A novel one-pot synthesis of flavones

Abstract

In this paper, a one-pot facile route for the BiCl₃/RuCl₃-mediated synthesis of functionalized flavones is described, including: (i) intermolecular ortho-acylation of substituted phenols with cinnamoyl chlorides, and (ii) intramolecular cyclodehydrogenation of the resulting o-hydroxychalcones. The reaction conditions are discussed herein.

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Introduction

For the flavonoid family, flavone (also called 2-arylchromone) with numerous biological activities is attracting many synthetic researchers to develop a number of versatile methodologies.¹ A recent review article^1a has revealed the synthetic history of functionalized flavones from the traditional well-known named reactions (e.g., Baker–Venkataraman,² Karl von-Auwers,³ Algar–Flynn–Oyamada,⁴ Allan–Robinson,⁵ Kostanecki,⁶ Mentzer⁷ and Wittig⁸) to modern novel transition-metal promoted protocols (e.g., Suzuki–Miyaura⁹ and Sonogashira¹⁰). By the use of other reaction conditions such as microwave irradiation,¹¹ ionic liquids improvement¹² and photolytic annulation,¹³ the unique methodologies of flavones and their derivatives have been established. For the synthetic chemistry of diversified flavones, the two-step process for (1) ortho-acylation of substituted phenols and (2) cyclodehydrogenation of the resulting o-hydroxychalcones is a general and direct route to provide access to the core structure, as shown in Scheme 1.

Scheme 1 Synthetic route of flavones.

By the involvement of transition metals, various ortho-acylations of phenols have been well-developed, including CuCl₂,^14a FeCl₃,^14b TiCl₄,^14c mercury lamp/photolysis,^14d MsOH/microwave.^14e For the following cyclodehydrogenation step, the uses of InCl₃/SiO₂,^15a FeCl₃·6H₂O/MeOH,^15b and CuI/ionic liquids^15c have been studied. In addition, transition metal-free oxidants-mediated reaction systems, for example, I₂/DMSO,^16a DDQ/dioxane,^16b NaIO₄/DMSO,^16c H₂O₂/NaOH,^16d SeO₂/dioxane^16e and Br₂/NaOH^16f have been investigated in the cyclodehydrogenation step.

Among these reported routes with the synthetic sequence of intermolecular ortho-acylation followed by intramolecular cyclodehydrogenation, we found that all attempts adopted a two-step stepwise process as the major focused design in the flavone family formation. Despite the above elegant synthetic routes, to date, there are no reports on the one-pot synthesis of substituted flavones on the basis of the formal (3 + 3) annulation. Herein, we present metal chlorides-mediated one-pot synthesis of flavones 4 (Scheme 2) via the combination of BiCl₃ andRuCl₃-mediated intermolecular ortho-acylation of substituted phenols 1 with cinnamoyl chlorides 2 (one carbon–carbon bond formation, green), and intramolecular cyclodehydrogenation of the corresponding o-hydroxychalcones 3 (one carbon–oxygen bond formation, green). These starting materials, 1 and 2, were obtained from commercial sources and used without further purification.

Scheme 2 Our synthetic route towards flavones.

Results and discussion

The initial study commenced with the treatment of the model substrate 1a (Ar = Ph, 1.0 mmol) with 2a (Ar′ = Ph, 1.0 mmol) and AlCl₃ (2.0 equiv.) in CCl₄ (20 mL) at reflux (77 °C) for 10 h. Only 3a was produced at a 54% yield. The results are shown in Table 1, entry 1. Entries 2–7 show that six trivalent transition-metal chlorides (2.0 equiv., InCl₃, FeCl₃, BiCl₃, CeCl₃, AuCl₃ and RuCl₃) were studied in CCl₄ (20 mL) at reflux for 10 h. However, only InCl₃ and FeCl₃ obtained sole 3a in 67% and 70% yields, respectively. BiCl₃ provided 65% yield of 3a along with trace amount of 4a. In particular, no reactions were observed for CeCl₃ and AuCl₃, while RuCl₃ produced a complex mixture. According to the experimental results, we understood that InCl₃ or FeCl₃-mediated ortho-acylation of 1a proceeded well, but they could not promote the conversion from 3a to 4a (entries 2 and 3). In addition to forming 3a, trace amount of 4a (3%) could be obtained in the presence of BiCl₃ (entry 4). For CeCl₃ and AuCl₃, the reactivity of Lewis acid was weak to a degree that no desired reaction was initiated (entries 5 and 6). Compared with other MCl₃, RuCl₃ with strong oxidation ability could force the ortho-acylation of 1a to complexation (entry 7). Next, we refocused the synthetic aim to study the equivalents of BiCl₃; however, after increasing the stoichiometric from 2.0 to 3.0 equiv., the conversion efficiency from 3a to 4a was similar to that of 2.0 equiv. (5%, entry 8).

Table 1 Reaction conditions^a

Entry	MCl3 (equiv.)	Solvent	Time (h)	3a/4a^b %
a The reactions were run on a 1.0 mmol scale with phenol 1a, cinnamoyl chloride 2a (1.0 equiv.), metal chlorides (MCl3, equiv.), solvent (20 mL), time (h), reflux.b Isolated yields.c No detection.d No reaction.e Unknown and unidentified complex mixture was isolated.
1	AlCl3 (2.0)	CCl4	10	54/—^c
2	InCl3 (2.0)	CCl4	10	67/—^c
3	FeCl3 (2.0)	CCl4	10	70/—^c
4	BiCl3 (2.0)	CCl4	10	65/3
5	CeCl3 (2.0)	CCl4	10	—^d
6	AuCl3 (2.0)	CCl4	10	—^d
7	RuCl3 (2.0)	CCl4	10	—^e
8	BiCl3 (3.0)	CCl4	10	68/5
9	BiCl3 (1.0)	CCl4	10	70/—^c
10	BiCl3 (1.0), RuCl3 (1.0)	CCl4	10	15/68
11	BiCl3 (1.0), RuCl3 (1.0)	MeNO2	10	—^e
12	BiCl3 (1.0), RuCl3 (1.0)	(CH2Cl)2	10	35/52
13	BiCl3 (1.0), RuCl3 (1.0)	CH2Cl2	10	78/10
14	BiCl3 (1.0), RuCl3 (1.0)	DMF	10	—^e
15	BiCl3 (1.0), RuCl3 (1.0)	CCl4	15	3/81
16	BiCl3 (1.0), RuCl3 (1.0)	CCl4	20	—^d/75
17	BiCl3 (1.0), CuCl2 (1.0)	CCl4	15	60/8
18	BiCl3 (1.0), FeCl3 (1.0)	CCl4	15	72/3
19	BiCl3 (1.0), AuCl3 (1.0)	CCl4	15	70/—^c

