Addition to electron deficient olefins of α-oxy carbon-centered radicals, generated from cyclic ethers and acetals by the reaction with alkylperoxy- λ3-iodane

Article abstract of DOI:10.3390/10010195

Thermal decomposition of 1-tert-butylperoxy-1,2-benziodoxol-3(1H)-one in cyclic ethers and acetals at 50°C generates α-oxy carbon-centered radicals, which undergo an addition reaction with vinyl sulfones and unsaturated esters.

Full text of DOI:10.3390/10010195

Molecules 2005, 10, 195-200
molecules
ISSN 1420-3049
http://www.mdpi.org
Addition to Electron Deficient Olefins of α-Oxy Carbon-
Centered Radicals, Generated from Cyclic Ethers and Acetals
by the Reaction with Alkylperoxy- λ3-iodane
Takuya Sueda, Yasunori Takeuchi, Takashi Suefuji and Masahito Ochiai *
Faculty of Pharmaceutical Sciences, University of Tokushima, 1-78 Shomachi, Tokushima 770-8505,
Japan, Tel. (+81) 88 633 7281, Fax (+81) 88 633 9504.
* Author to whom correspondence should be addressed; e-mail: mochiai@ph.tokushima-u.ac.jp
Received: 11 May 2004; in revised form: 24 November 2004 / Accepted: 25 November 2004 /
Published: 31 January 2005
Abstract: Thermal decomposition of 1-tert-butylperoxy-1,2-benziodoxol-3(1H)-one in
cyclic ethers and acetals at 50 °C generates α-oxy carbon-centered radicals, which
undergo an addition reaction with vinyl sulfones and unsaturated esters.
Keywords: Radical, iodane, ether, vinyl sulfone, maleate
Introduction
Commercially available crystalline 1-tert-butylperoxy-1,2-benziodoxol-3(1H)-one (1) serves as a
versatile oxidizing agent [1]; thus, sulfides, secondary and tertiary amines and amides are readily
oxidized with the tert-butylperoxy -λ3-iodane 1 to the corresponding sulfoxides, imines, tert-butyl-
peroxyamino acetals and imides, respectively [2]. Oxidation of 4-substituted phenols affords
4-(tert-butylperoxy)-2,5-cyclohexadien-1-ones in good yields [3].
t-BuOO
I
O
I
O
+
O
t-BuOO
O
1
2
The λ3-iodane 1 is stable in the solid state but gradually decomposes in solution at ambient
temperature to generate tert-butylperoxy radical and [9-I-2] iodanyl radical 2 through homolytic

