Cobalt-Catalyzed Oxygenation/Dearomatization of Furans

Jonathan P Oswald; K A Woerpel

doi:10.1021/acs.joc.8b01183

. Author manuscript; available in PMC: 2019 Aug 17.

Published in final edited form as: J Org Chem. 2018 May 29;83(16):9067–9075. doi: 10.1021/acs.joc.8b01183

Cobalt-Catalyzed Oxygenation/Dearomatization of Furans

Jonathan P Oswald ¹, K A Woerpel ^1,^*

PMCID: PMC6492292 NIHMSID: NIHMS1025706 PMID: 29768918

Abstract

The dearomatization of aromatic compounds using cobalt(II) acetylacetonate with triplet oxygen and triethylsilane converts furans, benzofurans, pyrroles, and thiophenes to a variety of products, including lactones, silyl peroxides, and ketones.

Graphical Abstract:

graphic file with name nihms-1025706-f0001.jpg

INTRODUCTION

The cobalt-catalyzed oxygenation of alkenes¹ is a synthetically useful reaction for the production of a number of oxidized products, including alcohols,^2,3 peroxides,^2–6 epoxides,⁶ and ketones.⁷ The conditions are mild, requiring a bis-(1,3-diketonato)cobalt(II) catalyst, such as Co(acac)₂, Co(thd)₂,^7,8 or Co(modp)₂ (Figure 1),^8–10 in the presence of a silane and triplet oxygen, usually at room temperature. The reaction is chemoselective for highly substituted electron-rich carbon–carbon double bonds over less substituted ones.¹⁰ Because the reaction generates a carbon-centered radical intermediate, functionalization typically occurs at the more substituted carbon atom. Alkenes with aromatic groups are also generally oxidized readily.^8,10,11 In this Article, we report that the cobalt catalyst is reactive enough that it can functionalize the π-system of some aromatic compounds, including furans, pyrroles, and thiophenes, resulting in dearomatization. These reactions lead to the formation of products such as lactones, silyl peroxides, and ketones.

RESULTS AND DISCUSSION

During our investigation into the synthesis of endoperoxides using Co(acac)₂, Et₃SiH, and oxygen gas,^9–11 we observed that furan-substituted alkenes gave products that suggested that the aromatic ring had reacted. Although phenyl groups are generally unreactive under these conditions,^8,10,11 furyl groups, considering that they are not as strongly stabilized by aromaticity,^12,13 could be reactive, as they are in other oxidation transformations.^14,15 Control experiments supported this hypothesis: when 2-acetylfuran (1) was treated with the standard oxidation conditions, lactone 2 was formed as the sole identifiable product (Scheme 1). The formation of this product was not anticipated, considering that it involved not only dearomatization, but also loss of a substituent (the acetyl group).

The yield of the dearomatized product 2 could be improved by adjusting the reaction conditions (Table 1). Because lactone 2 (Scheme 1) decomposed in the presence of Co(acac)₂ over time, the catalyst loading was decreased. Furthermore, t-BuOOH was added to decrease the induction period of the reaction,^11,16 which limited the exposure of the product to the reaction conditions. The addition of acetylacetone also allowed for decreased catalyst loading in addition to reduced reaction times (Table 1, entry 5), likely because it served as a supporting ligand to limit catalyst decomposition. Excessive amounts of acetylacetone did not have a positive impact on the yield, however (Table 1, entry 4). The addition of more equivalents of Et3SiH also increased the yield, suggesting that an unproductive pathway consumed the silane, although addition of more than 15 equivalents did not increase the yield significantly (Table 1, entry 10 and 11). Increasing the reaction temperature to 40 °C allowed the catalyst loading to be decreased to 2 mol %, and reactions were complete in four hours with a 62% yield, as determined by ¹H NMR spectroscopy (Table 1, entry 12). Other cobalt(II) catalysts were screened (Table 1, entry 7 and 8) using the optimized conditions, but they proved to be less effective than Co(acac)₂.

Table 1.

Optimization of Co-Catalyzed Oxgenation of Furans



Entry	CoL₂ (mol %)	Et₃SiH (equiv)	acetyl acetone (equiv)	temp	time	yield 2^a (NMR)
1	acac (40)	10	-	rt	24 h	38%
2	acac (40)	10	1	rt	2 h	45%
3	acac (40)	10	2	rt	2 h	49%
4	acac (40)	10	5	rt	2 h	39%
5	acac (10)	10	2	rt	2 h	48%
6	acac (5)	10	1	40 °C	1.5 h	49%
7	modp (5)	15	1	40 °C	1.5 h	24%
8	thd (5)	15	1	40 °C	1.5 h	28%
9	acac (5)	15	1	40 °C	1.5 h	58%
10	acac (5)	20	1	40 °C	1 h	59%
11	acac(5)	25	1	40 °C	1 h	53%
12	acac (2)	15	1	40 °C	4 h	62%

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Yield by ¹H NMR spectroscopy with mesitylene as internal standard.

An important clue as to how the acetyl group was removed was provided by experiments with a 2-furoic acid ester. When 2-methylfuroate (3) was subjected to the reaction conditions (Scheme 2), the lactone 2 was formed as the major isolable product, indicating that a carbomethoxy group can also be removed upon oxidation. In addition, however, two products were isolated that retained the carbomethoxy group. These products were the two diastereomers of a bis(silylperoxy) ester (4 and 5).

Scheme 2 — Co-Catalyzed Oxygenation of 2-Methyl Furoate

The isolation of both lactone products and bis(silylperoxy) esters suggested that the bis(peroxide), or a structurally similar intermediate, could be a precursor to the lactone products. Upon standing in a deuterated solvent, a purified sample of bis(silylperoxy) ester 4 decomposed into the lactone (Scheme 3). This observation suggests that an intermediate resembling the bis(peroxide) is the first-formed product in these reactions.

A mechanism can be proposed that is consistent with these observations (Scheme 4). First, addition of a cobalt-hydride¹¹ to the C₄–C₅ double bond of furan 1 would form a stabilized, captodative radical (I).¹⁷ Capture of this radical by O₂ at C₄, followed by silyl peroxide formation, precedes a second peroxidation via a captodative radical at C₂, which would form Co(III)–alkylperoxo complex II. This Co(III)–alkylperoxo complex resembles the intermediate in the conversion of bis(peroxides) 4 and 5 to lactone 2 (Scheme 3). Conversion of Co(III)–alkylperoxo complex II to lactone 2 likely first involves cyclization of II to dioxetane III, followed by a [2 + 2] cycloreversion of dioxetane III, resulting in cleavage of the carbonyl group and formation of lactone 2. Related cleavage reactions have been observed for other α-acylperoxides.^18–20 The Co(III)–alkylperoxo complex II is a more plausible intermediate than the corresponding silyl peroxide because although bis(peroxides) 4 and 5 are converted to lactone 2, it occurs more slowly (Scheme 3).

The cobalt-catalyzed oxygenation was general for several substituted furans (Table 2). When the furan was substituted at the 2-position with a carbonyl group, lactones were observed as the principal product. More sterically hindered furans 8a–8c, which were synthesized from furan 6 as outlined in Scheme 5, exhibited decreased yields and typically required longer reaction times (Table 2, entries 4–7), likely because of steric hindrance during the initial addition of the cobalt-hydride species.¹¹ Whereas furan-derived ketones and esters both gave the product where the side-chain had been removed, the corresponding carboxylic acid was unreactive (entry 3). The peroxidation of disubstituted furans was diastereoselective, forming the resulting lactones as single diastereomers (entries 4–7). The relative configuration of the disubstituted lactones was found to be trans, which was determined by converting silyl peroxide 9 to the known alcohol (9a, Scheme 6) and comparing the ¹H and ¹³C NMR chemical shifts to reported values.²¹ Isolating only one diastereomer²² of product was not expected because the cobalt-catalyzed oxygenation of alkenes is typically not diastereoselective.^23–25 Selectivity has only been observed in systems where the diastereotopic faces of the alkenes are sterically quite distinct.^26–29

Table 2.

