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Article

Transition Metal-Free Synthesis of 3-Acylquinolines through Formal [4+2] Annulation of Anthranils and Enaminones

by
Kai-Ling Zhang
1,†,
Jia-Cheng Yang
1,†,
Qin Guo
1 and
Liang-Hua Zou
1,2,*
1
Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Life Science and Health Engineering, Jiangnan University, Wuxi 214122, China
2
School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang 453007, China
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Catalysts 2023, 13(4), 778; https://doi.org/10.3390/catal13040778
Submission received: 29 March 2023 / Revised: 16 April 2023 / Accepted: 17 April 2023 / Published: 20 April 2023
(This article belongs to the Special Issue Catalytic Annulation Reactions)
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Abstract

:
A transition metal-free protocol has been developed for the synthesis of 3-acyl quinolines through aza-Michael addition and intramolecular annulation of enaminones with anthranils. Both methanesulfonic acid (MSA) and NaI play an important role in the reaction. This ring-opening/reconstruction strategy features easy operation, high yields, broad substrate scope and excellent efficiency.

1. Introduction

The quinoline skeleton, as one of the most prevalent heterocycles, widely exist in natural products and synthetic compounds [1,2,3,4]. In the past decades, significant attention has been devoted to the synthesis of quinolines because of their valuable biological and chemical properties in the application of medicals [5,6,7,8,9], ligands [10,11], and materials [12,13,14,15]. Therefore, the development of novel, practical, and efficient synthetic methods is highly desirable for the synthesis of quinoline derivatives [16,17].
Traditional strategies for the synthesis of quinolines, such as Friedlander synthesis [18] and Doebner–von Miller synthesis [19], could date back to a long time ago. The establishment of quinoline reservoirs nowadays has been broadly prepared by using aromatic amines, isoxazoles, or amino acids as nitrogen sources [20,21,22,23]. Transition metal catalysts were normally required for such multi-component coupling and cascade cyclization reactions [24,25,26,27,28,29,30,31,32]. Most of these methods suffered from some drawbacks such as a complex reaction system, harsh reaction conditions, and complex by-products. Consequently, the development of a transition metal-free protocol for the synthesis of quinoline derivatives appears desirable and synthetically attractive [33,34,35,36,37,38,39].
In particular, the synthesis of 3-acylquinolines has attracted significant attention due to their valuable application. Representative methods for the preparation of such compounds include (i) Fe powder-catalyzed reaction of 2-nitrobenzaldehyde with enaminones [40]; (ii) copper-catalyzed one-pot domino reactions starting from 2-aminobenzylalcohols and propiophenones [41]; and (iii) copper-catalyzed annulation of anthranils and saturated ketones [42]. Besides, several transition metal-free protocols have also been developed. In recent years, the application of enaminones [43,44,45] and anthranils [46,47,48,49,50,51,52,53] as useful building blocks have attracted significant attention in transition metal-catalyzed organic synthesis and construction of a variety of frameworks. Based on our previous work involving sulfoxonium ylides, aldehydes, and anthranils in constructing quinoline derivatives [54,55,56], we were intrigued to investigate the reactivity of enaminones in the annulation reactions for the construction of heterocycles [57,58]. Herein, we report a transition metal-free protocol for the synthesis of 3-acylquinolines under simple and easy-to-operate conditions.

2. Results

The initial screening and optimization of the reaction conditions were conducted with compounds 1a and 2a as substrates. Using 1a and 2a in a 2:1 ratio (on a 0.2 mmol scale), EtOH (2 mL) as a solvent and methanesulfonic acid (MSA) (0.3 mmol) as an additive, product 3aa was obtained in 31% yield by heating at 110 °C (Table 1, entry 1). Next, the use of other solvents, such as HFIP, DME, n-octanol, dioxane, THF, and DMSO, was investigated but no better results were achieved (Table 1, entries 2–7). No product was obtained in the absence of MSA (Table 1, entry 8). An attempt to employ a mixture of additives MSA and KBr (each 0.3 mmol) in EtOH or THF led to higher yields of 58% and 37%, respectively, indicating that EtOH was more suitable for this reaction (Table 1, entries 9 and 10). Next, we tried to use other salts instead of KBr as an additive, such as KI and NaI, affording product 3aa in 89% and 90% yields, respectively (Table 1, entries 11 and 12). When the reaction was performed at lower temperatures, the yields dropped significantly, while a higher temperature did not improve the reaction efficiency (Table 1, entries 13–16).
With the optimized reaction conditions in hand (Table 1, entry 10), the scope of the reaction of anthranil 1a with a variety of enaminones 2 was investigated and the results are summarized in Scheme 1. Substrates with various electron-donating or electron-withdrawing substituents were applied to the reaction system to provide a series of 3-acylquinolines. For example, the reaction of substrates bearing electron-donating substituents such as -Me, -OMe, -OPh, -NMe2, and -SMe afforded the corresponding products 3ab–3af in good yields ranging from 60% to 84%. For the substrates with -F, -Cl, -Br, and -I groups at the para-position, the reaction also proceeded well to give the corresponding products 3ag–3ai in high yields. Substrates containing substituents -CN, -NO2, and -CF3 were also successfully employed in the reaction, yielding products 3ak–3am in moderate yields. The reaction of one substrate bearing a phenyl group afforded the corresponding product 3an in 81% yield. It appeared that the steric factors did not influence the efficiency significantly. For example, various substituents at the ortho- or meta-position were well tolerated, providing the corresponding products 3ao–3at in similarly good yields ranging from 81% to 88%. Substrates bearing two substituents at the ortho- and meta-positions were also investigated, affording products 3au–3aw in 83%, 82%, and 81% yields, respectively. Furthermore, one substrate bearing electron-donating dioxolo-group was also successfully employed in the reaction, providing the desired product 3ax in 79% yield. The reaction of the substrate bearing naphthyl group afforded product 3ay in 84% yield. At last, substrates containing oxygen- or sulfur-heterocycle also reacted well with 1a, giving products 3az and 3az’ in 83% and 80% yields, respectively.
In order to further explore the scope of the reaction, a series of anthranil 1 were introduced to react with compound 2a under the optimized reaction conditions, and the results are summarized in Scheme 2. The reactions of various anthranil-bearing electron-donating substituent -OMe proceeded well, affording product 3ba in 83% yield. The substrate bearing halogen substituents -F, -Cl, and -Br could also be employed in the reaction, providing the corresponding products 3ca–3ea in high yields. Under the conditions, products 3fa–3ha with halogen substituents -F, -Cl, and -Br at 7-position were also successfully obtained in yields ranging from 83% to 88%. The reactions of anthranils bearing electron-withdrawing substituents -CF3 and -CO2Me provided products 3ia and 3ja in 80% and 75% yields, respectively. In addition, bisubstitued substrates were also investigated, affording the corresponding products 3ka–3ma in satisfying yields. Finally, one C3-aryl substituted example was investigated in the reaction, giving product 3na in 84% yield.
To test the scalability of the new protocol, gram-scale preparation was carried out under the standard conditions with 12 mmol of 1a and 6 mmol of 2a, and product 3aa was successfully obtained in 85% yield (1.192 g) (Scheme 3).
To elucidate the possible mechanism, several preliminary experiments were carried out. At first, 2-aminobenzaldehyde was employed instead of anthranil 2a to investigate whether it was an intermediate in the process, affording product 3aa in 56% yield (Scheme 4, Equation (a)). The results showed that 2-aminobenzaldehyde might be an intermediate for the transformation of anthranil 2a. Furthermore, radical scavengers, such as 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO), 2,6-bis(1,1-dimethylethyl)-4-methylphenol (BHT), and 1,1-diphenyltheylene, were tested in the reaction, affording the desired product 3aa in 70%, 87%, and 81% yields, respectively, indicating that there might be no radical step in the process (Scheme 4, Equation (b)). The 1H NMR spectrum of the intermolecular competition experiment between (E)-3-(dimethylamino)-1-(p-tolyl)prop-2-en-1-one (2b) and (E)-3-(dimethylamino)-1-(4-fluorophenyl)prop-2-en-1-one (2g) showed that the ratio of products 3ab and 3ag was 1:0.64. When the electron-deficient substrate was changed to (E)-3-(dimethylamino)-1-(4-(trifluoromethyl)phenyl)prop-2-en-1-one (2m), the ratio of products 3ab and 3am in the intermolecular competition experiment was 1:0.62. Both results indicated that substrates bearing electron-donating substituents were more active than that with electron-withdrawing substituents (Scheme 4, Equation (c)).
On the basis of our results and previous reports on enaminone 2a [59], a possible mechanism on the synthesis of 3aa is proposed as shown in Scheme 5. First, 2a is activated by methanesulfonic acid (MSA) to form intermediate A, which is attacked by 1a to give intermediate B. NaI is crucial for the success of this reaction, probably due to the fact that it can promote the stability of intermediate B. Then, intermediate C is produced, affording D through an intramolecular nucleophilic addition. Finally, D is converted into the desired product 3aa.

