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Abstract

Rh(III)-catalyzed C–H activation of salicylaldehyde followed by an insertion reaction with sulfoxonium ylides and cyclization is applied to the synthesis of flavonoids. This one-pot strategy exhibits good functional group tolerance and gives flavones in moderate-to-good yields.

Keywords

C–H functionalization rhodium salicylaldehyde sulfoxonium ylide

Introduction

Flavonoids are a class of natural products with various biological activities^1–7 and are widely used in medicines,^8,9 such as nobiletin,^10,11 luteolin,^12–15 and flavone-8-acetic acid.¹⁶ Therefore, the development of efficient methods to synthesize flavonoid scaffolds remains a topic of interest.^17–24 In recent years, transition metal catalyzed C–C bond and C–hetero bond formation are effective methods for the synthesis of flavonoids.^25,26 Baruah et al.²⁷ developed Ru(II)-catalyzed C–H activation and annulations of salicylaldehydes and alkynes to afford flavonoids (Scheme 1(a)). Sun et al.²⁸ prepared flavonoids via Rh(III)-catalyzed selective cyclization of salicylaldehyde and diazo compounds (Scheme 1(b)). These reactions showed significant advances in building the flavonoid scaffold, but these methods demonstrated some limitations, such as moderate yields and the employment of potentially dangerous diazo compounds. Recently, sulfoxonium ylides have received wide attention²⁹ as safer carbene precursor.^30–35 Based on our previous research on C–H bond activation^36,37 and heterocyclic chemistry, herein we report an efficient one-pot synthesis of flavonoids via Rh(III)-catalyzed C–H bond activation and annulation of salicylaldehydes^23,27 with sulfoxonium ylides (Scheme 1(c)).

Scheme 1.

Synthesis of flavonoids from salicylaldehydes.

Results and discussion

We envisaged that Rh(III)-catalyzed C–H activation of salicylaldehyde followed by the insertion reaction with the sulfoxonium ylide and cyclization might afford 2-phenyl-4H-chromen-4-one (3aa).^38–41 A preliminary attempt with 2.5 mol% of [Cp*RhCl₂]₂ and 1 equiv. of NaOAc in dichloroethane (DCE) was demonstrated to be effective, giving the desired product 3aa in 56% yield after the acid-promoted cyclization (Table 1, entry 1). Among a set of representative additives including NaOAc and AgOAc, CsOAc was optimal, promoting the yield of 3aa to 86% (entries 1–5). Furthermore, decreasing the additive loading to 0.5 equiv. did not diminish the yield (entry 6). Different solvents, such as MeOH, dioxane, toluene, acetonitrile, and acetic acid, were also screened; however, none of them gave higher yields compared to DCE (entries 7–11). After optimizing the reaction time and temperature, the highest yield (89%) was obtained (entries 12–14). Finally, a control experiment revealed that omission of [Cp*RhCl₂]₂ completely inhibited the reaction (entry 15).

Table 1.

Optimization of the reaction conditions^a.


Entry	Additive (equiv.)	Solvent	Time (h)	Yield^b (%)
1	NaOAc (1)	DCE	12	56
2	HOAc (1)	DCE	12	12
3	AgOAc (1)	DCE	12	80
4	CsOAc (1)	DCE	12	86
5	−	DCE	12	<5
6	CsOAc (0.5)	DCE	12	87
7	CsOAc (0.5)	MeOH	12	Trace
8	CsOAc (0.5)	Dioxane	12	67
9	CsOAc (0.5)	Toluene	12	26
10	CsOAc (0.5)	CH₃CN	12	71
11	CsOAc (0.5)	HOAc	12	<5
12	CsOAc (0.5)	DCE	6	89
13^c	CsOAc (0.5)	DCE	6	71
14^d	CsOAc (0.5)	DCE	6	87
15^e	CsOAc (0.5)	DCE	6	−

Reaction conditions: (1) 1a (0.2 mmol), 2a (0.3 mmol, 1.5 equiv.), base (0.5 equiv.), [Cp*RhCl₂]₂ (2.5 mol%) solvent (2.0 mL), 100 °C, Ar. (2) H₂SO₄/HOAc (1% v/v, 1 mL), 100 °C, 3 h.

Isolated yields.

At 80 °C.

At 120 °C.

In the absence of [Cp*RhCl₂]₂. The bold-faced values indicated the optimized conditions in this table.

With optimized reaction conditions in hand, we sought to evaluate the scope and generality of the salicylaldehydes in this reaction (Table 2). Salicylaldehydes bearing electron-donating substituents such as methyl and methoxy groups at 5-position gave the corresponding products 3ea and 3ga in 81% and 93% yields, respectively. Halides were also tolerated under the standard conditions, which provided the desired products 3ba–3da in 92%–94% yields. In contrast, a substrate with a strongly electron-withdrawing nitro groups gave a lower yield in this reaction, delivering the corresponding product 3fa in 36% yield. Steric effects were also investigated in this reaction; when the C3 position and C4 position of the salicylaldehydes contained Cl, Br, Me, or methoxy groups, the reactions proceeded well to provide 3ha–3la in 73%–93% yields. To our delight, a hydroxy group substituted piperonal also provided the desired product 3ma in 64% yield.

Table 2.

Substrate scope of salicylaldehydes^a.


Entry	Product	R	Yield^b (%)
1	3aa	H	89
2	3ba	5-F	93
3	3ca	5-Cl	94
4	3da	5-Br	92
5	3ea	5-Me	81
6	3fa	5-NO₂	36
7	3ga	5-MeO	93
8	3ha	4-Cl	88
9	3ia	4-Me	81
10	3ja	3-Br	73
11	3ka	3-Me	89
12	3la	3-MeO	93
13	3ma	1,3-Benzodioxole	64

Reaction conditions: (1) 1a (0.2 mmol), 2a (0.3 mmol, 1.5 equiv.), CsOAc (0.5 equiv.), [Cp*RhCl₂]₂ (2.5 mol%), DCE (2.0 mL), 100 °C, Ar. (2) H₂SO₄/HOAc (1% v/v, 1 mL), 100 °C, 3 h.

