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Abstract

A fast and efficient Selectfluor-triggered fluorination/cyclization reaction of o-hydroxyarylenaminones has been successfully developed. The reaction successfully provides an expedient method for the synthesis of 3-fluoro-chromones promoted by potassium carbonate, which shows readily available starting materials and is easy to operate. In addition, a plausible mechanism of this tandem cyclization reaction was proposed where 4H-chromen-4-one, 2-(dimethylamino)-3,3-difluorochroman-4-one, and 3,3-difluoro-2-hydroxychroman-4-one were not found to be the reactive intermediates. Moreover, these novel compounds have been obtained in moderate to good yields, and their structures have been confirmed by 1H NMR, 13C NMR, and high-resolution mass spectrometry.

Keywords

3-fluoro-chromones Selectfluor fluorination/cyclization

A direct fluorination/cyclization of o-hydroxyarylenaminones by Selectfluor-triggered has been successfully developed. The reaction successfully provides an expedient method for the synthesis of 3-fluoro-chromones promoted by potassium carbonate under mild reaction conditions, which shows readily available starting materials and operational simplicity. In addition, 4H-chromen-4-ones; 2-(dimethylamino)-3,3-difluorochroman-4-ones; and 3,3-difluoro-2-hydroxychroman-4-ones were not to be intermediates in this strategy. Accordingly, a plausible reaction mechanism was proposed. Moreover, these novel compounds have been obtained in moderate to good yields, and their structures have been confirmed by 1H NMR, 13C NMR, infrared spectroscopy, and high-resolution mass spectrometry.

Fluorinated organic compounds have attracted great attention in the field of medicinal chemistry owing to their unique physical and chemical properties, bioavailability, lipophilicity, and metabolic stability.^1–4 This is especially true in the pharmaceuticals and agrochemicals, where fluorine is often considered a bioisostere of hydrogen. At present, about 30% of all agrochemicals (such as pyroxsulam and fluxapyroxad and so on) and 20% of all pharmaceuticals (such as 5-fluorouracil and norfloxacin and so on) incorporate at least one fluorine atom.⁵ As such, many efforts have been put into the development of fluorinated molecules based on the C–F bond formation in the past decade.^6–10

Chromones and their derivatives are found in numerous natural products and pharmaceuticals^11–13 that show many biological activities, such as monoamine oxidase inhibitors and antitubercular activity.^14–18 They also exist widely in pigments, dyes, and essential nutrients for the human body.^19–22 Consequently, the development of effective methods to construct these heterocyclic scaffolds, especially C3-functionalized analogs, has been studied extensively.^23–31

Furthermore, enaminones have been recognized as a class of available and powerful synthetic building blocks owing to their versatile reactivity in a variety of organic transformations,^32–38 which were widely used in syntheses of many heterocyclic^39–47 and fused heterocyclic compounds.^48–56 Recently, many efforts have been devoted to develop new methods for the synthesis of 3-functionalized chromones from o-hydroxyarylenaminones via the electrophile-triggered cyclization reaction (Scheme 1(a)).^{29,30,57–66} As far as the reactions of enaminones with fluorination reagents are concerned, a difluorination of enaminones to access difluorinated carbonyl compounds by virtue of Selectfluor (1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate), cheap and easily available) as the fluorine source was reported by Shreeve’s group in 2005.⁶⁷ In 1996, Bolós’s group⁶⁸ synthesized 3-fluoro-chromones from o-hydroxyarylenaminones by using 1-fluoro-2,4,6-trimethylpyridinium triflate (NFTP) as the fluorine source, but it still suffers from more expensive fluorination reagent and substrate scope. Therefore, the development of an efficient method using Selectfluor as a fluorine source would be valuable. In 2017, the groups of Zhao⁶⁹ and Xu⁷⁰ developed a Selectfluor-triggered tandem cyclization of o-hydroxyarylenaminones to obtain 3,3-difluorinated 2-amino-substituted chromanones, respectively (Scheme 1(b)). In addition, the groups of Kandula⁷¹ and Zhao⁷² also reported a Selectfluor-triggered tandem cyclization strategy for constructing 3-fluoro-chromones via direct elimination of 3,3-difluorinated 2-amino chromanones at room temperature in a short time ago. As our ongoing interest in enaminone chemistry,^73–82 herein, we report a fast and efficient Selectfluor-triggered fluorination/cyclization reaction of o-hydroxyarylenaminones for the construction of 3-fluoro-chromones promoted by potassium carbonate (Scheme 1(c)). Interestingly, this reaction is mechanistically different compared to the previously reported methods^71,72 where 2-(dimethylamino)-3,3-difluorochroman-4-one.