3. Conclusions

In conclusion, a mild and efficient protocol has been developed for the synthesis of a broad range of 3-acyl quinolines under transition metal-free conditions. Various enaminones and anthranils were well employed in the reaction, providing a series of 3-acyl quinolines through aza-Michael addition and intramolecular annulation. Mechanism studies showed that no radical step was involved in the process. It was noteworthy that MSA and NaI played a significant role for the success of the transformation.

4. Experimental Section

General Information. All solvents were dried over molecular sieves. Unless otherwise noted, materials obtained from commercial suppliers were used without further purification. Anthranil 1n was purchased and other anthranils were all synthesized according to our previous work [55]. All the substrates enaminones were prepared according to the reference [60]. The products were isolated using column chromatography on silica gel (200–300 mesh) by using petroleum ether (PE, 30–60 °C) and ethyl acetate (EA) as eluents. All yields described herein were the isolated yields after column chromatography. Reaction progress and product mixtures were routinely monitored by using TLC using TLC SiO2 sheets, and compounds were visualized under ultraviolet light. 1H NMR, 13C NMR, and 19F NMR spectra were recorded on a Bruker AVANCE III 400 spectrometer. The spectra were recorded using CDCl3 as a solvent. 1H NMR chemical shifts are referenced to tetramethylsilane (TMS, 0 ppm). 19F NMR chemical shifts are referenced to p-fluorotoluene (p-fluorotoluene, 0 ppm). Abbreviations are as follows: s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet). High-resolution mass spectra (HRMS) were recorded on Agilent 6540 or FTICR-MS bruker7 T. Melting points were measured with a melting point instrument (Shanghai Yidian Physical Optical Instrument Co., Ltd., Shanghai, China, SGW, X-4A) and were uncorrected.
General procedure for the synthesis of 3aa: A mixture of 1a (0.4 mmol, 2.0 equiv), 2a (0.2 mmol, 1.0 equiv) and NaI (0.3 mmol, 1.5 equiv) were added in a Schlenk tube equipped with a stirring bar. Dry EtOH (2 mL) and MSA (0.3 mmol, 1.5 equiv) were added and the mixture was stirred at 110 °C in a pre-heated oil bath for 12 h under air atmosphere. Then, the mixture was cooled to room temperature and concentrated in vacuo, and the resulting residue was purified by using column chromatography on silica gel with EtOAc/petroleum ether, affording product 3aa as a white solid in 90% yield (42.1 mg).

4.1. Phenyl(quinolin-3-yl)methanone (3aa)

Compound 3aa was synthesized in accordance with the typical procedure. Purification using column chromatography on silica gel (PE:EA = 10:1) afforded product 3aa (42.1 mg, 90%) as a white solid.
1H NMR (400 MHz, CDCl3) δ ppm: 9.31 (d, J = 2.3 Hz, 1H), 8.54 (d, J = 2.2 Hz, 1H), 8.18 (d, J = 8.5 Hz, 1H), 7.91 (d, J = 8.3 Hz, 1H), 7.84 (td, J = 8.2, 2.1 Hz, 3H), 7.63 (q, J = 7.3 Hz, 2H), 7.53 (t, J = 7.7 Hz, 2H). 13C{1H} NMR (101 MHz, CDCl3) δ ppm: 194.8, 150.3, 149.4, 138.8, 137.0, 133.0, 131.8, 130.04, 130.0, 129.4, 129.1, 128.6, 127.6, 126.6. HRMS m/z (ESI) calcd for C16H12NO (M+H)+ 234.0913, found 234.0920. The NMR spectra are consistent with the reported literature [31].

4.2. Quinolin-3-yl(p-tolyl)methanone (3ab)

Compound 3ab was synthesized in accordance with the typical procedure. Purification using column chromatography on silica gel (PE:EA = 10:1) afforded product 3ab (41.4 mg, 84%) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm: 9.30 (d, J = 2.1 Hz, 1H), 8.54 (d, J = 2.1 Hz, 1H), 8.19 (d, J = 8.4 Hz, 1H), 7.91 (d, J = 9.5 Hz, 1H), 7.84 (t, J = 7.7 Hz, 1H), 7.78 (d, J = 8.1 Hz, 2H), 7.63 (t, J = 7.0 Hz, 1H), 7.33 (d, J = 7.9 Hz, 2H), 2.47 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ ppm: 194.5, 150.3, 149.3, 144.0, 138.6, 134.3, 131.7, 130.4, 130.2, 129.4, 129.3, 129.1, 127.5, 126.6, 21.7. The NMR spectra are consistent with the reported literature [31].

4.3. (4-Methoxyphenyl)(quinolin-3-yl)methanone (3ac)

Compound 3ac was synthesized in accordance with the typical procedure. Purification using column chromatography on silica gel (PE:EA = 10:1) afforded product 3ac (42.6 mg, 81%) as a white solid.
1H NMR (400 MHz, CDCl3) δ ppm: 9.26 (d, J = 2.2 Hz, 1H), 8.50 (d, J = 2.2 Hz, 1H), 8.18 (d, J = 8.5 Hz, 1H), 7.87 (td, J = 13.7, 8.6 Hz, 4H), 7.65–7.59 (m, 1H), 7.00 (d, J = 8.8 Hz, 2H), 3.89 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ ppm: 193.4, 163.7, 150.2, 149.2, 138.1, 132.5, 131.5, 130.8, 129.7, 129.4, 129.0, 127.4, 126.6, 113.9, 55.5. The NMR spectra are consistent with the reported literature [31].

