Catalytic radical addition of ketones to alkenes by a metal-dioxygen redox system

Article abstract of DOI:10.1039/b007182j

Radical addition of ketones to alkenes catalyzed by Mn(OAc)₂ combined with Co(OAc)₂ using dioxygen as oxidant was developed; for instance, the reaction of cyclohexanone with oct-1-ene in the presence of very small amounts of Mn(OAc)₂ and Co(OAc)₂ under air (1 atm) gave 2-octylcyclohexanone in good selectivity; from styrene, a six-membered cyclic peroxide was isolated in good yield.

Full text of DOI:10.1039/b007182j

Catalytic radical addition of ketones to alkenes by a metal–dioxygen redox
system
Takahiro Iwahama, Satoshi Sakaguchi and Yasutaka Ishii*
Department of Applied Chemistry, Faculty of Engineering & High Technology Research Center, Kansai University,
Suita, Osaka 564-8680, Japan. E-mail: ishii@ipcku.kansai-u.ac.jp
Received (in Cambridge, UK) 5th September 2000, Accepted 2nd October 2000
First published as an Advance Article on the web 9th November 2000
Table 1 Reaction of cyclohexanone (1) to oct-1-ene (2) by Mn(OAc)2
Radical addition of ketones to alkenes catalyzed by
combined with Co(OAc)2 under various conditionsa
Mn(OAc)2 combined with Co(OAc)2 using dioxygen as
oxidant was developed; for instance, the reaction of cyclo-
hexanone with oct-1-ene in the presence of very small
amounts of Mn(OAc)2 and Co(OAc)2 under air (1 atm) gave
2-octylcyclohexanone in good selectivity; from styrene, a six-
membered cyclic peroxide was isolated in good yield.
mol%
Oxygen source
(N2–O2 atm)
Conv.
Time/h (%)b
Select.
(%)c
Run
Mn
Co
1d
2d
3
4
5d
6
7
8
9f
10g
11
12
13
14
15
16
0.5
0.5
0.5
0.5
0.5
0.5
—
0.5
0.5
0.01
0.5
0.5
0.5
0.5
0.5
0.1
—
—
—
—
0.1
0.1
0.5
0.1
0.1
0.005
0.1
0.1
—
N2
Air
Air
N2
N2
Air
Air
Air
5
5
5
5
5
< 10
35
32
No reaction
< 8
41
< 2
57
57
30
11
72
49
69
87
70
4e
26e
69
Free radical reactions in organic synthesis have been recognized
as a powerful tool for the construction of C–C and C–X (X N H
or heteroatoms) bonds.1 However, a limited number of methods
have appeared for the generation of a-keto carbon radicals in
spite of their synthetic importance.1,2 Among the methods
developed for this purpose, peroxide- and metal-initiated
reactions of ketones are often used.2a–d Thus, the addition of a-
keto radicals to alkenes which leads to a-alkylated ketones is
practiced by the use of high oxidation state metal ions such as
Mn(III), Ce(IV), Ag(II) and Pb(IV).2c,d Unfortunately, most
reported procedures call for a large quantity of the metal
reagent. To the best of our knowledge, there is only one report
on the catalytic addition of a-keto radicals to alkenes via a
catalytic process using AgNO3 and Na2S2O3 as the reoxidant.3
If the addition of ketones to alkenes can be achieved by using a
catalytic amount of metal ions in combination with an
appropriate oxidizing agent, the reaction would become an
effective tool for the synthesis of a-alkylated ketones. From
environmental and economic aspects, molecular oxygen is the
best candidate as the oxidant to regenerate the reduced metal
ions to a high oxidation state, but such a catalytic system has not
yet been developed. Here we wish to report a novel catalytic
radical addition of ketones to alkenes by Mn(II) combined with
Co(II) under dioxygen [eqn. (1)].
5e
88
Trace
83
85
72
80
83
72
5
5
10
10
10
10
10
10
10
10
10
Air
Air
0.9+0.1
0.5+0.5
0.5+0.5
0.3+0.7
O2
0.1
0.1
0.05
81
62
85
0.5+0.5
a 2 (2 mmol) was allowed to react with 1 (20 mmol) under dioxygen in the
presence of Mn(OAc)2 and Co(OAc)2 in AcOH (2 mL) at 80 °C.
b Conversion of 2. c Based on 2 reacted. d Mn(OAc)3 was used instead of
Mn(OAc)2. e Yield based on 2 used. f AcOH (0.5 mL) was used. g 1 (5 eq.)
was used.
Mn(OAc)2 and Co(OAc)2 (run 10). Since Co(II) ions are well-
known to react easily with O2 to form a Co(III)–dioxygen
complex such as a superoxocobalt(III) or peroxocobalt(III
)
complex,4 it is thought that such a Co(III) species catalyzes the
reoxidation of the reduced Mn(II) to Mn(III) under O2.
The remarkable effect of oxygen concentration on the
reaction of 1 with 2 was observed (runs 11–16). When a mixed
gas of 0.5+0.5 atm of N2–O2 was employed, 3 was obtained in
83% selectivity at 72% conversion (run 12).
(1)
On the basis of these results, the addition of various ketones
to alkenes was examined under the optimized reaction condi-
tions (Table 2).
To highlight the possibility of using dioxygen as reoxidant,
the addition of cyclohexanone (1) to oct-1-ene (2) was carried
out in the presence of a catalytic amount of Mn(OAc)3 (0.5
mol%) having one-electron oxidizing ability under either an
inert gas (N2) or air (1 atm) in AcOH at 80 °C for 5 h (Table 1,
runs 1 and 2).† The reaction under N2 led to an adduct,
2-octylcyclohexanone (3), in low yield (4%), while the reaction
