Oxidation of alkynes by the HOF·CH3CN complex

Full text of DOI:10.1021/jo001101i

8816
J . Org. Chem. 2000, 65, 8816-8818
Oxidation of alkynes has been attempted several times
Oxid a tion of Alk yn es by th e HOF ‚CH3CN
in the past resulting in a commonly suggested mecha-
nism.10 This mechanism (Scheme 2) involves an oxirene
A which, although never isolated, was assumed to be the
first step. It has been also assumed that A can either
undergo an additional oxidation to give a double epoxide
B or lead via concerted rearrangement to an intermediate
C and a ketene of type D. These intermediates give rise
to all products described as shown in Scheme 1.
Com p lex
Sharon Dayan, Iris Ben-David, and Shlomo Rozen*
School of Chemistry, Raymond and Beverly Sackler Faculty
of Exact Sciences, Tel-Aviv University,
Tel-Aviv 69978, Israel
It was interesting to study the case of 1-pheny-1-
pentyne (10), an acetylene possessing both an aromatic
and an aliphatic side chain. The reaction with HOF‚CH3-
CN produces indeed a combination of all expected prod-
ucts with the diketone 1111 and 1-phenyl-1-butanone (12)
(22% yield) being the major components. The enone 1312
(cis:trans ) 2:3), its epoxide 14,12 and the R-fluoro ketone
1511 were also obtained in small quantities.
Using substrates bearing electron-withdrawing sub-
stituents on the triple bond, such as 4-phenyl-3-butyne-
2-one (16) and methyl phenylpropyolate (17), gave a
narrower product distribution. The ynone 16 required a
10-fold excess of the HOF‚CH3CN complex in order to
achieve a full conversion. The product which proved to
be 1-phenyl-1,2-propanedione (18), obtained in nearly
quantitative yield, resulted from the rearrangement of
the respective intermediate D (Scheme 2). In the case of
17 where such a rearrangement is less favorable, the
diketo ester 1913 was obtained (in its hydrate from) as
the only product in very high yield.
rozens@post.tau.ac.il
Received J uly 20, 2000
The HOF‚CH3CN complex discovered over a decade
ago1 is probably the best oxygen transfer agent organic
chemistry has to offer. It is simply prepared by bubbling
nitrogen-diluted fluorine into aqueous acetonitrile and
is stable at 0 °C for a few hours. It reacts very efficiently
with a large variety of organic compounds resulting either
in their oxidation or in transferring an oxygen atom from
the reagent to the substrate.2 One of the most useful
reactions of this complex is with olefins resulting in their
epoxidation,3 but its reactions with triple bonds has not
yet been investigated.
Several methods for the oxidation of alkynes are
described in the literature involving different types of
reagents such as metal oxidants,4 hydrogen peroxide
catalyzed by metal complexes,5 [fluoro(trifluoromethane-
sulfonyloxy)iodo]benzene,6 and dimethyldioxirane,7 each
used for a specific substrate. We found that the HOF‚
CH3CN complex is able to replace all the above reagents,
usually in better yields and always under much milder
conditions.
The reaction of diphenylacetylene (1) with 2.5 equiv8
of HOF‚CH3CN gave both benzil (2) as the main product
(55% yield) and benzophenone (3) (35% yield), a product
resulting from a loss of a carbon atom. A small amount
of R-fluoro-R-phenyl acetophenone (4)9 was also formed.
Aliphatic acetylenes such as 4-octyne (5) on the other
hand formed a mixture of cis and trans isomers of the
R,â-epoxy-4-octanone (6) as the major product (83%
yield).5a Small amounts (<10%) of 4-heptanone (7) (again
as a result of loss of a carbon) and 4,5-octane-dione (8)5b
were also detected. Working with less than 1 mol equiv
resulted in cis- and trans-3-octen-4-one (2:3 ratio) 95a as
the major product, indicating that the epoxides 6 result
from epoxidation of the respective unsaturated ketones
(Scheme 1).
Symmetrical acetylenes with electron-withdrawing
groups also react well. 2,5-Dimethyl-2,5-diacetoxy-3-
hexyne (20), gave a single product identified as 2,5-
dimethyl-2,5-diacetoxy-3,4-hexanedione (21),14 a product
formed via the bis epoxide B (Scheme 2).
