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Article

Photochemically-Enabled Umpolung Conversion of 2-Acyloxybenzaldehydes into 2-Hydroxybenzofuranones

by
Victoria E. Opryshko
1,
Svetlana A. Krasnova
1,
Andrey A. Mikhaylov
1,2,
Yulia A. Bogdanova
1,2,
Alexander Yu. Smirnov
1,2,
Mikhail S. Baranov
1,2 and
Dmitrii S. Ivanov
1,*
1
Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya 16/10, 117997 Moscow, Russia
2
Laboratory of Medicinal Substances Chemistry, Institute of Translational Medicine, Pirogov Russian National Research Medical University, Ostrovitianov 1, 117997 Moscow, Russia
*
Author to whom correspondence should be addressed.
Molecules 2025, 30(15), 3080; https://doi.org/10.3390/molecules30153080
Submission received: 7 July 2025 / Revised: 18 July 2025 / Accepted: 21 July 2025 / Published: 23 July 2025
(This article belongs to the Section Organic Chemistry)
Browse Figures
Versions Notes

Abstract

2-Acyloxybenzaldehydes are converted into 2-hydroxybenzofuranones in good to excellent yields (60–99%). The reaction proceeds at room temperature in DMSO upon 365 nm LED irradiation under photocatalyst-free conditions. The present atom-economical synthetic approach represents the aldehyde group umpolung reactivity.

Graphical Abstract

1. Introduction

Benzofuranones with a hemiacetal moiety (i.e., 2-hydroxybenzofuranones) are a common structural motif in natural compounds (Scheme 1). These compounds and the corresponding acetals were identified in fungi [1,2,3,4], plants [5,6], and bacteria [7,8]. These compounds exhibit various biological activities, including cytotoxic [9] and antifungal effects [5], cyclooxygenase-2 inhibition [10,11], and antioxidant properties [6]. 2-Hydroxybenzofuranones attract significant interest in the search for novel antibiotics [7,12,13,14,15,16].
Organic photochemistry is an important part of modern organic chemistry. The excitation of molecules opens a way to realize unique reactivity that is difficult to access by other methods [17]. Photochemical transformations are successfully used in the synthesis of natural and biologically active compounds [18,19], as well as in industrial [20] and pharmaceutical [21] processes. Application of powerful monochromatic light-emitting diodes (LEDs), flow chemistry, and photoelectrochemical reactions [22,23] expand the palette of modern photochemical methods. The use of natural sunlight [24,25] and atmospheric oxygen in photoreactions [26,27] aligns with the principles of “green chemistry” [28,29]. The unusual photoinduced reactivity can achieve umpolung reactions, in which the polarity of the functional group is inverted [30,31]. The strategy of carbonyl polarity reversal through radical processes gives rise to a wide range of products [32,33,34]. Thus, recent works present photoinduced umpolung aldehyde transformations achieved via either ketyl radical [35,36] or acyl radical reactions (Scheme 2) [37,38]. In our recent work, we demonstrated photochemical acyl radical generation from benzaldehyde derivatives that was applied for intramolecular cyclization into chromanones [39]. In this work, we continue the systematic investigation of photoinduced transformations of ortho-substituted benzaldehydes. We propose an approach that may combine both ketyl and acyl radical moieties for photoinduced umpolung transformation of 2-acyloxybenzaldehydes into 2-hydroxybenzofuranones.

2. Results and Discussion

During the performed systematic photochemical screening of salicylaldehyde derivatives reactivity, their acyl derivatives 1 were studied. We found that 2-acetoxybenzaldehyde 1a is converted into 2-hydroxybenzofuranone 2a under 365 nm irradiation in DMSO. While such cyclic hemiacetals have been previously reported, existing synthetic methods are typically complex and low-yielding [40,41], which prompted us to study the found phototransformation in more detail. We screened various solvents (see Supplementary Materials, Part 1) and demonstrated that DMSO is uniquely effective for this transformation (Table 1), similar to all those we have identified previously [39,42]. Aside from DMSO, the target product was formed only in DMF and DMAC, albeit in significantly lower yields. In all other solvents, complex mixtures were observed, along with the oxidation product of the starting aldehyde 1a—2-acetoxybenzoic acid.
The addition of small amounts of water or conducting the reaction in open air had negligible effects on the process (Supplementary Materials, Part 2). However, the observed oxidation to 2-acetoxybenzoic acid in several solvents (e.g., Table 1, Entry 1, 6, 9, 12) suggests that an inert atmosphere is preferable. Although the substrate absorbs weakly at 365 nm (see Supplementary Materials, Part 3), this irradiation wavelength successfully induced phototransformation, whereas longer wavelengths were ineffective. Optimizing the light source to match the absorption maximum (e.g., using shorter wavelengths) may further enhance reaction efficiency in future work. Heating slightly increased the reaction rate (Supplementary Materials, Part 4). However, since precise temperature control during phototransformation is challenging, we performed the reaction at room temperature.
Thus, we propose carrying out the reaction in dry DMSO under an inert atmosphere with 365 nm irradiation at room temperature. However, the reaction was found rather tolerant to set-up conditions (such as the presence of wet DMSO, open-air atmosphere, heating, or shorter-wavelength diodes), which could potentially be employed.
Using the optimized conditions, we investigated the reactivity of a series of derivatives 1 and 3. The structures of all corresponding reaction products 2 and 4 were confirmed by 1H and 13C NMR spectroscopy (Supplementary Materials, Part 8), HRMS analysis, and comparison with previously reported spectral data for analogous derivatives.
First, we studied the acetoxy derivatives 1 with different substitution patterns in the benzene ring (Scheme 3).
Based on the obtained results, it can be concluded that the yields of substituted compounds 2b–n are lower than the yield of compound 2a. Moreover, substrates 1a–n require a longer irradiation time for transformation. A noticeable decrease in the yield was observed for all derivatives containing substituents in position 5 (para to the oxygen atom). The only exception was derivative 2n with an electron-withdrawing substituent in this position, which was formed in high yield. A similar effect was observed for 3-substituted derivatives 2e and 2l. However, in all cases the reaction yields ranged from good to high, which indicates the sufficient versatility of the reaction for acetoxy derivatives.
Next, we briefly examined the scope of the reaction for other carboxylate derivatives 3 (Scheme 4). The yields for all these substances 4 are also lower than that of derivative 2a, and the transformation also requires a longer irradiation time. At the same time, it was impossible to reveal any strict dependence between the structure of the substrate and the yield of the reaction. The lowest yield was observed for the cyclohexyl derivative 4b, while the very similar isopropyl and cyclobutyl derivatives 4e and 4f showed the best yields. We also succeeded in obtaining derivatives with cyclohexyl and cyclobutyl (4b and 4f) but not with those belonging to a cyclopentyl group. The only reliable exception was the phototransformation of aryl derivatives (3l–o), for which the rate was very low and which led to the formation of complex mixtures.
A detailed analysis of substituent effects on products’ yields, including potential mechanistic explanations, is presented below, following the mechanistic discussion.
Hypothetically, hemiacetals 2 and 4 may exist in equilibrium with the open form [43]. However, we did not observe such forms for any of the products by NMR spectroscopy. The high stability of the hemiacetal can be explained by the increased electrophilicity of the 1,2-dicabonyl moiety and the cyclic structure of the product. However, product 4g, though capable of forming two diastereomers, was obtained exclusively as a single isomer, likely the thermodynamically stable one stabilized by intramolecular hydrogen bonding. The absence of the second diastereomer supports possible transition between the ketone and hemiacetal tautomers. Next, we further confirmed the tautomeric equilibrium showing that these substances can be used as 1,2-dicarbonyl compounds in the synthesis of heterocyclic derivatives. Thus, we synthesized three quinoxaline derivatives—5b, 5d, and 5f—in nearly quantitative yields and one imidazole 6b with 65% yield (Scheme 5).
Finally, we briefly studied the possible reaction mechanism. First, a detailed study of the transformation in DMSO-d6 (Supplementary Materials, Part 5) revealed that this reaction proceeds directly without detectable intermediates, forming a single product via the first-order reaction. Second, we demonstrated that the presence of TEMPO ((2,2,6,6-tetramethylpiperidin-1-yl)oxidanyl) and BHT (butylated hydroxytoluene, 2,6-di-tert-butyl-4-methylphenol) as radical scavengers led to only a slight decrease in the reaction rate (Supplementary Materials, Part 6). Furthermore, no adducts with TEMPO were detected by NMR analysis. These results indicate the absence of long-lived radical intermediates in the reaction course (and no formation of mono-radical species). Third, the cross-reaction experiment (Supplementary Materials, Part 7) between substrates 1n and 3e confirmed the intramolecular nature of the transformation (Scheme 6).
Based on the above observations, we propose two reaction pathways, as shown in Scheme 6. Both mechanisms involve excitation of the substrate to a biradical-like excited state (intermediate i1, [44] Scheme 6), which then undergoes transformation through alternative routes. The first preferred pathway (Path 1) involves 1,6-hydrogen atom transfer (1,6-HAT [34]) from the aldehyde to the ester oxygen, yielding intermediate i2 containing acyl and ketyl radical fragments. Radical recombination leads to the formation of the target benzofuranone 2a. The less favorable second pathway (Path 2) proceeds through initial C-C bond formation followed by 1,3-HAT. The first pathway is favored, as evidenced by the well-documented high reactivity of aldehydes as hydrogen atom donors in HAT processes [34]. Furthermore, 1,6-HAT is a common and well-established process, whereas 1,3-HAT is very rare [45]. Thus, the generation of the acyl radical by 1,6-HAT in this photoprocess is probably the key to the umpolung reactivity of the aldehyde group. Another possible reaction mechanism could involve a Paternò–Büchi-type [2+2] cycloaddition between the C=O bond of the aldehyde and the C=C bond of the enol, formed via acyl group isomerization. However, the successful phototransformation of 3h aldehyde with a pivaloyl moiety to the corresponding product 4h excludes this pathway.
NMR analysis of the crude reaction mixtures suggested the occurrence of side processes for unsuccessful substrates 3i–p. Typically, complex mixtures of unidentifiable compounds were obtained instead of the target products. For aryl-substituted substrates 3k–o, traces of salicylaldehyde and the corresponding carboxylic acids were detected in these crude mixtures (Scheme 6). We propose that these substrates’ degradation occurs via photoinduced C-O bond cleavage, as described for similar compounds [46]. Analogically, the photodegradation of 3j and 3i may be related to the increased stability of the cyclopentyl radical [47]. A similar hypothetical pathway for photodegradation of substrates 2b, 2c, 2e, and 2h with a substituent at the 5-position may involve elimination of the acyl fragment to form quinone methides [48]. The decrease in the yields of products 2f, 2g, and 2l was also accompanied by the formation of complex mixtures. The corresponding substituents (Ph, F, OMe) are likely to contribute to more effective electron delocalization and reactivity in side processes. Apparently, the photochemical “meta-effect” [49,50] plays a role in the HAT efficiency. Thus, the introduction of an electron-withdrawing group at the meta position to the aldehyde group (position 5, Scheme 3) leads to more efficient formation of product 2n compared to products 2k and 2l containing electron-donating groups at similar meta positions (3 and 5, Scheme 3). Similarly, product 2m is formed more efficiently than 2k and 2l, since the alkoxy electron-donating group is presented in the para position [51].