Isolated yields.

Subsequently, the scope of the sulfoxonium ylides was explored (Table 3). Sulfoxonium ylides bearing various electron-donating (Me and OMe) and electron-withdrawing groups (F, Cl, Br, and CF₃) on the phenyl ring reacted smoothly with 1a to afford corresponding products 3ab–3al in 73%–95% yields. It is worth noting that not only aryl-substituted sulfoxonium ylides, but also alkyl-substituted substrates could be transformed into the desired products, for example, 3am and 3ap in high yields (91% and 95%). Furthermore, thiophene- and naphthalene-substituted sulfoxonium ylides afford electron-donating products 3an and 3ao in 87% and 93% yield, respectively.

Table 3.

Substrate scope of the sulfoxonium ylides^a.


Entry	Product	R	Yield^b (%)
1	3ab	4-F-C₆H₄	88
2	3ac	4-Cl-C₆H₄	87
3	3ad	4-Br-C₆H₄	89
4	3ae	4-Me-C₆H₄	92
5	3af	4-F₃C-C₆H₄	88
6	3ag	4-MeO-C₆H₄	75
7	3ah	2-Cl-C₆H₄	74
8	3ai	2-Me-C₆H₄	83
9	3aj	2-MeO-C₆H₄	95
10	3ak	3-Me-C₆H₄	77
11	3al	3-Br-C₆H₄	73
12	3am	C(CH₃)₃	91
13	3an	2-Thienyl	87
14	3ao	2-Naphthyl	93
15	3ap	1-Adamantyl	95

Reaction conditions: (1) 1a (0.2 mmol), 2a (0.3 mmol, 1.5 equiv.), CsOAc (0.5 equiv.), [Cp*RhCl₂]₂ (2.5 mol%), DCE (2.0 mL), 100 °C, Ar. (2) H₂SO₄/HOAc (1% v/v, 1 mL), 100 °C, 3 h.

Isolated yields.

Based on previous literature reports on related systems,^{28,31,34,42,43} a plausible reaction mechanism is proposed in Scheme 2. Initially, salicylaldehyde 1a was activated by the Rh(III) catalyst to produce a rhodacyclic intermediate A. Next sulfoxonium ylide 2a reacted with A to afford intermediate B, which transformed into intermediate C by elimination of dimethyl sulfoxide (DMSO). Next, a six-membered rhodacyclic intermediate D formed by migratory insertion of the Rh–C bond into the activated carbene. Protonation of D would release the catalyst and afford 4, which is transformed into product 3aa via an acid-promoted cyclization.

Scheme 2.

Proposed reaction mechanism.

Conclusion

In summary, we have described a Rh(III)-catalyzed one-pot synthesis of flavones via the reaction of salicylaldehydes and sulfoxonium ylides. The reaction exhibits good functional group tolerance with a broad range of substrates, affording with moderate-to-good yields of the products under optimized conditions. Further investigations on the synthetic applications of this method are currently underway in our laboratory.

Experimental section

All commercially available reagents were used as received unless otherwise stated. Reactions were monitored by thin layer chromatography (TLC) and visualized under UV light (254 nm). Melting points were determined using a Büchi B-540 capillary melting point apparatus. Nuclear magnetic resonance (NMR) spectra were recorded on Varian spectrometer (400 MHz) with CDCl₃ as the solvent and tetramethylsilane (TMS) as an internal standard. High-resolution mass spectra (HRMS) were recorded on an electrospray ionization quadrupole time-of-flight (ESI-Q-TOF) System ESI spectrometer.

General procedure for the synthesis of 3

A sealed tube was charged with 1a (0.2 mmol, 1.0 equiv.), 2a (0.3 mmol, 1.5 equiv.), [Cp*RhCl₂]₂ (0.005 mmol, 2.5 mol%), and CsOAc (0.1 mmol, 0.5 equiv.) in DCE (2 mL). After the reaction mixture had been stirred at 100 °C under Ar for 6 h, 1 mL of H₂SO₄/HOAc (10 μL of H₂SO₄ dissolved in 0.99 mL of HOAc) was added at room temperature. After completion of the addition, the reaction mixture was then stirred at 100 °C for 3 h before being cooled to room temperature. The mixture was diluted with EtOAc (20 mL), washed with brine, and dried over anhydrous Na₂SO₄. After removal of the EtOAc, the residue was purified by chromatography on basic silica gel (PE/EtOAc = 8/1) to afford 3aa (40 mg, 89%) as a white solid.

2-Phenyl-4H-chromen-4-one (3aa): Product 3aa was obtained as a white solid (40 mg, 89%); m.p.: 96–98 °C. ¹H NMR (400 MHz, CDCl₃): δ = 8.24 (1H, d, J = 8.0 Hz, CH), 7.97–7.89 (2H, m, 2CH), 7.71 (1H, t, J = 7.8 Hz, CH), 7.61–7.49 (4H, m, 4CH), 7.43 (1H, t, J = 7.6 Hz, CH), 6.84 (1H, s, CH). ¹³C NMR (101 MHz, CDCl₃): δ = 178.48 (C_q), 163.40 (C_q), 156.24 (C_q), 133.77 (CH), 131.75 (C_q), 131.59 (CH), 129.03 (CH), 126.28 (CH), 125.69 (CH), 125.22 (CH), 123.95 (C_q), 118.07 (CH), 107.58 (CH). HRMS (ESI): m/z calcd for C₁₅H₁₁O₂ [M + H]⁺: 223.0754; found: 223.0743.