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In decreasing the equivalence of BiCl₃ from 2.0 to 1.0, no isolation of 4a was observed (entry 9). On the basis of the above phenomenon, we found that excess amounts of BiCl₃ could not completely drive the conversion of 3a to 4a. For this reason, another promoter was required to enhance the reaction condition. Hence, we turned the synthetic focus to study the combination of BiCl₃ and RuCl₃-mediated synthesis of flavones. In entry 10, we found that the combination of BiCl₃ (1 equiv.) and RuCl₃ (1 equiv.) provided 4a as the major product (68%) along with a 15% of 3a. With these results in hand, we envisioned that RuCl₃ could trigger the cyclodehydrogenation step to accomplish the synthesis of 4a. Three solvents having different boiling points, such as MeNO₂, (CH₂Cl)₂, CH₂Cl₂, and DMF were tested next. Using MeNO₂ (entry 11), complex unknown products were detected due to the high boiling temperature (101 °C). Entry 12 shows that (CH₂Cl)₂ produced a low conversion ratio (2/3) for 3a and 4a. For the low boiling point solvent, CH₂Cl₂ showed that only 10% of the amounts of 4a were isolated, and 3a was obtained as the major component (78%, entry 13). Among the three chloro-containing solvents, the temperature of boiling CH₂Cl₂ (40 °C) was low; as a result, the cyclodehydrogenation step could not be induced easier. Changing the solvent to DMF (entry 14), however, only unknown and unidentified complex mixture was isolated. Compared with CH₂Cl₂, CCl₄ and (CH₂Cl)₂ with higher boiling points (77 °C and 84 °C) could initiate the occurrence of the cyclodehydrogenation step, besides DMF (153 °C). According to the results, CCl₄ was the preferred solvent to obtain 4a. To achieve the exhaustive conversion, the reaction time was examined next. Elongating the times to 15 h and 20 h respectively, showed that the transformation from 3a to 4a was complete, and the afforded yields of 4a increased to 81% or 75%, respectively (entries 15 and 16). Even though the reaction time was elongated to 20 h, the yield of 4a could not be enhanced. Remarkably, adjusting the temperature from reflux to room temperature (25 °C), no reactions were observed by the combination of BiCl₃ and RuCl₃. To increase the yield of 4a, three combinations were examined next. In entry 17, the combination of BiCl₃ and CuCl₂ provided a 60% yield of 3a along with trace amount of 4a (8%). After changing CuCl₂ to FeCl₃, 72% yield of 3a and 3% yield of 4a were obtained for the combination of BiCl₃ and CuCl₂ (entry 18). The two results were similar to entries 4 and 8. Under the combination of BiCl₃ and AuCl₃ condition (entry 19), only 3a was isolated in a 70% yield, and no desired 4a was detected. Based on the results, we found that CuCl₂, FeCl₃ and AuCl₃ could not trigger the cyclodehydrogenation step easily. From the above screening reaction conditions, we envisioned that the combination of BiCl₃ (1.0 equiv.) and RuCl₃ (1.0 equiv.) could perform better for the formation of 4a in refluxing CCl₄ for 15 h (entry 15). All the conditions were routinely carried out under an atmosphere of air (open-vessel conditions). The heating mantle was used to provide a stable heat source.

To study the scope and limitations of this one-pot route, substituted phenols 1a–1k and cinnamoyl chlorides 2a–2o were examined further. With optimal conditions established (Table 1, entry 14), we found that the one-pot two-step route could allow a direct synthesis of diversified flavones 4a–4y in moderate to good yields (60–82%), as shown in Table 2, entries 1–26. For the electronic character of different Ar substituents on 1a–1k and Ar′ substituents on 2a–2o, these various substituents included: (1) electron-donating mono-, di- or trioxygenated aryl groups, (2) electron-neutral phenyl, biphenyl or naphthyl groups, (3) electron-withdrawing nitroaryl groups, (4) haloaryl groups and (5) heterocyclic furyl and thienyl groups were highly appropriate. However, when the Ar′ substituent was the 2-furyl group, the by-product 3q was obtained in a 10% yield. Furthermore, with the use of RuCl₃, the conversion from 3q to 4q was successful. Therefore, efficient formation of 4a–4y showed that these substituents (Ar and Ar′) did not affect the distribution of the provided yields, besides 4z (Ar = 4-NO₂C₆H₄). The structures of 4a–4y could be determined by ¹H NMR analysis. The structure of 4t was determined by single-crystal X-ray analysis.¹⁷

Table 2 Synthesis of 4a–4y ^a

Entry	1, Ar =	2, Ar′ =	4^b, (%)
a All reactions were run on a 1.0 mmol scale with phenols 1a–1k, cinnamoyl chlorides (2a–2o, 1.0 equiv.), BiCl3 (315 mg, 1.0 equiv.), CCl4 (20 mL), 10 h, reflux (77 °C); then RuCl3·3H2O (261 mg, 1.0 equiv.) was added into the reaction mixture, 5 h, reflux (monitored by TLC).b Isolated yields.c 3q (10%) was obtained.d No detection.
1	1a, Ph	2a, Ph	4a, 81
2	1a, Ph	2b, 4-MeOC6H4	4b, 82
3	1a, Ph	2c, 3-MeOC6H4	4c, 80
4	1a, Ph	2d, 3,4,5-(MeO)3C6H2	4d, 78
5	1a, Ph	2e, 2,3,4-(MeO)3C6H2	4e, 72
6	1a, Ph	2f, 3,4-CH2O2C6H3	4f, 73
7	1a, Ph	2g, 4-PhC6H4	4g, 80
8	1a, Ph	2h, 3,4-(MeO)2C6H3	4h, 72
9	1a, Ph	2i, 3,4-Cl2C6H3	4i, 78
10	1a, Ph	2a, Ph	4j, 80
11	1b, 4-MeOC6H4	2a, Ph	4k, 76
12	1c, 3-MeOC6H4	2a, Ph	4l, 68
13	1d, 3-MeO-5-HOC6H3	2a, Ph	4m, 64
14	1e, 3,5-(MeO)2C6H3	2j, 4-NO2C6H4	4n, 76
15	1a, Ph	2k, 2-naphthyl	4o, 70
16	1a, Ph	2l, 2-FC6H4	4p, 67
17	1a, Ph	2m, 2-furyl	4q, 60^c
18	1a, Ph	2n, 2-thienyl	4r, 62
19	1a, Ph	2o, 1-naphthyl	4s, 75
20	1f, 4-FC6H4	2h, 3,4-(MeO)2C6H3	4t, 73
21	1g, 4-ClC6H4	2h, 3,4-(MeO)2C6H3	4u, 72
22	1h, 4-BrC6H4	2h, 3,4-(MeO)2C6H3	4v, 66
23	1i, 4-MeC6H4	2h, 3,4-(MeO)2C6H3	4w, 74
24	1c, 3-MeOC6H4	2h, 3,4-(MeO)2C6H3	4x, 64
25	1j, 3-MeO-2-HOC6H3	2a, Ph	4y, 60
26	1k, 2-NO2C6H4	2a, Ph	4z, —^d

