Metal-free UV-Vis-light-induced aerobic oxidative hydroxylation of arylboronic acids in the absence of a photosensitizer

Abstract

A simple and efficient method has been developed for the metal-free photosynthesis of phenols with UV-Vis (ultraviolet-visible) light in quartz tubes. The protocol uses readily available arylboronic acids as the starting materials, triethylamine as the sacrificial electron donor, and air as the oxidant. The method shows high efficiency, environmental friendliness and mild reaction conditions, without the addition of a photosensitizer.

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Chemists have been making great efforts to find a green, efficient method for the synthesis of organic compounds. Photosynthesis has shown good potential for the synthesis of organic compounds as it is easily accessible and clean.¹ A lot of light sensitive materials have been reported to be good catalysts, such as TiO₂,² C₃N₄,³ Ru complexes,⁴ Ir complexes⁵ and organic compounds.⁶ In those studies, most attention was focused on visible light catalysts, because there is about 50% visible light in solar light. Recently, some progress has been made towards the synthesis of phenols using arylboronic acids as the substrate.⁷ Very recently, Xiao and co-workers developed a visible-light initiated aerobic oxidative hydroxylation method for arylboronic acids using air as the oxidant, in the presence of [Ru(bpy)₃Cl₂]·6H₂O.^8a Meanwhile, Scaiano's group reported the photocatalytic hydroxylation of arylboronic acids using methylene blue as the photosensitizer.^8b Both of these focused on visible light photocatalysis in glass tubes. Herein, we report a simple and highly efficient metal-free UV-Vis-light-induced hydroxylation method for arylboronic acids in quartz tubes, without the addition of a photosensitizer.

As is well known, about 8% of solar light is high energy ultraviolet light that can activate organoboron compounds.⁹ Based on previous results, we applied photocatalysis to our study on the transformation of arylboronic acids to phenols. First, 4-methoxylboronic acid (1i) was used as a model substrate to investigate suitable reaction conditions, including using light sources with different wavelengths, different solvents, different amines as the sacrificial electron donors, different reaction times and different atmospheres. As shown in Table 1, the effect of the solvent was investigated first, using light from a high pressure mercury lamp with all ranges of light wavelength as the light source, triethylamine as the sacrificial electron donor, and air as the oxidant at room temperature for 8 h (entries 1–7); the mixed solvent, CH₃CN–H₂O (1 : 10), afforded the highest yield (entry 7), because of the good dissolving power of 1i in the mixed solvent. Only trace amounts of the product were observed when the reaction was performed under a nitrogen atmosphere (entry 8), while an oxygen atmosphere provided a 97% yield (entry 9). The effect of the light wavelength was determined using light filters (10–13); the light with a full range of wavelengths afforded the best result (entry 7), with the by-products, biphenyl and diphenyl ether, determined by GC-MS (see the ESI).† When UV light (220–400 nm) was used, a 76% yield was observed (entry 8); in fact, light from the high pressure mercury lamp is of wide UV wavelength. Other amines were also used (entries 15 and 16), and these gave slightly lower yields. When the reaction time was shortened, the yields were decreased (entries 17 and 18). The amount of triethylamine was varied (entries 19–21), and the results showed that one equiv. of triethylamine was suitable. Therefore, suitable conditions for the photosynthesis of phenols from arylboronic acids are as follows: a high pressure mercury lamp with all ranges of light wavelength as the light source, triethylamine as the sacrificial electron donor, CH₃CN–H₂O (1 : 10) as the solvent, and air as the oxidant, at room temperature for 8 h.

Table 1 Photosynthesis of 4-methoxyphenol (2i) from 4-methoxyphenylboronic acid (1i): optimization of conditions^a

