Selectfluor-mediated tandem cyclization of enaminones with diselenides toward the synthesis of 3-selenylated chromones

Abstract

A practical and metal-free approach for the regioselective selenation of chromones employing Selectfluor reagent under mild conditions is described. The developed method is suitable for a wide substrate scope and affords 3-selenylated chromones in good to excellent yield with high selectivity. An ionic mechanism is proposed for this transformation. Furthermore, the application of potassium thiocyanate with enaminones for the synthesis of thiocyano chromones in this transformation is also successful.

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Introduction

A chromone moiety is the central structure in numerous natural products such as flavonoids, isoflavonoids, as well as other functionalized chromone molecules.¹ As privileged heterocyclic scaffolds, chromone and its derivatives, including both naturally occurring and laboratory synthesized ones, have been proved with high application potential in drug discovery.² Moreover, chromones have also exhibited attractive application in organic synthesis as well as the designation of molecules with useful optical functions.³ In particular, C3-substituted chromones have recently been drawing considerable attention as they exhibit a variety of physiological and biological activities, including anti-inflammatory,⁴ anti-dyslipidemic,⁵ antioxidant,⁶ antimicrobial,⁷ antitumor,⁸ anticancer,⁹ etc. Thus, considerable attention has been devoted to developing novel and efficient protocols for the synthesis of C3-substituted chromone derivatives, and several significant achievements have been reported for the synthesis of 3-substituted chromone derivatives.¹⁰

Organoselenium compounds have attracted considerable attention in medicinal chemistry owing to their well-known biological activities, which are mainly attributed to the fact that selenium atoms may serve as an electron donor or a hydrogen bond acceptor in these applications, altering the chemical characteristics of enzyme active sites.¹¹ Moreover, they have gained considerable interest due to their well-known fluorescent properties,¹² and wide applications in food chemistry and material science.¹³ In particular, recent studies revealed that chromones containing selenyl-substituents show unique bioactivities and chemical properties, and are widely adopted in drug design and regulation of biological processes.¹⁴ Therefore, many efforts have been devoted to the synthesis of more valuable 3-selenochromone derivatives.¹⁵ As the straightforward approach, the direct functionalization on naturally available or prior prepared chromone compounds offers access to 3-substituted chromone derivatives. Through this strategy, a seleno group could be introduced into the chromone framework.¹⁶ However, the limited natural sources or tedious preparation of chromone substrates have led to a high demand for alternative synthetic methods using easy and abundant industrial chemicals.

Among the readily available main building blocks, 2-hydroxyphenyl enaminones have been identified as particularly excellent candidates in the synthesis of functionalized chromones by means of tandem alkenyl C–H elaboration and chromone annulation.¹⁷ In the past decade, the enaminone-based chromone synthesis has gained splendid success by offering practical accesses to chromones containing different substituents.¹⁸ As 3-selenochromones are an important class of compounds, much efforts has been devoted to the assembly of this compound based on the featured chromone annulation of easily available 2-hydroxyphenyl enaminones. In 2016, Blond's group reported AgOTf-catalyzed synthesis of 3-selenochromones through the reaction of 2-hydroxyphenyl enaminones and pre-synthesized electrophilic selenium species (PhSeCl) (Scheme 1a).¹⁹ In 2017, Braga's group and Wan's group developed KIO₃-mediated synthesis of 3-selenochromones through the reaction of o-hydroxyphenyl enaminones and diaryl diselenides, employing green solvents such as glycerol and ethyl lactate, respectively (Scheme 1b).²⁰ In recent years, photoredox catalysis enabled by visible light has emerged as a fascinating and powerful synthetic protocol to promote a wide range of synthetically useful organic transformations.²¹ In 2021, a visible-light-promoted synthesis of 3-selenochromones was realized via the selenylation/cyclization of 2-hydroxyphenyl enaminones with diaryl diselenides in the presence of HOAc (Scheme 1c).²² Very recently, Braga's group developed trichloroisocyanuric acid (TCCA)-mediated synthesis of 3-selenochromones from 2-hydroxyphenyl enaminones with diaryl diselenides (Scheme 1d).²³ Regardless of their merits, the current strategies suffer from some disadvantages such as transition-metal as a catalyst, limited substrate scope, the inevitability of a strong oxidant, high reaction temperature, or complex reaction conditions. Therefore, more general and mild approaches for the construction of diversely 3-selenochromones are yet highly desirable to satisfy the requirement of discovering more chromone-based functional molecules or lead compounds.

Scheme 1 Different methods to 3-selenochromones from 2-hydroxyphenyl enaminones. (a) AgOTf-catalyzed cyclization; (b) KIO₃-mediated cyclization; (c) visible-light-promoted cyclization; (d) TCCA-mediated cyclization; (e) selectfluor-mediated cyclization.

Selectfluor is commercially available, exceptionally stable, and useful for a mild oxidant.²⁴ Several functionalized heterocyclic compounds have been synthesized successfully employing Selectfluor as an oxidant.²⁵ Recently, some functionalized heterocycles have been constructed by our group using Selectfluor reagent as an electrophilic reagent or oxidant.²⁶ Expanding the application of Selectfluor for the cross-coupling reaction is still challenging works. To the best of our knowledge, using stable and readily available diaryl diselenides as selenylating reagent, transition-metal free Selectfluor-promoted selenylation/cyclization of 2-hydroxyphenyl enaminones to access 3-arylselenenyl chromones remains yet elusive. As a part of our continuous interest in forming C–Se bond promoted by Selectfluor reagent, herein, we reported a practical and metal-free approach for the regioselective selenation of chromones employing Selectfluor reagent under mild conditions. Furthermore, the application of potassium thiocyanate with enaminones for the synthesis of 3-thiocyano chromones in this transformation is also successful (Scheme 1e). This protocol features a wide substrate scope, good to excellent yields, high selectivity, without the need for toxic metals, ligands, and bases, and could serve as an efficient approach for the construct 3-arylseleno/3-thiocyano chromones under mild conditions.

Results and discussion

Initially, the reaction of enaminone 1a and diphenyl diselenide 2a was screened as a model reaction to identify suitable reaction conditions (Table 1). To our delight, the reaction was performed in CH₃CN using tert-butyl hydroperoxide (TBHP, 70% water) as an oxidant at 90 °C for 6 h, and 30% yield of 3-arylseleno chromone 3a was obtained (entry 1, Table 1). Encouraged by this preliminary result, other oxidants including di-tert-butyl peroxide (DTBP), (NH₄)₂S₂O₈, K₂S₂O₈, Selectfluor, PhI(OAc)₂, and PhI(OCOCF₃)₂ were screened, the result showed that DTBP was noneffective, however Selectfluor could provide the highest yield (83%, entries 2–9, Table 1). Then, the effect of Selectfluor loading was investigated, and 1.0 equiv. was the best choice to give 83% yield (entries 5, 8 and 9, Table 1). The investigation of various solvents such as DMF, DMSO, THF, CH₃OH, DCE, dioxane, and H₂O, revealing that CH₃CN was the optimal solvent for this reaction and afforded 3a in 83% yield (entries 5 and 10–16). The molar ratio of 1a and 2a was also screened. Decreasing the amount of 2a from 1.0 to 0.5 equiv., the yield of 3a was reduced to 76%, and no obvious change in yield was observed increasing 2a loading for 1.0 to 1.5 equiv. (entries 5, 17 and 18, Table 1). Changing the temperature from 20 °C to 90 °C, 40 °C was the best to provide 85% yield (entries 5, 19–21, Table 1). Moreover, the effect of reaction time was also tested. 2 h was proved be optimal time, and provided 3a in 85% yield (entries 5 and 22–24, Table 1). No desired product 3a was detected in the absence of Selectfluor reagent (entry 25, Table 1), which indicated that Selectfluor was crucial for the reaction to occur. Therefore, the best conditions for the synthesis of 3a were identified as follows: the molar ratio of 1a and 2a is 1 : 1, 1.0 equiv. Selectfluor as the oxidant in CH₃CN at 40 °C for 2 h.

