Divergent Synthesis of Functionalized Quinolines from Aniline and

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Divergent Synthesis of Functionalized Quinolines from Aniline and Two Distinct Amino Acids Jia-Chen Xiang, Zi-Xuan Wang, Yan Cheng, Shi-Qing Xia, Miao Wang, Bo-Cheng Tang, Yan-Dong Wu, and An-Xin Wu J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b01501 • Publication Date (Web): 28 Jul 2017 Downloaded from http://pubs.acs.org on July 28, 2017

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The Journal of Organic Chemistry

Divergent Synthesis of Functionalized Quinolines from Aniline and Two Distinct Amino Acids Jia-Chen Xiang,a Zi-Xuan Wang,a Yan Cheng,a Shi-Qing Xia,a Miao Wang,a Bo-Cheng Tang,a Yan-Dong Wua and An-Xin Wu*ab a

Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry,

Central China Normal University, b

Hubei, Wuhan 430079, P. R. China

State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Gansu, Lanzhou 730000,

P. R. China Supporting Information Placeholder

TOC Graphic:

ABSTRACT:

A practicable quinoline synthesis from aniline and two amino acids was developed for

generating a wide range of quinolines with high efficiency and diversity. Thus it facilitated the creations of pharmaceutical derivatives, photochemical active compounds and challenging scaffolds. The concept of using two amino acids as heterocyclic precursors has been raised for the first time. Mechanistic studies revealed that I2 enabled decarboxylation, oxidative deamination and selective reconstruction of new C-N and C-C bonds processes. Amino acid, which industrially produced from fermentation process, is a versatile motif utilized in biochemistry,1 pharmaceutical chemistry2 and total synthesis.3 In Nature, amino acids are prebiotic material in the biosynthesis of heterocyclic alkaloids.4 If being used to prepared vital heterocycles biomimetically, these environmentally benign, non-fossil carbon and biomass feedstock are promising candidates for replacing fossil carbon sources such as crude oil, the reserve of which are dwindling.5 However, synthetic methodologies for directly converting amino acids into heterocycles are rare.6 More importantly, using two (or multi) amino acids together as heterocyclic precursors to improve the synthetic diversity,7 pot-economy8 and chemical ideality9 is fascinating and still need to be explored.10 We attempted to use two distinct amino acids simultaneously to prepare value added heterocycles. As one of the most common heterocyclic molecule,11 functionalized quinolines are present in many pharmacologically and biologically active chemicals,11b therefore methods for their synthesis are widely researched.12-14 However, existing methods are unable or tedious to prepare pharmaceutical and photochemically active quinoline compounds such as directly modified drug derivatives and conjugated fused rings due to the limilation of substrates scope or selectivity. A unified approcach for functionalized

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quinolines starts from commercially available and user-friendly materials is still desirable. Especially, a method that enables direct assembly of bioactive quinoline compounds from biomass amino acids in a metal-free condition could profoundly affect pharmaceutical manufacture.11b Herein, we detailed an protocol for unified quinoline synthesis using aniline and two distinct amino acids: one with only an α-H atom and the other with two β-H atoms. The

initial

investigation

focused

on

the

model

reaction

of

phenylalanine

(1a),

2-amino-2-(2-chlorophenyl)acetic acid (2j), and p-toluidine (3a) in DMSO. Based on the reaction conditions in our previous studies, 1.0 equiv of I2 was used as an additive (Table1, entry 1).10 Trifluoroacetic acid (50 mol%) was added to promote oxidative deamination of the amino acids. The desired 2,3-disubstituted quinoline 4j was obtained in 58% yield as the major product at 100 oC. Several Brønsted acids were investigated to increase the yield (entries 2–5). A higher yield, i.e., 81%, was achieved with the assistance of 50 mol% HI (entry 2). Next, we investigated the effect of I2 loading (entries 6–10). No reaction occurred in the absence of I2. However, more than 1.0 equiv of I2 reduced the yield (entries 9 and 10). Some other high-boiling-point solvents were also surveyed (entries 11–14). The yields obtained by using the polar solvents DMF, DMA, and NMP were lower than those achieved with DMSO. Sulfolane resulted in only a moderate yield. The ratios of three reactants were also carefully screened and the optimum ratios were 1:1:1 (Table 1).