Entry	Light source	Solvent	Amine	Yield (%)^b
a Reaction conditions: 4-methoxylboronic acid (1i) (1 mmol), solvent (2.0 mL), reaction time (8 h), N(Et)3 (1 mmol), under air for entries 1–7 and 10–21, under N2 for entry 8 and under O2 for entry 9, UV-Vis: full wavelength light from a high pressure mercury lamp without a filter.b Isolated yield. A/W = acetonitrile/water.c Under nitrogen atmosphere.d Under oxygen atmosphere.e Reaction time (4 h).f Reaction time (6 h).g N(Et)3 (2 mmol).h N(Et)3 (0.5 mmol).i In the absence of N(Et)3.
1	UV-Vis	H2O	N(Et)3	80
2	UV-Vis	CH3OH	N(Et)3	62
3	UV-Vis	CH3CN	N(Et)3	67
4	UV-Vis	C2H5OH	N(Et)3	54
5	UV-Vis	Toluene	N(Et)3	24
6	UV-Vis	DMSO	N(Et)3	84
7	UV-Vis	A/W (1 : 10)	N(Et)3	97
8	UV-Vis	A/W (1 : 10)	N(Et)3	Trace^c
9	UV-Vis	A/W (1 : 10)	N(Et)3	97^d
10	>400 nm	A/W (1 : 10)	N(Et)3	Trace
11	>350 nm	A/W (1 : 10)	N(Et)3	10
12	>280 nm	A/W (1 : 10)	N(Et)3	14
13	254 nm	A/W (1 : 10)	N(Et)3	54
14	220–400 nm	A/W (1 : 10)	N(Et)3	76
15	UV-Vis	A/W (1 : 10)	iPrN(Et)2	96
16	UV-Vis	A/W (1 : 10)	NH(Et)2	89
17	UV-Vis	A/W (1 : 10)	N(Et)3	68^e
18	UV-Vis	A/W (1 : 10)	N(Et)3	82^f
19	UV-Vis	A/W (1 : 10)	N(Et)3	97^g
20	UV-Vis	A/W (1 : 10)	N(Et)3	90^h
21	UV-Vis	A/W (1 : 10)	—	Trace^i

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With the optimized conditions for the photosynthesis of phenols from arylboronic acids in hand, we investigated the scope for the transformation of arylboronic acids to phenols. As shown in Table 2, the examined substrates provided good to excellent yields. For arylboronic acids, their reactivities were affected by the steric and electronic effects of the substrates; the substrates with electron-donating groups provided higher yields than those with electron-withdrawing groups, and the substrates with a bigger steric hindrance gave lower yields. Obviously, the substrates with fluoro (2l) or trifluoromethyl (2r) provided lower yields. The reactions had high tolerances for functional groups, including ether (2i–k), carbon-halo bonds (2l–n), nitro (2o, 2p), cyano (2q), carboxyl (2s and 2t), and ester (2u). Therefore, the present method showed a good way to synthesise phenols from arylboronic acids under light irradiation.

Table 2 Photosynthesis of phenols (2) from arylboronic acids (1)^a

2 (yield^b)
a Reaction conditions: arylboronic acid (1) (1.0 mmol), N(Et)3 (1.0 mmol), CH3CN–H2O (1 : 10) (2.0 mL), reaction temperature (rt, ∼25 °C), reaction time (8 h), under high pressure mercury lamp.b Isolated yield.

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Compared with Xiao and Scaiano's studies, the present reactions were performed in quartz tubes instead of glass tubes because quartz tubes are of a better transmittance for ultraviolet light than glass tubes. As shown in Scheme 1, two control experiments were carried out. The reaction of methoxyphenylboronic acid (1i) to 4-methoxyphenol (2i) in a quartz tube performed well, but a lower yield (12%) was obtained when the experiment was carried out in a glass tube. Therefore, ultraviolet light could be a key factor for the reactions in Table 2.

Scheme 1 Photosynthesis of 4-methoxyphenol (2i) from 4-methoxyphenylboronic acid (1i) in a quartz tube or a glass tube.

In previous work,⁸ the reaction was proposed to be a free radical process: the light sensor, such as [Ru(bpy)₃Cl₂]·6H₂O or methylene blue, first obtained an electron from amine, then transferred the electron to oxygen to form a superoxide anion, and the reaction of the superoxide anion with arylboronic acid then afforded phenol. However, the reports did not include the intermediates produced from arylboronic acids, and the source of the by-products, such as biphenyls and diphenyl ether, were not shown. In order to explore the present mechanism, electron paramagnetic resonance (EPR) was used to monitor the reaction process, and a radical trapper was applied to trap the free radicals generated during the reaction.⁹ As shown in Scheme 2, dimethyl pyridine N-oxide (DMPO) was chosen as the radical trapper to determine the oxide radicals. 0.1 equiv. of phenylboronic acid was quickly mixed with DMPO (50 mM) in 2 mL of CH₃CN–H₂O (1 : 10), and the mixture was moved into an EPR flat cell. In situ EPR spectra were elicited under irradiation from a high pressure mercury lamp for 4 min (Fig. 1).

