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Article

Tuning Benzylic C−H Functionalization of (Thio)xanthenes with Electrochemistry

by
Changji Wang
1,*,
Na Yang
2,
Chao Li
2,
Jian He
3 and
Hongji Li
2,*
1
School of Chemical Engineering, Anhui University of Science and Technology, 168 Taifeng Road, Huainan 232001, China
2
Key Laboratory of Green and Precise Synthetic Chemistry and Applications, Ministry of Education, School of Chemistry and Materials Science, Huaibei Normal University, Huaibei 235000, China
3
Hefei New Online Technology Co., Ltd., Hefei 235000, China
*
Authors to whom correspondence should be addressed.
Molecules 2023, 28(16), 6139; https://doi.org/10.3390/molecules28166139
Submission received: 28 July 2023 / Revised: 13 August 2023 / Accepted: 14 August 2023 / Published: 19 August 2023
(This article belongs to the Section Electrochemistry)
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Abstract

:
Here, we report a tunable electrochemical benzylic C−H functionalization of (thio)xanthenes with terminal alkynes and nitriles in the absence of any catalyst or external chemical oxidant. The benzylic C−H functionalization can be well controlled by varying the electrochemical conditions, affording the specific coupling products via C−C and C−N bond formation.

Graphical Abstract

1. Introduction

The C(sp3)−H functionalization represents a key challenge in the field of synthetic chemistry; in particular, the chemoselectivity is extremely difficult to be tuned and controlled even when some C(sp3)−H bonds are intrinsically reactive, such as the benzylic C(sp3)−H bond [1,2,3,4]. Currently, significant progress has been achieved in the direct functionalization of benzylic C(sp3)−H bond with strategies of transition metal catalysis, photochemistry and electrochemistry, thus effectively enhancing the efficiency of organic molecules syntheses [5,6,7,8,9,10]. Notably, (thio)xanthenes containing unique benzylic C(sp3)−H bonds are synthetic intermediates and also have received increasing attention due to their broad applications in the fields of photodynamic therapy, pharmaceuticals and fluorescent materials, among others (Figure 1) [11,12,13,14,15]. Accordingly, a number of methods have been established for the direct benzylic C(sp3)−H functionalization of (thio)xanthenes [16,17,18,19,20,21,22,23,24,25,26,27,28,29]. However, the success of previously reported methods heavily relied on the use of toxic Pd and Cu metal salts or stoichiometric amounts of chemical oxidants. The renaissance of electrochemical synthesis successfully avoids the above limitation that exists in the reported methods [30,31]. Hitherto, we [32,33,34,35] and some others [36,37,38,39,40] have reported several cross-coupling reactions of C−C, C−N, C−P and C−S with electrochemical methods that can enable the benzylic C(sp3)−H functionalization of (thio)xanthenes under given conditions (Scheme 1a–e) [32,33,34,35,36,37,38,39,40].
In addition, it is well known that tuning chemoselectivity involving unsaturated alkenes and alkynes is always a big challenge in the field of organic synthesis [41,42,43]. For alkyne addition, achieving high regioselectivity is very challenging, mainly due to critical conditions such as high temperature and transition metals. Additionally, most of the reported reactions involving nitrile often proceed in a sequence of distinct steps upon treatment with high temperatures, high pressure or strong inorganic acid, and overhydrolysis is not absolutely controlled. Although much advancement in benzylic C−H functionalization with electrochemistry has been achieved, investigation with an electrochemical method for tuning the electrochemical benzylic C−H functionalization of (thio)xanthenes with terminal alkynes and nitriles has been less explored. Herein, we will describe a rare approach for the direct benzylic C(sp3)−H functionalization of (thio)xanthenes that can be well tuned by varying the reaction temperature and reaction medium, leading to the formation of carbon−carbon and carbon−nitrogen bonds in an efficient manner, respectively (Scheme 1f).