Table 1. Reaction Optimization.a

entry

I2 (equiv)

solvent

acid

yield (%)b

1

1.0

DMSO

TFA

58

2

1.0

DMSO

HI

81

3

1.0

DMSO

sulfanilic acid

29

4

1.0

DMSO

TfOH

40

[c]

5

1.0

DMSO

PTA

trace

6

0

DMSO

HI

trace

7

0.2

DMSO

HI

trace

8

0.5

DMSO

HI

74

9

1.5

DMSO

HI

60

10

2.0

DMSO

HI

trace

11

1.0

DMF

HI

35

12

1.0

DMA

HI

34

13

1.0

NMP

HI

75

14

1.0

sulfolane

HI

56

a

1a (1.0 mmol), 2j (1.0 mmol), 3a (1.0 mmol), acid (0.5 mmol), I2 and solvent (3.0 mL) were added in a pressure vessel, then stirred at 100 oC for 10 h. b Isolated yields. c PTA = p-phthalic acid.


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After establishing the optimum conditions, we investigated the amino acid scope (Scheme 1). Phenylalanine derivatives with various groups on the phenyl ring were first examined. Compound 4a was obtained in 77% yield under the standard conditions. 2-Amino-3-(naphthalen-2-yl)propanoic acid, in which the electron-withdrawing naphthalene ring also causes steric hindrance, gave a good result (4b, 81%). The reaction of 4-nitro-substituted phenylalanine gave the desired product (4c, 80%). Slightly lower yields were achieved using phenylalanine analogs with electron-donating substituents on the aromatic ring (4d, 72%; 4e, 70%). The sensitive substrate tyrosine generated the corresponding quinoline in reasonable yield (4f, 75%). Amino acids with halogen substituents aromatic rings gave desired products smoothly (4g, 80%; 4h, 83%; 4i, 85%), which enabled further coupling derivatization. Various phenylglycine derivatives with halogen substituents were tolerated and furnished the desired products (4j, 81%; 4k, 76%). When a substrate bearing a hydroxyl group was used, the yield declined to a moderate level (4l, 44%). Notably, 3-arylquinolines were obtained using glycine as substrate 2 (4m, 72%; 4n, 45%). When aspartic acid was used as 1, 2-phenylquinoline and its derivatives were formed through spontaneous decarboxylation in the presence of I2. Aspartic acid acts as a two-carbon unit to participate in the transformation, which provides a delightful improvement in reaction scopes (4o, 70%; 4p, 37%).

Based on these results, aspartic acid derivatives

bearing different functional groups, e.g., asparaginate and methyl ester, were examined to give medium yields (4q–4s, 42-74%). 3-(4-Hydroxyphenyl)quinoline derivatives (4t, 69%), which have attracted attention because of their biological activities11c, were also obtained using our method. This reaction system was also compatible with aliphatic amino acids with two β-H atoms. For example, a combination of norleucine and phenylglycine gave the desired product 4u in 50% yield. Amino acid bearing a sensitive cyclopropane could also afford the desired product 4v in 65% yield without ring opening. Furthermore, methionine could transform into the target molecular with a sulfur methyl side chain (4w, 48%). Scheme 1. Scope of Amino Acids.



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a

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Reaction conditions: 1 (1.0 mmol), 2 (1.0 mmol), 3 (1.0 mmol), HI (0.5 mmol, 57 wt% solution in H2O), I2 (1.0 mmol), and

DMSO (3.0 mL) were added to a pressure vessel. The mixture was stirred at 100 °C for 10 h. Isolated yield.