Substituted Furan Screen



Entry	R¹	R²	Co(acac)₂ mol %	time	Yield
1	H	Me	5	2 h	23%
2	H	OMe	5	2.5 h	15%
3	H	OH	40	24 h	-
4	Me	Me	5	4 h	19%
5	Me	H	20	4 h	8%
6	Me	4-MeOC₆H₄	5	2 h	7%
7	Me	4-CF ₃C₆H₄	5	2 h	4%

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Scheme 5 — Disubstituted Furan Synthesis

Considering that the yields determined by NMR spectroscopy (Table 1) for 2-acetylfuran (1) are about 40% higher than the isolated yield of this compound (Table 2, entry 1), the product must be unstable. In general, α-peroxy carbonyl compounds can be difficult to synthesize and isolate in high yield.^30–32 The products were found to be sensitive to chromatography, which was determined by converting the silyl peroxide to the more stable silyl ether (10, Scheme 7) using triphenylphosphine,³³ which resulted in an increased yield compared to the silyl peroxide (Table 2, entry 1). The products were also found to decompose during the course of the reaction. In the dearomatization reaction, the peroxide moiety is sensitive to the reaction conditions used, particularly to the presence of the metal catalyst.¹¹ Evidence for this sensitivity was found when furan 8c was subjected to peroxidation conditions, resulting in formation of lactone 9 in addition to carboxylic acid 11 (Scheme 8). Silyl ester 12 could have been an intermediate, but it likely hydrolyzed to the carboxylic acid 11.³⁴ Based on the yields of carboxylic acid 11 (Scheme 8), most of the starting material was converted to lactone 9 through the mechanism shown in Scheme 4, but during the course of the reaction, lactone 9 decomposed.

Scheme 8 — Formation of Carboxylic Acid 11^a

The presence of a carbonyl group was not essential to observe peroxidation of furans, although different types of products were formed. Peroxidation of 2-methylfuran (13) formed only one product,³⁵ bis(silylperoxide) 14 (Scheme 9, eq 1), although the yield was low due to instability of bis(silylperoxide) 14 to chromatography. This product can be rationalized as involving initial peroxidation of 13 to form IV, followed by fragmentation to generate cobalt-alkyl species V (Scheme 9, eq 2). This complex would lead to the primary silyl peroxide, and then a second peroxidation would form bis(silylperoxide) 14 (Scheme 9, eq 2). 2-Benzylfuran (15, Scheme 9, eq 3) was also subjected to peroxidation conditions and instead of isolating a ring-opened product as seen with 2-methylfuran (13, Scheme 9, eq 1), diastereomeric bis(silylperoxides) 16 and 17 were isolated (Scheme 9, eq 3). In this case, the electron-withdrawing effect of the phenyl group seems to discourage the ring-opening mechanism depicted in Scheme 9, eq 2.

An experiment with dihydropyran 18 provided additional evidence supporting this ring-opening mechanistic hypothesis (Scheme 9, eq 2). Treatment of pyran 18 to the reaction conditions also produced a ring-opened product (19, Scheme 9, eq 4), likely through a similar pathway. The product, a primary peroxide, is difficult to synthesize by traditional cobalt-catalyzed peroxidation of alkenes, which forms secondary and tertiary peroxides.⁴

The position of the carbonyl group on the furan influences reactivity. When the carbonyl group was placed at the 3-position, as seen in ethyl 3-furoate (20), lactone 21 and bis(silylperoxide) 22 were isolated (Scheme 10). A possible explanation for the formation of lactone 21 first involves formation of cobalt-alkyl species VI (Scheme 10). Decomposition of the peroxide at C₂ of cobalt-alkyl species VI would generate the lactone (Scheme 10), a process observed for furans substituted at this position with a hydroperoxyl group.^36–38 Finally, another peroxide formation at C₄ would occur to give lactone 21 (Scheme 10). Bis(silylperoxide) 22 (Scheme 10) could be formed through a ring-opening mechanism analogous to the one shown in Scheme 9.

Scheme 10 — Co-Catalyzed Oxygenation of Ethyl 3-Furoate

Other furan-containing aromatic compounds undergo dearomatization during cobalt-catalyzed oxygenation. Both 2,3-benzofuran (23) and 1,3-diphenyl isobenzofuran (25) produced oxidized products upon exposure to the reaction conditions optimized for 2-acetylfuran (Scheme 11). 2,3-Benzofuran (23) produced the corresponding silyl peroxide (24, Scheme 11, eq 5), which likely involves a stabilized benzylic radical intermediate.¹⁰ The reaction of 1,3-diphenylisobenzofuran (25) produced dione 26 (Scheme 11, eq 6), a transformation that may follow a similar mechanism to the one proposed for reactions of 25 with peroxyl radicals.³⁹

Scheme 11 — Co-Catalyzed Oxygenation of Benzofurans

This cobalt-catalyzed dearomatization is not limited to furans. Pyrroles and thiophenes showed similar reactivity. Cobalt-catalyzed oxygenation of protected pyrrole 27 generated lactam 28 and only one isolable diastereomer of bis(silylperoxide) 29 (Scheme 12, eq 7), which is structurally analogous to bis(silylperoxide) 4 and 5 generated from 2-methylfuroate (Scheme 2). Just as in the case of the furan, this bis(silylperoxide) was shown to be a competent intermediate for the formation of the lactam (Scheme 12, eq 8). Similarly, 2-acetylthiophene (30) generated thiolactone 31, although this reaction only proceeded to 1% conversion after 23 h (Scheme 12, eq 9). The yields and rates of reaction of the five-membered ring heteroaromatic compounds correlate with the degree of aromaticity that these three heteroarenes exhibit. Furans, the least aromatic of the three, converted most rapidly, while thiophenes showed the lowest conversions because of their greater aromaticity.¹³

Scheme 12 — Co-Catalyzed Oxygenation of Pyrroles and Thiophenes

Indole (32) also reacted when subjected to cobalt-catalyzed oxygenation, although the reaction was slow. A trace amount of conjugated indolinone 33 (Scheme 13) was isolated, but indole 32 went mostly unreacted after 18 h. Indolinone 33 could be formed by incorporation of acetylacetonate into a 3H-indol-3-one.⁴⁰

Scheme 13 — Co-Catalyzed Oxygenation of Indoles

The cobalt-catalyzed oxygenation is not restricted to heteroaromatic compounds. Phenanthrene (34) was oxidized under these reaction conditions to form dione 35 (Scheme 14, eq 10). Anthracene (36) and naphthalene (37) were unreactive to cobalt-catalyzed oxygenation (Scheme 14, eq 11).^2,41

Scheme 14 — Co-Catalyzed Oxygenation of Arenes

CONCLUSION

In summary, we have demonstrated that cobalt-catalyzed oxygenation of aromatic compounds can occur. Under optimal conditions, furans, pyrroles, and thiophenes were dearomatized, yielding the corresponding lactones, lactams, and thiolactones. A mechanism has been suggested involving the formation of a bis(peroxy) intermediate, followed by cleavage of the carbonyl group. More structurally complex aromatic compounds, such as benzofuran and indole derivatives, were also oxidized. Cobalt-catalyzed oxygenation of indole allows for the incorporation of acetylacetonate, generating a highly conjugated indole derivative. Even arenes could be oxidized, indicating this reaction is not restricted to heteroarenes.

EXPERIMENTAL SECTION

General Information.

All ¹H and ¹³C NMR spectra were recorded at ambient temperature using Brunker AVIII-400 (400 and 100 MHz, respectively), AV-500 (500 and 125 MHz, respectively) and AVIII-600 with TCI cryoprobe (600 and 150 MHz, respectively) spectrometers. The data were reported as follows: chemical shifts are reported in ppm from internal tetramethylsilane or from residual solvent peaks (¹H NMR: CDCl₃ δ 7.26; C₆D₆ δ 7.16; DMSO δ 2.50; and ¹³C NMR: CDCl₃ δ 77.23; C₆D₆ δ 128.4; DMSO δ 39.5) on the δ scale, multiplicity (s = singlet, br = broad, d = doublet, t = triplet, q = quartet, quint = quintet, m = multiplet), coupling constants (Hz), and integration. Multiplicity of carbon peaks was determined using HSQC or DEPT experiments. Infrared (IR) spectra were recorded using a Thermo Nicolet AVATAR Fourier Transform IR spectrometer using attenuated total reflectance (ATR). High-resolution mass spectra (HRMS) were recorded using an Agilent 6224 Accurate-Mass time-of-flight spectrometer with atmospheric pressure chemical ionization (APCI) or electrospray ionization (ESI) ionization sources. Melting points were reported uncorrected. Analytical thin layer chromatography was performed on Silicycle silica gel 60 Å F254 plates. Liquid chromatography was performed using forced flow (flash chromatography) of the indicated solvent system on Silicycle silica gel (SiO₂) 60 (230–400 mesh). THF and Et₂O were dried and degassed using a solvent purification system before use. All reactions were run under a nitrogen atmosphere in glassware that had been flame-dried under vacuum unless otherwise stated. All reactions that were ran under an oxygen atmosphere used glassware that was not flame dried. The synthesis and characterization of compounds were reported previously. Unless otherwise noted, all reagents were commercially available. Compounds 3,⁴² 15,⁴³ and 27,⁴⁴ were prepared by known methods. Co(acac)₂,⁴⁵ Co(thd)2,⁶ and Co(modp)₂,⁸ were synthesized by known methods.