under air afforded 3 in better yield (26%). This fact indicates
that the reduced Mn(II) species can be continually reoxidized to
Mn(III) by O2 making use of Mn(OAc)2, which is cheaper than
Mn(OAc)3, more viable for reactions under O2 instead of
Mn(OAc)3. In fact, Mn(OAc)2 in the presence of O2 promoted
the reaction to a similar extent as Mn(OAc)3 did (run 3).
Needless to say, the reaction did not take place at all by
Mn(OAc)2 under N2 (run 4).
Both cyclic and aliphatic ketones were added to 2 to give the
corresponding adducts in fair to good yields (runs 1–4). The
reaction of an unsymmetrical ketone such as pentan-2-one (4)
with 2 led to two structural isomers, 3-ethylundecan-2-one (5)
and tridecan-4-one (6), in a ratio of ca. 6+1. The preferential
formation of 5 is believed to be due to the fact that the secondary
carbon radical is more easily generated than the primary one.
From isopropenyl acetate, g-acetoxy ketone was obtained in
relatively good selectivity (run 5). The reaction of 1 with styrene
(7) did not form the expected adduct but gave a cyclic peroxide
(8) in 41% yield (run 6). Such six-membered cyclic peroxides
are known to exhibit significant biological activities.5 The
peroxide 8 may be formed through the reaction path shown in
Scheme 1. A benzyl radical (B) derived from the addition of an
a-keto radical (A) to 7 reacts with O2 rather than 1, giving an
alkylperoxy radical (C) which then undergoes intramolecular
cyclization leading to 8.6 It is believed that the benzyl radical B
which is stabilized by conjugation with the phenyl group is
The present reaction was found to be facilitated by adding a
small amount of Co(OAc)2 (0.1 mol%) to Mn(OAc)2 (0.5
mol%) to give 3 in 88% selectivity at 41% conversion (run 6),
while the reaction was not induced by Co(II) alone (run 7).‡ The
addition proceeded smoothly even with a very small amount of
DOI: 10.1039/b007182j
Chem. Commun., 2000, 2317–2318
This journal is © The Royal Society of Chemistry 2000
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Table 2 Reaction of various ketones with alkenesa
Scheme 1
This work was partly supported by the Japan Society for the
Promotion of Science under the Research for the Future
program, JSPS.
Notes and references
† A typical procedure for reaction of cyclohexanone 1 with oct-1-ene 2: To
a solution of 1 (20 mmol), Mn(OAc)2 (0.1–0.5 mol%) and Co(OAc)2
(0.05–0.1 mol%) in AcOH (2 mL) in a two-necked flask equipped with a
balloon filled with an appropriate concentration of O2 was added 2 (2
mmol), and the mixture was stirred at 80 °C for 5 h. After evaporation of
AcOH and unreacted 1, 2-octylcyclohexanone (3) was isolated by flash
chromatography on silica gel (n-hexane–AcOEt = 5+1).
‡ By the reaction using the combined catalytic systems of Mn(OAc)2 with
other metals such as Cu(OAc)2, VO(acac)2, Ni(acac)2 and Fe(acac)3, the
yield of 3 was not improved.
1 B. Giese, Radicals in Organic Synthesis: Formation of Carbon–Carbon
Bonds, Pergamon, Oxford, 1986.
2 (a) J. C. Allen, J. I. G. Cadogan and D. H. Hey, J. Chem. Soc., 1965, 1918;
(b) E. I. Heiba and R. M. Dessau, J. Am. Chem. Soc., 1971, 93, 524; (c)
M. Hajek and J. Malek, Synthesis, 1976, 315; (d) M. Hajek, P. Silhavy
and J. Malek, Tetrahedron Lett., 1974, 36, 3193; (e) M. S. Kharash, J.
Kuderna and W. Nudenberg, J. Org. Chem., 1953, 18, 1225; (f) H. J.
Schafer, Angew. Chem., Int. Ed. Engl., 1981, 20, 911.
3 A. Citterio, F. Ferrario and S. De Bernardinis, J. Chem. Res. (S), 1983,
310.
4 (a) R. S. Drago, J. P. Cannady and K. A. Leslie, J. Am. Chem. Soc., 1980,
102, 6014; (b) E. C. Niederhoffer, J. H. Timmons and A. E. Martell,
Chem. Rev., 1984, 84, 137.
5 I. Saito and S. S. Nittala, The Chemistry of Functional Groups, Peroxides,
ed. S. Patai, Wiley, New York, 1983.
6 C.-Y. Qian, H. Nishino, K. Kurosawa and J. D. Korp, J. Org. Chem.,
1993, 58, 4448.
7 It is well-known that Co ions catalyze the decomposition of alkyl
hydroperoxides; R. A. Sheldon and J. K. Kochi, Metal Catalyzed
Oxidations of Organic Compounds, Academic Press, New York, 1981.
unable to abstract a hydrogen atom from 1. Since Co ions are
known to promote the redox decomposition of the peroxides,7
the reaction was conducted without Co(II) to give 8 in 70% yield
(run 7).
In conclusion, we have developed a novel catalytic method
for the addition of ketones to alkenes by the combined use of
Mn(II) and Co(II) salts using dioxygen as the reoxidant. This
method provides an alternative route to a-alkylated cycloalkan-
ones which are attractive compounds as fine chemicals such as
fragrances. Further investigation to extend the present method
and to elucidate the role of the Co(II) species is currently in
progress.
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Chem. Commun., 2000, 2317–2318