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On the basis of the experimental results, a plausible mechanism for the formation of 4 is illustrated in Scheme 3. Initially, BiCl₃-mediated complexation of 2 forms A by one bismuth–chloro (Bi–Cl) bond formation. Then, by the removal of ^ϴBiCl₄, B with a styryl acylium center could be generated. Following the Friedel–Crafts ortho-acylation process, B reacts with 1 to lead 3 via one carbon–carbon (C–C) bond formation (green mark).^18a Dubac et al. have reported similar reactions. In addition to BiCl₃, other bismuth salts-mediated Friedel–Crafts reactions have been well-documented.^18b-18d Then, by the involvement of RuCl₃, C with a ruthenium(III)-chelated complex was produced. Furthermore, the intramolecular oxa-Michael addition provided D via one carbon-oxygen (C–O) bond formation (green mark). After the proton exchange, E could be formed along with the releasing HCl. Finally, dehydrogenation of E obtained 4 by the removal of RuCl and HCl.¹⁹ Under the cyclodehydrogenation step, Laurenczy et al. reported the redox conversion between Ru(III) and Ru(I).^19a

Scheme 3 Plausible mechanism.

On the other hand, as an extension of the one-pot two-step synthetic route, changing the combination from BiCl₃/RuCl₃ to BiCl₃/ZnCl₂ was examined. However, the flavanone skeleton 5a was isolated at a 90% yield, and no flavone 4a was detected. A possible reason could be that ZnCl₂ lacks sufficient oxidative ability to completely promote the cyclodehydrogenation under the redox condition such that it only served a Lewis acid role in promoting the formation of 5a via an intramolecular annulation of 3a. Herein, we also developed the BiCl₃/ZnCl₂-mediated one-pot two-step, novel route for the synthesis of flavanone skeleton (Scheme 4).

Scheme 4 Synthesis of 5a.

With the results in mind, cinnamoyl chlorides 2a–2o were adjusted next to crotonoyl chloride (2p) or acryloyl chloride (2q) under one-pot condition (Scheme 5). As shown in eqn (1), the BiCl₃/RuCl₃ mediated reaction of 1a with 2p provided 6a with the chromen-4-one skeleton in only a 31% yield. Compared with 4a (81%), the isolated yield of 6a (31%) was low. The possible reason could be that with the hydrogen on E (yellow, Scheme 3), the low acidity was not easy to abstract by the RuCl₃ for the dehydrogenation step to be triggered efficiently. On the basis of the results, we demonstrated that benzylic hydrogen was acidic and easily eliminated. Furthermore, by the removal of the β-methyl group on 2, BiCl₃/RuCl₃ mediated reaction of 1a with 2q was shown in eqn (2). In particular, only 7a was generated in a 67% yield. However, an intramolecular dehydrogenation step was not initiated so that the predicted 7b was not obtained. The resulting phenomenon meant that cyclodehydrogenation only occurred in cinnamoyl substituents (with benzylic hydrogen). Although substrate 2 was limited to the cinnamoyl substituents, it still provided a novel one-pot synthesis of the flavone skeleton.

Scheme 5 Synthesis of 6a and 7a.

Conclusion

In summary, we have developed a concise route for the effective synthesis of functionalized flavones via BiCl₃/RuCl₃ mediating the one-pot, direct intermolecular ortho-acylation of substituted phenols with cinnamoyl chlorides followed by intramolecular cyclodehydrogenation of the resulting o-hydroxychalcones under refluxing CCl₄ reaction conditions. The process provides a cascade pathway of one carbon–oxygen and one carbon–carbon bond formation. Related plausible mechanisms have been proposed. Further studies regarding the efficient synthetic routes towards flavones will be conducted and published in due course.

Experimental

General

All reagents and solvents were obtained from commercial sources and used without further purification. Reactions were routinely carried out under an atmosphere of air with magnetic stirring. Products in organic solvents were dried with anhydrous magnesium sulfate before concentration in vacuo. Melting points were determined with a SMP3 melting apparatus. ¹H and ¹³C NMR spectra were recorded on a Varian INOVA-400 spectrometer operating at 400 and at 100 MHz, respectively. Chemical shifts (δ) are reported in parts per million (ppm) and the coupling constants (J) are given in Hertz. High resolution mass spectra (HRMS) were measured with a mass spectrometer Finnigan/Thermo Quest MAT 95XL. X-ray crystal structures were obtained with an Enraf-Nonius FR-590 diffractometer (CAD4, Kappa CCD).

A representative synthetic procedure of compounds 4a–4y and 3q is as follows

BiCl₃ (315 mg, 1.0 mmol) was added to a solution of phenols 1a–1k (1.0 mmol) in CCl₄ (20 mL) at 25 °C. The reaction mixture was stirred at 25 °C for 10 min. Cinnamoyl chlorides 2a–2o (1.0 mmol) was added to the reaction mixture at 25 °C. The reaction mixture was stirred at reflux for 10 h (monitored by TLC). Then, RuCl₃·3H₂O (261 mg, 1.0 mmol) was added to the reaction mixture (containing o-hydroxychalcones 3) at reflux. The reaction mixture was stirred at reflux for 5 h (monitored by TLC). The reaction mixture was cooled to 25 °C and the solvent was concentrated. The residue was diluted with water (10 mL) and the mixture was extracted with CH₂Cl₂ (3 × 30 mL). The combined organic layers were washed with brine (2 × 20 mL), dried (MgSO₄), filtered and evaporated to afford crude product under reduced pressure. Purification on silica gel (hexanes/EtOAc = 20/1–4/1) afforded 4a–4y and 3q.