To further judge the practicability of our method, we investigated aniline substrates 3 with different aromatic and heterocyclic rings (Scheme 2). A series of 4-substituted anilines containing electron-donating and withdrawing groups were tested. There was no obvious substituent effect and the corresponding products were efficiently constructed (5a–5d, 68-77%). Fused-ring quinolines derived from 1-naphthylamine and 2-naphthylamine were tolerated in the reaction (5e, 61%; 5f, 66%). Conjugated aromatic substituents pyrene substrate gave 5g in 31% yield. Fluorenes with an aromatic amine were used to afford quinoline derivatives with four consecutive fused rings (5h–5k, 44-74%). The framework of 5j which containing a highly planar structure and four free rotation benzene rings increased the possibility of this kind of material to express AIE effect.15 In addition, the heterocyclic substrate 5-methyl-1H-pyrazol-3-amine provided the desired product 5k in 70% yield. Moreover, Using bis-amines, this transformation could provide a smooth way

to

afford

functionalized

biquinolines.

p-phenylenediamine,

biphenyldiamine

and

4,4'-methylenedianiline were extensively investigated and compounds 5l, 5m and 5n were synthesized for the first time. Notably, 5l is an analogue of n-type organic semiconductor16a which literaturely needs five linear steps synthesis including a Friedlander quinoline synthesis from commercial available materials.16b Biquinolines 5m and 5n with carbon linkages are reported exhibiting potential antimalarial activities.11 It is attractive for the incorporation of pyridine rings into natural products and drug candidates containing an aniline backbone. The late-stage modification was conducted using naturally occurring coumarin 120. Two compounds 5o and 5p were obtained in 74% overall yield with a regioselective ratio of 1:1.4. The commercial available anti-steroid drug aminoglutethimide was converted to the corresponding quinoline


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derivative in 67% yield (5q). Derivatives of the chiral lactone drug (1S)-(−)-camphanic acid chloride participated in this reaction to generate the desired quinoline 5r (53%).

Scheme 2. Scope of Aniline Substrates.

a

Reaction conditions: 1a (1.0 mmol), 2a (1.0 mmol), 3 (1.0 mmol), HI (0.5 mmol, 57 wt% solution in H2O), I2 (1.0 mmol), and

DMSO (3.0 mL) were added to a pressure vessel. The mixture was stirred at 100 °C for 10 h. †These types of functionalized quinoline were synthesized for the first time. ‡0.5 equiv (0.5 mmol) of 3 was used.

Scheme 3. Control Experiments.



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Control experiments were performed to clarify the mechanism (Scheme 3). Compounds 1a and 2a were stirred under the standard conditions without addition of 3a. The α,β-unsaturated aldehyde M1 was formed (Scheme 3, entry 1). Treatment of 1a under the same conditions gave a 3,5-disubstituted pyridine 9, which was derived from the phenylacetaldehyde intermediate M2 in our previous work10 (Scheme 3, entry 2). The benzaldehyde derivative M3 was isolated when 2a alone was subjected to these conditions (Scheme 3, entry 3). These results indicate that both amino acids were transformed into the corresponding aldehydes. The user-unfriendly materials phenylacetaldehyde and benzaldehyde together with p-toluidine (1:1:1) as the starting material gave 4a in 57% yield with other inevitable byproducts (Scheme 3, entry 4).18 Compared to the result in standard conditions (Scheme 1, 77%), this result suggested that the amino groups of amino acid, aniline and the ammonia which generated in situ from oxidative cleavage promote the transformation through endogenous imine activation process. To prove this point, exogenous amino compounds such as ammonium hydroxide (1.0 equiv) and excessive p-toluidine (0.5 equiv) were added respectively as parallel experiments (Scheme 3, entry 3). The yields of 4a were slightly improved in both cases as expected (61% and 69%). However, we consider the direct use of aldehydes to be toxic to both human and the environment. Moreover, 4j could not be obtained when M1 was reacted with 3a, which suggested that M1 might not be the key intermediate (Scheme 3, entry 5). The use of phenethylamine and benzylamine instead of amino acids as starting materials did not give 4j (Scheme 3, entry 6). This suggested that decarboxylative oxidation is essential in the transformation.19 On the basis of the results described and previous studies,20, 21 we have proposed a preliminary mechanistic insight (Scheme 4). The transformation is triggered by I2-enabled decarboxylative oxidation reactions of amino acids to afford imine intermediates (i). The imines then undergo rapid hydrolysis in an acidic medium to generate the corresponding aldehyde (iii) and ammonia. This cascade reaction is catabolism processes to activate the amino acids in situ. Phenylalanine and phenylglycine afford phenylacetaldehyde (iii-1) and benzaldehyde (iii-2), respectively. Condensation of iii-1 with endogenous amino species (amino acids or ammonia or aniline) leads the formation of imine M4.21 Through tautomerism, enamine intermediate M5 can be generated reversibly. Parallelly, benzaldehyde iii-2 undergoes condensation with aniline to give imine M6. Then M6 is captured by M5 to generate intermediate M7. Under the assistance of imine activation process, Friedel–Crafts reaction provides tetrahydroquinoline M8. Regeneration of the oxidant iodine by the