4.4. (4-Phenoxyphenyl)(quinolin-3-yl)methanone (3ad)

Compound 3ad was synthesized in accordance with the typical procedure. Purification using column chromatography on silica gel (PE:EA = 10:1) afforded product 3ad (46.0 mg, 71%) as a white solid, m.p. 78–80 °C; 1H NMR (400 MHz, CDCl3) δ ppm: 9.29 (d, J = 2.1 Hz, 1H), 8.53 (d, J = 2.2 Hz, 1H), 8.18 (d, J = 8.5 Hz, 1H), 7.93–7.87 (m, 2H), 7.87–7.81 (m, 2H), 7.63 (t, J = 7.5 Hz, 1H), 7.41 (t, J = 7.9 Hz, 2H), 7.21 (t, J = 7.4 Hz, 1H), 7.09 (dd, J = 18.3, 8.7 Hz, 4H). 13C{1H} NMR (101 MHz, CDCl3) δ ppm: 193.4, 162.2, 155.2, 150.2, 149.3, 138.3, 132.4, 131.6, 131.3, 130.4, 130.1, 129.4, 129.0, 127.5, 126.6, 124.8, 120.3, 117.3. HRMS m/z (ESI) calcd for C22H15NO2(M+H)+ 326.1176, found 326.1183.

4.5. (4-(Dimethylamino)phenyl)(quinolin-3-yl)methanone (3ae)

Compound 3ae was synthesized in accordance with the typical procedure. Purification using column chromatography on silica gel (PE:EA = 5:1) afforded product 3ae (33.1 mg, 60%) as a yellow solid, m.p. 118–120 °C; 1H NMR (400 MHz, CDCl3) δ ppm: 9.25 (d, J = 2.2 Hz, 1H), 8.49 (d, J = 3.1 Hz, 1H), 8.18 (d, J = 8.5 Hz, 1H), 7.91 (d, J = 7.9 Hz, 1H), 7.85–7.79 (m, 3H), 7.62 (ddd, J = 8.1, 6.9, 1.2 Hz, 1H), 6.73–6.69 (m, 2H), 3.10 (s, 6H). 13C{1H} NMR (101 MHz, CDCl3) δ ppm: 192.7, 153.6, 150.4, 148.9, 137.6, 132.7, 131.8, 131.1, 129.3, 128.9, 127.3, 126.8, 124.2, 110.7, 40.0. HRMS m/z (ESI) calcd for C18H16N2O (M+H)+ 277.1335, found 277.1327.

4.6. (Methylthio)phenyl)(quinolin-3-yl)methanone (3af)

Compound 3af was synthesized in accordance with the typical procedure. Purification using column chromatography on silica gel (PE:EA = 10:1) afforded product 3af (43.1 mg, 77%) as a white solid, m.p. 110–112 °C; 1H NMR (400 MHz, CDCl3) δ ppm: 9.27 (d, J = 2.1 Hz, 1H), 8.50 (d, J = 2.2 Hz, 1H), 8.17 (d, J = 8.5 Hz, 1H), 7.89 (d, J = 8.2 Hz, 1H), 7.84–7.76 (m, 3H), 7.61 (t, J = 7.5 Hz, 1H), 7.31 (d, J = 8.2 Hz, 2H), 2.53 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ ppm: 193.7, 150.2, 149.3, 146.3, 138.3, 133.0, 131.6, 130.5, 130.3, 129.4, 129.0, 127.5, 126.5, 124.9, 14.7. HRMS m/z (ESI) calcd for C17H13NOS (M+H)+ 280.0791, found 280.0784.

4.7. (4-Fluorophenyl)(quinolin-3-yl)methanone (3ag)

Compound 3ag was synthesized in accordance with the typical procedure. Purification using column chromatography on silica gel (PE:EA = 10:1) afforded product 3ag (43.0 mg, 86%) as a white solid.
1H NMR (400 MHz, CDCl3) δ ppm: 9.28 (d, J = 2.2 Hz, 1H), 8.52 (d, J = 2.8 Hz, 1H), 8.18 (d, J = 8.6 Hz, 1H), 7.93–7.88 (m, 3H), 7.85 (ddd, J = 8.5, 6.9, 1.5 Hz, 1H), 7.66–7.62 (m, 1H), 7.21 (t, J = 8.6 Hz, 2H). 13C{1H} NMR (101 MHz, CDCl3) δ ppm: 193.4, 165.7 (d, J = 255.4 Hz), 150.1, 149.4, 138.6, 133.2 (d, J = 2.8 Hz), 132.6 (d, J = 9.4 Hz), 131.9, 129.3, 127.7, 126.5, 115.9 (d, J = 21.9 Hz). 19F NMR (376 MHz, CDCl3) δ ppm: −104.4. The NMR spectra are consistent with the reported literature [31].

4.8. (4-Chlorophenyl)(quinolin-3-yl)methanone (3ah)

Compound 3ah was synthesized in accordance with the typical procedure. Purification using column chromatography on silica gel (PE:EA = 10:1) afforded product 3ah (47.1 mg, 88%) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm: 9.28 (d, J = 2.2 Hz, 1H), 8.52 (d, J = 2.3 Hz, 1H), 8.18 (d, J = 8.5 Hz, 1H), 7.92–7.83 (m, 2H), 7.82–7.79 (m, 2H), 7.64 (ddd, J = 8.1, 6.9, 1.2 Hz, 1H), 7.53–7.46 (m, 2H). 13C{1H} NMR (101 MHz, CDCl3) δ ppm: 193.6, 150.0, 149.5, 139.6, 138.7, 135.2, 132.0, 131.4, 129.6, 129.4, 129.1, 129.0, 127.7, 126.5. The NMR spectra are consistent with the reported literature [31].

4.9. (4-Bromophenyl)(quinolin-3-yl)methanone (3ai)

Compound 3ai was synthesized in accordance with the typical procedure. Purification using column chromatography on silica gel (PE:EA = 10:1) afforded product 3ai (53.5 mg, 86%) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm: 9.29 (d, J = 2.2 Hz, 1H), 8.53 (d, J = 1.3 Hz, 1H), 8.19 (d, J = 9.5 Hz, 1H), 7.92 (d, J = 8.1 Hz, 1H), 7.86 (ddd, J = 8.5, 6.9, 1.4 Hz, 1H), 7.76–7.72 (m, 2H), 7.70–7.63 (m, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ ppm: 193.8, 150.1, 149.5, 138.8, 135.7, 132.0, 132.0, 131.5, 129.6, 129.5, 129.1, 128.3, 127.7, 126.5. The NMR spectra are consistent with the reported literature [31].

4.10. (4-Iodophenyl)(quinolin-3-yl)methanone (3aj)

Compound 3aj was synthesized in accordance with the typical procedure. Purification using column chromatography on silica gel (PE:EA = 10:1) afforded product 3aj (66.3 mg, 82%) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm: 9.28 (d, J = 2.2 Hz, 1H), 8.51 (d, J = 1.5 Hz, 1H), 8.18 (d, J = 8.5 Hz, 1H), 7.92–7.83 (m, 4H), 7.66–7.60 (m, 1H), 7.59–7.53 (m, 2H). 13C{1H} NMR (101 MHz, CDCl3) δ ppm: 194.0, 150.0, 149.5, 138.7, 137.9, 136.2, 132.0, 131.3, 129.5, 129.4, 127.7, 126.4, 101.0. The NMR spectra are consistent with the reported literature [22].

