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Article

Radical-Induced Cascade Annulation/Hydrocarbonylation for Construction of 2-Aryl-4H-chromen-4-ones

by
Xinwei He
*,
Keke Xu
,
Yanan Liu
,
Demao Wang
,
Qiang Tang
,
Wenjie Hui
,
Haoyu Chen
and
Yongjia Shang
Key Laboratory of Functional Molecular Solids, Ministry of Education, Anhui Laboratory of Molecule-Based Materials (State Key Laboratory Cultivation Base), College of Chemistry and Materials Science, Anhui Normal University, Wuhu 241000, China
*
Author to whom correspondence should be addressed.
Molecules 2022, 27(21), 7412; https://doi.org/10.3390/molecules27217412
Submission received: 8 October 2022 / Revised: 22 October 2022 / Accepted: 26 October 2022 / Published: 1 November 2022
(This article belongs to the Special Issue New Insights in Organic Radicals)
Browse Figures
Versions Notes

Abstract

:
A robust metal- and solvent-free cascade radical-induced C-N cleavage/intramolecular 6-endo-dig annulation/hydrocarbonylation for the synthesis of the valuable 2-aryl-4H-chromen-4-ones is described. This practical synthesis strategy utilizes propargylamines and air as the oxygen source and green carbonylation reagent, in which propargylamines are activated by the inexpensive and available dimethyl 2,2′-azobis(2-methylpropionate) (AIBME) and (PhSe)2 as the radical initiators. This simple and green protocol features wide substrate adaptability, good functional group tolerance, and amenability to scaling up and derivatizations.

1. Introduction

Chromone frameworks are frequently found in bioactive natural products, including natural flavone and isoflavone products [1,2,3,4]; biologically and therapeutically active drugs [5,6,7,8], such as anti-inflammatory, antiviral, antimicrobial, antioxidative, and anticancer agents; and drug candidates for neurodegenerative diseases and adenosine receptors [9,10,11,12]. The importance of their structures greatly promoted the development of diverse procedures for their formation. Typically, chromones can be prepared by the classical synthetic routes, including Claisen condensation [13,14], Baker–Venkataraman [15], Kostanecki–Robinson reaction [16,17], benzopyrylium salts [18,19,20], and Vilsmeier–Haack reaction [21,22], utilizing ortho-hydroxyarylalkylketones as starting materials. In addition, phenols, salicylic acid, and derivatives have also been used to synthesize chromones via the Simonis [23,24] and Ruhemann [25] reactions and others [26,27,28,29,30,31].
Given the promising potential of 2-aryl-4H-chromen-4-ones in drug discovery and pharmaceutical applications, consequently, much effort has been focused on the development of new synthetic methods. Several practical and convenient transition-metal-catalyzed coupling methods have been used for the formation of 2-aryl-4H-chromen-4-ones due to their importance [32,33,34]. During the last decades, transition-metal-catalyzed coupling reactions have provided one of the most attractive methodologies for C−C bond formation. The application of palladium-catalyzed protocols, including oxidative arylation of chromones with phenylboronic acids (Scheme 1a) [35,36,37], and carbonylative cyclization using CO gas as a carbonyl source (Scheme 1b) [38,39,40,41,42,43,44], for the construction of chromones has attracted significant attention for a long time. Additionally, the Pd-catalyzed intramolecular acylation and oxidative cyclization can be used to synthesize 2-aryl-4H-chromen-4-ones (Scheme 1c) [45,46]. Recently, other methods involving intramolecular annulation of 2-alkoxyphenylacetophenones (Scheme 1d) [47,48] and 2′-hydroxychalcones (Scheme 1e) [49,50,51,52] via C–O bond formations have also been reported. Moreover, the synthesis of 2-aryl-4H-chromen-4-ones can be accomplished through the regioselectivite 6-endo-dig cyclization of ortho-hydroxyphenyl propagylic alcohols and ortho-hydroxyphenyl alkynones (Scheme 1f) [53,54,55,56,57]. Thus, these methods are good supplements to classical methods, but they generally have drawbacks of requiring harsh reaction conditions such as strong acids or bases, stoichiometric oxidants, and a long reaction time. In addition, transition-metal-catalyzed annulations often require the use of highly toxic carbon monoxide or expensive palladium catalyst and ligand at high temperatures. Inspired by our pioneering results, in which multireactive propargylamines displayed unique feature of cyclization, and in continuation of our interest in developing new synthetic protocols to build valuable heterocyclic frameworks [58,59,60,61,62,63,64], we herein disclose a cascade annulation of propargylamines for the synthesis of 2-aryl-4H-chromen-4-ones under green and operationally simple metal- and solvent-free conditions, which is unprecedented in previous works (Scheme 1g). This cascade process presumably involves a sequence of radical-induced C-N cleavage, followed by C-O coupling, intramolecular 6-endo-dig annulation, thermal hemolytic cleavage, and oxidative hydrocarbonylation.

2. Results and Discussion

We commenced with an investigation of propargylamine 1aa as a model substrate with air as the oxygen and carbonyl source to identify the reaction conditions (Table 1). The initial test of 1aa in the presence of diphenyl diselenide and dimethyl 2,2′-azobis(2-methylpropionate) (AIBME) in 1,2-dichloroethane (DCE) under an air atmosphere gave the desired product 2aa in a 63% isolated yield (entry 1). The influence of the solvents in this model reaction was then examined, and inferior results were obtained (entries 2–6). The following screening of the amount of diphenyl diselenide and AIBME (entries 7–12) showed that the 0.5 equiv. of diphenyl diselenide and 3.0 equiv. of AIBME was the best choice (entry 8). Changing the radical initiator from AIBME to AIBN (azodiisobutyronitrile) decreased the yield to 37% (entry 13). Interestingly, the yield of 2aa increased to 85% and 78% when the reaction was performed under solvent-free and blue LED light conditions, respectively (entries 14, 15). Furthermore, the effect of the reaction temperature and time was investigated, and the results revealed that these attempts did not show any improvement in the obtainable yield (entries 16–19). After extensive experimentation, we selected the conditions used in entry 14 as the optimal ones for the further investigations.
With the optimized conditions in hand, the influence of the substituents at the phenolic or alkynyl arene rings was first evaluated (Scheme 2). Generally, electron-donating (e.g., –Me, –OMe) and electron-withdrawing R groups (e.g., –F, –Cl, –Br) were well tolerated, giving the desired products 2ba–2fa in 63–72% yields. Substrates with multiple halo substituents and a bulky tert-butyl group at the ortho- and para-phenolic position were compatible under this reaction system with slightly lower yields (products 2ga, 2ha, and 2ia). Moreover, substituents at the meta-phenolic position were well tolerated, affording the desired products 2ja and 2ka in 45% and 67% yields, respectively. Subsequently, the scope and generality of the substituents on the alkynyl arene rings were explored. Substituents with electron-donating groups (–OMe, –Me) and electron-withdrawing groups (–F, –Cl, –Br) at the 2-, 3-, and 4-positions of the benzene rings were well tolerated, affording the corresponding products 2ab–2ai in 60–83% yields. In particular, trifluoromethyl as a strong electron-withdrawing substituent afforded the desired product 2aj in a 59% yield. Moreover, reactions with alkenyl-, thienyl-, and pyrenyl-containing substrates proceeded smoothly as well, giving the products 2ka, 2la, and 2ma in 65%, 69%, and 73% yields, respectively. It is notable that the halo moiety, e.g., –F, –Cl, and –Br, located at either the phenolic or alkynyl arene rings, remained intact (products 2da–2ha, 2ja–2ka, 2ad–2ah). These results exhibit an excellent opportunity for further arene functionalization by transition-metal-catalyzed cross-couplings.
Furthermore, we investigated various propargylamines bearing with different substituents on both the phenolic and alkynyl arene rings to showcase the prospective utility of this protocol (Scheme 3). Substituents with electron-rich (e.g., –Me, –Et, –OMe) groups and electron-deficient (e.g., –F, –Cl, –Br) groups at the phenolic and alkynyl arene rings were well-tolerated. The corresponding products 2bb–2en were obtained in good-to-excellent yields (62–91%). Moreover, the extended π structure did not show an influence, and the desired product 2bo was successfully obtained in a 78% yield. In addition, the structure of compound 2bo was unambiguously characterized via single crystal X-ray crystallographic analysis (details appear in Supplementary Materials).
To further prove the robustness and the general utility of this protocol, we carried out the reaction of propargylamine 1aa on the gram scale under the standard condition. When the reaction was amplified to a large scale (scaled up to 50 times), the protocol worked well, and the corresponding product 2aa was isolated in a 75% yield (Scheme 4a), which showed promise for this synthetic strategy as a useful tool in practical synthetic terms. Taking advantage of the flavones, we then explored their reactivity in further synthetic transformations. Rhodium-catalyzed oxidative C-H functionalization at the C-5 position of chromones successfully realized the formation of alkenyl flavones 4aa, 4ab, and 4af in 80%, 75%, and 71% yields, respectively (Scheme 4b).
Insights into this cascade reaction were gained by performing control experiments to clarify the reaction mechanism. To find the source of oxygen, the reaction with propargylamine 1aa was initially carried out in the presence of an oxygen and nitrogen atmosphere. In both cases, the desired product 2aa was isolated in 85% and 0% yields, respectively, clearly indicating an oxygen supply from molecular oxygen of air (Scheme 5a). Moreover, the desired product 2aa was not obtained when the reaction was carried out using ortho-hydroxyphenyl alkynone 5 instead of ortho-hydroxyphenyl propargylamine 1 under the standard conditions (Scheme 5b). The reaction of 2′-hydroxychalcone 6 was further examined under the standard conditions, providing the desired product 2aa in an 8% yield (Scheme 5c). Moreover, the addition of radical scavengers, namely (2,2,6,6-tetramethyl-1-piperidinyl)oxyl (TEMPO) and 2,6-di-tert-butyl-4-methylphenol (BHT), under the standard conditions significantly inhibited the reaction. The radical-trapping products 7 and 8 were detected by GC-MS, implying that the reaction proceeds via the radical pathway (Scheme 5d,e). Furthermore, the control experiments showed that AIBME and (PhSe)2 were both necessary for this transformation (Scheme 5f).
Based on the literature reports [65,66,67] and the results of the above control experiments, a plausible mechanism is proposed (Scheme 6). Initially, AIBME releases nitrogen under thermal conditions to form the free radical A, which attacks (PhSe)2 to generate the phenylselenyl radical (PhSe∙) and compound B (detected by CC-Ms) via radical transfer. Phenylselenyl radical then reacts with propargylamine 1aa to form the radical intermediate C and 1-(phenylselanyl)piperidine (detected by GC-MS) through C-N cleavage. The subsequent direct coupling of the intermediate C with molecular O2 (from air) gives rise to an O-radical D, which undergoes radical substitution with propargylamine 1aa to afford intermediate E. Then, the intramolecular 6-endo-dig annulation of intermediate E via nucleophilic addition of the OH group to alkynes gives the intermediate F, which undergoes thermal hemolytic cleavage to generate the radical intermediate G. Finally, the oxidation of intermediate G results in the desired product 2aa in the presence of air as the sole oxidant, yielding the hydroxyl radical, which could be quenched by the radical intermediate A to yield methyl 2-hydroxy-2-methylpropanoate (detected by GC-MS).