6-Fluoro-2-phenyl-4H-chromen-4-one (3ba): Product 3ba was obtained as a yellow solid (45 mg, 93%); m.p.: 105–107 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.96–7.83 (3H, m, 3CH), 7.63–7.50 (4H, m, 4CH), 7.43 (1H, t, J = 8.0 Hz, CH), 6.82 (1H, s, CH). ¹³C NMR (101 MHz, CDCl₃): δ = 177.63 (C_q), 163.69 (C_q), 160.81 (C_q), 158.35 (C_q), 152.45 (CH), 131.65 (d, ²J_C–F = 28.2 Hz, C_q), 129.09 (CH), 126.31 (CH), 125.16 (d, ³J_C–F = 7.2 Hz, C_q), 121.91 (d, ²J_C–F = 25.6 Hz, CH), 120.16 (d, ³J_C–F = 8.0 Hz, CH), 110.64 (d, ²J_C–F = 23.8 Hz, CH), 106.90 (CH). HRMS (ESI): m/z calcd for C₁₅H₉FNaO₂ [M + Na]⁺: 263.0479; found: 263.0473.

6-Chloro-2-phenyl-4H-chromen-4-one (3ca): Product 3ca was obtained as a yellow solid (48 mg, 94%); m.p.: 178–180 °C. ¹H NMR (400 MHz, CDCl₃): δ = 8.19 (1H, d, J = 2.4 Hz, CH), 7.97–7.84 (2H, m, 2CH), 7.64 (1H, dd, J = 9.0, 2.4 Hz, CH), 7.58–7.50 (4H, m, 4CH), 6.83 (1H, s, CH). ¹³C NMR (101 MHz, CDCl₃): δ = 177.19 (C_q), 163.65 (C_q), 154.53 (C_q), 133.93 (CH), 131.84 (C_q), 131.36 (CH), 131.17 (C_q), 129.09 (CH), 126.29 (CH), 125.15 (C_q), 124.91 (CH), 119.79 (CH), 107.46 (CH). HRMS (ESI): m/z calcd for C₁₅H₉ClNaO₂ [M + Na]⁺: 279.0183; found: 279.0175.

6-Bromo-2-phenyl-4H-chromen-4-one (3da): Product 3da was obtained as a yellow solid (55 mg, 92%); m.p.: 192 –194 °C. ¹H NMR (400 MHz, CDCl₃): δ= 8.35 (1H, d, J = 2.4 Hz, CH), 7.91 (2H, dd, J = 8.0, 1.8 Hz, 2CH), 7.78 (1H, dd, J = 9.0, 2.6 Hz, CH), 7.58–7.50 (3H, m, 3CH), 7.47 (1H, d, J = 9.0 Hz, CH), 6.83 (1H, s, CH). ¹³C NMR (101 MHz, CDCl₃): δ= 177.04 (Cq), 163.65 (Cq), 154.96 (Cq), 136.69 (CH), 131.85 (CH), 131.32 (Cq), 129.08 (CH), 128.33 (CH), 126.29 (CH), 125.27 (Cq), 120.01 (CH), 118.64 (Cq), 107.52 (CH). HRMS (ESI): m/z calcd for C₁₅H₉BrNaO₂ [M + Na]⁺: 322.9678; found: 322.9686.

6-Methyl-2-phenyl-4H-chromen-4-one (3ea): Product 3ea was obtained as a yellow solid (38 mg, 81%); m.p.: 124–126 °C. ¹H NMR (400 MHz, CDCl₃): δ = 8.02 (1H, s, CH), 7.97–7.89 (2H, m, 2CH), 7.59–7.43 (5H, m, 5CH), 6.82 (1H, s, CH), 2.47 (3H, s, CH₃). ¹³C NMR (101 MHz, CDCl₃): δ = 178.62 (C_q), 163.24 (C_q), 154.53 (C_q), 135.19 (CH), 134.98 (C_q), 131.88 (CH), 131.48 (C_q), 128.99 (CH), 126.25 (CH), 125.03 (CH), 123.62 (C_q), 117.82 (CH), 107.44 (CH), 20.94 (CH₃). HRMS (ESI): m/z calcd for C₁₆H₁₂O₂ [M + H]⁺: 237.0910; found: 237.0903.

6-Nitro-2-phenyl-4H-chromen-4-one (3fa): Product 3fa was obtained as a yellow solid (19 mg, 36%); m.p.: 195–197 °C. ¹H NMR (400 MHz, CDCl₃): δ = 9.11 (1H, d, J = 2.8 Hz, CH), 8.55 (1H, dd, J = 9.0, 2.8 Hz, CH), 7.94 (2H, dd, J = 8.0, 1.4 Hz, 2CH), 7.74 (1H, d, J = 9.0 Hz, CH), 7.67–7.51 (3H, m, 3CH), 6.90 (1H, s, CH). ¹³C NMR (101 MHz, CDCl₃): δ = 176.64 (C_q), 164.10 (C_q), 159.03 (C_q), 144.80 (C_q), 132.35 (CH), 130.72 (C_q), 129.26 (CH), 128.11 (CH), 126.41 (CH), 124.05 (CH), 122.48 (C_q), 119.81 (CH), 107.83 (CH). HRMS (ESI): m/z calcd for C₁₅H₁₀NO₄ [M + H]⁺: 268.0604; found: 268.0608.

6-Methoxy-2-phenyl-4H-chromen-4-one (3ga): Product 3ga was obtained as a yellow solid (47 mg, 93%); m.p.: 161–163 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.97–7.85 (2H, m, 2CH), 7.60 (1H, d, J = 3.0 Hz, CH), 7.55–7.48 (4H, m, 4CH), 7.30 (1H, dd, J = 9.0, 3.0 Hz, CH), 6.83 (1H, s, CH), 3.91 (3H, s, CH₃). ¹³C NMR (101 MHz, CDCl₃): δ = 178.41 (C_q), 163.12 (C_q), 156.97 (C_q), 151.06 (C_q), 131.84 (C_q), 131.46 (CH), 128.99 (CH), 126.21 (CH), 124.64 (C_q), 123.80 (CH), 119.49 (CH), 106.86 (CH), 104.78 (CH), 55.92 (CH₃). HRMS (ESI): m/z calcd for C₁₆H₁₃O₃ [M + H]⁺: 253.0859; found: 253.0849.

