Generation of β-keto radicals from cyclopropanols catalyzed by AgNO3

Article abstract of DOI:10.1246/cl.2006.18

Various β-keto radicals are generated from cyclopropanols by treatment with a catalytic amount of AgNO₃ and (NH₄) ₂S₂O₈ as a reoxidant in the presence of pyridine. Thus, generated β-keto radicals react with alkenes to yield addition products. Copyright

Full text of DOI:10.1246/cl.2006.18

18
Chemistry Letters Vol.35, No.1 (2006)
Generation of ꢀ-Keto Radicals from Cyclopropanols Catalyzed by AgNO3
Shunsuke Chiba, Zhengyan Cao, Serry Atta Atta El Bialy, and Koichi Narasakaꢀ
Department of Chemistry, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033
(Received October 3, 2005; CL-051257)
Various ꢀ-keto radicals are generated from cyclopropanols
salts under harsh conditions (for example, refluxing in water),5
this catalytic reaction under milder conditions presumably pro-
ceeds via AgI–Ag0 cycle.11
by treatment with a catalytic amount of AgNO3 and (NH4)2S2O8
as a reoxidant in the presence of pyridine. Thus, generated ꢀ-
keto radicals react with alkenes to yield addition products.
cat. AgNO3
(NH4)2S2O8
additive
O
O
O
OTBS
Ph
OH
Me
+
(1)
+
Ph
Ph
Ph
Ph
In the previous papers, our laboratory reported that the treat-
ment of cyclopropanols with manganese(III) tris(2-pyridinecar-
boxylate) [Mn(pic)3] generates ꢀ-keto radicals,1 which add to ei-
ther electron-rich or deficient alkenes to give the corresponding
addition products (Scheme 1).2
DMF, rt
1a
2a
3aa
4
in the absence of additive
in the presence of pyridine
20%
86%
53%
10%
Next, the reactions of 1a and various silyl enol ethers were
examined as shown in Table 1. Silyl enol ethers having a termi-
nal methylene moiety 2b and 2c gave the corresponding prod-
ucts 3ab and 3ac in good yield (Runs 1 and 2). In the case of tri-
substituted silyl enol ether 2d, the reaction proceeded slowly to
give the desired product 3ad in only 19% yield with the adduct
of ꢀ-keto radical and pyridine 512 in 27% yield and with a 25%
recovery of 1a (Run 3).
OTBS
Ph
O
O
Ph OH
Mn(pic)3 (2.4 mol amt.)
+
Ph
Ph
DMF, 0 °C, 0.5 h
89%
Mn(pic)3
−TBSX
OTBS
Ph
O
O
OTBS
Ph
O
OTBS
Ph
O
Mn(pic)3
Ph
Ph
Ph
Ph
A wide range of cyclopropanols13 reacted with silyl enol
ethers 2a and 2b as summarized in Table 2. 1-Phenethylcyclo-
propanol (1b) reacted with 2a and 2b to afford the corresponding
adducts in good yield (Run 1 and 2). As shown in Run 3–5, 1-tri-
methylsilylcyclopropanol (1c) and cyclopropanone hemiacetal
1d could be employed as ꢀ-trimethylsilylcarbonyl and ꢀ-eth-
oxycarbonyl radical sources, respectively. The reaction of bicy-
clo[4.1.0]heptan-1-ol (1e) gave the ring-expanded seven-mem-
bered adduct 3ea as a major product (Run 6). 1-(2-Oxoalkyl)-
cyclopropanol derivative 1f was found to act as a ꢀ-diketone unit
to give tricarbonyl compound 3fa by the reaction with 2a in
moderate yield (Run 7), while the protection of the carbonyl
group of 1f as an acetal improved the yield to 79% (Run 8).
Three component coupling14 was carried out with the com-
bination of cyclopropanols and electoron-deficient and rich al-
3
3
TBS = t-BuMe2Si
Scheme 1.
Though this oxidative radical generation exhibits wide gen-
erality, the use of a stoichiometric amount of Mn(pic)3 prevents
the application to a large-scale synthesis. In fact, in our total syn-
thesis of a natural product, sordaricin,3 it was desired to improve
this stoichiometric reaction to a catalytic process. Herein, we
would like to report a catalytic ꢀ-keto radical formation from
cyclopropanol derivatives by the use of AgNO3–(NH4)2S2O8–
pyridine system.
Peroxodisulfate salts, [M2þS2O82ꢁ] are widely used as an
oxidant of metal salts.4 For example, Citterio et al. reported
the generation of ꢁ-keto radicals from ketones by the use of a
catalytic amount of AgNO3 and Na2S2O8 as a reoxidant in aque-
ous media, in which AgII species were supposed to participate in
the oxidation.5
Table 1. The reactions of 1-phenylcyclopropanol (1a) with
various silyl enol ethers 2a
We considered that cyclopropanols might be oxidized even
with AgI species under mild reaction conditions and examined
the reaction of 1-phenylcyclopropanol (1a)6 and ꢁ-(t-butyldi-
methylsiloxy)styrene (2a) with the combination of cat. AgNO3
and (NH4)2S2O8 (Eq 1).7 When a 0.1 molar amount of AgNO3
and 2.4 molar amounts of (NH4)2S2O8 were added to a mixture
of 1a and 2a in DMF, the reaction proceeded at room tempera-
ture to afford the addition product 3aa and propiophenone (4) in
20 and 53% yield, respectively. Then, the reaction was examined
in the presence of various amines, which would act as a trapping
reagent of the acid generating during this oxidation and also as a
ligand coordinating to AgI species.8 When 2 molar amounts of
pyridine was added, the yield of 3aa was improved to 86%,9
while 2,6-lutidine, 2,2-bipyridine, pyrazine, and DBU were not
so effective for this reaction.10 Contrary to the formation of high-
ly reactive AgII species by the oxidation with peroxodisulfate
Run
Silyl enol ether
OTBS
Time/h
Product (yield/%)b
O
O
1
3
(78)
Ph
Bu
Bu
3ab
3ac
2b
O
O
O
OTBS
(75)
(19)
2
2
6
Ph
Ph
Me
Ph
Me
2c
O
OTBS
3c
Me
Ph
Me
2d
3ad
O
N
Ph
5
aReaction conditions; DMF, rt. 1a:2:AgNO3:(NH4)2S2O8:pyridine =
1:2:0.1:2.4:2. bIsolated yield based on cyclopropanol 1a. 5 was obtained
in 27% yield, and 1a was recovered in 25% yield.
c
Copyright Ó 2006 The Chemical Society of Japan