2-Phenylchromen-4-one (4a)²⁰. Yield = 81% (180 mg); white solid; mp = 90–92 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]⁺ calcd for C₁₅H₁₁O₂ 223.0759, found 223.0768; ¹H NMR (400 MHz, CDCl₃): δ 8.24 (dd, J = 1.6, 8.0 Hz, 1H), 7.94–7.92 (m, 2H), 7.71 (dt, J = 2.0, 8.8 Hz, 1H), 7.57 (dd, J = 0.8, 8.0 Hz, 1H), 7.55–7.50 (m, 3H), 7.42 (dt, J = 0.8, 8.0 Hz, 1H), 6.86 (s, 1H); ¹³C{¹H} NMR (100 MHz, CDCl₃): δ 178.4, 163.5, 156.3, 133.8, 131.7, 131.6, 129.0 (2×), 126.3 (2×), 125.7, 125.2, 123.9, 118.1, 107.5.

2-(4-Methoxyphenyl)chromen-4-one (4b)²¹. Yield = 82% (207 mg); white solid; mp = 172–174 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]⁺ calcd for C₁₆H₁₃O₃ 253.0865, found 253.0872; ¹H NMR (400 MHz, CDCl₃): δ 8.22 (dd, J = 1.6, 8.0 Hz, 1H), 7.90 (d, J = 9.2 Hz, 2H), 7.69 (dt, J = 1.6, 8.4 Hz, 1H), 7.56 (dd, J = 0.8, 8.4 Hz, 1H), 7.42 (dt, J = 1.2, 8.0 Hz, 1H), 7.03 (d, J = 9.2 Hz, 2H), 6.81 (s, 1H), 3.89 (s, 3H); ¹³C{¹H} NMR (100 MHz, CDCl₃): δ 178.4, 163.7, 162.5, 156.2, 133.7, 128.6, 128.1 (2×), 125.7, 125.2, 123.9, 117.9, 114.5 (2×), 106.0, 55.5.

2-(3-Methoxyphenyl)chromen-4-one (4c)²². Yield = 80% (202 mg); white solid; mp = 92–94 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]⁺ calcd for C₁₆H₁₃O₃ 253.0865, found 253.0874; ¹H NMR (400 MHz, CDCl₃): δ 8.24 (dd, J = 1.6, 8.0 Hz, 1H), 7.72 (dt, J = 2.0, 8.4 Hz, 1H), 7.59 (dd, J = 0.8, 8.4 Hz, 1H), 7.53 (dt, J = 1.2, 8.0 Hz, 1H), 7.46–7.42 (m, 3H), 7.09 (ddd, J = 0.8, 2.4, 8.8 Hz, 1H), 6.89 (s, 1H), 3.90 (s, 3H); ¹³C{¹H} NMR (100 MHz, CDCl₃): δ 178.5, 160.0, 156.3, 134.0, 133.1, 130.2, 125.7 (2×), 125.4, 118.9, 118.1 (2×), 117.4, 111.8, 107.6, 55.5.

2-(3,4,5-Trimethoxyphenyl)chromen-4-one (4d)²³. Yield = 78% (243 mg); white solid; mp = 168–170 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]⁺ calcd for C₁₈H₁₇O₅ 313.1076, found 313.1084; ¹H NMR (400 MHz, CDCl₃): δ 8.25 (dd, J = 1.6, 8.0 Hz, 1H), 7.73 (dt, J = 1.6, 8.4 Hz, 1H), 7.61 (d, J = 8.0 Hz, 1H), 7.46 (dt, J = 1.6, 7.6 Hz, 1H), 7.16 (s, 2H), 6.89 (s, 1H), 3.97 (s, 6H), 3.94 (s, 3H); ¹³C{¹H} NMR (100 MHz, CDCl₃): δ 178.4, 163.4, 156.3, 153.6 (2×), 141.3, 134.0, 126.8, 125.7, 125.5, 123.9, 118.1, 107.1, 103.9 (2×), 61.1, 56.4 (2×).

2-(2,3,4-Trimethoxyphenyl)chromen-4-one (4e). Yield = 72% (225 mg); white solid; mp = 152–154 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]⁺ calcd for C₁₈H₁₇O₅ 313.1076, found 313.1067; ¹H NMR (400 MHz, CDCl₃): δ 8.24 (dd, J = 2.0, 8.4 Hz, 1H), 7.68 (dt, J = 2.0, 8.4 Hz, 1H), 7.56 (d, J = 9.2 Hz, 1H), 7.52 (dt, J = 1.6, 8.4 Hz, 1H), 7.41 (dt, J = 1.2, 8.0 Hz, 1H), 7.02 (s, 1H), 6.81 (d, J = 8.8 Hz, 1H), 3.96 (s, 3H), 3.94 (s, 3H), 3.92 (s, 3H); ¹³C{¹H} NMR (100 MHz, CDCl₃): δ 178.8, 161.5, 156.5, 156.3, 153.2, 133.5, 128.4, 125.7, 125.0, 124.2, 123.8, 119.1, 117.9, 111.1, 107.4, 61.2, 61.0, 56.1.

2-Benzo[1,3]dioxol-5-ylchromen-4-one (4f)²⁴. Yield = 73% (194 mg); white solid; mp = 200–202 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]⁺ calcd for C₁₆H₁₁O₄ 267.0657, found 267.0650; ¹H NMR (400 MHz, CDCl₃): δ 8.22 (dd, J = 1.6, 8.0 Hz, 1H), 7.70 (dt, J = 1.6, 8.4 Hz, 1H), 7.55 (d, J = 8.0 Hz, 1H), 7.51 (dd, J = 1.6, 8.0 Hz, 1H), 7.42 (dt, J = 0.8, 8.0 Hz, 1H), 7.38 (d, J = 1.6 Hz, 1H), 6.94 (d, J = 8.4 Hz, 1H), 6.81 (s, 1H), 6.08 (s, 2H); ¹³C{¹H} NMR (100 MHz, CDCl₃): δ 178.3, 163.5, 156.1, 150.8, 148.5, 133.9, 125.7, 125.6, 125.3, 123.6, 121.7, 118.0, 108.8, 106.4, 106.3, 102.0.

