Iron-catalyzed regioselective direct coupling of aromatic aldehydes with coumarins leading to 3-aroyl coumarins

Abstract

An efficient protocol for iron-catalyzed cross-coupling of coumarins with aromatic aldehydes has been developed. The various 3-aroyl coumarins were selectively afforded in moderate yields. Some notable features of this protocol are high efficiency, wide functional group tolerance, and commercially available and cheap aromatic aldehydes and coumarins as starting materials. Furthermore, these reaction conditions were also applicable to N-methyl quinolinones, affording the corresponding 3-aroyl quinolinone derivatives in good yields.

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Introduction

Coumarins are significant natural products, which display wide and interesting pharmacological properties such as anti-breast cancer,¹ anti-HIV,² anti-Alzheimer,³ vasorelaxant and platelet antiaggregatory activities.⁴ Coumarin derivatives containing carbonyl groups have proven to be useful skeletons in organic synthesis as valuable building blocks and in pharmaceuticals due to their biological and physical properties.⁵ In particular, 3-carbonyl coumarin represents an important structural element in an anticoagulant agent (A),⁶ monoamine oxidase (MAO)-B inhibitor (B),⁷ antioxidant (C)⁸ and α-glucosidase antihyperglycemic inhibitor (D)⁹ (Scheme 1). Moreover, 3-aroyl coumarin derivatives also exhibited characteristics of triplet sensitizers.^5c Thus, the development of novel and efficient methods for construction of this kind of compound will be of great value for the screening of novel functional active molecules.

Scheme 1 Several examples illustrating the importance of 3-carbonyl coumarins.

Traditional procedures to synthesize 3-aroyl coumarins involved the Knoevenagel condensation of substituted salicylaldehydes with β-ketoesters in the presence of piperidine in acetonitrile, or using alkaline protease from Bacillus Licheniformis as a catalyst.¹⁰ Prakash Rao's group reported a method toward 3-aroyl coumarins by the condensation of α-aroylketene dithioacetals (AKDTAs) and 2-hydroxybenzaldehydes in the presence of catalytic amount of piperidine (Scheme 2a).¹¹ Transition metal-free cross-coupling has been employed as an environmentally friendly and alternative approach to replace the metal catalyzed/mediated transformations.¹² Recently, Wu's group described a metal-free TBAB-mediated oxidative tandem coupling of alkynoates with aldehydes for selective synthesis of 3-acylcoumarins (Scheme 2b).¹³ Wang's group used carboxylic acids as the coupling partners, to react with alkynoates by a silver-mediated catalyst to obtain 3-aroyl coumarins (Scheme 2c).¹⁴ Duan's group also reported a synthetic method for preparation of monosubstituted and polysubstituted coumarins by a silver-catalyzed decarboxylative acylation reactions using α-oxocarboxylic acids as acyl sources (Scheme 2d).¹⁵ Despite these methods having had various levels of success, some problems exist with these procedures, such as: (1) requirement of complicated starting materials, which are not commercially available or are expensive, and (2) a narrow scope of substrates. Therefore, developing a general and applicable strategy for a variety of 3-aroyl coumarins is still desirable. Recently, transition metal-catalyzed oxidative acylations of inactive sp² C–H bonds with aldehydes as acyl surrogates were reported.¹⁶ Guided by recent studies on base promoted hemolytic aromatic substitution (BHAS) using aromatic aldehydes as C-radical precursors,¹⁷ we decided to investigate the modular synthesis of 3-aroyl coumarins by BHAS. Herein, we disclose an efficient, practical procedure to synthesize various 3-aroyl coumarins via iron-catalyzed cross-coupling radical reactions of commercially available aromatic dehydes with coumarins (Scheme 2e).

Scheme 2

Results and discussion

We initiated our investigation with the reaction of coumarin 1a with benzaldehyde 2a as a model reaction to identify the optimal reaction conditions. Several parameters, such as catalyst sources, the quantity of catalyst and oxidant t-butylhydroperoxide (TBHP), solvents and reaction temperature were screened. The results are listed in Table 1. The initial reaction was conducted in chlorobenzene using a 4-fold excess of benzaldehyde and 3.0 equiv. of TBHP in the presence of Cu(OAc)₂ as the catalyst (10 mol%) at 120 °C under a nitrogen for 12 h, which led to disappointing result (Table 1, entry 1). A variety of Cu and Fe salts (e.g. CuCl₂, CuCl, CuI, Fe(NO₃)₃, FeCl₃, and FeCl₂) were tested (Table 1, entries 2–7), Cu salts were not efficient catalysts. Pleasingly, FeCl₂ was clearly the ideal choice for this reaction, 3aa was formed in 46% yield (Table 1, entry 7). Bu₄NI has been successfully used in radical chemistry recently,¹⁸ but Bu₄NI turned out to be an inefficient catalyst in this reaction (Table 1, entry 8). With the optimal catalyst in hand we also varied the amount of catalyst and found 10 mol% to be the ideal loading (Table 1, entries 7, 9–11). A variety of solvents (e.g. CH₃CN, DMSO, dioxane, ClCH₂CH₂Cl, and DMF) were tested (Table 1, entries 7, 12–16), chlorobenzene was clearly the best choice for this catalytic system (Table 1, entries 7). To our delight, the yield was improved to 54% when the amount of TBHP was changed to 4.0 eq., which indicated that the TBHP played an important role in this reaction (Table 1, entries 7, 17–19). Slightly lower yield (49%) was achieved upon lowering the amount of benzaldehyde to 3.0 equiv. However, the product yields dramatically dropped to 23% and 7% if 2.0 equiv. and 1.0 equiv. of benzaldehyde were used under otherwise identical conditions (Table 1, entries 20–22). Various reaction temperatures were also examined, and 120 °C was found to be the best choice. In the absence of nitrogen, the yield of 3aa was decreased to 36% (Table 1, entries 23). Additionally, a controlled experimental showed that the yield of 3aa was only 10% without the catalyst (Table 1, entries 24).