Scheme 1.

Reaction of enaminones with Selectfluor for the synthesis of 3-fluoro-chromones.

Results and discussion

Initially, o-hydroxyarylenaminone (1a) and Selectfluor (2) were used as model substrates to optimize the fluorination/cyclization reaction. The reaction was carried out in the absence of a catalyst in MeCN at room temperature for 0.5 h, giving the desired product 3a in 35% yield (Table 1, entry 1). Encouraged by this result, different solvents were probed, but lower yields or no formation of 3a were observed (entry 1 vs entries 2–7). To improve the yield of the reaction in MeCN, several additives, oxidants, acids, and bases were systematically investigated as shown in Table 1, entries 8 to 17. We determined that 3a was obtained in slightly higher yields when K₂CO₃ was used as an additive (entry 14 vs entries 8–13). Improving the reaction temperature led to evident improvement in the yield of 3a, with 100°C found to be optimal (entry 16 vs entries 14–15, and 17).

Table 1.

Screening of the reaction conditions.^a


Entry	Additive (equiv.)	Solvent	T (°C)	Yield (%)^b
1	–	MeCN	R.T	35
2	–	1,4-Dioxane	R.T	22
3	–	DCM	R.T	23
4	–	EtOH	R.T	18
5	–	Water	R.T	24
6	–	DMF	R.T	20
7	–	DMSO	R.T	n.d.^c
8	K₂S₂O₈ (1.0)	MeCN	R.T	27
9	DTBP (1.0)	MeCN	R.T	26
10	AgNO₃ (1.0)	MeCN	R.T	24
11	p-TSA(1.0)	MeCN	R.T	25
12	Et₃N (1.0)	MeCN	R.T	26
13	KOH (1.0)	MeCN	R.T	37
14	K₂CO₃ (1.0)	MeCN	R.T	40
15	K₂CO₃ (1.0)	MeCN	60	48
16	K₂CO₃ (1.0)	MeCN	100	60
17	K₂CO₃ (1.0)	MeCN	120	52

DCM: dichloromethane; DMF: dimethylformamide; DMSO: dimethyl sulfoxide; R.T.: room temperature.

Reaction conditions: 1a (0.5 mmol), 2 (1.1 mmol) in 2-mL solvent for 0.5 h.

Isolated yields.

Not detected.

Under the optimized conditions, the substrate scope of this reaction was then investigated with a range of accessible o-hydroxyarylenaminones 1 (Table 2). Various single-substituted aryl o-hydroxyarylenaminones, including 5-substituted aryl (R = OMe, Me, F, Cl, Br, and NO₂), 4-substituted aryl (R = OMe, Me, F, Cl, and Br), and 3-F aryl, smoothly underwent the fluorination/cyclization reaction, providing the resulting 3-fluoro-chromones (3a–3m) in moderate yields (35%–60%). Furthermore, o-hydroxyarylenaminones 1n–1r with multisubstituents were compatible with the transformation as well, leading to the corresponding products 3n–3r in 42–48 yields.

Table 2.

Substrate scopes.^{a, b}


Entry	R	3	Yield (%)	Entry	R	3	Yield (%)
1	6-H (1a)	3a	60	10	7-F (1j)	3j	49
2	6-OMe (1b)	3b	53	11	7-Cl (1k)	3k	49
3	6-Me (1c)	3c	57	12	7-Br (1l)	3l	38
4	6-F (1d)	3d	40	13	8-F (1m)	3m	35
5	6-Cl (1e)	3e	45	14	6-Me, 8-Me (1n)	3n	48
6	6-Br (1f)	3f	42	15	6-Cl, 8-Me (1o)	3o	46
7	6-NO₂ (1g)	3g	45	16	6-Me, 8-NO₂ (1p)	3p	44
8	7-OMe (1h)	3h	51	17	6-Cl, 8-Cl (1q)	3q	45
9	7-Me (1i)	3i	53	18	6-Cl, 8-Br (1r)	3r	42

Reaction conditions: 1 (0.5 mmol), 2 (1.1 mmol), and K₂CO₃ (1.0 equiv.) in 2 mL of MeCN, stirred at 100 °C for 0.5 h.