3. Materials and Methods

3.1. Materials

Commercially available reagents were used without additional purification. E. Merck Kieselgel 60 (Darmstadt, Germany) was used for column chromatography.
Thin-layer chromatography (TLC) was performed on silica gel 60 F254 glass-backed plates (MERCK, Darmstadt, Germany). Visualization was performed using UV light (254 or 312 nm) or staining with KMnO4.
NMR spectra were recorded on a Bruker Avance III 800 (with a 5 mm CPTXI cryoprobe) and Bruker Fourier 300 (Billerica, MA, USA). Chemical shifts were reported relative to residue peaks of DMSO-d6 (2.51 ppm: for 1H and 39.5 ppm: for 13C).
Melting points were measured on an SMP 30 apparatus without correction.
High-resolution mass spectra (HRMS) were recorded on AB Sciex TripleTOF® 5600+ system (Framingham, MA, USA) using electrospray ionization (ESI). The measurements were performed in positive ion mode (interface capillary voltage—5500 V); mass range was from m/z 50 to m/z 3000; external or internal calibration was carried out with ESI Tuning Mix, Agilent (Santa Clara, CA, USA). A syringe injection was used for solutions in acetonitrile, methanol, or water (flow rate 20 μL/min). Nitrogen was applied as a dry gas; interface temperature was set at 180 °C. IUPAC compound names were generated using ChemDraw 12.0 Software.
Photoinduced processes were performed on Evoluchem™ PhotoRedOx box (HepatoChem, Beverly, MA, USA). A 365 nm (LG, HCK1012-01-006, 25 mW/cm2), 405 nm (LG, HCK1012-01-010, 28 mW/cm2), and 450 nm (CREE-XPE, HCK1012-01-002, 20 mW/cm2) light-emitting diode (LED) lamp from Evoluchem™ was used. This device is equipped with a fan to maintain room temperature during the irradiation process.
Optical properties of compound 1a were investigated using a 10 µM solution in dry DMSO on a Cary 100 Bio spectrophotometer (Varian, Palo Alto, CA, USA).
Data processing was performed using OriginPro 8.6 software (https://www.originlab.com/).