Molecules 2004, 9
196
cleavage of the hypervalent iodine(III)-peroxy bond. These radicals are responsible for the oxidation of
benzyl and allyl ethers with the λ3-iodane 1 in the presence of alkali metal carbonates, yielding the
corresponding esters via the intermediacy of benzylic and allylic radicals [4]. Recently, we found that
the gentle heating of a THF solution of the peroxy-λ3-iodane 1 at 50 °C for 10 h under argon produced
a mixture of o-iodobenzoic acid (5, 55%) and the acid-labile 2-tetrahydrofuranyl o-iodobenzoate (6,
45%) (Scheme 2) [5]. The formation of o-iodobenzoate 6 probably involves the following sequence:
(a) α-hydrogen atom abstraction from THF by the tert-butylperoxy radical and/or the iodanyl radical 2
to give the α-tetrahydrofuranyl radical 3, (b) a single-electron transfer from α-THF radical 3 to the
peroxy-λ3-iodane 1 (or tert-butylperoxy radical and the iodanyl radical 2), generating the oxonium ion
4, and finally, (c) nucleophilic attack of o-iodobenzoic acid 5, generated in situ on 4, yielding the ester
6. This mechanism was supported by the finding that the decomposition of the λ3-iodane 1 in THF in
the presence of an alcohol results in a competition between the formation of 6 and the tetra-
hydrofuranylation of the alcohol.
I
Scheme 1
CO2H
O
I
5
1
t-BuOO
O
+
O
O
O
O
6
3
4
Since α-THF radical 3 is nucleophilic in nature and undergoes addition to electron-deficient olefins
such as maleate esters [6] and vinyl sulfones [7], it seems reasonable to assume that, when the
decomposition of the peroxy-λ3-iodane 1 in THF is carried out in the presence of an electrophilic
olefin, addition of α-THF radical 3 to the double bond would take place, if the radical addition is faster
than a single-electron transfer from α-THF radical 3 to the peroxy-λ3-iodane 1. We report herein the
λ3-iodane-induced addition of α-oxy carbon-centered radicals generated from cyclic ethers and acetals
to electron deficient olefins, which proceeds under mild conditions.
Results and Discussion
Exposure of phenyl vinyl sulfone (7) to an equivalent amount of the peroxy-λ3-iodane 1 in THF
at 50 °C for 24 h under argon resulted in an addition reaction of THF with formation of 2-[2-(phenyl-
sulfonyl)ethyl]tetrahydrofuran (8a) in 83% yield (Scheme 2 and Table 1, Entry 2). Use of 0.3
equivalents of 1 decreased the yield of 8a to 66%. 1,3-Dioxolane serves as an excellent hydrogen
donor for the attack of electrophilic radicals such as t-BuO· [8]. Thus, in 1,3-dioxolane with the use of
0.3 equivalents of 1, the addition product 8c was obtained in 76% yield. Less reactive tetrahydropyran
(THP) and 1,4-dioxane afforded moderate yields (50-52%) of 2-alkylated ethers 8b and 8d,
respectively (Table 1, Entries 3 and 5). These reactivity differences seem to correlate well with their
corresponding C-H bond dissociation energies: THF (2-H), 89.8 kcal/mol; 1,3-dioxolane (2-H), 90.0
kcal/mol; THP (2-H), 92.1 kcal/mol; 1,4-dioxane, 93.2 kcal/mol [8a]. Attempted addition of
1,3-dioxolane to (E)-1-propenyl phenyl sulfone was found to be fruitless [7c,d].

Molecules 2004, 9
Scheme 2
197
O
SO2Ph
1
SO2Ph
+
50 ÞC, 24 h, Ar
O
7
8a
The formation of the 2-alkylated 1,3-dioxolane 8c in good yield is very interesting, because
2-alkyl- and 2-aryl-1,3-dioxolanes undergo oxidative ring cleavage by the reaction with the
peroxy-λ3-iodane 1 in the presence of tert-butyl hydroperoxide and potassium carbonate in benzene at
room temperature, yielding glycol monoesters [9].
Table 1. Addition of cyclic ethers to phenyl vinyl sulfone 7 a
λ3-Iodane
1 (equiv)
Product
8
Entry
Ether
THF
THF
THP
Structure
Yield (%) b
O
O
O
SO2Ph
1
2
3
0.3
8a
8a
8b
66
SO2Ph
1
83
50
SO2Ph
1
O
SO2Ph
SO2Ph
4
5
0.3
1
1,3-dioxolane
1,4-dioxane
8c
76
52
O
O
8d
O
O
Me
6
1 c
1,3-dioxolane
8e
0
SO2Ph
O
a Reactions were carried out at 50 °C for 24 h under argon. b Isolated yields.
c Reaction with (E)-1-propenyl phenyl sulfone.
Unsaturated esters serve as efficient acceptors for α-oxy carbon-centered radicals generated from
cyclic ethers and acetals [10]. The reaction with diethyl fumarate (E)-(9) in the presence of the
peroxy-λ3-iodane 1 (1 equiv.) in THF at 50 °C for 24 h under argon afforded diethyl
2-tetrahydrofuranylsuccinate (10a) as a 1:1 mixture of diastereoisomers in 47% yield (Table 2). With
diethyl maleate (Z)-(9), a higher yield (61%) of the succinate 10a (a 1:1 mixture of diastereoisomers)
was obtained. 1,3-Dioxolane also undergoes an addition reaction toward the unsaturated diesters to
give diethyl (1,3-dioxolan-2-yl)succinate (10b) in high yields (Table 2, Entries 3 and 4). In these
reactions, diethyl maleate (Z)-(9) served as a more efficient acceptor of α-oxy carbon-centered radicals
than diethyl fumarate (E)-(9) [10a,b].

