sports, Science
and Technology, Japan (23750109 to H.N.).
REFERENCES
■
(1) (a) Hintermann, L.; Labonne, A. Synthesis 2007, 1121−1150.
(b) Alonso, F.; Beletskaya, I. P.; Yus, M. Chem. Rev. 2004, 104, 3079−
C
dx.doi.org/10.1021/ja310282t | J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
Communication
3159. (c) Beller, M.; Seayad, J.; Tillack, A.; Jiao, H. Angew. Chem., Int.
Ed. 2004, 43, 3368−3398. (d) Brenzovich, W. E. Angew. Chem., Int. Ed.
2012, 51, 8933−8935.
(2) (a) Kutscheroff, M. Chem. Ber. 1881, 14, 1540−1542.
(b) Kutscheroff, M. Chem. Ber. 1884, 17, 13−29. (c) Thomas, R. J.;
Campbell, K. N.; Hennion, G. F. J. Am. Chem. Soc. 1938, 60, 718−720.
(d) Nishizawa, M.; Skwarczynski, M.; Imagawa, H.; Sugihara, T. Chem.
Lett. 2002, 31, 12−13.
(18) (a) Yamada, H.; Shimizu, S.; Kobayashi, M. Chem. Rec. 2001, 1,
152−161. (b) Prasad, S.; Bhalla, T. C. Biotechnol. Adv. 2010, 28, 725−
741.
(19) (a) Chin, J.; Kim, J. H. Angew. Chem., Int. Ed. Engl. 1990, 29,
523−525. (b) Kim, J. H.; Britten, J.; Chin, J. J. Am. Chem. Soc. 1993,
115, 3618−3622. (c) Gonzalez, G.; Moullet, B.; Martinez, M.;
Merbach, A. E. Inorg. Chem. 1994, 33, 2330−2333. (d) Swartz, R. D.;
Coggins, M. K.; Kaminsky, W.; Kovacs, J. A. J. Am. Chem. Soc. 2011,
133, 3954−3963.
(20) (a) Nielsen, L. P. C.; Stevenson, C. P.; Blackmond, D. G.;
Jacobsen, E. N. J. Am. Chem. Soc. 2004, 126, 1360−1362. (b) Iwakura,
I.; Ikeno, T.; Yamada, T. Angew. Chem., Int. Ed. 2005, 44, 2524−2527.
(3) (a) Hiscox, W.; Jennings, P. W. Organometallics 1990, 9, 1997−
1999. (b) Jennings, P. W.; Hartman, J. W.; Hiscox, W. C. Inorg. Chim.
Acta 1994, 222, 317−322.
(4) (a) Damiano, J. P.; Postel, M. J. Organomet. Chem. 1996, 522,
303−305. (b) Wu, X.-F.; Bezier, D.; Darcel, C. Adv. Synth. Catal. 2009,
351, 367−370.
(5) Fukuda, Y.; Shiragami, H.; Utimoto, K.; Nozaki, H. J. Org. Chem.
1991, 56, 5816−5819.
(6) Hirabayashi, T.; Okimoto, Y.; Saito, A.; Morita, M.; Sakaguchi, S.;
Ishii, Y. Tetrahedron 2006, 62, 2231−2234.
(7) (a) Thuong, M. B. T.; Mann, A.; Wagner, A. Chem. Commun.
2012, 48, 434−436. (b) Venkateswara, K. T.; Prasad, P. S. S.; Lingaiah,
N. Green Chem. 2012, 14, 1507−1514.
(8) Jin, X.; Oishi, T.; Yamaguchi, K.; Mizuno, N. Chem.Eur. J.
2011, 17, 1261−1267.
(9) (a) Fukuda, Y.; Utimoto, K. J. Org. Chem. 1991, 56, 3729−3731.
(b) Fukuda, Y.; Utimoto, K. Bull. Chem. Soc. Jpn. 1991, 64, 2013−
2015. (c) Teles, J. H.; Brode, S.; Chabanas, M. Angew. Chem., Int. Ed.