2-Biphenyl-4-ylchromen-4-one (4g)²⁵. Yield = 80% (238 mg); white solid; mp = 141–143 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]⁺ calcd for C₂₁H₁₅O₂ 299.1072, found 299.1077; ¹H NMR (400 MHz, CDCl₃): δ 8.26 (dd, J = 1.6, 8.0 Hz, 1H), 8.03 (d, J = 8.4 Hz, 2H), 7.76 (d, J = 8.4 Hz, 2H), 7.74 (dt, J = 1.6, 8.4 Hz, 1H), 7.67–7.61 (m, 3H), 7.51–7.40 (m, 4H), 7.00 (s, 1H), ¹³C{¹H} NMR (100 MHz, CDCl₃): δ 178.4, 163.6, 156.3, 144.6, 139.7, 134.0, 130.3, 129.0 (2×), 128.3, 127.7 (2×), 127.2 (2×), 126.9 (2×), 125.7, 125.4, 123.7, 118.1, 107.1.

2-(3,4-Dimethoxyphenyl)chromen-4-one (4h)²⁶. Yield = 72% (203 mg); white solid; mp = 118–120 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]⁺ calcd for C₁₇H₁₅O₄ 283.0970, found 283.0976; ¹H NMR (400 MHz, CDCl₃): δ 8.23 (dd, J = 1.6, 8.0 Hz, 1H), 7.70 (dt, J = 1.6, 8.4 Hz, 1H), 7.59 (d, J = 8.4 Hz, 1H), 7.58 (d, J = 8.4 Hz, 1H), 7.43 (dt, J = 1.2, 8.0 Hz, 1H), 7.42 (d, J = 8.0 Hz, 1H), 7.00 (d, J = 8.4 Hz, 1H), 6.82 (s, 1H), 3.99 (s, 3H), 3.97 (s, 3H); ¹³C{¹H} NMR (100 MHz, CDCl₃): δ 178.4, 163.6, 156.2, 152.2, 149.3, 133.7, 125.7, 125.2, 124.2, 123.8, 120.1, 118.0, 111.2, 108.9, 106.4, 56.1 (2×).

2-(3,4-Dichlorophenyl)chromen-4-one (4i)²⁶. Yield = 78% (226 mg); white solid; mp = 202–204 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]⁺ calcd for C₁₅H₉Cl₂O₂ 290.9980, found 290.9987; ¹H NMR (400 MHz, CDCl₃): δ 8.23 (dd, J = 1.6, 8.0 Hz, 1H), 8.24 (d, J = 1.6 Hz, 1H), 7.75–7.71 (m, 2H), 7.60 (dt, J = 0.8, 8.4 Hz, 2H), 7.45 (dt, J = 0.8, 8.0 Hz, 1H), 6.80 (s, 1H); ¹³C{¹H} NMR (100 MHz, CDCl₃): δ 178.1, 160.9, 156.1, 136.0, 134.1, 133.7, 131.7, 131.1, 128.1, 125.8, 125.6, 125.3, 123.9, 118.1, 108.2.

6-Methoxy-2-phenylchromen-4-one (4j)²². Yield = 80% (202 mg); white solid; mp = 165–167 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]⁺ calcd for C₁₆H₁₃O₃ 253.0865, found 253.0873; ¹H NMR (400 MHz, CDCl₃): δ 7.94–7.90 (m, 2H), 7.59 (d, J = 3.2 Hz, 1H), 7.54–7.49 (m, 4H), 7.29 (dd, J = 3.2, 9.2 Hz, 1H), 6.87 (s, 1H), 3.90 (s, 3H); ¹³C{¹H} NMR (100 MHz, CDCl₃): δ 178.3, 163.3, 157.0, 151.1, 131.8, 131.6, 129.0 (2×), 126.3 (2×), 124.4, 123.9, 119.5, 106.7, 104.8, 55.9.

7-Methoxy-2-phenylchromen-4-one (4k)²². Yield = 76% (192 mg); white solid; mp = 106–108 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]⁺ calcd for C₁₆H₁₃O₃ 253.0865, found 253.0860; ¹H NMR (400 MHz, CDCl₃): δ 8.12 (dd, J = 0.4, 8.4 Hz, 1H), 7.91–7.88 (m, 2H), 7.53–7.48 (m, 3H), 6.99–6.96 (m, 2H), 6.80 (s, 1H), 3.93 (s, 3H); ¹³C{¹H} NMR (100 MHz, CDCl₃): δ 177.8, 164.3, 163.2, 158.0, 131.7, 131.5, 129.0 (2×), 127.0, 126.2 (2×), 117.6, 114.5, 107.3, 100.4, 55.8.

5-Hydroxy-7-methoxy-2-phenylchromen-4-one (4l)²⁷. Yield = 68% (182 mg); white solid; mp = 167–169 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]⁺ calcd for C₁₆H₁₃O₄ 269.0814, found 269.0821; ¹H NMR (400 MHz, CDCl₃): δ 10.81 (br s, 1H), 7.87–7.85 (m, 2H), 7.54–7.48 (m, 3H), 6.63 (s, 1H), 6.47 (d, J = 2.4 Hz, 1H), 6.35 (d, J = 2.4 Hz, 1H), 3.86 (s, 3H); ¹³C{¹H} NMR (100 MHz, CDCl₃): δ 182.4, 165.5, 163.9, 162.1, 157.7, 131.8, 131.2, 129.0 (2×), 126.2 (2×), 105.8, 105.6, 98.1, 92.6, 55.7.

5,7-Dimethoxy-2-phenylchromen-4-one (4m)²². Yield = 64% (181 mg); white solid; mp = 145–147 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]⁺ calcd for C₁₇H₁₅O₄ 283.0970, found 283.0973; ¹H NMR (400 MHz, CDCl₃): δ 7.88–7.83 (m, 2H), 7.54–7.45 (m, 3H), 6.67 (s, 1H), 6.56 (d, J = 2.4 Hz, 1H), 6.36 (d, J = 2.0 Hz, 1H), 3.95 (s, 3H), 3.90 (s, 3H); ¹³C{¹H} NMR (100 MHz, CDCl₃): δ 177.6, 164.0, 160.9, 160.6, 159.9, 131.5, 131.1, 128.9 (2×), 125.9 (2×), 109.3, 109.0, 96.2, 92.8, 56.4, 55.7.