Molecules 2004, 9
Scheme 3
198
X
X
EtO2C
1
+
EtO2C
O
50 ÞC, 24 h, Ar
O
CO2Et
CO2Et
(E)-9
(Z)-9
10
Table 2. Addition of cyclic ethers to unsaturated esters 9 a
Product
Entry
Olefin
Ether
10
Yield (%) b
47 (53) c
61 (70) c
81
1
2
3
4
(E)-9
(Z)-9
(E)-9
(Z)-9
THF
THF
1,3-dioxolane
1,3-dioxolane
10a
10a
10b
10b
88
a Reactions were carried out using one equiv. of the peroxy-λ3-iodane 1 at 50 °C
for 24 h under argon. b Isolated yields. Values in parentheses are GC yields. c A
1:1 mixture of stereoisomers.
The addition of cyclic ethers to the electron-deficient olefins probably involves the reaction
sequence shown in Scheme 4. Addition of the nucleophilic α-oxy carbon-centered radical 3 to the
electron-deficient olefins produces the carbon radicals 11 bonded to the electron-withdrawing group
(EWG). This process may compete with a single-electron transfer from α-THF radical 3 to the
peroxy-λ3-iodane 1 (or tert-butylperoxy radical and the iodanyl radical 2), generating the oxonium ion
4.
Scheme 4
EWG
O
EWG
+
t-BuOO
O
O
t-BuOOH
11
3
O
EWG
O
+
O
Experimental
General
1H-NMR spectra were recorded in CDCl3 on JEOL AL 300 or JNM GX-400 spectrometers using
tetramethylsilane as an internal standard. The IR spectra were recorded on a Jasco FT-IR 420