4.11. 4-(Quinoline-3-carbonyl)benzonitrile (3ak)

Compound 3ak was synthesized in accordance with the typical procedure. Purification using column chromatography on silica gel (PE:EA = 5:1) afforded product 3ak (35.5 mg, 69%) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm: 9.28 (d, J = 2.2 Hz, 1H), 8.51 (d, J = 2.2 Hz, 1H), 8.18 (d, J = 8.4 Hz, 1H), 7.92 (t, J = 7.4 Hz, 3H), 7.88 (d, J = 7.5 Hz, 1H), 7.83 (d, J = 8.1 Hz, 2H), 7.65 (t, J = 7.5 Hz, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ ppm: 193.3, 149.8, 149.7, 140.4, 139.0, 132.4, 132.4, 130.1, 129.5, 129.2, 128.8, 127.9, 126.4, 117.7, 116.2. The NMR spectra are consistent with the reported literature [31].

4.12. (4-Nitrophenyl)(quinolin-3-yl)methanone (3al)

Compound 3al was synthesized in accordance with the typical procedure. Purification using column chromatography on silica gel (PE:EA = 5:1) afforded product 3al (35.4 mg, 60%) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm: 9.32 (d, J = 2.2 Hz, 1H), 8.54 (d, J = 2.2 Hz, 1H), 8.39 (d, J = 8.7 Hz, 2H), 8.20 (d, J = 8.5 Hz, 1H), 8.01 (d, J = 8.8 Hz, 2H), 7.93 (d, J = 8.3 Hz, 1H), 7.89 (t, J = 7.6 Hz, 1H), 7.70–7.64 (m, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ ppm: 193.1, 150.2, 149.8, 142.1, 139.1, 132.5, 130.7, 129.6, 129.3, 128.8, 128.0, 126.4, 123.8. The NMR spectra are consistent with the reported literature [31].

4.13. Quinolin-3-yl(4-(trifluoromethyl)phenyl)methanone (3am)

Compound 3am was synthesized in accordance with the typical procedure. Purification using column chromatography on silica gel (PE:EA = 10:1) afforded product 3am (47.6 mg, 78%) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm: 9.32 (d, J = 2.2 Hz, 1H), 8.54 (d, J = 2.3 Hz, 1H), 8.20 (d, J = 8.5 Hz, 1H), 7.92 (d, J = 8.2 Hz, 3H), 7.88 (ddd, J = 8.5, 6.9, 1.5 Hz, 1H), 7.81 (d, J = 7.9 Hz, 2H), 7.66 (ddd, J = 8.1, 6.9, 1.1 Hz, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ ppm: 193.8, 150.0, 149.7, 140.0, 139.1, 134.3 (q, J = 32.7 Hz), 132.3, 130.1, 129.5, 129.2, 129.1, 127.8, 126.4, 125.7 (q, J = 3.5 Hz), 123.5 (q, J = 272.5 Hz). 19F NMR (376 MHz, CDCl3) δ ppm: −62.9. The NMR spectra are consistent with the reported literature [31].

4.14. [1,1′-Biphenyl]-4-yl(quinolin-3-yl)methanone (3an)

Compound 3an was synthesized in accordance with the typical procedure. Purification using column chromatography on silica gel (PE:EA = 10:1) afforded product 3an (50.2 mg, 81%) as a white solid.
1H NMR (400 MHz, CDCl3) δ ppm: 9.35 (d, J = 2.2 Hz, 1H), 8.59 (d, J = 2.1 Hz, 1H), 8.21 (d, J = 8.5 Hz, 1H), 7.94 (t, J = 8.3 Hz, 3H), 7.85 (t, J = 8.4 Hz, 1H), 7.75 (d, J = 8.1 Hz, 2H), 7.65 (t, J = 6.6 Hz, 3H), 7.45 (dt, J = 29.3, 7.4 Hz, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ ppm: 194.3, 150.2, 149.4, 145.8, 139.6, 138.6, 135.6, 131.7, 130.6, 130.2, 129.4, 129.1, 129.0, 128.3, 127.5, 127.2, 127.2, 126.6. The NMR spectra are consistent with the reported literature [22].

4.15. Quinolin-3-yl(o-tolyl)methanone (3ao)

Compound 3ao was synthesized in accordance with the typical procedure. Purification using column chromatography on silica gel (PE:EA = 10:1) afforded product 3ao (40.4 mg, 82%) as a white solid.
1H NMR (400 MHz, CDCl3) δ ppm: 9.36 (d, J = 2.2 Hz, 1H), 8.47 (d, J = 2.2 Hz, 1H), 8.18 (d, J = 7.4 Hz, 1H), 7.89–7.82 (m, 2H), 7.64–7.59 (m, 1H), 7.46 (t, J = 7.5 Hz, 1H), 7.40–7.34 (m, 2H), 7.32–7.28 (m, 1H), 2.40 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ ppm: 197.0, 150.3, 149.7, 139.4, 137.5, 137.3, 132.1, 131.4, 131.0, 130.1, 129.4, 129.3, 128.9, 127.5, 126.7, 125.4, 20.1. The NMR spectra are consistent with the reported literature [31].

4.16. (2-Fluorophenyl)(quinolin-3-yl)methanone (3ap)

Compound 3ap was synthesized in accordance with the typical procedure. Purification using column chromatography on silica gel (PE:EA = 10:1) afforded product 3ap (44.1 mg, 88%) as a white solid.
1H NMR (400 MHz, CDCl3) δ ppm: 9.33 (s, 1H), 8.54 (s, 1H), 8.17 (d, J = 8.5 Hz, 1H), 7.92–7.82 (m, 2H), 7.69–7.58 (m, 3H), 7.33 (td, J = 7.5, 1.1 Hz, 1H), 7.21 (t, J = 9.2 Hz, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ ppm: 191.8, 160.2 (d, J = 253.0 Hz), 158.9, 149.8, 134.0 (d, J = 8.4 Hz), 134.0, 132.2, 131.0 (d, J = 2.6 Hz), 129.9, 129.4, 127.5, 126.1, 126.0, 124.7 (d, J = 3.4 Hz), 116.5 (d, J = 21.8 Hz). 19F NMR (376 MHz, CDCl3) δ ppm: −109.7. The NMR spectra are consistent with the reported literature [31].

4.17. (2-chlorophenyl)(quinolin-3-yl)methanone (3aq)

Compound 3aq was synthesized in accordance with the typical procedure. Purification using column chromatography on silica gel (PE:EA = 10:1) afforded product 3aq (47.2 mg, 88%) as a white solid.
1H NMR (400 MHz, CDCl3) δ ppm: 9.34 (d, J = 2.2 Hz, 1H), 8.47 (d, J = 3.0 Hz, 1H), 8.17 (d, J = 8.4 Hz, 1H), 7.90–7.83 (m, 2H), 7.63–7.59 (m, 1H), 7.51 (d, J = 3.0 Hz, 2H), 7.49–7.41 (m, 2H). 13C{1H}NMR (101 MHz, CDCl3) δ ppm: 193.9, 149.9, 139.5, 137.6, 132.4, 131.8, 131.4, 130.3, 129.5, 129.4, 128.9, 127.6, 127.0, 126.7. The NMR spectra are consistent with the reported literature [31].