Table 1 Optimization of reaction conditions^a

Entry	Catalyst (mol%)	TBHP (eq.)	Solvent	Temp (°C)	Yield^b (%)
a Reaction conditions: 1a (0.25 mmol), 2a (1.0 mmol), catalyst, and TBHP in solvent (2 mL) with stirring under nitrogen for 12 h.b Isolated yield.c 3.0 eq. 2a was used.d 2.0 eq. 2a was used.e 1.0 eq. 2a was used.f Without nitrogen.g Without a catalyst.
1	Cu(OAc)2 (10)	3.0	PhCl	120	Trace
2	CuCl2 (10)	3.0	PhCl	120	11
3	CuCl (10)	3.0	PhCl	120	10
4	CuI (10)	3.0	PhCl	120	Trace
5	Fe(NO3)3 (10)	3.0	PhCl	120	30
6	FeCl3 (10)	3.0	PhCl	120	32
7	FeCl2 (10)	3.0	PhCl	120	46
8	Bu4NI (10)	3.0	PhCl	120	Trace
9	FeCl2 (5)	3.0	PhCl	120	21
10	FeCl2 (15)	3.0	PhCl	120	34
11	FeCl2 (20)	3.0	PhCl	120	35
12	FeCl2 (10)	3.0	CH3CN	90	10
13	FeCl2 (10)	3.0	DMSO	120	Trace
14	FeCl2 (10)	3.0	Dioxane	90	Trace
15	FeCl2 (10)	3.0	DCE	90	18
16	FeCl2 (10)	3.0	DMF	120	Trace
17	FeCl2 (10)	1.0	PhCl	120	Trace
18	FeCl2 (10)	2.0	PhCl	120	17
19	FeCl2 (10)	4.0	PhCl	120	54
20^c	FeCl2 (10)	4.0	PhCl	120	49
21^d	FeCl2 (10)	4.0	PhCl	120	23
22^e	FeCl2 (10)	4.0	PhCl	120	7
23^f	FeCl2 (10)	4.0	PhCl	120	36
24^g	—	4.0	PhCl	120	10

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With optimized conditions in hand (Table 1, entry 19) we next studied the scope and limitations of the 3-aroyl coumarins synthesis by firstly varying the aromatic aldehyde component in the reaction with coumarin 1a (Table 2). The coupling of coumarin 1a and aromatic aldehyde 2b–l with electron-donating (CH₃, OCH₃, OCH₂O, etc.) and electron-withdrawing groups (F, Cl, Br, etc.) on the aromatic ring were found to be favored in the acylation reaction to afford regioselectively the corresponding products 3ab–al in moderate to good yields. Moreover, aromatic aldehydes with electron-donating groups could give better yields than those with electron-withdrawing group. The result showed that electronic effects in the aldehyde component turned out to be weak. In addition, ortho-substituted benzaldehydes 2f, 2j–l smoothly underwent this coupling reaction to generate the corresponding products 3af, 3aj–al in moderate yield. Notably, a 59% yield of 3ag was produced in the reaction of coumarin and α-naphthaldehyde 2g. The steric hindrance of aromatic aldehyde did not obviously affect this transformation. It was gratifying to find that heterocyclic aromatic aldehydes 2m, 2n also reacted smoothly with coumarin, leading to the corresponding products 3am, 3an in good yields. Unfortunately, aliphatic aldehydes failed to deliver the desired products with the current catalytic system.

Table 2 Synthesis of 3-aroyl coumarins from coumarins and aromatic aldehydes^a

a Reaction conditions: coumarins (0.25 mmol), aromatic aldehydes (1.0 mmol), 10 mol% FeCl₂ and 4 eq. TBHP in 2 mL PhCl solvent, 120 °C, under nitrogen for 12 h.b Isolated yields.

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To further explore the substrate scope and limitations of this process, a broad range of coumarins 1b–f were screened, as shown in Table 2. The coupling of benzaldehyde 2a or 2e and coumarins 1b–f with electron-rich and electron-deficient groups (OH, OCH₃, OC₂H₅, OCOCH₃, NO₂) at the 6-position or 7-position were found to be favored in the acylation reaction to afford the corresponding products 3ba–fe in moderate yields. Electronic effects in the coumarin structure turned out to be stronger, and a sharp decrease yield of 38% 3de was afforded when coumarin 2d with electron-deficient –NO₂ group was employed. Notably, the –OH and –OCOCH₃ moieties on the phenyl ring of coumarins were tolerated under these coupling conditions and offer versatile synthetic functionally for further elaboration. It is worthy of note that these standard reaction conditions were applied to 4-substituted coumarins, affording the corresponding products 3ea and 3fe in 66% and 64% yields, respectively. The results indicated that the steric hinderance of coumarins played a weak role in this reaction. Unfortunately, the yield of this reaction is typically 50–65% under the present reaction condition. After the reaction was finished, there were still some unreacted starting materials. The yield didn't increase obviously though the reaction time was increased. Moreover, there are few by-products made for this reaction, and no multiple substitutions were found.

Finally, a series of N-methyl quinolinone derivatives was also investigated under the optimal conditions. As expected, the acyl groups were exclusively added to the 3-position of 2-quinolinone derivatives, affording dialkyl 2-quinolinone-3-yl phosphonates in 55–77% yields. Notably, the N-methyl 2-quinolinones were well tolerated, and they could react smoothly with aromatic aldehyde or heterocyclic aldehydes, producing the desired products. Moreover, N-methyl quinolinones with electron-rich (OCH₃) and electron-poor (Br) groups on the phenyl ring were tolerated under these coupling conditions. Unfortunately, 2-quinolinone derivatives failed to deliver the coupling products with the current catalytic system (Table 3).

Table 3 Synthesis of 1-methyl-3-aroyl quinolinones from heteroarene 4 and aromatic aldehyde 2^a

a Reaction conditions: N-methyl quinolinones (0.25 mmol), aromatic aldehydes (1.0 mmol), 10 mol% FeCl₂ and 4 eq. TBHP in 2 mL PhCl solvent, 120 °C, under nitrogen for 12 h.b Isolated yields.

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To clarify the reaction mechanism, some controlled experiments were performed (Scheme 3). When the reaction of coumarin 1a with benzaldehyde 2a was carried out under the standard conditions by addition of 3 equivalents radical scavengers, such as TEMPO and BHT, the yields of the desired product 3aa were decreased dramatically. These results indicated that the reaction might proceed via a radical pathway. Based on these results and previous studies,^16f,17d a possible reaction mechanism was proposed as shown in Scheme 4. Initiation likely occurs by reducing tBuOOH with FeX₂ to give the tert-butoxyl radical along with an Fe(III) complex. The tert-butoxyl radical then abstracts the H-atom from the aldehyde to give acyl radical A which attacks selectively C3-position of coumarin to give the carbon radical B stabilized by the phenyl group. The radical B is stable because it could form four resonant structures, and the electron is dispersed to phenyl group. On the contrary, acyl radical A attacks C4-position of coumarin to give another carbon radical stabilized only by the adjacent carbonyl group. Subsequently, a single-electron transfer (SET) from B to Fe(III) would release the intermediate C, simultaneously Fe(III) was reduced into Fe(II). After that, the intermediate C loses a hydrogen, delivering the desired product.