Molecules 2004, 9
199
spectrometer. The mass spectra were taken on a JEOL JMS-DX300 spectrometer. Analytical gas
chromatography (GC) was carried out on a Shimazu GC-8A gas chromatograph with a column of 10%
silicone SF-96 on Chromosorb W (AW-DMCS). Preparative thin-layer chromatography (TLC) was
carried out on Kieselgel 60 F254 (Merk).
General Procedure for Addition of Cyclic Ethers to Phenyl Vinyl Sulfone (2). A Typical Example:
2-[2-(Phenylsulfonyl)ethyl]tetrahydrofuran (8a) (Table 1, Entry 2).
To a mixture of tert-butylperoxy-λ3-iodane 1 (67 mg, 0.2 mmol) and phenyl vinyl sulfone (2, 34
mg, 0.2 mmol) was added THF (1.2 mL) at room temperature under argon and the stirred mixture was
heated at 50 °C for 24 h. The reaction was quenched by addition of a 5% aqueous K2CO3 solution and
the mixture extracted with dichloromethane. The combined organic extracts were washed with water
and brine, dried over anhydrous Na2SO4, and concentrated in vacuo to give an oil which was purified
1
by preparative TLC (hexane-ethyl acetate 6:4) to give the sulfone 8a (39.7 mg, 83%)[7a]; H-NMR
(300 MHz): δ 7.92 (2H, d, J= 7.7 Hz), 7.67 (1H, t, J= 6.9 Hz), 7.57 (2H, dd, J= 6.9, 7.7 Hz), 3.90-3.63
(3H, m), 3.37-3.23 (1H, m), 3.20-3.08 (1H, m), 2.07-1.76 (5H, m), 1.53-1.39 (H, m).
2-[2-(Phenylsulfonyl)ethyl]tetrahydropyran (8b): 1H-NMR (400 MHz) δ 7.91 (2H, d, J= 8.0 Hz), 7.65
(1H, t, J= 8.0 Hz), 7.56 (2H, t, J= 8.0 Hz), 3.88 (1H, br d, J = 12.0 Hz), 3.37-3.23 (3H, m), 3.20-3.10
(1H, m), 1.96-1.85 (1H, m), 1.85-1.72 (2H, m), 1.56-1.39 (4H, m), 1.30-1.17 (1H, m); IR (neat) ν
(cm-1) 3063, 2935, 2847, 1585, 1446, 1308, 1146, 1086, 1047, 880, 742, 690; EIMS m/z (%) 254 (M+,
24), 225 (19), 143 (15), 112 (100), 85 (42), 77 (33); HRMS (EI) calcd. for C13H18O3S (M+): 254.0977,
found 254.0990.
1
2-[2-(Phenylsulfonyl)ethyl]-1,3-dioxolane (8c) [7b]: H-NMR (300 MHz): δ 7.92 (2H, d, J= 7.7 Hz),
7.67 (1H, t, J= 6.9 Hz), 7.57 (2H, dd, J= 6.9, 7.7 Hz), 4.97 (1H, t, J= 3.6 Hz), 3.95-3.79 (4H, m),
3.31-3.14 (2H, m), 2.13-2.03 (2H, m).
2-[2-(Phenylsulfonyl)ethyl]-1,4-dioxane (8d) [7b]: 1H-NMR (300 MHz): δ 7.91 (2H, br d, J= 7.7 Hz),
7.67 (1H, br t, J= 6.9 Hz), 7.58 (2H, dd, J= 6.9, 7.7 Hz), 3.73-3.08 (9H, m), 1.90-1.66 (2H, m).
General Procedure for Addition of Cyclic Ethers to Unsaturated Ester (9). A Typical Example:
Diethyl (Tetrahydrofuran-2-yl)succinate (10a) (Table 2, Entry 1).
To a stirred suspension of tert-butylperoxy-λ3-iodane 1 (50 mg, 0.15 mmol) in THF (1.5 mL) was
added diethyl fumarate (E)-(9) (26 mg, 0.15 mmol) at room temperature under argon and the mixture
was heated at 50 °C for 24 h. The reaction was quenched by addition of a 5% aqueous K2CO3 solution
and the mixture was extracted with diethyl ether. The combined organic extracts were washed with
water and brine, dried over anhydrous Na2SO4, and concentrated in vacuo to give an oil, which was
purified by preparative TLC (hexane-ethyl acetate 6:4) to give the ester 10a (17.2 mg, 47%) as a 1:1
mixture of diastereoisomers (as determined by analytical GC) [6]. Ester 10a with a larger Rf value:
1H-NMR (300 MHz): δ 4.17 (2H, q, J= 6.9 Hz), 4.13 (2H, q, J= 6.9 Hz), 4.00 (1H, q, J= 6.9 Hz),