3. Materials and Methods

The detailed procedures for the synthesis and characterization of the products are given in Appendix A.

4. Conclusions

In summary, we established a novel and straightforward metal- and solvent-free cascade reaction of propargylamines with air for the construction of 2-aryl-4H-chromen-4-ones with substantial substitution diversity in generally good yields. This cascade process presumably involves a sequence of radical-induced C-N cleavage, followed by C-O coupling, intramolecular 6-endo-dig annulation, thermal hemolytic cleavage, and oxidative hydrocarbonylation. The preliminary mechanistic studies suggest that this reaction probably proceeds via a radical pathway. The practical protocol employs air as an oxygen source and represents a simple, economically acceptable, and eco-friendly route toward the straightforward construction of a 2-aryl-4H-chromen-4-one skeleton. In addition, the current strategy can be scaled-up to a gram-scale reaction and the synthetic utility of this transformation was also accomplished.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/molecules27217412/s1.

Author Contributions

Conceptualization, X.H.; methodology, K.X. and Y.S.; formal analysis, Y.L. and D.W.; investigation, K.X. and W.H.; data curation, Q.T. and H.C.; writing—original draft preparation, K.X.; writing—review and editing, X.H.; supervision, X.H.; project administration, X.H. All authors have read and agreed to the published version of the manuscript.

Funding

This work was supported by the Anhui Provincial Natural Science Foundation (No. 1808085MB41), the National Natural Science Foundation of China (No. 21772001), and the University Synergy Innovation Program of Anhui Province (No. GXXT-2020-074).

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

The data presented in this study are available in this article, Characterization data for product 3 and 4, including 1H- and 13C-NMR spectroscopies, are available online. CCDC 2195370 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by emailing data_request@ccdc.cam.ac.uk, or by contacting. The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; Fax: +44-1223-336033.

Conflicts of Interest

The authors declare no conflict of interest.

Sample Availability

Samples of the compounds are available from the authors.

