Catalytic radical addition of carbonyl compounds to alkenes by Mn(II)/Co(II)/O2 system

Article abstract of DOI:10.1021/jo0162282

The radical addition of enolizable carbonyl compounds such as malonates and malononitrile to alkenes was successfully achieved through a catalytic process using the Mn(II)/Co(II)/O₂ system to afford the corresponding adducts in fair to good yields. Dimethyl malonate added to 1,5-cyclooctadiene to produce a fused bicycle compound.

Full text of DOI:10.1021/jo0162282

970
J . Org. Chem. 2002, 67, 970-973
Ca ta lytic Ra d ica l Ad d ition of Ca r bon yl Com p ou n d s to Alk en es by
Mn (II)/Co(II)/O2 System
Kouji Hirase, Takahiro Iwahama, Satoshi Sakaguchi, and Yasutaka Ishii*
Department of Applied Chemistry, Faculty of Engineering & High Technology Research Center,
Kansai University, Suita, Osaka 564-8680, J apan
ishii@ipcku.kansai-u.ac.jp
Received October 23, 2001
The radical addition of enolizable carbonyl compounds such as malonates and malononitrile to
alkenes was successfully achieved through a catalytic process using the Mn(II)/Co(II)/O2 system to
afford the corresponding adducts in fair to good yields. Dimethyl malonate added to 1,5-
cyclooctadiene to produce a fused bicycle compound.
The carbon-carbon bond-forming reaction through a
types of R-alkylated ketones. The Mn(II)/Co(II)/O2 redox
system may enable catalytic accesses to Mn(III)-promoted
radical reactions, which are carried out by the use of a
stoichiometric amount of Mn(III) reagents.
We have examined a catalytic radical addition of
enolizable methylene compounds such as malonates and
R-keto esters to alkenes using the Mn(II)/Co(II)/O2 redox
system.
The addition of dimethyl malonate (1a ) to 1-octene (2a )
was chosen as a model reaction and was carried out in
the presence of a catalytic amount of Mn(OAc)2 combined
with Co(OAc)2 in a mixed gas of O2 and N2 in acetic acid
under various reaction conditions (eq 1 and Table 1).
radical process has attracted wide interest in synthetic
organic chemistry, and the rapid development in this
area made it possible for chemists to apply a variety of
synthetic reactions.1 It is known that a number of
carbon-carbon bond-forming free-radical reactions are
mediated by transition metals, and high oxidation state
metal ions such as Mn(III), Ce(IV), Co(III), Ag(II), and
Pb(IV) promote the addition of R-keto radicals derived
from ketones to alkenes.2 Among these metal oxidants,
Mn(OAc)3 is widely used as a powerful reagent for various
types of organic synthesis,3 but most reactions are carried
out with the use of a large amount of a metal reagent
4
except for a few methods mediated by AgNO3/Na2S2O3
5
and Mn(OAc)3/KMnO4 systems. Nowadays, from an
environmental and practical point of view, organic syn-
thesis using a stoichiometric amount of a metal reagent
may be restricted to a small-scale reaction.
We have recently developed a catalytic radical addition
of simple ketones to alkenes by the use of a novel redox
system consisting of Mn(II)/Co(II)/O2.6 Thus, R-alkylated
ketones, which are conventionally prepared by the reac-
tion of enolates with alkyl halides, could be prepared by
the radical addition of ketones to alkenes in the presence
of catalytic amounts of Mn(II) (0.5 mol %) and Co(II) (0.1
mol %) under air or dioxygen as a terminal oxidant. This
method can be applied to large-scale synthesis of various
The reaction of 1a (30 mmol) with 2a (2 mmol) in the
presence of Mn(OAc)2 (0.04 mmol) and Co(OAc)2 (0.02
mmol) under a mixed gas of O2/N2 (0.1 atm/0.9 atm) in
acetic acid (2 mL) at 90 °C for 3 h produced dimethyl
octylmalonate (3a ) (60%) and a diadduct, dimethyl 2-(2-
hexyldecyl)malonate (5a a ) (10%), as major products at
96% conversion of 2a (Table 1, run 1). The reaction at
100 °C under these conditions gave almost the same
results as that at 90 °C, but the yield of 3a a considerably
decreased in the reaction at 80 °C (Table 1, runs 2 and
3). The reaction in the absence of either Mn(OAc)2 or Co-
(OAc)2 led to 3a a in poor yield (Table 1, runs 4 and 5).