Scheme 3 Controlled experiments.

Scheme 4 Proposed reaction mechanism for C-3 arylation of coumarins.

Experimental

General information

All reactions were carried out under a nitrogen atmosphere. Anhydrous solvents were obtained by standard procedure. All substrates were purchased from J & K Scientific Ltd used without further purification. Column chromatography was performed using 200–300 mesh silica with the indicated solvent system according to standard techniques. Analytical thin-layer chromatography (TLC) was performed on precoated, glass-backed silica gel plates. Visualization of the developed chromatogram was performed by UV absorbance (254 nm or 365 nm). Nuclear magnetic resonance spectra were recorded on Bruker Avance 400 MHz spectrometer. Chemical shifts for ¹H NMR spectra are recorded in parts per million from tetramethylsilane. Data were reported as follows: chemical shift, multiplicity (s = singlet, d = doublet, t = triplet, m = multiplet and br = broad), coupling constant in Hz and integration. Chemical shifts for ¹³C NMR spectra were recorded in parts per million from tetramethylsilane. High resolution mass spectra (HR MS) were obtained on Q-TOF using the ESI technique. IR spectra were recorded on Shimadazu IR-408 fourier transform infrared spectrophotometer using a thin film supported on KBr pellets. Melting points were measured on an XT4A microscopic apparatus and were uncorrected.

General procedure for 3-benzoyl coumarin derivatives

In a 25 mL Schlenk tube, coumarins 1 (0.25 mmol), aromatic aldehydes 2 (1.0 mmol), TBHP (1.0 mmol) and FeCl₂ (0.025 mmol) were added and charged with nitrogen (3 cycles). Chlorobenzene (2 mL) was then added, and the reaction mixture was heated in the oil bath at 120 °C for 12 h (monitored by TLC). After the reaction mixture had been cooled to room temperature, and the solvent was removed with the aid of a rotary evaporator. 2 mL ethylacetate was added to the residue. The solution was filtrated, and the filtrate was distilled under vacuum. The crude product was purified by silica gel column chromatography using ethylacetate/petroleum ether (1 : 5 to 2 : 1) as eluant to obtain the desired product 3.

3-Benzoyl-2H-chromen-2-one (3aa). Colorless crystal, mp 134–135 °C (134–136 °C).^{19 1}H NMR (400 MHz, CDCl₃) δ: 8.06 (s, 1H), 7.87 (d, J_H–H = 7.2 Hz, 2H), 7.65 (td, J_H–H = 8.7 Hz, J_H–H = 1.5 Hz, 1H), 7.60 (dd, J_H–H = 7.9 Hz, J_H–H = 1.5 Hz, 1H), 7.48 (d, J_H–H = 7.9 Hz, 2H), 7.40 (t, J_H–H = 8.3 Hz, 1H), 7.35 (td, J_H–H = 7.8 Hz, J_H–H = 0.8 Hz, 1H). ¹³C NMR (100 MHz, CDCl₃) δ: 191.7 (C=O), 158.4 (C=O), 154.7, 145.4 (CH), 136.2, 133.8 (CH), 133.7 (CH), 129.6 (CH), 129.2 (CH), 128.6 (CH), 125.0 (CH), 118.2, 116.9 (CH). IR (KBr) ν (cm⁻¹): 1714, 1654 (C=O), 1608, 1565, 1448 (Ar⁻). ESI MS m/z: 251.0705 [M + H]⁺ (calcd for C₁₆H₁₁O₃⁺ 251.0703).

3-(4-Methylbenzoyl)-2H-chromen-2-one (3ab). Colorless crystal, mp 132–133 °C (132–134 °C).^{19 1}H NMR (400 MHz, CDCl₃) δ: 8.05 (s, 1H), 7.78 (d, J_H–H = 8.2 Hz, 2H), 7.63 (td, J_H–H = 8.7 Hz, J_H–H = 1.5 Hz, 1H), 7.60 (dd, J_H–H = 7.8 Hz, J_H–H = 1.5 Hz, 1H), 7.39 (d, J_H–H = 8.2 Hz, 2H), 7.32 (td, J_H–H = 8.2 Hz, J_H–H = 7.8 Hz, 1H), 7.27 (d, J_H–H = 8.0 Hz, 1H), 2.42 (s, 3H). ¹³C NMR (100 MHz, CDCl₃) δ: 191.2 (CO), 158.5 (C=O), 154.7, 145.1 (CH), 144.9, 133.6 (CH), 133.5, 129.8 (CH), 129.4 (CH), 129.2 (CH), 127.2, 124.9 (CH), 118.2, 116.9 (CH), 21.8 (CH₃). IR (KBr) ν (cm⁻¹): 1720, 1658 (C=O), 1608, 1567, 1455 (Ar⁻). ESI MS m/z: 265.1 [M + H]⁺ (calcd for C₁₇H₁₃O₃⁺ 265.0).

3-(Benzo[d][1,3]dioxole-5-carbonyl)-2H-chromen-2-one (3ac). Slight yellow solid, mp 155–156 °C. ¹H NMR (400 MHz, CDCl₃) δ: 8.01 (s, 1H), 7.78 (d, J_H–H = 8.2 Hz, 2H), 7.64 (td, J_H–H = 8.6 Hz, J_H–H = 1.5 Hz, 1H), 7.59 (dd, J_H–H = 7.7 Hz, J_H-H = 1.5 Hz, 1H), 7.44 (dd, J_H–H = 8.2 Hz, J_H–H = 1.5 Hz, 1H), 7.40–7.38 (m, 2H), 7.35 (t, J_H–H = 7.7 Hz, 1H), 6.84 (d, J_H–H = 8.1 Hz, 1H), 6.07 (s, 2H). ¹³C NMR (100 MHz, CDCl₃) δ: 189.7 (C=O), 158.5 (C=O), 154.6, 152.7, 148.3, 144.6 (CH), 133.5 (CH), 130.7, 129.0 (CH), 127.4, 126.9 (CH), 124.9 (CH), 118.2, 116.9 (CH), 108.9 (CH), 108.0 (CH), 102.1 (CH₂). IR (KBr) ν (cm⁻¹): 1720 (C=O), 1606, 1488, 1440 (Ar⁻). HR MS m/z: 295.0603 [M + H]⁺ (calcd for C₁₇H₁₁O₅⁺ 295.0601).