3.2. Synthesis of the Starting Compounds 1 and 3

3.2.1. Synthesis of the Starting Compound 1

A mixture of the corresponding 2-hydroxybenzaldehyde (10 mmol), acetyl chloride (13 mmol), and K2CO3 (2.76 g, 20 mmol), in freshly distilled CH3CN (50 mL) was heated at 65 °C for 10 h. Next, the reaction mixtures were dissolved in 200 mL of EtOAc, washed with saturated KCl solution (3 × 50 mL), and dried over Na2SO4. All volatiles were removed in vacuo, and the residue was purified with flash chromatography (eluent: mixture of hexane and EtOAc, v/v 50:1).
  • 2-Formylphenyl acetate (1a). Yield, 1.36 g (83%). 1H NMR (800 MHz, DMSO-d6) δ, ppm: 10.08 (1H, s), 7.91 (1H, dd, J = 7.6, 1.6 Hz), 7.76 (1H, td, J = 7.7, 1.6 Hz), 7.50 (1H, t, J = 7.5 Hz), 7.31 (1H, d, J = 8.1 Hz), 2.35 (3H, s). The spectral properties corresponded to the literature data [52].
  • 2-Formyl-4-methylphenyl acetate (1b). Yield, 1.60 g (90%). 1H NMR (800 MHz, DMSO-d6) δ, ppm: 10.04 (1H, s), 7.70 (1H, d, J = 1.7 Hz), 7.55 (1H, dd, J = 8.2, 1.7 Hz), 7.18 (1H, d, J = 8.2 Hz), 2.38 (3H, s), 2.33 (3H, s). The spectral properties corresponded to the literature data [53].
  • 4-Ethyl-2-formylphenyl acetate (1c). Yield, 1.84 g (96%); yellowish viscous oil. 1H NMR (800 MHz, DMSO-d6) δ, ppm: 10.05 (1H, s), 7.73 (1H, d, J = 2.0 Hz), 7.59 (1H, dd, J = 8.2, 2.0 Hz), 7.21 (1H, d, J = 8.2 Hz), 2.69 (2H, q, J = 7.6 Hz), 2.33 (3H, s), 1.21 (3H, t, J = 7.6 Hz). 13C NMR (75 MHz, DMSO-d6) δ, ppm: 190.0, 169.4, 149.2, 142.2, 135.0, 129.7, 127.6, 123.6, 27.3, 20.6, 15.3. HRMS (ESI) m/z: 193.0854 found (calcd for C11H13O3+, [M + H]+ 193.0859).
  • 5-(Tert-butyl)-2-formylphenyl acetate (1d). Yield, 2.14 g (97%); yellowish viscous oil. 1H NMR (800 MHz, DMSO-d6) δ, ppm: 10.00 (1H, s), 7.84 (1H, d, J = 8.1 Hz), 7.52–7.53 (1H, m), 7.28 (1H, d, J = 1.8 Hz), 2.34 (3H, s), 1.30 (9H, s). 13C NMR (75 MHz, DMSO-d6) δ, ppm: 189.5, 169.3, 159.6, 151.0, 130.9, 125.6, 123.5, 120.5, 35.2, 30.5, 20.7. HRMS (ESI) m/z: 221.1171 found (calcd for C13H17O3+, [M + H]+ 221.1172).
  • 2,4-Di-tert-butyl-6-formylphenyl acetate (1e). Yield, 2.24 g (81%). 1H NMR (800 MHz, DMSO-d6) δ, ppm: 9.92 (1H, s), 7.82 (1H, d, J = 2.4 Hz), 7.71 (1H, d, J = 2.4 Hz), 2.38 (3H, s), 1.34 (18H, m). The spectral properties corresponded to the literature data [54].
  • 3-Formyl-[1,1′-biphenyl]-4-yl acetate (1f). Yield, 2.28 g (95%); white solid; m.p., 118–120 °C. 1H NMR (800 MHz, DMSO-d6) δ, ppm: 10.14 (1H, s), 8.18 (1H, d, J = 2.0 Hz), 8.04 (1H, dd, J = 8.3, 2.0 Hz), 7.74 (2H, d, J = 7.5 Hz), 7.51 (2H, t, J = 7.5 Hz), 7.43 (1H, t, J = 7.3 Hz), 7.40 (1H, d, J = 8.3 Hz), 2.37 (3H, s). 13C NMR (75 MHz, DMSO-d6) δ, ppm: 190.2, 169.2, 150.2, 138.5, 138.2, 133.5, 129.4, 129.1, 128.2, 128.0, 126.7, 124.4, 20.7. HRMS (ESI) m/z: 241.0860 found (calcd for C15H13O3+, [M + H]+ 241.0859).
  • 4-Fluoro-2-formylphenyl acetate (1g). Yield, 1.70 g (93%). 1H NMR (800 MHz, DMSO-d6) δ, ppm: 10.05 (1H, d, J = 1.9 Hz), 7.68 (1H, dd, J = 8.4, 3.2 Hz), 7.63 (1H, td, J = 8.4, 3.2 Hz), 7.39 (1H, dd, J = 8.9, 4.5 Hz), 2.35 (3H, s). The spectral properties corresponded to the literature data [55].
  • 4-Chloro-2-formylphenyl acetate (1h). Yield, 1.95 g (97%). 1H NMR (800 MHz, DMSO-d6) δ, ppm: 10.04 (1H, s), 7.92 (1H, d, J = 2.6 Hz), 7.82 (1H, dd, J = 8.6, 2.6 Hz), 7.38 (1H, d, J = 8.6 Hz), 2.35 (3H, s). The spectral properties corresponded to the literature data [56].
  • 3-Chloro-2-formylphenyl acetate (1i). Yield, 1.57g (79%), yellowish viscous oil. 1H NMR (800 MHz, DMSO-d6) δ, ppm: 10.30 (1H, s), 7.72 (1H, t, J = 8.1 Hz), 7.57 (1H, dd, J = 8.0, 0.8 Hz), 7.28 (1H, d, J = 8.0 Hz), 2.31 (3H, s). 13C NMR (75 MHz, DMSO-d6) δ, ppm: 188.6, 168.9, 150.8, 136.6, 135.6, 128.6, 124.8, 123.4, 20.6. HRMS (ESI) m/z: 199.0156 found (calcd for C9H8ClO3+, [M + H]+ 199.0156).
  • 5-Bromo-2-formylphenyl acetate (1j). Yield, 2.16 g (89%). 1H NMR (800 MHz, DMSO-d6) δ, ppm: 10.06 (1H, s), 7.84 (1H, d, J = 8.3 Hz), 7.72 (1H, d, J = 8.3 Hz), 7.67 (1H, d, J = 1.1 Hz), 2.35 (3H, s). The spectral properties corresponded to the literature data [57].
  • 2-Formyl-4-methoxyphenyl acetate (1k). Yield, 1.57 g (81%). 1H NMR (800 MHz, DMSO-d6) δ, ppm: 10.04 (1H, s), 7.38 (1H, d, J = 3.2 Hz), 7.30–7.31 (1H, m), 7.23 (1H, d, J = 8.8 Hz), 3.83 (3H, s), 2.33 (3H, s). The spectral properties corresponded to the literature data [58].
  • 2-Formyl-6-methoxyphenyl acetate (1l). Yield, 1.55 g (80%). 1H NMR (800 MHz, DMSO-d6) δ, ppm: 10.10 (1H, s), 7.47–7.50 (1H, m), 7.44 (2H, d, J = 4.8 Hz), 3.84 (3H, s), 2.35 (3H, s). The spectral properties corresponded to the literature data [59].
  • 5-Ethoxy-2-formylphenyl acetate (1m). Yield, 1.92 g (92%); yellow solid; m.p., 58–60 °C. 1H NMR (800 MHz, DMSO-d6) δ, ppm: 9.90 (1H, s), 7.84 (1H, d, J = 8.6 Hz), 7.02 (1H, dd, J = 8.6, 2.2 Hz), 6.85 (1H, d, J = 2.2 Hz), 4.15 (2H, q, J = 6.9 Hz), 2.33 (3H, s), 1.35 (3H, t, J = 6.9 Hz). 13C NMR (201 MHz, DMSO-d6) δ, ppm: 188.3, 168.9, 164.1, 152.9, 132.9, 121.3, 112.7, 109.4, 64.2, 20.6, 14.3. HRMS (ESI) m/z: 209.0808 found (calcd for C11H13O4+, [M + H]+ 209.0808).
  • Methyl 4-acetoxy-3-formylbenzoate (1n). Yield, 1.89 g (85%); yellow solid; m.p., 88–90 °C. 1H NMR (800 MHz, DMSO-d6) δ, ppm: 10.14 (1H, s), 8.45 (1H, d, J = 1.2 Hz), 8.28 (1H, dd, J = 8.4, 1.2 Hz), 7.49 (1H, d, J = 8.4 Hz), 3.90 (3H, s), 2.38 (3H, s). 13C NMR (75 MHz, DMSO-d6) δ, ppm: 189.6, 168.8, 164.8, 154.3, 135.8, 131.7, 128.0, 127.9, 124.6, 52.5, 20.7. HRMS (ESI) m/z: 223.0602 found (calcd for C11H11O5+, [M + H]+ 223.0601).