Optimization of Co-Catalyzed Oxygenation of Furans.

Optimization reactions were performed as follows: A flask containing DCE (1,2-dichloroethane, 5 mL) was sparged with oxygen for 15 min. To a separate flask was added CoL₂ followed by 2-acetylfuran (0.050 g, 0.227 mmol). The oxygenated DCE (1.1 mL) was added to the reaction flask and the reaction flask was sparged with oxygen for 5 min. A solution of tert-butyl hydroperoxide in CH₂Cl₂ (1.0 M, 0.011 mL, 0.011 mmol) was added, followed by acetylacetone. Triethylsilane was added and the mixture stirred at the corresponding temperature under a balloon of oxygen for the time described in Table 1. The reaction mixture was filtered through a 3-cm plug of silica, eluted with CH₂Cl₂ (50 mL), and concentrated in vacuo. CDCl₃ (0.70 mL) was added and the crude reaction mixture was transferred to an NMR tube followed by mesitylene (0.020 mL, 0.144 mmol, internal standard). The yield of lactone 2 was determined based on ¹H NMR spectroscopic analysis of the area of the internal standard (δ 6.77) and the area of the methine group (δ 4.80) of lactone 2.

Synthesis of Disubstituted Furan Substrates

Alcohol 7a.

To a solution of furan 6 (0.271 mL, 2.73 mmol) in THF (4.1 mL) was added a solution of methylmagnesium chloride in Et₂O (3.0 M, 1.0 mL, 3.0 mmol). The resulting reaction mixture was stirred for 30 min. Saturated aqueous NH₄Cl (4 mL) was added and the mixture was extracted with diethyl ether (3 × 4 mL). The combined organic layers were dried over Na₂SO₄, and concentrated in vacuo. Alcohol 7a was isolated as a yellow oil (0.316 g, 92%) and used without further purification. The spectroscopic data are consistent with the data reported:^{46 1}H NMR (500 MHz, CDCl₃) δ 6.07 (d, J = 3.0, 1H), 5.87 (d, J = 2.9, 1H), 4.78 (q, J = 6.5, 1H), 2.54 (s, 1H), 2.26 (s, 3H), 1.48 (d, J = 6.5, 3H); ¹³C NMR (125 MHz, CDCl₃) δ 156.0, 151.6, 106.0, 105.9, 63.6, 21.3, 13.6; IR (ATR) 3345, 2979, 1563, 1220, 1073, 1015, 782 cm⁻¹.

Alcohol 7b.

To a solution of magnesium turnings (0.078 g, 3.21 mmol) in THF (2.4 mL) was added 4-bromoanisole (0.201 mL, 1.60 mmol). The resulting solution was stirred for 1 h, then furan 6 (0.160 mL, 1.60 mmol) was added. The resulting solution was stirred for 1 h. Saturated aqueous NH₄Cl (3 mL) was added and the mixture was extracted with Et₂O (3 × 3 mL). The combined organic layers were dried over Na₂SO₄ and concentrated in vacuo. Alcohol 7b was isolated as a yellow oil (0.302 g, 86%) and used without further purification: ¹H NMR (500 MHz, CDCl₃) δ 7.37 (d, J = 8.5, 2H), 6.91 (d, J = 8.5, 2H), 5.95 (d, J = 3.0, 1H), 5.89 (d, J = 2.9, 1H), 5.73 (d, J = 4.2, 1H), 3.82 (s, 3H), 2.32 (d, J = 4.3, 1H), 2.29 (s, 3H); ¹³C NMR (125 MHz, CDCl₃) δ 159.6 (C), 154.6 (C), 152.5 (C), 133.5 (C), 128.2 (CH), 114.0 (CH), 108.5 (CH), 106.3 (CH), 70.0 (CH), 55.5 (CH₃), 13.8 (CH₃); IR (ATR) 3409, 1611, 1511, 1172, 1030, 778 cm ⁻¹; HRMS (APCI) m/z calcd for C₁₃H₁₃O₂ (M + H – H₂O)⁺ 201.0910, found 201.0909.

Alcohol 7c.

To a solution of magnesium turnings (0.076 g, 3.11 mmol) in THF (2.3 mL) was added 4-bromobenzotrifluoride (0.220 mL, 1.56 mmol). The resulting solution was stirred for 1 h, then 6 (0.155 mL, 1.56 mmol) was added. The resulting solution was stirred for 1 h. Saturated aqueous NH₄Cl (3 mL) was added and the mixture was extracted with Et₂O (3 × 3 mL). The combined organic layers were dried over Na₂SO₄ and concentrated in vacuo. Purification by flash chromatography (hexanes:EtOAc = 90:10) afforded alcohol 7c (0.317 g, 80%) as a yellow oil: ¹H NMR (600 MHz, CDCl₃) δ 7.63 (d, J = 8.3, 2H), 7.57 (d, J = 8.1, 2H), 5.97 (d, J = 3.1, 1H), 5.91 (d, J = 3.1, 1H), 5.82 (d, J = 3.9, 1H), 2.61 (d, J = 3.8, 1H), 2.28 (s, 3H); ¹³C NMR (150 MHz, CDCl₃) δ 153.5 (C), 153.0 (C), 144.9 (C), 130.2 (q, J = 31.5, C), 127.1 (CH), 125.5 (q, J = 3.0, CH), 124.3 (q, J = 270.3, C), 109.1 (CH), 106.5 (CH), 69.6 (CH), 13.7 (CH₃); IR (ATR) 3332, 1620, 1322, 1162, 1120, 1066, 1016, 779 cm ⁻¹; HRMS (ESI) m/z calcd for C₁₃H₁₀F₃O (M + H – H₂O)⁺ 239.0678, found 239.0681. Anal. Calcd for C₁₃H₁₁F₃O₂: C, 60.94; H, 4.33. Found: C, 61.03; H, 4.41.

Ketone 8a.

To a solution of alcohol 7a (0.316 g, 2.50 mmol) in EtOAc (4.5 mL) was added 2-iodoxybenzoic acid (2.10 g, 7.51 mmol). The resulting suspension was heated to reflux for 16 h. The reaction mixture was cooled to room temperature and filtered through a glass frit. The filter cake was washed with EtOAc (3 × 5 mL) and the filtrate was concentrated in vacuo. Purification by flash chromatography (hexanes:EtOAc = 90:10) afforded ketone 8a (0.227 g, 73%) as a yellow oil. The spectroscopic data are consistent with the data reported:^{47 1}H NMR (500 MHz, CDCl₃) δ 7.10 (d, J = 3.4, 1H), 6.16 (d, J = 3.4, 1H), 2.43 (s, 3H), 2.40 (s, 3H); ¹³C NMR (125 MHz, CDCl₃) δ 186.3, 158.1, 151.8, 119.6, 109.1, 25.9, 14.3; IR (ATR) 1669, 1515, 1372, 1209, 1027, 667 cm⁻¹; HRMS (APCI) m/z calcd for C₇H₉O₂ (M + H)⁺ 125.0597, found 125.0596.

Ketone 8b.

To a solution of alcohol 7b (0.301 g, 1.38 mmol) in EtOAc (2.5 mL) was added 2-iodoxybenzoic acid (1.15 g, 4.14 mmol). The resulting suspension was heated to reflux for 16 h. The reaction mixture was cooled to room temperature and filtered through a glass frit. The filter cake was washed with EtOAc (3 × 5 mL) and the filtrate was concentrated in vacuo. Purification by flash chromatography (hexanes:EtOAc = 90:10) afforded ketone 8b (0.115 g, 39%) as a yellow oil: ¹H NMR (500 MHz, CDCl₃) δ 7.97 (d, J = 8.9, 2H), 7.10 (d, J = 3.4, 1H), 6.96 (d, J = 8.9, 2H), 6.20 (d, J = 3.5, 1H), 3.87 (s, 3H), 2.44 (s, 3H); ¹³C NMR (125 MHz, CDCl₃) δ 181.1 (C), 163.2 (C), 158.2 (C), 151.4 (C), 131.6 (CH), 130.4 (C), 122.0 (CH), 113.8 (CH), 109.0 (CH), 55.6 (CH₃), 14.3 (CH₃); IR (ATR) 1631, 1597, 1502, 1254, 1161, 1025, 883, 762 cm⁻¹; HRMS (APCI) m/z calcd for C₁₃H₁₃O₃ (M + H)⁺ 217.0859, found 217.0857.

Ketone 8c.