Isolated yields.

To gain insight into the mechanistic details of this fluorination/cyclization reaction, several control experiments were performed (Scheme 2). First, when the reaction of 4H-chromen-4-one 4 with Selectfluor 2 was performed under standard conditions, the expected product 3a was not observed at all (Scheme 2(a)). We isolated traces of 2-(dimethylamino)-3,3-difluorochroman-4-one 5 and 3,3-difluoro-2-hydroxychroman-4-one 6 at low temperatures during the conditions optimizing studies. When 5 and 6 were separately subjected to the standard reaction condition, the desired product 3a was not obtained (Scheme 2(b) and 2(c)). Interestingly, compound 5 was converted to compound 6 in 86% yield (Scheme 2(d)). Hence, compounds 4, 5, and 6 are unlikely the reactive intermediates during the fluorination/cyclization process.

Scheme 2.

Control experiments.

Based on the above observations and previous reports, a plausible mechanism for the synthesis of 3-fluoro-chromones 3 was shown in Scheme 3. Initially, o-hydroxyarylenaminone formed species 7 via imine–enamine tautomerization, which rapidly quenched with Selectfluor to deliver species 8. Then, the intermediate 9 could be generated through keto–enol tautomerization, which sequentially produced the cyclic species 10 and released a molecule of HBF₄. The subsequent deamination ultimately generated the desired 3-fluoro-chromone 3a.

Scheme 3.

Proposed mechanism.

Conclusion

In conclusion, we successfully developed a facile and general approach accessing a range of 3-fluoro-chromones from o-hydroxyarylenaminones. Importantly, several species, such as 4H-chromen-4-ones; 2-(dimethylamino)-3,3-difluorochroman-4-ones; and 3,3-difluoro-2-hydroxychroman-4-ones, are proved not to be the reactive intermediates during the reaction process. This transformation involves the Selectfluor-triggered fluorination of the enaminone moiety, followed by subsequent intramolecular cyclization and deamination.

Experimental

All compounds were fully characterized by spectroscopic data. The nuclear magnetic resonance (NMR) spectra were recorded on a DRX600 spectrometer (1H: 600 MHz, 13C: 150 MHz), chemical shifts (δ) are expressed in ppm, and J values are given in Hz, and deuterated CDCl₃ was used as solvent. The reactions were monitored by thin-layer chromatography (TLC) using silica gel GF254. The melting points were determined on XT-4A melting point apparatus and are uncorrected. High-resolution mass spectrometry (HRMS) was performed on an Agilent liquid chromatography–mass spectrometry (LC/MS) time-of-flight (TOF) instrument.

All chemicals and solvents were used as received without further purification unless otherwise stated. Column chromatography was performed on silica gel (200–300 mesh).

Compounds 1a–1r were prepared according to the literature.^83,84 Selectfluor was purchased from Adamas-beta and Aldrich Corporation Limited.

General procedure for the synthesis of 3-fluoro-chromones 3a–3r

0.5-mmol-substituted o-hydroxyarylenaminones 1, 1.1-mmol Selectfluor 2 (389.4 mg), 0.5-mmol K₂CO₃ (69 mg), and 2.0-mL MeCN were charged into a 10-mL Ace Glass pressure tubes, and the mixture was stirred at 100 °C for 0.5 h until 1 was completely consumed. The mixture was cooled to room temperature. Quenched with water (15 mL), and then EtOAc (15 mL × 3) was added. The organic phase was washed with water (10 mL), dried over Na₂SO₄, concentrated, and purified by flash column chromatography to afford 3-fluoro-chromones 3.

3-Fluoro-4H-chromen-4-one (3a): Yield: 60%; white solid; m.p. 163–165 °C; 1H NMR (600 MHz, CDCl₃): δ 8.32 (dd, J = 8.0, 1.3 Hz, 1H, C=CH), 8.18 (d, J = 3.4 Hz, 1H, ArH), 7.75–7.73 (m, 1H, ArH), 7.54 (d, J = 8.5 Hz, 1H, ArH), 7.47 (t, J = 7.6 Hz, 1H, ArH); 13C NMR (150 MHz, CDCl₃): δ 170.6 (d, J = 15.5 Hz, C=O), 155.8 (C9), 149.4 (d, J = 249.2 Hz, C2), 142.9 (d, J = 40.0 Hz, C1), 134.1 (C7), 126.0 (d, J = 3.4 Hz, C5), 125.3 (C6), 124.8 (d, J = 7.7 Hz, C4), 118.4 (C8); HRMS (TOF ES⁺): m/z calcd for C₉H₆FO₂⁺ [(M + H)⁺], 165.0346; found, 165.0348.