Table 1 Optimization of reaction conditions^a

Entry	Oxidant (equiv.)	Solvent	Temp (°C)	Time (h)	Yield^b (%)
a Reaction conditions: enaminone 1a (0.2 mmol, 38.2 mg), diphenyl diselenide 2a (0.2 mmol, 62.8 mg), Selectfluor agent in solvent (2.0 mL).b Isolated yield.c The molar ratio of 1a and 2a is 1 : 0.5.d The molar ratio of 1a and 2a is 1 : 1.5.
1	TBHP (1.0)	CH3CN	90	6	30
2	DTBP (1.0)	CH3CN	90	6	0
3	(NH4)2S2O8 (1.0)	CH3CN	90	6	52
4	K2S2O8 (1.0)	CH3CN	90	6	60
5	Selectfluor (1.0)	CH3CN	90	6	83
6	PhI(OAc)2 (1.0)	CH3CN	90	6	79
7	PhI(OCOCF3)2 (1.0)	CH3CN	90	6	60
8	Selectfluor (0.5)	CH3CN	90	6	78
9	Selectfluor (1.5)	CH3CN	90	6	83
10	Selectfluor (1.0)	DMF	90	6	40
11	Selectfluor (1.0)	DMSO	90	6	45
12	Selectfluor (1.0)	THF	90	6	38
13	Selectfluor (1.0)	CH3OH	90	6	42
14	Selectfluor (1.0)	DCE	90	6	Trace
15	Selectfluor (1.0)	Dioxane	90	6	Trace
16	Selectfluor (1.0)	H2O	90	6	0
17^c	Selectfluor (1.0)	CH3CN	90	6	76
18^d	Selectfluor (1.0)	CH3CN	90	6	83
19	Selectfluor (1.0)	CH3CN	20	6	65
20	Selectfluor (1.0)	CH3CN	40	6	85
21	Selectfluor (1.0)	CH3CN	60	6	85
22	Selectfluor (1.0)	CH3CN	40	1	75
23	Selectfluor (1.0)	CH3CN	40	2	85
24	Selectfluor (1.0)	CH3CN	40	3	85
25	—	CH3CN	40	2	0

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With the optimal reaction conditions identified, the scope and generality of this transformation were firstly evaluated using divergent enaminones (Table 2). Generally, the process is compatible for enaminones with different R groups at the benzene ring containing electron-donating (Me, OMe) and electron-withdrawing (F, Cl, and Br) substituents, which reacted with diphenyl diselenide 2a gave the corresponding products 3aa–3fa in 76–90% yields under the standard conditions. It is noteworthy that an exclusive C-3 site selectivity in this selenylation/cyclization was observed for all the different enaminones. Of particular note was the successful synthesis of the expected 3-arylseleno chromones (3ea, 3fa) bearing chloro and bromo moiety, which provided an opportunity for further functional modification. Furthermore, di-substituted substrates were also suitable for this transformation, delivering the respective products (3ga, 3ha) in good to excellent yields. Notedly, when enaminone at the benzene ring with a strong electron-withdrawing –NO₂ group was employed, the selenylation/cyclization reaction could tolerate the reaction conditions to provide 3ia in 75% yield. Gratifyingly, when a fused aromatic substrate (naphthyl) was employed, the reaction could also proceed smoothly to obtain the desired 3ja in excellent yields (83%).

Table 2 Scope of enaminones for the tandem cyclization^a,b

a Reaction conditions: enaminone 1 (0.2 mmol), diphenyl diselenide 2a (0.2 mmol, 62.8 mg), Selectfluor agent (0.2 mmol, 70.8 mg) in CH₃CN (2.0 mL) at 40 °C for 2.0 h.b Isolated yield.

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Subsequently, we turned our attention to explore the substrate range of diselenides under the standard conditions (Table 3). All of diaryl diselenides 2 with various groups (Me, Et, t-Bu, OMe, F, Cl, Br, I, and OCF₃) work well with 2-hydroxyphenyl enaminone 1a, providing the corresponding 3-arylselenenyl enaminone derivatives in good to excellent yields (3a–3p, 55–94%). The diaryl diselenides with electron-donating groups (–Me, –Et, –^tBu, –OMe) could provide higher yields than those with electron-withdrawing (–F, –Cl, –Br, –I, –OCF₃) substituents. Gratifyingly, when diaryl diselenide with electron-withdrawing group (–OCF₃) was employed, this transformation could proceed smoothly to obtain the corresponding product 3p in 73% yield. Moreover, the reaction proceeded smoothly with 1,2-di(naphthalen-2-yl)diselane, furnishing the desired product 3q in 70% yield. Unfortunately, 1,2-di(naphthalen-1-yl)diselane was used as substrate under the standard conditions, this reaction failed to afford the desired product 3t, which suggests that the steric effect had an important effect on this transformation. Besides the generally good results employing conventional diaryl diselenides, a notable point was that heteroaryl diselenide, 1,2-di(thiophen-2-yl)diselane, also exhibited satisfactory tolerance to the synthetic protocol to provide the desired product 3r, albeit in low yield (58%). Interestingly, when aliphatic diselenide, 1,2-dibenzyldiselane, was employed, the reaction could also proceed smoothly to obtain the desired product 3s in excellent yields (84%).

Table 3 Scope of diselenides on the tandem cyclization of enaminones^a,b

a Reaction conditions: enaminone 1a (0.2 mmol, 38.2 mg), diaryl diselenide 2 (0.2 mmol), Selectfluor agent (0.2 mmol, 70.8 mg) in CH₃CN (2.0 mL) at 40 °C for 2.0 h.b Isolated yield.

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Organic thiocyanates as key skeletal structures are moieties possessing enriched biological and pharmaceutical activities in both synthesized and naturally occurring molecules.²⁷ Moreover, the enriched reactivity of the thiocyano group also endows organic thiocyanates with widespread application as building blocks in organic synthesis.²⁸ However, the synthesis of thiocyanochromenones is rare.²⁹ In order to testify the utility and robustness of this protocol, Selectfluor-promoted synthesis of 3-thiocyanochromenone derivatives was explored (Table 4). We were glad to find that our protocol was applied well in the synthesis of 3-thiocyanochromenone derivatives using KSCN as a thiocyano source under the standard conditions. In general, all of enaminones 1 at the benzene ring with either electron-donating groups (Me, OMe) or electron-withdrawing groups (F, Cl, and Br) reacted smoothly to provide the corresponding products 5a–5h in good yields (76–86%). Unfortunately, enaminone with strong electron-withdrawing group (–NO₂) failed to provide the desired product (5i), potentially due to the low reactivity of this intermediate, thus producing difficultly the cyclizing product. Gratifyingly, disubstituted enaminones also actively participated in this transformation to dispense the desired products 5j and 5k in 82% and 76% yield, respectively.

Table 4 Synthesis of 3-thiocyanochromones^a,b

a Reaction conditions: enaminones 1 (0.2 mmol), potassium thiocyanate 4 (0.2 mmol, 19.4 mg), Selectfluor agent (0.2 mmol, 70.8 mg) in CH₃CN (2.0 mL) at 40 °C for 2.0 h.b Isolated yield.

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Additionally, to verify the utility of this protocol, gram–scale reactions were conducted using 2-hydroxyphenyl enaminone 1a (5 mmol, 0.955 g) with diphenyl diselenide 2a under the standard conditions. As expected, the corresponding desired products 3a and 5a were obtained in 80% and 76% yield, respectively (Scheme 2a), which provides promising application in preparative synthesis. Then, the synthetic transformation of 5a was carried out to explore the thiocyano group with widespread application as a building block in organic synthesis (Scheme 2b).

Scheme 2 Gram-scale synthesis of 3a/5a, and synthetic transformation of 5a.