To a solution of alcohol 7c (0.245 g, 0.960 mmol) in EtOAc (1.7 mL) was added 2-iodoxybenzoic acid (0.621 g, 2.87 mmol). The resulting suspension was heated to reflux for 16 h. The reaction mixture was cooled to room temperature and filtered through a glass frit. The filter cake was washed with EtOAc (3 × 5 mL) and the filtrate was concentrated in vacuo. Purification by flash chromatography (hexanes:EtOAc = 95:5) afforded ketone 8c (0.124 g, 51%) as a white solid: mp 110−114 °C; ¹H NMR (600 MHz, CDCl₃) δ 8.02 (d, J = 7.8, 2H), 7.75 (d, J = 7.8, 2H), 7.15 (d, J = 2.8, 1H), 6.26 (d, J = 2.6, 1H), 2.49 (s, 3H); ¹³C NMR (150 MHz, CDCl₃) δ 181.0 (C), 159.7 (C), 150.8 (C), 140.9 (C), 133.8 (q, J = 31.5, C), 129.6 (CH), 125.6 (q, J = 3.0, CH) 123.9 (q, J = 271.7, C), 123.7 (CH), 109.7 (CH), 14.4 (CH₃); IR (ATR) 1637, 1514, 1329, 1163, 1067, 767 cm⁻¹; HRMS (APCI) m/z calcd for C₁₃H₁₀F₃O₂ (M + H)⁺ 255.0627, found 255.0631. Anal. Calcd for C₁₃H₉F₃O₂: C, 61.42; H, 3.57. Found: C, 61.15; H, 3.53.

Representative Procedure for the Co-Catalyzed Oxygenation of Aromatic Compounds (Lactone 2).

A flask containing DCE (1,2-dichloroethane, 10 mL) was sparged with oxygen for 15 min. To a separate flask was added Co(acac)₂ (0.013 g, 0.050 mmol) followed by furan 1 (0.110 g, 1.00 mmol). The oxygenated DCE (4.5 mL) was added to the reaction flask and the reaction vessel was sparged with oxygen for 5 min. A solution of tert-butyl hydroperoxide in CH₂Cl₂ (1.0 M, 0.050 mL, 0.050 mmol) was added followed by acetylacetone (0.103 mL, 1.00 mmol). Triethylsilane (2.39 mL, 15.0 mmol) was added and the reaction mixture was stirred at 40 °C under a balloon of oxygen for 2 h. The reaction mixture was filtered through a 3-cm plug of silica, eluted with CH₂Cl₂ (50 mL), and concentrated in vacuo. Purification by flash chromatography (pentane:Et₂O = 80:20) afforded lactone 2 (0.050 g, 23%) as a colorless oil: ¹H NMR (500 MHz, CDCl₃) δ 4.81 (t, J = 5.5, 1H), 4.57 (d, J = 10.9, 1H), 4.34 (dd, J = 10.9, 4.7, 1H), 2.71 (dd, J = 18.5, 6.5, 1H), 2.62 (d, J = 18.5, 1H), 0.96 (t, J = 8.0, 9H), 0.67 (q, J = 8.0, 6H); ¹³C NMR (125 MHz, CDCl₃) δ 175.3 (C), 79.9 (CH), 71.7 (CH₂), 33.1 (CH₂), 6.7 (CH₃), 3.8 (CH₂); IR (ATR) 2957, 2878, 1785, 1165, 1005, 793, 741 cm⁻¹; HRMS (APCI) m/z calcd for C₁₀H₂₁O₄Si (M + H)⁺ 233.1204, found 233.1203.

Lactone 2 and bis(silylperoxy) esters 4 and 5.

Lactone 2 and bis(silylperoxy) esters 4 and 5 were prepared using the representative procedure for the Co-catalyzed oxygenation of aromatic compounds using methyl 2-furoate (3, 0.085 mL, 0.793 mmol), Co(acac)₂ (0.010 g, 0.040 mmol), tert-butyl hydroperoxide (0.040 mL, 0.040 mmol), acetylacetone (0.081 mL, 0.793 mmol), and triethylsilane (1.89 mL, 11.9 mmol) in DCE (3.6 mL). The reaction time was 2.5 h. Purification by flash chromatography (hexane:EtOAc = 90:10) afforded lactone 2 as a colorless oil (0.028 g, 15%) and diastereomeric silyl peroxides 4 and 5 separately as colorless oils (0.015 g, 4%; 0.017 g, 5%, respectively). The spectroscopic data are consistent with the data reported above for lactone 2. Bis(silylperoxy) ester 4: ¹H NMR (600 MHz, CDCl₃) δ 4.70 (m, 1H), 4.36 (d, J = 10.4, 1H), 4.05 (dd, J = 10.4, 4.3, 1H), 3.80 (s, 3H), 2.42 (dd, J = 15.8, 2.6, 1H), 2.36 (dd, J = 15.7, 6.4, 1H), 0.95 (m, 18H), 0.66 (m, 12H); ¹³C NMR (150 MHz, CDCl₃) δ 167.6 (C), 110.6 (C), 83.5 (CH), 72.2 (CH₂), 52.8 (CH₃), 38.9 (CH₂), 6.84 (CH₃), 6.76 (CH₃), 3.87 (CH₂), 3.82 (CH₂); IR (ATR) 2954, 1772, 1751, 1127, 1005, 800, 730 cm⁻¹; HRMS (ESI) m/z calcd for C₁₈H₃₈NaO₇Si₂ (M + Na)⁺ 445.2048, found 445.2050. Bis(silylperoxy) ester 5: ¹H NMR (600 MHz, CDCl₃) δ 4.71 (m, 1H), 4.32 (dd, J = 10.2, 6.0, 1H), 4.15 (dd, J = 10.2, 3.6, 1H), 3.82 (s, 3H), 2.38 (d, J = 4.8, 2H), 0.99 (t, J = 8.4, 18H), 0.70 (m, 12H); ¹³C NMR (150 MHz, CDCl₃) 168.1 (C), 109.9 (CH), 82.7 (CH), 72.6 (CH₂), 52.8 (CH₃), 39.1 (CH₂), 6.85 (CH₃), 6.74 (CH₃), 3.8 (CH₂); IR (ATR) 2954, 1767, 1240, 1106, 807, 740 cm⁻¹; HRMS (ESI) m/z calcd for C₁₈H₃₈NaO₇Si₂ (M + Na)⁺ 445.2048, found 445.2047.

Lactone 9 prepared from furan 8a.

Lactone 9 was prepared using the representative procedure for the Co-catalyzed oxygenation of aromatic compounds using ketone 8a (0.100 g, 0.806 mmol), Co(acac)₂ (0.010 g, 0.040 mmol), tert-butyl hydroperoxide (0.040 mL, 0.040 mmol), acetylacetone (0.083 mL, 0.806 mmol), and triethylsilane (1.93 mL, 12.1 mmol) in DCE (3.7 mL). The reaction time was 4 h. Purification by flash chromatography (hexane:EtOAc = 90:10) afforded lactone 9 as a colorless oil (0.038 g, 19%): ¹H NMR (600 MHz, C₆D₆) δ 4.55 (q, J = 6.9, 1H), 3.85 (d, J = 6.9, 1H), 2.31 (dd, J = 18.4, 2.2, 1H), 2.09 (dd, J = 18.4, 6.9, 1H), 0.94 (t, J = 8.0, 9H), 0.75 (d, J = 6.9, 3H), 0.60 (q, J = 7.9, 6H); ¹³C NMR (150 MHz, CDCl₃) δ 172.7 (C), 84.8 (CH), 78.4 (CH), 31.9 (CH₂), 18.5 (CH₃), 6.5 (CH₃), 3.6 (CH₂); IR (ATR) 1789, 1617, 1453, 1329, 1166, 743 cm⁻¹; HRMS (APCI) m/z calcd for C₁₁H₂₂NaO₄Si (M + Na)⁺ 269.1180, found 269.1184.

Lactone 9 prepared from furan 8b.

Lactone 9 was prepared using the representative procedure for the Co-catalyzed oxygenation of aromatic compounds using ketone 8b (0.100 g, 0.463 mmol), Co(acac)₂ (0.006 g, 0.023 mmol), tert-butyl hydroperoxide (0.023 mL, 0.023 mmol), acetylacetone (0.047 mL, 0.463 mmol), and triethylsilane (1.11 mL, 6.94 mmol) in DCE (2.1 mL). The reaction time was 3 h. Purification by repeated flash chromatography (twice, pentane:Et₂O = 90:10) afforded lactone 9 as a colorless oil (0.008 g, 7%). The spectroscopic data matched the reported values above for lactone 9.

Lactone 9 prepared from furan 8c.