3-Fluoro-6-methoxy-4H-chromen-4-one (3b): Yield: 53%; white solid; m.p. 174–176 °C; 1H NMR (600 MHz, CDCl₃): δ 8.03 (d, J = 2.6 Hz, 1H, C=CH), 7.60 (t, J = 8.4 Hz, 1H, ArH), 7.06 (dd, J = 8.5, 0.7 Hz, 1H, ArH), 6.84 (d, J = 8.3 Hz, 1H, ArH), 4.00 (s, 3H, ArOCH₃); 13C NMR (150 MHz, CDCl₃): δ 170.3 (d, J = 16.5 Hz, C=O), 160.4 (d, J = 2.8 Hz, C6), 157.9 (C9), 149.6 (d, J = 245.7 Hz, C2), 140.7 (d, J = 40.5 Hz, C1), 138.5 (C4), 134.3 (C5), 110.3 (C7), 106.2 (C8), 56.5 (OCH₃). HRMS (TOF ES⁺): m/z calcd for C₁₀H₈FO₃⁺ [(M + H)⁺], 195.0452; found, 195.0452.

3-Fluoro-6-methyl-4H-chromen-4-one (3c): Yield: 57%; white solid; m.p. 83–85 °C; 1H NMR (600 MHz, CDCl₃): δ 8.16 (d, J = 3.4 Hz, 1H, C=CH), 8.10 (d, J = 1.0 Hz, 1H, ArH), 7.54 (dd, J = 8.6, 2.2 Hz, 1H, ArH), 7.43 (d, J = 8.6 Hz, 1H, ArH), 2.49 (s, 3H, ArCH₃); 13C NMR (150 MHz, CDCl₃): δ 170.6 (d, J = 15.3 Hz, C=O), 154.2 (C9), 149.3 (d, J = 248.2 Hz, C2), 142.8 (d, J = 40.0 Hz, C1), 135.5 (C7), 125.2 (d, J = 3.5 Hz, C5), 124.5 (d, J = 7.7 Hz, C4), 118.1 (C8), 20.9 (CH₃). HRMS (TOF ES⁺): m/z calcd for C₁₀H₈FO₂⁺ [(M + H)⁺], 179.0503; found, 179.0504.

3,6-Difluoro-4H-chromen-4-one (3d): Yield: 40%; white solid; m.p. 149–151 °C; 1H NMR (600 MHz, CDCl₃): δ 8.20 (d, J = 3.3 Hz, 1H, C=CH), 7.96 (dd, J = 8.1, 3.1 Hz, 1H, ArH), 7.56 (dd, J = 9.2, 4.1 Hz, 1H, ArH), 7.49–7.46 (m, 1H, ArH); 13C NMR (150 MHz, CDCl₃): δ 169.7 (d, J = 15.9 Hz, C=O), 159.5 (d, J = 248.6 Hz, C6), 152.09 (C9), 149.0 (d, J = 249.2 Hz, C2), 143.2 (d, J = 40.0 Hz, C1), 126.1 (t, J = 8.1 Hz, C4), 122.6 (d, J = 25.7 Hz, C7), 120.6 (d, J = 8.3 Hz, C8), 110.9 (dd, J = 24.2, 3.8 Hz, C5). HRMS (TOF ES⁺): m/z calcd for C₉H₅F₂O₂⁺ [(M + H)⁺], 183.0252; found, 183.0254.

6-Chloro-3-fluoro-4H-chromen-4-one (3e): Yield: 45%; light yellow solid; m.p. 135–137 °C; 1H NMR (600 MHz, CDCl₃): δ 8.27 (dd, J = 2.4, 1.0 Hz, 1H, C=CH), 8.19 (dd, J = 3.3, 1.2 Hz, 1H, ArH), 7.69–7.66 (m, 1H, ArH), 7.50 (dd, J = 9.0, 0.9 Hz, 1H, ArH); 13C NMR (150 MHz, CDCl₃): δ 169.4 (d, J = 16.0 Hz, C=O), 154.1 (C9), 149.3 (d, J = 250.2 Hz, C2), 143.2 (d, J = 40.1 Hz, C1), 134.4 (C7), 131.6 (C6), 125.8 (d, J = 8.2 Hz, C4), 125.3 (d, J = 3.6 Hz, C5), 120.1 (C8). HRMS (TOF ES⁺): m/z calcd for C₉H₅ClFO₂⁺ [(M + H)⁺], 198.9957; found, 198.9957.