To investigate the possible process of the reaction, several control experiments were designed as outlined in Scheme 3. Initially, the entry directly employing chromone 6 and diphenyl diselenide 2a with standard reaction conditions was found to be incapable of yielding target product 3a, and 92% of the substrate 6 was recovered (Scheme 3a), which showed that the annulation to chromone was not the initial step in the reaction. Subsequently, radical trapping experiments of enaminone 1a and diphenyl diselenide 2a were examined in the presence of 2,2,6,6-tetramethyl-1-piperidinyloxyl (TEMPO, 3.0 equiv.) or 2,6-di-tert-butyl-4-methylphenol (BHT, 3.0 equiv.) under the standard conditions, and the desired product 3a was provided in 70% and 73% yield, respectively (Scheme 3b). These results indicate that the reaction might not involve radical intermediates, which was in agreement with the case in previous work.^26a Furthermore, when phenyl hypochloroselenoite was added to the reaction system instead of diphenyl diselenide 2a under the standard conditions, the product 3a was obtained with 82% yield (Scheme 3c), demonstrating that this transformation may proceed via an ion pathway, instead of a radical pathway.

Scheme 3 Control experiments. (a) Direct selenylation of chromone; (b) radical trapping experiments; (c) phenyl hypochloroselenoite as selenylation reagent.

On the basis of these results and previous reports,^19–23 a plausible mechanism for this transformation was proposed (Scheme 4). Initially, the reaction involves the oxidation of diphenyl diselenide by Selectfluor reagent to form the electrophilic species I and II.^26b,d Then, these species attack C–C double bond of 2-hydroxyphenyl enaminone 1a to form species III. Subsequently, the species III would afford the cyclic intermediate IV through the intramolecular nucleophilic attack of the carbon atom of the C=N moiety. The intermediate V is made by the proton transfer. Finally, the elimination of dimethylamine from the intermediate V would furnish the expected product 3a. For the synthetic mechanism of 3-thiocyanochromenone derivatives, the thiocyano cation could be formed with KSCN using Selectfluor reagent as an oxidant. 3-Thiocyanochromenone derivatives could be provided by the similar mechanism.

Scheme 4 Proposed reaction mechanism.

Conclusions

In conclusion, an intriguing Selectfluor-promoted, metal-free, and efficient synthetic approach to access 3-selenylated chromones have been developed from enaminones and easily available diaryl diselenides. This approach exhibits a broad substrate scope, simple procedure, mild reaction condition, good to excellent yields and high selectivity. Furthermore, the application of potassium thiocyanate with enaminones for the synthesis of 3-thiocyanochromenone derivatives is also successful.

Experimental

General information

All chemicals were commercially available and used as received without further. Column chromatography was performed using 300–400 mesh silica. Nuclear magnetic resonance spectra were recorded on Bruker Avance 400 MHz spectrometer. Chemical shifts for ¹H NMR spectra are recorded in parts per million from tetramethylsilane. Data were reported as follows: chemical shift, multiplicity (s = singlet, d = doublet, t = triplet, m = multiplet and br = broad), coupling constant in Hz and integration. Chemical shifts for ¹³C NMR spectra were recorded in parts per million from tetramethylsilane. Chemical shifts for ¹⁹F NMR spectra were recorded in parts per million with fluorobenzene as external standard. High resolution mass spectra (HR MS) were obtained on Thermo Scientific LTQ Orbitrap XL instrument using the ESI technique. IR spectra were recorded on WQF-510 Fourier transform infrared spectrophotometer. Melting points were measured on an XT4A microscopic apparatus uncorrected.

General experimental procedure for the synthesis of 3-arylselenenyl chromones (3)

Enaminones 1 (0.2 mmol), diaryl diselenides 2 (0.2 mmol), Selectfluor agent (0.2 mmol, 70.8 mg), and acetonitrile (2.0 mL) were added to a 10 mL reaction tube. The mixture was stirred at 40 °C for 2 h. After completion of the reaction, the solvent was distilled under vacuum. Then, the resulting mixture was dissolved with ethyl acetate (20 mL), washed with saturated sodium chloride solution (10 mL × 2). The organic phase was dried over anhydrous Na₂SO₄ and concentrated under vacuum. The residue was purified by silica gel column chromatography to give 3-arylseleno chromones 3 using ethyl acetate/petroleum ether as eluant.

7-Methyl-3-(phenylselanyl)-4H-chromen-4-one (3aa). Light yellow crystal, mp 107–108 °C (lit.^16b 99–100 °C); IR (KBr) ν (cm⁻¹): 2921, 1644, 1621, 1476, 1435, 1344, 1298, 1064; ¹H NMR (400 MHz, CDCl₃) δ: 8.10 (d, J_H–H = 8.0 Hz, 1H), 7.85 (s, 1H), 7.59–7.57 (m, 2H), 7.29–7.26 (m, 3H), 7.22–7.20 (m, 2H), 2.46 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 175.0 (C=O), 156.5, 155.6 (CH), 145.3, 133.7 (CH), 129.5 (CH), 128.3, 128.0 (CH), 127.1 (CH), 126.1 (CH), 120.9, 117.7 (CH), 117.6, 21.8 (CH₃); HR MS (ESI) m/z: calcd for C₁₆H₁₃O₂Se [M + H]⁺ 317.0075, found 317.0069.

6-Methyl-3-(phenylselanyl)-4H-chromen-4-one (3ba). Colorless crystal, mp 96–97 °C (lit.^16b 99–100 °C); IR (KBr) ν (cm⁻¹): 1640, 1616, 1598, 1477, 1436, 1308, 1227, 1067; ¹H NMR (400 MHz, CDCl₃) δ: 8.02 (d, J_H–H = 1.0 Hz, 1H), 7.90 (s, 1H), 7.60–7.57 (m, 2H), 7.47 (dd, J_H–H = 8.5 Hz, J_H–H = 2.0 Hz, 1H), 7.33 (d, J_H–H = 8.6 Hz, 1H), 7.29–7.28 (m, 3H), 2.44 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 175.3 (C=O), 155.9 (CH), 154.6 (CH), 135.6, 135.1 (CH), 133.6 (CH), 129.5 (CH), 128.4, 128.0 (CH), 125.6 (CH), 122.8, 117.8 (CH), 117.4, 20.9 (CH₃); HR MS (ESI) m/z: calcd for C₁₆H₁₃O₂Se [M + H]⁺ 317.0075, found 317.0068.

6-Methoxy-3-(phenylselanyl)-4H-chromen-4-one (3ca). Colorless crystal, mp 99–100 °C (lit.^20a 99–101 °C); IR (KBr) ν (cm⁻¹): 2932, 1630, 1615, 1546, 1487, 1264; ¹H NMR (400 MHz, CDCl₃) δ: 7.92 (s, 1H), 7.60–7.58 (m, 3H), 7.37 (d, J_H–H = 9.2 Hz, 1H), 7.30–7.24 (m, 4H), 3.88 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 175.0 (C=O), 157.2, 155.8 (CH), 151.2, 133.6 (CH), 129.5 (CH), 128.4, 128.0 (CH), 124.0 (CH), 123.8, 119.5 (CH), 116.8, 105.2 (CH), 55.9 (CH₃); HR MS (ESI) m/z: calcd for C₁₆H₁₃O₃Se [M + H]⁺ 333.0024, found 333.0019.

7-Fluoro-3-(phenylselanyl)-4H-chromen-4-one (3da). Colorless crystal, mp 115–116 °C (lit.^16b 120–121 °C); IR (KBr) ν (cm⁻¹): 1605, 1474, 1431, 1349, 1251, 1092; ¹H NMR (400 MHz, CDCl₃) δ: 8.26–8.22 (m, 1H), 7.79 (s, 1H), 7.61–7.59 (m, 2H), 7.32–7.30 (m, 3H), 7.16–7.11 (m, 2H); ¹³C NMR (100 MHz, CDCl₃) δ: 174.3 (C=O), 165.6 (d, J_F–C = 254.2 Hz), 157.3 (d, J_F–C = 13.2 Hz), 155.3 (CH), 134.1 (CH), 129.6 (CH), 129.0 (CH), 128.9 (CH), 128.3 (CH), 127.6, 119.9 (d, J_F–C = 2.3 Hz), 118.4, 114.4 (d, J_F–C = 22.7 Hz, CH), 104.7 (d, J_F–C = 25.2 Hz, CH); ¹⁹F NMR (376 MHz, CDCl₃) δ: −102.1. HR MS (ESI) m/z: calcd for C₁₅H₁₀FO₂Se [M + H]⁺ 320.9825, found 320.9818.