Appendix A. Experimental Section

Unless otherwise noted, all reagents were purchased from commercial suppliers and used without purification. All cascade reactions were performed in a resealable screw-capped Schlenk flask (approximately a 15 mL volume) in the presence of a Teflon-coated magnetic stirrer bar (4 mm× 10 mm). Reactions were monitored using thin-layer chromatography (TLC) on commercial silica gel plates (GF 254). Visualization of the developed plates was performed under UV lights (GF 254 nm). Flash column chromatography was performed on silica gel (200–300 mesh). 1H NMR spectra were recorded on a 400 MHz spectrometer and 13C NMR spectra were recorded on a 100 MHz spectrometer. Chemical shifts were expressed in parts per million (δ) and the signals were reported as s (singlet), d (doublet), dd (doublet of doublet), t (triplet), q (quartet), and m (multiplet), and coupling constants (J) were given in Hz. Chemical shifts as internal standard were referenced to CDCl3 (δ = 7.26 for 1H and δ = 77.16 for 13C NMR) as internal standard. HRMS analysis with a quadrupole time-of-flight mass spectrometer yielded ion mass/charge (m/z) ratios in atomic mass units. The melting points were measured using an SGWX-4 melting point apparatus and were not corrected. The X-ray source used for the single-crystal X-ray diffraction analysis of compound 3na was Mo Kα (λ = 0.71073 Å), and the thermal ellipsoid was drawn at the 30% probability level.
General procedure for the synthesis of 2-aryl-4H-chromen-4-ones 2. A mixture of propargylamines 1 (0.2 mmol), diphenyl diselenide (0.1 mmol), and dimethyl 2,2′-azobis(2-methylpropionate) (0.6 mmol) were added to a resealable screw-capped Schlenk tube. The resulting mixture was stirred in an oil bath preheated to 80 °C under an open air atmosphere for 10 h (monitored by TLC). Upon completion of the reaction, the reaction mixture was cooled to room temperature, extracted with CH2Cl2 (3 × 10 mL), and washed with brine. The organic layers were combined, dried over Na2SO4, filtered, and then evaporated under a vacuum. The residue was purified using flash column chromatography with a silica gel (200–300 mesh), using ethyl acetate and petroleum ether (1:5, v/v) as the elution solvent to give the desired products 2.
General procedure for the synthesis of compound 4. A mixture of 2-aryl-4H-chromen-4-ones 2 (0.2 mmol), butyl acrylate 3 (0.6 mmol), [Cp*RhCl2]2 (0.005 mol), AgOTf (0.04 mmol), and AgOAc (0.4 mmol) were added to a resealable screw-capped Schlenk tube. Then 1,2-dichloroethane (2 mL) was added. The tube sealed with a Teflon-coated cap and the resulting mixture was stirred in an oil bath preheated to 60 °C for 48 h (monitored by TLC). Upon completion of the reaction, the reaction mixture was cooled to room temperature, extracted with CH2Cl2 (3 × 10 mL), and washed with brine. The organic layers were combined, dried over Na2SO4, filtered, and then evaporated under a vacuum. The residue was purified using flash column chromatography with a silica gel (200–300 mesh) using ethyl acetate and petroleum ether (1:5, v/v) as the elution solvent to give the desired products 4aa, 4ab, and 4af in 80%, 75%, and 71% yields, respectively.
2-Phenyl-4H-chromen-4-one (2aa). This compound was purified by column chromatography (ethyl acetate/petroleum ether = 1:5, Rf = 0.5) to afford a yellow solid in an 85% yield (38 mg); mp 122–124 °C; 1H NMR (400 MHz, CDCl3) δ 8.24 (dd, J = 7.9 Hz, 1.6 Hz, 1H), 7.55–7.93 (m, 2H), 7.74 (td, J = 7.7 Hz, 1.7 Hz, 1H), 7.62 (d, J = 8.4 Hz, 1H), 7.58–7.53 (m, 3H), 7.46 (t, J = 8.0 Hz, 1H), 6.84 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 178.54, 163.45, 156.29, 133.83, 131.80, 131.65, 129.09, 126.33, 125.74, 125.28, 123.98, 118.13, 107.63; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C15H11 O2 223.0754; Found 223.0752.
6-Methyl-2-phenyl-4H-chromen-4-one (2ba). This compound was purified by column chromatography (ethyl acetate/petroleum ether = 1:5, Rf = 0.4) to afford a yellow solid in a 72% yield (34mg); mp 100–102 °C; 1H NMR (400 MHz, CDCl3) δ 8.02 (s, 1H), 7.94–7.91 (m, 2H), 7.53 (dd, J = 5.3 Hz, 1.8 Hz, 3H), 7.51 (d, J = 2.2 Hz, 1H), 7.47 (d, J = 8.5 Hz, 1H), 6.82 (s, 1H), 2.47 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 178.60, 163.27, 154.54, 135.20, 134.99, 131.90, 131.49, 129.00, 126.26, 125.04, 123.59, 117.83, 107.44, 20.95; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C16H13O2 237.0910; Found 237.0900.
6-Methoxy-2-phenyl-4H-chromen-4-one (2ca). This compound was purified by column chromatography (ethyl acetate/petroleum ether = 1:5, Rf = 0.3) to afford a yellow solid in a 70% yield (35 mg); mp 152–153 °C; 1H NMR (400 MHz, CDCl3) δ 7.93–7.91 (m, 2H), 7.60 (d, J = 3.1 Hz, 1H), 7.53–7.50 (m, 4H), 7.30 (dd, J = 9.1 Hz, 3.1 Hz, 1H), 6.82 (s, 1H), 3.91 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 178.34, 163.20, 157.01, 151.10, 131.88, 131.49, 129.02, 126.24, 124.55, 123.83, 119.51, 106.84, 104.83, 55.94; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C16H13O3 253.0859; Found 253.0856.
6-Fluoro-2-phenyl-4H-chromen-4-one (2da). This compound was purified by column chromatography (ethyl acetate/petroleum ether = 1:5, Rf = 0.6) to afford a yellow solid in a 65% yield (31 mg); mp 125–127 °C; 1H NMR (400 MHz, CDCl3) δ 7.93–7.91 (m, 2H), 7.87 (dd, J = 8.2 Hz, 3.1 Hz, 1H), 7.60–7.51 (m, 4H), 7.45–7.40 (m, 1H), 6.83 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 177.63 (d, JC-F = 2.4 Hz), 163.69, 159.59 (d, JC-F = 245.4 Hz), 152.45 (d, JC-F = 1.7 Hz), 131.79, 131.52, 129.09, 126.31, 125.18 (d, JC-F = 7.3 Hz), 122.03 (d, JC-F = 25.3 Hz), 120.19 (d, JC-F = 8.0 Hz), 110.76 (d, JC-F = 23.5 Hz), 106.90; 19F NMR (376 MHz, CDCl3) δ -115.08; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C15H10FO2 241.0659; Found 241.0663.
6-Chloro-2-phenyl-4H-chromen-4-one (2ea). This compound was purified by column chromatography (ethyl acetate/petroleum ether = 1:5, Rf = 0.6) to afford a yellow solid in a 63% yield (32 mg); mp 181–182 °C; 1H NMR (400 MHz, CDCl3) δ 8.20 (d, J = 2.6 Hz, 1H), 7.93–7.90 (m, 2H), 7.65 (dd, J = 8.9 Hz, 2.6 Hz, 1H), 7.57–7.52 (m, 4H), 6.84 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 177.22, 163.72, 154.58, 133.97, 131.86, 131.41, 131.21, 129.11, 126.33, 125.19, 124.91, 119.80, 107.48; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C15H10ClO2 257.0364; Found 257.0355.
6-Bromo-2-phenyl-4H-chromen-4-one (2fa). This compound was purified by column chromatography (ethyl acetate/petroleum ether = 1:5, Rf = 0.7) to afford a yellow solid in a 70% yield (42 mg); mp 188–190 °C; 1H NMR (400 MHz, CDCl3) δ 8.36 (d, J = 2.5 Hz, 1H), 7.91 (dd, J = 7.6 Hz, 1.6 Hz, 2H), 7.79 (dd, J = 8.9 Hz, 2.5 Hz, 1H), 7.56–7.53 (m, 3H), 7.48 (d, J = 8.8 Hz, 1H), 6.83 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 177.01, 163.68, 155.00, 136.71, 131.86, 131.39, 129.11, 128.38, 126.32, 125.28, 120.03, 118.67, 107.56; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C15H10BrO2 300.9859; Found 300.9853.