6-Bromo-3-fluoro-4H-chromen-4-one (3f): Yield: 42%; white solid; m.p. 179–181 °C; 1H NMR (600 MHz, CDCl₃): δ 8.45 (d, J = 2.4 Hz, 1H, ArH), 8.19 (d, J = 3.3 Hz, 1H, C=CH), 7.82 (dd, J = 8.9, 2.5 Hz, 1H, ArH), 7.44 (d, J = 8.9 Hz, 1H, ArH); 13C NMR (150 MHz, CDCl₃): δ 169.3 (d, J = 16.0 Hz, C=O), 154.6 (C9), 149.3 (d, J = 250.5 Hz, C2), 143.2 (d, J = 40.1 Hz, C1), 137.2 (C7), 128.6 (d, J = 3.4 Hz, C5), 126.2 (d, J = 8.1 Hz, C4), 120.3 (C8), 119.0 (C6). HRMS (TOF ES⁺): m/z calcd for C₉H₅BrFO₂⁺ [(M + H)⁺], 242.9451; found, 242.9451.

3-Fluoro-6-nitro-4H-chromen-4-one (3g): Yield: 45%; yellow solid; m.p. 114–116 °C; 1H NMR (600 MHz, CDCl₃): δ 9.21 (d, J = 2.7 Hz, 1H, ArH), 8.57 (dd, J = 9.2, 2.7 Hz, 1H, ArH), 8.26 (d, J = 3.1 Hz, 1H, C=CH), 7.72 (d, J = 9.2 Hz, 1H, ArH); 13C NMR (150 MHz, CDCl₃): δ 169.3 (C=O), 158.4 (C9), 149.5 (d, J = 253.8 Hz, C2), 144.8 (C6), 143.5 (d, J = 40.3 Hz, C1), 128.4 (C7), 125.0 (C4), 122.9 (d, J = 3.3 Hz, C5), 120.3 (C8). HRMS (TOF ES⁺): m/z calcd for C₉H₅FNO₄⁺ [(M + H)⁺], 210.0197; found, 210.0196.

3-Fluoro-7-methoxy-4H-chromen-4-one (3h): Yield: 51%; white solid; m.p. 138–140 °C; 1H NMR (600 MHz, CDCl₃): δ 8.20 (d, J = 9.0 Hz, 1H, ArH), 8.10 (d, J = 3.3 Hz, 1H, C=CH), 7.03 (dd, J = 9.0, 2.3 Hz, 1H, ArH), 6.88 (d, J = 2.3 Hz, 1H, ArH), 3.93 (s, 3H, ArOCH₃); 13C NMR (150 MHz, CDCl₃): δ 170.0 (d, J = 15.9 Hz, C=O), 164.4 (C7), 157.7 (C9), 149.4 (d, J = 248.7 Hz, C2), 142.4 (d, J = 40.5 Hz, C1), 127.3 (d, J = 3.5 Hz, C5), 118.6 (d, J = 7.4 Hz, C4), 115.0 (C6), 100.3 (C8), 56.0 (OCH₃). HRMS (TOF ES⁺): m/z calcd for C₁₀H₈FO₃⁺ [(M + H)⁺], 195.0452; found, 195.0452.

3-Fluoro-7-methyl-4H-chromen-4-one (3i): Yield: 53%; white solid; m.p. 137–139 °C; 1H NMR (600 MHz, CDCl₃): δ 8.19 (d, J = 8.2 Hz, 1H, ArH), 8.13 (d, J = 3.4 Hz, 1H, C=CH), 7.31 (s, 1H, ArH), 7.28 (d, J = 4.0 Hz, 1H, ArH), 2.52 (s, 3H, ArCH₃); 13C NMR (150 MHz, CDCl₃): δ 170.5 (d, J = 15.6 Hz, C=O), 156.0 (C9), 149.3 (d, J = 248.7 Hz, C2), 145.7 (C2), 142.6 (d, J = 40.0 Hz, C8), 126.9 (C1), 125.7 (d, J = 3.3 Hz, C6), 122.6 (d, J = 7.5 Hz, C5), 118.0 (C3), 21.8 (C13). HRMS (TOF ES⁺): m/z calcd for C₁₀H₈FO₂⁺ [(M + H)⁺], 179.0503; found, 179.0503.