7-Chloro-3-(phenylselanyl)-4H-chromen-4-one (3ea). Light yellow crystal, mp 111–112 °C (lit.^16b 112–113 °C); IR (KBr) ν (cm⁻¹): 1651, 1602, 1576, 1477, 1339, 1282, 1021; ¹H NMR (400 MHz, CDCl₃) δ: 8.13 (d, J_H–H = 8.6 Hz, 1H), 7.76 (s, 1H), 7.60–7.58 (m, 2H), 7.40 (d, J_H–H = 1.8 Hz, 1H), 7.35–7.27 (m, 4H); ¹³C NMR (100 MHz, CDCl₃) δ: 174.3 (C=O), 156.3, 155.0 (CH), 139.8, 134.2 (CH), 129.6 (CH), 128.4 (CH), 127.6 (CH), 127.5, 126.4 (CH), 121.4, 118.6, 118.0 (CH); HR MS (ESI) m/z: calcd for C₁₅H₁₀ClO₂Se [M + H]⁺ 336.9529, found 336.9519.

6-Bromo-3-(phenylselanyl)-4H-chromen-4-one (3fa). Colorless crystal, mp 90–91 °C (lit.^16b 90–91 °C); IR (KBr) ν (cm⁻¹): 1645, 1601, 1540, 1422, 1348, 1297, 1058; ¹H NMR (400 MHz, CDCl₃) δ: 8.34 (d, J_H–H = 2.4 Hz, 1H), 7.83 (s, 1H), 7.73 (dd, J_H–H = 8.9 Hz, J_H–H = 2.4 Hz, 1H), 7.61–7.58 (m, 1H), 7.33–7.30 (m, 4H); ¹³C NMR (100 MHz, CDCl₃) δ: 173.9 (C=O), 155.4 (CH), 155.0, 136.8 (CH), 134.1 (CH), 129.6 (CH), 128.8 (CH), 128.4 (CH), 127.5, 124.2, 120.0 (CH), 118.9, 118.3; HR MS (ESI) m/z: calcd for C₁₅H₁₀BrO₂Se [M + H]⁺ 380.9024, found 380.9010.

6,8-Dichloro-3-(phenylselanyl)-4H-chromen-4-one (3ga). Light yellow crystal, mp 114–115 °C (lit.^20a 113–115 °C); IR (KBr) ν (cm⁻¹): 1644, 1591, 1447, 1356, 1296, 1197; ¹H NMR (400 MHz, CDCl₃) δ: 8.08 (d, J_H–H = 2.5 Hz, 1H), 7.76 (s, 1H), 7.68 (d, J_H–H = 2.5 Hz, 1H), 7.64–7.61 (m, 2H), 7.36–7.30 (m, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 173.5 (C=O), 154.2 (CH), 150.6, 134.8 (CH), 133.9 (CH), 131.1, 129.8 (CH), 128.8 (CH), 126.6, 124.4, 124.3 (CH), 119.3; HR MS (ESI) m/z: calcd for C₁₅H₉Cl₂O₂Se [M + H]⁺ 370.9139, found 370.9141.

6,8-Dibromo-3-(phenylselanyl)-4H-chromen-4-one (3ha). Orange yellow crystal, mp 115–116 °C (lit.^20a 118–119 °C); IR (KBr) ν (cm⁻¹): 1656, 1540, 1449, 1345, 1288, 1069; ¹H NMR (400 MHz, CDCl₃) δ: 8.29 (d, J_H–H = 2.4 Hz, 1H), 8.00 (d, J_H–H = 2.4 Hz, 1H), 7.77 (s, 1H), 7.64–7.62 (m, 2H), 7.37–7.31 (m, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 173.5 (C=O), 154.2 (CH), 152.0, 139.5 (CH), 134.8 (CH), 129.8 (CH), 128.8 (CH), 128.2 (CH), 126.6, 124.7, 119.3, 118.7, 112.8; HR MS (ESI) m/z: calcd for C₁₅H₉Br₂O₂Se [M + H]⁺ 458.8129, found 458.8134.

6-Nitro-3-(phenylselanyl)-4H-chromen-4-one (3ia). Yellow crystal, mp 108–109 °C (lit.^16b 115–116 °C); IR (KBr) ν (cm⁻¹): 1637, 1574, 1437, 1344, 1206, 1089; ¹H NMR (400 MHz, CDCl₃) δ: 9.08 (d, J_H–H = 2.7 Hz, 1H), 8.48 (dd, J_H–H = 9.1 Hz, J_H–H = 2.4 Hz, 1H), 7.76 (s, 1H), 7.65–7.63 (m, 2H), 7.59 (d, J_H–H = 9.2 Hz, 1H), 7.39–7.32 (m, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 173.9 (C=O), 159.0, 154.4 (CH), 144.9, 134.9 (CH), 129.8 (CH), 128.9 (CH), 128.0 (CH), 126.4, 123.0 (CH), 122.7, 120.0, 119.9 (CH); HR MS (ESI) m/z: calcd for C₁₅H₁₀NO₄Se [M + H]⁺ 347.9770, found 347.9773.

3-(Phenylselanyl)-4H-benzo[h]chromen-4-one (3ja). Light yellow crystal, mp 110–112 °C (lit.^16b 105–106 °C); IR (KBr) ν (cm⁻¹): 1618, 1559, 1464, 1301, 1260, 1155; ¹H NMR (400 MHz, CDCl₃) δ: 8.35 (d, J_H–H = 8.2 Hz, 1H), 8.13 (d, J_H–H = 8.8 Hz, 1H), 7.90–7.87 (m, 2H), 7.72 (d, J_H–H = 8.7 Hz, 1H), 7.69–7.59 (m, 4H), 7.34–7.31 (m, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 175.0 (C=O), 153.8 (CH), 135.7, 134.4 (CH), 129.7 (CH), 129.4 (CH), 128.4 (CH), 128.1 (CH), 127.5, 127.2 (CH), 125.6 (CH), 123.8, 122.1 (CH), 121.0 (CH), 120.2, 119.1; HR MS (ESI) m/z: calcd for C₁₉H₁₃O₂Se [M + H]⁺ 353.0075, found 353.0069.

3-(Phenylselanyl)-4H-chromen-4-one (3a). Light yellow crystal, mp 63–64 °C (lit.²² yellow liquid); IR (KBr) ν (cm⁻¹): 1626, 1610, 1461, 1342, 1110; ¹H NMR (400 MHz, CDCl₃) δ: 8.24–8.21 (m, 1H), 7.89 (s, 1H), 7.68–7.63 (m, 1H), 7.60–7.58 (m, 2H), 7.43–7.38 (m, 2H), 7.31–7.27 (m, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 175.2 (C=O), 156.3, 155.8 (CH), 133.9 (CH), 133.8 (CH), 129.5 (CH), 128.1 (CH), 126.3 (CH), 125.5 (CH), 123.1, 118.0 (CH), 117.8; HR MS (ESI) m/z: calcd for C₁₅H₁₁O₂Se [M + H]⁺ 302.9919, found 302.9911.

3-(o-Tolylselanyl)-4H-chromen-4-one (3b). Light yellow crystal, mp 95–96 °C (lit.²² 118–119 °C); IR (KBr) ν (cm⁻¹): 2920, 1643, 1610, 1343, 1251, 1073; ¹H NMR (400 MHz, CDCl₃) δ: 8.25 (dd, J_H–H = 8.5 Hz, J_H–H = 1.8 Hz, 1H), 7.69–7.65 (m, 2H), 7.48 (dd, J_H–H = 7.5 Hz, J_H–H = 0.8 Hz, 1H), 7.44–7.41 (m, 2H), 7.25–7.23 (m, 2H), 7.21–7.08 (m, 1H), 2.50 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 175.3 (C=O), 156.4, 154.7 (CH), 140.6, 134.4 (CH), 133.8 (CH), 130.5 (CH), 128.5 (CH), 128.4, 127.0 (CH), 126.3 (CH), 125.5 (CH), 122.9, 118.0 (CH), 117.3, 22.3 (CH₃); HR MS (ESI) m/z: calcd for C₁₆H₁₃O₂Se [M + H]⁺ 317.0075, found 317.0070.