To know the influence of oxygen concentration on the
present reaction, the reaction was examined under vary-
ing oxygen pressure (Table 1, runs 6-9). The reaction
under 1 atm of O2 gave 3a a (43%) and dimethyl 2-(2-
oxooctyl)malonate (4a a ) (5%) along with a complex
mixture of undesired oxygenated products (Table 1, run
6). The formation of the oxygenated product 4a a is due
to the trapping of O2 by an adduct radical derived from
1a and 2a as discussed later. When the amount of Co-
* To whom correspondence should be addressed. Fax: +81-6-6339-
4026.
(1) (a) Radicals in Organic Synthesis; Renaud, P., Sibi, M. P., Eds.;
Wiley-VCH: New York, 2001; Vol. 1, Basic principles, and Vol. 2,
Applications. (b) Free Radical Chain Reactions in Organic Synthesis;
Motherwell, W. B., Chich, D., Eds.; Academic: London, 1992. (c)
Curran, D. P. In Comprehensive Organic Synthesis; Trost, B., Fleming,
M. I., Eds.; Pergamon: Oxford, 1991; Vol.4, Chapters 4.1 and 4.2. (d)
Curran, D. P. Synthesis 1988, 417 (part 1), 489 (part 2). (e) Radicals
in Organic Synthesis: Formation of Carbon-Carbon Bonds; Giese, B.,
Ed.; Pergamon Press: Oxford, 1986.
(2) (a) Organic Synthesis by Oxidation with Metal Compounds; Migs,
W. J ., de J onge, C. R. H. I., Eds.; Plenum Press: New York, 1986. (b)
Hajek, M.; Malek, J . Synthesis 1976, 315. (c) Hajek, M.; Silhavy P.;
Malek, J . Tetrahedron Lett. 1974, 36, 3193.
(3) (a) Heiba, E. I.; Dessau, R. M. J . Am. Chem. Soc. 1972, 92, 2888.
(b) Heiba, E. I.; Dessau, R. M. J . Am. Chem. Soc. 1971, 93, 524.
(4) Citterio, A.; Ferrario, F.; de Bernardinis, S. J . Chem. Res., Synop.
1983, 310.
(5) Linker, T.; Kersten, B.; Linker, U.; Peter, K.; Peter, E. von
Schnering, H. G. Synlett. 1996, 468.
(6) Iwahama, T.; Sakaguchi, S.; Ishii, Y. Chem. Commun. 2000,
2317.
10.1021/jo0162282 CCC: $22.00 © 2002 American Chemical Society
Published on Web 01/12/2002

Catalytic Radical Addition of Carbonyl Compounds to Alkenes
J . Org. Chem., Vol. 67, No. 3, 2002 971
Ta ble 1. Rea ction of Dim eth yl Ma lon a te (1a ) w ith
1-Octen e (2a ) by Mn (OAc)2 a n d Co(OAc)2 u n d er Va r iou s
Con d ition sa
approaches the exo direction of 2c to give 3a c having an
exo configuration (Table 2, run 2, and Figure 2, Support-
ing Information). It is reported that the peroxide-initiated
radical addition of aldehyde to 2c takes place stereose-
lectively to form the corresponding exo adduct.7
yieldc (%)
Mn(OAc)2 Co(OAc)2 time convnb
run
(mol %)
(mol %)
(h)
(%)
3a a
4a a
5a a
When 1-octyne (2d ) was used as the alkyne, about a
1:1 isomeric mixture of adduct 3a d was obtained in 55%
yield (Table 2, run 3). It was found that diethyl malonate
(1b) adds smoothly to 2a to form the corresponding
adduct, 3ba , in 80% (Table 2, run 4). We next examined
the reaction of R-diketo compounds such as acetoacetic
ester with 2a (Table 2, run 5). Ethyl acetoacetate (1c)
was less reactive than malonic esters 1a and 1b. The
addition of R-acetyl-γ-butyrolactone (1d ) to 2a proceeded
even in the presence of a very small amount of Mn(OAc)2
(0.5 mol %) and Co(OAc)2 (0.1 mol %) to form adduct 3d a
in 60% yield (Table 2, run 6). Malononitrile (1e) was a
sluggish substrate, but n-octyl malonitrile (3ea ) was
obtained in good yield (78%) by allowing it to react with
2a using Mn(OAc)2 (5 mol %) and Co(OAc)2 (1 mol %)
(Table 2, run 7).