2. Results and Discussion

Initially, we chose xanthene 1a and phenylacetylene 2a as coupling partners for the optimization of reaction conditions, and the results are listed in Table 1. Based on our recent findings regarding electrochemical benzylic C−H functionalization [32,33,34,35], acetonitrile was preferentially selected as a reaction medium for this investigation. With nBu4NPF6 as an electrolyte, the reaction of 1a with 2a was performed under constant-current conditions (8 mA) in an undivided cell equipped with a carbon anode and a platinum cathode. After proceeding at room temperature under an air atmosphere for 3 h, the product 3a was isolated in 32% yield. Meanwhile, the formation of 4a generated from the reaction of 1a with CH3CN was obtained with a 40% yield (entry 1). The ratio of 3a/4a was effectively improved by varying the reaction temperature from 30 to 60 °C (entries 2–4). Remarkably, reaction temperature could control the formation of 3a as a major product, but higher temperature (60–70 °C) led to an inferior yield of 3a (entries 5 and 6). Furthermore, the use of C(+)|Ni(−) or Pt(+)|C(−) still resulted in the mixture of 3a/4a (entries 7 and 8). Additionally, the amount of water extremely affects the formation of 3a (for details, see Table S1 in Supporting Information). Interestingly, we then found that the model reaction with GF(+)|GF(−) as electrode generated 4a as a sole product, albeit with 43% isolated yield (entry 9). Screening of both electrolytes and constant current failed to enhance the yield of 3a (entries 10–13). We clearly observed that the reaction temperature and electrode could affect the formation of 3a and 4a (entries 4, 7–9). Subsequently, with GF(+)|GF(−) as an electrode, 4a was formed at rt to give a 35% yield (entry 14). The use of dry CH3CN could enhance the yield of 4a (entries 15–16). Replacing n-Bu4NBF4 with n-Bu4NPF6 did not improve the benzylic C−H amination of xanthene electrolytes (entry 17). Our attempt to improve the yield of 4a by varying the constant current from 5 to 10 mA was unsuccessful (entries 18–19). The above model reaction did not proceed without an electric current (entry 20). Notably, Faraday efficiency values for 3a and 4a were determined as 45.6% and 28.5%, respectively (for details, see the Supporting Information).
With the optimized reaction conditions in hand, we next focused on the scope of this tunable benzylic C−H functionalization of xanthenes (Scheme 2). We first examined the electrochemical reaction of the aromatic terminal alkynes with xanthenes under the optimized conditions described in entry 4 of Table 1. Several typical terminal alkynes were used to react with xanthene 1a under standard conditions and produced the cross-coupling products in good yields. On the terminal alkyne substrates listed in Scheme 2, the ones having electron-rich groups, such as Me, n-amyl and 4-Et-Phenyl, incorporated at para-position reacted with 1a to generate the asymmetric ɑ-alkylated aryl ketones 3b-d in 63–75% isolated yields. However, the use of a methyl group at the ortho-, meta-position in alkynes led to decreasing yields of the target product 3e and 3f at 53% and 68%, respectively. The results indicate that there might be a detrimental steric effect in this electrochemical benzylic C−H functionalization. We found that this reaction was also applicable to 1-ethynylnaphthalene and produced 3g in 61% yield. Several typical substituted xanthenes were then examined under the above system, showing that yield of the product was insensitive to the position of the alkyl group on the aromatic ring (3h–j). Unfortunately, it was found that 9H-thioxanthene and 9,10-dihydroacridines did not react with 2a under the standard reaction conditions.
We next explored the Ritter-type amination of xanthenes with nitriles under the optimal electrochemical conditions described in Table 1, and the results are listed in Scheme 3. With acetonitrile as a solvent and substrate, a variety of 2-substituted xanthenes including Me, Et, Ph and CF3 were all viable substrates and afforded amination products in 56–75% yields (4b–e). This result indicates that the introduction of an electron-withdrawing group does not favor this electrochemical process. Then, we examined the xanthene derivatives having Me or Ph substituents at the 4-position and found that the reaction proceeded smoothly to form the corresponding products in acceptable yields (4f and 4g). Next, the reactions with dimethylsubstituted xanthenes generated the corresponding products in 67–72% yields (4h–j). Similarly, the reaction with asymmetric xanthenes having a naphthyl group also proceeded smoothly, affording the amination products in moderate yields (4k–m). Additionally, the common solvent n-butyronitrile was employed as a substrate to react with 1a under optimal conditions, generating the compound 4n in 50% yield. Finally, in the case of thioxanthene, the desired product 4o was obtained in 64% yield.
To gain insight into the reaction mechanism, some experiments were specially conducted under given conditions. We observed that the oxidation potential of xanthene 2a (first peak at Ep 1.74 V) is lower than that of 1a (Ep 2.23 V) with the method of cyclic voltammograms (CVs), as shown in Figure 2, indicating that preferential oxidation of 2a occurred and enabled the following electrophilic addition to alkyne (Scheme 4) [35,44]. Then, an experiment involving the mixture of 1a/1a-D2 and 2a revealed a KIE value showing that cleavage of benzylic C(sp3)−H of xanthene may not be involved in the rate-determining step (Scheme 4a). Importantly, replacing 2a with halogenated alkynes 6a–c as substrates did not yield any product, thus showing the critical role of terminal alkynes (Scheme 4b).
According to the experiment results and previous reports, Refs. [32,33,34,35,36,37,38,39,40], a possible mechanism for the direct electrochemical reaction of xanthenes with terminal alkynes is proposed (Scheme 5). Initially, xanthene 1a was oxidized into I followed by losing a proton to yield II. Then, intermediate II underwent anodic oxidation to produce a key cationic intermediate III. On one hand, III could be attacked by terminal alkyne 1a to generate IV, and IV would be trapped by H2O to give the V. Subsequently, V underwent deprotonation and isomerization to afford 2a (Path a) [35,44]. On the other hand, intermediate III would be trapped by an acetonitrile molecule (Ritter-type reaction) to generate 3a (Path b) [45].

3. Materials and Methods

3.1. General Considerations

NMR spectra were recorded on a Bruker-600 (Bruker, Germany (600 MHz for 1H; 151 MHz for 13C). 1H NMR spectra were referenced relative to internal Si(Me)4 (TMS) at δ 0.00 ppm or CDCl3 at δ 7.26 ppm. 13C NMR spectra were recorded at ambient temperature on Bruker-600 (151 MHz) spectrometers and are referenced relative to CDCl3 at δ 77.16 ppm. Data for 1H, 13C NMR are recorded as follows: chemical shift (δ, ppm), multiplicity (s = singlet, d = doublet, t = triplet, m = multiplet, q = quartet, quint = quintet, br = broad), integration and coupling constant (Hz). High-resolution mass spectra were recorded on a P-SIMS-Gly produced by Bruker Daltonics Inc. (Bruker, Germany) using electrospray-ionization time of flight (ESI-TOF) and an Agilent Technologies 7250 GCQTOF using EI-TOF (Agilent Technologies, CA, USA). n-Bu4NBF4, phenylacetylene and CH3CN were purchased from Energy Chemical Company and Taitan Chemical Company in China. Other substituted xanthenes and thioxanthenes were synthesized according to the known methods [32,34].