7-Chloro-2-phenyl-4H-chromen-4-one (3ha): Product 3ha was obtained as a yellow solid (45 mg, 88%); m.p.: 159–161 °C. ¹H NMR (400 MHz, CDCl₃): δ = 8.17 (1H, d, J = 8.6 Hz, CH), 7.90 (2H, d, J = 6.6 Hz, 2CH), 7.61 (1H, s, CH), 7.54 (3H, d, J = 6.8 Hz, 3CH), 7.39 (1H, d, J = 8.2 Hz, CH), 6.82 (1H, s, CH).¹³C NMR (101 MHz, CDCl₃): δ = 177.94 (C_q), 163.51 (C_q), 156.34 (C_q), 139.75 (C_q), 131.82 (C_q), 131.32 (CH), 129.09 (CH), 127.06 (CH), 126.26 (CH), 126.06 (CH), 122.83 (C_q), 118.17 (CH), 107.87 (CH). HRMS (ESI): m/z calcd for C₁₅H₉ClNaO₂ [M + Na]⁺: 279.0183; found: 279.0174.

7-Methyl-2-phenyl-4H-chromen-4-one (3ia): Product 3ia was obtained as a yellow solid (38 mg, 81%); m.p.: 124–126 °C. ¹H NMR (400 MHz, CDCl₃): δ = 8.11 (1H, d, J = 8.0 Hz, CH), 7.96–7.87 (2H, m, 2CH), 7.52 (3H, d, J = 4.0 Hz, 3CH), 7.38 (1H, s, CH), 7.23 (1H, d, J = 8.0 Hz, CH), 6.80 (1H, s, CH), 2.51 (3H, s, CH₃). ¹³C NMR (101 MHz, CDCl₃): δ = 178.42 (C_q), 163.10 (C_q), 156.37 (C_q), 145.10 (C_q), 131.87 (C_q), 131.46 (CH), 128.99 (CH), 126.70 (CH), 126.21 (CH), 125.41 (CH), 121.68 (CH), 117.83 (C_q), 107.50 (CH), 21.84 (CH₃). HRMS (ESI): m/z calcd for C₁₆H₁₂NaO₂ [M + Na]⁺: 259.0730; found: 259.0724.

8-Bromo-2-phenyl-4H-chromen-4-one (3ja): Product 3ja was obtained as a yellow solid (44 mg, 73%); m.p.: 174–176 °C. ¹H NMR (400 MHz, CDCl₃): δ = 8.18 (1H, d, J = 8.8 Hz, CH), 8.05–8.00 (2H, m, 2CH), 7.92 (1H, d, J = 8.4 Hz, CH), 7.60–7.51 (3H, m, 3CH), 7.30 (1H, t, J = 7.8 Hz, CH), 6.88 (1H, s, CH). ¹³C NMR (101 MHz, CDCl₃): δ = 177.84 (C_q), 163.34 (C_q), 152.73 (C_q), 137.14 (CH), 131.95 (C_q), 131.20 (CH), 129.16 (CH), 126.46 (CH), 125.82 (CH), 125.32 (CH), 125.07 (C_q), 111.98 (C_q), 107.19 (CH). HRMS (ESI): m/z calcd for C₁₅H₉BrNaO₂ [M + Na]⁺: 322.9678; found: 322.9669.

8-Methyl-2-phenyl-4H-chromen-4-one (3ka): Product 3ka was obtained as a yellow solid (42 mg, 89%); m.p.: 164–166 °C. ¹H NMR (400 MHz, CDCl₃): δ = 8.07 (1H, d, J = 7.8 Hz, CH), 7.98–7.90 (2H, m, 2CH), 7.57–7.49 (4H, m, 4CH), 7.30 (1H, t, J = 7.6 Hz, CH), 6.84 (1H, s, CH), 2.61 (3H, s, CH₃). ¹³C NMR (101 MHz, CDCl₃): δ = 178.85 (C_q), 162.86 (C_q), 154.66 (C_q), 134.69 (C_q), 132.01 (C_q), 131.53 (CH), 129.07 (CH), 127.49 (CH), 126.16 (CH), 124.73 (CH), 123.82 (CH), 123.28 (C_q), 107.29 (CH), 15.83 (CH₃). HRMS (ESI): m/z calcd for C₁₆H₁₂NaO₂ [M + Na]⁺: 259.0730; found: 259.0720.

8-Methoxy-2-phenyl-4H-chromen-4-one (3la): Product 3la was obtained as a yellow solid (46 mg, 93%); m.p.: 197–199 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.99–7.95 (2H, m, 2CH), 7.78 (1H, dd, J = 8.0, 1.0 Hz, CH), 7.54–7.50 (3H, m, 3CH), 7.33 (1H, t, J = 8.0 Hz, CH), 7.22–7.15 (1H, m, CH), 6.85 (1H, s, CH), 4.03 (3H, s, CH₃). ¹³C NMR (101 MHz, CDCl₃): δ = 178.46 (C_q), 163.01 (C_q), 149.09 (C_q), 146.62 (C_q), 131.79 (C_q), 131.54 (CH), 129.00 (CH), 126.33 (CH), 124.91 (CH), 124.81 (C_q), 116.39 (CH), 114.40 (CH), 107.31 (CH), 56.35 (CH₃). HRMS (ESI): m/z calcd for C₁₆H₁₂NaO₃ [M + Na]⁺: 275.0679; found: 275.0672.