1
2
2
2
2
-
2
2
2
2
2
1
2
2
1
1
1
-
1
1
1
1
1
0.5
1
1
1
3
3
3
2
2
2
2
2
2
2
2
3
3
96
99
78
20
5
98
97
82
73
80
93
95
100
60
63
39
3
n.d.
43
55
44
42
43
54
49
87
1
1
1
10
12
12
<1
n.d.
5
10
12
14
10
9
2d
3e
4
<1
n.d.
5
3
1
<1
1
2
1
<1
5
6f
7g
8h
9i
10
11
12d,j
13d,j,k
8
11
a
Compound 2a (2 mmol) was allowed to react with 1a (30 mmol)
under N2/O2 ) 0.9/0.1 atm in the presence of Mn(OAc)2 and
Co(OAc)2 in AcOH (2 mL) at 90 °C. Conversion of 2a . c Based on
b
2a reacted. 100 °C. e 80 °C. f O2 (1 atm). N2/O2 ) 0.5/0.5 atm.
d
g
h
i
j
k
Air (1 atm). N2/O2 ) 0.95/0.05 atm. Without AcOH. 1a (87
mmol) was used.
A plausible reaction path of the present reaction of 1a
to 2a is illustrated in Scheme 1.
In a previous paper,6 we showed that Mn(II) can be
continuously reoxidized to Mn(III) by the action of a Co-
(III)-dioxygen complex like a superoxocobalt(III) gener-
ated in situ from Co(II) and O2.8 The Mn(III) oxidizes 1a
to give a radical species (A) that readily adds to the
alkene 2a to form an adduct radical (B). The resulting
radical intermediate B reacts with 1a , O2, or 2a to lead
to 3a a , 4a a , or 5a a , respectively.
The reaction of 1a with 1,5-cyclooctadiene (6) led to
the formation of a fused product 7 (70%) via intramo-
lecular radical cyclization (eq 2). The structure of 7 was
found to be a cis-fused product by comparing its spectral
data with those of literature values.5 The formation of 7
was rationally explained by Scheme 2. An adduct radical
(C) derived from 1a and 6 undergoes intramolecular
cyclization followed by hydrogen atom abstraction from
the substrate affording the fused adduct 7.
F igu r e 1. Effect of the amount of 1a . Reaction conditions:
1a (10-87 mmol), 2a (2 mmol), Mn(OAc)2 (2 mol %), Co(OAc)2
(1 mol %), AcOH (2 mL), 100 °C, 3 h, N2/O2 ) 0.9/0.1 atm.
(OAc)2 or Mn(OAc)2 was halved, the yield of 3a a de-
creased to 43% or 54%, respectively (Table 1, runs 10 and
11). It is interesting to note that the present reaction
could be successfully carried out without any solvent,
when 1a was used instead of a solvent, to form 3a a in
87% yield (Table 1, run 13). After the reaction, unreacted
1a was recovered in over 80% yield from a reaction
mixture by distillation.
Figure 1 shows the influence of the ratio of 1a to 2a
on the yield of 3a a and 5a a . The yield of the 3a a
increased with increasing the concentration of 1a to 2a .
When alkene 2a was allowed to react with excess 1a (87
mmol), 2a was completely converted into adducts 3a a
(91%) and 5a a (9%).
Table 2 shows the reactions between several enolizable
methylene compounds and alkenes by the Mn(II)/Co(II)/
O2 redox-couple under selected reaction conditions.