6,8-Dichloro-2-phenyl-4H-chromen-4-one (2ga). This compound was purified by column chromatography (ethyl acetate/petroleum ether = 1:5, Rf = 0.6) to afford a yellow solid in a 51% yield (29 mg); mp 165–167 °C; 1H NMR (400 MHz, CDCl3) δ 8.10 (d, J = 2.5 Hz, 1H), 7.99 (dd, J = 7.7 Hz, 1.5 Hz, 2H), 7.74 (d, J = 2.5 Hz, 1H), 7.68–7.50 (m, 3H), 6.87 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 176.50, 163.50, 150.49, 133.80, 132.20, 130.89, 130.88, 129.23, 126.43, 125.73, 124.50, 123.90, 107.22; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C15H9Cl2O2 290.9974; Found 290.9977.
6,8-Dibromo-2-phenyl-4H-chromen-4-one (2ha). This compound was purified by column chromatography (ethyl acetate/petroleum ether = 1:5, Rf = 0.4) to afford a yellow solid in a 52% yield (39 mg); mp 166–168 °C; 1H NMR (400 MHz, CDCl3) δ 8.30 (d, J = 2.4 Hz, 1H), 8.04 (d, J = 2.3 Hz, 1H), 8.01 (dd, J = 7.5 Hz, 1.5 Hz, 2H), 7.61–7.52 (m, 3H), 6.87 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 176.45, 163.67, 151.83, 139.36, 132.24, 130.91, 129.27, 127.83, 126.52, 126.04, 118.55, 113.11, 107.18; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C15H9Br2O2 378.8964; Found 378.8965.
6,8-Di-tert-butyl-2-phenyl-4H-chromen-4-one (2ia). This compound was purified by column chromatography (ethyl acetate/petroleum ether = 1:5, Rf = 0.6) to afford a yellow solid in a 55% yield (36 mg); mp 105–107 °C; 1H NMR (400 MHz, CDCl3) δ 8.14 (d, J = 2.5 Hz, 1H), 8.06–7.89 (m, 2H), 7.75 (d, J = 2.5 Hz, 1H), 7.55 (t, J = 3.2 Hz, 3H), 6.87 (s, 1H), 1.60 (s, 9H), 1.40 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 179.16, 163.08, 153.32, 147.63, 138.40, 132.35, 131.35, 129.17, 128.97, 126.40, 124.18, 119.77, 107.40, 35.27, 35.01, 31.37, 30.29; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C23H27O2 335.2006; Found 335.1996.
5-Chloro-2-phenyl-4H-chromen-4-one (2ja). This compound was purified by column chromatography (ethyl acetate/petroleum ether = 1:5, Rf = 0.6) to afford a yellow solid in a 45% yield (23 mg); mp 117–118 °C; 1H NMR (400 MHz, CDCl3) δ 7.92–7.89 (m, 2H), 7.56–7.52 (m, 4H), 7.50 (dd, J = 7.6 Hz, 1.4 Hz, 1H), 7.40 (dd, J = 7.6 Hz, 1.4 Hz, 1H), 6.79 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 177.23, 161.72, 157.82, 133.51, 132.80, 131.73, 131.05, 129.06, 128.14, 126.16, 121.02, 117.31, 108.86; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C15H10ClO2 257.0364; Found 257.0358.
7-Chloro-2-phenyl-4H-chromen-4-one (2ka). This compound was purified by column chromatography (ethyl acetate/petroleum ether = 1:5, Rf = 0.6) to afford a yellow solid in a 67% yield (34 mg); mp 154–156 °C; 1H NMR (400 MHz, CDCl3) δ 8.17 (d, J = 8.5 Hz, 1H), 7.91 (dd, J = 7.6 Hz, 1.6 Hz, 2H), 7.61 (d, J = 1.9 Hz, 1H), 7.56–7.51 (m, 3H), 7.39 (dd, J = 8.4 Hz, 2.0 Hz, 1H), 6.82 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 177.52, 163.56, 156.34, 139.76, 131.82, 131.35, 129.10, 127.08, 126.27, 126.07, 122.49, 118.17, 107.77; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C15H10ClO2 257.0364; Found 257.0357.
8-(tert-Butyl)-2-phenyl-4H-chromen-4-one (2la). This compound was purified by column chromatography (ethyl acetate/petroleum ether = 1:5, Rf = 0.6) to afford a yellow solid in a 90% yield (50 mg); mp 186–188 °C; 1H NMR (400 MHz, CDCl3) δ 8.16 (dd, J = 7.8 Hz, 1.5 Hz, 1H), 8.99–7.96 (m, 2H), 7.69 (dd, J = 7.6 Hz, 1.4 Hz, 1H), 7.56 (t, J = 3.2 Hz, 3H), 7.36 (t, J = 7.7 Hz, 1H), 6.87 (s, 1H), 1.60 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 178.83, 163.36, 155.15, 139.06, 132.23, 131.46, 131.12, 129.19, 126.45, 124.83, 124.80, 124.04, 107.57, 35.11, 30.22; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C19H19O2 279.1380; Found 279.1375.
2-(p-Tolyl)-4H-chromen-4-one (2ab). This compound was purified by column chromatography (ethyl acetate/petroleum ether = 1:5, Rf = 0.4) to afford a yellow solid in an 83% yield (39 mg); mp 112–113 °C; 1H NMR (400 MHz, CDCl3) δ 8.25 (dd, J = 7.9 Hz, 1.8 Hz, 1H), 7.83 (d, J = 8.2 Hz, 2H), 7.71–7.67 (m, 1H), 7.57 (d, J = 8.5 Hz, 1H), 7.43–7.39 (m, 1H), 7.33 (d, J = 8.0 Hz, 2H), 6.80 (s, 1H), 2.44 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 178.16, 163.30, 155.92, 141.92, 133.32, 129.44, 128.64, 125.91, 125.35, 124.80, 123.66, 117.72, 106.66, 21.21; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C16H13O2 237.0910; Found 237.0920.
2-(4-Methoxyphenyl)-4H-chromen-4-one (2ac). This compound was purified by column chromatography (ethyl acetate/petroleum ether = 1:5, Rf = 0.3) to afford a yellow solid in a 65% yield (33 mg); mp 146–147 °C; 1H NMR (400 MHz, CDCl3) δ 8.23 (dd, J = 7.9 Hz, 1.7 Hz, 1H), 7.90 (d, J = 8.9 Hz, 2H), 7.70–7.66 (m, 1H), 7.55 (d, J = 8.4 Hz, 1H), 7.43–7.38 (m, 1H), 7.04 (d, J = 8.9 Hz, 2H), 6.75 (s, 1H), 3.89 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 178.42, 163.45, 162.42, 156.21, 133.57, 128.02, 125.69, 125.09, 124.06, 123.95, 117.96, 114.48, 106.21, 55.52; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C16H13O3 253.0859; Found 253.0869.
2-(4-Fluorophenyl)-4H-chromen-4-one (2ad). This compound was purified by column chromatography (ethyl acetate/petroleum ether = 1:5, Rf = 0.6) to afford a yellow solid in a 63% yield (30 mg); mp 140–142 °C; 1H NMR (400 MHz, CDCl3) δ 8.23 (dd, J = 7.8 Hz, 1.7 Hz, 1H), 7.95–7.90 (m, 2H), 7.72–7.68 (m, 1H), 7.56 (d, J = 8.0 Hz, 1H), 7.44–7.40 (m, 1H), 7.23–7.18 (m, 2H), 6.77 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 178.27, 165.99 (d, JC-F = 251.68 Hz), 162.39, 156.16, 133.82, 128.48 (d, JC-F = 8.8 Hz), 127.97 (d, JC-F = 3.3 Hz), 125.73, 125.31, 123.84, 117.99, 116.28 (d, JC-F = 27.31 Hz), 107.37; 19F NMR (376 MHz, CDCl3) δ −107.48; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C15H10FO2 241.0659; Found 241.0655.
2-(4-Chlorophenyl)-4H-chromen-4-one (2ae). This compound was purified by column chromatography (ethyl acetate/petroleum ether = 1:5, Rf = 0.7) to afford a yellow solid in a 65% yield (33 mg); mp 179–180 °C; 1H NMR (400 MHz, CDCl3) δ 8.23 (d, J = 7.8 Hz, 1H), 7.86 (d, J = 8.4 Hz, 2H), 7.71 (t, J = 7.6 Hz, 1H), 7.56 (d, J = 8.5 Hz, 1H), 7.50 (d, J = 8.5 Hz, 2H), 7.42 (t, J = 7.6 Hz, 1H), 6.79 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 178.25, 162.21, 156.14, 137.87, 133.90, 130.22, 129.36, 127.52, 125.73, 125.36, 123.88, 118.02, 107.67; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C15H10ClO2 257.0364; Found 257.0363.
2-(4-Bromophenyl)-4H-chromen-4-one (2af). This compound was purified by column chromatography (ethyl acetate/petroleum ether = 1:5, Rf = 0.7) to afford a yellow solid in a 75% yield (45 mg); mp 152–153 °C; 1H NMR (400 MHz, CDCl3) δ 8.23 (dd, J = 7.9 Hz, 1.6 Hz, 1H), 7.79 (d, J = 8.6 Hz, 2H), 7.73–7.70 (m, 1H), 7.66 (d, J = 8.6 Hz, 2H), 7.56 (d, J = 8.4 Hz, 1H), 7.45–7.41 (m, 1H), 6.80 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 178.28, 162.30, 156.15, 133.93, 132.34, 130.68, 127.69, 126.31, 125.73, 125.39, 123.88, 118.03, 107.68; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C15H10BrO2 300.9859; Found 300.9866.