4.18. Quinolin-3-yl(m-tolyl)methanone (3ar)

Compound 3ar was synthesized in accordance with the typical procedure. Purification using column chromatography on silica gel (PE:EA = 10:1) afforded product 3ar (40.1 mg, 81%) as a white solid.
1H NMR (400 MHz, CDCl3) δ ppm: 9.31 (d, J = 2.2 Hz, 1H), 8.55 (d, J = 2.2 Hz, 1H), 8.19 (d, J = 8.5 Hz, 1H), 7.92 (d, J = 8.1 Hz, 1H), 7.85 (ddd, J = 8.5, 6.9, 1.5 Hz, 1H), 7.69–7.61 (m, 3H), 7.48–7.39 (m, 2H), 2.44 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ ppm: 195.1, 150.3, 149.4, 138.8, 138.6, 137.0, 133.8, 131.8, 130.4, 130.2, 129.4, 129.1, 128.4, 127.5, 127.3, 126.6, 21.3. The NMR spectra are consistent with the reported literature [31].

4.19. (3-Bromophenyl)(quinolin-3-yl)methanone (3as)

Compound 3as was synthesized in accordance with the typical procedure. Purification using column chromatography on silica gel (PE:EA = 10:1) afforded product 3as (54.1 mg, 86%) as a white solid.
1H NMR (400 MHz, CDCl3) δ ppm: 9.28 (d, J = 2.2 Hz, 1H), 8.53 (d, J = 2.2 Hz, 1H), 8.18 (d, J = 8.4 Hz, 1H), 7.99 (s, 1H), 7.92 (d, J = 9.5 Hz, 1H), 7.87–7.83 (m, 1H), 7.78–7.72 (m, 2H), 7.63 (t, J = 7.5 Hz, 1H), 7.40 (t, J = 7.8 Hz, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ ppm: 193.3, 150.0, 149.6, 138.8, 135.8, 132.7, 132.1, 130.1, 129.5, 129.4, 129.2, 128.4, 127.7, 126.5, 122.9. The NMR spectra are consistent with the reported literature [35].

4.20. (3-Chlorophenyl)(quinolin-3-yl)methanone (3at)

Compound 3at was synthesized in accordance with the typical procedure. Purification using column chromatography on silica gel (PE:EA = 10:1) afforded product 3at (43.2 mg, 85%) as a white solid.
1H NMR (400 MHz, CDCl3) δ ppm: 9.29 (d, J = 2.2 Hz, 1H), 8.53 (d, J = 2.2 Hz, 1H), 8.18 (d, J = 8.5 Hz, 1H), 7.92 (d, J = 9.6 Hz, 1H), 7.87–7.82 (m, 2H), 7.70 (d, J = 7.6 Hz, 1H), 7.66–7.59 (m, 2H), 7.46 (t, J = 7.8 Hz, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ ppm: 193.4, 150.0, 149.6, 138.8, 138.6, 135.0, 132.9, 132.0, 129.9, 129.8, 129.5, 129.4, 129.2, 128.0, 127.7, 126.5. The NMR spectra are consistent with the reported literature [31].

4.21. (2,4-Dimethoxyphenyl)(quinolin-3-yl)methanone (3au)

Compound 3au was synthesized in accordance with the typical procedure. Purification using column chromatography on silica gel (PE:EA = 10:1) afforded product 3au (48.6 mg, 83%) as a yellow solid, m.p. 82–84 °C; 1H NMR (400 MHz, CDCl3) δ ppm: 9.18 (d, J = 2.2 Hz, 1H), 8.53 (d, J = 2.2 Hz, 1H), 8.14 (d, J = 9.3 Hz, 1H), 7.90 (d, J = 8.3 Hz, 1H), 7.80 (t, J = 7.7 Hz, 1H), 7.58 (d, J = 8.4 Hz, 2H), 6.62 (dd, J = 8.5, 2.2 Hz, 1H), 6.52 (d, J = 2.2 Hz, 1H), 3.89 (s, 3H), 3.65 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ ppm: 193.7, 164.4, 159.9, 150.7, 149.3, 138.1, 133.0, 131.8, 131.6, 129.4, 127.3, 127.1, 120.7, 105.4, 98.8, 55.7, 55.6. HRMS m/z (ESI) calcd for C18H15NO3 (M+H)+ 294.1125, found 294.1133.

4.22. (2,4-Difluorophenyl)(quinolin-3-yl)methanone (3av)

Compound 3av was synthesized in accordance with the typical procedure. Purification using column chromatography on silica gel (PE:EA = 10:1) afforded product 3av (44.1 mg, 82%) as a white solid, m.p. 94–96 °C; 1H NMR (400 MHz, CDCl3) δ ppm: 9.29 (s, 1H), 8.52 (s, 1H), 8.17 (d, J = 7.5 Hz, 1H), 7.91 (d, J = 8.2 Hz, 1H), 7.87–7.82 (m, 1H), 7.76–7.69 (m, 1H), 7.62 (ddd, J = 8.1, 6.9, 1.2 Hz, 1H), 7.09–7.04 (m, 1H), 6.95 (ddd, J = 10.1, 8.7, 2.4 Hz, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ ppm: 190.3, 163.2 (ddd, J = 438.1, 256.3, 12.1 Hz), 149.7 (d, J = 13.8 Hz), 138.8 (d, J = 2.0 Hz), 132.9 (dd, J = 10.4, 4.0 Hz), 132.2, 129.4 (d, J = 11.5 Hz), 127.6, 126.6, 122.8 (dd, J = 14.0, 3.7 Hz), 112.4 (dd, J = 21.7, 3.6 Hz), 104.9 (t, J = 25.6 Hz) 19F NMR (376 MHz, CDCl3) δ ppm: −101.8, −104.5. HRMS m/z (ESI) calcd for C16H9F2NO (M+H)+ 270.0725, found 270.0723.

4.23. (2,4-Dichlorophenyl)(quinolin-3-yl)methanone (3aw)

Compound 3aw was synthesized in accordance with the typical procedure. Purification using column chromatography on silica gel (PE:EA = 10:1) afforded product 3aw (48.6 mg, 81%) as a white solid.
1H NMR (400 MHz, CDCl3) δ ppm: 9.30 (d, J = 2.2 Hz, 1H), 8.45 (d, J = 2.2 Hz, 1H), 8.16 (d, J = 8.5 Hz, 1H), 7.87 (t, J = 8.3 Hz, 2H), 7.61 (t, J = 7.6 Hz, 1H), 7.52 (s, 1H), 7.42 (s, 2H). 13C{1H} NMR (101 MHz, CDCl3) δ ppm: 192.8, 149.9, 149.7, 139.4, 137.4, 135.9, 132.5, 130.5, 130.2, 129.5, 128.7, 127.7, 127.5, 126.6. The NMR spectra are consistent with the reported literature [31].