6-Phenyl-8H-[1,3]dioxolo[4,5-g]chromen-8-one (3ma): Product 3ma was obtained as a yellow solid (34 mg, 64%); m.p.: 207–209 °C. ¹H NMR (400 MHz, CDCl₃): δ 7.90–7.86 (2H, m, 2CH), 7.60–7.46 (4H, m, 4CH), 6.97 (1H, s, CH), 6.77 (1H, s, CH), 6.12 (2H, s, CH₂). ¹³C NMR (101 MHz, CDCl₃): δ = 177.41 (C_q), 162.70 (C_q), 153.49 (C_q), 152.76 (C_q), 146.18 (C_q), 131.71 (C_q), 131.34 (CH), 128.99 (CH), 126.04 (CH), 118.98 (C_q), 106.98 (CH), 102.42 (CH), 102.31 (CH₂), 98.04 (CH). HRMS (ESI): m/z calcd for C₁₆H₁₁O₄ [M + H]⁺: 267.0652; found: 267.0655.

2-(4-Fluorophenyl)-4H-chromen-4-one (3ab): Product 3ab was obtained as a yellow solid (42 mg, 88%); m.p.: 145–147 °C. ¹H NMR (400 MHz, CDCl₃): δ = 8.31–8.16 (1H, m, CH), 7.97–7.91 (2H, m, 2CH), 7.78–7.67 (1H, m, CH), 7.57 (1H, d, J = 8.4 Hz, CH), 7.43 (1H, t, J = 7.6 Hz, CH), 7.22 (2H, t, J = 8.6 Hz, 2CH), 6.78 (1H, s, CH).¹³C NMR (101 MHz, CDCl₃): δ = 178.30 (C_q), 164.73 (d, ¹J_C–F = 253.2 Hz, C_q), 162.37 (C_q), 156.15 (C_q), 133.82 (CH), 128.48 (d, ³J_C–F = 9.0 Hz, CH), 127.96 (d, ⁴J_C–F = 3.2 Hz, C_q), 125.72 (CH), 125.30 (CH), 123.87 (C_q), 117.99 (CH), 116.28 (d, ²J_C–F = 22.0 Hz, CH), 107.36 (CH). HRMS (ESI): m/z calcd for C₁₅H₁₀FO₂ [M + H]⁺: 241.0659; found: 241.0662.

2-(4-Chlorophenyl)-4H-chromen-4-one (3ac): Product 3ac was obtained as a yellow solid (45 mg, 87%); m.p.: 185–187 °C. ¹H NMR (400 MHz, CDCl₃): δ = 8.23 (1H, dd, J = 8.0, 1.4 Hz, CH), 7.87 (2H, d, J = 8.6 Hz, 2CH), 7.75–7.67 (1H, m, CH), 7.56 (1H, d, J = 8.4 Hz, CH), 7.50 (2H, d, J = 8.6 Hz, 2CH), 7.43 (1H, t, J = 7.6 Hz, CH), 6.80 (1H, s, CH). ¹³C NMR (101 MHz, CDCl₃): δ = 178.23 (C_q), 162.17 (C_q), 156.12 (C_q), 137.85 (C_q), 133.89 (CH), 130.20 (CH), 129.35 (CH), 127.51 (C_q), 125.71 (CH), 125.35 (CH), 123.87 (C_q), 118.01 (CH), 107.66 (CH). HRMS (ESI): m/z calcd for C₁₅H₁₀ClO₂ [M + H]⁺: 257.0364; found: 257.0368.

2-(4-Bromophenyl)-4H-chromen-4-one (3ad): Product 3ad was obtained as a yellow solid (54 mg, 89%); m.p.: 176–178 °C. ¹H NMR (400 MHz, CDCl₃): δ = 8.29–8.18 (1H, m, CH), 7.80 (2H, d, J = 8.6 Hz, 2CH), 7.74–7.69 (1H, m, CH), 7.67 (2H, d, J = 8.6 Hz, 2CH), 7.57 (1H, d, J = 8.2 Hz, CH), 7.43 (1H, t, J = 7.6 Hz, CH), 6.81 (1H, s, CH). ¹³C NMR (101 MHz, CDCl₃): δ = 178.28 (C_q), 162.25 (C_q), 156.13 (C_q), 133.91 (CH), 132.33 (CH), 130.67 (CH), 127.68 (C_q), 126.29 (C_q), 125.72 (CH), 125.37 (CH), 123.94 (C_q), 118.03 (CH), 107.70 (CH). HRMS (ESI): m/z calcd for C₁₅H₁₀BrO₂ [M + H]⁺: 300.9859; found: 300.9867.

2-(p-Tolyl)-4H-chromen-4-one (3ae): Product 3ae was obtained as a yellow solid (43 mg, 92%); m.p.: 109–111 °C. ¹H NMR (400 MHz, CDCl₃): δ = 8.23 (1H, d, J = 8.0 Hz, CH), 7.82 (2H, d, J = 8.0 Hz, 2CH), 7.69 (1H, t, J = 7.8 Hz, CH), 7.56 (1H, d, J = 8.4 Hz, CH), 7.41 (1H, t, J = 7.6 Hz, CH), 7.32 (2H, d, J = 8.0 Hz, 2CH), 6.80 (1H, s, CH), 2.43 (3H, s, CH₃). ¹³C NMR (101 MHz, CDCl₃): δ = 178.44 (C_q), 163.57 (C_q), 156.20 (C_q), 142.22 (C_q), 133.62 (CH), 129.73 (CH), 128.90 (CH), 126.19 (C_q), 125.63 (CH), 125.09 (CH), 123.94 (C_q), 118.02 (CH), 106.93 (CH), 21.52 (CH₃). HRMS (ESI): m/z calcd for C₁₆H₁₃O₂ [M + H]⁺: 237.0910; found: 237.0914.