2-(2-Fluorophenyl)-4H-chromen-4-one (2ag). This compound was purified by column chromatography (ethyl acetate/petroleum ether = 1:5, Rf = 0.4) to afford a yellow solid in a 70% yield (33 mg); mp 97–98 °C; 1H NMR (400 MHz, CDCl3) δ 8.24 (dd, J = 7.9 Hz, 1.7 Hz, 1H), 7.95–7.91 (m, 1H), 7.71–7.68 (m, 1H), 7.55–7.50 (m, 2H), 7.45–7.41 (m, 1H), 7.34–7.30 (m, 1H), 7.23–7.20 (m, 1H), 6.94 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 178.42, 161.82 (d, JC-F = 354.4 Hz), 158.81 (d, JC-F = 3.8 Hz), 156.37, 133.89, 132.90 (d, JC-F = 9.0 Hz), 129.08, 129.07, 125.76, 125.30, 124.64 (d, JC-F = 3.8 Hz), 123.84, 120.38 (d, JC-F = 10.1 Hz), 118.08, 116.99 (d, JC-F = 22.4 Hz), 112.44 (d, JC-F = 11.2 Hz); 19F NMR (376 MHz, CDCl3) δ-110.82; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C15H10FO2 241.0659; Found 241.0669.
2-(3-Chlorophenyl)-4H-chromen-4-one (2ah). This compound was purified by column chromatography (ethyl acetate/petroleum ether = 1:5, Rf = 0.5) to afford a yellow solid in a 60% yield (30 mg); mp 110–112 °C; 1H NMR (400 MHz, CDCl3) δ 8.23 (dd, J = 7.9 Hz, 1.7 Hz, 1H), 7.93 (t, J = 1.9 Hz, 1H), 7.80–7.78 (m, 1H), 7.74–7.70 (m, 1H), 7.59 (d, J = 8.3 Hz, 1H), 7.53–7.50 (m, 1H), 7.48–7.42 (m, 2H), 6.81 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 178.24, 161.79, 156.16, 135.26, 134.00, 133.59, 131.51, 130.32, 126.36, 125.76, 125.44, 124.38, 123.92, 118.09, 108.17; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C15H10ClO2 257.0364; Found 257.0366.
2-(m-Tolyl)-4H-chromen-4-one (2ai). This compound was purified by column chromatography (ethyl acetate/petroleum ether = 1:5, Rf = 0.6) to afford a yellow solid in a 72% yield (34 mg); mp 108–109 °C; 1H NMR (400 MHz, CDCl3) δ 8.24 (dd, J = 8.0 Hz, 1.7 Hz, 1H), 7.74–7.72 (m, 2H), 7.70–7.68 (m, 1H), 7.59 (d, J = 8.1 Hz, 1H), 7.44–7.39 (m, 2H), 7.36 (d, J = 7.6 Hz, 1H), 6.82 (s, 1H), 2.47 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 178.47, 163.64, 156.29, 138.84, 133.70, 132.40, 131.76, 128.93, 126.86, 125.70, 125.17, 123.99, 123.51, 118.08, 107.57, 21.51; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C16H13O2 237.0910; Found 237.0909.
2-(3,5-Bis(trifluoromethyl)phenyl)-4H-chromen-4-one (2aj). This compound was purified by column chromatography (ethyl acetate/petroleum ether = 1:5, Rf = 0.6) to afford a yellow solid in a 59% yield (42 mg); mp 154–155 °C; 1H NMR (400 MHz, CDCl3) δ 8.36 (s, 2H), 8.25 (dd, J = 8.0 Hz, 1.6 Hz, 1H), 8.05 (s, 1H), 7.79–7.75 (m, 1H), 7.65 (d, J = 8.2 Hz, 1H), 7.50–7.46 (m, 1H), 6.92 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 177.80, 159.81, 156.09, 134.41, 134.14, 133.32 (q, JC-F = 33.7 Hz), 126.91, 126.26, 126.22, 125.90, 125.88, 124.89 (q, JC-F = 3.6 Hz), 124.75, 124.20, 123.89, 121.49, 118.77, 118.18, 109.21; 19F NMR (376 MHz, CDCl3) δ-62.96; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C17H9F6O2 359.0501; Found 359.0499.
2-(Thiophen-3-yl)-4H-chromen-4-one (2ak). This compound was purified by column chromatography (ethyl acetate/petroleum ether = 1:5, Rf = 0.5) to afford a yellow solid in a 65% yield (29 mg); mp 107–108 °C; 1H NMR (400 MHz, CDCl3) δ 8.22 (dd, J = 7.9 Hz, 1.8 Hz, 1H), 8.03 (dd, J = 3.0 Hz, 1.3 Hz, 1H), 7.70–7.66 (m, 1H), 7.53 (d, J = 8.3 Hz, 1H), 7.50 (dd, J = 5.2, 1.4 Hz, 1H), 7.46 (dd, J = 5.1, 3.0 Hz, 1H), 7.43–7.38 (m, 1H), 6.68 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 178.44, 159.53, 156.04, 134.20, 133.70, 127.36, 126.82, 125.67, 125.14, 125.04, 123.97, 117.94, 107.16; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C13H9O2S 229.0318; Found 229.0319.
2-(Naphthalen-2-yl)-4H-chromen-4-one (2al). This compound was purified by column chromatography (ethyl acetate/petroleum ether = 1:5, Rf = 0.5) to afford a yellow solid in a 69% yield (37 mg); mp 100–102 °C; 1H NMR (400 MHz, CDCl3) δ 8.32 (dd, J = 8.0 Hz, 1.7 Hz, 1H), 8.15–8.13 (m, 1H), 8.04 (d, J = 8.2 Hz, 1H), 7.97–7.94 (m, 1H), 7.78 (dd, J = 7.2 Hz, 1.2 Hz, 1H), 7.73–7.70 (m, 1H), 7.61–7.56 (m, 3H), 7.54 (d, J = 8.1 Hz, 1H), 7.50–7.46 (m, 1H), 6.70 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 178.28, 165.43, 156.72, 133.87, 133.72, 131.50, 130.65, 130.38, 128.72, 127.95, 127.43, 126.58, 125.86, 125.37, 125.06, 124.87, 124.02, 118.24, 113.07; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C19H13O2 273.0910; Found 273.0900.
2-(Pyren-2-yl)-4H-chromen-4-one (2am). This compound was purified by column chromatography (ethyl acetate/petroleum ether = 1:5, Rf = 0.6) to afford a yellow solid in a 73% yield (50 mg); mp 216–219 °C; 1H NMR (400 MHz, CDCl3) δ 8.43 (d, J = 9.3 Hz, 1H), 8.35 (d, J = 7.9 Hz, 1H), 8.27–8.24 (m, 4H), 8.18–8.15 (m, 2H), 8.11–8.05 (m, 2H), 7.75 (t, J = 7.8 Hz, 1H), 7.60 (d, J = 8.4 Hz, 1H), 7.50 (t, J = 7.6 Hz, 1H), 6.85 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 178.17, 165.54, 156.84, 133.86, 133.05, 131.12, 130.49, 129.21, 129.13, 128.93, 127.11, 127.05, 126.70, 126.49, 126.25, 126.00, 125.85, 125.37, 124.77, 124.61, 124.33, 123.96, 123.80, 118.24, 113.69; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C25H15O2 347.1067; Found 347.1070.
6-Methyl-2-(p-tolyl)-4H-chromen-4-one (2bb). This compound was purified by column chromatography (ethyl acetate/petroleum ether = 1:5, Rf = 0.6) to afford a yellow solid in a 91% yield (45 mg); mp 136–137 °C; 1H NMR (400 MHz, CDCl3) δ 8.04 (s, 1H), 7.84 (d, J = 8.3 Hz, 2H), 7.53 (dd, J = 8.6 Hz, 1.9 Hz, 1H), 7.49 (d, J = 8.5 Hz, 1H), 7.35 (d, J = 8.1 Hz, 2H), 6.81 (s, 1H), 2.49 (s, 3H), 2.46 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 178.60, 163.46, 154.50, 142.11, 135.07, 134.86, 129.72, 129.05, 126.18, 125.01, 123.60, 117.79, 106.81, 21.52, 20.94; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C17H15O2 251.1067; Found 251.1072.
2-(4-Methoxyphenyl)-6-methyl-4H-chromen-4-one (2bc). This compound was purified by column chromatography (ethyl acetate/petroleum ether = 1:5, Rf = 0.8) to afford a yellow solid in a 76% yield (40 mg); mp 162–163 °C; 1H NMR (400 MHz, CDCl3) δ 8.01 (s, 1H), 7.88 (d, J = 8.9 Hz, 2H), 7.49 (dd, J = 8.6 Hz, 1.8 Hz, 1H), 7.45 (d, J = 8.5 Hz, 1H), 7.02 (d, J = 8.9 Hz, 2H), 6.73 (s, 1H), 3.89 (s, 3H), 2.47 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 178.54, 163.31, 162.32, 154.47, 135.03, 134.76, 127.97, 125.03, 124.18, 123.57, 117.70, 114.43, 106.06, 55.50, 20.93; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C17H15O3 267.1016; Found 267.1020.
2-(4-Fluorophenyl)-6-methyl-4H-chromen-4-one (2bd). This compound was purified by column chromatography (ethyl acetate/petroleum ether = 1:5, Rf = 0.4) to afford a yellow solid in a 75% yield (38 mg); mp 124–126 °C; 1H NMR (400 MHz, CDCl3) δ 8.01 (s, 1H), 7.95–7.89 (m, 2H), 7.51 (dd, J = 8.6 Hz, 2.2 Hz, 1H), 7.46 (d, J = 8.5 Hz, 1H), 7.25–7.16 (m, 2H), 6.75 (s, 1H), 2.47 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 178.44, 164.69 (d, JC-F = 251.9 Hz), 162.28, 154.45, 135.33, 135.06, 128.45 (d, JC-F = 8.8 Hz), 128.09 (d, JC-F = 3.3 Hz), 125.07, 123.48, 117.75, 116.25 (d, JC-F = 22.1 Hz), 107.21, 20.94; 19F NMR (376 MHz, CDCl3) δ -107.67; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C16H12FO2 255.0816; Found 255.0811.