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interaction of HI and DMSO20 leads to further oxidative aromatization of M8 to give the final quinoline products via amine elimination.

Scheme 4. Possible Reaction Mechanism.

In summary, we have developed a novel method for 2,3-disubstituted, 2-substituted and 3-substituted quinoline syntheses from one aniline and two distinct amino acids. Functionalized quinolines with various substituent patterns including challenging fused rings and biquinolines which have never been prepared before can be readily reached. The use of renewable resources amino acids and metal-free conditions makes this reaction a user-friendly process, which will be useful in pharmaceutical discovery, photochemical application and industrial production. Mechanistically, an I2-enabled decarboxylation and deamination process activates two distinct amino acids in situ, and then I2 further promotes new C-N and C-C bonds formation as a terminal oxidant. The development of using two (or multi) amino acids as heterocyclic precursors to prepare value added targets is currently underway in our laboratory.

Experimental Section General All substrates and reagents were commercially available and used without further purification. TLC analysis was performed using pre-coated glass plates. Column chromatography was performed using alkaline aluminum oxide (200–300 mesh). IR spectra were recorded on a Perkin-Elmer PE-983 infrared spectrometer as KBr pellets with absorption in cm–1.1H spectra were recorded in CDCl3 or DMSO-d6 on 600 MHz NMR spectrometers and resonances (δ) are given in parts per million relative to tetramethylsilane. Data are reported as follows: chemical shift, multiplicity (s = singlet, d = doublet, t = triplet, m = multiplet q = quadruple), coupling constants (Hz) and integration. 13C spectra were recorded in CDCl3 or DMSO-d6 on 150 MHz. NMR spectrometers and resonances (δ) are given in ppm. HRMS were obtained on a Bruker 7-tesla FT-ICR MS equipped with an electrospray source. The X-ray crystal structure determinations were obtained on a Bruker SMART APEX CCD system. Melting points were determined using XT-4 apparatus.



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General procedure for the synthesis For 4 and 5 (4a as an example) A mixture of phenylalanine 1a (1.0 mmol), phenylglycine 2a (1.0 mmol), aniline 3a (1.0 mmol), HI (50 mmol%), I2 (1.0 mmol) and DMSO (3.0 mL) were added in a pressure vessel, then stirred at 100 oC for 10 h. Then added 50 mL water and 30 mL saturated brine solution to the mixture and extracted with EtOAc 3 times (3 × 50 mL). The extract was washed with 10% Na2S2O3 solution, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified by column chromatography (eluent: petroleum ether /EtOAc=10/1) to afford the product 4a as yellow oil in 77% (226 mg).

Analytical Data for Compounds 4 and 5 6-Methyl-2,3-diphenylquinoline (4a): 77% yield (226 mg); Yellow oil; IR νmax: 1632, 1495, 1053, 1027, 1006, 824, 762, 701, 625, 572 cm−1; 1H NMR (DMSO-d6) δ 8.21 (s, 1H), 7.97 (d, J = 8.4 Hz, 1H), 7.75 (s, 1H), 7.59 (d, J = 8.4 Hz, 1H), 7.36 (d, J = 7.2 Hz, 2H), 7.27 (m, 6H), 7.22 (d, J = 6.0 Hz, 2H), 2.49 (s, 3H).