3.2.2. Synthesis of the Starting Compounds 3a–3d, 3h–3l, and 3p

Corresponding 2-hydroxybenzaldehyde (10 mmol) and Et3N (15 mmol) were dissolved in freshly distilled CH2Cl2 (50 mL) and cooled to 0 °C. The corresponding acyl chloride (15 mmol) was added dropwise, and the resulted mixture was stirred at room temperature overnight. Next, the reaction mixtures were dissolved in 200 mL of CH2Cl2, washed with saturated KCl solution (3 × 50 mL), and dried over Na2SO4. All volatiles were removed in vacuo, and the residue was purified with flash chromatography (eluent: mixture of hexane and EtOAc, v/v 20:1).
  • 2-Formylphenyl 2-methoxyacetate (3a). Yield, 1.16 g (60%); white oil. 1H NMR (800 MHz, DMSO-d6) δ, ppm: 10.08 (1H, s), 7.94 (1H, dd, J = 7.6, 1.7 Hz), 7.76–7.79 (1H, m), 7.50–7.55 (1H, m), 7.35 (1H, d, J = 8.1 Hz), 4.45 (2H, s), 3.42 (3H, s). 13C NMR (75 MHz, DMSO-d6) δ, ppm: 190.1, 169.0, 150.3, 135.8, 131.5, 127.8, 126.9, 123.7, 68.8, 58.7. HRMS (ESI) m/z: 195.0652 found (calcd for C10H11O4+, [M + H]+ 195.0652).
  • 2-Formylphenyl cyclohexanecarboxylate (3b). Yield, 1.59 g (69%). 1H NMR (800 MHz, DMSO-d6) δ, ppm: 10.04 (1H, s), 7.91 (1H, dd, J = 7.7, 1.6 Hz), 7.74–7.77 (1H, m), 7.49 (1H, t, J = 7.5 Hz), 7.27 (1H, d, J = 8.1 Hz), 2.71 (1H, tt, J = 11.1, 3.7 Hz), 1.75 (2H, ddd, J = 13.2, 3.8, 3.7 Hz), 1.60–1.67 (2H, m), 1.51–1.59 (2H, m), 1.24–1.37 (4H, m). The spectral properties corresponded to the literature data [60].
  • 2-Formylphenyl 2-(neopentyloxy)acetate (3c). Yield, 1.63 g (65%); white oil. 1H NMR (800 MHz, DMSO-d6) δ, ppm: 10.08 (1H, s), 7.93 (1H, dd, J = 7.6, 1.5 Hz), 7.77 (1H, td, J = 7.7, 1.4 Hz), 7.52 (1H, t, J = 7.5 Hz), 7.35 (1H, d, J = 8.1 Hz), 4.51 (2H, s), 3.28 (2H, s), 0.91 (9H, s). 13C NMR (75 MHz, DMSO-d6) δ, ppm: 190.1, 169.3, 150.5, 135.7, 131.2, 127.9, 126.8, 123.7, 81.2, 67.9, 31.8, 26.5. HRMS (ESI) m/z: 251.1280 found (calcd for C14H19O4+, [M + H]+ 251.1278).
  • 2-Formylphenyl 5-phenylpentanoate (3d). Yield, 1.97 g (70%); white oil. 1H NMR (800 MHz, DMSO-d6) δ, ppm: 10.05 (1H, s), 7.91 (1H, dd, J = 7.6, 1.6 Hz), 7.75 (1H, td, J = 7.7, 1.7 Hz), 7.49 (1H, t, J = 7.5 Hz), 7.26–7.31 (3H, m), 7.22 (2H, d, J = 7.1 Hz), 7.18 (1H, t, J = 7.3 Hz), 2.72 (2H, t, J = 6.9 Hz), 2.64 (2H, t, J = 6.9 Hz), 1.66–1.73 (4H, m). 13C NMR (75 MHz, DMSO-d6) δ, ppm: 189.9, 171.7, 151.0, 141.9, 135.7, 131.0, 128.3, 128.2, 127.9, 126.6, 125.7, 123.8, 34.8, 33.0, 30.3, 23.7. HRMS (ESI) m/z: 283.1330 found (calcd for C18H19O3+, [M + H]+ 283.1329).
  • 2-Formylphenyl pivalate (3h). Yield, 1.96 g (95%); white oil. 1H NMR (300 MHz, DMSO-d6) δ, ppm: 10.03 (1H, s) 7.92 (1H, dd, J = 7.7, 1.5 Hz) 7.76 (1H, td, J = 7.7, 1.7 Hz) 7.50 (1H, t, J = 7.6 Hz) 7.27 (1H, d, J = 8.2 Hz) 1.35 (9H, s). 13C NMR (75 MHz, DMSO-d6) δ, ppm: 189.4, 176.2, 151.3, 135.7, 130.9, 128.1, 126.6, 123.6, 38.8, 26.7. HRMS (ESI) m/z: 207.1018 found (calcd for C12H15O3+, [M + H]+ 207.1016).
  • 2-Formylphenyl cyclopentanecarboxylate (3i). Yield, 2.04 g (88%); white oil. 1H NMR (800 MHz, DMSO-d6) δ, ppm 10.06 (1H, s), 7.91 (1H, dd, J = 7.6, 1.4 Hz), 7.74–7.77 (1H, m), 7.49 (1H, t, J = 7.5 Hz), 7.28 (1H, d, J = 8.0 Hz), 2.69 (2H, d, J = 7.4 Hz), 2.26–2.32 (1H, m), 1.83–1.88 (2H, m), 1.61–1.66 (2H, m), 1.52–1.56 (2H, m), 1.24–1.28 (2H, m). 13C NMR (75 MHz, DMSO-d6) δ, ppm: 189.7, 171.3, 151.1, 135.7, 130.8, 128.0, 126.6, 123.7, 35.6, 31.9, 24.6. HRMS (ESI) m/z: 233.1169 found (calcd for C14H17O3+, [M + H]+ 233.1172).
  • 2-Formylphenyl cyclopentanecarboxylate (3j). Yield, 1.42 g (65%). 1H NMR (800 MHz, DMSO-d6) δ, ppm: 10.05 (1H, s), 7.91 (1H, dd, J = 7.6, 1.6 Hz), 7.74–7.76 (1H, m), 7.49 (1H, t, J = 7.5 Hz), 7.30 (1H, d, J = 8.1 Hz), 3.14 (1H, quin, J = 7.9 Hz), 1.92–2.02 (4H, m), 1.61–1.70 (4H, m). The spectral properties corresponded to the literature data [61].
  • 2-Formylphenyl benzoate (3k). Yield, 1.24 g (55%). 1H NMR (800 MHz, DMSO-d6) δ, ppm: 10.10 (1H, s), 8.17 (2H, dd, J = 8.3, 1.2 Hz), 7.99 (1H, dd, J = 7.7, 1.6 Hz), 7.80–7.83 (1H, m), 7.76–7.79 (1H, m), 7.62–7.65 (2H, m), 7.57 (1H, t, J = 7.5 Hz), 7.48 (1H, d, J = 8.0 Hz). The spectral properties corresponded to the literature data [62].
  • 2-Formylphenyl 4-(2-methoxyethoxy)benzoate (3l). Yield, 1.38 g (46%); white oil. 1H NMR (800 MHz, DMSO-d6) δ, ppm: 10.09 (1H, s), 8.11 (2H, m), 7.97 (1H, dd, J = 7.7, 1.6 Hz), 7.80 (1H, td, J = 7.7, 1.7 Hz), 7.54 (1H, t, J = 7.5 Hz), 7.45 (1H, d, J = 8.1 Hz), 7.15 (2H, m), 4.23–4.26 (2H, m), 3.70–3.72 (2H, m), 3.33 (3H, s). 13C NMR (201 MHz, DMSO-d6) δ, ppm: 189.5, 164.1, 163.1, 151.2, 135.6, 132.2, 131.0, 128.1, 126.6, 123.9, 120.6, 114.7, 70.1, 67.4, 58.2. HRMS (ESI) m/z: 301.1071 found (calcd for C17H17O5+, [M + H]+ 301.1071).
  • Ethyl (2-formylphenyl) succinate (3p). Yield, 2.25 g (90%). 1H NMR (800 MHz, DMSO-d6) δ, ppm: 10.09 (1H, s), 7.90 (1H, dd, J = 7.7, 1.5 Hz), 7.77 (1H, td, J = 7.7, 1.6 Hz), 7.49 (1H, t, J = 7.5 Hz), 7.28 (1H, d, J = 8.1 Hz), 4.10 (2H, q, J = 7.1 Hz), 2.95 (2H, t, J = 6.6 Hz), 2.71 (2H, t, J = 6.6 Hz), 1.19 (3H, t, J = 7.1 Hz). The spectral properties corresponded to the literature data [63].

3.2.3. Synthesis of the Starting Compounds 3e–3g and 3m–3o

A mixture of the corresponding 2-hydroxybenzaldehyde (10 mmol), corresponding acid (10 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (3.10 g, 20 mmol), and 4-dimethylaminopyridine (0.24 g, 2 mmol) in freshly distilled CH2Cl2 (50 mL) was stirred at room temperature overnight. All volatiles were removed in vacuo, and the residue was purified with flash chromatography (eluent: mixture of hexane and EtOAc, v/v 20:1).
  • 2-Formylphenyl isobutyrate (3e). Yield, 1.23 g (64%). 1H NMR (800 MHz, DMSO-d6) δ, ppm: 10.05 (1H, s), 7.92 (1H, dd, J = 7.6, 1.6 Hz), 7.74–7.77 (1H, m), 7.50 (1H, t, J = 7.5 Hz), 7.29 (1H, d, J = 8.1 Hz), 2.92 (1H, spt, J = 7.0 Hz), 1.28 (6H, d, J = 7.0 Hz). The spectral properties corresponded to the literature data [61].
  • Tert-butyl (2-formylphenyl) carbonate (3f). Yield, 1.18 g (58%); white oil. 1H NMR (800 MHz, DMSO-d6) δ, ppm: 10.04 (1H, s), 7.92 (1H, dd, J = 7.7, 1.6 Hz), 7.73–7.78 (1H, m), 7.47–7.53 (1H, m), 7.30 (1H, d, J = 8.1 Hz), 3.48–3.61 (1H, m), 2.37–2.43 (2H, m), 2.28–2.33 (2H, m), 1.99–2.04 (1H, m), 1.88–1.94 (1H, m). 13C NMR (75 MHz, DMSO-d6) δ, ppm: 189.8, 173.1, 151.0, 135.6, 131.2, 128.0, 126.6, 123.7, 37.1, 24.6, 17.8. HRMS (ESI) m/z: 205.0854 found (calcd for C12H13O3+, [M + H]+ 205.0859).
  • Bis(2-formylphenyl) glutarate (3g). Yield, 1.36 g (40%). 1H NMR (800 MHz, DMSO-d6) δ, ppm: 10.09 (2H, s), 7.93 (2H, dd, J = 7.7, 1.7 Hz), 7.76 (2H, td, J = 7.7, 1.7 Hz), 7.51 (2H, td, J = 7.5, 0.5 Hz), 7.30–7.36 (2H, m), 2.86 (4H, t, J = 7.4 Hz), 2.07 (2H, quin, J = 7.4 Hz). The spectral properties corresponded to the literature data [64].
  • 2-Formylphenyl nicotinate (3m). Yield, 1.10 g (48%). 1H NMR (800 MHz, DMSO-d6) δ, ppm: 10.12 (1H, s), 9.27–9.31 (1H, m), 8.93 (1H, dd, J = 4.8, 1.6 Hz), 8.50 (1H, dt, J = 7.9, 1.9 Hz), 8.01 (1H, dd, J = 7.7, 1.6 Hz), 7.83 (1H, td, J = 7.7, 1.7 Hz), 7.67–7.69 (1H, m), 7.59 (1H, t, J = 7.5 Hz), 7.52 (1H, d, J = 8.1 Hz). The spectral properties corresponded to the literature data [65].
  • 2-Formylphenyl isonicotinate (3n). Yield, 1.25 g (55%). 1H NMR (800 MHz, DMSO-d6) δ, ppm: 10.10 (1H, s), 8.91 (2H, dd, J = 4.6, 1.3 Hz), 8.04 (2H, dd, J = 4.4, 1.6 Hz), 8.02 (1H, dd, J = 7.7, 1.6 Hz), 7.83 (1H, td, J = 7.8, 1.7 Hz), 7.60 (1H, t, J = 7.5 Hz), 7.52 (1H, d, J = 8.0 Hz). The spectral properties corresponded to the literature data [66].
  • 2-Formylphenyl furan-2-carboxylate (3o). Yield, 1.12 g (52%). 1H NMR (800 MHz, DMSO-d6) δ, ppm: 10.10 (1H, s), 8.06–8.18 (1H, m), 7.98 (1H, dd, J = 7.6, 1.6 Hz), 7.80 (1H, td, J = 7.8, 1.7 Hz), 7.63 (1H, d, J = 3.5 Hz), 7.56 (1H, t, J = 7.5 Hz), 7.47 (1H, d, J = 8.1 Hz), 6.83 (1H, dd, J = 3.5, 1.7 Hz). The spectral properties corresponded to the literature data [65].