3.2. Typical Procedure for the Synthesis of 3a

To an undivided cell (10 mL columnar round-bottom flask with a 24# mouth) fitted with a carbon rod (Φ 6 mm) anode and a platinum cathode (10 mm × 10 mm × 0.3 mm), the solid reagents xanthene (0.45 mmol) and n-Bu4NPF6 (0.36 mmol) were added. Then, the liquid reagents phenylacetylene (0.3 mmol), H2O (1.2 mmol) and CH3CN (5 mL) were added in sequence via syringe. Electrolysis was carried out with a constant current (5 mA) at 50 °C for 5 h. Then, the solvent was evaporated to dryness under reduced pressure, and the residue was purified by column chromatography on silica gel to give product 3a as a white solid (63.8 mg, 71% yield).
  • 1-Phenyl-2-(9H-xanthen-9-yl)ethan-1-one (3a) was prepared following general procedure [46], and the reaction mixture was purified by flash column chromatography with petroleum ether and ethylacetate (PE/EA = 100:1) to afford the product 3a (63.8 mg, 71% yield). 1H NMR (600 MHz, CDCl3) δ 7.81 (d, J = 7.2 Hz, 2H), 7.50 (t, J = 7.2 Hz, 1H), 7.37 (t, J = 7.8 Hz, 2H), 7.32 (dd, J = 7.2, 1.2 Hz, 2H), 7.23–7.19 (m, 2H), 7.12 (d, J = 8.4 Hz, 2H), 7.04–7.00 (m, 2H), 4.85 (t, J = 6.0 Hz, 1H), 3.35 (d, J = 6.6 Hz, 2H). 13C NMR (151 MHz, CDCl3) δ 197.9, 152.4, 137.0, 133.1, 128.8, 128.5, 128.1, 127.9, 125.5, 123.5, 116.6, 49.7, 34.7. HRMS (ESI) calcd. for C21H16NaO2+ ([M + Na]+): 323.1043, found: 323.1044.
  • 1-(p-tolyl)-2-(9H-Xanthen-9-yl)ethan-1-one (3b) was prepared following general procedure, [47] and the reaction mixture was purified by flash column chromatography with petroleum ether and ethylacetate (PE/EA = 100:1) to afford the product 3b (59.2 mg, 63% yield). White solid; m.p.: 108~109 °C. 1H NMR (600 MHz, CDCl3) δ 7.71 (d, J = 7.8 Hz, 2H), 7.32 (dd, J = 7.8, 1.2 Hz, 2H), 7.22–7.19 (m, 2H), 7.17 (d, J = 8.4 Hz, 2H), 7.11 (dd, J = 7.8, 1.2 Hz, 2H), 7.03–7.00 (m, 2H), 4.85 (t, J = 6.6 Hz, 1H), 3.32 (d, J = 6.6 Hz, 2H), 2.36 (s, 3H). 13C NMR (151 MHz, CDCl3) δ 197.69, 152.46, 144.09, 134.68, 129.33, 128.98, 128.36, 127.95, 125.75, 123.59, 116.65, 49.77, 34.81, 21.73. HRMS (ESI) calcd. for C22H18NaO2+ ([M + Na]+): 337.1199, found: 337.1203.
  • 1-(4-Pentylphenyl)-2-(9H-xanthen-9-yl)ethan-1-one (3c) was prepared following general procedure, and the reaction mixture was purified by flash column chromatography with petroleum ether and ethylacetate (PE/EA = 100:1) to afford the product 3c (82.2 mg, 75% yield). White solid; m.p.: 117~118 °C. 1H NMR (600 MHz, CDCl3) δ 7.73 (d, J = 8.4 Hz, 2H), 7.32 (dd, J = 7.8, 1.2 Hz, 2H), 7.22–7.16 (m, 2H), 7.17 (d, J = 8.4 Hz, 2H), 7.11 (d, J = 8.4 Hz, 2H), 7.03–7.00 (m, 2H), 4.85 (t, J = 6.6 Hz, 1H), 3.33 (d, J = 6.6 Hz, 2H), 2.60 (t, J = 7.8 Hz, 2H), 1.58–1.32 (m, 2H), 1.31–1.25 (m, 4H), 0.88 (t, J = 7.2 Hz, 3H). 13C NMR (151 MHz, CDCl3) δ 197.5, 152.3, 148.9, 134.7, 128.9, 128.6, 128.3, 127.8, 125.7, 123.5, 116.5, 49.7, 34.6, 31.4, 30.8, 22.5, 22.3, 14.0. HRMS (ESI) calcd. for C26H26NaO2+ ([M + Na]+): 393.1825, found: 393.1826.
  • 1-(4′-Ethyl-[1,1′-biphenyl]-4-yl)-2-(9H-xanthen-9-yl)ethan-1-one (3d) was prepared following general procedure, and the reaction mixture was purified by flash column chromatography with petroleum ether and ethylacetate (PE/EA = 100:1) to afford the product 3d (78.6 mg, 65% yield). White solid; m.p.: 122~123 °C. 1H NMR (600 MHz, CDCl3) δ 7.86 (d, J = 8.4 Hz, 2H), 7.59 (d, J = 8.4 Hz, 2H), 7.51 (d, J = 7.8 Hz, 2H), 7.34 (dd, J = 7.8, 1.8 Hz, 2H), 7.29 (d, J = 8.4 Hz, 2H), 7.23–7.20 (m, 2H), 7.13 (dd, J = 7.8, 0.6 Hz, 2H), 7.03 (td, J = 7.2, 1.2 Hz, 2H), 4.88 (t, J = 6.6 Hz, 1H), 3.38 (d, J = 6.6 Hz, 2H), 2.70 (q, J = 7.8 Hz, 2H), 1.28 (s, 3H). 13C NMR (151 MHz, CDCl3) δ 197.6, 152.5, 145.9, 144.8, 137.2, 135.6, 129.0, 128.8, 128.6, 128.0, 127.3, 127.0, 125.7, 123.6, 116.7, 49.9, 34.9, 28.7, 15.7. HRMS (ESI) calcd. for C29H24NaO2+ ([M + Na]+): 427.1669, found: 427.1668.