2-(4-Nitrophenyl)chromen-4-one (4n)²¹. Yield = 76% (203 mg); white solid; mp = 128–130 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]⁺ calcd for C₁₅H₁₀NO₄ 268.0610, found 268.0618; ¹H NMR (400 MHz, CDCl₃): δ 8.39 (d, J = 9.2 Hz, 2H), 8.24 (dd, J = 1.6, 8.0 Hz, 1H), 8.11 (d, J = 9.2 Hz, 2H), 7.76 (dt, J = 1.6, 8.8 Hz, 1H), 7.61 (dd, J = 0.8, 8.4 Hz, 1H), 7.47 (dt, J = 1.2, 8.0 Hz, 1H), 6.92 (s, 1H); ¹³C{¹H} NMR (100 MHz, CDCl₃): δ 178.0, 160.6, 156.2, 149.4, 137.6, 134.4, 127.2 (2×), 125.9, 125.8, 124.2 (2×), 123.6, 118.1, 109.6.

2-Naphthalen-2-ylchromen-4-one (4o)²⁸. Yield = 70% (190 mg); white solid; mp = 141–143 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]⁺ calcd for C₁₉H₁₃O₂ 273.0916, found 273.0925; ¹H NMR (400 MHz, CDCl₃): δ 8.52 (s, 1H), 8.23 (dd, J = 1.6, 8.0 Hz, 1H), 8.02–7.90 (m, 4H), 7.76 (dt, J = 1.6, 8.4 Hz, 1H), 7.67 (dd, J = 0.8, 8.4 Hz, 1H), 7.64–7.57 (m, 2H), 7.47 (dt, J = 1.2, 7.6 Hz, 1H), 7.07 (s, 1H); ¹³C{¹H} NMR (100 MHz, CDCl₃): δ 178.5, 163.7, 156.4, 134.8, 134.0, 132.9, 129.1, 129.0, 128.8, 128.1, 127.9, 127.1 (2×), 125.8, 125.4, 123.8, 122.6, 118.1, 107.7.

2-(2-Fluorophenyl)chromen-4-one (4p)²⁹. Yield = 67% (161 mg); white solid; mp = 100–102 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]⁺ calcd for C₁₅H₁₀FO₂ 241.0665, found 241.0669; ¹H NMR (400 MHz, CDCl₃): δ 8.25 (dd, J = 1.6, 8.0 Hz, 1H), 7.94 (dt, J = 1.6, 8.0 Hz, 1H), 7.72 (dt, J = 1.6, 8.0 Hz, 1H), 7.57–7.50 (m, 2H), 7.44 (dt, J = 1.2, 7.6 Hz, 1H), 7.33 (dt, J = 1.2, 8.0 Hz, 1H), 7.24 (dd, J = 1.2, 8.4 Hz, 1H), 6.96 (s, 1H); ¹³C{¹H} NMR (100 MHz, CDCl₃): δ 178.5, 160.6 (d, J = 254.0 Hz), 158.9, 156.4, 133.9, 132.9 (d, J = 9.1 Hz), 129.1, 125.8, 125.3 (2×), 124.6 (d, J = 3.8 Hz), 123.8, 118.1, 117.0 (d, J = 22.7 Hz), 112.4 (d, J = 10.6 Hz).

2-Furan-2-ylchromen-4-one (4q)³⁰. Yield = 60% (127 mg); white solid; mp = 122–124 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]⁺ calcd for C₁₃H₉O₃ 213.0552, found 213.0559; ¹H NMR (400 MHz, CDCl₃): δ 8.22 (dd, J = 2.0, 8.0 Hz, 1H), 7.68 (dt, J = 2.0, 8.4 Hz, 1H), 7.63 (dd, J = 0.8, 2.0 Hz, 1H), 7.50 (dd, J = 0.8, 8.4 Hz, 1H), 7.41 (dt, J = 0.8, 8.0 Hz, 1H), 7.15 (d, J = 3.2 Hz, 1H), 6.76 (s, 1H), 6.62 (dd, J = 2.0, 3.2 Hz, 1H); ¹³C{¹H} NMR (100 MHz, CDCl₃): δ 177.9, 155.8, 155.2, 146.4, 145.8, 133.8, 125.8, 125.2, 124.1, 117.9, 113.1, 112.5, 105.5.

3-Furan-2-yl-1-(2-hydroxyphenyl)propenone (3q). Yield = 10% (21 mg); white solid; mp = 105–107 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]⁺ calcd for C₁₃H₁₁O₃ 215.0708, found 215.0714; ¹H NMR (400 MHz, CDCl₃): δ 12.89 (s, 1H), 7.92 (dd, J = 2.0, 8.4 Hz, 1H), 7.68 (d, J = 14.8 Hz, 1H), 7.560 (dd, J = 0.8, 1.2 Hz, 1H), 7.558 (d, J = 14.8 Hz, 1H), 7.49 (dt, J = 1.6, 8.8 Hz, 1H), 7.02 (dd, J = 0.8, 8.4 Hz, 1H), 6.94 (dt, J = 1.2, 8.4 Hz, 1H), 6.77 (d, J = 3.2 Hz, 1H), 6.54 (dd, J = 1.6, 3.2 Hz, 1H); ¹³C{¹H} NMR (100 MHz, CDCl₃): δ 193.3, 163.5, 151.5, 145.4, 136.3, 131.1, 129.6, 120.0, 118.8, 118.5, 117.6, 117.1, 112.9.

2-Thiophen-2-ylchromen-4-one (4r)³⁰. Yield = 62% (141 mg); white solid; mp = 93–95 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]⁺ calcd for C₁₃H₉O₂S 229.0323, found 229.0332; ¹H NMR (400 MHz, CDCl₃): δ 8.21 (dd, J = 1.6, 7.6 Hz, 1H), 7.34 (dd, J = 1.2, 3.6 Hz, 1H), 7.69 (dt, J = 1.6, 8.4 Hz, 1H), 7.58 (dd, J = 1.2, 4.8 Hz, 1H), 7.54 (dd, J = 0.8, 8.4 Hz, 1H), 7.42 (dt, J = 1.2, 8.4 Hz, 1H), 7.19 (dd, J = 3.6, 4.8 Hz, 1H), 6.72 (s, 1H); ¹³C{¹H} NMR (100 MHz, CDCl₃): δ 177.9, 159.1, 155.9, 135.2, 133.8, 130.3, 128.5, 128.5, 125.7, 125.3, 124.0, 117.9, 106.2.