2-[4-(Trifluoromethyl)phenyl]-4H-chromen-4-one (3af): Product 3af was obtained as a yellow solid (51 mg, 88%); m.p.: 139–141 °C. ¹H NMR (400 MHz, CDCl₃): δ = 8.24 (1H, d, J = 8.0 Hz, CH), 8.05 (2H, d, J = 8.2 Hz, 2CH), 7.80 (2H, d, J = 8.2 Hz, 2CH), 7.74 (1H, t, J = 7.8 Hz, CH), 7.60 (1H, d, J = 8.4 Hz, CH), 7.45 (1H, t, J = 7.6 Hz, CH), 6.88 (1H, s, CH). ¹³C NMR (101 MHz, CDCl₃): δ = 178.17 (C_q), 161.58 (C_q), 156.17 (C_q), 135.16 (d, ⁴J_C–F = 1.0 Hz, C_q), 134.10 (C_q), 133.12 (d, ²J_C–F = 33.0 Hz, CH), 126.62 (CH), 126.03 (q, ³J_C–F = 3.8 Hz, CH), 125.78 (CH), 125.54 (CH), 123.92 (C_q), 123.58 (d, ¹J_C–F = 272.6 Hz, C_q), 118.10 (CH), 108.73 (CH). HRMS (ESI): m/z calcd for C₁₆H₁₀F₃O₂ [M + H]⁺: 291.0627; found: 291.0632. The NMR data agree with those in a literature report.⁴⁴

2-(4-Methoxyphenyl)-4H-chromen-4-one (3ag): Product 3ag was obtained as a yellow solid (38 mg, 75%); m.p.: 151–153 °C. ¹H NMR (400 MHz, CDCl₃): δ = 8.23 (1H, d, J = 8.0 Hz, CH), 7.89 (2H, d, J = 8.8 Hz, 2CH), 7.69 (1H, t, J = 7.8 Hz, CH), 7.55 (1H, d, J = 8.4 Hz, CH), 7.41 (1H, t, J = 7.6 Hz, CH), 7.03 (2H, d, J = 8.8 Hz, 2CH), 6.76 (1H, s, CH), 3.89 (3H, s, CH₃). ¹³C NMR (101 MHz, CDCl₃): δ = 178.34 (C_q), 163.40 (C_q), 162.38 (C_q), 156.15 (C_q), 133.54 (CH), 127.98 (CH), 125.63 (CH), 125.05 (CH), 123.98 (C_q), 123.88 (C_q), 117.93 (CH), 114.43 (CH), 106.14 (CH), 55.48 (CH₃). HRMS (ESI): m/z calcd for C₁₆H₁₂NaO₃ [M + Na]⁺: 275.0679; found: 275.0685.

2-(2-Chlorophenyl)-4H-chromen-4-one (3ah): Product 3ah was obtained as a yellow solid (38 mg, 74%); m.p.: 113–115 °C. ¹H NMR (400 MHz, CDCl₃): δ = 8.26 (1H, d, J = 7.8 Hz, CH), 7.71 (1H, t, J = 7.6 Hz, CH), 7.64 (1H, d, J = 7.0 Hz, CH), 7.53 (2H, t, J = 8.2 Hz, 2CH), 7.49–7.38 (3H, m, 3CH), 6.66 (1H, s, CH). ¹³C NMR (101 MHz, CDCl₃): δ = 178.13 (C_q), 162.63 (C_q), 156.57 (C_q), 133.91 (CH), 132.91 (C_q), 131.90 (C_q), 131.76 (CH), 130.79 (CH), 130.63 (CH), 127.07 (CH), 125.74 (CH), 125.33 (CH), 123.83 (C_q), 118.18 (CH), 112.99 (CH). HRMS (ESI): m/z calcd for C₁₅H₉ClNaO₂ [M + Na]⁺: 279.0183; found: 279.0184.

2-(o-Tolyl)-4H-chromen-4-one (3ai): Product 3ai was obtained as a yellow oil (39 mg, 83%). ¹H NMR (400 MHz, CDCl₃): δ = 8.26 (1H, d, J = 8.0 Hz, CH), 7.70 (1H, t, J = 7.8 Hz, CH), 7.51 (2H, dd, J = 13.8, 8.0 Hz, 2CH), 7.46–7.39 (2H, m, 2CH), 7.33 (2H, d, J = 7.2 Hz, 2CH), 6.50 (1H, s, CH), 2.49 (3H, s, CH₃). ¹³C NMR (101 MHz, CDCl₃): δ = 178.29 (C_q), 166.08 (C_q), 156.42 (C_q), 136.75 (C_q), 133.74 (C_q), 132.56 (CH), 131.22 (CH), 130.68 (CH), 129.16 (CH), 126.17 (CH), 125.70 (CH), 125.20 (CH), 123.74 (C_q), 118.01 (CH), 111.90 (CH), 20.52 (CH₃). HRMS (ESI): m/z calcd for C₁₆H₁₂NaO₂ [M + Na]⁺: 259.0730; found: 259.0720.

2-(2-Methoxyphenyl)-4H-chromen-4-one (3aj): Product 3aj was obtained as a yellow solid (48 mg, 95%); m.p.: 101–102 °C. ¹H NMR (400 MHz, CDCl₃): δ = 8.23 (1H, dd, J = 8.0, 1.6 Hz, CH), 7.91 (1H, dd, J = 7.8, 1.6 Hz, CH), 7.70–7.65 (1H, m, CH), 7.53 (1H, d, J = 8.2 Hz, CH), 7.51–7.45 (1H, m, CH), 7.40 (1H, t, J = 7.6 Hz, CH), 7.15 (1H, s, CH), 7.11 (1H, t, J = 7.2 Hz, CH), 7.05 (1H, d, J = 8.4 Hz, CH), 3.94 (3H, s, CH₃). ¹³C NMR (101 MHz, CDCl₃): δ = 178.89 (C_q), 160.84 (C_q), 157.96 (C_q), 156.46 (C_q), 133.50 (CH), 132.38 (CH), 129.25 (CH), 125.58 (CH), 124.87 (CH), 123.79 (C_q), 120.80 (C_q), 120.69 (CH), 118.00 (CH), 112.63 (CH), 111.72 (CH), 55.65 (CH₃). HRMS (ESI): m/z calcd for C₁₆H₁₂NaO₃ [M + Na]⁺: 275.0679; found: 275.0668.