Compound 1a reacted with some difficulty to methyl-
substituted alkene, 2-methyl-1-heptene (2b), compared
with that to the normal alkene 2a , giving adduct 3a b in
slightly lower yield and several unidentified products
were produced (Table 2, run 1). In general, the addition
of an attacking radical to methyl-substituted alkene is
known to inhibit the reaction owing to the steric hin-
drance. The reaction of 1a with 2-norbornene (2c) af-
forded an adduct, 3a c, in 80% yield (Table 2, run 2).
Hydrolysis of the resulting 3a c led to the corresponding
dicarboxylic acid whose X-ray analysis indicated that 1a
In summary, we have succeeded in the catalytic
radical-addition of enolaziable compounds to alkenes by
an Mn(II)/Co(II)/O2 redox system to form the correspond-
ing adducts in fair to good yields.
Exp er im en ta l Section
1
Gen er a l P r oced u r e. H and 13C NMR spectra were mea-
sured at 270 and 67.5 MHz, respectively, in CDCl3 with TMS
as the internal standard. IR spectra were measured as films
on NaCl plates. GLC analysis was performed with a flame
ionization detector using a 1 mm × 30 m capillary column (OV-
1). All starting materials were commercially available and used
without any purification.
(7) Stockmann, H. J . Org. Chem. 1964, 29, 245.
(8) Redox potentials of Mn(III)/Mn(II) (1.51 eV) and Co(III)/Co(II)
(1.82 eV) in water were reported the following paper: Sheldon, R. A.;
Kochi, J . K. Oxid. Combust. Rev. 1973, 5, 135.

972 J . Org. Chem., Vol. 67, No. 3, 2002
Ta ble 2. Ad d ition of Va r iou s En oliza ble Com p ou n d s to Alk en esa
Hirase et al.
a
Alkenes (2 mmol) were allowed to react with enolizable compounds in the presence of Mn(OAc)2 (2 mol %) and Co(OAc)2 (1 mol %) in
AcOH (2 mL) at 90 °C for 5 h under N2/O2 ) 0.9/0.1 atm. Conversion of alkenes. c Based on alkenes used. 100 °C. e 8 h. f See Figure
b
d
g
h
2. 50 °C, 48 h. 3 h.
Sch em e 1
Sch em e 2
Compounds 3a a ,9 3a d ,10 3ba ,11 3ca ,12 and 3ea 13 were
reported previously.
Dim et h yl 2-(2-h exyld ecyl)m a lon a t e (5a a ): 1H NMR δ
0.85-1.25 (m, 34H), 1.86 (t, 2H, J ) 8.3 Hz), 3.70 (s, 3H), 3.73
(9) Elinson, M. N.; Feducovich, S. K.; Zakharenkov, A. A.; Ugrak,
B. I.; Nikishin, G. I.; Lindeman, S. V.; Struchkov, J . T. Tetrahedron
1995, 51, 5035.
(10) Tsuboi, S.; Muranaka, K.; Sakai, T.; Takeda, A. J . Org. Chem.
1986, 51, 4944.
(11) (a) Peek, R.; Streukens, M.; Thomas, H. G.; Vanderfuhr, A.;
Wellen, U. Chem. Ber. 1994, 127, 1257. (b) Uno, M.; Takahashi, T.;
Takahashi, S. J . Chem. Soc., Perkin Trans. 1 1990, 647.
(12) (a) Botta, M.; Cavalieri, M.; Ceci, D.; De Angelis, F.; Finizia,
G.; Nicoletti, R. Tetrahedron 1984, 40, 3313. (b) Hajek, M.; Malek, J .
Synthesis 1977, 454. (c) Duus, F. Tetrahedron 1972, 28, 5923.
Gen er a l P r oced u r e for th e Rea ction of 1a a n d 2a . To
a solution of 1a (30 mmol), Mn(OAc)2 (2 mol %), and Co(OAc)2
(1 mol %) in AcOH (2 mL) in a two-necked flask equipped with
a balloon filled with an appropriate concentration of O2 was
added 2a (2 mmol), and the mixture was stirred at 90 °C for
3 h. After evaporation of AcOH, the product 3a a was isolated
by flash chromatography on silica gel (n-hexane-AcOEt ) 5:1).