2-Naphthalen-1-ylchromen-4-one (4s)²⁰. Yield = 75% (204 mg); white solid; mp = 139–141 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]⁺ calcd for C₁₉H₁₃O₂ 273.0916, found 273.0910; ¹H NMR (400 MHz, CDCl₃): δ 8.32 (dd, J = 1.6, 8.0 Hz, 1H), 8.16–8.12 (m, 1H), 8.04 (d, J = 8.4 Hz, 1H), 7.98–7.94 (m, 1H), 7.78 (d, J = 6.4 Hz, 1H), 7.74 (dt, J = 1.6, 8.8 Hz, 1H), 7.61–7.54 (m, 4H), 7.49 (dt, J = 1.2, 8.0 Hz, 1H), 6.73 (s, 1H); ¹³C{¹H} NMR (100 MHz, CDCl₃): δ 178.3, 165.6, 156.8, 134.0, 133.8, 131.6, 130.6, 130.4, 128.7, 128.0, 127.5, 126.6, 125.9, 125.4, 125.1, 124.9, 124.0, 118.3, 113.0.

2-(3,4-Dimethoxyphenyl)-6-fluorochromen-4-one (4t). Yield = 73% (219 mg); white solid; mp = 168–170 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]⁺ calcd for C₁₇H₁₄FO₄ 301.0876, found 301.0879; ¹H NMR (400 MHz, CDCl₃): δ 7.86 (dd, J = 2.8, 8.0 Hz, 1H), 7.60–7.55 (m, 2H), 7.42 (dt, J = 3.2, 8.8 Hz, 1H), 7.38 (br s, 1H), 6.99 (d, J = 8.0 Hz, 1H), 6.81 (s, 1H), 3.98 (s, 3H), 3.97 (s, 3H); ¹³C{¹H} NMR (100 MHz, CDCl₃): δ 177.5 (d, J = 2.3 Hz), 163.9, 160.8, 158.4, 152.4, 149.4, 124.9 (d, J = 7.6 Hz), 123.8, 121.8 (d, J = 25.7 Hz), 120.2, 120.0 (d, J = 7.6 Hz, 1H), 111.2, 110.6 (d, J = 23.5 Hz), 108.9, 105.7, 56.13, 56.11. Single-crystal X-ray diagram: crystal of compound 4t was grown by slow diffusion of EtOAc into a solution of compound 4t in CH₂Cl₂ to yield colorless prisms. The compound crystallizes in the monoclinic crystal system, space group Pn, a = 4.0051(3) Å, b = 10.1298(8) Å, c = 16.3327(12) Å, V = 662.13(9) ų, Z = 2, d_calcd = 1.506 g cm⁻³, F(000) = 312, 2θ range 2.010–26.380°, R indices (all data) R1 = 0.0307, wR2 = 0.0827.

6-Chloro-2-(3,4-dimethoxyphenyl)chromen-4-one (4u)³¹. Yield = 72% (228 mg); white solid; mp = 199–201 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]⁺ calcd for C₁₇H₁₄ClO₄ 317.0581, found 317.0588; ¹H NMR (400 MHz, CDCl₃): δ 8.20 (d, J = 2.4 Hz, 1H), 7.63 (d, J = 2.8 Hz, 1H), 7.56 (dd, J = 2.4, 8.4 Hz, 1H), 7.54 (dd, J = 0.4, 8.8 Hz, 1H), 7.37 (d, J = 2.0 Hz, 1H), 6.99 (d, J = 8.4 Hz, 1H), 6.78 (s, 1H), 3.99 (s, 3H), 3.97 (s, 3H); ¹³C{¹H} NMR (100 MHz, CDCl₃): δ 177.1, 163.8, 154.5, 152.4, 149.4, 133.8, 131.1, 125.2, 124.9, 123.8, 120.2, 119.7, 111.2, 108.9, 106.3, 56.1 (2×).

6-Bromo-2-(3,4-dimethoxyphenyl)chromen-4-one (4v)³². Yield = 66% (238 mg); white solid; mp = 206–208 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]⁺ calcd for C₁₇H₁₄BrO₄ 361.0076, found 361.0081; ¹H NMR (400 MHz, CDCl₃): δ 8.34 (d, J = 2.4 Hz, 1H), 7.77 (dd, J = 2.4, 8.8 Hz, 1H), 7.55 (dd, J = 2.0, 8.4 Hz, 1H), 7.47 (d, J = 8.8 Hz, 1H), 7.36 (d, J = 2.0 Hz, 1H), 6.98 (d, J = 8.4 Hz, 1H), 6.81 (s, 1H), 3.98 (s, 3H), 3.97 (s, 3H); ¹³C{¹H} NMR (100 MHz, CDCl₃): δ 176.9, 163.9, 154.9, 152.5, 149.4, 136.6, 128.3, 125.1, 123.7, 120.3, 119.9, 118.7, 111.2, 108.9, 106.2, 56.1 (2×).

2-(3,4-Dimethoxyphenyl)-6-methylchromen-4-one (4w)³³. Yield = 74% (219 mg); white solid; mp = 182–184 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]⁺ calcd for C₁₈H₁₇O₄ 297.1127, found 297.1138; ¹H NMR (400 MHz, CDCl₃): δ 8.05 (br s, 1H), 7.64–7.52 (m, 3H), 7.44 (br s, 1H), 7.15 (br s, 1H), 7.00 (s, 1H), 3.98 (s, 6H), 2.50 (s, 3H); ¹³C{¹H} NMR (100 MHz, CDCl₃): δ 178.4, 164.8, 154.6, 152.7, 149.4, 135.7, 125.6, 125.0, 123.8, 123.1, 120.8, 117.9, 117.6, 111.3, 109.1, 56.3, 56.2, 21.0.