4.24. Benzo[d][1,3]dioxol-5-yl(quinolin-3-yl)methanone (3ax)

Compound 3ax was synthesized in accordance with the typical procedure. Purification using column chromatography on silica gel (PE:EA = 10:1) afforded product 3ax (43.6 mg, 79%) as a white solid.
1H NMR (400 MHz, CDCl3) δ ppm: 9.24 (d, J = 2.2 Hz, 1H), 8.49 (d, J = 2.2 Hz, 1H), 8.17 (d, J = 8.5 Hz, 1H), 7.90 (d, J = 8.1 Hz, 1H), 7.82 (t, J = 7.7 Hz, 1H), 7.61 (t, J = 7.5 Hz, 1H), 7.40 (d, J = 1.8 Hz, 2H), 6.88 (d, J = 8.5 Hz, 1H), 6.08 (s, 2H). 13C{1H} NMR (101 MHz, CDCl3) δ ppm: 193.0, 152.0, 150.1, 149.2, 148.3, 138.1, 131.6, 131.4, 130.6, 129.4, 129.0, 127.5, 127.0, 126.5, 109.6, 107.9, 102.0. The NMR spectra are consistent with the reported literature [22].

4.25. Naphthalen-2-yl(quinolin-3-yl)methanone (3ay)

Compound 3ay was synthesized in accordance with the typical procedure. Purification using column chromatography on silica gel (PE:EA = 10:1) afforded product 3ay (48.7 mg, 84%) as a white solid.
1H NMR (400 MHz, CDCl3) δ ppm: 9.38 (d, J = 2.2 Hz, 1H), 8.61 (d, J = 2.8 Hz, 1H), 8.31 (s, 1H), 8.22 (d, J = 9.5 Hz, 1H), 7.99 (d, J = 1.3 Hz, 2H), 7.95–7.82 (m, 4H), 7.68–7.54 (m, 3H).13C{1H} NMR (101 MHz, CDCl3) δ ppm: 194.8, 150.3, 149.4, 138.8, 135.4, 134.2, 132.2, 132.1, 131.8, 130.3, 129.4, 129.1, 128.7, 128.7, 127.8, 127.6, 127.0, 126.6, 125.4. The NMR spectra are consistent with the reported literature [31].

4.26. Quinolin-3-yl(thiophen-2-yl)methanone (3az)

Compound 3az was synthesized in accordance with the typical procedure. Purification using column chromatography on silica gel (PE:EA = 10:1) afforded product 3az (38.6 mg, 80%) as a white solid.
1H NMR (400 MHz, CDCl3) δ ppm: 9.43 (d, J = 2.2 Hz, 1H), 8.80 (d, J = 2.2 Hz, 1H), 8.15 (d, J = 8.4 Hz, 1H), 7.93 (d, J = 8.1 Hz, 1H), 7.81 (t, J = 7.1 Hz, 1H), 7.74 (s, 1H), 7.61 (t, J = 7.5 Hz, 1H), 7.36 (d, J = 3.6 Hz, 1H), 6.64 (d, J = 3.7 Hz, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ ppm: 180.3, 152.3, 149.7, 149.4, 147.4, 138.2, 131.8, 129.6, 129.4, 129.2, 127.5, 126.7, 120.7, 112.6. The NMR spectra are consistent with the reported literature [31].

4.27. Furan-2-yl(quinolin-3-yl)methanone (3az′)

Compound 3az′ was synthesized in accordance with the typical procedure. Purification using column chromatography on silica gel (PE:EA = 10:1) afforded product 3az′ (36.8 mg, 83%) as a white solid.
1H NMR (400 MHz, CDCl3) δ ppm: 9.33 (d, J = 2.2 Hz, 1H), 8.63 (d, J = 2.2 Hz, 1H), 8.17 (d, J = 8.5 Hz, 1H), 7.93 (d, J = 8.2 Hz, 1H), 7.83 (t, J = 8.4 Hz, 1H), 7.78 (d, J = 4.9 Hz, 1H), 7.71 (s, 1H), 7.63 (t, J = 7.5 Hz, 1H), 7.20 (t, J = 4.4 Hz, 1H).13C{1H} NMR (101 MHz, CDCl3) δ ppm: 186.1, 149.5, 149.4, 143.1, 137.6, 135.0 (2C), 131.7, 130.6, 129.4, 129.0, 128.3, 127.6, 126.6. The NMR spectra are consistent with the reported literature [31].

4.28. (6-Methoxyquinolin-3-yl)(phenyl)methanone (3ba)

Compound 3ba was synthesized in accordance with the typical procedure. Purification using column chromatography on silica gel (PE:EA = 10:1) afforded product 3ba (46.1 mg, 83%) as a white solid.
1H NMR (400 MHz, CDCl3) δ ppm: 9.14 (d, J = 2.1 Hz, 1H), 8.44 (d, J = 2.2 Hz, 1H), 8.07 (d, J = 9.8 Hz, 1H), 7.87–7.84 (m, 2H), 7.67–7.62 (m, 1H), 7.55–7.46 (m, 3H), 7.14 (d, J = 2.8 Hz, 1H), 3.93 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ ppm: 195.1, 158.4, 147.9, 145.6, 137.4, 137.1, 133.0, 130.7, 130.3, 130.0, 128.6, 127.8, 124.8, 106.0, 55.6. The NMR spectra are consistent with the reported literature [31].

4.29. (6-Fluoroquinolin-3-yl)(phenyl)methanone (3ca)

Compound 3ca was synthesized in accordance with the typical procedure. Purification using column chromatography on silica gel (PE:EA = 10:1) afforded product 3ca (42.5 mg, 85%) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm: 9.26 (d, J = 2.1 Hz, 1H), 8.49 (d, J = 2.2 Hz, 1H), 8.19 (dd, J = 9.2, 5.2 Hz, 1H), 7.85 (dd, J = 8.3, 1.3 Hz, 2H), 7.68–7.59 (m, 2H), 7.56–7.51 (m, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ ppm: 194.6, 160.9 (d, J = 250.3 Hz), 149.6 (d, J = 2.8 Hz), 137.9 (d, J = 5.6 Hz), 136.7, 133.2, 132.0 (d, J = 9.2 Hz), 130.7, 130.0, 128.7, 127.3 (d, J = 10.2 Hz), 122.0 (d, J = 25.8 Hz), 112.0 (d, J = 21.8 Hz). 19F NMR (376 MHz, CDCl3) δ ppm: −111.2. The NMR spectra are consistent with the reported literature [31].

4.30. (6-Chloroquinolin-3-yl)(phenyl)methanone (3da)

Compound 3da was synthesized in accordance with the typical procedure. Purification using column chromatography on silica gel (PE:EA = 10:1) afforded product 3da (43.3 mg, 83%) as a white solid.
1H NMR (400 MHz, CDCl3) δ ppm: 9.31 (d, J = 2.1 Hz, 1H), 8.45 (d, J = 2.1 Hz, 1H), 8.10–8.04 (m, 2H), 7.92–7.84 (m, 3H), 7.69–7.65 (m, 1H), 7.55 (t, J = 7.7 Hz, 2H). 13C{1H} NMR (101 MHz, CDCl3) δ ppm: 194.5, 150.4, 147.7, 137.7, 136.7, 133.4, 133.3, 132.7, 131.0, 130.8, 130.0, 128.7, 127.6, 127.2. The NMR spectra are consistent with the reported literature [31].