3-(m-Tolylselanyl)-4H-chromen-4-one (3c). Light yellow crystal, mp 73–74 °C; IR (KBr) ν (cm⁻¹): 2915, 1651, 1551, 1455, 1359, 1334, 1306, 1069; ¹H NMR (400 MHz, CDCl₃) δ: 8.23 (dd, J_H–H = 8.4 Hz, J_H–H = 1.7 Hz, 1H), 7.85 (s, 1H), 7.68–7.63 (m, 1H), 7.43–7.38 (m, 4H), 7.18 (t, J_H–H = 7.6 Hz, 1H), 7.11 (d, J_H–H = 7.6 Hz, 1H), 2.31 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 175.2 (C=O), 156.3, 155.4 (CH), 139.4, 134.5 (CH), 133.7 (CH), 131.0 (CH), 129.3 (CH), 129.0 (CH), 127.7, 126.3 (CH), 125.5, 123.1, 118.0 (CH), 21.3 (CH₃); HR MS (ESI) m/z: calcd for C₁₆H₁₃O₂Se [M + H]⁺ 317.0075, found 317.0070.

3-(p-Tolylselanyl)-4H-chromen-4-one (3d). Light yellow crystal, mp 85–86 °C (lit.²² 83–84 °C); IR (KBr) ν (cm⁻¹): 2918, 1641, 1606, 1550, 1486, 1360, 1341, 1326, 1207; ¹H NMR (400 MHz, CDCl₃) δ: 8.23 (dd, J_H–H = 8.5 Hz, J_H–H = 1.9 Hz, 1H), 7.77 (s, 1H), 7.67–7.63 (m, 1H), 7.53 (d, J_H–H = 8.1 Hz, 2H), 7.42–7.38 (m, 2H), 7.12 (d, J_H–H = 7.8 Hz, 2H), 2.33 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 175.2 (C=O), 156.3, 154.8 (CH), 138.5, 134.6 (CH), 133.7 (CH), 130.4 (CH), 126.2 (CH), 125.4 (CH), 123.8, 123.0, 118.6, 118.0 (CH), 21.2 (CH₃); HR MS (ESI) m/z: calcd for C₁₆H₁₃O₂Se [M + H]⁺ 317.0075, found 317.0070.

3-((3,4-Dimethylphenyl)selanyl)-4H-chromen-4-one (3e). Light yellow crystal, mp 110–111 °C; IR (KBr) ν (cm⁻¹): 2917, 1620, 1606, 1554, 1450, 1312, 1107; ¹H NMR (400 MHz, CDCl₃) δ: 8.23(dd, J_H–H = 8.0 Hz, J_H–H = 1.6 Hz, 1H), 7.74 (s, 1H), 7.67–7.63 (m, 1H), 7.42–7.35 (m, 4H), 7.07 (d, J_H–H = 7.8 Hz, 1H),2.24 (s, 3H), 2.23 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 175.2 (C=O), 156.3, 154.5 (CH), 138.2, 137.2, 135.7 (CH), 133.7 (CH), 132.2 (CH), 130.8 (CH), 126.3 (CH), 125.4 (CH), 123.9, 123.0, 118.7, 118.0 (CH), 19.6 (CH₃), 19.5 (CH₃); HR MS (ESI) m/z: calcd for C₁₇H₁₅O₂Se [M + H]⁺ 331.0232, found 331.0226.

3-((4-Ethylphenyl)selanyl)-4H-chromen-4-one (3f). Light yellow crystal, mp 98–99 °C (lit.³⁰ yellow oil liquid); IR (KBr) ν (cm⁻¹): 2963, 1636, 1610, 1462, 1342, 1309, 1109, 1057; ¹H NMR (400 MHz, CDCl₃) δ: 8.24 (dd, J_H–H = 8.4 Hz, J_H–H = 1.8 Hz, 1H), 7.79 (s, 1H), 7.68–7.64 (m, 1H), 7.55 (d, J_H–H = 8.2 Hz, 2H), 7.43–7.39 (m, 2H), 7.15 (d, J_H–H = 8.2 Hz, 2H), 2.63 (q, J_H–H = 7.6 Hz, 2H), 1.22 (t, J_H–H = 7.6 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 175.4 (C=O), 156.3 (CH), 154.9 (CH), 144.8, 134.6 (CH), 133.7 (CH), 129.2 (CH), 126.3 (CH), 125.4 (CH), 124.1, 123.0, 118.5, 118.0 (CH), 28.5 (CH₂), 15.4 (CH₃); HR MS (ESI) m/z: calcd for C₁₇H₁₅O₂Se [M + H]⁺ 331.0232, found 331.0227.

3-((4-(tert-Butyl)phenyl)selanyl)-4H-chromen-4-one (3g). Light yellow crystal, mp 110–111 °C; IR (KBr) ν (cm⁻¹): 2959, 2922, 1642, 1607, 1555, 1459, 1342, 1111; ¹H NMR (400 MHz, CDCl₃) δ: 8.24 (dd, J_H–H = 8.4 Hz, J_H–H = 1.5 Hz, 1H), 7.82 (s, 1H), 7.65 (td, J_H–H = 7.8 Hz, J_H–H = 1.7 Hz, 1H), 7.55 (d, J_H–H = 8.4 Hz, 2H), 7.42–7.39 (m, 2H), 7.33 (d, J_H–H = 8.5 Hz, 2H), 1.30 (s, 9H); ¹³C NMR (100 MHz, CDCl₃) δ: 175.3 (C=O), 156.3, 155.0 (CH), 151.6, 134.2 (CH), 133.7 (CH), 126.7 (CH), 126.3 (CH), 125.4 (CH), 124.1, 123.0, 118.3, 118.0 (CH), 34.6, 31.2 (CH₃); HR MS (ESI) m/z: calcd for C₁₉H₁₉O₂Se [M + H]⁺ 359.0545, found 259.0538.

3-((4-Methoxyphenyl)selanyl)-4H-chromen-4-one (3h). Light yellow crystal, mp 125–126 °C (lit.²² 131–132 °C); IR (KBr) ν (cm⁻¹): 2959, 1643, 1581, 1552, 1462, 1245, 1022; ¹H NMR (400 MHz, CDCl₃) δ: 8.22 (dd, J_H–H = 8.3 Hz, J_H–H = 1.6 Hz, 1H), 7.66–7.59 (m, 4H), 7.41–7.37 (m, 2H), 6.86 (d, J_H–H = 8.8 Hz, 2H), 3.80 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 175.3 (C=O), 160.2, 156.3, 153.8 (CH), 137.1 (CH), 133.6 (CH), 126.1 (CH), 125.3 (CH), 122.8, 119.3, 118.0 (CH), 117.0, 115.3 (CH), 55.3 (CH₃); HR MS (ESI) m/z: calcd for C₁₆H₁₃O₃Se [M + H]⁺ 333.0024, found 333.0018.