3,7-Difluoro-4H-chromen-4-one (3j): Yield: 49%; white solid; m.p. 113–115 °C; 1H NMR (600 MHz, CDCl₃): δ 8.35–8.33 (m, 1H, ArH), 8.17 (d, J = 3.2 Hz, 1H, C=CH), 7.23–7.20 (m, 2H, ArH); 13C NMR (150 MHz, CDCl₃): δ 169.7 (d, J = 16.1 Hz, C=O), 165.8 (d, J = 256.6 Hz, C7), 156.8 (d, J = 13.5 Hz, C9), 149.4 (d, J = 250.4 Hz, C2), 143.1 (dd, J = 40.5, 1.4 Hz, C1), 128.6 (dd, J = 10.7, 3.5 Hz, C5), 121.7 (d, J = 7.8 Hz, C4), 114.5 (d, J = 23.1 Hz, C6), 105.1 (d, J = 25.6 Hz, C8). HRMS (TOF ES⁺): m/z calcd for C₉H₅F₂O₂⁺ [(M + H)⁺], 183.0252; found, 183.0250.

7-Chloro-3-fluoro-4H-chromen-4-one (3k): Yield: 49%; yellow solid; m.p. 136–138 °C; 1H NMR (600 MHz, CDCl₃): δ 8.25 (d, J = 8.6 Hz, 1H, ArH), 8.16 (d, J = 3.3 Hz, 1H, C=CH), 7.56 (d, J = 1.8 Hz, 1H, ArH), 7.44 (dd, J = 8.6, 1.7 Hz, 1H, ArH); 13C NMR (150 MHz, CDCl₃): δ 169.8 (d, J = 16.0 Hz, C=O), 155.8 (C9), 149.4 (d, J = 250.6 Hz, C2), 143.0 (d, J = 40.3 Hz, C1), 140.5 (C7), 127.4 (d, J = 3.4 Hz, C5), 126.3 (C6), 123.4 (d, J = 8.0 Hz, C4), 118.4 (C8). HRMS (TOF ES⁺): m/z calcd for C₉H₅ClFO₂⁺ [(M + H)⁺], 198.9957; found, 198.9958.

7-Bromo-3-fluoro-4H-chromen-4-one (3l): Yield: 38%; white solid; m.p. 168–170 °C; 1H NMR (600 MHz, CDCl₃): δ 8.16 (m, 1H, ArH and C=CH), 7.74 (d, J = 1.0 Hz, 1H, ArH), 7.59 (d, J = 8.6 Hz, 1H, ArH); 13C NMR (150 MHz, CDCl₃): δ 169.9 (d, J = 16.0 Hz, C=O), 155.8 (C9), 149.4 (d, J = 250.8 Hz, C2), 143.0 (d, J = 40.3 Hz, C1), 129.1 (C6), 128.6 (C7), 127.4 (d, J = 3.4 Hz, C5), 123.7 (d, J = 8.0 Hz, C4), 121.5 (C8). HRMS (TOF ES⁺): m/z calcd for C₉H₅BrFO₂⁺ [(M + H)⁺], 242.9451; found, 242.9452.

3,8-Difluoro-4H-chromen-4-one (3m): Yield: 35%; white solid; m.p. 156–158 °C; 1H NMR (600 MHz, CDCl₃): δ 8.24 (d, J = 3.2 Hz, 1H, C=CH), 8.09–8.07 (m, 1H, ArH), 7.73–7.49 (m, 1H, ArH), 7.43–7.39 (m, 1H, ArH); 13C NMR (150 MHz, CDCl₃): δ 169.7 (dd, J = 16.0, 2.6 Hz, C=O), 151.3 (d, J = 254.5 Hz, C8), 149.5 (d, J = 250.9 Hz, C2), 144.7 (d, J = 10.9 Hz, C9), 142.8 (d, J = 40.8 Hz, C1), 126.8 (d, J = 7.8 Hz, C4), 125.3 (d, J = 6.6 Hz, C5), 121.1 (t, J = 4.0 Hz, C6), 119.8 (d, J = 16.5 Hz, C7). HRMS (TOF ES⁺): m/z calcd for C₉H₅F₂O₂⁺ [(M + H)⁺], 183.0252; found, 183.0247.

