Addition to Electron Deficient Olefins of α-Oxy Carbon- Centered Radicals, Generated from Cyclic Ethers and Acetals by the Reaction with Alkylperoxy- λ³-iodane

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.

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].

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 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.

Scheme 1.

Scheme 1.

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].

Scheme 2.

Scheme 2.

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

Entry	λ3-Iodane 1 (equiv)	Ether	Product
			Structure	8	Yield (%) b
1	0.3	THF		8a	66
2	1	THF		8a	83
3	1	THP		8b	50
4	0.3	1,3-dioxolane		8c	76
5	1	1,4-dioxane		8d	52
6	1 c	1,3-dioxolane		8e	0

^a Reactions were carried out at 50 °C for 24 h under argon. ^b Isolated yields.

^c Reaction with (E)-1-propenyl phenyl sulfone.

Table 1. Addition of cyclic ethers to phenyl vinyl sulfone 7 ^a

Entry	λ3-Iodane 1 (equiv)	Ether	Product
			Structure	8	Yield (%) b
1	0.3	THF		8a	66
2	1	THF		8a	83
3	1	THP		8b	50
4	0.3	1,3-dioxolane		8c	76
5	1	1,4-dioxane		8d	52
6	1 c	1,3-dioxolane		8e	0

^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].

Scheme 3.

Scheme 3.

Table 2. Addition of cyclic ethers to unsaturated esters 9 ^a

Entry	Olefin	Ether	Product
			10	Yield (%) b
1	(E)-9	THF	10a	47 (53) c
2	(Z)-9	THF	10a	61 (70) c
3	(E)-9	1,3-dioxolane	10b	81
4	(Z)-9	1,3-dioxolane	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.

Table 2. Addition of cyclic ethers to unsaturated esters 9 ^a

Entry	Olefin	Ether	Product
			10	Yield (%) b
1	(E)-9	THF	10a	47 (53) c
2	(Z)-9	THF	10a	61 (70) c
3	(E)-9	1,3-dioxolane	10b	81
4	(Z)-9	1,3-dioxolane	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.

Scheme 4.

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 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 Ethersto 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 by preparative TLC (hexane-ethyl acetate 6:4) to give the sulfone 8a (39.7 mg, 83%) [7a]; ¹H-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.

2-[2-(Phenylsulfonyl)ethyl]-1,3-dioxolane (8c) [7b]: ¹H-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), 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).

Diethyl (1,3-Dioxolan-2-yl)succinate (10b) [10a]: ¹H-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).