  • 1-(o-tolyl)-2-(9H-Xanthen-9-yl)ethan-1-one (3e) was prepared following general procedure, and the reaction mixture was purified by flash column chromatography with petroleum ether and ethylacetate (PE/EA = 100:1) to afford the product 3e (49.8 mg, 53% yield). White solid; m.p.: 105~106 °C. 1H NMR (600 MHz, CDCl3) δ 7.33 (d, J = 7.2 Hz, 2H), 7.30–7.27 (m, 2H), 7.21 (t, J = 7.8 Hz, 2H), 7.18 (d, J = 7.2 Hz, 1H), 7.12–7.09 (m, 3H), 7.04 (t, J = 7.2 Hz, 2H), 4.84 (t, J = 6.6 Hz, 1H), 3.26 (d, J = 6.6 Hz, 2H), 2.43 (s, 3H). 13C NMR (151 MHz, CDCl3) δ 202.1, 152.5, 138.2, 132.0, 131.4, 128.9, 128.6, 128.0, 125.7, 125.7, 123.6, 116.7, 52.7, 35.0, 21.2. HRMS (ESI) calcd. for C22H18NaO2+ ([M + Na]+): 337.1199, found: 337.1201.
  • 1-(m-tolyl)-2-(9H-Xanthen-9-yl)ethan-1-one (3f) was prepared following general procedure, and the reaction mixture was purified by flash column chromatography with petroleum ether and ethylacetate (PE/EA = 100:1) to afford the product 3f (60.0 mg, 68% yield). White solid; m.p.: 111~112 °C. 1H NMR (600 MHz, CDCl3) δ 7.54–7.50 (m, 2H), 7.24 (t, J = 7.2 Hz, 2H), 7.20–7.16 (m, 2H), 7.13 (t, J = 7.8 Hz, 2H), 7.04 (d, J = 7.8 Hz, 2H), 6.95 (t, J = 7.2 Hz, 2H), 4.77 (t, J = 6.6 Hz, 1H), 3.26 (d, J = 6.6 Hz, 2H), 2.26 (s, 3H). 13C NMR (151 MHz, CDCl3) 198.3, 152.6, 138. 6, 137.2, 134.1, 129.1, 128.9, 128.6, 128.1, 125.8, 125.5, 123.7, 116.8, 50.0, 34.9, 21.5.
  • 1-(Naphthalen-1-yl)-2-(9H-xanthen-9-yl)ethan-1-one (3g) was prepared following general procedure, and the reaction mixture was purified by flash column chromatography with petroleum ether and ethylacetate (PE/EA = 100:1) to afford the product 3g (64.2 mg, 61% yield). White solid; m.p.: 116~117 °C. 1H NMR (600 MHz, CDCl3) δ 8.50 (d, J = 8.4 Hz, 1H), 7.91 (d, J = 7.8 Hz, 1H), 7.84 (d, J = 7.8 Hz, 1H), 7.59–7.55 (m, 1H), 7.59–7.50 (m, 1H), 7.48 (dd, J = 7.2, 1.1 Hz, 1H), 7.38 (dd, J = 7.2, 1.2 Hz, 2H), 7.36–7.32 (m, 1H), 7.24–7.21 (m, 2H), 7.12 (dd, J = 8.4, 1.2 Hz, 2H), 7.06–7.03 (m, 2H), 4.94 (t, J = 6.6 Hz, 1H), 3.42 (d, J = 6.6 Hz, 2H). 13C NMR (151 MHz, CDCl3) δ 202.2, 152.5, 136.1, 134.0, 132.9, 130.2, 128.9, 128.6, 128.1, 127.9, 126.6, 125.8, 125.5, 124.4, 123.7, 53.2, 35.5. HRMS (ESI) calcd. for C25H18NaO2+ ([M+Na]+): 373.1199, found: 373.1200.
  • 2-(2-Methyl-9H-xanthen-9-yl)-1-phenylethan-1-one (3h) was prepared following general procedure, and the reaction mixture was purified by flash column chromatography with petroleum ether and ethylacetate (PE/EA = 100:1) to afford the product 3h (65.8 mg, 70% yield). White solid; m.p.: 102~103 °C. 1H NMR (600 MHz, CDCl3) δ 7.81 (d, J = 7.8 Hz, 2H), 7.50 (t, J = 7.2 Hz, 1H), 7.37 (t, J = 7.2 Hz, 2H), 7.31 (d, J = 7.8 Hz, 1H), 7.19 (t, J = 7.2 Hz, 1H), 7.10 (d, J = 7.8 Hz, 2H), 7.02–6.89 (m, 3H), 4.80 (t, J = 6.6 Hz, 1H), 3.35 (d, J = 6.6 Hz, 2H), 2.27 (s, 3H). 13C NMR (151 MHz, CDCl3) δ 198.2, 152.6, 150.3, 137.2, 133.21, 133.0, 129.2, 129.0, 128.6, 128.6, 128.2, 127.9, 125.7, 125.3, 123.4, 116.6, 116.4, 49.9, 34.8, 20.8.
  • 2-(4-Methyl-9H-xanthen-9-yl)-1-phenylethan-1-one (3i) was prepared following general procedure, and the reaction mixture was purified by flash column chromatography with petroleum ether and ethylacetate (PE/EA = 100:1) to afford the product 3i (67.8 mg, 72% yield). White solid; m.p.: 107~108 °C. 1H NMR (600 MHz, CDCl3) δ 7.71 (d, J = 8.4 Hz, 2H), 7.33 (d, J = 7.8 Hz, 2H), 7.23 –7.20 (m, 2H), 7.17 (d, J = 8.4 Hz, 2H), 7.12 (d, J = 8.4 Hz, 2H), 7.02 (t, J = 7.8 Hz, 2H), 4.86 (t, J = 6.6 Hz, 1H), 3.33 (d, J = 6.6 Hz, 2H), 2.36 (s, 3H). 13C NMR (151 MHz, CDCl3) δ 197.5, 152.3, 143.9, 134.5, 130.0, 129.8, 129.5, 129.5, 129.2, 128.8, 128.3, 128.2, 127.8, 127.3, 125.6, 123.4, 116.5, 49.6, 34.7, 21.6. HRMS (ESI) calcd. for C22H18NaO2+ ([M + Na]+): 337.1199, found: 337.1196.
  • 2-(4-(tert-Butyl)-9H-xanthen-9-yl)-1-phenylethan-1-one (3j) was prepared following general procedure, and the reaction mixture was purified by flash column chromatography with petroleum ether and ethylacetate (PE/EA = 100:1) to afford the product 3j (74.0 mg, 70% yield). White solid; m.p.: 113~114 °C. 1H NMR (600 MHz, CDCl3) δ 7.78–7.75 (m, 2H), 7.41–7.38 (m, 2H), 7.32 (dd, J = 7.8, 1.2 Hz, 2H), 7.22–7.19 (m, 2H), 7.12 (dd, J = 8.4, 1.2 Hz, 2H), 7.02 (td, J = 7.2, 1.2 Hz, 2H), 4.87 (t, J = 6.6 Hz, 1H), 3.34 (d, J = 6.6 Hz, 2H), 1.30 (s, 9H). 13C NMR (151 MHz, CDCl3) δ 196.4, 155.9, 151.3, 133.4, 128.8, 128.7, 127.8, 127.3, 127.0, 126.8, 126.3, 124.7, 124.6, 124.4, 122.4, 121.8, 115.5, 48.7, 34.0, 33.5, 29.9. HRMS (ESI) calcd. for C25H24NaO2+ ([M + Na]+): 379.1669, found: 379.1670.