Chemistry Letters Vol.35, No.1 (2006)
19
Table 2. The oxidative radical reaction of various cyclopropa-
nols 1 with silyl enol ethers 2a and 2ba
radical addition of bicyclo[n.1.0] compounds bearing an alkene
moiety at the suitable position (Eq 2). 5-(3-Butenyl)bicyclo-
[4.1.0]heptan-1-ol (7a) and 6-(3-butenyl)bicyclo[5.1.0]octan-1-
ol (7b) were successfully transformed to bicyclo[5.3.0]decan-
3-one derivative 8a having a guaiane skeleton, and bicyclo-
[6.3.0]dodecan-3-one derivative 8b with high stereoselectivity2e
under this catalytic system in the presence of 1,4-cyclohexadiene
as a radical-trapping reagent.
Run
1
Cyclopropanol
2a or 2b
Product (yield/%)b
O
O
Ph
OH
2a
(81)
Ph
Ph
Ph
Ph
Ph
3ba
3bb
1b
1b
O
O
2
3
2b
2a
(72)
Bu
0.1 mol amt. AgNO3
O
O
O
O
Me3Si
OH
1.5 mol amt. (NH4)2S2O8
2.0 mol amt. pyridine
(56)
H
Me3Si
O
OH
3ca
3cb
3da
1c
1c
3.0 mol amt.
(2)
H
n
n
4
5
2b
2a
(66)
Bu
DMF, rt, 4 h
Me3Si
EtO
7a (n = 1)
7b (n = 2)
8a (n = 1); 85%
8b (n = 2); 80%
O
O
O
EtO
OH
(76)
O
This work was supported by the Grant-in-Aid for The 21st
Century COE program for Frontiers in Fundamental Chemistry
from Ministry of Education, Culture, Sports, Science and
Technology, Japan.
1d
OH
O
O
6
2a
Ph
Ph
(59)
O
(13)
3ea′
1e
1f
3ea
O
References and Notes
Me
OH
O
1
There are some reports on the generation of ꢀ-keto radicals from
cyclopropanols and their addition reactions by the stoichiometric
use of metallic oxidants. For example, see: a) FeIII, CuII: S. E.
Schaafsma, R. Jorritsma, H. Steinberg, T. J. de Boer, Tetrahedron
Lett. 1973, 14, 827. b) CuII: B. B. Snider, T. Kwon, J. Org. Chem.
1992, 57, 2399. c) FeIII: K. I. Booker-Milburn, A. Barker, W.
Brailsford, B. Cox, T. E. Mansley, Tetrahedron 1998, 54, 15321.
a) N. Iwasawa, S. Hayakawa, K. Isobe, K. Narasaka, Chem. Lett.
1991, 1193. b) N. Iwasawa, S. Hayakawa, M. Funahashi, K. Isobe,
K. Narasaka, Bull. Chem. Soc. Jpn. 1993, 66, 819. c) N. Iwasawa,
M. Funahashi, S. Hatakawa, K. Narasaka, Chem. Lett. 1993, 545.
d) K. Narasaka, Pure Appl. Chem. 1997, 69, 601. e) N. Iwasawa,
M. Funahashi, S. Hatakawa, T. Ikeno, K. Narasaka, Bull. Chem.
Soc. Jpn. 1999, 72, 85.
7
8
2a
2a
(51)
O
Me
Ph
3fa
Me
OH
O
O
O
O
O
O
(79)
Me
Ph
1g
3ga
aReaction conditions; DMF, rt, 2.5–5.5 h. 1:2:AgNO3:(NH4)2S2O8:
pyridine = 1:2:0.1:2.4:2. bIsolated yield based on cyclopropanol 1.
2
Table 3. Three component coupling reactionsa
cat. AgNO3
(NH4)2S2O8
pyridine
OTBS
EWG
3
4
5
M. Kitamura, S. Chiba, K. Narasaka, Chem. Lett. 2004, 33, 942.
F. Minisci, A. Citterio, Acc. Chem. Res. 1983, 16, 27.
A. Citterio, F. Ferrario, S. de Bernardinis, J. Chem. Res., Synop.
1983, 310.
+
+
cyclopropanols
product
Ph
2a
DMF, rt
1
2c, d
Run
1
Cyclopropanol
EWG
Product (yield/%)b,c
6