3-Fluoro-6,8-dimethyl-4H-chromen-4-one (3n): Yield: 48%; light yellow solid; m.p. 77–79 °C; 1H NMR (600 MHz, CDCl₃): δ 8.19 (d, J = 3.3 Hz, 1H, C=CH), 7.92 (s, 1H, ArH), 7.38 (s, 1H, ArH), 2.47 (s, 3H, ArCH₃), 2.43 (s, 3H, ArCH₃); 13C NMR (150 MHz, CDCl₃): δ 170.8 (d, J = 15.1 Hz, C=O), 152.8 (C9), 149.3 (d, J = 247.8 Hz, C2), 142.6 (d, J = 39.8 Hz, C1), 136.4 (C7), 135.0 (C6), 127.6 (C8), 124.5 (d, J = 7.6 Hz, C4), 122.8 (d, J = 3.4 Hz, C5), 20.9 (CH₃), 15.5 (CH₃). HRMS (TOF ES⁺): m/z calcd for C₁₁H₁₀FO₂⁺ [(M + H)⁺], 193.0659; found, 193.0659.

6-Chloro-3-fluoro-7-methyl-4H-chromen-4-one (3o): Yield: 46%; white solid; m.p. 128–130 °C; 1H NMR (600 MHz, CDCl₃): δ 7.81 (s, 1H, ArH), 6.89 (s, 1H, ArH), 5.66 (s, 1H, ArH), 2.35 (s, 3H, ArCH₃); 13C NMR (150 MHz, CDCl₃): δ 179.4 (C=O), 155.2 (C9), 147.8 (C8), 129.7 (C6), 127.3 (C7), 120.9 (C5), 117.9 (C4), 107.3 (dd, J = 261.5, 249.1 Hz, C2), 94.3 (dd, J = 35.2, 28.1 Hz, C1), 21.2 (CH₃). HRMS (TOF ES⁺): m/z calcd for C₁₀H₇ClFO₂⁺ [(M + H)⁺], 213.0113; found, 213.0116.

3-Fluoro-6-methyl-8-nitro-4H-chromen-4-one (3p): Yield: 44%; light yellow solid; m.p. 160–162 °C; 1H NMR (600 MHz, CDCl₃): δ 8.39 (s, 1H, ArH), 8.27 (d, J = 2.9 Hz, 1H, C=CH), 8.23 (s, 1H, ArH), 2.59 (s, 3H, ArCH₃); 13C NMR (150 MHz, CDCl₃): δ 168.9 (d, J = 16.3 Hz, C=O), 150.2 (C9), 147.4 (d, J = 249.8 Hz, C2), 143.2 (d, J = 40.4 Hz, C1), 138.7 (C8), 135.7 (C6), 131.4 (d, J = 2.9 Hz, C5), 131.3 (C7), 126.5 (d, J = 8.2 Hz, C4), 20.8 (CH₃). HRMS (TOF ES⁺): m/z calcd for C₁₀H₇FNO₄⁺ [(M + H)⁺], 224.0354; found, 224.0354.

6,8-Dichloro-3-fluoro-4H-chromen-4-one (3q): Yield: 45%; light yellow solid; m.p. 108–110 °C; 1H NMR (600 MHz, CDCl₃): δ 8.27 (d, J = 3.0 Hz, 1H, C=CH), 8.23–8.14 (m, 1H, ArH), 7.79 (dd, J = 3.7, 2.5 Hz, 1H, ArH); 13C NMR (150 MHz, CDCl₃): δ 168.8 (d, J = 16.4 Hz, C=O), 150.2 (C9), 149.3 (d, J = 241.5 Hz, C2), 143.3 (d, J = 40.5 Hz, C1), 134.4 (C7), 131.4 (C6), 126.7 (d, J = 8.3 Hz, C4), 124.8 (C5), 124.1 (C8). HRMS (TOF ES⁺): m/z calcd for C₉H₄Cl₂FO₂⁺ [(M + H)⁺], 232.9567; found, 232.9571.