3.3. Photoinduced Synthesis of the 2-Hydroxy-Benzofuran-3(2H)-Ones 2 and 4

The corresponding starting compound 1 or 3 (1.0 mmol) was dissolved in freshly distilled DMSO (20 mL) in a Schlenk vessel. The mixtures were degassed under vacuum and filled with argon three times. The solvent screening demonstrated that wet DMSO can be used, and the reaction can be performed in open air. However, given the potential for oxidation of the starting aldehydes to corresponding 2-acyloxybenzoic acids and the fact that screening was performed only on aldehyde 1a, carrying out the reaction under inert conditions seems preferable. Obtained solutions were irradiated with 365 nm LED lamp in Evoluchem™ PhotoRedOx box with stirring. The process was carried out strictly with two samples at a time. This approach allowed us to claim approximately identical irradiation conditions for all samples, since the Schlenk vessels were installed symmetrically into the reactor each time. It is very important that during the entire irradiation process, the internal ventilation cooling system of the reactor must be turned on to maintain the room temperature of the reaction mixture. The progress of the reaction was monitored by TLC and 1H NMR. After the completion of the reaction, reaction mixtures were dissolved in 200 mL of EtOAc, washed with saturated KCl solution (10 × 30 mL), and dried over Na2SO4. All volatiles were removed in vacuo, and the residue was purified with flash chromatography (eluent: mixture of hexane and EtOAc, v/v 5:1).
  • 2-Hydroxy-2-methylbenzofuran-3(2H)-one (2a). Yield, 162 mg (99%). Reaction time, ~12 h. 1H NMR (800 MHz, DMSO-d6) δ, ppm: 7.72–7.74 (1H, m), 7.69 (1H, s), 7.62 (1H, dd, J = 7.6, 0.8 Hz), 7.14 (1H, d, J = 8.3 Hz), 7.12 (1H, t, J = 7.4 Hz), 1.45 (3H, s). The spectral properties corresponded to the literature data [39].
  • 2-Hydroxy-2,5-dimethylbenzofuran-3(2H)-one (2b). Yield, 134 mg (75%); yellow solid; m.p., 100–102 °C. Reaction time, ~48 h. 1H NMR (800 MHz, DMSO-d6) δ, ppm m: 7.63 (1H, s), 7.55 (1H, dd, J = 8.4, 1.6 Hz), 7.41 (1H, s), 7.04 (1H, d, J = 8.4 Hz), 2.30 (3H, s), 1.43 (3H, s). 13C NMR (201 MHz, DMSO-d6) δ, ppm: 199.2, 167.8, 140.0, 131.0, 123.8, 118.3, 112.9, 104.3, 21.8, 20.0. HRMS (ESI) m/z: 179.0704 found (calcd for C10H11O3+, [M + H]+ 179.0703).
  • 5-Ethyl-2-hydroxy-2-methylbenzofuran-3(2H)-one (2c). Yield, 134 mg (70%). Reaction time, ~48 h. 1H NMR (800 MHz, DMSO-d6) δ, ppm: 7.62 (1H, s), 7.60 (1H, dd, J = 8.5, 2.0 Hz), 7.43 (1H, d, J = 1.4 Hz), 7.06 (1H, d, J = 8.4 Hz), 2.61 (2H, q, J = 7.6 Hz), 1.44 (3H, s), 1.17 (3H, t, J = 7.6 Hz). The spectral properties corresponded to the literature data [39].
  • 6-(Tert-butyl)-2-hydroxy-2-methylbenzofuran-3(2H)-one (2d). Yield, 152 mg (69%); white solid; m.p., 48–50 °C. Reaction time, ~24 h. 1H NMR (800 MHz, DMSO-d6) δ, ppm: 7.60 (1H, s), 7.54 (1H, d, J = 8.1 Hz), 7.19 (1H, d, J = 8.1 Hz), 7.11 (1H, s), 1.44 (3H, s), 1.30 (10H, s). 13C NMR (75 MHz, DMSO-d6) δ, ppm: 198.5, 169.9, 163.5, 124.1, 119.6, 116.0, 109.7, 104.4, 35.7, 30.6, 21.7. HRMS (ESI) m/z: 221.1172 found (calcd for C13H17O3+, [M + H]+ 221.1172).
  • 5,7-Di-tert-butyl-2-hydroxy-2-methylbenzofuran-3(2H)-one (2e). Yield, 180 mg (65%); yellow solid; m.p., 138–140 °C. Reaction time, ~48 h. 1H NMR (800 MHz, DMSO-d6) δ, ppm: 7.61 (1H, d, J = 2.1 Hz), 7.60 (1H, s), 7.37 (1H, d, J = 2.1 Hz), 1.45 (3H, s), 1.38 (9H, s), 1.29 (9H, s). 13C NMR (75 MHz, DMSO-d6) δ, ppm: 199.9, 166.4, 144.0, 134.7, 132.3, 118.3, 117.5, 103.8, 34.3, 34.0, 31.1, 28.9, 21.8. HRMS (ESI) m/z: 277.1803 found (calcd for C17H25O3+, [M + H]+ 277.1798).
  • 2-Hydroxy-2-methyl-5-phenylbenzofuran-3(2H)-one (2f). Yield, 163 mg (68%); yellow solid; m.p., 121–123 °C. Reaction time, ~24 h. 1H NMR (800 MHz, DMSO-d6) δ, ppm: 8.06 (1H, dd, J = 8.6, 2.0 Hz), 7.85 (1H, d, J = 2.0 Hz), 7.78 (1H, s), 7.66–7.70 (2H, m), 7.46 (2H, t, J = 7.7 Hz), 7.35–7.39 (1H, m), 7.25 (1H, d, J = 8.6 Hz), 1.50 (3H, s). 13C NMR (201 MHz, DMSO-d6) δ, ppm: 199.1, 168.9, 138.8, 137.8, 134.2, 129.0, 127.4, 126.5, 121.9, 119.1, 113.8, 104.9, 21.7. HRMS (ESI) m/z: 241.0859 found (calcd for C15H13O3+, [M + H]+ 241.0859).
  • 5-Fluoro-2-hydroxy-2-methylbenzofuran-3(2H)-one (2g). Yield, 120 mg (66%). Reaction time, ~24 h. 1H NMR (800 MHz, DMSO-d6) δ, ppm: 7.78 (1H, s), 7.63 (1H, td, J = 9.0, 2.9 Hz), 7.47 (1H, dd, J = 7.0, 2.9 Hz), 7.20 (1H, dd, J = 9.0, 3.7 Hz), 1.46 (3H, s). The spectral properties corresponded to the literature data [39].
  • 5-Chloro-2-hydroxy-2-methylbenzofuran-3(2H)-one (2h). Yield, 147 mg (74%); yellow solid; m.p., 90–92 °C. Reaction time, ~48 h. 1H NMR (800 MHz, DMSO-d6) δ, ppm: 7.84 (1H, s), 7.77 (1H, dd, J = 8.8, 2.4 Hz), 7.69 (1H, d, J = 2.4 Hz), 7.21 (1H, d, J = 8.8 Hz), 1.47 (3H, s). 13C NMR (201 MHz, DMSO-d6) δ, ppm: 198.3, 167.9, 138.6, 125.8, 123.8, 119.9, 115.3, 105.3, 21.6. HRMS (ESI) m/z: 199.0154 found (calcd for C9H8ClO3+, [M + H]+ 199.0156).
  • 4-Chloro-2-hydroxy-2-methylbenzofuran-3(2H)-one (2i). Yield, 159 mg (80%); yellow solid; m.p., 80–82 °C. Reaction time, ~24 h. 1H NMR (800 MHz, DMSO-d6) δ, ppm: 7.82 (1H, s), 7.70 (1H, t, J = 8.1 Hz), 7.14 (1H, d, J = 7.8 Hz), 7.12 (1H, d, J = 8.3 Hz), 1.47 (3H, s). 13C NMR (201 MHz, DMSO-d6) δ, ppm: 196.4, 170.2, 139.6, 130.5, 122.5, 115.5, 112.1, 104.7, 21.6. HRMS (ESI) m/z: 199.0157 found (calcd for C9H8ClO3+, [M + H]+ 199.0156).
  • 6-Bromo-2-hydroxy-2-methylbenzofuran-3(2H)-one (2j). Yield, 190 mg (78%); white solid; m.p., 96–98 °C. Reaction time, ~24 h. 1H NMR (700 MHz, DMSO-d6) δ, ppm: 7.85 (1H, s), 7.57 (1H, dd, J = 8.1, 0.3 Hz), 7.50 (1H, d, J = 1.3 Hz), 7.30 (1H, dd, J = 8.1, 1.3 Hz), 1.47 (3H, s). 13C NMR (75 MHz, DMSO-d6) δ, ppm: 198.1, 169.6, 132.6, 126.1, 125.2, 117.9, 116.5, 105.3, 21.6. HRMS (ESI) m/z: 242.9648 found (calcd for C9H8BrO3+, [M + H]+ 242.9651).
  • 2-Hydroxy-5-methoxy-2-methylbenzofuran-3(2H)-one (2k). Yield, 165 mg (85%); light green solid; m.p., 100–102 °C. Reaction time, ~48 h. 1H NMR (800 MHz, DMSO-d6) δ, ppm: 7.63 (1H, s), 7.35 (1H, dd, J = 8.9, 2.8 Hz), 7.09 (1H, d, J = 8.9 Hz), 7.08 (1H, d, J = 2.8 Hz), 3.77 (3H, s), 1.43 (3H, s). 13C NMR (75 MHz, DMSO-d6) δ, ppm: 199.5, 164.6, 154.3, 128.1, 118.4, 114.3, 105.2, 104.7, 55.8, 21.8. HRMS (ESI) m/z: 195.0652 found (calcd for C10H11O4+, [M + H]+ 195.0652).