Terminal arylacetylenes react quickly with the oxidiz-
ing complex to produce benzaldehydes. Small amounts
of further oxidation to the corresponding acids could also
be detected. Thus, the reaction of phenyl acetylene (22)
with 5 mol equiv of the oxidizing complex yielded 85% of
benzaldehyde (23) and 5% of benzoic acid (24). Electron-
donating or -withdrawing substituents on the aromatic
ring do not affect the outcome. The oxidation of 4-methyl
phenyl acetylene (25) gave 80% 4-methyl benzaldehyde
(26) and 9% of 4-methylbenzoic acid (27), and 4-chlo-
rophenylacetylene (28) was likewise converted to 4-chlo-
robenzaldehyde (29) accompanied by a small amount of
4-chlorobenzoic acid (30) (Scheme 1).
The reaction of terminal aliphatic alkynes is less
efficient than the ones described above. 1-Heptyne (31)
and 1-octyne (32), for example, require a considerable
excess of the oxidizing agent in order to achieve a full
* To whom correspondence should be addressed. Fax: +972 3
6409293.
(1) Rozen, S.; Brand, M. Angew. Chem., Int. Ed. Engl. 1986, 25, 554.
(2) Rozen, S. Acc. Chem. Res. 1996, 29, 243.
(3) Rozen, S.; Kol, M. J . Org. Chem. 1990, 55, 5155. Rozen, S.;
Bareket, Y.; Dayan, S Tetrahedron Lett. 1996, 37, 531.
(4) Wolfe, S.; Ingold, C. F. J . Am. Chem. Soc. 1983, 105, 7755.
(5) (a) Sakaguchi, S.; Watase, S.; Katayama, Y.; Sakata, Y.; Nish-
iyama, Y.; Ishii, Y. J . Org. Chem. 1994, 59, 5681. (b) Zhu, Z.; Espenson,
J . H. J . Org. Chem. 1995, 60, 7728.
(10) E. G. Lewars, Chem. Rev. 1983, 83, 519.
(11) Stavber, S.; Zupan, M. J . Org. Chem. 1987, 52, 5022.
(12) Enders, D.; Zhu, J .; Raabe, G. Angew. Chem., Int. Ed. Engl.
1996, 35, 5, 1725.
(13) Wasserman, H. H.; Baldino, C. M.; Coats, S. J . J . Org. Chem.
1995, 60, 8231.
(6) Pirguliyev, N. S.; Brel, V. K.; Zefirov, N. S.; Stang, P. J .
Mendeleev Commun. 1999, 189.
(14) Although previously mentioned in the literature: Lehmann, A.
Oertel, M. Chem. Tech. 1959, 11, 453 (Chem. Abstr. 1960, 54, 4377b)s
compound 21 has never been properly identified. Its physical properties
(7) Murray, R. W.; Singh, M. J . Org. Chem. 1993, 58, 5076.
(8) Such a concentration constitutes of up to 50% excess of the
reagent since 2 mol/equiv is the minimum needed for the oxidation of
a triple bond. Using less reagent does not change the distribution of
the products but lowers the conversion of the acetylenic substrate.
(9) Merritt, R. F.; Ruff, J . K. J . Org. Chem., 1965, 30, 328.
are as following: oil, IR (in CH2Cl2 solution): 1724, 1742 (sh) cm-1
;
1H NMR: 1.59 (s, 12H), 2.06 ppm (s, 6H); 13C NMR: 20.7, 24.1, 82.1,
170.8, 194.5 ppm; MS (CI): m/e 259.117195 (M + 1)+, calcd for C12H19
-
O6 259.118164.
10.1021/jo001101i CCC: $19.00 © 2000 American Chemical Society
Published on Web 11/16/2000

Notes
J . Org. Chem., Vol. 65, No. 25, 2000 8817
Sch em e 1
Sch em e 2
39 and 40, and additional small amounts of the corre-
sponding acids 41 and 42.
Terminal aliphatic alkynes containing an adjacent
electron-withdrawing group are even less reactive with
the electrophilic HOF‚CH3CN, and 3-acetoxy-1-octyne
(43) with its acetoxy group does not react even after
prolonged treatment with a large excess of the oxidant.