13

C NMR (DMSO-d6) δ 156.6, 145.3,

140.2, 139.7, 136.9, 136.3, 133.8, 132.1, 129.8, 129.5, 128.5, 128.2, 127.8, 127.7, 127.2, 126.8, 126.5, 21.2. HRMS (ESI): m/z [M+H]+ calcd for C22H18N : 296.1434.; found: 296.1448 6-Methyl-3-(naphthalen-2-yl)-2-phenylquinoline (4b): 81% yield (278 mg); Yellow crystalline; mp = 107-109 ℃; IR νmax: 1623, 1595, 1487, 1261, 1027, 913, 819, 746, 718, 695, 574, 477 cm−1; 1H NMR (CDCl3) δ 8.12 (s, 1H), 8.11 (s, 1H), 7.83 (s, 1H), 7.77 (t, J = 7.8 Hz, 2H), 7.61 (d, J = 8.4 Hz, 1H), 7.57 (s, 1H), 7.54 (d, J = 8.4 Hz, 1H), 7.45 (m, 4H), 7.20 (m, 3H), 7.15 (d, J = 8.4 Hz, 1H), 2.52 (s, 3H). 13C NMR (CDCl3) δ 157.3, 145.9, 140.3, 137.7, 137.3, 136.5, 134.2, 133.3, 132.1, 131.9, 129.9, 129.0, 128.2, 127.9, 127.6, 127.3, 127.2, 126.9, 126.1, 126.0, 21.6. HRMS (ESI): m/z [M+H]+ calcd for C26H20N : 346.1590; found: 346.1597. 6-Methyl-3-(4-nitrophenyl)-2-phenylquinoline (4c): 80% yield (273 mg); Yellow crystalline; mp = 172-174 ℃; IR νmax: 1595, 1514, 1493, 1344, 1272, 933, 845, 839, 766, 750, 721, 702, 579 cm−1; 1H NMR (CDCl3) δ 8.13 (d, J = 8.4 Hz, 2H), 8.10 (s, 2H), 7.65 (s, 1H), 7.61 (d, J = 8.4 Hz, 1H), 7.39 (m, 4H), 7.30 (m, 3H), 2.57 (s, 3H). 13C NMR (CDCl3) δ 156.7, 147.0, 146.7, 146.2, 139.6, 137.2, 132.8, 132.1, 130.5, 129.9, 129.1, 128.3, 128.2, 126.8, 126.3, 123.4, 21.7. HRMS (ESI): m/z [M+H]+ calcd for C22H17N2O2 : 341.1285; found: 341.1287 3-(4-methoxyphenyl)-6-methyl-2-phenylquinoline (4d): 72% yield (235 mg); Brown oil; IR νmax: 1631, 1610, 1512, 1259, 1178, 1024, 832, 796, 696, 581 cm−1; 1H NMR (DMSO-d6) δ 8.23 (s, 1H), 7.96 (d, J = 7.8 Hz, 1H), 7.79 (s, 1H), 7.61 (d, J = 8.4 Hz, 1H), 7.37 (s, 2H), 7.31 (s, 3H), 7.16 (d, J = 6.6 Hz, 2H), 6.88 (d, J = 6.6 Hz, 2H), 3.75 (s, 3H), 2.52 (s, 3H).

13

C NMR

(DMSO-d6) δ 158.5, 156.8, 145.1, 140.5, 136.7, 136.4, 133.6, 132.0, 130.8, 129.8, 128.5, 127.9, 127.8, 127.0, 126.5, 113.8, 55.1, 21.3. HRMS (ESI): m/z [M+H]+ calcd for C23H20NO : 326.1539.; found: 326.1547 3-(4-(benzyloxy)phenyl)-6-methyl-2-phenylquinoline (4e): 70% yield (280 mg); Brown oil; IR νmax: 1608, 1510, 1488, 1452, 1368, 1284, 1240, 1176, 1023, 831, 760, 735, 719, 697, 581 cm−1; 1H NMR (CDCl3) δ 8.08 (d, J = 8.4 Hz, 1H), 8.01 (s, 1H), 7.57 (s, 1H), 7.53 (d, J =