  • 2-Hydroxy-7-methoxy-2-methylbenzofuran-3(2H)-one (2l). Yield, 126 mg (65%); yellow solid; m.p., 100–102 °C. Reaction time, ~48 h. 1H NMR (800 MHz, DMSO-d6) δ, ppm: 7.72 (1H, s), 7.35 (1H, d, J = 7.8 Hz), 7.16 (1H, d, J = 7.7 Hz), 7.05 (1H, t, J = 7.8 Hz), 3.87 (3H, s), 1.45 (3H, s). 13C NMR (75 MHz, DMSO-d6) δ, ppm: 199.4, 159.6, 146.0, 122.2, 119.9, 119.4, 115.3, 104.6, 55.9, 21.7. HRMS (ESI) m/z: 195.0652 found (calcd for C10H11O4+, [M + H]+ 195.0652).
  • 6-Ethoxy-2-hydroxy-2-methylbenzofuran-3(2H)-one (2m). Yield, 194 mg (90%); yellow solid; m.p., 78–80 °C. Reaction time, ~24 h. 1H NMR (800 MHz, DMSO-d6) δ, ppm: 7.63 (1H, s), 7.50 (1H, d, J = 8.4 Hz), 6.65 (1H, d, J = 1.9 Hz), 6.62–6.65 (1H, m), 4.14 (2H, q, J = 7.0 Hz), 1.43 (3H, s), 1.35 (3H, t, J = 7.0 Hz). 13C NMR (75 MHz, DMSO-d6) δ, ppm: 196.5, 171.9, 167.8, 125.8, 111.3, 111.2, 105.1, 96.8, 64.3, 21.9, 14.3. HRMS (ESI) m/z: 209.0813 found (calcd for C11H13O4+, [M + H]+ 209.0808).
  • Methyl 2-hydroxy-2-methyl-3-oxo-2,3-dihydrobenzofuran-5-carboxylate (2n). Yield, 198 mg (89%); yellow solid; m.p., 88–90 °C. Reaction time, ~24 h. 1H NMR (800 MHz, DMSO-d6) δ, ppm: 8.29 (1H, dd, J = 8.7, 1.8 Hz), 8.13 (1H, d, J = 1.8 Hz), 7.98 (1H, s), 7.28 (1H, d, J = 8.7 Hz), 3.86 (3H, s), 1.50 (3H, s). 13C NMR (201 MHz, DMSO-d6) δ, ppm: 198.3, 172.0, 165.1, 139.5, 126.1, 123.3, 118.8, 113.8, 106.0, 52.3, 21.5. HRMS (ESI) m/z: 223.0597 found (calcd for C11H11O5+, [M + H]+ 223.0601).
  • 2-Hydroxy-2-(methoxymethyl)benzofuran-3(2H)-one (4a). Yield, 165 mg (85%); yellow solid; m.p., 98–100 °C. Reaction time, ~24 h. 1H NMR (800 MHz, DMSO-d6) δ, ppm: 7.92 (1H, s), 7.72 (1H, ddd, J = 8.4, 7.2, 1.4 Hz), 7.59 (1H, dd, J = 7.6, 0.9 Hz), 7.17 (1H, d, J = 8.3 Hz), 7.08–7.12 (1H, m), 3.66–3.70 (1H, m), 3.61–3.65 (1H, m), 3.16 (3H, s). 13C NMR (201 MHz, DMSO-d6) δ, ppm: 198.6, 170.5, 138.9, 124.1, 121.7, 119.7, 113.0, 103.6, 73.4, 59.0. HRMS (ESI) m/z: 195.0650 found (calcd for C10H11O4+, [M + H]+ 195.0652).
  • 2-Cyclohexyl-2-hydroxybenzofuran-3(2H)-one (4b). Yield, 139 mg (60%); yellow solid; m.p., 73–75 °C. Reaction time, ~24 h. 1H NMR (800 MHz, DMSO-d6) δ, ppm: 7.70–7.72 (1H, m), 7.58 (1H, dd, J = 7.6, 0.8 Hz), 7.56 (1H, s), 7.15 (1H, d, J = 8.3 Hz), 7.09 (1H, t, J = 7.4 Hz), 1.91 (1H, d, J = 12.8 Hz), 1.78–1.81 (1H, m), 1.69–1.72 (1H, m), 1.57–1.63 (2H, m), 1.43 (1H, d, J = 13.0 Hz), 1.03–1.17 (5H, m). 13C NMR (201 MHz, DMSO-d6) δ, ppm: 200.1, 170.3, 138.9, 123.9, 121.6, 120.1, 112.9, 106.7, 43.2, 25.8, 25.6, 25.4, 25.2, 25.1. HRMS (ESI) m/z: 233.1173 found (calcd for C14H17O3+, [M + H]+ 233.1172).
  • 2-Hydroxy-2-((neopentyloxy)methyl)benzofuran-3(2H)-one (4c). Yield, 155 mg (62%); white solid; m.p., 63–65 °C. Reaction time, ~12 h. 1H NMR (800 MHz, DMSO-d6) δ, ppm: 7.88 (1H, s), 7.70 (1H, ddd, J = 8.3, 7.2, 1.4 Hz), 7.59 (1H, dd, J = 7.6, 0.8 Hz), 7.16 (1H, d, J = 8.3 Hz), 7.08 (1H, t, J = 7.4 Hz), 3.72–3.75 (1H, m), 3.67–3.70 (1H, m), 3.04 (1H, d, J = 8.6 Hz), 2.93 (1H, d, J = 8.6 Hz), 0.56 (9H, s). 13C NMR (201 MHz, DMSO-d6) δ, ppm: 199.0, 170.5, 138.7, 123.7, 121.5, 120.1, 112.7, 104.1, 81.3, 72.4, 31.6, 26.0. HRMS (ESI) m/z: 251.1279 found (calcd for C14H19O4+, [M + H]+ 251.1278).
  • 2-Hydroxy-2-(4-phenylbutyl)benzofuran-3(2H)-one (4d). Yield, 212 mg (75%); yellow solid; m.p., 78–80 °C. Reaction time, ~24 h. 1H NMR (800 MHz, DMSO-d6) δ, ppm: 7.72 (1H, ddd, J = 8.3, 7.2, 1.4 Hz), 7.64 (1H, s), 7.60 (1H, dd, J = 7.6, 0.8 Hz), 7.24 (2H, t, J = 7.6 Hz), 7.12–7.16 (4H, m), 7.11 (1H, t, J = 7.4 Hz), 1.82–1.87 (1H, m), 1.79 (1H, ddd, J = 14.0, 11.1, 5.2 Hz), 1.50–1.55 (2H, m), 1.36–1.40 (1H, m), 1.15–1.24 (2H, m), 0.73–0.88 (1H, m). 13C NMR (201 MHz, DMSO-d6) δ, ppm: 199.5, 169.9, 142.0, 139.0, 128.2, 128.1, 125.6, 124.3, 121.7, 119.3, 113.1, 105.6, 35.0, 34.9, 30.9, 21.7. HRMS (ESI) m/z: 283.1322 found (calcd for C18H19O3+, [M + H]+ 283.1329).
  • 2-Hydroxy-2-isopropylbenzofuran-3(2H)-one (4e). Yield, 173 mg (90%); yellow solid; m.p., 58–60 °C. Reaction time, ~24 h. 1H NMR (800 MHz, DMSO-d6) δ, ppm: 7.68–7.74 (1H, m), 7.53–7.64 (2H, m), 7.17 (1H, d, J = 8.3 Hz), 7.10 (1H, t, J = 7.4 Hz), 2.05–2.12 (1H, m), 0.99 (3H, d, J = 6.8 Hz), 0.78 (3H, d, J = 6.8 Hz). 13C NMR (75 MHz, DMSO-d6) δ, ppm: 200.1, 170.4, 139.0, 124.1, 121.6, 120.1, 112.9, 107.0, 33.4, 15.9, 15.5. HRMS (ESI) m/z: 193.0859 found (calcd for C11H13O3+, [M + H]+ 193.0859).
  • 2-Cyclobutyl-2-hydroxybenzofuran-3(2H)-one (4f). Yield, 198 mg (97%); yellow solid; m.p., 62–64 °C. Reaction time, ~24 h. 1H NMR (800 MHz, DMSO-d6) δ, ppm: 7.73 (1H, ddd, J = 8.4, 7.2, 1.5 Hz), 7.62 (1H, s), 7.59 (1H, dd, J = 7.6, 0.9 Hz), 7.19 (1H, d, J = 8.3 Hz), 7.05–7.13 (1H, m), 2.67–2.76 (1H, m), 2.09–2.15 (1H, m), 1.94–1.99 (1H, m), 1.80–1.87 (2H, m), 1.70–1.76 (2H, m). 13C NMR (75 MHz, DMSO-d6) δ, ppm: 199.4, 170.1, 139.1, 124.2, 121.7, 119.9, 113.1, 105.7, 22.0, 21.0, 17.5. HRMS (ESI) m/z: 205.0858 found (calcd for C12H13O3+, [M + H]+ 205.0859).
  • 2,2′-(Propane-1,3-diyl)bis(2-hydroxybenzofuran-3(2H)-one) (4g). Yield, 238 mg (70%); white solid; m.p., 128–130 °C. Reaction time, ~24 h. 1H NMR (800 MHz, DMSO-d6) δ, ppm: 7.69–7.73 (2H, m), 7.65 (2H, d, J = 2.2 Hz), 7.59 (2H, d, J = 7.6 Hz), 7.13 (2H, dd, J = 8.3, 3.4 Hz), 7.10 (2H, t, J = 7.4 Hz), 1.76–1.81 (2H, m), 1.70–1.75 (2H, m), 1.36–1.41 (1H, m), 1.14–1.26 (1H, m). 13C NMR (75 MHz, DMSO-d6) δ, ppm: 199.4, 169.8, 139.1, 124.4, 121.8, 119.2, 113.2, 105.4, 34.9, 15.5. HRMS (ESI) m/z: 341.1018 found (calcd for C19H17O6+, [M + H]+ 341.1020).
  • 2-(tert-butyl)-2-hydroxybenzofuran-3(2H)-one (4h). Yield, 134 mg (65%); yellow oil. Reaction time, ~24 h. 1H NMR (300 MHz, DMSO-d6) δ, ppm: 7.66–7.75 (1H, m) 7.61–7.56 (2H, m) 7.15 (1H, d, J = 8.3 Hz) 7.08 (1H, t, J = 7.4 Hz) 0.97 (9H, s). 13C NMR (75 MHz, DMSO-d6) δ, ppm: 200.1, 170.3, 138.9, 124.0, 121.5, 120.5, 112.8, 108.1, 37.3, 23.8. HRMS (ESI) m/z: 207.1019 found (calcd for C12H15O3+, [M + H]+ 207.1016).