3.3. Typical Procedure for the Synthesis of 4a

To an undivided cell (10 mL columnar round-bottom flask with a 24# mouth) fitted with a graphite felt anode (10 mm × 10 mm × 3 cm) and a graphite felt cathode (10 mm × 10 mm × 3 cm), the solid reagents xanthene (0.3 mmol) and n-Bu4NPF6 (0.36 mmol) were added. Then, the liquid CH3CN (5 mL) was added in sequence via syringe. The electrolysis was carried out with a constant current (5 mA) at room temperature for 5 h. Then, the solvent was evaporated to dryness under reduced pressure, and the residue was purified by column chromatography on silica gel to give product 4a as a white solid (48.7 mg, 68% yield).
  • N-(9H-xanthen-9-yl)acetamide (4a) was prepared following general procedure, and the reaction mixture was purified by flash column chromatography with petroleum ether and ethylacetate (PE/EA = 5:1) to afford the product 4a (48.7 mg, 68% yield). White solid; m.p.: 238~239 °C. 1H NMR (600 MHz, CDCl3) δ 7.48–7.46 (m, 2H), 7.32–7.28 (m, 2H), 7.13–7.10 (m, 4H), 6.49 (d, J = 9.0 Hz, 1H), 6.05 (br, d, J = 9.0 Hz, 1H), 2.00 (s, 3H). 13C NMR (151 MHz, CDCl3) δ 169.2, 151.3, 129.8, 129.4, 123.7, 121.3, 116.8, 44.0, 23.5. HRMS (ESI) calcd. for C15H13NNaO2+ ([M + Na]+): 262.0838, found: 262.0839.
  • N-(2-Methyl-9H-xanthen-9-yl)acetamide (4b) was prepared following general procedure, and the reaction mixture was purified by flash column chromatography with petroleum ether and ethylacetate (PE/EA = 5:1) to afford the product 4b (49.5 mg, 65% yield). White solid; m.p.: 242~243 °C. 1H NMR (600 MHz, CDCl3) δ 7.46 (d, J = 7.8 Hz, 1H), 7.31–7.27 (m, 1H), 7.11–7.08 (m, 3H), 7.00 (d, J = 8.4 Hz, 1H), 6.46 (d, J = 9.0 Hz, 1H), 6.00 (br, d, J = 9.0 Hz, 1H), 2.32 (s, 3H), 2.01 (s, 3H). 13C NMR (151 MHz, CDCl3) δ 169.2, 151.4, 149.2, 133.2, 130.2, 129.8, 129.8, 129.3, 123.5, 121.3, 120.8, 116.7, 116.5, 44.1, 23.6, 20.8. HRMS (ESI) calcd. for C16H15NNaO3+ ([M + Na]+): 276.0095, found: 276.0092.
  • N-(2-Methoxy-9H-xanthen-9-yl)acetamide (4c) was prepared following general procedure, and the reaction mixture was purified by flash column chromatography with petroleum ether and ethylacetate (PE/EA = 5:1) to afford the product 4c (60.3 mg, 75% yield). White solid; m.p.: 251~252 °C. 1H NMR (600 MHz, CDCl3) δ 7.46 (d, J = 7.2 Hz, 1H), 7.31–7.27 (m, 1H), 7.11–7.07 (m, 2H), 7.04 (d, J = 9.0 Hz, 1H), 6.98 (d, J = 3.0 Hz, 1H), 6.87 (dd, J = 9.0, 3.0 Hz, 1H), 6.47 (d, J = 9.0 Hz, 1H), 6.01 (br, d, J = 9.0 Hz, 1H), 3.79 (s, 3H), 2.01 (s, 3H). 13C NMR (151 MHz, CDCl3) δ 169.2, 155.7, 151.5, 145.4, 129.8, 129.4, 123.5, 121.7, 120.7, 117.7, 116.7, 116.4, 112.8, 55.9, 44.5, 23.6. HRMS (ESI) calcd. for C16H15NNaO3+ ([M + Na]+): 292.0944, found 292.0947.
  • N-(2-Phenyl-9H-xanthen-9-yl)acetamide (4d) was prepared following general procedure, and the reaction mixture was purified by flash column chromatography with petroleum ether and ethylacetate (PE/EA = 5:1) to afford the product 4d (57.7 mg, 61% yield). White solid; m.p.: 247~248 °C. 1H NMR (600 MHz, CDCl3) δ 7.70 (d, J = 1.8 Hz, 1H), 7.58–7.56 (m, 2H), 7.54 (dd, J = 9.0, 2.4 Hz, 1H), 7.51–7.49 (m, 1H), 7.43 (t, J = 7.2 Hz, 2H), 7.36–7.30 (m, 2H), 7.18 (d, J = 8.4 Hz, 1H), 7.14–7.11 (m, 2H), 6.57 (d, J = 9.6 Hz, 1H), 6.06 (br, J = 9.6 Hz, 1H), 2.01 (s, 3H). 13C NMR (151 MHz, CDCl3) δ 169.2, 151.2, 150.8, 140.2, 136.9, 129.9, 129.5, 129.0, 128.2, 128.2, 127.4, 127.0, 123.8, 121.5, 121.2, 117.2, 116.8, 44.1, 23.6. HRMS (ESI) calcd. for C21H17NNaO2+ ([M + Na]+): 338.1151, found: 338.1147.
  • N-(2-(Trifluoromethyl)-9H-xanthen-9-yl)acetamide (4e) was prepared following general procedure, and the reaction mixture was purified by flash column chromatography with petroleum ether and ethylacetate (PE/EA = 5:1) to afford the product 4e (51.6 mg, 56% yield). White solid; m.p.: 244~245 °C. 1H NMR (600 MHz, CDCl3) δ 7.75 (s, 1H), 7.55 (dd, J = 8.4, 1.2 Hz, 1H), 7.45 (d, J = 8.4 Hz, 1H), 7.35–7.31 (m, 1H), 7.20 (d, J = 8.4 Hz, 1H), 7.15 (t, J = 7.8 Hz, 1H), 7.13 (d, J = 8.4 Hz, 1H), 6.52 (d, J = 9.0 Hz, 1H), 6.10 (br, s, 1H), 2.04 (s, 3H). 13C NMR (151 MHz, CDCl3) δ 169.4, 153.5, 150.7, 129.8, 129.64, 127.4 (q, J = 3.6), 126.5 (q, J = 3.2), 125.9 (q, J = 271.5), 124.5, 123.1, 121.8, 121.3, 120.7, 117.4, 116.9, 43.7, 23.5. 19F NMR (565 MHz, CDCl3) δ − 77.30. HRMS (ESI) calcd. for C16H12F3NNaO2+ ([M + Na]+): 330.0172, found: 330.0175.