4.31. (6-Bromoquinolin-3-yl)(phenyl)methanone (3ea)

Compound 3ea was synthesized in accordance with the typical procedure. Purification using column chromatography on silica gel (PE:EA = 10:1) afforded product 3ea (54.2 mg, 87%) as a white solid.
1H NMR (400 MHz, CDCl3) δ ppm: 9.31 (d, J = 2.1 Hz, 1H), 8.45 (d, J = 2.1 Hz, 1H), 8.10–8.04 (m, 2H), 7.91 (dd, J = 8.9, 2.2 Hz, 1H), 7.87–7.83 (m, 2H), 7.69–7.65 (m, 1H), 7.55 (t, J = 7.7 Hz, 2H). 13C{1H} NMR (101 MHz, CDCl3) δ ppm: 194.5, 150.6, 148.0, 137.6, 136.7, 135.2, 133.3, 131.1, 131.0, 130.7, 130.0, 128.7, 127.7, 121.5. The NMR spectra are consistent with the reported literature [31].

4.32. (7-Fluoroquinolin-3-yl)(phenyl)methanone (3fa)

Compound 3fa was synthesized in accordance with the typical procedure. Purification using column chromatography on silica gel (PE:EA = 10:1) afforded product 3fa (44.1 mg, 88%) as a white solid.
1H NMR (400 MHz, CDCl3) δ ppm: 9.31 (d, J = 2.2 Hz, 1H), 8.55 (d, J = 2.4 Hz, 1H), 7.93 (dd, J = 9.0, 6.0 Hz, 1H), 7.86–7.79 (m, 3H), 7.68–7.63 (m, 1H), 7.54 (t, J = 7.7 Hz, 2H), 7.42 (td, J = 8.5, 2.5 Hz, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ ppm: 194.5, 164.4 (d, J = 254.1 Hz), 151.4, 150.6 (d, J = 13.0 Hz), 138.6, 136.8, 133.1, 131.4 (d, J = 10.2 Hz), 123.0, 129.5, 128.7, 123.6, 118.3 (d, J = 25.6 Hz), 113.4 (d, J = 20.6 Hz) 19F NMR (376 MHz, CDCl3) δ ppm: −104.8. The NMR spectra are consistent with the reported literature [31].

4.33. (7-Chloroquinolin-3-yl)(phenyl)methanone (3ga)

Compound 3ga was synthesized in accordance with the typical procedure. Purification using column chromatography on silica gel (PE:EA = 10:1) afforded product 3ga (44.8 mg, 84%) as a white solid.
1H NMR (400 MHz, CDCl3) δ ppm: 9.32 (d, J = 2.2 Hz, 1H), 8.54 (d, J = 2.2 Hz, 1H), 8.19 (d, J = 2.0 Hz, 1H), 7.88–7.84 (m, 3H), 7.69–7.64 (m, 1H), 7.61–7.52 (m, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ ppm: 194.5, 151.3, 149.7, 138.5, 137.9, 136.7, 133.2, 130.3, 130.1, 130.0, 128.8, 128.7, 128.5, 125.0. The NMR spectra are consistent with the reported literature [31].

4.34. (7-Bromoquinolin-3-yl)(phenyl)methanone (3ha)

Compound 3ha was synthesized in accordance with the typical procedure. Purification using column chromatography on silica gel (PE:EA = 10:1) afforded product 3ha (52.1 mg, 83%) as a white solid.
1H NMR (400 MHz, CDCl3) δ ppm: 9.31 (d, J = 2.1 Hz, 1H), 8.53 (dd, J = 2.1, 0.8 Hz, 1H), 8.38 (d, J = 2.0 Hz, 1H), 7.85 (dd, J = 8.3, 1.3 Hz, 2H), 7.79 (d, J = 8.6 Hz, 1H), 7.73 (dd, J = 8.7, 1.9 Hz, 1H), 7.69–7.65 (m, 1H), 7.57–7.53 (m, 2H). 13C{1H} NMR (101 MHz, CDCl3) δ ppm: 194.5, 151.3, 149.9, 138.6, 136.7, 133.2, 131.9, 131.3, 130.3, 130.2, 130.0, 128.7, 126.3, 125.2. The NMR spectra are consistent with the reported literature [31].

4.35. Phenyl(7-(trifluoromethyl)quinolin-3-yl)methanone (3ia)

Compound 3ia was synthesized in accordance with the typical procedure. Purification using column chromatography on silica gel (PE:EA = 10:1) afforded product 3ia (47.1 mg, 80%) as a white solid, m.p. 88–92 °C; 1H NMR (400 MHz, CDCl3) δ ppm: 9.39 (d, J = 2.2 Hz, 1H), 8.60 (d, J = 2.2 Hz, 1H), 8.50 (s, 1H), 8.06 (d, J = 8.2 Hz, 1H), 7.88–7.85 (m, 2H), 7.81 (dd, J = 8.5, 1.8 Hz, 1H), 7.68 (t, J = 7.5 Hz, 1H), 7.56 (t, J = 7.6 Hz, 2H). 13C{1H} NMR (101 MHz, CDCl3) δ ppm: 194.4, 151.5, 148.4, 138.2, 136.5, 133.4, 133.2 (q, J = 33.0 Hz), 131.7, 130.3, 130.0, 128.8, 128.1, 127.3 (q, J = 4.3 Hz), 123.6 (q, J = 271.5 Hz), 123.2 (d, J = 3.0 Hz). 19F NMR (376 MHz, CDCl3) δ ppm: −62.8. HRMS m/z (ESI) calcd for C17H10F3NO (M+H)+ 302.0787, found 302.0779.

4.36. Methyl 3-benzoylquinoline-7-carboxylate (3ja)

Compound 3ja was synthesized in accordance with the typical procedure. Purification using column chromatography on silica gel (PE:EA = 10:1) afforded product 3ja (43.6 mg, 75%) as a white solid, m.p. 142–145 °C; 1H NMR (400 MHz, CDCl3) δ ppm: 9.36 (d, J = 2.2 Hz, 1H), 8.87 (s, 1H), 8.56 (d, J = 3.1 Hz, 1H), 8.21 (dd, J = 8.5, 1.7 Hz, 1H), 7.97 (d, J = 8.9 Hz, 1H), 7.88–7.85 (m, 2H), 7.69–7.64 (m, 1H), 7.57–7.52 (m, 2H), 4.02 (s, 3H).13C{1H} NMR (101 MHz, CDCl3) δ ppm: 194.5, 166.3, 151.1, 148.8, 138.2, 136.6, 133.3, 132.8, 131.8, 131.4, 130.0, 129.3, 129.0, 128.7, 127.0, 52.7. HRMS m/z (ESI) calcd for C18H13NO3 (M+H)+ 292.0968, found 292.0961.

4.37. (6,8-Dichloroquinolin-3-yl)(phenyl)methanone (3ka)

Compound 3ka was synthesized in accordance with the typical procedure. Purification using column chromatography on silica gel (PE:EA = 10:1) afforded product 3ka (46.5 mg, 78%) as a white solid.
1H NMR (400 MHz, CDCl3) δ ppm: 9.37 (d, J = 2.1 Hz, 1H), 8.49 (d, J = 2.1 Hz, 1H), 7.94 (d, J = 2.2 Hz, 1H), 7.87–7.83 (m, 3H), 7.68 (t, J = 7.4 Hz, 1H), 7.55 (t, J = 7.8 Hz, 2H). 13C{1H} NMR (101 MHz, CDCl3) δ ppm: 194.0, 150.9, 144.1, 138.1, 137.8, 136.4, 135.0, 133.6, 132.9, 132.2, 131.7, 130.1, 128.8, 128.3, 126.7, 126.5. The NMR spectra are consistent with the reported literature [16].