2-(3,4-Dimethoxyphenyl)-7-methoxychromen-4-one (4x)³⁴. Yield = 64% (200 mg); white solid; mp = 172–174 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]⁺ calcd for C₁₈H₁₇O₅ 313.1076, found 313.1085; ¹H NMR (400 MHz, CDCl₃): δ 8.14 (d, J = 8.8 Hz, 1H), 7.57 (dd, J = 2.0, 8.8 Hz, 1H), 7.38 (d, J = 2.0 Hz, 1H), 7.02–6.97 (m, 3H), 6.89 (s, 1H), 3.99 (s, 3H), 3.97 (s, 3H), 3.95 (s, 3H); ¹³C{¹H} NMR (100 MHz, CDCl₃): δ 177.7, 164.4, 163.8, 158.0, 152.3, 149.3, 127.0, 124.0, 120.2, 117.1, 114.7, 111.2, 108.9, 105.8, 100.4, 56.13, 56.10, 55.9.

8-Hydroxy-7-methoxy-2-phenylchromen-4-one (4y). Yield = 60% (161 mg); white solid; mp = 236–238 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]⁺ calcd for C₁₆H₁₃O₄ 269.0814, found 269.0816; ¹H NMR (400 MHz, CDCl₃): δ 8.01–7.99 (m, 2H), 7.80 (d, J = 9.2 Hz, 1H), 7.56–7.50 (m, 3H), 7.06 (d, J = 9.2 Hz, 1H), 6.96 (s, 1H), 4.05 (s, 3H), 2.80 (br s, 1H); ¹³C{¹H} NMR (100 MHz, CDCl₃): δ 178.3, 150.0, 144.9, 134.0, 131.6, 130.8, 129.1 (3×), 126.4 (2×), 116.5 (2×), 108.6, 106.7, 56.7.

2-Phenylchroman-4-one (5a)³⁵. BiCl₃ (315 mg, 1.0 mmol) was added to a solution of phenol 1a (94 mg, 1.0 mmol) in CCl₄ (20 mL) at 25 °C. The reaction mixture was stirred at 25 °C for 10 min. Cinnamoyl chloride 2a (167 mg, 1.0 mmol) was added to the reaction mixture at 25 °C. The reaction mixture was stirred at reflux for 10 h. Then, ZnCl₂ (136 mg, 1.0 mmol) was added to the reaction mixture at reflux. The reaction mixture was stirred at reflux for 5 h. The reaction mixture was cooled to 25 °C and the solvent was concentrated. The residue was diluted with water (10 mL) and the mixture was extracted with CH₂Cl₂ (3 × 30 mL). The combined organic layers were washed with brine (2 × 20 mL), dried (MgSO₄), filtered and evaporated to afford crude product under reduced pressure. Purification on silica gel (hexanes/EtOAc = 20/1–4/1) afforded 5a. Yield = 90% (202 mg); colorless solid; mp = 77–79 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]⁺ calcd for C₁₅H₁₃O₂ 225.0916, found 225.0924; ¹H NMR (400 MHz, CDCl₃): δ 7.95 (dd, J = 2.0, 8.0 Hz, 1H), 7.54–7.38 (m, 6H), 7.08–7.04 (m, 2H), 5.49 (dd, J = 2.8, 13.2 Hz, 1H), 3.10 (dd, J = 13.2, 16.8 Hz, 1H), 2.90 (dd, J = 2.8, 16.8 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 191.9, 161.5, 138.7, 136.2, 128.8 (2×), 128.7, 127.0, 126.1 (2×), 121.6, 120.9, 118.1, 79.6, 44.6.

2-Methyl-chromen-4-one (6a).³⁶ and chroman-4-one (7a)³⁷. BiCl₃ (315 mg, 1.0 mmol) was added to a solution of phenol 1a (94 mg, 1.0 mmol) in CCl₄ (20 mL) at 25 °C. The reaction mixture was stirred at 25 °C for 10 min. Crotonoyl chloride 2p (104 mg, 1.0 mmol) or acryloyl chloride 2q (90 mg, 1.0 mmol) was added to the reaction mixture at 25 °C. The reaction mixture was stirred at reflux for 10 h. Then, RuCl₃·3H₂O (261 mg, 1.0 mmol) was added to the reaction mixture at reflux. The reaction mixture was stirred at reflux for 5 h. The reaction mixture was cooled to 25 °C and the solvent was concentrated. The residue was diluted with water (10 mL) and the mixture was extracted with CH₂Cl₂ (3 × 30 mL). The combined organic layers were washed with brine (2 × 20 mL), dried (MgSO₄), filtered and evaporated to afford crude product under reduced pressure. Purification on silica gel (hexanes/EtOAc = 20/1–4/1) afforded 6a and 7a. For 6a: yield = 31% (50 mg); colorless solid; mp = 62–64 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]⁺ calcd for C₁₀H₉O₂ 161.0603, found 161.0612; ¹H NMR (400 MHz, CDCl₃): δ 8.17 (dd, J = 1.6, 8.0 Hz, 1H), 7.63 (dt, J = 1.6, 8.8 Hz, 1H), 7.41 (dd, J = 0.8, 8.0 Hz, 1H), 7.35 (dt, J = 0.8, 8.0 Hz, 1H), 6.17 (s, 1H), 2.38 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ 178.2, 166.2, 156.5, 133.4, 125.6, 124.9, 123.6, 117.8, 110.6, 20.6. For 7a: yield = 67% (99 mg); colorless liquid; HRMS (ESI-TOF) m/z: [M + H]⁺ calcd for C₉H₉O₂ 161.0603, found 161.0612; ¹H NMR (400 MHz, CDCl₃): δ 7.86 (dd, J = 2.0, 8.0 Hz, 1H), 7.44 (dt, J = 1.6, 8.4 Hz, 1H), 6.98 (dt, J = 1.2, 8.0 Hz, 1H), 6.94 (dd, J = 1.2, 8.4 Hz, 1H), 4.50 (t, J = 6.4 Hz, 2H), 2.78 (t, J = 6.4 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃): δ 191.7, 161.8, 135.8, 127.0, 121.2 (2×), 117.8, 66.9, 37.7.

Conflicts of interest

There are no conflicts to declare.

Acknowledgements

The authors would like to thank the Ministry of Science and Technology of the Republic of China (Taiwan) for its financial support (MOST 109-2113-M-037-014-MY3).

Notes and references

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Footnote

† Electronic supplementary information (ESI) available: Scanned photocopies of NMR spectral data for all compounds and X-ray analysis data of 4t were supported. CCDC 1957347. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/d1ra00534k

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