  • N-(4-Methyl-9H-xanthen-9-yl)acetamide (4f) was prepared following general procedure, and the reaction mixture was purified by flash column chromatography with petroleum ether and ethylacetate (PE/EA = 5:1) to afford the product 4f (52.5 mg, 69% yield). White solid; m.p.: 239~240 °C. 1H NMR (600 MHz, CDCl3) 7.50 (d, J = 7.2 Hz, 1H), 7.31 (t, J = 8.4 Hz, 2H), 7.16 (d, J = 8.4 Hz, 2H), 7.13–7.10 (m, 1H), 7.02 (t, J = 7.8 Hz, 1H), 6.50 (d, J = 9.0 Hz, 1H), 5.92 (br, d, J = 8.4 Hz, 1H), 2.40 (s, 3H), 2.00 (s, 3H). 13C NMR (151 MHz, CDCl3) δ 169.0, 151.2, 151.0, 139.6, 129.7, 129.4, 129.2, 124.6, 123.5, 121.3, 118.1, 116.9, 116.6, 43.8, 23.4, 21.2. HRMS (ESI) calcd. for C16H15NNaO2+ ([M + Na]+): 276.0995, found: 276.0997.
  • N-(4-Phenyl-9H-xanthen-9-yl)acetamide (4g) was prepared following general procedure, and the reaction mixture was purified by flash column chromatography with petroleum ether and ethylacetate (PE/EA = 5:1) to afford the product 4g (54.7 mg, 58% yield). White solid; m.p.: 251~152 °C. 1H NMR (600 MHz, CDCl3) δ 7.60 (d, J = 7.0 Hz, 2H), 7.51–7.46 (m, 4H), 7.42–7.38 (m, 1H), 7.36 (dd, J = 7.8, 1.6 Hz, 1H), 7.29–7.26 (m, 1H), 7.19 (t, J = 7.8 Hz, 1H), 7.12 (td, J = 7.8, 1.2 Hz, 1H), 7.03 (d, J = 8.4 Hz, 1H), 6.56 (d, J = 9.0 Hz, 1H), 6.06 (br, J = 8.4 Hz, 1H), 2.02 (s, 3H). 13C NMR (151 MHz, CDCl3) δ 169.2, 151.3, 148.3, 137.5, 130.8, 130.2, 129.8, 129.6, 129.3, 129.1, 128.3, 127.5, 123.9, 123.7, 122.0, 121.3, 116.9, 44.5, 23.6. HRMS (ESI) calcd. for C21H17NNaO2+ ([M + Na]+): 338.1151, found: 338.1151.
  • N-(2,3-Dimethyl-9,10-dihydroanthracen-9-yl)acetamide (4h) was prepared following general procedure, and the reaction mixture was purified by flash column chromatography with petroleum ether and ethylacetate (PE/EA = 5:1) to afford the product 4h (57.2 mg, 72% yield). White solid; m.p.: 247~248 °C. 1H NMR (600 MHz, CDCl3) δ 7.66 (dd, J = 7.8, 0.6 Hz, 1H), 7.30–7.27 (m, 1H), 7.12 (d, J = 8.4 Hz, 1H), 7.10–7.07 (m, 2H), 6.92 (d, J = 8.4 Hz, 1H), 6.55 (d, J = 9.0 Hz, 1H), 5.85 (br, d, J = 7.8 Hz, 1H), 2.27 (s, 3H), 2.26 (s, 3H), 1.91 (s, 3H). 13C NMR (151 MHz, CDCl3) δ 168.4, 151.1, 150.8, 136.8, 131.9, 130.7, 130.2, 129.2, 123.6, 122.8, 119.0, 116.3, 114.1, 42.9, 23.3, 20.2, 15.2. HRMS (ESI) calcd. for C17H17NNaO2+ ([M + Na]+): 290.1151, found: 290.1152.
  • N-(1,3-Dimethyl-9,10-dihydroanthracen-9-yl)acetamide (4i) was prepared following general procedure, and the reaction mixture was purified by flash column chromatography with petroleum ether and ethylacetate (PE/EA = 5:1) to afford the product 4i (51.6 mg, 67% yield). White solid; m.p.: 244~245 °C. 1H NMR (600 MHz, CDCl3) δ 7.66–7.63 (m, 1H), 7.29 (td, J = 7.8, 1.8 Hz, 1H), 7.11–7.08 (m, 2H), 6.82 (d, J = 4.8 Hz, 2H), 6.47 (d, J = 9.6 Hz, 1H), 5.78 (br, d, J = 9.0 Hz, 1H), 2.34 (s, 3H), 2.32 (s, 3H), 1.91 (s, 3H). 13C NMR (151 MHz, CDCl3) δ 168.4, 152.4, 151.3, 139.4, 138.6, 130.2, 129.2, 126.4, 123.7, 122.9, 116.5, 116.2, 115.1, 42.4, 23.4, 21.2, 18.7. HRMS (ESI) calcd. for C17H17NNaO2+ ([M + Na]+): 290.1151, found: 290.1155.
  • N-(1,2,3,10-Tetrahydrocyclopenta[b]xanthen-10-yl)acetamide (4j) was prepared following general procedure, and the reaction mixture was purified by flash column chromatography with petroleum ether and ethylacetate (PE/EA = 5:1) to afford the product 4j (51.9 mg, 70% yield). White solid; m.p.: 236~237 °C. 1H NMR (600 MHz, CDCl3) δ 7.58 (dd, J = 8.4, 1.8 Hz, 1H), 7.30–7.27 (m, 1H), 7.18 (d, J = 8.4 Hz, 1H), 7.11–7.07 (m, 2H), 6.94 (d, J = 8.4 Hz, 1H), 6.48 (d, J = 9.6 Hz, 1H), 5.81 (br, d, J = 9.6 Hz, 1H), 2.99–2.94 (m, 1H), 2.90 (t, J = 8.4 Hz, 2H), 2.87–2.81 (m, 1H), 2.17–2.08 (m, 2H), 1.96 (s, 3H). 13C NMR (151 MHz, CDCl3) δ 168.5, 151.327, 150.6, 144.8, 139.4, 130.2, 129.3, 125.1, 123.6, 122.2, 116.6, 116.4, 114.9, 42.8, 32.5, 31.4, 25.7, 23.4. HRMS (ESI) calcd. for C18H17NNaO2+ ([M + Na]+): 302.1151, found 302.1154.