3-(4-Methoxybenzoyl)-2H-chromen-2-one (3ad). White solid, mp 175–176 °C (174–175 °C).^{5c 1}H NMR (400 MHz, CDCl₃) δ: 8.03 (s, 1H), 7.88 (d, J_H–H = 8.8 Hz, 2H), 7.64 (td, J_H–H = 8.5 Hz, J_H–H = 1.3 Hz, 1H), 7.60 (dd, J_H–H = 7.7 Hz, J_H–H = 1.1 Hz, 1H), 7.40 (d, J_H–H = 8.2 Hz, 1H), 7.33 (t, J_H–H = 7.3 Hz, 1H), 6.95 (d, J_H–H = 8.8 Hz, 1H), 3.88 (s, 3H). ¹³C NMR (100 MHz, CDCl₃) δ: 190.0 (C=O), 164.3, 158.6 (C=O), 154.6, 144.6 (CH), 133.4 (CH), 132.2 (CH), 129.0 (CH), 129.0, 127.6, 124.9 (CH), 118.3, 116.9 (CH), 113.9 (CH), 55.6 (OCH₃). IR (KBr) ν (cm⁻¹): 1714, 1646 (C=O), 1606, 1596, 1513 (Ar⁻). ESI MS m/z: 281.1 [M + H]⁺ (calcd for C₁₇H₁₃O₄⁺ 281.0).

3-(3,4-Dimethoxybenzoyl)-2H-chromen-2-one (3ae). White solid, mp 193–194 °C. ¹H NMR (400 MHz, CDCl₃) δ: 8.02 (s, 1H), 7.66–7.55 (m, 3H), 7.42 (td, J_H–H = 8.8 Hz, J_H–H = 1.7 Hz, 2H), 7.36 (t, J_H–H = 7.5 Hz, 1H), 6.88 (d, J_H–H = 8.4 Hz, 1H), 3.96 (s, 3H), 3.95 (s, 3H). ¹³C NMR (100 MHz, CDCl₃) δ: 190.0 (C=O), 158.6 (C=O), 154.6, 154.2, 149.3, 144.4 (CH), 133.3 (CH), 129.1, 128.9 (CH), 127.5, 125.5 (CH), 124.9 (CH), 118.2, 116.9 (CH), 110.9 (CH), 109.9 (CH), 56.2 (OCH₃), 56.1 (OCH₃). IR (KBr) ν (cm⁻¹): 1708, 1654 (C=O), 1592, 1581, 1515, 1454 (Ar⁻). HR MS m/z: 311.0916 [M + H]⁺ (calcd for C₁₈H₁₅O₅⁺ 311.0914).

3-(2-Methoxybenzoyl)-2H-chromen-2-one (3af). White solid, mp 158–159 °C. ¹H NMR (400 MHz, CDCl₃) δ: 8.16 (s, 1H), 7.77 (dd, J_H–H = 7.6 Hz, J_H–H = 1.8 Hz, 1H), 7.63–7.59 (m, 2H), 7.52 (td, J_H–H = 7.8 Hz, J_H–H = 1.8 Hz, 1H), 7.37 (d, J_H–H = 8.2 Hz, 1H), 7.33 (td, J_H–H = 7.6 Hz, J_H–H = 0.9 Hz, 1H), 7.08 (td, J_H–H = 7.6 Hz, J_H–H = 0.7 Hz, 1H), 6.93 (d, J_H–H = 8.3, 1H). ¹³C NMR (100 MHz, CDCl₃) δ: 190.7 (C=O), 158.9, 158.7 (C=O), 154.7, 143.6 (CH), 134.4 (CH), 133.2 (CH), 130.7 (CH), 129.5 (CH), 129.4, 127.6, 124.7 (CH), 121.1 (CH), 118.7, 116.7 (CH), 111.4 (CH), 55.7 (OCH₃). IR (KBr) ν (cm⁻¹): 1718, 1660 (C=O), 1606, 1575, 1482, 1455 (Ar⁻). HR MS m/z: 281.0808 [M + H]⁺ (calcd for C₁₇H₁₃O₄⁺ 281.0808).

3-(1-Naphthoyl)-2H-chromen-2-one (3ag). Colorless crystal, mp 252–253 °C (above 200 °C).^{19 1}H NMR (400 MHz, CDCl₃) δ: 8.54 (d, J_H–H = 8.4 Hz, 1H), 8.20 (s, 1H), 8.04 (d, J_H–H = 8.2 Hz, 1H), 7.92 (d, J_H–H = 7.6 Hz, 1H), 7.74 (dd, J_H–H = 7.2 Hz, J_H–H = 1.0 Hz, 1H), 7.67–7.56 (m, 4H), 7.48 (t, J_H–H = 7.5 Hz, 1H), 7.39 (d, J_H–H = 8.3 Hz, 2H), 7.34 (td, J_H–H = 7.6 Hz, J_H–H = 0.8 Hz, 1H). ¹³C NMR (100 MHz, CDCl₃) δ: 193.2 (C=O), 158.1 (C=O), 155.0, 146.7 (CH), 134.5, 134.0 (CH), 133.9, 133.3 (CH), 130.7, 129.6 (CH), 129.5 (CH), 128.6 (CH), 128.2 (CH), 127.5, 126.7 (CH), 125.4 (CH), 124.9 (CH), 124.3 (CH), 118.2, 116.9 (CH). IR (KBr) ν (cm⁻¹): 1737, 1658 (C=O), 1608, 1563, 1508, 1454 (Ar⁻). ESI MS m/z: 301.0855 [M + H]⁺ (calcd for C₂₀H₁₃O₃⁺ 301.0859).