2-(m-Tolyl)-4H-chromen-4-one (3ak): Product 3ak was obtained as a yellow solid (36 mg, 77%); m.p.: 108–110 °C. ¹H NMR (400 MHz, CDCl₃): δ = 8.23 (1H, d, J = 8.0 Hz, CH), 7.76–7.66 (3H, m, 3CH), 7.58 (1H, d, J = 8.4 Hz, CH), 7.45–7.38 (2H, m, 2CH), 7.35 (1H, d, J = 7.6 Hz, CH), 6.82 (1H, s, CH), 2.46 (3H, s, CH₃). ¹³C NMR (101 MHz, CDCl₃): δ = 178.50 (C_q), 163.60 (C_q), 156.25 (C_q), 138.81 (C_q), 133.69 (CH), 132.38 (CH), 131.70 (CH), 128.91 (C_q), 126.82 (CH), 125.66 (CH), 125.15 (CH), 124.00 (C_q), 123.48 (CH), 118.06 (CH), 107.54 (CH), 21.49 (CH₃). HRMS (ESI): m/z calcd for C₁₆H₁₂NaO₂ [M + Na]⁺: 259.0730; found: 259.0719.

2-(3-Bromophenyl)-4H-chromen-4-one (3al): Product 3al was obtained as a yellow solid (44 mg, 73%); m.p.: 90–92 °C.¹H NMR (400 MHz, CDCl₃): δ = 8.23 (1H, d, J = 7.0 Hz, CH), 8.08 (1H, s, CH), 7.83 (1H, d, J = 8.0 Hz, CH), 7.75–7.69 (1H, m, CH), 7.67 (1H, d, J = 8.0 Hz, CH), 7.59 (1H, d, J = 8.4 Hz, CH), 7.47–7.36 (2H, m, 2CH), 6.80 (1H, s, CH). ¹³C NMR (101 MHz, CDCl₃): δ = 178.17 (C_q), 161.64 (C_q), 156.13 (C_q), 134.41 (CH), 133.98 (CH), 133.77 (CH), 130.53 (CH), 129.22 (C_q), 125.73 (CH), 125.42 (CH), 124.81 (C_q), 123.89 (C_q), 123.22 (CH), 118.08 (CH), 108.16 (CH). HRMS (ESI): m/z calcd for C₁₅H₁₀BrO₂ [M + H]⁺: 300.9859; found: 300.9869.

2-(tert-Butyl)-4H-chromen-4-one (3am): Product 3am was obtained as a yellow solid (37 mg, 91%); m.p.: 72–74 °C. ¹H NMR (400 MHz, CDCl₃): δ = 8.18 (1H, d, J = 8.0 Hz, CH), 7.66 (1H, t, J = 7.8 Hz, CH), 7.46 (1H, d, J = 8.4 Hz, CH), 7.38 (1H, t, J = 7.6 Hz, CH), 6.29 (1H, s, CH), 1.36 (9H, s, 3CH₃). ¹³C NMR (101 MHz, CDCl₃): δ = 178.94 (C_q), 176.04 (C_q), 156.44 (C_q), 133.43 (CH), 125.52 (CH), 124.78 (CH), 123.40 (C_q), 117.80 (CH), 106.65 (CH), 36.47 (C_q), 27.85 (CH₃). HRMS (ESI): m/z calcd for C₁₃H₁₄NaO₂ [M + Na]⁺: 225.0886; found: 225.0891.

2-(Thiophen-2-yl)-4H-chromen-4-one (3an): Product 3an was obtained as a yellow solid (40 mg, 87%); m.p.: 93–95 °C. ¹H NMR (400 MHz, CDCl₃): δ = 8.21 (1H, dd, J = 8.0, 1.6 Hz, CH), 7.73 (1H, d, J = 3.0 Hz, CH), 7.71–7.65 (1H, m, CH), 7.58 (1H, d, J = 5.0 Hz, CH), 7.53 (1H, d, J = 8.4 Hz, CH), 7.41 (1H, t, J = 7.6 Hz, CH), 7.21–7.17 (1H, m, CH), 6.71 (1H, s, CH). ¹³C NMR (101 MHz, CDCl₃): δ = 177.89 (C_q), 158.99 (C_q), 155.87 (C_q), 135.11 (C_q), 133.71 (CH), 130.23 (CH), 128.46 (CH), 128.41 (CH), 125.64 (CH), 125.23 (CH), 123.95 (C_q), 117.90 (CH), 106.16 (CH). HRMS (ESI): m/z calcd for C₁₃H₉O₂S [M + H]⁺: 229.0318; found: 229.0307.

2-(Naphthalen-2-yl)-4H-chromen-4-one (3ao): Product 3ao was obtained as a yellow solid (51 mg, 93%); m.p.: 157–159 °C. ¹H NMR (400 MHz, CDCl₃): δ = 8.47 (1H, s, CH), 8.29–8.22 (1H, m, CH), 8.01–7.86 (4H, m, 4CH), 7.75–7.69 (1H, m, CH), 7.63 (1H, d, J = 8.0 Hz, CH), 7.60–7.55 (2H, m, 2CH), 7.43 (1H, t, J = 7.2 Hz, CH), 6.96 (1H, s, CH). ¹³C NMR (101 MHz, CDCl₃): δ = 178.41 (C_q), 163.27 (C_q), 156.29 (C_q), 134.61 (C_q), 133.77 (CH), 132.85 (C_q), 129.01 (CH), 128.90 (CH), 128.85 (CH), 127.98 (CH), 127.79 (CH), 127.04 (C_q), 126.88 (CH), 125.69 (CH), 125.21 (CH), 123.99 (CH), 122.47 (C_q), 118.08 (CH), 107.85 (CH). HRMS (ESI): m/z calcd for C₁₉H₁₃O₂ [M + H]⁺: 273.091; found: 273.0922.