In conclusion, it was found that the HOF‚CH3CN
complex efficiently oxidizes internal carbon-carbon triple
bonds. In contrast to some previous reports of the
oxidation of alkynes,4 the HOF‚CH3CN complex, being a
strong electrophile, reacts more rapidly with aromatic
alkynes than with aliphatic ones. All products obtained
can be explained by assuming a primary formation of an
“oxirene species” which undergoes further rearrangement
or oxidation reactions (Scheme 2).
Exp er im en ta l Section
1H NMR spectra were recorded using Bruker AC-200 with
CDCl3 as a solvent and Me4Si as an internal standard. The
proton broad band decoupled 13C NMR spectra were recorded
at 90.5 MHz. Here too, CDCl3 served as a solvent with TMS as
an internal standard. GC-MS spectra were measured with a VG
(15) Miiyashita, M.; Suzuki, T.; Hoshino, M.; Yoshikoshi, A. Tetra-
hedron 1997, 53, 12469.
(16) Corey, E. J .; Mehrotra, M. M.Tetrahedron Lett. 1986, 27, 5173.
(17) Choudary, B. M.; Prasad, D.; Valli, V. L. K. Tetrahedron Lett.
1990, 31, 7521. As with compound 13, these minor enones were
obtained as mixtures of cis:trans ) 2:3.
conversion, resulting in a complex mixture of products
composed of the corresponding R,â-epoxy aldehydes 3315
and 34,16 R,â-unsaturated ones 35 and 36,17 R-keto
aldehydes 3718 and 38,19 one carbon smaller aldehydes
(18) Verhe, R.; Courthein, D.; Kimpe, N.; Buyck, L.; Schamp, N.
Synthesis 1982, 667.
(19) Rosowsky, A.; Chen, K. K. N. J . Org. Chem. 1973, 38, 2073.

8818 J . Org. Chem., Vol. 65, No. 25, 2000
Notes
micromass 7070H instrument. IR spectra were recorded as neat
films, in CHCl3 solution or in KBr pellets on a Bruker Vector22
FTIR spectrophotometer. The spectral properties of all products
presented in this work are in excellent agreement with the
literature. With the exception of the commercial compounds, they
all have been referenced in the previous section.
Gen er a l P r oced u r e for Wor k in g w ith F lu or in e a n d
P r od u cin g HOF ‚CH3CN. Fluorine is a strong oxidant and a
corrosive material. It should be used only with an appropriate
vacuum line constructed in a well-ventilated area. If elementary
precautions are taken, work with fluorine is relatively simple,
and we have had no bad experiences working with it. A proposed
detailed setup for working with pure fluorine and details for
producing the HOF‚CH3CN complex have been published re-
cently.20 For the occasional user, prediluted 10% fluorine in
nitrogen, which is commercially available, simplifies the whole
process.
then cooled to 0 °C and added to 3-10-fold excess of the HOF‚
CH3CN complex. After about 5-10 min, the reaction mixture
was warmed to room temperature, neutralized with sodium
bicarbonate, filtered, evaporated almost to dryness, extracted
with CHCl3, and dried over MgSO4. When necessary, the
products were isolated and purified by flash chromatography
using Merck Silicagel 60 H, P.E/EtOAc serving as eluent. The
outcome of the reaction was analyzed by NMR (1H, 13C, and 19F),
IR, and GCMS. The spectral data of the noncommercial known
products were compared with the literature reports, and in every
case an excellent agreement was obtained.
Ack n ow led gm en t. This research was supported by
the Israel Science Foundation founded by the Israel
Academy of Sciences and Humanities.
Gen er a l Oxid a tion P r oced u r e. About 2.5 mmols of an
alkyne were dissolved in 10-20 mL of CHCl3. The mixture was
Su p p or tin g In for m a tion Ava ila ble: IR, HRMS,1H and
13C spectra of compound 21. This material is available free of
charge via the Internet at http://pubs.acs.org..
(20) Dayan, S.; Kol, M.; Rozen, S. Synthesis 1999, 1427. Rozen, S.;
Dayan, S. Angew. Chem., Int. Ed. Engl. 1999, 38, 3471.
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