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8.4 Hz, 1H), 7.48 – 7.39 (m, 5H), 7.37 (t, J = 7.2 Hz, 3H), 7.32 (d, J = 7.2 Hz, 2H), 7.13 (d, J = 7.8 Hz, 2H), 6.88 (d, J = 8.4 Hz, 2H), 5.02 (s, 2H), 2.53 (s, 3H). 13C NMR (CDCl3) δ 157.9, 157.5, 145.6, 140.6, 136.7, 136.5, 133.9, 132.6, 131.7, 130.8, 129.9, 128.9, 128.5, 128.0, 127.9, 127.7, 127.5, 127.3, 126.1, 114.5, 69.9, 21.6. HRMS (ESI): m/z [M+H]+ calcd for C29H24NO : 402.1852; found: 402.1860. 4-(6-methyl-2-phenylquinolin-3-yl)phenol (4f): 75% yield (234 mg); Yellow crystalline; mp = 74-76 ℃; IR νmax: 1632, 1591, 1269, 1234, 1050, 1026, 1004, 817, 763, 697 cm−1; 1H NMR (DMSO-d6) δ 9.54 (s, 1H), 8.18 (s, 1H), 7.93 (d, J = 7.8 Hz, 1H), 7.76 (s, 1H), 7.58 (d, J = 7.8 Hz, 1H), 7.37 (s, 2H), 7.29 (s, 3H), 7.02 (d, J = 7.2 Hz, 2H), 6.70 (d, J = 7.2 Hz, 2H). 13C NMR (DMSO-d6) δ 156.8, 156.7, 145.0, 140.6, 136.4, 136.3, 134.0, 131.8, 130.7, 130.1, 129.8, 128.4, 127.8, 127.7, 127.0, 126.4, 115.2, 21.3. HRMS (ESI): m/z [M+H]+ calcd for C22H17NO : 312.1383; found: 312.1389. 3-(4-chlorophenyl)-6-methyl-2-phenylquinoline (4g): 80% yield (265 mg); Yellow crystalline; mp = 155-157 ℃; IR νmax: 1640, 1487, 1189, 1088, 1026, 833, 697, 531 cm−1; 1H NMR (DMSO-d6) δ 8.28 (s, 1H), 7.97 (d, J = 8.4 Hz, 1H), 7.80 (s, 1H), 7.64 (d, J = 8.4 Hz, 1H), 7.37 (m, 4H), 7.32 (s, 3H), 7.25 (m, 2H), 2.52 (s, 3H).