3-(4-Fluorobenzoyl)-2H-chromen-2-one (3ah). Slight yellow solid, mp 167–168 °C. ¹H NMR (400 MHz, CDCl₃) δ: 8.12 (s, 1H), 7.93–7.90 (m, 2H), 7.66 (td, J_H–H = 8.6 Hz, J_H–H = 1.5 Hz, 1H), 7.61 (dd, J_H–H = 7.8 Hz, J_H–H = 1.4 Hz, 2H), 7.42 (d, J_H–H = 8.3 Hz, 1H), 7.37 (t, J_H–H = 7.6 Hz, 1H), 7.16 (t, J_H–H = 8.6 Hz, 1H). ¹³C NMR (100 MHz, CDCl₃) δ: 190.2 (C=O), 166.2 (d, J_F–C = 254.7 Hz), 158.5 (C=O), 154.8, 145.7 (CH), 133.8 (CH), 132.3 (d, J_F–C = 9.5 Hz, CH), 129.3 (CH), 126.8, 125.1 (CH), 118.2, 116.9 (CH), 115.8 (d, J_F–C = 22.1 Hz, CH). ¹⁹F NMR (376 MHz, CDCl₃) δ: −103.5. IR (KBr) ν (cm⁻¹): 1709 (C=O), 1662 (C=O), 1610, 1597 (Ar⁻), 1244 (C–O), 1159 (C–F). HR MS m/z: 369.0604 [M + H]⁺ (calcd for C₁₆H₁₀FO₃⁺ 369.0608).

3-(4-Chlorobenzoyl)-2H-chromen-2-one (3ai). Colorless crystal, mp 205–206 °C (above 200 °C).^{19 1}H NMR (400 MHz, CDCl₃) δ: 8.14 (s, 1H), 7.82 (d, J_H–H = 8.5 Hz, 2H), 7.68 (t, J_H–H = 7.5 Hz, 1H), 7.62 (d, J_H–H = 7.7 Hz, 2H), 7.46 (d, J_H–H = 8.5 Hz, 1H), 7.42 (d, J_H–H = 8.5 Hz, 1H), 7.37 (t, J_H–H = 7.5 Hz, 1H). ¹³C NMR (100 MHz, CDCl₃) δ: 190.5 (C=O), 158.5 (C=O), 154.8, 146.1 (CH), 140.3, 134.6, 133.9 (CH), 130.9 (CH), 129.3 (CH), 128.9 (CH), 126.5, 125.1 (CH), 118.1, 117.0 (CH). IR (KBr) ν (cm⁻¹): 1712, 1680 (C=O), 1608, 1587, 1452 (Ar⁻), 1243 (C–O), 758 (C–Cl). ESI MS m/z: 285.1 [M + H]⁺ (calcd for C₁₆H₁₀ClO₃⁺ 285.0).

3-(2-Chlorobenzoyl)-2H-chromen-2-one (3aj). Slight yellow solid, mp 199–200 °C. ¹H NMR (400 MHz, CDCl₃) δ: 8.36 (s, 1H), 7.67–7.64 (m, 2H), 7.56 (d, J_H–H = 7.5 Hz, 1H), 7.45 (d, J_H–H = 6.2 Hz, 1H), 7.47–7.33 (m, 4H). ¹³C NMR (100 MHz, CDCl₃) δ: 191.2 (C=O), 158.1 (C=O), 155.3, 147.1 (CH), 138.2, 134.3 (CH), 132.3 (CH), 131.6, 129.9 (CH), 129.9 (CH), 127.2 (CH), 126.2, 124.9 (CH), 118.4, 116.9 (CH). IR (KBr) ν (cm⁻¹): 1716, 1660 (C=O), 1608, 1563, 1452 (Ar⁻), 1224 (C–O), 757 (C–Cl). HR MS m/z: 285.0317 [M + H]⁺ (calcd for C₁₆H₁₀ClO₃⁺ 285.0313).

3-(2-Bromobenzoyl)-2H-chromen-2-one (3ak). Slight yellow solid, mp 127–128 °C. ¹H NMR (400 MHz, CDCl₃) δ: 8.39 (s, 1H), 7.66 (t, J_H–H = 7.6 Hz, 2H), 7.60 (d, J_H–H = 7.9 Hz, 1H), 7.50 (dd, J_H–H = 7.6 Hz, J_H–H = 1.6 Hz, 1H), 7.44 (t, J_H–H = 7.4 Hz, 1H), 7.38–7.33 m, 3H). ¹³C NMR (100 MHz, CDCl₃) δ: 191.8 (C=O), 157.9 (C=O), 155.4, 147.7 (CH), 140.3, 134.5 (CH), 133.1 (CH), 132.2 (CH), 130.0 (CH), 129.8 (CH), 127.6 (CH), 125.5, 125.0 (CH), 119.7, 118.4, 116.9 (CH). IR (KBr) ν (cm⁻¹): 1747, 1668 (C=O), 1606, 1558, 1454 (Ar⁻), 1234 (C–O), 759 (C–Br). HR MS m/z: 328.9812 [M + H]⁺ (calcd for C₁₆H₁₀BrO₃⁺ 328.9808).

3-(2,4-Dichlorobenzoyl)-2H-chromen-2-one (3al). Slight yellow solid, mp 158–159 °C. ¹H NMR (400 MHz, CDCl₃) δ: 8.41 (s, 1H), 7.70–7.66 (m, 2H), 7.52 (d, J_H–H = 8.3 Hz, 1H), 7.43–7.35 (m, 4H). ¹³C NMR (100 MHz, CDCl₃) δ: 190.2 (C=O), 158.2 (C=O), 155.3, 147.4 (CH), 137.9, 136.7, 134.6 (CH), 132.5, 130.9 (CH), 130.0 (CH), 129.8 (CH), 127.6 (CH), 126.0, 125.1 (CH), 118.4, 117.0 (CH). IR (KBr) ν (cm⁻¹): 1722 (C=O), 1660 (C=O), 1608, 1556 (Ar⁻), 777 (C–Cl). HR MS m/z: 318.9927 [M + H]⁺ (calcd for C₁₆H₉Cl₂O₃⁺ 318.9923).

3-(5-Methylthiophene-2-carbonyl)-2H-chromen-2-one (3am). Slight yellow solid, mp 153–154 °C. ¹H NMR (400 MHz, CDCl₃) δ: 8.06 (s, 1H), 7.65 (td, J_H–H = 7.3 Hz, J_H–H = 1.2 Hz, 1H), 7.58 (d, J_H–H = 7.7 Hz, 1H), 7.54 (d, J_H–H = 3.8 Hz, 1H), 7.40 (d, J_H–H = 8.3 Hz, 1H), 7.34 (t, J_H–H = 7.5 Hz, 1H), 2.57 (s, 3H). ¹³C NMR (100 MHz, CDCl₃) δ: 182.4 (C=O), 158.3 (C=O), 154.6, 152.4, 144.3 (CH), 140.6, 136.0 (CH), 133.5 (CH), 129.1 (CH), 127.2 (CH), 126.9, 124.9 (CH), 118.1, 116.9 (CH), 16.3 (CH₃). IR (KBr) ν (cm⁻¹): 2954, 2922 (–CH₃), 1720 (C=O), 1630 (C=O), 1603, 1566 (Ar⁻), 1250 (C–S). HR MS m/z: 271.0420 [M + H]⁺ (calcd for C₁₅H₁₁O₃S⁺ 271.0423).

