J . Org. Chem. 2001, 66, 4087-4090
4087
by Muzart and Piva by using tert-butyl hydroxide (TBHP)
with catalytic amounts of CrO3 and p-toluenesulfonic
acid.12 However, an excess of TBHP (up to 7 equiv) and
a long reaction time were required. Oxidation of a variety
of alkynes13 and acetylenic fatty esters14 with TBHP
catalyzed by selenium dioxide has also been reported. A
mixture of monooxygenated and dioxygenated acetylenic
alcohols or ketones was obtained. Recently, Ishii and co-
workers reported a successful catalytic aerobic oxidation
of alkynes to conjugated acetylenic ketones using N-
hydroxyphthalimide (NHPI) combined with a transition
metal under mild conditions.15 For example, oxidation of
4-octyne with NHPI (10 mol %) and [Co(acac)2] (0.5 mol
%) in acetonitrile under oxygen at 50 °C for 6 h gave 85%
conversion with 72% selectivity to 4-octyne-3-one. Some
byproducts such as acetylenic alcohol, acetylenic dike-
tone, and a cleaved product, butanoic acid, were also
produced.
A Con ven ien t Syn th esis of r,â-Acetylen ic
Keton es
Pei Li,*,† Wai Man Fong,† Lisa C. F. Chao,‡
Stephen H. C. Fung,‡ and Ian D. Williams‡
Department of Applied Biology and Chemical Technology,
The Hong Kong Polytechnic University, Hung Hom,
Kowloon, Hong Kong, People’s Republic of China, and
Department of Chemistry, The Hong Kong University of
Science and Technology, Clear Water Bay, Kowloon, Hong
Kong, People’s Republic of China
bcpeili@polyu.edu.hk
Received J anuary 22, 2001
R,â-Acetylenic ketones are extremely versatile inter-
mediates for the preparation of various heterocyclic
compounds,1 anticancer agents,2 pyroazole derivatives,3
nucleosides,4 sex pheromones5 and â-keto-1,3-dithianes6
as well as other compounds.7 Thus, considerable effort
has been devoted to the preparation of conjugated acety-
lenic ketones based on a wide variety of synthetic
approaches including the acylation of metal acetylides,8
Cu(I)-catalyzed cross coupling between terminal alkynes
and acid chlorides,9 and multistep synthesis.10 Besides
these methods, direct R-oxidation of alkynes to the
corresponding R,â-acetylenic ketones has been attempted
previously with varying success. For example, Shaw and
Sherry reported the use of chromium trioxide-pyridine
complex or sodium chromate in the oxidation of various
alkynes.11 An excess of oxidant was required, and low
yields were obtained. This reaction was improved slightly
As part of a continuing effort to develop novel selective
oxidation of organic compounds using inexpensive transi-
tion metal catalysts and molecular oxygen,16 herein we
report a copper(II) chloride-catalyzed oxidation of alkynes
(RCtCCH2R′) with oxygen and tert-butyl hydroperoxide
in tert-butyl alcohol to the corresponding R,â-acetylenic
ketones, RCtCCOR′, under mild conditions (eq 1). The
method gives both high conversion and selectivity in the
formation of the R,â-acetylenic ketone. This is facilitated
since the intermediate acetylenic alcohol, RCtCCH(OH)-
R′, a frequent side product of other syntheses, is smoothly
converted to the ketone under the reaction conditions and
the product ketone is deactivated from further reaction.
The reaction is an example of highly regio- and chemose-
lective C-H bond activation.
Since metal-catalyzed decomposition of hydroperoxides
depends on the nature of metal complexes, a wide range
of TBHP autoxidation conditions using different metal
catalysts including Co(acac)3, CoBr2, CoCl2, Co(OAc)2‚
4H2O, CrCl3‚6H2O, CuCl2‚2H2O, FeCl2.nH2O, and MnCl2‚
6H2O were examined, using 4-octyne as a model sub-
strate. Table 1 shows that all of the metal catalysts gave
high conversions ranging from 81 to 96%, with cobalt and
copper catalysts leading to the highest selectivity for the
4-octyn-3-one. Use of iron and manganese chlorides gave
a higher yield of the alcohol, 4-octyn-3-ol. These findings
suggest that the metal catalysts used have a similar
ability to decompose the TBHP into the radical species
* Author to whom correspondence should be addressed. Phone:
(852)-2766-5616. Fax: (852)-2364-9932.