3-((3-Methoxyphenyl)selanyl)-4H-chromen-4-one (3i). Light yellow crystal, mp 89–90 °C (lit.^16b 88–89 °C); IR (KBr) ν (cm⁻¹): 2962, 1648, 1586, 1551, 1454, 1288, 1038; ¹H NMR (400 MHz, CDCl₃) δ: 8.23 (dd, J_H–H = 7.9 Hz, J_H–H = 1.4 Hz, 1H), 7.91 (s, 1H), 7.68–7.64 (m, 1H), 7.43–7.39 (m, 2H), 7.20 (t, J_H–H = 7.8 Hz, 1H), 7.18–7.14 (m, 2H), 6.84–6.81 (m, 1H), 3.77 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 175.1 (C=O), 160.0, 156.3, 155.8 (CH), 133.8 (CH), 130.3 (CH), 129.0, 126.3 (CH), 125.8 (CH), 125.5 (CH), 123.1, 118.9 (CH), 118.0 (CH), 117.6, 113.9 (CH), 55.3 (CH₃); HR MS (ESI) m/z: calcd for C₁₆H₁₃O₃Se [M + H]⁺ 333.0024, found 333.0018.

3-((4-Fluorophenyl)selanyl)-4H-chromen-4-one (3j). Light yellow crystal, mp 93–94 °C (lit.^16b 94–95 °C); IR (KBr) ν (cm⁻¹): 1643, 1361, 1221, 1064; ¹H NMR (400 MHz, CDCl₃) δ: 8.23 (dd, J_H–H = 8.3 Hz, J_H–H = 1.5 Hz, 1H), 7.90 (s, 1H), 7.69–7.65 (m, 1H), 7.64–7.60 (m, 2H), 7.44–7.40 (m, 2H), 7.00 (t, J_H–H = 8.7 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃) δ: 175.2 (C=O), 162.9 (d, J_F–C = 247.0 Hz), 156.3, 155.5 (CH), 136.4 (d, J_F–C = 7.9 Hz), 133.9, 126.3, 125.6, 123.1, 122.6, 122.5, 118.0, 116.7 (d, J_F–C = 21.3 Hz); ¹⁹F NMR (376 MHz, CDCl₃) δ: −112.9. HR MS (ESI) m/z: calcd for C₁₅H₁₀FO₂Se [M + H]⁺ 320.9825, found 320.9818.

3-((4-Chlorophenyl)selanyl)-4H-chromen-4-one (3k). Light yellow crystal, mp 133–134 °C (lit.²² 133–134 °C); IR (KBr) ν (cm⁻¹): 1628, 1551, 1460, 1308, 1249, 1075; ¹H NMR (400 MHz, CDCl₃) δ: 8.23 (dd, J_H–H = 8.0 Hz, J_H–H = 1.4 Hz, 1H), 8.01 (s, 1H), 7.71–7.66 (m, 1H), 7.52 (d, J_H–H = 8.5 Hz, 2H), 7.46–7.41 (m, 2H), 7.26–7.24 (m, 2H); ¹³C NMR (100 MHz, CDCl₃) δ: 175.0 (C=O), 156.4 (CH), 156.3, 134.8 (CH), 134.3, 133.9 (CH), 129.6 (CH), 126.6, 126.4 (CH), 125.7 (CH), 123.2, 118.1 (CH), 117.2; HR MS (ESI) m/z: calcd for C₁₅H₁₀ClO₂Se [M + H]⁺ 336.9529, found 336.9519.

3-((3-Chlorophenyl)selanyl)-4H-chromen-4-one (3l). Light yellow crystal, mp 89–90 °C (lit.^16b 90–91 °C); IR (KBr) ν (cm⁻¹): 1652, 1605, 1564, 1552, 1405, 1360, 1308, 1101; ¹H NMR (400 MHz, CDCl₃) δ: 8.24 (dd, J_H–H = 8.0 Hz, J_H–H = 1.4 Hz, 1H), 8.09 (s, 1H), 7.72–7.67 (m, 1H), 7.53 (t, J_H–H = 1.6 Hz, 1H), 7.47–7.42 (m, 3H), 7.25–7.18 (m, 2H); ¹³C NMR (100 MHz, CDCl₃) δ: 175.0 (C=O), 157.1 (CH), 156.4, 134.9, 134.0 (CH), 132.4 (CH), 130.9 (CH), 130.4 (CH), 128.0 (CH), 126.4 (CH), 125.8 (CH), 123.3, 118.1 (CH), 116.6; HR MS (ESI) m/z: calcd for C₁₅H₁₀ClO₂Se [M + H]⁺ 336.9529, found 336.9521.

3-((4-Bromophenyl)selanyl)-4H-chromen-4-one (3m). Light yellow crystal, mp 124–125 °C (lit.^16b 129–130 °C); IR (KBr) ν (cm⁻¹): 1627, 1608, 1549, 1379, 1329, 1100; ¹H NMR (400 MHz, CDCl₃) δ: 8.23 (dd, J_H–H = 8.0 Hz, J_H–H = 1.6 Hz, 1H), 8.03 (s, 1H), 7.71–7.66 (m, 1H), 7.46–7.38 (m, 6H); ¹³C NMR (100 MHz, CDCl₃) δ: 175.0 (C=O), 156.6 (CH), 156.3, 134.9 (CH), 134.0 (CH), 132.5 (CH), 127.4, 126.4 (CH), 125.7 (CH), 123.2, 122.4, 118.1 (CH), 117.0; HR MS (ESI) m/z: calcd for C₁₅H₁₀BrO₂Se [M + H]⁺ 380.9024, found 380.9014.

3-((2-Bromophenyl)selanyl)-4H-chromen-4-one (3n). Yellow crystal, mp 130–131 °C; IR (KBr) ν (cm⁻¹): 1637, 1610, 1549, 1436, 1313, 1167; ¹H NMR (400 MHz, CDCl₃) δ: 8.23 (dd, J_H–H = 8.0 Hz, J_H–H = 1.6 Hz, 1H), 8.05 (s, 1H), 7.71–7.67 (m, 1H), 7.59 (d, J_H–H = 8.4 Hz, 2H), 7.46–7.41 (m, 2H), 7.30 (d, J_H–H = 8.4 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃) δ: 175.0 (C=O), 159.3 (CH), 156.5, 134.1 (CH), 133.0, 132.9 (CH), 131.1 (CH), 128.1 (CH), 128.0 (CH), 126.6 (CH), 125.9 (CH), 124.3, 123.6, 118.2 (CH), 115.2; HR MS (ESI) m/z: calcd for C₁₅H₁₀BrO₂Se [M + H]⁺ 380.9024, found 380.9013.

3-((4-Iodophenyl)selanyl)-4H-chromen-4-one (3o). Light yellow crystal, mp 121–122 °C; IR (KBr) ν (cm⁻¹): 1629, 1548, 1458, 1309, 1063; ¹H NMR (400 MHz, CDCl₃) δ: 8.23 (dd, J_H–H = 7.9 Hz, J_H–H = 1.6 Hz, 1H), 8.05 (s, 1H), 7.71–7.67 (m, 1H), 7.59 (d, J_H–H = 8.3 Hz, 2H), 7.46–7.42 (m, 2H), 7.30 (d, J_H–H = 8.4 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃) δ: 175.0 (C=O), 156.8, 156.4, 138.4, 134.9, 134.0, 128.5, 126.4, 125.7, 123.3, 118.1, 116.9, 93.8; HR MS (ESI) m/z: calcd for C₁₅H₁₀IO₂Se [M + H]⁺ 428.8885, found 428.8874.

3-((4-(Trifluoromethoxy)phenyl)selanyl)-4H-chromen-4-one (3p). Light yellow crystal, mp 90–91 °C; IR (KBr) ν (cm⁻¹): 1640, 1611, 1554, 1461, 1112, 1062; ¹H NMR (400 MHz, CDCl₃) δ: 8.24 (dd, J_H–H = 7.8 Hz, J_H–H = 1.6 Hz, 1H), 8.07 (s, 1H), 7.71–7.67 (m, 1H), 7.61 (d, J_H–H = 8.8 Hz, 2H), 7.46–7.42 (m, 2H), 7.13 (dd, J_H–H = 8.7 Hz, J_H–H = 0.7 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃) δ: 175.1 (C=O), 156.9 (CH), 156.4, 149.1 (q, J_F–C = 1.5 Hz), 134.8 (CH), 134.0 (CH), 126.9, 126.4 (CH), 125.8 (CH), 123.3, 121.9 (CH), 118.1 (CH), 116.9; ¹⁹F NMR (376 MHz, CDCl₃) δ: −57.8. HR MS (ESI) m/z: calcd for C₁₆H₁₀F₃O₃Se [M + H]⁺ 386.9742, found 386.9734.