3.4. Synthesis of the Heterocyclic Derivatives 5 and 6

3.4.1. Synthesis of the Heterocyclic Derivatives 5

A mixture of the corresponding 2-hydroxybenzofuran-3(2H)-one 2b, 2d, or 4f (0.07 mmol) and o-phenylenediamine (8 mg, 0.07 mmol) in freshly distilled MeOH (0.5 mL) was stirred at room temperature for 10 min. All volatiles were removed in vacuo, and the residue was purified with flash chromatography (eluent: mixture of hexane and EtOAc, v/v 10:1).
  • 4-Methyl-2-(3-methylquinoxalin-2-yl)phenol (5b). Yield, 17 mg (99%); pale yellow solid; m.p., 190–192 °C. 1H NMR (300 MHz, DMSO-d6) δ, ppm: 9.63 (1H, s), 7.96–8.10 (2H, m), 7.71–7.87 (2H, m), 7.07–7.18 (2H, m), 6.88 (1H, d, J = 8.1 Hz), 2.57 (3H, s), 2.27 (3H, s). 13C NMR (75 MHz, DMSO-d6) δ, ppm: 154.1, 154.0, 152.4, 140.6, 140.3, 130.7, 130.7, 129.6, 129.1, 128.7, 128.1, 127.8, 126.1, 115.6, 22.7, 20.0. HRMS (ESI) m/z: 251.1180 found (calcd for C16H15N2O+, [M + H]+ 251.1179).
  • 2-(3-Cyclobutylquinoxalin-2-yl)phenol (5d). Yield, 19 mg (97%); yellow oil. 1H NMR (300 MHz, DMSO-d6) δ, ppm: 9.73 (1H, s), 8.11 (1H, dd, J = 7.7, 1.3 Hz), 8.04 (1H, dd, J = 7.7, 1.4 Hz), 7.74–7.88 (2H, m), 7.29–7.38 (1H, m), 7.20–7.28 (1H, m), 6.88–7.03 (2H, m), 3.87 (1H, quin, J = 8.5 Hz), 2.29–2.45 (2H, m), 1.68–2.06 (4H, m). 13C NMR (75 MHz, DMSO-d6) δ, ppm: 158.7, 154.8, 153.3, 140.7, 140.3, 130.3, 130.1, 129.6, 129.1, 128.7, 128.4, 126.2, 119.0, 115.5, 39.0, 27.2, 17.4. HRMS (ESI) m/z: 277.1333 found (calcd for C18H17N2O+, [M + H]+ 277.1335).
  • 2-(3-(4-Phenylbutyl)quinoxalin-2-yl)phenol (5f). Yield, 23 mg (93%); yellow oil. 1H NMR (300 MHz, DMSO-d6) δ, ppm: 9.81 (1H, s), 7.96–8.13 (2H, m), 7.72–7.88 (2H, m), 7.30–7.40 (1H, m), 7.17–7.30 (3H, m), 7.03–7.17 (3H, m), 6.88–7.03 (2H, m), 2.91 (2H, t, J = 7.5 Hz), 2.43–2.49 (2H, m), 1.59–1.74 (2H, m), 1.43–1.57 (2H, m). 13C NMR (75 MHz, DMSO-d6) δ, ppm: 157.1, 154.6, 153.9, 142.0, 140.7, 140.3, 130.5, 130.2, 129.7, 129.1, 128.7, 128.2 (4C), 128.2, 126.3, 125.6, 119.2, 115.6, 34.8, 34.5, 30.6, 27.1. HRMS (ESI) m/z: 355.1804 found (calcd for C24H23N2O+, [M + H]+ 355.1805).