2-(4-Chlorophenyl)-6-methyl-4H-chromen-4-one (2be). This compound was purified by column chromatography (ethyl acetate/petroleum ether = 1:5, Rf = 0.7) to afford a yellow solid in a 72% yield (38 mg); mp 165–167 °C; 1H NMR (400 MHz, CDCl3) δ 8.02 (s, 1H), 7.87 (d, J = 8.6 Hz, 2H), 7.52 (t, J = 8.6 Hz, 2H), 7.49 (s, 1H), 7.46 (d, J = 8.6 Hz, 1H), 6.78 (s, 1H), 2.48 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 178.42, 162.12, 154.47, 137.78, 135.41, 135.14, 130.39, 129.35, 127.53, 125.10, 123.56, 117.79, 107.55, 20.95; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C16H12ClO2 271.0520; Found 271.0512.
2-(4-Bromophenyl)-6-methyl-4H-chromen-4-one (2bf). This compound was purified by column chromatography (ethyl acetate/petroleum ether = 1:5, Rf = 0.4) to afford a yellow solid in a 69% yield (43 mg); mp 196–198 °C; 1H NMR (400 MHz, CDCl3) δ 8.00 (s, 1H), 7.78 (d, J = 8.6 Hz, 2H), 7.65 (d, J = 8.7 Hz, 2H), 7.51 (dd, J = 8.6 Hz, 2.2 Hz, 1H), 7.45 (d, J = 8.6 Hz, 1H), 6.77 (s, 1H), 2.46 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 178.34, 162.10, 154.41, 135.38, 135.11, 132.28, 130.79, 127.64, 126.16, 125.06, 123.53, 117.77, 107.51, 20.93; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C16H12BrO2 315.0015; Found 315.0017.
6-Methyl-2-(4′-propyl-[1,1′-biphenyl]-4-yl)-4H-chromen-4-one (2bo). This compound was purified by column chromatography (ethyl acetate/petroleum ether = 1:5, Rf = 0.4) to afford a yellow solid in a 78% yield (55 mg); mp 152–153 °C; 1H NMR (400 MHz, CDCl3) δ 8.02 (s, 1H), 7.98 (d, J = 8.4 Hz, 2H), 7.73 (d, J = 8.5 Hz, 2H), 7.57 (d, J = 8.2 Hz, 2H), 7.54–7.42 (m, 2H), 7.29 (d, J = 8.2 Hz, 2H), 6.85 (s, 1H), 2.78–2.55 (m, 2H), 2.47 (s, 3H), 1.70 (d, J = 7.5 Hz, 2H), 0.99 (t, J = 7.3 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 178.52, 163.07, 154.52, 144.23, 142.95, 137.04, 135.16, 134.93, 130.25, 129.10, 127.35, 126.92, 126.66, 125.04, 123.63, 117.80, 107.14, 37.70, 24.49, 20.93, 13.84; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C25H23O2 355.1693; Found 355.1691.
6-Methoxy-2-(p-tolyl)-4H-chromen-4-one (2cb). This compound was purified by column chromatography (ethyl acetate/petroleum ether = 1:5, Rf = 0.3) to afford a yellow solid in an 80% yield (42 mg); mp 147–148 °C; 1H NMR (400 MHz, CDCl3) δ 7.82 (d, J = 8.3 Hz, 2H), 7.60 (d, J = 3.1 Hz, 1H), 7.50 (d, J = 9.1 Hz, 1H), 7.32 (d, J = 8.1 Hz, 2H), 7.29 (dd, J = 9.1 Hz, 3.1 Hz, 1H), 6.79 (s, 1H), 3.91 (s, 3H), 2.44 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 178.34, 163.38, 156.92, 151.05, 142.11, 129.74, 129.04, 126.16, 124.56, 123.69, 119.47, 106.25, 104.80, 55.94, 21.53; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C17H15O3 267.1016; Found 267.1026.
6-Methoxy-2-(4-methoxyphenyl)-4H-chromen-4-one (2cc). This compound was purified by column chromatography (ethyl acetate/petroleum ether = 1:5, Rf = 0.3) to afford a yellow solid in an 84% yield (48 mg); mp 187–188 °C; 1H NMR (400 MHz, CDCl3) δ 7.87 (d, J = 8.9 Hz, 2H), 7.59 (d, J = 3.1 Hz, 1H), 7.48 (d, J = 9.1 Hz, 1H), 7.33–7.22 (m, 1H), 7.02 (d, J = 8.9 Hz, 2H), 6.74 (s, 1H), 3.91 (s, 3H), 3.89 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 178.23, 163.19, 162.30, 156.88, 150.98, 127.91, 124.49, 124.12, 123.53, 119.35, 114.42, 105.47, 104.86, 55.92, 55.48; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C17H15O4 283.0965; Found 283.0971.
2-(4-Fluorophenyl)-6-methoxy-4H-chromen-4-one (2cd). This compound was purified by column chromatography (ethyl acetate/petroleum ether = 1:5, Rf = 0.5) to afford a yellow solid in a 78% yield (42 mg); mp 144–146 °C; 1H NMR (400 MHz, CDCl3) δ 7.94–7.89 (m, 2H), 7.59 (d, J = 3.1 Hz, 1H), 7.50 (d, J = 9.2 Hz, 1H), 7.29 (dd, J = 9.2 Hz, 3.2 Hz, 1H), 7.24–7.17 (m, 2H), 6.76 (s, 1H), 3.91 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 178.17, 165.94 (d, J = 251.5 Hz), 162.19, 157.06, 150.99, 128.42 (d, J = 8.8 Hz), 128.07 (d, J = 3.3 Hz), 124.45, 123.87, 119.42, 116.26 (d, J = 22.0 Hz), 106.63, 104.87, 55.95; 19F NMR (376 MHz, CDCl3) δ-107.68; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C16H12FO3 271.0765; Found 271.0759.
2-(4-Chlorophenyl)-6-methoxy-4H-chromen-4-one (2ce). This compound was purified by column chromatography (ethyl acetate/petroleum ether = 1:5, Rf = 0.5) to afford a yellow solid in a 72% yield (41 mg); mp 167–168 °C; 1H NMR (400 MHz, CDCl3) δ 7.85 (d, J = 8.6 Hz, 2H), 7.58 (d, J = 3.1 Hz, 1H), 7.49 (d, J = 8.8 Hz, 3H), 7.29 (dd, J = 9.2 Hz, 3.2 Hz, 1H), 6.78 (s, 1H), 3.91 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 178.14, 161.98, 157.09, 150.96, 137.75, 130.30, 129.33, 127.46, 124.49, 123.94, 119.45, 106.89, 104.84, 55.94; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C16H12ClO3 287.0469; Found 287.0475.
2-(4-Bromophenyl)-6-methoxy-4H-chromen-4-one (2cf). This compound was purified by column chromatography (ethyl acetate/petroleum ether = 1:5, Rf = 0.6) to afford a yellow solid in a 75% yield (49 mg); mp 189–190 °C; 1H NMR (400 MHz, CDCl3) δ 7.78 (d, J = 8.7 Hz, 2H), 7.65 (d, J = 8.7 Hz, 2H), 7.58 (d, J = 3.1 Hz, 1H), 7.49 (d, J = 9.1 Hz, 1H), 7.29 (dd, J = 9.2 Hz, 3.2 Hz, 1H), 6.78 (s, 1H), 3.91 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 178.12, 162.04, 157.09, 150.95, 132.30, 130.77, 127.62, 126.16, 124.50, 123.95, 119.46,106.90, 104.84, 55.94; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C16H12BrO3 330.9964; Found 330.9960.
6-Chloro-2-(p-tolyl)-4H-chromen-4-one (2db). This compound was purified by column chromatography (ethyl acetate/petroleum ether = 1:5, Rf = 0.5) to afford a yellow solid in a 72% yield (38 mg); mp 177–178 °C; 1H NMR (400 MHz, CDCl3) δ 8.19 (d, J = 2.6 Hz, 1H), 7.81 (d, J = 8.3 Hz, 2H), 7.63 (dd, J = 8.9 Hz, 2.6 Hz, 1H), 7.52 (d, J = 8.9 Hz, 1H), 7.33 (d, J = 8.0 Hz, 2H), 6.79 (s, 1H), 2.44 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 177.20, 163.89, 154.53, 142.58, 133.82, 131.08, 129.83, 128.55, 126.25, 125.14, 124.92, 119.75, 106.83, 21.55; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C16H12ClO2 271.0520; Found 271.0527.
6-Chloro-2-(4-methoxyphenyl)-4H-chromen-4-one (2dc). This compound was purified by column chromatography (ethyl acetate/petroleum ether = 1:5, Rf = 0.5) to afford a yellow solid in a 62% yield (35 mg); mp 173–174 °C; 1H NMR (400 MHz, CDCl3) δ 8.18 (d, J = 2.6 Hz, 1H), 7.87 (d, J = 9.0 Hz, 2H), 7.62 (dd, J = 8.9, 2.6 Hz, 1H), 7.51 (d, J = 8.9 Hz, 1H), 7.03 (d, J = 9.0 Hz, 2H), 6.74 (s, 1H), 3.90 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 177.10, 163.70, 162.61, 154.49, 133.71, 131.02, 128.06, 125.15, 124.91, 123.62, 119.66, 114.54, 106.05, 55.52; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C16H12ClO3 287.0469; Found 287.0474.