3-(5-Methylfuran-2-carbonyl)-2H-chromen-2-one (3an). Slight yellow solid, mp 157–158 °C. ¹H NMR (400 MHz, CDCl₃) δ: 8.12 (s, 1H), 7.64 (t, J_H–H = 7.5 Hz, 2H), 7.60 (d, J_H–H = 7.8 Hz, 1H), 7.39 (d, J_H–H = 8.3 Hz, 1H), 7.33 (t, J_H–H = 7.6 Hz, 1H), 7.25 (d, J_H–H = 3.5 Hz, 1H), 6.24 (d, J_H–H = 3.4 Hz, 1H), 2.43 (s, 3H). ¹³C NMR (100 MHz, CDCl₃) δ: 177.1 (C=O), 159.7 (C=O), 158.2, 154.6, 150.5, 145.0 (CH), 133.6 (CH), 129.2 (CH), 126.5, 124.9 (CH), 123.3 (CH), 118.2, 116.8 (CH), 109.7 (CH), 14.2 (CH₃). IR (KBr) ν (cm⁻¹): 1720, 1644 (C=O), 1606, 1567, 1508 (Ar⁻), 1211, 1174 (C–O). HR MS m/z: 255.0656 [M + H]⁺ (calcd for C₁₅H₁₁O₄⁺ 255.0652).

3-Benzoyl-7-methoxy-2H-chromen-2-one (3ba). Slight yellow crystal, mp 153–154 °C (152–153 °C).^{5c 1}H NMR (400 MHz, CDCl₃) δ: 8.07 (s, 1H), 7.85 (d, J_H–H = 7.5 Hz, 2H), 7.58 (t, J_H–H = 7.5 Hz, 1H), 7.50–7.44 (m, 3H), 6.90 (dd, J_H–H = 8.6 Hz, J_H–H = 2.3 Hz, 1H), 6.85 (d, J_H–H = 2.3 Hz, 1H), 3.90 (s, 3H). ¹³C NMR (100 MHz, CDCl₃) δ: 191.9 (C=O), 164.6, 158.7 (C=O), 157.1, 146.4, 136.7, 133.4, 130.4, 129.5, 128.4, 122.8, 113.5, 111.8, 100.6, 56.0. IR (KBr) ν (cm⁻¹): 1707, 1657 (C=O), 1616, 1508, 1450 (Ar⁻), 1227 (C–O). ESI MS m/z: 281.2 [M + H]⁺ (calcd for C₁₇H₁₃O₄⁺ 281.0).

7-Hydroxy-3-(4-methoxybenzoyl)-2H-chromen-2-one (3ce). Slight yellow crystal, mp 200–201 °C (190–191 °C).^{20 1}H NMR (400 MHz, DMSO) δ: 10.94 (s, 1H), 8.27 (s, 1H), 7.86 (dd, J_H–H = 6.8 Hz, J_H–H = 2.0 Hz, 2H), 7.68 (d, J_H–H = 8.5 Hz, 1H), 7.05 (dd, J_H–H = 6.8 Hz, J_H–H = 2.0 Hz, 2H), 6.85 (dd, J_H–H = 8.5 Hz, J_H–H = 2.2 Hz, 1H), 6.79 (d, J_H–H = 2.2 Hz, 1H), 3.86 (s, 3H). ¹³C NMR (100 MHz, DMSO) δ: 190.7 (C=O), 164.0, 163.4, 158.9 (C=O), 156.8, 146.2 (CH), 132.4 (CH), 131.7 (CH), 129.7, 122.2, 114.3 (CH), 114.2 (CH), 111.2, 102.5 (CH), 56.0 (CH₃). IR (KBr) ν (cm⁻¹): 3340 (–OH), 2924, 2843 (–CH₃), 1689, 1622 (C=O), 1601, 1564, 1454 (Ar⁻), 1230 (C–O). ESI MS m/z: 297.3 [M + H]⁺ (calcd for C₁₇H₁₃O₅⁺ 297.1).

3-(4-Methoxybenzoyl)-6-nitro-2H-chromen-2-one (3de). Slight yellow crystal, mp 219–220 °C. ¹H NMR (400 MHz, DMSO) δ: 8.82 (d, J_H–H = 2.7 Hz, 1H), 8.51 (dd, J_H–H = 9.1 Hz, J_H–H = 2.7 Hz, 1H), 8.49 (s, 1H), 7.98 (dd, J_H–H = 7.0 Hz, J_H–H = 2.0 Hz, 2H), 7.72 (d, J_H–H = 9.1 Hz, 1H), 7.08 (dd, J_H–H = 7.0 Hz, J_H–H = 2.0 Hz, 2H), 3.88 (s, 3H). ¹³C NMR (100 MHz, DMSO) δ: 189.8 (C=O), 164.6, 158.1 (C=O), 157.7, 144.1, 143.5, 132.8, 129.0, 128.8, 128.0, 125.7, 119.2, 118.3, 114.6, 56.2. IR (KBr) ν (cm⁻¹): 1751, 1652 (C=O), 1614, 1596, 1571 (Ar⁻), 1529, 1346 (–NO₂), 1257 (C–O). HR MS m/z: 326.0660 [M + H]⁺ (calcd for C₁₇H₁₂O₆⁺ 326.0659).