1998, 37, 1415−1418. (d) Mizushima, E.; Sato, K.; Hayashi, T.;
Tanaka, M. Angew. Chem., Int. Ed. 2002, 41, 4563−4565. (e) Casado,
R.; Contel, M.; Laguna, M.; Romero, P.; Sanz, S. J. Am. Chem. Soc.
2003, 125, 11925−11935. (f) Zhou, C.-Y.; Chan, P. W. H.; Che, C.-M.
Org. Lett. 2006, 8, 325−328. (g) Marion, N.; Ramon, R. S.; Nolan, S.
P. J. Am. Chem. Soc. 2009, 131, 448−449. (h) Leyva, A.; Corma, A. J.
Org. Chem. 2009, 74, 2067−2074. (i) Hashmi, A. S. K.; Hengst, T.;
Lothschutz, C.; Rominger, F. Adv. Synth. Catal. 2010, 352, 1315−
̈
1337. (j) Huang, J.; Zhu, F.; He, W.; Zhang, F.; Wang, W.; Li, H. J.
Am. Chem. Soc. 2010, 132, 1492−1493. (k) Nun, P.; Ramon, R. S.;
Gaillard, S.; Nolan, S. P. J. Organomet. Chem. 2011, 696, 7−11.
(l) Ghosh, N.; Nayak, S.; Sahoo, A. K. J. Org. Chem. 2011, 76, 500−
511. (m) Wang, D.; Cai, R.; Sharma, S.; Jirak, J.; Thummanapelli, S.
K.; Akhmedov, N. G.; Zhang, H.; Liu, X.; Petersen, J. L.; Shi, X. J. Am.
Chem. Soc. 2012, 134, 9012−9019.
(10) Anti-Markovnikov hydration of terminal alkynes to aldehydes
can be mediated by ruthenium complexes. See: (a) Tokunaga, M.;
Wakatsuki, Y. Angew. Chem., Int. Ed. 1998, 37, 2867−2869.
(b) Tokunaga, M.; Suzuki, T.; Koga, N.; Fukushima, T.; Horiuchi,
A.; Wakatsuki, Y. J. Am. Chem. Soc. 2001, 123, 11917−11924.
(c) Boeck, F.; Kribber, T.; Xiao, L.; Hintermann, L. J. Am. Chem. Soc.
2011, 133, 8138−8141.
(11) Mizushima, E.; Cui, D. M.; Nath, D. C. D.; Hayashi, T.; Tanaka,
M. Org. Synth. 2006, 83, 55−60.
(12) Hatano, K.; Usui, K.; Ishida, Y. Bull. Chem. Soc. Jpn. 1981, 54,
413−419.
(13) (a) Ready, J. M.; Jacobsen, E. N. J. Am. Chem. Soc. 1999, 121,
6086−6087. (b) Schaus, S. E.; Brandes, B. D.; Larrow, J. F.; Tokunaga,
M.; Hansen, K. B.; Gould, A. E.; Furrow, M. E.; Jacobsen, E. N. J. Am.
Chem. Soc. 2002, 124, 1307−1315.
(14) Diketone 3b is a synthetic intermediate for a sex pheromone.
See: Keinan, E.; Sinha, S. C.; Sinha-Bagchi, A. J. Org. Chem. 1992, 57,
3631−3636.
(15) (a) Green, T. W.; Wuts, P. G. M. Protective Groups in Organic
Synthesis, 4th ed.; Wiley: New York, 2007. (b) Kocienski, P. J.
Protecting Groups, 3rd ed.; Thieme: Stuttgart, Germany, 2005.
(16) Hydration of 2c to 3c using the (Ph3P)AuCH3/H2SO4 and
AuSPhosNTf2 systems resulted in 0 and 80% retention of the silyl
ether linkage, respectively.9h
(17) (a) Tsuji, J. Palladium Reagents and Catalysts; Wiley: Chichester,
U.K., 1995; pp 19−124. (b) Cornell, C. N.; Sigman, M. S. Inorg. Chem.
2007, 46, 1903−1909.
D
dx.doi.org/10.1021/ja310282t | J. Am. Chem. Soc. XXXX, XXX, XXX−XXX