6-Chloro-2-(4-chlorophenyl)-4H-chromen-4-one (2de). This compound was purified by column chromatography (ethyl acetate/petroleum ether = 1:5, Rf = 0.3) to afford a yellow solid in a 68% yield (39 mg); mp 202–203 °C; 1H NMR (400 MHz, CDCl3) δ 8.19 (d, J = 2.5 Hz, 1H), 7.85 (d, J = 8.7 Hz, 2H), 7.65 (dd, J = 8.9 Hz, 2.6 Hz, 1H), 7.52 (dd, J = 8.9 Hz, 5.8 Hz, 3H), 6.79 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 176.98, 162.50, 154.46, 138.19, 134.10, 131.38, 129.86, 129.46, 127.56, 125.22, 124.85, 119.75, 107.57; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C15H9Cl2O2 290.9974; Found 290.9977.
2-(4-Bromophenyl)-6-chloro-4H-chromen-4-one (2df). This compound was purified by column chromatography (ethyl acetate/petroleum ether = 1:5, Rf = 0.4) to afford a yellow solid in a 75% yield (50 mg); mp 200–202 °C; 1H NMR (400 MHz, CDCl3) δ 8.19 (d, J = 2.4 Hz, 1H), 7.78 (d, J = 8.8 Hz, 2H), 7.72–7.60 (m, 3H), 7.53 (d, J = 8.9 Hz, 1H), 6.80 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 176.98, 162.58, 154.46, 134.11, 132.43, 131.39, 130.32, 127.71, 126.62, 125.23, 124.86, 119.76, 107.59; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C15H9BrClO2 334.9469; Found 334.9462.
6-Bromo-2-(p-tolyl)-4H-chromen-4-one (2eb). This compound was purified by column chromatography (ethyl acetate/petroleum ether = 1:5, Rf = 0.5) to afford a yellow solid in a 75% yield (47 mg); mp 185–186 °C; 1H NMR (400 MHz, CDCl3) δ 8.35 (d, J = 2.5 Hz, 1H), 7.81 (d, J = 8.2 Hz, 2H), 7.77 (dd, J = 8.8 Hz, 2.5 Hz, 1H), 7.46 (d, J = 8.8 Hz, 1H), 7.33 (d, J = 8.0 Hz, 2H), 6.80 (s, 1H), 2.44 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 177.05, 163.90, 155.00, 142.61, 136.60, 129.85, 128.57, 128.37, 126.27, 125.33, 120.01, 118.57, 106.95, 21.58; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C16H12BrO2 315.0015; Found 315.0024.
6-Bromo-2-(4-methoxyphenyl)-4H-chromen-4-one (2ec). This compound was purified by column chromatography (ethyl acetate/petroleum ether = 1:5, Rf = 0.5) to afford a yellow solid in a 69% yield (45 mg); mp 187–188 °C; 1H NMR (400 MHz, CDCl3) δ 8.34 (d, J = 2.5 Hz, 1H), 7.88–7.84 (m, 2H), 7.76 (dd, J = 8.8 Hz, 2.5 Hz, 1H), 7.44 (d, J = 8.8 Hz, 1H), 7.04–7.00 (m, 2H), 6.74 (s, 1H), 3.89 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 176.94, 163.70, 162.62, 154.92, 136.48, 128.34, 128.06, 125.27, 123.59, 119.89, 118.49, 114.54, 106.11, 55.52; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C16H12BrO3 330.9964; Found 330.9970.
6-Bromo-2-(4-chlorophenyl)-4H-chromen-4-one (2ee). This, 136.87, 129.85, 129.47, 128.43, 127.57, 125.22, 119.99, 118.84, 107.67. HRMS (ESI-TO compound was purified by column chromatography (ethyl acetate/petroleum ether = 1:5, Rf = 0.6) to afford a yellow solid in a 72% yield (48 mg); mp 214–215 °C; 1H NMR (400 MHz, CDCl3) δ 8.35 (d, J = 2.5 Hz, 1H), 7.85 (d, J = 8.5 Hz, 2H), 7.79 (dd, J = 8.8 Hz, 2.5 Hz, 1H), 7.51 (d, J = 8.6 Hz, 2H), 7.47 (d, J = 8.9 Hz, 1H), 6.80 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 176.84, 162.51, 154.91, 138.20, 136.87, 129.85, 129.47, 128.43, 127.57, 125.22, 119.99, 118.84, 107.67. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C15H9ClBrO2 334.9469; Found 334.9474.
6-Bromo-2-(4-bromophenyl)-4H-chromen-4-one (2ef). This compound was purified by column chromatography (ethyl acetate/petroleum ether = 1:5, Rf = 0.6) to afford a yellow solid in a 66% yield (49 mg); mp 219–220 °C; 1H NMR (400 MHz, CDCl3) δ 8.35 (d, J = 2.5 Hz, 1H), 7.80–7.77 (m, 2H), 7.76 (s, 1H), 7.67 (d, J = 8.7 Hz, 2H), 7.46 (d, J = 8.9 Hz, 1H), 6.80 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 176.83, 162.57, 154.89, 136.87, 132.43, 130.30, 128.42, 127.70, 126.64, 125.22, 119.99, 118.85, 107.67; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C15H9Br2O2 378.8964; Found 378.8970.
6-Bromo-2-(4-ethylphenyl)-4H-chromen-4-one (2en). This compound was purified by column chromatography (ethyl acetate/petroleum ether = 1:5, Rf = 0.5) to afford a yellow solid in an 85% yield (55 mg); mp 129–130 °C; 1H NMR (400 MHz, CDCl3) δ 8.36 (d, J = 2.4 Hz, 1H), 7.84 (d, J = 8.4 Hz, 2H), 7.78 (dd, J = 8.8 Hz, 2.5 Hz, 1H), 7.47 (d, J = 8.8 Hz, 1H), 7.36 (d, J = 8.4 Hz, 2H), 6.81 (s, 1H), 2.74 (d, J = 7.6 Hz, 2H), 1.29 (d, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 177.08, 163.95, 155.01, 148.84, 136.60, 128.78, 128.67, 128.36, 126.40, 125.32, 120.01, 118.57, 106.98, 28.85, 15.23; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C17H14BrO2 329.0172; Found 329.0169.
Butyl (E)-3-(4-oxo-2-phenyl-4H-chromen-5-yl)acrylate (4aa). This compound was purified by column chromatography (ethyl acetate/petroleum ether = 1:5, Rf = 0.6) to afford a yellow solid in an 80% yield (55 mg); mp 93–94 °C; 1H NMR (400 MHz, CDCl3) δ 9.03 (d, J = 15.9 Hz, 1H), 7.92 (d, J = 8.0 Hz, 2H), 7.66 (t, J = 7.9 Hz, 1H), 7.60 (d, J = 8.3 Hz, 1H), 7.54 (d, J = 6.3 Hz, 3H), 7.47 (d, J = 7.2 Hz, 1H), 6.81 (s, 1H), 6.27 (d, J = 15.9 Hz, 1H), 4.24 (t, J = 6.6 Hz, 2H), 1.91–1.67 (m, 2H), 1.55–1.38 (m, 2H), 0.97 (t, J = 7.3 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 179.58, 166.61, 162.21, 157.21, 144.58, 137.06, 133.03, 131.70, 131.23, 129.06, 126.22, 124.74, 121.67, 121.43, 119.54, 108.72, 64.52, 30.74, 19.21, 13.80; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C22H21O4 349.1434; Found 349.1435.
Butyl €-3-(4-oxo-2-(p-tolyl)-4H-chromen-5-yl)acrylate (4ab). This compound was purified by column chromatography (ethyl acetate/petroleum ether = 1:5, Rf = 0.6) to afford a yellow solid in a 75% yield (54 mg); mp 128–129 °C; 1H NMR (400 MHz, CDCl3) δ 9.04 (d, J = 15.9 Hz, 1H), 7.81 (d, J = 8.2 Hz, 2H), 7.69–7.62 (m, 1H), 7.59 (dd, J = 8.3 Hz, 1.0 Hz, 1H), 7.46 (d, J = 7.3 Hz, 1H), 7.32 (d, J = 8.0 Hz, 2H), 6.76 (s, 1H), 6.26 (d, J = 15.9 Hz, 1H), 4.24 (t, J = 6.7 Hz, 2H), 2.44 (s, 3H), 1.80–1.70 (m, 2H), 1.55–1.36 (m, 2H), 0.97 (t, J = 7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 179.58, 166.63, 162.39, 157.16, 144.66, 142.36, 136.99, 132.89, 129.76, 128.35, 126.13, 124.63, 121.55, 121.43, 119.52, 108.07, 64.50, 30.73, 21.55, 19.20, 13.79; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C23H23O4 363.1591; Found 363.1593.
Butyl (E)-3-(2-(4-bromophenyl)-4-oxo-4H-chromen-5-yl)acrylate (4af). This compound was purified by column chromatography (ethyl acetate/petroleum ether = 1:5, Rf = 0.6) to afford a yellow solid in a 71% yield (60 mg); mp 156–157 °C; 1H NMR (400 MHz, CDCl3) δ 9.01 (d, J = 15.9 Hz, 1H), 7.78 (d, J = 8.6 Hz, 2H), 7.72–7.64 (m, 3H), 7.59 (d, J = 7.6 Hz, 1H), 7.48 (d, J = 7.4 Hz, 1H), 6.77 (s, 1H), 6.27 (d, J = 15.9 Hz, 1H), 4.24 (t, J = 6.7 Hz, 2H), 1.84–1.67 (m, 2H), 1.54–1.40 (m, 2H), 0.97 (t, J = 7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 179.37, 166.57, 161.13, 157.10, 144.41, 137.11, 133.18, 132.36, 130.15, 127.62, 126.41, 124.88, 121.80, 121.37, 119.48, 108.81, 64.55, 30.73, 19.21, 13.79; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C22H22BrO4 427.0539; Found 427.0547.