2-(Adamantan-1-yl)-4H-chromen-4-one (3ap): Product 3ap was obtained as a white solid (53 mg, 95%); m.p.: 100–102 °C. ¹H NMR (400 MHz, CDCl₃): δ = 8.18 (1H, dd, J = 8.0, 1.6 Hz, CH), 7.68–7.62 (1H, m, CH), 7.45 (1H, d, J = 8.2 Hz, CH), 7.40–7.33 (1H, m, CH), 6.20 (1H, s, CH), 2.13 (3H, s, 3CH), 2.00–1.96 (6H, m, 3CH₂), 1.86–1.73 (6H, m, 3CH₂). ¹³C NMR (101 MHz, CDCl₃): δ = 179.03 (C_q), 175.77 (C_q), 156.45 (C_q), 133.34 (CH), 125.53 (CH), 124.70 (CH), 123.61 (C_q), 117.79 (CH), 106.59 (CH), 39.47 (CH), 38.17 (CH₂), 36.41 (CH₂), 27.94 (CH₂). HRMS (ESI): m/z calcd for C₁₉H₂₁O₂ [M + Na]⁺: 281.1536; found: 281.1529.

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: This work was supported by the National Natural Science Foundation of China (NSFC; Grant Numbers 21676252 and 21506191).

ORCID iD

Chuanming Yu

References

Yadava

Tiwari

J Asian Nat Prod Res 2005; 7: 185.

Shankar

Goel

Gupta

, et al. Curr Pharm Rep 2017; 3: 423.

Albouchi

Avola

Dico

GML

, et al. Molecules 2018; 23: 2526.

Kowalski

Koceva-Chyla

Szczupak

, et al. J Organomet Chem 2013; 741: 153.

Rocha-Pereira

Cunha

Pinto

, et al. Bioorg Med Chem 2010; 18: 4195.

Mulholland

Schwikkard

Crouch

NR.

Nat Prod Rep 2013; 30: 1165.

Shahinozzaman

Taira

Ishii

, et al. Molecules 2018; 23: 2479.

Dyrager

Mollers

Kjall

, et al. J Med Chem 2011; 54: 7427.

Gaspar

Matos

Garrido

, et al. Chem Rev 2014; 114: 4960.

10.

Song

Gao

, et al. J Nutr Biochem 2017; 42: 17.

11.

Sang

Pan

M-H

, et al. Bioorg Med Chem Lett 2007; 17: 5177.

12.

Wang

Luo

, et al. Molecules 2018; 23: 2513.

13.

Kim

Lee

Yun

J-M.

Phytother Res 2014; 28: 1383.

14.

Meng

Chai

, et al. Chem Biol Interact 2016; 257: 26.

15.

H-e

Chen

Sun

X-B

, et al. RSC Adv 2015; 5: 4898.

16.

Hida

Tamiya

Nishio

, et al. Cancer Sci 2011; 102: 845.

17.

Zhao

Angew Chem Int Ed 2011; 50: 3769.

18.

Kim

Ham

Hong

Org Biomol Chem 2012; 10: 7305.

19.

Yang

Alper

J Org Chem 2010; 75: 948.

20.

Yue

Peng

Wang

, et al. J Org Chem 2017; 82: 5481.

21.

Mal

Kaur

Haque

, et al. J Org Chem 2015; 80: 6400.

22.

Yang

Wang

, et al. J Mol Catal A: Chem 2017; 426: 24.

23.

Zhang

, et al. Org Biomol Chem 2011; 9: 6930.

24.

Zhu

Wang

, et al. Catal Sci Technol 2016; 6: 2905.

25.

Lee

Shin

, et al. Bioorg Med Chem Lett 2017; 27: 2613.

26.

Yatabe

Jin

Yamaguchi

, et al. Angew Chem Int Ed 2015; 54: 13302.

27.

Baruah

Kaishap

Gogoi

Chem Commun 2016; 52: 13004.

28.

Sun

Gao

Yang

, et al. Org Lett 2016; 18: 6464.

29.

Burtoloso

ACB

Dias

RMP

Leonarczyk

IA.

Eur J Org Chem 2013; 2013: 5005.

30.

Shi

Wang

Zeng

, et al. Adv Synth Catal 2018; 360: 4049.

31.

Xiong

Sun

, et al. Org Lett 2018; 20: 1396.

32.

Yang

Zhou

, et al. Org Lett 2017; 19: 4307.

33.

Zheng

Yang

, et al. Chem Commun 2018; 54: 670.

34.

Liu

C-F

Liu

Dong

J Org Chem 2019; 84: 409.

35.

Yan

, et al. Org Lett 2018; 20: 5981.

36.

Zhang

Zheng

Chen

, et al. Org Chem Front 2018; 5: 2969.

37.

Jiang

Chen

Zhu

, et al. J Org Chem 2017; 82: 10665.

38.

Dixit

Tripathi

Tamrakar

, et al. Bioorg Med Chem 2007; 15: 727.

39.

Kim

Keyser

Schneekloth

Jr.

Bioorg Med Chem Lett 2014; 24: 1094.

40.

Sagrera

Bertucci

Vazquez

, et al. Bioorg Med Chem 2011; 19: 3060.

41.

Goel

Dixit

Synlett 2004; 11: 1990.

42.

Silva

Pinto

Rocha

, et al. Synlett 2012; 23: 559.

43.

Barros

AIRNA

Silva

AMS

. Monatsh Chem 2006; 137: 1505.

44.

X-F

Neumann

Beller

Chem Eur J 2012; 18: 12595.

Rhodium(III)-catalyzed one-pot synthesis of flavonoids from salicylaldehydes and sulfoxonium ylides

Abstract

Keywords

Introduction

Results and discussion

Conclusion

Experimental section

General procedure for the synthesis of 3

Footnotes

Declaration of conflicting interests

Funding

ORCID iD

References