Lactone 9 was prepared using the representative procedure for the Co-catalyzed oxygenation of aromatic compounds using ketone 8c (0.100 g, 0.393 mmol), Co(acac)₂ (0.005 g, 0.020 mmol), tert-butyl hydroperoxide (0.020 mL, 0.050 mmol), acetylacetone (0.040 mL, 0.393 mmol), and triethylsilane (0.942 mL, 15.0 mmol) in DCE (1.8 mL). The reaction time was 2.25 h. Purification by repeated flash chromatography (twice, pentane:Et₂O = 90:10) afforded lactone 9 as a colorless oil (0.004 g, 4%). The spectroscopic data match the reported values above for lactone 9.

Lactone 9 prepared from furan 6.

Lactone 9 was prepared using the representative procedure for the Co-catalyzed oxygenation of aromatic compounds using furan 6 (0.100 mL, 1.00 mmol), Co(acac)₂ (0.051 g, 0.200 mmol), tert-butyl hydroperoxide (0.050 mL, 0.050 mmol), acetylacetone (0.103 mL, 1.00 mmol), and triethylsilane (2.39 mL, 15.0 mmol) in DCE (4.5 mL). The reaction time was 4 h. Purification by flash chromatography (pentane:Et₂O = 95:5 → pentane:Et₂O = 90:10) afforded lactone 9 as a colorless oil (0.020 g, 8%). The spectroscopic data match the reported values above for lactone 9.

Alcohol 9a.

To a solution of lactone 9 (0.038 g, 0.154 mmol) in EtOAc (0.70 mL) was added triphenylphosphine (0.061 g, 0.231 mmol). The reaction mixture was stirred at room temperature for 5 h, then it was concentrated in vacuo. Purification by flash column chromatography (hexane:EtOAc = 90:10) afforded the silyl ether product as a colorless oil (0.020 g, 57%): ¹H NMR (600 MHz, C₆D₆) δ 4.02 (m, 1H), 3.48 (q, J = 5.4, 1H), 2.24 (dd, J = 17.2, 6.6, 1H), 2.10 (dd, J = 17.2, 5.3, 1H), 0.89 (d, J = 6.6, 3H), 0.82 (t, J = 8.0, 9H), 0.37 (q, J = 8.0, 6H); ¹³C NMR (150 MHz, C₆D₆) δ 173.5 (C), 83.3 (CH), 74.0 (CH), 38.5 (CH₂), 18.5 (CH₃), 7.1 (CH2), 5.2 (CH₃); IR ATR 2956, 2877, 1786, 1168, 1077, 1010, 747 cm⁻¹; HRMS (ESI) m/z calcd for C₁₁H₂₂NaO₃Si (M + Na)⁺ 253.1230, found 253.1231.

To a solution of the above silyl ether (0.020 g, 0.089 mmol) in Et₂O (0.89 mL) was added a solution of tetrabutylammonium fluoride in THF (1.0 M, 0.13 mL, 0.13 mmol). The resulting reaction mixture was stirred for 1.5 h. H₂O (1 mL) was added and the mixture was extracted with Et₂O (3 × 1 mL). The combined organic layers were dried over Na₂SO₄ and concentrated under a stream of nitrogen. Purification by flash chromatography (hexane:EtOAc = 50:50) afforded alcohol 9a as a colorless oil (0.001 g, 10%). The spectroscopic data are consistent with the data reported:^{21 1}H NMR (600 MHz, CDCl₃) δ 4.50 (m, 1H), 4.27 (m, 1H), 2.87 (dd, J = 17.9, 6.5, 1H), 2.53 (dd, J = 17.9, 3.8, 1H), 2.00 (d, J = 4.2, 1H), 1.39 (d, J = 6.6, 3H); ¹³C NMR (150 MHz, CDCl₃) δ 174.7, 83.9, 73.3, 37.6, 18.8.

Silyl ether 10.

A flask containing DCE (1,2-dichloroethane, 10 mL) was sparged with oxygen for 15 min. To a separate flask was added Co(acac)₂ (0.013 g, 0.05 mmol) followed by 2-acetylfuran (0.110 g, 1.00 mmol). The oxygenated DCE (4.5 mL) was added to the reaction flask and the reaction vessel was sparged with oxygen for 5 min. A solution of tert-butyl hydroperoxide (0.050 mL, 0.050 mmol) in CH₂Cl₂ was added followed by acetylacetone (0.103 mL, 1.00 mmol). Triethylsilane (2.39 mL, 15.0 mmol) was added and the reaction mixture was stirred at 40 °C under a balloon of oxygen for 2 h. Triphenylphosphine (0.262 g, 1.00 mmol) was added directly to the reaction mixture, which was stirred at room temperature for 3 h. The reaction mixture was filtered through a 3-cm plug of silica, eluted with CH₂Cl₂ (50 mL), and concentrated in vacuo. Purification by flash chromatography (pentane:Et₂O = 80:20) afforded silyl ether 10 (0.072 g, 33%) as a colorless oil: ¹H NMR (500 MHz, CDCl₃) δ 4.58 (m, 1H), 4.35 (dd, J = 9.7, 4.7, 1H), 4.14 (dd, J = 9.7, 1.8, 1H), 2.67 (dd, J = 17.5, 6.2, 1H), 2.41 (dd, J = 17.5, 2.4, 1H), 0.92 (t, J = 8.1, 9H), 0.59 (q, J = 8.0, 6H); ¹³C NMR (125 MHz, CDCl₃) δ 175.9 (C), 76.3 (CH), 67.9 (CH₂), 38.3 (CH₂), 6.7 (CH₃), 4.7 (CH₂); IR (ATR) 2955, 2877, 1780, 1162, 1092, 999, 727 cm⁻¹; HRMS (APCI) m/z calcd for C₁₀H₂₁O₃Si (M + H)⁺ 217.1254, found 217.1256. Anal. Calcd for C₁₀H₂₀O₃Si: C, 55.52; H, 9.32. Found: C, 55.78; H, 9.21.

Lactone 9 and Carboxylic acid 11 from furan 8c.

Lactone 9 was prepared using the using the representative procedure for the Co-catalyzed oxygenation of aromatic compounds using ketone 8c (0.055 g, 0.220 mmol), Co(acac)₂ (0.003 g, 0.011 mmol), tert-butyl hydroperoxide (0.011 mL, 0.011 mmol), acetylacetone (0.022 mL, 0.220 mmol), and triethylsilane (0.530 mL, 3.30 mmol) in DCE (1.0 mL). The reaction time was 2.5 h. CDCl₃ (0.70 mL) was added and the crude reaction mixture was transferred to an NMR tube followed by mesitylene (0.031 mL, 0.220 mmol, internal standard). The yield of lactone 9 and carboxylic acid 11 was determined based on ¹H NMR spectroscopic analysis of the area of the internal standard (δ 6.77) and the area of the methine group of lactone 9 (δ 4.81) and carboxylic acid 11 (δ 8.16). Purification by flash chromatography (hexane:EtOAc = 75:25 → hexane:EtOAc = 50:50) afforded an analytical sample of carboxylic acid 11 (0.004 g, 10%) as a white solid. The spectroscopic data are consistent with the data reported:^{48 1}H NMR (600 MHz, DMSO) δ 8.14 (d, J = 8.0, 2H), 7.88 (d, J = 8.1, 2H); ¹³C NMR (150 MHz, DMSO) δ 166.2, 134.9, 132.3 (q, J = 31.6), 130.1, 125.6, 124.7 (q, J = 272.2); IR (ATR) 3312, 1762 cm⁻¹.

Silyl peroxide 14.

Silyl peroxide 14 was prepared using the representative procedure for the Co-catalyzed oxygenation of aromatic compounds using 2-methylfuran (13, 0.080 mL, 0.914 mmol), Co(acac)₂ (0.012 g, 0.046 mmol), tert-butyl hydroperoxide (0.046 mL, 0.046 mmol), acetylacetone (0.093 mL, 0.914 mmol), and triethylsilane (2.19 mL, 13.7 mmol) in DCE (4.2 mL). The reaction time was 2 h. Purification by flash chromatography (hexane:EtOAc = 95:5) afforded silyl peroxide 14 as a colorless oil (0.015 g, 4%): ¹H NMR (600 MHz, CDCl₃) δ 4.44 (m, 1H), 4.34 (dd, J = 12.1, 3.8, 1H), 4.27 (dd, J = 12.1, 5.7, 1H), 4.20 (dd, J = 12.1, 5.6, 1H), 4.08 (dd, J = 12.1, 4.9, 1H), 2.08 (s, 3H), 0.98 (m, 18H), 0.70 (m, 12H); ¹³C NMR (150 MHz, CDCl₃) δ 171.0 (C), 80.8 (CH), 74.4 (CH₂), 62.2 (CH₂), 21.0 (CH₃), 6.85 (CH₃), 6.84 (CH₃), 3.81 (CH₂), 3.79 (CH₂); IR (ATR) 2958, 2878, 1747, 1236, 849, 740 cm⁻¹; HRMS (APCI) m/z calcd for C₁₇H₃₉O₆Si₂ (M + H)⁺ 395.2279, found 395.2277.