Scheme 2 Photosynthesis of phenol (2a) from phenylboronic acid (1a) trapped by DMPO.

Fig. 1 In situ EPR spectra for the reaction shown in Scheme 2. (a) Measurement spectrum; (b) simulated spectrum for a hydroxyl free radical (g = 2.0023, A_H = 1.50 mT, A_N = 1.50 mT); (c) simulated spectrum for a carbon central free radical (g = 2.0023, A_H = 2.40 mT, A_N = 1.58 mT); (d) simulated spectrum for a hydroxyl free radical and carbon central free radical.

It was shown that both hydroxyl free radicals (star) and carbon central free radicals (dot) existed in the reaction (Fig. 1a). According to the simulated spectra of the hydroxyl free radical (Fig. 1b) and the carbon central free radical (Fig. 1c), there was a good agreement with the measured spectrum (Fig. 1a) and simulated spectrum for the hydroxyl free radical and carbon central free radical (Fig. 1d). The A-values coincided with the literature values as reported by Mason and Kalyanaraman (for the hydroxyl free radical, A_H = 1.5 mT, A_N = 1.5 mT),^10a,b and Jones (for the phenyl radical which is a carbon central radical, A_N = 1.60 mT, A_H = 2.46 mT).^10c We therefore supposed that the carbon central free radical was produced from arylboronic acids.

A control experiment was performed using ¹⁸O-labeled water as the solvent. As shown in Scheme 3, no ¹⁸O-labeled product was found by mass spectrometry, and the result indicated that the oxygen in 2i was from the O₂ in air (not from water). A similar result was reported by Xiao's group.^8a Water provided a proton and a hydroxyl anion in the reaction. However, the hydroxyl anion didn't take part in the formation of the product.

Scheme 3 Control experiment using ¹⁸O-labeled water as the solvent.

As we have determined the involvement of a carbon central free radical and a hydroxyl free radical as mentioned above, a possible mechanism for the photosynthesis of phenols from arylboronic acids is proposed in Scheme 4. In the presence of triethylamine, arylboronic acid (1) is activated by UV-Vis light to form I, and the treatment of I with oxygen generates a superoxide free radical (II) and a nitrogen cation (III). The reaction of II with a proton from water provides an HO₂˙ free radical (IV),¹¹ and the treatment of IV with III affords a hydroxyl free radical (V), leaving a cation, VI.^8a The reaction of V with arylboronic acids gives a carbon central free radical (VII), leaving boronic acid. The combination of VII with V affords the target product (2) (Route 1). In addition, the reaction of phenol with V gives a free radical (VIII), the conjugation of VIII with VII leads to a byproduct (3) (Route 2), and the dimerization of VII also yields a byproduct (4) (Route 3).

Scheme 4 Proposed mechanism for the photosynthesis of phenols from arylboronic acids under irradiation from a high pressure mercury lamp.

In conclusion, we have developed a simple and efficient method for the metal-free photosynthesis of phenols with UV-Vis (ultraviolet-visible) light in quartz tubes. The protocol uses readily available arylboronic acids as the starting materials, triethylamine as the sacrificial electron donor, CH₃CN–H₂O (1 : 10) as the solvent, and air as the oxidant, and the method shows high efficiency, environmental friendliness and mild reaction conditions, without the addition of a photosensitizer. The EPR experiments show the existence of a carbon free radical and a hydroxyl free radical in the reactions, which is helpful for the elucidation of the reaction mechanism. Further investigation on this mechanism is in progress.

The authors wish to thank the National Natural Science Foundation of China (Grant no. 21105054) for financial support.

Notes and references

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Footnote

† Electronic supplementary information (ESI) available: General procedure for synthesis, characterization data, and ¹H and ¹³C NMR spectra of compounds 2a–w. See DOI: 10.1039/c3ra46516k

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