1a was decomposed at 0.05–0.1 V by cyclic voltammetry. [1 mA in
DMF; supporting electrocycle: 0.1 M n-Bu4NClO4; working elec-
trode: glassy carbon; counter electrode: platinum wire; reference
electrode: Ag/AgCl [E1=2 (ferrocene/ferricinium) = þ0:65 V] at
O
NC
O
Ph
OH
CN
(62)
(65)
Ph
Ph
Ph
2c
1a
1b
1d
6a
25 ꢂC; scan rate: 100 mV sꢁ1
.
O
NC
O
Ph
OH
CN
2
3
7
In the case of the combined use of a 0.1 molar amount of Mn(pic)3
and (NH4)2S2O8 in DMF, the reaction proceeded at 50 ꢂC to afford
3a and 4 in 10 and 22% yield, respectively.
Ph
2c
6b
EtO2C
O
O
EtO
OH
ꢀ
CO2Et
8
9
K. Nilsson, A. Oskarsson, Acta Chem. Scand., Ser. A 1982, 36, 605.
(59)
EtO
Ph
When 1a was treated in the absence of 2a, propiophenone 4, the self-
coupling product of the ꢀ-keto radical, and the adduct of ꢀ-keto radi-
cal and pyridine 5 were obtained in 12, 31, and 6% yield, respective-
ly. When 2a was treated in the absence of the cyclopropanol, 2a was
recovered without the formation of the self-coupling product of 2a.
2d
6d
aReaction conditions; DMF, rt, 3.5–4 h. 1a:2:AgNO3:(NH4)2S2O8:pyridine
= 1:2:0.1:2.4:2. bIsolated yield based on cyclopropanol 1a. cThe undesira-
ble cross-addition products 3 were obtained in 6% (3aa), 5% (3ba), and
14% (3da) yield, respectively.
10 When 2,6-lutidine was added, the reaction did not proceed at all. In
the cases of pyrazine, 2,2-bipyridine, and DBU, 3aa was obtained in
41, 55, and 66% yield, respectively.
11 The oxidation potential of Ag(II) species is enough to oxidize silyl
enol ethers. Under the present catalytic system, silyl enol ethers were
not oxidized as mentioned in Ref. 10. The one electron oxidation
potential of various silyl enol ethers, see: S. Fukuzumi, M. Fujita,
J. Otera, Y. Fujita, J. Am. Chem. Soc. 1992, 114, 10271.
12 F. Minisci, C. Giordano, E. Vismara, S. Levi, V. Tortelli, J. Am.
Chem. Soc. 1984, 106, 7146.
kenes. Electron-deficient alkenes were expected to react firstly
with nucleophilic ꢀ-keto radicals to generate electron-deficient
radicals, which would be trapped finally with electron-rich al-
kenes. As expected, cyclopropanols (1a, 1b, and 1d) reacted
with electoron-deficient alkenes (2c or 2d), and electron-rich
alkene 2a in this order, and the three components coupling
products (6a, 6b, and 6d) were obtained in good to moderate
yield with a small amount of cyclopropanol-electron-rich alkene
addition products 3 (Table 3).
13 For synthetic methods of cyclopropanols 1, see: O. G. Kulinkovich,
Chem. Rev. 2003, 103, 2597, and references therein.
14 K. Mizuno, M. Ikeda, S. Toda, Y. Otsuji, J. Am. Chem. Soc. 1988,
110, 1288.
This catalytic system could be applied to the intramolecular
Published on the web (Advance View) November 29, 2005; DOI 10.1246/cl.2006.18