Bis(silylperoxide) 16 and 17.

Bis(silylperoxides) 16 and 17 were prepared using the representative procedure for the Co-catalyzed oxygenation of aromatic compounds using 2-benzylfuran (15, 0.055 g, 0.348 mmol), Co(acac)₂ (0.005 g, 0.017 mmol), tert-butyl hydroperoxide (0.017 mL, 0.017 mmol), acetylacetone (0.036 mL, 0.348 mmol), and triethylsilane (0.833 mL, 5.22 mmol) in DCE (1.6 mL). The reaction time was 2.5 h. Purification by flash chromatography (hexane → hexane:EtOAc = 98:2) afforded bis(silylperoxides) 16 and 17 as an inseparable 59:41 mixture of diastereomers: ¹H NMR (600 MHz, CDCl₃) δ 7.32–7.21 (m, 8.5H), 4.75 (m, 0.6H), 4.43 (m, 1H), 4.17 (d, J = 9.8, 0.7H), 4.13 (dd, J = 9.8, 4.4, 0.7H), 4.09 (dd, J = 9.6, 6.4, 1H), 4.00 (dd, J = 9.7, 4.9, 1H), 3.25 (d, J = 10.6, 0.7H), 3.23 (d, J = 10.5, 1H), 3.15 (d, J = 13.9, 1H), 2.27 (dd, J = 15.0, 7.2, 0.7H), 2.08 (dd, J = 15.0, 8.1, 1H), 1.96 (m, 1.7H), 1.05–0.93 (m, 36.9H), 0.80–0.62 (m, 24.6H); ¹³C NMR (150 MHz, CDCl₃) δ 136.9 (C), 136.6 (C), 130.74 (CH), 130.71 (CH), 128.2 (CH), 128.1 (CH), 126.69 (CH), 126.66 (CH), 114.6 (C), 114.0 (C), 85.3 (CH), 83.7 (CH), 72.7 (CH₂), 71.9 (CH₂), 42.2 (CH₂), 40.9 (CH₂), 37.5 (CH₂), 37.2 (CH₂), 6.93 (CH₃), 6.91 (CH₃), 6.90 (CH₃), 6.84 (CH₃), 4.04 (CH₂), 3.99 (CH₂), 3.89 (CH₂), 3.80 (CH₂); IR (ATR) 2954, 2877, 1456, 1239, 1006, 803, 740, 701 cm⁻¹; HRMS (APCI) m/z calcd for C₂₃H₄₆NO₅Si₂ (M + NH₄)⁺ 472.2909, found 472.2904.

Silyl peroxide 19.

Silyl peroxide 19 was prepared using the representative procedure for the Co-catalyzed oxygenation of aromatic compounds using pyran 18 (0.054 mL, 0.594 mmol), Co(acac)₂ (0.008 g, 0.030 mmol), tert-butyl hydroperoxide (0.030 mL, 0.030 mmol), acetylacetone (0.061 mL, 0.594 mmol), and triethylsilane (1.42 mL, 8.92 mmol) in DCE (2.7 mL). The reaction time was 2 h. Purification by flash chromatography (hexane:EtOAc = 95:5) afforded silyl peroxide 19 as a colorless oil (0.038 g, 26%): ¹H NMR (600 MHz, CDCl₃) δ 8.05 (s, 1H), 4.18 (t, J = 6.3, 2H), 4.00 (t, J = 6.1, 2H), 1.73 (m, 4H), 0.99 (t, J = 8.0, 9H), 0.69 (q, J = 7.9, 6H); ¹³C NMR (150 MHz, CDCl₃) δ 161.3 (CH), 76.3 (CH₂), 63.9 (CH₂), 25.5 (CH₂), 24.6 (CH₂), 6.9 (CH₃), 3.9 (CH₂); IR (ATR) 2955, 2877, 1726, 1168, 1006, 863, 730 cm⁻¹; HRMS (APCI) m/z calcd for C₁₁H₂₄KO₄Si (M + K)⁺ 287.1075, found 287.1067.

Lactone 21 and Silyl peroxide 22.

Lactone 21 and silyl peroxide 22 were prepared using the representative procedure for the Co-catalyzed oxygenation of aromatic compounds using ethyl 3-furoate (20, 0.096 mL, 0.714 mmol), Co(acac)₂ (0.009 g, 0.036 mmol), tert-butyl hydroperoxide (0.036 mL, 0.036 mmol), acetylacetone (0.073 mL, 0.714 mmol), and triethylsilane (1.71 mL, 10.7 mmol) in DCE (3.2 mL). The reaction time was 2.5 h. Purification by flash chromatography (hexane:EtOAc = 95:5) afforded lactone 21 as a colorless oil (0.037 g, 17%) and silyl peroxide 22 as a colorless oil (0.044 g, 14%). Lactone 21: ¹H NMR (600 MHz, CDCl₃) δ 4.58 (d, J = 10.9, 1H), 4.53 (d, J = 10.9, 1H), 4.27 (q, J = 7.2, 2H), 3.04 (d, J = 18.5, 1H), 2.90 (d, J = 18.6, 1H), 1.31 (t, J = 7.2, 3H), 0.96 (t, J = 8.0, 9H), 0.68 (q, J = 7.9, 6H); ¹³C NMR (150 MHz, CDCl₃) δ 173.4 (C), 168.4 (C), 87.9 (C), 71.7 (CH₂), 62.5 (CH₂), 36.3 (CH₂), 14.2 (CH₃), 6.7 (CH₃), 3.7 (CH₂); IR (ATR) 2957, 1794, 1743, 1310, 1030, 803, 742 cm⁻¹; HRMS (APCI) m/z calcd for C₁₃H₂₅O₆Si (M + H)⁺ 305.1415, found 305.1417. Silyl peroxide 22: ¹H NMR (600 MHz, CDCl₃) δ 8.08 (s, 1H), 4.81 (d, J = 12.0, 1H), 4.62 (d, J = 12.1, 1H), 4.32 (d, J = 12.0, 1H), 4.22 (m, 2H), 4.17 (d, J = 12.0, 1H), 1.29 (t, J = 7.2, 3H), 0.95 (t, J = 8.1, 18H), 0.66 (m, 12H); ¹³C NMR (150 MHz, CDCl₃) δ 168.6 (C), 160.7 (CH), 85.6 (C), 74.0 (CH₂), 61.6 (CH₂), 60.6 (CH₂), 14.2 (CH₃), 6.77 (CH₃), 6.73 (CH₃), 3.79 (CH₂), 3.73 (CH₂); IR (ATR) 2956, 2878, 1735, 1172, 1019, 847, 733 cm⁻¹; HRMS (APCI) m/z calcd for C₁₉H₄₄NO₈Si₂ (M + NH₄)⁺ 470.2600, found 470.2600.

Silyl peroxide 24.

Silyl peroxide 24 was prepared using the representative procedure for the Co-catalyzed oxygenation of aromatic compounds using benzofuran 23 (0.090 mL, 0.847 mmol), Co(acac)₂ (0.011 g, 0.042 mmol), tert-butyl hydroperoxide (0.042 mL, 0.042 mmol), and triethylsilane (0.676 mL, 4.23 mmol) in DCE (3.8 mL). The reaction time was 6 h. Purification by flash chromatography (pentane → pentane:Et₂O = 95:5) afforded silyl peroxide 24 (0.099 g, 44%) as a colorless oil: ¹H NMR (600 MHz, CDCl₃) δ 7.43 (d, J = 7.2, 1H), 7.30 (t, J = 7.8, 1H), 6.93 (t, J = 7.2, 1H), 6.89 (d, J = 7.8, 1H), 5.61 (dd, J = 6.0, 1.8, 1H), 4.78 (dd, J = 11.4, 2.0, 1H), 4.47 (dd, J = 11.1, 6.0, 1H), 0.99, (t, J = 7.8, 9H), 0.70 (q, J = 7.8, 6H); ¹³C NMR (150 MHz, CDCl₃) δ 161.8 (C), 131.6 (CH), 127.3 (CH), 123.5 (C), 120.7 (CH), 110.7 (CH), 84.9 (CH), 75.4 (CH₂), 6.9 (CH3), 3.9 (CH₂); IR (ATR) 2954, 2877, 1612, 1600, 1479, 1246, 1015, 963, 832 cm⁻¹; HRMS (APCI) m/z calcd for C₁₄H₂₁O₂Si (M + H – H₂O)⁺ 249.1305, found 249.1306.

Dione 26.