13

C NMR (DMSO-d6) δ 156.5, 145.4, 140.0,

138.6, 137.1, 136.6, 132.7, 132.4, 132.2, 131.4, 129.8, 128.5, 128.4, 128.0, 127.9, 126.8, 126.6, 21.3. HRMS (ESI): m/z [M+H]+ calcd for C22H17ClN : 330.1044; found: 330.1047. 3-(4-fluorophenyl)-6-methyl-2-phenylquinoline (4h): 83% yield (259 mg); Yellow crystalline; mp = 79-82 ℃; IR νmax: 1629, 1601, 1508, 1367, 1217, 1156, 836, 698, 579, 524 cm−1; 1H NMR (DMSO-d6) δ 8.27 (s, 1H), 7.97 (d, J = 7.2 Hz, 1H), 7.79 (s, 1H), 7.63 (d, J = 7.8 Hz, 1H), 7.35 (s, 2H), 7.30 (s, 3H), 7.27 (s, 2H), 7.16 (s, 2H), 2.52 (s, 3H). 13C NMR (DMSO-d6) δ 162.3, 160.7, 156.6, 145.3, 140.1, 137.0, 136.5, 136.1, 132.9, 132.2, 131.6, 131.6, 129.8, 128.5, 127.9, 127.8, 126.8, 126.5, 115.3, 115.1, 21.3. HRMS (ESI): m/z [M+H]+ calcd for C22H17FN : 314.1340; found: 314.1350. 3-(3,4-dichlorophenyl)-6-methyl-2-phenylquinoline (4i): 85% yield (307 mg); Yellow crystalline; mp = 133-135 ℃; IR νmax: 1487, 1361, 1027, 922, 825, 793, 709, 609 cm−1; 1H NMR (DMSO-d6) δ 8.34 (s, 1H), 7.98 (d, J = 8.4 Hz, 1H), 7.80 (s, 1H), 7.65 (d, J = 8.4 Hz, 1H), 7.58 – 7.51 (m, 2H), 7.36 (m, 5H), 7.13 (d, J = 7.8 Hz, 1H), 2.53 (s, 3H). 13C NMR (DMSO-d6) δ 156.3, 145.5, 140.4, 139.8, 137.3, 136.7, 132.6, 131.4, 131.0, 130.3, 130.1, 130.0, 129.8, 128.5, 128.2, 128.0, 126.7, 126.6, 21.3. HRMS (ESI): m/z [M+H]+ calcd for C22H16Cl2N : 364.0654; found: 364.0663. 2-(2-chlorophenyl)-6-methyl-3-phenylquinoline (4j): 81% yield (266 mg); Black oil; IR νmax: 1623, 1497, 1448, 1346, 1029, 905, 826, 762, 696, 666 cm−1; 1H NMR (CDCl3) δ 8.09 (m, 2H), 7.64 (s, 1H), 7.57 (d, J = 8.4 Hz, 1H), 7.41 – 7.38 (m, 1H), 7.28 – 7.19 (m, 8H), 2.56 (s, 3H). 13C NMR (CDCl3) δ 156.0, 145.4, 139.8, 139.0, 137.0, 136.1, 135.3, 132.9, 132.0, 131.4, 129.4, 129.4, 129.2, 129.0, 127.8, 127.6, 127.1, 126.5, 126.3, 21.6. HRMS (ESI): m/z [M+H]+ calcd for C22H17ClN : 330.1044; found: 330.1040. 2-(4-fluorophenyl)-6-methyl-3-phenylquinoline (4k): 76% yield (237 mg); Yellow oil; IR νmax: 1601, 1486, 1221, 1015, 844, 824, 798, 700, 571 cm−1; 1H NMR (DMSO-d6) δ 8.28 (s, 1H), 7.98 (d, J = 8.4 Hz, 1H), 7.82 (s, 1H), 7.64 (d, J = 8.4 Hz, 1H), 7.39 (m, 2H),



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Page 10 of 16

7.37 – 7.31 (m, 3H), 7.26 (d, J = 6.6 Hz, 2H), 7.12 (t, J = 8.4 Hz, 2H), 2.53 (s, 3H). 13C NMR (DMSO-d6) δ 162.7, 161.0, 155.6, 145.2, 139.6, 137.1, 136.7, 136.5, 133.8, 132.3, 132.0, 129.6, 128.4, 127.4, 126.9, 126.5, 114.8, 114.6, 21.3. HRMS (ESI): m/z [M+H]+ calcd for C22H17FN : 314.1340; found: 314.1343. 4-(6-methyl-3-phenylquinolin-2-yl)phenol (4l): 44% yield (137 mg); Brown crystalline; mp = 206-209 ℃; IR νmax: 1603, 1493, 1447, 1348, 1281, 1169, 1024, 906, 826, 762, 696, 516 cm−1; 1H NMR (DMSO-d6) δ 9.16 (s, 1H), 8.51 (s, 1H), 7.95 (d, J = 7.8 Hz, 1H), 7.85 (s, 2H), 7.79 (s, 1H), 7.60 (d, J = 7.8 Hz, 1H), 7.55 (s, 2H), 7.45 (s, 1H), 2.51 (s, 3H). 13C NMR (DMSO-d6) δ 148.6, 145.5, 137.2, 136.5, 132.9, 132.2, 131.8, 129.3, 128.5, 128.2, 127.7, 127.2, 127.1, 21.2. HRMS (ESI): m/z [M+H]+ calcd for C22H18NO : 312.1383; found: 312.1389. 6-Methyl-3-phenylquinoline (4m): 72% yield (158 mg); Yellow crystalline; mp = 47-50 ℃; IR νmax: 1726, 1632, 1496, 1455, 1188, 1131, 823, 760, 690 cm−1; 1H NMR (DMSO-d6) δ 9.16 (s, 1H), 8.51 (s, 1H), 7.94 (d, J = 8.4 Hz, 1H), 7.86 (m, 2H), 7.79 (s, 1H), 7.60 (d, J = 7.8 Hz, 1H), 7.54 (s, 2H), 7.45 (s, 1H), 2.50 (s, 3H).