Molecules 2004, 9
200
3.87-3.67 (2H, m), 2.93-2.86 (1H, m), 2.78 (1H, dd, J= 8.8, 16.5 Hz), 2.69 (1H, dd, J= 5.2, 16.5 Hz),
2.07-1.67 (4H, m), 1.27 (3H, t, J= 6.9 Hz), 1.24 (3H, t, J= 6.9 Hz). Ester 10a with a smaller Rf value:
1H-NMR (300 MHz): δ 4.19 (2H, q, J= 6.9 Hz), 4.13 (2H, q, J= 6.9 Hz), 4.12-4.02 (1H, m), 3.92-3.81
(1H, m), 3.79-3.68 (1H, m), 3.13-3.03 (1H, m), 2.75 (1H, dd, J= 9.6, 16.5 Hz), 2.47 (1H, dd, J= 4.1,
16.5 Hz), 2.0-1.81 (3H, m), 1.73-1.61 (1H, m), 1.27 (3H, t, J= 6.9 Hz), 1.25 (3H, t, J= 6.9 Hz).
1
Diethyl (1,3-Dioxolan-2-yl)succinate (10b) [10a]: H-NMR (300 MHz): δ 5.21 (1H, d, J= 3.9 Hz),
4.21 (2H, q, J= 6.9 Hz), 4.14 (2H, q, J= 6.9 Hz), 4.05-3.84 (4H, m), 3.23 (1H, dt, J= 9.4, 3.9 Hz), 2.78
(1H, dd, J= 9.4, 17.1 Hz), 2.61 (1H, dd, J= 3.9, 17.1 Hz), 1.28 (3H, t, J= 6.9 Hz), 1.26 (3H, t, J= 6.9
Hz).
References
1. For reviews, see: (a) Ochiai, M. In Topics in Current Chemistry; Wirth, T., Ed.; Springer: Berlin,
2003; Vol. 224, p. 5-68; (b) Ochiai, M. TCI Mail 1999, No. 104, 2-11; (c) Zhdankin, V. V. Rev.
Heteroatom Chem. 1997, 17, 133-151; (d) Zhdankin, V. V.; Stang, P. J. Chem. Rev. 2002, 102,
2523-2584; (e) Muraki, T.; Togo, H.; Yokoyama, M. Rev. Heteroatom Chem. 1997, 17, 213-243.
2. (a) Ochiai, M.; Nakanishi, A.; Ito, T. J. Org. Chem. 1997, 62, 4253-4259; (b) Ochiai, M.;
Kajishima, D.; Sueda, T. Heterocycles 1997, 46, 71-76; (c) Ochiai, M.; Kajishima, D.; Sueda, T.
Tetrahedron Lett. 1999, 40, 5541-5544.
3. Ochiai, M.; Nakanishi, A.; Yamada, A. Tetrahedron Lett. 1997, 38, 3927-3930.
4. (a) Ochiai, M.; Ito, T.; Takahashi, H.; Nakanishi, A.; Toyonari, M.; Sueda, T.; Goto, S.; Shiro, M.
J. Am. Chem. Soc. 1996, 118, 7716-7730; (b) Ochiai, M.; Ito, T.; Masaki, Y.; Shiro, M. J. Am.
Chem. Soc. 1992, 114, 6269-6270.
5. Ochiai, M.; Sueda, T. Tetrahedron Lett. 2004, 45, 3557-3559.
6. Rosenthal, I.; Elad, D. Tetrahedron 1967, 23, 3193-3204.
7. (a) Matthews, D. P.; McCarthy, J. R. J. Org. Chem. 1990, 55, 2973-2975; (b) Boivin, J.; Crepon,
E.; Zard, S. Z. Bull. Soc. Chim. Fr. 1992, 129, 145-150; (c) Togo, H.; Aoki, M.; Yokoyama, M.
Chem. Lett. 1992, 2169-2172; (d) Togo, H.; Aoki, M.; Yokoyama, M. Tetrahedron 1993, 49,
8241-8256.
8. (a) Shtarev, A. B.; Tian, F.; Dolbier, W. R.; Smart, B. E. J. Am. Chem. Soc. 1999, 121,
7335-7341; (b) Malatesta, V.; Ingold, K. U. J. Am. Chem. Soc. 1981, 103, 609-614; (c) Malatesta,
V.; Scaiano, J. C. J. Org. Chem. 1982, 47, 1455-1459.
9. Sueda, T.; Fukuda, S.; Ochiai, M. Org. Lett. 2001, 3, 2387-2390.
10. (a) Watanabe, Y.; Tsuji, Y.; Takeuchi, R. Bull. Chem. Soc. Jpn. 1983, 56, 1428-1430; (b)
Tsujimoto, S.; Sakaguchi, S.; Ishii, Y. Tetrahedron Lett. 2003, 44, 5601-5604; (c) Hirano, K.;
Sakaguchi, S.; Ishii, Y. Tetrahedron Lett. 2002, 43, 3617-3620; (d) Rosenthal, I.; Elad, D. J. Org.
Chem. 1968, 33, 805-811; (e) Kim, Y. H.; Yang, S. G. Rev. Heteroatom Chem. 1999, 20, 69-96.
© 2005 by MDPI (http://www.mdpi.org). Reproduction is permitted for noncommercial purposes.