Dione 26 was prepared using the representative procedure for the Co-catalyzed oxygenation of aromatic compounds using isobenzofuran 25 (0.050 g, 0.185 mmol), Co(acac)₂ (0.002 g, 0.009 mmol), tert-butyl hydroperoxide (0.009 mL, 0.009 mmol), and triethylsilane (0.440 mL, 2.78 mmol) in DCE (1.7 mL). The reaction time was 18 h. Following the workup as described above, dione 26 isolated as a white, off-yellow solid (0.041 g, 78%). Characterization was performed without further purification. The spectroscopic data are consistent with the data reported:⁴⁹ mp 130–133 °C, which is lower than reported literature value (138–139 °C)⁴⁹ due to residual impurities; ¹H NMR (600 MHz, CDCl₃) δ 7.72 (d, J = 1.2, 2H), 7.70 (d, J = 1.1, 2H), 7.63 (d, J = 1.1, 4H), 7.53 (m, 2H), 7.39 (m, 4H); ¹³C NMR (150 MHz, CDCl₃) δ 196.8 (C), 140.2 (C), 137.4 (C), 133.2 (CH), 130.6 (CH), 130.0 (CH), 129.9 (CH), 128.5 (CH); IR (ATR) 1659, 1596, 1278, 937, 704 cm⁻¹; HRMS (ESI) m/z calcd for C₂₀H₁₄NaO₂ (M + Na)⁺ 309.0886, found 309.0898.

Lactam 28 and Bis(silylperoxy) ketone 29.

Lactam 28 and bis(silyl peroxy) ketone 29 were prepared using the representative procedure for the Co-catalyzed oxygenation of aromatic compounds using pyrrole 27 (0.100 g, 0.380 mmol), Co(acac)₂ (0.020 g, 0.076 mmol), tert-butyl hydroperoxide (0.019 mL, 0.019 mmol), acetylacetone (0.039 mL, 0.380 mmol), and triethylsilane (0.909 mL, 5.70 mmol) in DCE (1.7 mL). The reaction time was 2.5 h. Purification by flash chromatography (pentane:Et₂O = 95:5 → pentane:Et2O = 90:10) afforded lactam 28 as a colorless oil (0.024 g, 16%) and silyl peroxide 29 as a colorless oil (0.004 g, 2%). Lactam 28: ¹H NMR (600 MHz, CDCl₃) δ 7.93 (d, J = 8.4, 2H), 7.33 (d, J = 8.4, 2H), 4.64 (t, J = 5.4, 1H), 4.24 (d, J = 12.0, 1H), 4.00 (dd, J = 12.0, 5.4, 1H), 2.72 (dd, J = 18.4, 6.7, 1H), 2.53 (d, J = 18.3, 1H), 2.44 (s, 3H), 0.92 (t, J = 7.8, 9H), 0.61 (q, J = 7.8, 6H); ¹³C NMR (150 MHz, CDCl₃) δ 170.9 (C), 145.4 (C), 135.4 (C), 129.8 (CH), 128.3 (CH), 76.0 (CH), 51.6 (CH₂), 37.3 (CH₂), 21.9 (CH₃), 6.8 (CH₃), 3.8 (CH₂); IR (ATR) 2956, 2877, 1742, 1362, 1169, 1089, 663 cm⁻¹; HRMS (ESI) m/z calcd for C₁₇H₂₇NNaO₅SSi (M + Na)⁺ 408.1271, found 408.1268. Anal. Calcd for C₁₇H₂₇NO₅SSi: C, 52.99; H, 7.06. Found: C, 52.69; H, 7.06. Bis(silylperoxy) ketone 29: ¹H NMR (600 MHz, CDCl₃) δ 7.80 (d, J = 8.4, 2H), 7.29 (d, J = 8.3, 2H), 4.87 (m, 1H), 3.78 (dd, J = 9.6, 6.6, 1H), 3.48 (dd, J = 9.6, 3.6, 1H), 2.60 (dd, J = 14.4, 7.6, 1H), 2.42 (s, 3H), 2.40 (s, 3H), 2.28 (dd, J = 14.2, 5.7, 1H), 0.99 (t, J = 7.8, 9H), 0.94 (t, J = 7.8, 9H), 0.73 (q, J = 7.8, 6H), 0.69 (q, J = 7.8, 6H); ¹³C NMR (150 MHz, CDCl₃) δ 201.6 (C), 143.7 (C), 136.0 (C), 129.5 (CH), 128.4 (CH), 103.3 (C), 82.2 (CH), 53.4 (CH2), 41.0 (CH₂), 27.4 (CH₃), 21.8 (CH₃), 6.84 (CH₃), 6.83 (CH₃), 4.0 (CH₂), 3.8 (CH₂); IR (ATR) 2956, 2877, 1737, 1349, 1011, 784, 676 cm⁻¹; HRMS (APCI) m/z calcd for C₂₅H₄₉N₂O₇SSi₂ (M + NH₄)⁺ 577.2794, found 577.2799.

Thiolactone 31.

Thiolactone 31 was prepared using the representative procedure for the Co-catalyzed oxygenation of aromatic compounds using thiophene 30 (0.085 mL, 0.793 mmol), Co(acac)₂ (0.041 g, 0.159 mmol), tert-butyl hydroperoxide (0.039 mL, 0.039 mmol), acetylacetone (0.081 mL, 0.793 mmol), and triethylsilane (1.89 mL, 11.9 mmol) in DCE (3.6 mL). The reaction time was 23 h. Purification by flash chromatography (hexane:EtOAc = 90:10) afforded thiolactone 31 as a colorless oil (0.001 g, 1%). ¹H NMR (600 MHz, CDCl₃) δ 4.85 (m, 1H), 3.78 (dd, J = 12.2, 2.2, 1H), 3.59 (dd, J = 12.3, 4.6, 1H), 2.77 (dd, J = 17.4, 5.4, 1H), 2.72 (dd, J = 17.4, 3.0, 1H), 1.00 (t, J = 7.8, 9H), 0.71 (q, J = 7.8, 6H); ¹³C NMR (150 MHz, CDCl₃) δ 205.3 (C), 81.2 (CH), 45.3 (CH₂), 36.3 (CH₂), 6.9 (CH₃), 3.9 (CH₂); IR (ATR) 2955, 1711, 1008, 792, 742 cm⁻¹; HRMS (APCI) m/z calcd for C₁₀H₁₉O₂SSi (M + H – H₂O)⁺ 231.0870, found 231.0870.

Dione 33.

Dione 33 was prepared using the representative procedure for the Co-catalyzed oxygenation of aromatic compounds using indole 32 (0.100 g, 0.854 mmol), Co(acac)₂ (0.044 g, 0.171 mmol), tert-butyl hydroperoxide (0.043 mL, 0.043 mmol), and triethylsilane (0.273 mL, 1.71 mmol) in DCE (3.9 mL). The reaction time was 18 h. Workup was performed as describe above except the silica plug was eluted with 100 mL of hexane:EtOAc (80:20). Purification by flash chromatography (hexane:EtOAc = 85:15 → hexane:EtOAc = 80:20 → hexane:EtOAc = 70:30) afforded dione 33 as a red solid (0.003 g, 2%): mp 205−208 °C; ¹H NMR (600 MHz, CDCl₃) δ 10.19 (br, 1H), 7.65 (d, J = 9.0, 1H), 7.52 (t, J = 9.6, 1H), 7.03 (t, J = 9.0, 1H), 6.95 (d, J = 9.6, 1H), 2.58 (s, 3H), 2.28 (s, 3H); ¹³C NMR (150 MHz, CDCl₃) δ 203.7 (C), 197.9 (C), 188.8 (C), 153.1 (C), 140.4 (C), 137.9 (CH), 125.9 (CH), 122.8 (CH), 119.6 (C), 117.0 (C), 112.4 (CH), 32.5 (CH₃), 29.2 (CH₃); IR (ATR) 3300, 1714, 1682, 1639, 1614, 1573, 1464, 1176 cm⁻¹; HRMS (APCI) m/z calcd for C₁₃H₁₀NO₂ (M + H – H₂O)⁺ 212.0706, found 212.0706.

Dione 35.