Catalytic Radical Addition of Carbonyl Compounds to Alkenes
J . Org. Chem., Vol. 67, No. 3, 2002 973
(s, 3H); 13C NMR δ 13.8, 22.3, 23.6, 25.9, 28.8, 28.9, 29.2, 29.3,
29.5, 29.6, 31.5, 32.0, 32.8, 35.1, 49.4, 51.8, 51.9, 52.0, 52.1,
57.3, 169.7, 172.0; IR 2924, 1738, 1462, 1229, 1173 cm-1; MS
(70 eV) m/e ) 55, 132, 145, 179, 307.
1H), 3.02 (d, 1H, J ) 11.5 Hz); 13C NMR (CD3OD) δ 29.5, 30.8,
36.1, 37.3, 38.0, 41.0, 43.1, 59.0, 172.2, 172.6; IR 2950, 1693,
1419, 1240 cm-1
.
r-Acetyl-r-octyl-γ-bu tyr ola cton e (3d a ): 1H NMR δ 0.87
(t, 3H, J ) 7.3 Hz), 1.18-1.25 (m, 12H), 1.77 (dt, 1H, J ) 4.7,
12.0 Hz), 1.98-2.06 (m, 1H), 2.09-2.17 (m, 1H), 2.32 (s, 3H),
2.90-2.96 (m, 1H), 4.13 (dq, 1H, J ) 10.9, 9.1 Hz), 4.29 (dt,
1H, J ) 2.9, 8.7 Hz); 13C NMR δ 14.2, 22.8, 25.2, 25.6, 29.3,
29.3, 29.4, 29.8, 32.0, 35.3, 61.8, 66.4, 175.8, 202.7; IR 2925,
1769, 1465, 1359, 1026 cm-1; MS (70 eV) m/e ) 43, 55, 81,
128, 198.
1
Dim eth yl 2-(2-m eth ylh ep tyl)m a lon a te (3a b): H NMR
δ 0.86-0.89 (m, 6H), 1.13-1.28 (m, 9H), 1.64-1.71 (m, 1H)
1.92-2.03 (m, 1H), 3.47 (t, 1H, J ) 6.8 Hz), 3.73 (s, 6H); 13C
NMR δ 14.1, 19.2, 22.6, 30.8, 32.0, 35.9, 36.6, 49.7, 49.8, 52.3,
52.4, 52.5, 169.9, 170.0; IR 2925, 1738, 1434, 1199, 1154, 1011
cm-1; MS (70 eV) m/e ) 55, 132, 145, 173.
Dim eth yl 2-(2-n or bor n yl)m a lon a te (3a c): 1H NMR δ
1.07-1.29 (m, 6H), 1.48-1.56 (m, 3H), 2.01 (br, 1H), 2.16-
2.33 (m, 2H), 3.13 (d, 1H, J ) 11.7 Hz), 3.70 (s, 3H), 3.74 (s,
3H); 13C NMR δ 28.2, 29.5, 35.2, 35.9, 36.5, 39.5, 41.7, 52.2,
52.2, 57.2, 168.9, 169.2; IR 2953, 1756, 1436, 1220 cm-1; MS
(70 eV) m/e ) 59, 95, 132, 157, 195.
Ack n ow led gm en t. This work was partly supported
by a Grant-in-Aid for Scientific Research (S) (No.
13853008) from the J apan Society for the Promotion of
Science (J SPS).
2-(2-Nor bor n yl)m a lon ic a cid : 1H NMR (CD3OD) δ 1.12-
1.36 (m, 5H), 1.44-1.62 (m, 3H), 2.05-2.14 (m, 2H), 2.99 (br,
Su p p or tin g In for m a tion Ava ila ble: Copies of 13C and
1H NMR and IR spectra for all of the products and Figure 2.
This material is available free of charge via the Internet at
http://pubs.acs.org.
(13) (a) Bauer, T.; Thomann, R.; Muelhaupt, R. Macromolecules
1998, 31, 7651. (b) Lehn, J . M.; Mascal, M.; DeCian, A.; Fischer, J . J .
Chem. Soc., Perkin Trans. 2 1992, 461. (c) Curran, D. P.; Seong, C. M.
Synlett 1991, 107.
J O0162282