3-Benzoyl-4-methyl-2-oxo-2H-chromen-7-yl acetate (3ea). Slight yellow solid, mp 114–115 °C. ¹H NMR (400 MHz, CDCl₃) δ: 7.91 (dd, J_H–H = 8.0 Hz, J_H–H = 0.8 Hz, 2H), 7.71 (d, J_H–H = 8.7 Hz, 1H), 7.61 (td, J_H–H = 7.4 Hz, J_H–H = 1.2 Hz, 1H), 7.47 (t, J_H–H = 8.0 Hz, 2H), 7.18 (d, J_H–H = 2.2 Hz, 1H), 7.14 (dd, J_H–H = 8.7 Hz, J_H–H = 2.2 Hz, 1H), 2.35 (s, 3H), 2.33 (s, 3H). ¹³C NMR (100 MHz, CDCl₃) δ: 192.9 (C=O), 168.6, 158.4 (C=O), 153.7, 153.6, 149.7, 136.0, 134.3 (CH), 129.3 (CH), 129.0 (CH), 126.2 (CH), 125.3, 118.7 (CH), 117.4, 110.5 (CH), 21.1 (CH₃), 16.0 (CH₃). IR (KBr) ν (cm⁻¹): 3066, 2925 (–CH₃), 1768, 1720, 1670 (C=O), 1614, 1450 (Ar⁻), 1186 (C–O). HR MS m/z: 323.0916 [M + H]⁺ (calcd for C₁₉H₁₅O₅⁺ 323.0914).

7-Ethoxy-3-(4-methoxybenzoyl)-4-methyl-2H-chromen-2-one (3fe). Slight yellow solid, mp 121–122 °C. ¹H NMR (400 MHz, CDCl₃) δ: 7.91 (dd, J_H–H = 9.7 Hz, J_H–H = 2.7 Hz, 1H), 7.58 (d, J_H–H = 8.9 Hz, 1H), 6.95–6.89 (m, 3H), 6.84 (d, J_H–H = 2.4 Hz, 1H), 4.11 (q, J_H–H = 7.0 Hz, 2H), 3.86 (s, 3H), 2.31 (s, 3H), 1.47 (t, J_H–H = 7.0 Hz, 3H). ¹³C NMR (100 MHz, CDCl₃) δ: 191.9 (C=O), 164.4, 162.6, 159.2 (C=O), 154.9, 150.2, 131.9 (CH), 129.6, 126.2 (CH), 122.8, 114.2 (CH), 113.2 (CH), 112.9, 101.3 (CH), 64.3 (CH₂), 55.6 (OCH₃), 15.9 (CH₃), 14.5 (CH₃). IR (KBr) ν (cm⁻¹): 1714, 1660 (C=O), 1600, 1558 (Ar⁻), 1259 (C–O). HR MS m/z: 339.1229 [M + H]⁺ (calcd for C₂₀H₁₉O₅⁺ 339.1227).

General procedure for 3-benzoyl quinolin derivatives

In a 25 mL Schlenk tube, N-methyl quinolinones 4 (0.25 mmol), aromatic aldehyde 2 (1.0 mmol), TBHP (1.0 mmol) and FeCl₂ (0.025 mmol) were added and charged with nitrogen (3 cycles). Chlorobenzene (2 mL) was then added, and the reaction mixture was heated in the oil bath at 120 °C for 12 h (monitored by TLC). After the reaction mixture had been cooled to room temperature, and the solvent was removed with the aid of a rotary evaporator. 2 mL ethylacetate was added to the residue. The solution was filtrated, and the filtrate was distilled under vacuum. The crude product was purified by silica gel column chromatography using ethylacetate/petroleum ether (1 : 5 to 2 : 1) as eluant to provide the desired products 5.

1-Methyl-3-(4-methylbenzoyl)quinolin-2(1H)-one (5ab). Slight yellow crystal, mp 143–144 °C. ¹H NMR (400 MHz, CDCl₃) δ: 7.94 (s, 1H), 7.78 (dd, J_H–H = 6.6 Hz, J_H–H = 1.6 Hz, 2H), 7.68–7.63 (m, 2H), 7.41 (d, J_H–H = 8.5 Hz, 1H), 7.28 (td, J_H–H = 7.9 Hz, J_H–H = 0.8 Hz, 1H), 7.24 (d, J_H–H = 7.9 Hz, 2H), 3.74 (s, 3H), 2.40 (s, 3H). ¹³C NMR (100 MHz, CDCl₃) δ: 193.7 (C=O), 160.0 (C=O), 144.2, 140.8, 139.8 (CH), 134.5, 132.1 (CH), 131.8, 129.9 (CH), 129.7 (CH), 129.2 (CH), 122.6 (CH), 119.5, 114.3 (CH), 29.6 (CH₃), 21.8 (CH₃). IR (KBr) ν (cm⁻¹): 3054, 2923 (–CH₃), 1639 (C=O), 1589, 1571 (Ar⁻), 1290 (C–N). HR MS m/z: 278.1178 [M + H]⁺ (calcd for C₁₈H₁₆NO₂⁺ 278.1176).

3-(4-Methoxybenzoyl)-1-methylquinolin-2(1H)-one (5ad). Slight yellow crystal, mp 165–166 °C. ¹H NMR (400 MHz, CDCl₃) δ: 7.91 (s, 1H), 7.87 (dd, J_H–H = 6.9 Hz, J_H–H = 4.8 Hz, 2H), 7.67–7.61 (m, 2H), 7.40 (d, J_H–H = 8.4 Hz, 1H), 7.27 (td, J_H–H = 7.8 Hz, J_H–H = 0.7 Hz, 1H), 6.91 (dd, J_H–H = 6.9 Hz, J_H–H = 2.0 Hz, 2H), 3.85 (s, 3H), 3.74 (s, 3H). ¹³C NMR (100 MHz, CDCl₃) δ: 192.5 (C=O), 163.8, 160.0 (C=O), 140.7, 139.5 (CH), 132.1 (CH), 132.0 (CH), 129.9, 129.8 (CH), 122.6 (CH), 119.6, 114.3 (CH), 113.7 (CH), 55.5 (CH₃), 29.6 (CH₃). IR (KBr) ν (cm⁻¹): 2919, 2850 (–CH₃), 1650, 1639 (C=O), 1602, 1589, 1573 (Ar⁻), 1255 (C–N). HR MS m/z: 294.1126 [M + H]⁺ (calcd for C₁₈H₁₆NO₃⁺ 294.1125).