Dione 35 was prepared using the representative procedure for the Co-catalyzed oxygenation of aromatic compounds using arene 34 (0.100 g, 0.561 mmol), Co(acac)₂ (0.029 g, 0.112 mmol), tert-butyl hydroperoxide (0.028 mL, 0.028 mmol), acetylacetone (0.057 mL, 0.561 mmol), and triethylsilane (1.34 mL, 8.42 mmol) in DCE (2.6 mL). The reaction time was 17 h. Purification by flash chromatography (hexane:EtOAc:Et3N = 85:14:1) afforded dione 35 as an orange solid (0.009 g, 8%). The spectroscopic data are consistent with the data reported:⁵⁰ mp 192–194 °C, which is lower than reported literature value (207–208 °C)⁵⁰ due to impurities which could not be removed by chromatography; ¹H NMR (500 MHz, CDCl₃) δ 8.20 (d, J = 8.0, 2H), 8.03 (d, J = 8.0, 2H), 7.73 (t, J = 7.5, 2H), 7.48 (t, J = 8.0, 2H); ¹³C NMR (125 MHz, CDCl₃) δ 180.6 (C), 136.2 (CH), 136.1 (C), 131.3 (C), 130.7 (CH), 129.8 (CH), 124.2 (CH); IR (ATR) 1679, 1596, 1452, 1286, 924, 766 cm⁻¹; HRMS (APCI) m/z calcd for C₁₄H₉O₂ (M + H)⁺ 209.0597, found 209.0597.

Supplementary Material

Supplemental

NIHMS1025706-supplement-Supplemental.pdf^{(12.5MB, pdf)}

ACKNOWLEDGMENT

This research was supported by the National Institute of General Medical Sciences of the National Institutes of Health (1R01GM118730). NMR spectra acquired with the TCI cryoprobe and Bruker Advance 400 were supported by the National Institutes of Health (OD016343) and the National Science Foundation (CHE-01162222), respectively. We thank Dr. Chin Lin for his assistance with NMR spectroscopy and mass spectrometry.

Footnotes

Notes

The authors declare no competing financial interest.

ASSOCIATED CONTENT

Supporting Information

Spectral data and stereochemical proof of alcohol 9a. The Support-ing Information is available free of charge on the ACS Publications website.

REFERENCES

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Supplemental

NIHMS1025706-supplement-Supplemental.pdf^{(12.5MB, pdf)}

[R1] (1).Crossley SWM; Obradors C; Martinez RM; Shenvi RA Mn-, Fe-, and Co-Catalyzed Radical Hydrofunctionalizations of Olefins. Chem. Rev 2016, 116, 8912–9000. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R2] (2).Okamoto T; Oka S Oxygenation of Olefins under Reductive Conditions. Cobalt-Catalyzed Selective Conversion of Aromatic Olefins to Benzylic Alcohols by Molecular Oxygen and Tetrahydroborate. J. Org. Chem 1984, 49, 1589–1594. [Google Scholar]

[R3] (3).Isayama S; Mukaiyama T Hydration of Olefins with Molecular Oxygen and Triethylsilane Catalyzed by Bis(trifluoroacetylacetonato)cobalt(II). Chem. Lett 1989, 18, 569–572. [Google Scholar]

[R4] (4).Isayama S; Mukaiyama T Novel Method for the Preparation of Triethylsilyl Peroxides from Olefins by the Reaction with Molecular Oxygen and Triethylsilane Catalyzed by Bis(1,3-diketonato)cobalt(II). Chem. Lett 1989, 18, 573–576. [Google Scholar]

[R5] (5).Wu J-M; Kunikawa S; Tokuyasu T; Masuyama A; Nojima M; Kim H-S Co-Catalyzed Autoxidation of Alkene in the Presence of Silane. The Effect of the Structure of Silanes on the Efficiency of the Reaction and on the Product Distribution. Tetrahedron 2005, 61, 9961–9968. [Google Scholar]

[R6] (6).O’Neill PM; Hindley S; Pugh MD; Davies J; Bray PG; Park BK; Kapu DS; Ward SA; Stocks PA Co(thd)₂: A Superior Catalyst for Aerobic Epoxidation and Hydroperoxysilylation of Unactivated Alkenes: Application to the Synthesis of Spiro-1,2,4-Trioxanes. Tetrahedron Lett 2003, 44, 8135–8138. [Google Scholar]

[R7] (7).Ma X; Herzon SB Synthesis of Ketones and Esters from Heteroatom-Functionalized Alkenes by Cobalt-Mediated Hydrogen Atom Transfer. J. Org. Chem 2016, 81, 8673–8695. [DOI] [PubMed] [Google Scholar]

[R8] (8).Isayama S An Efficient Method for the Direct Peroxygenation of Various Olefinic Compounds with Molecular Oxygen and Triethylsilane Catalyzed by a Cobalt(II) Complex. Bull. Chem. Soc. Jpn 1990, 63, 1305–1310. [Google Scholar]

[R9] (9).Tokuyasu T; Kunikawa S; Abe M; Masuyama A; Nojima M; Kim H-S; Begum K; Wataya Y Synthesis of Antimalarial Yingzhaosu A Analogues by the Peroxidation of Dienes with Co(II)/O₂/Et₃SiH. J. Org. Chem 2003, 68, 7361–7367. [DOI] [PubMed] [Google Scholar]

[R10] (10).Tokuyasu T; Kunikawa S; McCullough KJ; Masuyama A; Nojima M Synthesis of Cyclic Peroxides by Chemo- and Regioselective Peroxidation of Dienes with Co(II)/O₂/Et₃SiH. J. Org. Chem 2005, 70, 251–260. [DOI] [PubMed] [Google Scholar]

[R11] (11).Tokuyasu T; Kunikawa S; Masuyama A; Nojima M Co(III)–Alkyl Complex- and Co(III)–Alkylperoxo Complex-Catalyzed Triethylsilylperoxidation of Alkenes with Molecular Oxygen and Triethylsilane. Org. Lett 2002, 4, 3595–3598. [DOI] [PubMed] [Google Scholar]

[R12] (12).Fringuelli F; Marino G; Taticchi A; Grandolini G A Comparative Study of the Aromatic Character of Furan, Thiophen, Selenophen, and Tellurophen. J. Chem. Soc., Perkin Trans. 2 1974, 0, 332–337. [Google Scholar]

[R13] (13).Bernadi F; Bottoni A; Venturini A An Ab Initio SCFMO Study of the Aromaticity of Some Cyclic Compounds. J. Mol. Struct. (Theochem) 1988, 163, 173–189. [Google Scholar]

[R14] (14).Achmatowicz O; Bukowski P; Szechner B; Zweirzchowska Z Synthesis of Methyl 2,3-Dideoxy-DL-Alk-2-Enopyranosides from Furan Compounds: A General Approach to the Total Synthesis of Monosaccharides. Tetrahedron 1971, 27, 1973–1996. [Google Scholar]

[R15] (15).Hao H-D; Trauner D Furans as Versatile Synthons: Total Syntheses of Caribenol A and Caribenol B. J. Am. Chem. Soc 2017, 139, 4117–4122. [DOI] [PubMed] [Google Scholar]

[R16] (16).Saussine L; Brazi E; Robine A; Mimoun H; Fischer J; Weiss R Cobalt(III) Alkylperoxy Complexes. Synthesis, X-Ray Structure, and Role in the Catalytic Decomposition of Alkyl Hydroperoxides and in the Hydroxylation of Hydrocarbons. J. Am. Chem. Soc 1985, 107, 3534–3540. [Google Scholar]

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PERMALINK

Cobalt-Catalyzed Oxygenation/Dearomatization of Furans

Jonathan P Oswald

K A Woerpel

Abstract

Graphical Abstract:

INTRODUCTION

Figure 1.

RESULTS AND DISCUSSION

Scheme 1.

Table 1.

Scheme 2.

Scheme 3.

Scheme 4.

Table 2.

Scheme 5.

Scheme 6.

Scheme 7.

Scheme 8.

Scheme 9.

Scheme 10.

Scheme 11.

Scheme 12.

Scheme 13.

Scheme 14.

CONCLUSION

EXPERIMENTAL SECTION

General Information.

Optimization of Co-Catalyzed Oxygenation of Furans.

Synthesis of Disubstituted Furan Substrates

Alcohol 7a.

Alcohol 7b.

Alcohol 7c.

Ketone 8a.

Ketone 8b.

Ketone 8c.

Representative Procedure for the Co-Catalyzed Oxygenation of Aromatic Compounds (Lactone 2).

Lactone 2 and bis(silylperoxy) esters 4 and 5.

Lactone 9 prepared from furan 8a.

Lactone 9 prepared from furan 8b.

Lactone 9 prepared from furan 8c.

Lactone 9 prepared from furan 6.

Alcohol 9a.

Silyl ether 10.

Lactone 9 and Carboxylic acid 11 from furan 8c.

Silyl peroxide 14.

Bis(silylperoxide) 16 and 17.

Silyl peroxide 19.

Lactone 21 and Silyl peroxide 22.

Silyl peroxide 24.

Dione 26.

Lactam 28 and Bis(silylperoxy) ketone 29.

Thiolactone 31.

Dione 33.

Dione 35.

Supplementary Material

ACKNOWLEDGMENT

Footnotes

REFERENCES

Associated Data

Supplementary Materials

ACTIONS

PERMALINK

RESOURCES

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