8-Bromo-6-chloro-3-fluoro-4H-chromen-4-one (3r): Yield: 42%; light brown solid; m.p. 102–104 °C; 1H NMR (600 MHz, CDCl₃): δ 8.27 (d, J = 3.0 Hz, 1H, C=CH), 8.25 (d, J = 2.4 Hz, 1H, ArH), 7.96 (d, J = 2.4 Hz, 1H, ArH); 13C NMR (150 MHz, CDCl₃): δ 168.8 (d, J = 16.3 Hz, C=O), 151.0 (C9), 149.2 (d, J = 252.2 Hz, C2), 143.4 (d, J = 40.4 Hz, C1), 137.4 (C7), 131.8 (C6), 126.5 (d, J = 8.3 Hz, C4), 124.9 (d, J = 3.3 Hz, C5), 113.1 (C8). HRMS (TOF ES⁺): m/z calcd for C₉H₄BrClFO₂⁺ [(M + H)⁺], 276.9062; found, 276.9063.

2-(Dimethylamino)-3,3-difluorochroman-4-one (5): Yield: 13%; white solid; m.p. 220–222 °C; 1H NMR (600 MHz, CDCl₃): δ 7.85 (d, J = 7.9 Hz, 1H, ArH), 7.54 (d, J = 7.7 Hz, 1H, Ar6H), 7.11–6.96 (m, 2H, ArH), 4.91 (dd, J = 20.7, 2.6 Hz, 1H, O-CH), 2.62 (s, 6H, 2NCH₃); 13C NMR (150 MHz, CDCl₃): δ 181.68 (d, J = 25.3 Hz, C=O), 160.8 (C9), 137.8 (C7), 128.2 (C5), 122.5 (C6), 118.5 (C8), 111.1 (C4), 108.1 (d, J = 256.2, C2), 93.84 (dd, J = 26.6, 20.9 Hz, C1), 41.1 (NCH₃). HRMS (TOF ES⁺): m/z calcd for C₁₁H₁₂F₂NO₂⁺ [(M + H)⁺], 228.0831; found, 228.0834.

3,3-Difluoro-2-hydroxychroman-4-one (6): Yield: 32%; colorless oil; m.p. 220–222 °C; 1H NMR (600 MHz, CDCl₃): δ 7.84 (d, J = 7.9 Hz, 1H, ArH), 7.59–7.48 (m, 1H, ArH), 7.08 (t, J = 7.5 Hz, 1H, ArH), 6.97 (d, J = 8.4 Hz, 1H, ArH), 5.69 (t, J = 4.0 Hz, 1H, C=CH), 4.81 (d, J = 56.6 Hz, 1H, O-CH); 13C NMR (150 MHz, CDCl₃): δ 181.2 (C=O), 157.1 (C9), 138.3 (C7), 127.8 (C5), 123.3 (C6), 118.9 (C8), 109.2 (C4), 105.8 (d, J = 248.9 Hz, C2), 94.2 (dd, J = 35.0, 28.0 Hz, C1). HRMS (TOF ES⁺): m/z calcd for C₉H₇F₂O₃⁺ [(M + H)⁺], 201.0358; found, 201.0360.

Supplemental Material

Revised_Supporting_Information_Yu_Fuchao – Supplemental material for Selectfluor-triggered fluorination/cyclization of o-hydroxyarylenaminones: A facile access to 3-fluoro-chromones

Supplemental material, Revised_Supporting_Information_Yu_Fuchao for Selectfluor-triggered fluorination/cyclization of o-hydroxyarylenaminones: A facile access to 3-fluoro-chromones by Yanqin Wang, Biao Hu, Qiaohe Zhang, Siyun Zhao, Yuxuan Zhao, Biao Zhang and Fuchao Yu in Journal of Chemical Research

Footnotes

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The study received financial support from the National Natural Science Foundation of China (21402070 and 21961018) and the Analytical & Testing Foundation of Kunming University of Science and Technology (2017T20130137).

ORCID iD

Fuchao Yu

Supplemental material

Supplemental material for this article is available online.

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Supplementary Material

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Selectfluor-triggered fluorination/cyclization of o -hydroxyarylenaminones: A facile access to 3-fluoro-chromones

Abstract

Keywords

Results and discussion

Conclusion

Experimental

General procedure for the synthesis of 3-fluoro-chromones 3a–3r

Supplemental Material

Revised_Supporting_Information_Yu_Fuchao – Supplemental material for Selectfluor-triggered fluorination/cyclization of o-hydroxyarylenaminones: A facile access to 3-fluoro-chromones

Footnotes

Declaration of conflicting interests

Funding

ORCID iD

Supplemental material

References

Supplementary Material