3-(2-Methoxybenzoyl)-1-methylquinolin-2(1H)-one (5af). Slight yellow crystal, mp 165–166 °C. ¹H NMR (400 MHz, CDCl₃) δ: 8.11 (s, 1H), 7.69 (td, J_H–H = 7.3 Hz, J_H–H = 1.6 Hz, 2H), 7.63 (td, J_H–H = 7.3 Hz, J_H–H = 1.6 Hz, 1H), 7.48 (td, J_H–H = 6.4 Hz, J_H–H = 1.8 Hz, 1H), 7.37 (d, J_H–H = 8.5 Hz, 1H), 7.27 (td, J_H–H = 7.8 Hz, J_H–H = 0.8 Hz, 1H), 7.05 (td, J_H–H = 7.5 Hz, J_H–H = 0.7 Hz, 1H), 6.91 (d, J_H–H = 8.2 Hz, 1H), 3.69 (s, 3H), 3.68 (s, 3H). ¹³C NMR (100 MHz, CDCl₃) δ: 193.2 (C=O), 160.2, 158.6 (C=O), 141.0, 139.7 (CH), 133.5 (CH), 133.2, 132.1 (CH), 130.5 (CH), 130.3 (CH), 129.1, 122.4 (CH), 120.9 (CH), 119.8, 114.2 (CH), 111.4 (CH), 55.7 (CH₃), 29.4 (CH₃). IR (KBr) ν (cm⁻¹): 2922, 250 (–CH₃), 1643 (C=O), 1589, 1568, 1485, 1462 (Ar⁻), 1296 (C–N), 1250 (C–O). HR MS m/z: 294.1127 [M + H]⁺ (calcd for C₁₈H₁₆NO₃⁺ 294.1125).

1-Methyl-3-(5-methylfuran-2-carbonyl)quinolin-2(1H)-one (5an). Slight yellow crystal, mp 114–116 °C. ¹H NMR (400 MHz, CDCl₃) δ: 7.97 (s, 1H), 7.67–7.62 (m, 2H), 7.40 (d, J_H–H = 8.4 Hz, 1H), 7.60 (dd, J_H–H = 7.8 Hz, J_H–H = 1.5 Hz, 1H), 7.39 (d, J_H–H = 8.2 Hz, 2H), 7.32 (td, J_H–H = 8.2 Hz, J_H–H = 7.8 Hz, 1H), 7.27 (d, J_H–H = 8.0 Hz, 1H), 2.42 (s, J_H–H = 2.43, 3H). ¹³C NMR (100 MHz, CDCl₃) δ: 191.2 (C=O), 158.5 (C=O), 154.7, 145.1 (CH), 144.9, 133.6 (CH), 133.5, 129.8 (CH), 129.4 (CH), 129.2 (CH), 127.2, 124.9 (CH), 118.2, 116.9 (CH), 21.8 (CH₃). IR (KBr) ν (cm⁻¹): 2922, 2852 (–CH₃), 1657, 1643 (C=O), 1591, 1512 (Ar⁻), 1292 (C–N), 1207 (C–O). HR MS m/z: 268.0967 [M + H]⁺ (calcd for C₁₆H₁₄NO₃⁺ 268.0968).

7-Methoxy-3-(4-methoxybenzoyl)-1-methylquinolin-2(1H)-one (5bd). Slight yellow crystal, mp 179–181 °C. ¹H NMR (400 MHz, CDCl₃) δ: 7.90 (s, 1H), 7.86 (d, J_H–H = 8.9 Hz, 2H), 7.55 (d, J_H–H = 8.7 Hz, 1H), 6.92 (d, J_H–H = 8.9 Hz, 1H), 6.87 (dd, J_H–H = 8.6 Hz, J_H–H = 2.3 Hz, 1H), 6.81 (d, J_H–H = 2.3 Hz, 1H), 3.95 (s, 3H), 3.86 (s, 3H), 3.71 (s, 3H). ¹³C NMR (100 MHz, CDCl₃) δ: 192.8 (C==O), 163.6, 163.1, 160.4 (C=O), 142.7, 140.1 (CH), 132.0 (CH), 131.5 (CH), 130.3, 128.5, 113.8, 113.6 (CH), 110.5 (CH), 98.5 (CH), 55.7 (CH₃), 55.4 (CH₃), 29.6 (CH₃). IR (KBr) ν (cm⁻¹): 2920, 2946 (–CH₃), 1655, 1645 (C=O), 1620, 1589, 1593 (Ar⁻), 1254 (C–N), 1236 (C–O). HR MS m/z: 324.1232 [M + H]⁺ (calcd for C₁₉H₁₈NO₄⁺ 324.1230).

6-Bromo-3-(4-methoxybenzoyl)-1-methylquinolin-2(1H)-one (5cd). Slight yellow crystal, mp 182–183 °C. ¹H NMR (400 MHz, CDCl₃) δ: 7.84 (d, J_H–H = 8.9 Hz, 2H), 7.78 (s, 1H), 7.73 (d, J_H–H = 2.2 Hz, 1H), 7.69 (dd, J_H–H = 8.6 Hz, J_H–H = 2.2 Hz, 1H), 7.28 (d, J_H–H = 8.6 Hz, 1H), 6.90 (d, J_H–H = 8.9 Hz, 1H), 3.85 (s, 3H), 3.71 (s, 3H). ¹³C NMR (100 MHz, CDCl₃) δ: 191.9 (C=O), 164.0, 159.6 (C=O), 139.5, 137.9 (CH), 134.5 (CH), 133.2, 132.0 (CH), 131.7 (CH), 129.5, 121.0, 116.1 (CH), 115.3, 113.8 (CH), 55.5 (CH₃), 29.8 (CH₃). IR (KBr) ν (cm⁻¹): 2918, 2843 (–CH₃), 1658, 1637 (C=O), 1606, 1577, 1562 (Ar⁻), 1267 (C–N), 1178 (C–O), 810 (C–Br). HR MS m/z: 372.0233 [M + H]⁺ (calcd for C₁₈H₁₅BrNO₃⁺ 372.0230).

Conclusions

In conclusion, a novel, simple and efficient protocol for the synthesis of 3-aroyl coumarins via iron-catalyzed direct coupling of coumarins with aromatic aldehyde has been developed. Various 3-aroyl coumarins were obtained in moderate to good yields. The aroyl substituents were introduced into coumarins or other heteroarenes with complete regioselectivity at the 3-position.

Acknowledgements

We gratefully acknowledge the National Natural Science Foundation of China (No. 21302042 and 21172055), the Program for Innovative Research Team from Zhengzhou (No. 131PCXTD605), Department of Henan Province Natural Science and Technology Foundation (No. 142102210410) and Natural Science Foundation in Henan Province Department of Education (No. 14B150053).

Notes and references

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Footnote

† Electronic supplementary information (ESI) available. See DOI: 10.1039/c5ra16573c

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