  • N-(10-Methoxy-12H-benzo[a]xanthen-12-yl)acetamide (4k) was prepared following general procedure, and the reaction mixture was purified by flash column chromatography with petroleum ether and ethylacetate (PE/EA = 3:1) to afford the product 4k (61.3 mg, 64% yield). White solid; m.p.: 258~259 °C. 1H NMR (600 MHz, CDCl3) δ 8.07 (d, J = 8.4 Hz, 1H), 7.84 (d, J = 6.6 Hz, 1H), 7.82 (d, J = 8.4 Hz, 1H), 7.60 (t, J = 6.6 Hz, 1H), 7.46 (t, J = 7.2 Hz, 1H), 7.30 (d, J = 9.0 Hz, 1H), 7.25 (d, J = 3.0 Hz, 1H), 7.13 (d, J = 9.0 Hz, 1H), 7.08 (d, J = 9.4 Hz, 1H), 6.92 (dd, J = 8.4, 3.0 Hz, 1H), 5.85 (br, d, J = 9.6 Hz, 1H), 3.83 (s, 3H), 1.92 (s, 3H). 13C NMR (151 MHz, CDCl3) δ 168.7, 156.2, 150.3, 144.8, 131.8, 130. 5, 130.4, 128.7, 127.8, 124.8, 123.0, 122.5, 118.0, 117.6, 116.8, 112.6, 111.5, 56.0, 42.2, 23.4. HRMS (ESI) calcd. for C20H17NNaO2+ ([M + Na]+): 342.1101, found 342.1102.
  • N-(7H-benzo[c]xanthen-7-yl)acetamide (4l) was prepared following general procedure, and the reaction mixture was purified by flash column chromatography with petroleum ether and ethylacetate (PE/EA = 5:1) to afford the product 4l (47.6 mg, 55% yield). White solid; m.p.: 250~251 °C. 1H NMR (600 MHz, CDCl3)δ 8.43 (d, J = 8.4 Hz, 1H), 7.83 (d, J = 7.2 Hz, 1H), 7.60 –7.54 (m, 4H), 7.51–7.48 (m, 1H), 7.38–7.35 (m, 1H), 7.30 (dd, J = 8.4, 1.2 Hz, 1H), 7.19–7.16 (m, 1H), 6.66 (d, J = 9.0 Hz, 1H), 6.04 (br, d, J = 9.0 Hz, 1H), 2.02 (s, 3H). 13C NMR (151 MHz, CDCl3) δ 169.1, 151.0, 146.3, 134.0, 129.9, 129.3, 127.6, 127.0, 126.3, 126.3, 124.0, 123.9, 123.3, 121.8, 121.2, 116.8, 114.8, 44.2, 23.5. HRMS (ESI) calcd. for C19H15
  • N-(12H-benzo[a]xanthen-12-yl)acetamide (4m) was prepared following general procedure, and the reaction mixture was purified by flash column chromatography with petroleum ether and ethylacetate (PE/EA = 5:1) to afford the product 4m (50.3 mg, 58% yield). White solid; m.p.: 249~250 °C. 1H NMR (600 MHz, CDCl3) δ 8.43 (d, J = 8.4 Hz, 1H), 7.83 (d, J = 7.8 Hz, 1H), 7.60–7.54 (m, 4H), 7.50 (d, J = 8.4 Hz, 1H), 7.37 (t, J = 7.8 Hz, 1H), 7.30 (d, J = 7.8 Hz, 1H), 7.17 (t, J = 7.2 Hz, 1H), 6.67 (d, J = 9.6 Hz, 1H), 6.01 (br, J = 9.0 Hz, 1H), 2.02 (s, 3H). 13C NMR (151 MHz, CDCl3) δ 169.1, 151.1, 146.4, 134.1, 130.0, 129.4, 127.8, 127.1, 126.4, 126.4, 124.1, 123.4, 121.9, 121.4, 116.9, 114.9, 44.4, 23.6. HRMS (ESI) calcd. for C19H15NNaO2+ ([M + Na]+): 312.0095, found 312.0098.
  • N-(9H-xanthen-9-yl)butyramide (4n) was prepared following general procedure, and the reaction mixture was purified by flash column chromatography with petroleum ether and ethylacetate (PE/EA = 9:1) to afford the product 4n (40.1 mg, 50% yield). White solid; m.p.: 262~263 °C. 1H NMR (600 MHz, CDCl3) δ 7.45 (d, J = 7.8 Hz, 2H), 7.30 (t, J = 7.2 Hz, 2H), 7.12–7.09 (m, 4H), 6.52 (d, J = 9.0 Hz, 1H), 6.05 (br, d, J = 8.4 Hz, 1H), 2.17 (t, J = 7.8 Hz, 2H), 1.72–1.67 (m, 2H), 0.94 (t, J = 7.2 Hz, 3H). 13C NMR (151 MHz, CDCl3) δ 172.2, 151.2, 129.8, 129.4, 123.7, 121.4, 116.8, 43.8, 38.9, 19.3, 13.9. HRMS (ESI) calcd. for C18H19NO2+ ([M + H]+): 267.1379, found: 267.1377.
  • N-(9H-thioxanthen-9-yl)acetamide (4o) was prepared following general procedure, and the reaction mixture was purified by flash column chromatography with petroleum ether and ethylacetate (PE/EA = 5:1) to afford the product 4o (48.9 mg, 64% yield). White solid; m.p.: 237~238 °C. 1H NMR (600 MHz, CDCl3) δ 7.58 (dd, J = 6.0, 2.4 Hz, 2H), 7.47–7.45 (m, 2H), 7.28–7.25 (m, 4H), 6.30 (d, J = 9.0 Hz, 1H), 6.23 (br, d, J = 7.2 Hz, 1H), 1.88 (s, 3H). 13C NMR (151 MHz, CDCl3) δ 169.0, 134.9, 133.0, 129.6, 128.0, 127.2, 127.2, 53.4, 23.5. HRMS (ESI) calcd. for C15H13NNaOS+ ([M + Na]+): 278.0610, found: 278.0613.