3-(Naphthalen-2-ylselanyl)-4H-chromen-4-one (3q). Light yellow crystal, mp 77–78 °C (lit.²² white liquid); IR (KBr) ν (cm⁻¹): 1627, 1604, 1554, 1499, 1253, 1108; ¹H NMR (400 MHz, CDCl₃) δ: 8.40 (d, J_H–H = 7.8 Hz, 1H), 8.25 (dd, J_H–H = 8.0 Hz, J_H–H = 1.6 Hz, 1H), 7.96 (dd, J_H–H = 7.1 Hz, J_H–H = 1.1 Hz, 1H), 7.90 (d, J_H–H = 8.2 Hz, 1H), 7.86 (dd, J_H–H = 7.0 Hz, J_H–H = 1.6 Hz, 1H), 7.65–7.61 (m, 1H), 7.57–7.50 (m, 2H), 7.44–7.38 (m, 2H), 7.34 (d, J_H–H = 8.5 Hz, 1H), 7.32 (s, 1H); ¹³C NMR (100 MHz, CDCl₃) δ: 175.4 (C=O), 156.2, 153.3 (CH), 135.4 (CH), 134.3, 134.2, 133.7 (CH), 130.2 (CH), 128.7 (CH), 127.7 (CH), 127.4 (CH), 126.6 (CH), 126.1 (CH), 125.9, 125.4 (CH), 122.7, 118.3, 118.0 (CH); HR MS (ESI) m/z: calcd for C₁₉H₁₃O₂Se [M + H]⁺ 353.0075, found 353.0069.

3-(Thiophen-2-ylselanyl)-4H-chromen-4-one (3r). Light yellow crystal, mp 119–120 °C (lit.^16b 120–121 °C); IR (KBr) ν (cm⁻¹): 1629, 1609, 1548, 1458, 1329, 1201, 1063; ¹H NMR (400 MHz, CDCl₃) δ: 8.22 (dd, J_H–H = 8.3 Hz, J_H–H = 1.7 Hz, 1H), 7.69–7.64 (m, 1H), 7.59 (s, 1H), 7.49 (d, J_H–H = 8.4 Hz, 1H), 7.43–7.40 (m, 3H), 7.07–7.05 (m, 1H); ¹³C NMR (100 MHz, CDCl₃) δ: 175.1 (C=O), 156.3, 153.3 (CH), 137.9 (CH), 133.8 (CH), 132.7 (CH), 128.6 (CH), 126.1 (CH), 125.5 (CH), 122.7, 120.0, 119.9, 118.0 (CH); HR MS (ESI) m/z: calcd for C₁₃H₉O₂SSe [M + H]⁺ 308.9483, found 308.9477.

3-(Benzylselanyl)-4H-chromen-4-one (3s). Light yellow crystal, mp 109–110 °C (lit.^16b 94–95 °C); IR (KBr) ν (cm⁻¹): 1610, 1556, 1463, 1378, 1073; ¹H NMR (400 MHz, CDCl₃) δ: 8.27 (dd, J_H–H = 8.0 Hz, J_H–H = 1.6 Hz, 1H), 7.87 (s, 1H), 7.69–7.64 (m, 1H), 7.45–7.39 (m, 2H), 7.23–7.13 (m, 5H), 4.10 (s, 2H); ¹³C NMR (100 MHz, CDCl₃) δ: 175.8 (C=O), 157.5 (CH), 156.3, 138.5, 133.7 (CH), 128.9 (CH), 128.4 (CH), 126.8 (CH), 126.3 (CH), 125.6 (CH), 123.3, 118.1 (CH), 114.2, 29.7 (CH₂); HR MS (ESI) m/z: calcd for C₁₆H₁₃O₂Se [M + H]⁺ 317.0075, found 317.0070.

General experimental procedure for the synthesis of 3-thiocyano chromones (5)

Enaminones 1 (0.2 mmol), potassium thiocyanate 4 (0.2 mmol, 19.4 mg), Selectfluor agent (0.2 mmol, 70.8 mg), and acetonitrile (2.0 mL) were added to a 10 mL reaction tube. The mixture was stirred at 40 °C for 2 h. After completion of the reaction, the solvent was distilled under vacuum. Then, the resulting mixture was dissolved with ethyl acetate (20 mL), washed with saturated sodium chloride solution (10 mL × 2). The organic phase was dried over anhydrous Na₂SO₄ and concentrated under vacuum. The residue was purified by silica gel column chromatography to give 3-thiocyano chromones 5 using ethyl acetate/petroleum ether as eluant.

3-Thiocyanato-4H-chromen-4-one (5a). Light yellow crystal, mp 139–140 °C (lit.^29d 149–150 °C); IR (KBr) ν (cm⁻¹): 1651, 1550, 1457, 1363, 1204, 1086; ¹H NMR (400 MHz, CDCl₃) δ: 8.34 (s, 1H), 8.25 (dd, J_H–H = 8.0 Hz, J_H–H = 1.5 Hz, 1H), 7.80–7.76 (m, 1H), 7.56–7.50 (m, 2H); ¹³C NMR (100 MHz, CDCl₃) δ: 173.0 (C=O), 156.3, 155.4 (CH), 135.0 (CH), 126.6 (CH), 126.1 (CH), 122.6, 118.4 (CH), 112.5, 108.9; HR MS (ESI) m/z: calcd for C₁₀H₆NO₂S [M + H]⁺ 204.0114, found 204.0109.

6-Methyl-3-thiocyanato-4H-chromen-4-one (5b). Light yellow crystal, mp 124–125 °C (lit.^29e 134–135 °C); IR (KBr) ν (cm⁻¹): 3070, 1648, 1559, 1479, 1331, 1147, 1125; ¹H NMR (400 MHz, CDCl₃) δ: 8.31 (s, 1H), 8.02 (d, J_H–H = 1.1 Hz, 1H), 7.58 (dd, J_H–H = 8.6 Hz, J_H–H = 2.0 Hz, 1H), 7.44 (d, J_H–H = 8.6 Hz, 1H), 2.48 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 173.0 (C=O), 155.3 (CH), 154.6, 136.9, 136.2 (CH), 125.3 (CH), 122.3, 118.1 (CH), 112.2, 109.0, 21.0 (CH₃); HR MS (ESI) m/z: calcd for C₁₁H₈NO₂S [M + H]⁺ 218.0270, found 218.0266.

7-Methyl-3-thiocyanato-4H-chromen-4-one (5c). Colorless crystal, mp 135–136 °C; IR (KBr) ν (cm⁻¹): 2922, 1608, 1436, 1245, 1211, 1199, 1092; ¹H NMR (400 MHz, CDCl₃) δ: 8.18 (d, J_H–H = 8.9 Hz, 1H), 8.07 (d, J_F–H = 3.2 Hz, 1H), 7.02 (dd, J_H–H = 8.9 Hz, J_H–H = 2.2 Hz, 1H), 6.86 (d, J_F–H = 2.2 Hz, 1H), 3.91 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 164.4 (C=O), 157.7, 150.6, 148.1, 142.5, 142.1, 127.3, 127.2, 114.9, 100.3, 55.9 (CH₃); HR MS (ESI) m/z: calcd for C₁₁H₈NO₂S [M + H]⁺ 218.0270, found 218.0267.

7-Methoxy-3-thiocyanato-4H-chromen-4-one (5d). Light yellow crystal, mp 157–158 °C (lit.^29e 159–160 °C); IR (KBr) ν (cm⁻¹): 2923, 2162, 1729, 1614, 1433, 1375, 1276, 1241, 1081; ¹H NMR (400 MHz, CDCl₃) δ: 8.23 (s, 1H), 8.13 (d, J_H–H = 8.9 Hz, 1H), 7.05 (dd, J_H–H = 8.9 Hz, J_H–H = 2.4 Hz, 1H), 6.89 (d, J_F–H = 2.4 Hz, 1H), 3.93 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 172.2 (C=O), 165.0, 158.2, 154.5 (CH), 127.4 (CH), 116.3, 115.9 (CH), 112.7, 109.1, 100.5 (CH), 56.0 (CH₃); HR MS (ESI) m/z: calcd for C₁₁H₈NO₃S [M + H]⁺ 234.0219, found 234.0212.