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Molecules 27 07412 sch001 550
Scheme 1. Modern strategies for accessing 2-aryl-4H-chromen-4-ones.
Scheme 1. Modern strategies for accessing 2-aryl-4H-chromen-4-ones.
Molecules 27 07412 sch001
Molecules 27 07412 sch002 550
Scheme 2. Substituent effect at the phenolic and alkynyl arene rings. Reaction conditions: propargylamines 1 (0.2 mmol), (PhSe)2 (0.1 mmol), and AIBME (0.6 mmol) at 80 °C for 10 h under air atmosphere. Isolated yields were reported.
Scheme 2. Substituent effect at the phenolic and alkynyl arene rings. Reaction conditions: propargylamines 1 (0.2 mmol), (PhSe)2 (0.1 mmol), and AIBME (0.6 mmol) at 80 °C for 10 h under air atmosphere. Isolated yields were reported.
Molecules 27 07412 sch002
Molecules 27 07412 sch003 550
Scheme 3. Substrate scope of various propargylamines. Reaction conditions: propargylamines 1 (0.2 mmol), (PhSe)2 (0.1 mmol), and AIBME (0.6 mmol) at 80 °C for 10 h under air atmosphere. Isolated yields were reported.
Scheme 3. Substrate scope of various propargylamines. Reaction conditions: propargylamines 1 (0.2 mmol), (PhSe)2 (0.1 mmol), and AIBME (0.6 mmol) at 80 °C for 10 h under air atmosphere. Isolated yields were reported.
Molecules 27 07412 sch003
Molecules 27 07412 sch004 550
Scheme 4. Synthetic applications.
Scheme 4. Synthetic applications.
Molecules 27 07412 sch004
Molecules 27 07412 sch005 550
Scheme 5. Mechanistic studies.
Scheme 5. Mechanistic studies.
Molecules 27 07412 sch005
Molecules 27 07412 sch006 550
Scheme 6. A plausible mechanism for the cascade reaction of proparylamines with air.
Scheme 6. A plausible mechanism for the cascade reaction of proparylamines with air.
Molecules 27 07412 sch006
Table
Table 1. Optimization of reaction conditions a.
Table 1. Optimization of reaction conditions a.
Molecules 27 07412 i001
EntryVariation from the Standard Conditions Yield (%) b
1none63
2MeCN instead of DCE40
3toluene instead of DCE45
4DMSO instead of DCE42
5DMF instead of DCE35
6acetone instead of DCE0
70.2 equiv. of (PhSe)2 was used55
80.5 equiv. of (PhSe)2 was used71
91.5 equiv. of (PhSe)2 was used59
102.0 equiv. of (PhSe)2 was used64
11 c2.0 equiv. of AIBME was used44
12 c4.0 equiv. of AIBME was used52
13 cAIBN instead of AIBME37
14 csolvent-free85
15 c,dproceeded under blue LED light78
16 c,dAt 60 °C36
17 c,dAt 100 °C54
18 c,dFor 8 h59
19 c,dFor 18 h83
a Reaction conditions: propargylamine 1aa (0.2 mmol), (PhSe)2 (0.2 mmol), and AIBME (0.6 mmol) in DCE (2 mL) at 80 °C for 10 h under air atmosphere. b Isolated yields. c The amount of (PhSe)2 was 0.5 equivalent. d Proceeded under solvent-free conditions.
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MDPI and ACS Style

He, X.; Xu, K.; Liu, Y.; Wang, D.; Tang, Q.; Hui, W.; Chen, H.; Shang, Y. Radical-Induced Cascade Annulation/Hydrocarbonylation for Construction of 2-Aryl-4H-chromen-4-ones. Molecules 2022, 27, 7412. https://doi.org/10.3390/molecules27217412

AMA Style

He X, Xu K, Liu Y, Wang D, Tang Q, Hui W, Chen H, Shang Y. Radical-Induced Cascade Annulation/Hydrocarbonylation for Construction of 2-Aryl-4H-chromen-4-ones. Molecules. 2022; 27(21):7412. https://doi.org/10.3390/molecules27217412

Chicago/Turabian Style

He, Xinwei, Keke Xu, Yanan Liu, Demao Wang, Qiang Tang, Wenjie Hui, Haoyu Chen, and Yongjia Shang. 2022. "Radical-Induced Cascade Annulation/Hydrocarbonylation for Construction of 2-Aryl-4H-chromen-4-ones" Molecules 27, no. 21: 7412. https://doi.org/10.3390/molecules27217412

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