† The Hong Kong Polytechnic University.
‡ The Hong Kong University of Science and Technology.
(1) (a) Cabarrocas, G.; Ventura, M,; Maestro, M.; Mahia, J .; Villa-
lgordo, J . M. Tetrahedron: Asymmetry 2000, 11, 2483 and reference
cited therein. (b) Serrat, X.; Cabarrocas, G.; Rafel, S.; Ventura, M.;
Linden, A.; Villalgordo, J . M. Tetrahedron: Asymmetry 1999, 10, 3417.
(c) J eevanandam, A.; Narkuman, K.; Cartwright, C.; Ling, Y. Tetra-
hedron Lett. 1999, 40, 4841. (d) Arzoumanian, H.; J ean, M.; Nuel, D.;
Cabrera, A.; Gutierrez, J . L. G.; Rosas, N. Organometallics 1995, 14,
5438.
(2) (a) Kundu, N. G.; Pal, M.; Chowdhury, C. J . Chem. Res., Synop.
1995, 4. (b) Kundu, N. G.; Dasgupta, S. K. J . Chem. Soc., Perkin Trans.
1 1993, 2657.
(3) Holla, B. S.; Udupa, K. V.; Sridhar, K. R. Bull. Chem. Soc. J pn.
1989, 62, 3409.
(4) Adlington, R. M.; Baldwin, J . E.; Pritchard, G. J .; Spencer, K.
Tetrahedron Lett. 2000, 41, 575, and reference cited therein.
(5) Midland, M. M.; Nguyen, N. H. J . Org. Chem. 1981, 46, 4108.
(6) Ranu, B. C.; Bhar, S.; Chakraborti, R. J . Org. Chem. 1992, 57,
7349.
(7) (a) Kabalka, G. W.; Yu, S.; Li, N.; Lipprandt, U. Tetrahedron
Lett. 1999, 40. 37. (b) Wei, H.; Kim, S. H.; Caputo, T. D.; Purkiss, D.
W.; Li, G. Tetrahedron 2000, 56, 2397.
(8) (a) Verkruijsse, H. D,; Heus-Kloos, Y. A.; Brandsma, L. J .
Organomet. Chem. 1988, 289. (b) Hirao, T.; Misu, D.; Agawa, T.
Tetrahedron Lett. 1986, 27, 933. (c) Smith, A. B.; Levenberg, P. A.;
Suits, J . Z. Synthesis 1986, 184. (d) Brown, H. C.; Racherla, U. S.;
Singh, S. M. Tetrahedron Lett. 1984, 25, 2411.
(9) (a) Chowdhury, C.; Kundu, N. Tetrahedron 1999, 55, 7011. (b)
Chowdhury, C.; Kundu, N. Tetrahedron Lett. 1996, 37, 7323. (c)
Shergina, S. I.; Sokolov, I. E.; Zanina, A. S. Mendeleev Commun. 1994,
207.
(12) Muzart, J .; Piva, O. Tetrahedron Lett. 1988, 29, 2321.
(13) Chabaud, B.; Sharpless, K. B. J . Org. Chem. 1979, 44, 4202.
(14) J ie, L. K.; Pasha, M. K.; Alam, M. S. Lipids 1997, 32, 1119.
(15) Sakaguchi, S.; Takase, T.; Iwahama, T.; Ishii, Y. Chem. Com-
mun. 1998, 2037.
(16) (a) Li, P.; Alper, H. J . Mol. Catal. 1990, 61, 51. (b) Li, P.; Alper,
H. J . Mol. Catal. 1992, 72, 143. (c) Li, P.; Alper, H. Can. J . Chem.
1993, 71, 84. (d) Lin, Y. H.; Williams, I. D.; Li, P. Appl. Catal. A:
General 1997, 150, 221. (e) Li, P.; Fung, H. C.; Chao, L. C. F.; Lin, Y.
H.; Williams, I. D. J . Mol. Catal. A: Chemical 1999, 145, 111.
(10) (a) Katritzky, A. R.; Lang, H. J . Org. Chem. 1995, 60, 7612 and
references therein. (b) Cupps, T. L.; Boutin, R. H.; Rapoport, H. J . Org.
Chem. 1985, 50, 3972.
(11) Shaw, J . E.; Sherry, J . J . Tetrahedron Lett. 1971, 46, 4379.
10.1021/jo015534c CCC: $20.00 © 2001 American Chemical Society
Published on Web 05/05/2001