3.4.2. Synthesis of the Heterocyclic Derivative 6

A mixture of the 2-hydroxy-2,5-dimethylbenzofuran-3(2H)-one (2b) (24 mg, 0.14 mmol), 4-bromobenzaldehyde (25 mg, 0.14 mmol), ammonium acetate (21 mg, 0.35 mmol), and H2O (0.1 mL) in EtOH (0.4 mL) was stirred at 70 °C for 8 h. All volatiles were removed in vacuo, and the residue was purified with flash chromatography (eluent: mixture of toluene and EtOAc, v/v 50:1).
  • 2-(2-(4-Bromophenyl)-5-methyl-1H-imidazol-4-yl)-4-methylphenol (6b). Yield, 30 mg (65%); pale yellow solid; m.p., 230–232 °C. 1H NMR (300 MHz, DMSO-d6) δ, ppm: 12.89 (1H, br. s.), 12.20 (1H, s), 7.85 (2H, m, J = 8.5 Hz), 7.71 (2H, m, J = 8.5 Hz), 7.30 (1H, s), 6.92 (1H, d, J = 7.9 Hz), 6.76 (1H, d, J = 8.2 Hz), 2.54 (3H, s), 2.26 (3H, s). 13C NMR (75 MHz, DMSO-d6) δ, ppm: 153.5, 140.5, 134.9, 132, 128.3, 128.0, 127.0, 126.5, 126.0, 124.7, 121.5, 118.1, 116.3, 20.4, 12.0. HRMS (ESI) m/z: 329.0280 found (calcd for C16H14BrN2O+, [M + H]+ 329.0284).

4. Conclusions

In this paper, we present a non-catalytic and atom-economical photochemical transformation of 2-acyloxybenzaldehydes to 2-hydroxybenzofuranones under 365 nm irradiation. This approach represents the carbonyl umpolung, which likely proceeds through generation and recombination of acyl and ketyl radicals. The resulting structural motif is widespread in natural compounds with various bioactivities. The proposed method utilizes readily available substrates and mild reaction conditions for the synthesis of masked 1,2-dicarbonyl compounds. A representative group of 2-acyloxybenzaldehydes with various substituents in both the aromatic ring and the acyl moiety was converted to 2-hydroxybenzofuranones with yields of 60–99%. A notable yield decrease is shown for 2-acyloxybenzaldehydes with substituents in the fifth position of the cycle. The approach cannot be utilized for derivatives containing benzoyl or aromatic heterocyclic groups. The synthetic utility of the 2-hydroxybenzofuranones in subsequent chemical transformations was briefly studied. These compounds were converted into quinoxaline and imidazole derivatives in good yields.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/molecules30153080/s1, Table S1: Solvent’s screening results for compound 1a; Table S2: Wet and open air conditions screening results for compound 1a; Table S3: Yield of 2a at different wavelengths; Figure S1: The absorption spectrum of the compound 1a. Irradiation wavelengths is marked with a dashed line; Table S4: Study of photoreactions with different temperature; Figure S2: Photochemical set-up with heating; Figure S3: Photochemical set-up in NMR tubes; Figure S4: Kinetic study of compound 1a; Figure S5: 1H NMR of kinetic experiment; Figure S6: Kinetic study of compound 1a phototranformation with BHT and TEMPO. Reference [67] is cited in the Supplementary Materials.

Author Contributions

Conceptualization, M.S.B., A.A.M. and D.S.I.; methodology, M.S.B. and A.A.M.; validation, M.S.B. and D.S.I.; investigation, V.E.O., S.A.K. and A.Y.S.; resources, M.S.B.; data curation, M.S.B., A.Y.S. and Y.A.B.; writing—original draft preparation, A.Y.S. and V.E.O.; writing—review and editing, M.S.B., D.S.I. and A.A.M.; visualization, V.E.O.; supervision, M.S.B. and D.S.I.; project administration, M.S.B.; funding acquisition, M.S.B. All authors have read and agreed to the published version of the manuscript.

Funding

This research was funded by the Russian Science Foundation, grant No. 25-13-00043.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

All data are contained within the article and Supplementary Materials.

Conflicts of Interest

The authors declare no conflicts of interest.

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Molecules 30 03080 sch001
Scheme 1. Natural and biologically active compounds containing 2-hydroxybenzofuranone core.
Scheme 1. Natural and biologically active compounds containing 2-hydroxybenzofuranone core.
Molecules 30 03080 sch001
Molecules 30 03080 sch002
Scheme 2. Umpolung approaches to aldehyde group phototransformations [35,38,39].
Scheme 2. Umpolung approaches to aldehyde group phototransformations [35,38,39].
Molecules 30 03080 sch002
Molecules 30 03080 sch003
Scheme 3. Scope of 2-acetyloxybenzaldehydes 1 photoreaction. The times for complete conversion of the starting compounds 1 are indicated.
Scheme 3. Scope of 2-acetyloxybenzaldehydes 1 photoreaction. The times for complete conversion of the starting compounds 1 are indicated.
Molecules 30 03080 sch003
Molecules 30 03080 sch004
Scheme 4. Scope of the 2-acyloxybenzaldehydes 3 photoreaction. The times for complete conversion of the starting compounds 3 are indicated.
Scheme 4. Scope of the 2-acyloxybenzaldehydes 3 photoreaction. The times for complete conversion of the starting compounds 3 are indicated.
Molecules 30 03080 sch004
Molecules 30 03080 sch005
Scheme 5. Synthesis of heterocyclic derivatives 5 and 6 from furanones 1 and 3.
Scheme 5. Synthesis of heterocyclic derivatives 5 and 6 from furanones 1 and 3.
Molecules 30 03080 sch005
Molecules 30 03080 sch006
Scheme 6. Proposed reaction mechanism and related studies.
Scheme 6. Proposed reaction mechanism and related studies.
Molecules 30 03080 sch006
Table 1. Solvents’ screening results for 1a. For more details, see Supplementary Materials, Part 1.
Table 1. Solvents’ screening results for 1a. For more details, see Supplementary Materials, Part 1.
No.SolventRemaining 1a, %2a, %2-Acetoxybenzoic Acid, %
1CCl40090
2DMSO<1990
3DMF<18 *0
4DMAC<111 *0
5PhMe90 *0
6DCM9067
7MeOH20 *0
8THF00 *0
9acetone0053
10TEA00 *0
11(CF3)2CHOH9200
12CH3CN0076
* Complex reaction by-products.
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Opryshko, V.E.; Krasnova, S.A.; Mikhaylov, A.A.; Bogdanova, Y.A.; Smirnov, A.Y.; Baranov, M.S.; Ivanov, D.S. Photochemically-Enabled Umpolung Conversion of 2-Acyloxybenzaldehydes into 2-Hydroxybenzofuranones. Molecules 2025, 30, 3080. https://doi.org/10.3390/molecules30153080

AMA Style

Opryshko VE, Krasnova SA, Mikhaylov AA, Bogdanova YA, Smirnov AY, Baranov MS, Ivanov DS. Photochemically-Enabled Umpolung Conversion of 2-Acyloxybenzaldehydes into 2-Hydroxybenzofuranones. Molecules. 2025; 30(15):3080. https://doi.org/10.3390/molecules30153080

Chicago/Turabian Style

Opryshko, Victoria E., Svetlana A. Krasnova, Andrey A. Mikhaylov, Yulia A. Bogdanova, Alexander Yu. Smirnov, Mikhail S. Baranov, and Dmitrii S. Ivanov. 2025. "Photochemically-Enabled Umpolung Conversion of 2-Acyloxybenzaldehydes into 2-Hydroxybenzofuranones" Molecules 30, no. 15: 3080. https://doi.org/10.3390/molecules30153080

APA Style

Opryshko, V. E., Krasnova, S. A., Mikhaylov, A. A., Bogdanova, Y. A., Smirnov, A. Y., Baranov, M. S., & Ivanov, D. S. (2025). Photochemically-Enabled Umpolung Conversion of 2-Acyloxybenzaldehydes into 2-Hydroxybenzofuranones. Molecules, 30(15), 3080. https://doi.org/10.3390/molecules30153080

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