7-Fluoro-3-thiocyanato-4H-chromen-4-one (5e)^29c. Colorless crystal, mp 120–121 °C; IR (KBr) ν (cm⁻¹): 1638, 1439, 1375, 1234, 1141; ¹H NMR (400 MHz, CDCl₃) δ: 8.31 (s, 1H), 8.30–8.26 (m, 1H), 7.28–7.22 (m, 2H); ¹³C NMR (100 MHz, CDCl₃) δ: 172.0 (C=O), 166.2 (d, J_F–C = 256.7 Hz), 157.3 (d, J_F–C = 13.2 Hz), 155.1 (CH), 128.8 (d, J_F–C = 10.8 Hz, CH), 119.5 (d, J_F–C = 2.3 Hz), 115.6 (d, J_F–C = 22.7 Hz, CH), 113.2, 108.6, 105.2 (d, J_F–C = 25.6 Hz, CH); ¹⁹F NMR (376 MHz, CDCl₃) δ: −99.5; HR MS (ESI) m/z: calcd for C₁₀H₅FNO₂S [M + H]⁺ 222.0020, found 222.0014.

7-Chloro-3-thiocyanato-4H-chromen-4-one (5f). Colorless crystal, mp 165–166 °C (lit.^29f 176–178 °C); IR (KBr) ν (cm⁻¹): 2158, 1634, 1607, 1423, 1347, 1163, 1066; ¹H NMR (400 MHz, CDCl₃) δ: 8.30 (s, 1H), 8.19 (d, J_H–H = 8.6 Hz, 1H), 7.52 (d, J_H–H = 1.8 Hz, 1H), 7.48 (d, J_H–H = 8.6 Hz, J_H–H = 1.8 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃) δ: 172.2 (C=O), 156.3 (CH), 155.0, 141.3 (CH), 127.5, 127.4 (CH), 121.1, 118.5 (CH), 113.3, 108.5; HR MS (ESI) m/z: calcd for C₁₀H₅ClNO₂S [M + H]⁺ 237.9724, found 237.9720.

6-Chloro-3-thiocyanato-4H-chromen-4-one (5g). Colorless crystal, mp 137–138 °C (lit.^29d 136–137 °C); IR (KBr) ν (cm⁻¹): 2160, 1647, 1605, 1556, 1462, 1301, 1093, 836; ¹H NMR (400 MHz, CDCl₃) δ: 8.33 (s, 1H), 8.20 (d, J_H–H = 2.5 Hz, 1H), 7.72 (d, J_H–H = 9.0 Hz, J_H–H = 2.5 Hz, 1H), 7.52 (d, J_H–H = 9.0 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃) δ: 171.9 (C=O), 155.3 (CH), 154.6, 135.2 (CH), 132.7, 125.4 (CH), 123.5, 120.1 (CH), 112.9, 108.5; HR MS (ESI) m/z: calcd for C₁₀H₅ClNO₂S [M + H]⁺ 237.9724, found 237.9720.

6-Bromo-3-thiocyanato-4H-chromen-4-one (5h). Light yellow crystal, mp 180–181 °C (lit.^29f 189–191 °C); IR (KBr) ν (cm⁻¹): 2919, 1648, 1458, 1377, 1299, 1019; ¹H NMR (400 MHz, DMSO-d₆) δ: 9.06 (s, 1H), 8.20 (d, J_H–H = 2.4 Hz, 1H), 8.07 (dd, J_H–H = 9.0 Hz, J_H–H = 2.4 Hz, 1H), 7.76 (d, J_H–H = 9.0 Hz, 1H); ¹³C NMR (100 MHz, DMSO-d₆) δ: 171.9 (C=O), 161.5, 155.3, 138.3, 127.8, 124.6, 121.9, 119.5, 110.9, 110.8; HR MS (ESI) m/z: calcd for C₁₀H₅BrNO₂S [M + H]⁺ 281.9219, found 281.9215.

6,8-Dichloro-3-thiocyanato-4H-chromen-4-one (5j). Colorless crystal, mp 123–124 °C; IR (KBr) ν (cm⁻¹): 2166, 1630, 1555, 1444, 1309, 1108, 876; ¹H NMR (400 MHz, CDCl₃) δ: 8.39 (s, 1H), 8.31 (d, J_H–H = 2.5 Hz, 1H), 7.82 (d, J_H–H = 2.5 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃) δ: 171.4 (C=O), 154.7 (CH), 150.7, 135.1 (CH), 132.5, 124.9, 124.2, 124.1 (CH), 113.8, 108.0; HR MS (ESI) m/z: calcd for C₁₀H₄Cl₂NO₂S [M + H]⁺ 271.9334, found 271.9330.

6,8-Dibromo-3-thiocyanato-4H-chromen-4-one (5k). Colorless crystal, mp 139–140 °C; IR (KBr) ν (cm⁻¹): 2163, 1630, 1589, 1541, 1449, 1431, 1305, 1092, 775; ¹H NMR (400 MHz, CDCl₃) δ: 8.41 (s, 1H), 8.31 (d, J_H–H = 2.2 Hz, 1H), 8.13 (d, J_H–H = 2.2 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃) δ: 171.3 (C=O), 154.9 (CH), 152.0, 140.8 (CH), 127.9 (CH), 124.4, 120.1, 113.6, 113.2, 108.0; HR MS (ESI) m/z: calcd for C₁₀H₄Br₂NO₂S [M + H]⁺ 359.8324, found 359.8317.

Synthesis of 3-((trifluoromethyl)thio)-4H-chromen-4-one (6a). A mixture of 3-thiocyanato-4H-chromen-4-one 5a (0.3 mmol, 60.9 mg), trimethyl(trifluoromethyl)silane (TMSCF₃, 0.45 mmol, 63.9 mg), CuCl₂ (0.06 mmol, 8.0 mg), Cs₂CO₃ (0.3 mmol, 97.8 mg) and DMF (5.0 mL) was added to a 25 mL reaction tube. The mixture was stirred at room temperature. After completion of the reaction, the solvent was distilled under vacuum. Then, the resulting mixture was dissolved with ethyl acetate (20 mL), washed with saturated sodium chloride solution (10 mL × 2). The organic phase was dried over anhydrous Na₂SO₄ and concentrated under vacuum. The residue was purified by silica gel column chromatography to give 3-((trifluoromethyl)thio)-4H-chromen-4-one 6a using ethyl acetate/petroleum ether as eluant.

Colorless crystal, mp 120–121 °C (lit.³¹ 122–123 °C); ¹H NMR (400 MHz, CDCl₃) δ: 8.39 (s, 1H), 8.29 (dd, J_H–H = 7.8 Hz, J_H–H = 1.3 Hz, 1H), 7.77–7.73 (m, 1H), 7.52–7.48 (m, 2H); ¹³C NMR (100 MHz, CDCl₃) δ: 174.3 (C=O), 162.3, 156.2, 134.6, 138.9 (q, J_F–C = 306.2 Hz), 126.7, 126.5, 123.9, 118.2, 111.3; ¹⁹F NMR (376 MHz, CDCl₃) δ: −42.8; HR MS (ESI) m/z: calcd for C₁₀H₆F₃O₂S [M + H]⁺ 247.0035, found 247.0036.

Conflicts of interest

There are no conflicts to declare.

Acknowledgements

This work was supported by the Fundamental Research Funds for the Henan Provincial Colleges and Universities in Henan University of Technology (No. 2017RCJH08).

Notes and references

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Footnote

† Electronic supplementary information (ESI) available. See DOI: https://doi.org/10.1039/d3ra05246j

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