4.38. (6,7-Dimethoxyquinolin-3-yl)(phenyl)methanone (3la)

Compound 3la was synthesized in accordance with the typical procedure. Purification using column chromatography on silica gel (PE:EA = 10:1) afforded product 3la (46.8 mg, 80%) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm: 9.11 (d, J = 2.1 Hz, 1H), 8.41 (d, J = 2.9 Hz, 1H), 7.85–7.82 (m, 2H), 7.64–7.59 (m, 1H), 7.54–7.47 (m, 3H), 7.10 (s, 1H), 4.06 (s, 3H), 4.00 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ ppm: 195.1, 154.4, 150.4, 148.5, 147.0, 137.3, 136.8, 132.7, 129.9, 128.5, 122.3, 107.8, 106.0, 56.3, 56.1. The NMR spectra are consistent with the reported literature [31].

4.39. [1,3]Dioxolo [4,5-g]quinolin-7-yl(phenyl)methanone (3ma)

Compound 3ma was synthesized in accordance with the typical procedure. Purification using column chromatography on silica gel (PE:EA = 10:1) afforded product 3ma (45.1 mg, 81%) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm: 9.08 (d, J = 2.2 Hz, 1H), 8.37 (d, J = 2.1 Hz, 1H), 7.85–7.81 (m, 2H), 7.63 (t, J = 7.4 Hz, 1H), 7.52 (t, J = 7.6 Hz, 2H), 7.43 (s, 1H), 7.11 (s, 1H), 6.15 (s, 2H). 13C{1H} NMR (101 MHz, CDCl3) δ ppm: 194.9, 152.7, 148.6, 148.5, 148.4, 137.4, 137.3, 137.2, 132.8, 128.6, 128.5, 123.8, 105.8, 103.6, 102.2. The NMR spectra are consistent with the reported literature [31].

4.40. (6-Chloro-4-phenylquinolin-3-yl)(phenyl)methanone (3na)

Compound 3na was synthesized in accordance with the typical procedure. Purification using column chromatography on silica gel (PE:EA = 10:1) afforded product 3na (57.0 mg, 84%) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm: 8.96 (s, 1H), 8.17 (d, J = 9.7 Hz, 1H), 7.73 (dd, J = 6.9, 2.4 Hz, 2H), 7.59 (dd, J = 8.3, 1.4 Hz, 2H), 7.44 (t, J = 7.4 Hz, 1H), 7.34–7.27 (m, 5H), 7.26–7.23 (m, 2H). 13C{1H} NMR (101 MHz, CDCl3) δ ppm: 196.4, 148.6, 147.1, 146.1, 137.0, 134.2, 133.6, 133.4, 132.5, 131.4, 129.9, 129.7, 128.8, 128.4, 128.3, 127.2, 125.4. The NMR spectra are consistent with the reported literature [61].

Supplementary Materials

The following supporting information can be downloaded at https://www.mdpi.com/article/10.3390/catal13040778/s1.

Author Contributions

Methodology, K.-L.Z.; writing—review and editing, K.-L.Z. and J.-C.Y.; review and editing, Q.G.; supervision, L.-H.Z.; project administration, L.-H.Z. All authors have read and agreed to the published version of the manuscript.

Funding

The financial support from the Open Research Fund of School of Chemistry and Chemical Engineering, Henan Normal University (2022B01) is greatly appreciated.

Data Availability Statement

Data supporting reported results can be found in Supplementary Materials.

Conflicts of Interest

The authors declare no conflict of interest.

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Catalysts 13 00778 sch001 550
Scheme 1. Reaction conditions: 1a (0.4 mmol), 2 (0.2 mmol), methanesulfonic acid (MSA) (0.3 mmol), NaI (0.3 mmol), EtOH (2 mL), 110 °C, air, 12 h.
Scheme 1. Reaction conditions: 1a (0.4 mmol), 2 (0.2 mmol), methanesulfonic acid (MSA) (0.3 mmol), NaI (0.3 mmol), EtOH (2 mL), 110 °C, air, 12 h.
Catalysts 13 00778 sch001
Catalysts 13 00778 sch002 550
Scheme 2. Reaction conditions: 1 (0.4 mmol), 2a (0.2 mmol), methanesulfonic acid (MSA) (0.3 mmol), NaI (0.3 mmol), EtOH (2 mL), 110 °C, air, 12 h.
Scheme 2. Reaction conditions: 1 (0.4 mmol), 2a (0.2 mmol), methanesulfonic acid (MSA) (0.3 mmol), NaI (0.3 mmol), EtOH (2 mL), 110 °C, air, 12 h.
Catalysts 13 00778 sch002
Catalysts 13 00778 sch003 550
Scheme 3. Gram-scale reaction.
Scheme 3. Gram-scale reaction.
Catalysts 13 00778 sch003
Catalysts 13 00778 sch004 550
Scheme 4. Control reactions.
Scheme 4. Control reactions.
Catalysts 13 00778 sch004
Catalysts 13 00778 sch005 550
Scheme 5. Proposed mechanism for the synthesis of 3aa.
Scheme 5. Proposed mechanism for the synthesis of 3aa.
Catalysts 13 00778 sch005
Table
Table 1. Optimization of reaction conditions for the synthesis of 3aa a.
Table 1. Optimization of reaction conditions for the synthesis of 3aa a.
Catalysts 13 00778 i001
EntryAdditiveSolventTemp. (°C)Yield b (%)
1MSAEtOH11031
2MSAHFIP1105
3MSADME11011
4MSAn-octanol1100
5MSAdioxane11018
6MSATHF11029
7MSADMSO1100
8/EtOH1100
9MSA/KBrEtOH11058
10MSA/KBrTHF11037
11MSA/KIEtOH11089
12MSA/NaIEtOH11090
13MSA/NaIEtOH7043
14MSA/NaIEtOH8065
15MSA/NaIEtOH9084
16MSA/NaIEtOH12090
a Reaction conditions: 1a (0.4 mmol), 2a (0.2 mmol), additive (0.3 mmol), EtOH (2 mL), 110 °C, air, 12 h. b Isolated yield.
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Zhang, K.-L.; Yang, J.-C.; Guo, Q.; Zou, L.-H. Transition Metal-Free Synthesis of 3-Acylquinolines through Formal [4+2] Annulation of Anthranils and Enaminones. Catalysts 2023, 13, 778. https://doi.org/10.3390/catal13040778

AMA Style

Zhang K-L, Yang J-C, Guo Q, Zou L-H. Transition Metal-Free Synthesis of 3-Acylquinolines through Formal [4+2] Annulation of Anthranils and Enaminones. Catalysts. 2023; 13(4):778. https://doi.org/10.3390/catal13040778

Chicago/Turabian Style

Zhang, Kai-Ling, Jia-Cheng Yang, Qin Guo, and Liang-Hua Zou. 2023. "Transition Metal-Free Synthesis of 3-Acylquinolines through Formal [4+2] Annulation of Anthranils and Enaminones" Catalysts 13, no. 4: 778. https://doi.org/10.3390/catal13040778

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