4. Conclusions

In summary, we have developed an electrochemical benzylic C−H functionalization of (thio)xanthenes with terminal alkynes and nitriles in the absence of any catalyst or external chemical oxidant. The method enables selective benzylic C−H bond functionalization by varying electrochemical conditions, providing an efficient approach to synthesizing xanthene derivatives under mild conditions. Efforts in our laboratory are ongoing to explore other challenging inert C−H functionalizations.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/molecules28166139/s1, Figure S1: Experiment setup for electrochemical benzylic C-H functionalization; Experiment procedure for the CV experiments; 1H, 13C, 19F NMR spectra of the products; Determination of Faradaic efficiency; Figure S2: The cyclic voltammograms recorded in CH3CN with 0.1 M n-Bu4NBF4 as the supporting electrolyte [1a (10 mM), 2a (10 mM)]; Table S1: Effect of water on the synthesis of 3a.

Author Contributions

C.W. and H.L. supervised the project and wrote the manuscript; N.Y. and C.L. analyzed data and discussed with C.W., H.L. and J.H.; N.Y. and C.L. performed the experiments. All authors contributed to the revision. All authors have read and agreed to the published version of the manuscript.

Funding

This research was funded by the Natural Science Foundation for Distinguished Young Scholars of Anhui Province, China (No. 2022AH020039) and the National Science Foundation of China (No. 21772061).

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Conflicts of Interest

The authors declare no conflict of interest.

Sample Availability

Samples of the compounds are available from the authors.

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Molecules 28 06139 g001
Figure 1. Representative molecules accessible from (thio)xanthenes.
Figure 1. Representative molecules accessible from (thio)xanthenes.
Molecules 28 06139 g001
Molecules 28 06139 sch001
Scheme 1. Electrochemical methods for the benzylic C(sp3)−H functionalization of (thio)xanthenes.
Scheme 1. Electrochemical methods for the benzylic C(sp3)−H functionalization of (thio)xanthenes.
Molecules 28 06139 sch001
Molecules 28 06139 sch002
Scheme 2. Cross-coupling reaction of xanthenes with terminal alkynes a,b. a Reaction conditions: 1 (0.45 mmol), 2 (0.3 mmol), n-Bu4NPF6 (1.2 equiv), H2O (4 equiv), CH3CN (5.0 mL), carbon rod (Φ 6 mm) anode, Pt plate (1 cm × 1 cm) cathode, constant current = 8 mA, 50 °C, 3 h (Q = 2.98 F mol−1). b Isolated yields are shown.
Scheme 2. Cross-coupling reaction of xanthenes with terminal alkynes a,b. a Reaction conditions: 1 (0.45 mmol), 2 (0.3 mmol), n-Bu4NPF6 (1.2 equiv), H2O (4 equiv), CH3CN (5.0 mL), carbon rod (Φ 6 mm) anode, Pt plate (1 cm × 1 cm) cathode, constant current = 8 mA, 50 °C, 3 h (Q = 2.98 F mol−1). b Isolated yields are shown.
Molecules 28 06139 sch002
Molecules 28 06139 sch003
Scheme 3. Direct benzylic C−H amination of (thio)xanthenes with nitriles a,b. a Reaction conditions: 1a (0.3 mmol), n-Bu4NPF6 (1.2 equiv), CH3CN (5.0 mL), graphite felt (1 cm × 1 cm) anode, graphite felt (1 cm × 1 cm) cathode, constant current = 8 mA, air, rt, 5 h. (Q = 4.97 F mol−1). b Isolated yields are shown.
Scheme 3. Direct benzylic C−H amination of (thio)xanthenes with nitriles a,b. a Reaction conditions: 1a (0.3 mmol), n-Bu4NPF6 (1.2 equiv), CH3CN (5.0 mL), graphite felt (1 cm × 1 cm) anode, graphite felt (1 cm × 1 cm) cathode, constant current = 8 mA, air, rt, 5 h. (Q = 4.97 F mol−1). b Isolated yields are shown.
Molecules 28 06139 sch003
Molecules 28 06139 g002
Figure 2. The cyclic voltammograms recorded in CH3CN with 0.1 M n-Bu4NBF4 as a supporting electrolyte (1a (1 mM), 2a (1 mM)).
Figure 2. The cyclic voltammograms recorded in CH3CN with 0.1 M n-Bu4NBF4 as a supporting electrolyte (1a (1 mM), 2a (1 mM)).
Molecules 28 06139 g002
Molecules 28 06139 sch004
Scheme 4. Mechanistic studies and control experiments.
Scheme 4. Mechanistic studies and control experiments.
Molecules 28 06139 sch004
Molecules 28 06139 sch005
Scheme 5. Possible reaction mechanism.
Scheme 5. Possible reaction mechanism.
Molecules 28 06139 sch005
Table 1. Optimization of the reaction conditions a,b.
Table 1. Optimization of the reaction conditions a,b.
Molecules 28 06139 i001
EntryElectrodeTemp (°C)Yield (%)
3a4a
1C(+)|Pt(−)rt3240
2C(+)|Pt(−)303837
3C(+)|Pt(−)404521
4C(+)|Pt(−)50716
5C(+)|Pt(−)6065trace
6C(+)|Pt(−)7052trace
7C(+)|Ni(−)501425
8Pt(+)|C(−)504617
9GF(+)|GF(−)50n.d.43
10 cC(+)|Pt(−)50558
11 dC(+)|Pt(−)503710
12 eC(+)|Pt(−)5048trace
13 fC(+)|Pt(−)5022trace
14GF(+)|GF(−)rtn.d.35
15 fGF(+)|GF(−)rtn.d.50
16 f,gGF(+)|GF(−)rt n.d.77
17 c,f,gGF(+)|GF(−)rtn.d.61
18 d,f,gGF(+)|GF(−)rtn.d.33
19 e,f,gGF(+)|GF(−)rtn.d.58
20 hGF(+)|GF(−)rtn.d.n.d.
a Reaction conditions: 1a (0.45 mmol), 2a (0.3 mmol), n-Bu4NPF6 (1.2 equiv.), H2O (4.0 equiv.), MeCN (5 mL), constant current = 8 mA, air, 3–5 h. b Isolated yields. c n-Bu4NBF4 (1.2 equiv.). d Constant current = 5 mA. e Constant current = 10 mA. f Five hours. g Dry CH3CN. h No electric current. n.d. = Not detected.
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Wang, C.; Yang, N.; Li, C.; He, J.; Li, H. Tuning Benzylic C−H Functionalization of (Thio)xanthenes with Electrochemistry. Molecules 2023, 28, 6139. https://doi.org/10.3390/molecules28166139

AMA Style

Wang C, Yang N, Li C, He J, Li H. Tuning Benzylic C−H Functionalization of (Thio)xanthenes with Electrochemistry. Molecules. 2023; 28(16):6139. https://doi.org/10.3390/molecules28166139

Chicago/Turabian Style

Wang, Changji, Na Yang, Chao Li, Jian He, and Hongji Li. 2023. "Tuning Benzylic C−H Functionalization of (Thio)xanthenes with Electrochemistry" Molecules 28, no. 16: 6139. https://doi.org/10.3390/molecules28166139

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