13

C NMR (DMSO-d6) δ 148.6,

145.5, 137.2, 136.5, 132.8, 132.2, 131.8, 129.3, 128.5, 128.2, 127.7, 127.2, 127.1, 21.2. HRMS (ESI): m/z [M+H]+ calcd for C16H14N : 220.1121; found: 220.1125. 3-Phenylquinoline (4n): 45% yield (92 mg); Yellow oil; IR νmax: 1641, 1492, 1186, 1125, 1025, 902, 786, 762, 696 cm−1; 1H NMR (DMSO-d6) δ 9.26 (s, 1H), 8.66 (s, 1H), 8.07 (s, 2H), 7.90 (d, J = 7.2 Hz, 2H), 7.78 (t, J = 7.2 Hz, 1H), 7.65 (t, J = 7.2 Hz, 1H), 7.56 (m, 2H), 7.47 (t, J = 7.2 Hz, 1H). 13C NMR (DMSO-d6) δ 149.5, 146.8, 137.1, 132.9, 129.6, 129.3, 128.7, 128.5, 128.3, 127.7, 127.2, 127.1, 124.9. HRMS (ESI): m/z [M+H]+ calcd for C15H12N : 206.0964; found: 206.0967. 6-Methyl-2-phenylquinoline (4o): 70% yield (152 mg); Yellow crystalline; mp = 54-56 ℃; IR νmax: 1724, 1612, 1490, 1463, 1447, 1283, 832, 755, 693, 564 cm−1; 1H NMR (DMSO-d6) δ 8.33 (d, J = 8.4 Hz, 1H), 8.26 (d, J = 6.0 Hz, 2H), 8.09 (d, J = 8.4 Hz, 1H), 7.98 (d, J = 8.4 Hz, 1H), 7.74 (s, 1H), 7.61 (d, J = 8.4 Hz, 1H), 7.55 (t, J = 6.6 Hz, 2H), 7.52 – 7.46 (m, 1H). 13C NMR (DMSO-d6) δ 155.2, 146.2, 139.4, 138.7, 136.5, 136.0, 132.1, 129.4, 128.9, 128.8, 127.1, 127.0, 126.5, 118.7, 21.2. HRMS (ESI): m/z [M+H]+ calcd for C16H14N : 220.1121; found: 220.1142. 2-Phenylquinoline (4p)：： 37% yield (76 mg); White crystalline; mp = 60-63 ℃; IR νmax: 1726, 1615, 1489, 1281, 829, 771, 691, 675 cm−1; 1H NMR (DMSO-d6) δ 8.45 (d, J = 8.4 Hz, 1H), 8.28 (d, J = 6.0 Hz, 2H), 8.15 (d, J = 8.4 Hz, 1H), 8.08 (d, J = 7.8 Hz, 1H), 8.00 (d, J = 7.8 Hz, 1H), 7.78 (t, J = 6.6 Hz, 1H), 7.63 – 7.58 (m, 1H), 7.55 (d, J = 6.0 Hz, 2H), 7.51 (d, J = 6.6 Hz, 1H). 13C NMR (150 MHz, DMSO-d6) 13C NMR (DMSO-d6) δ 156.1, 147.6, 138.7, 137.3, 130.0, 129.7, 129.1, 128.9, 127.9, 127.3, 127.0, 126.5, 118.8. HRMS (ESI): m/z [M+H]+ calcd for C15H12N : 206.0964; found: 206.0969. 6-Methyl-2-phenylquinoline-3-carboxamide (4q)：： 53% yield (139 mg); White crystalline; mp = 119-121 ℃; IR νmax: 1669, 1626, 1381, 1340, 923, 824, 714, 698 cm−1; 1H NMR (DMSO-d6) δ 8.35 (s, 1H), 8.11 (s, 1H), 7.97 (d, J = 7.8 Hz, 1H), 7.83 (s, 1H), 7.79 (d, J = 6.6 Hz, 2H), 7.66 (d, J = 7.8 Hz, 2H), 7.47 (d, J = 6.6 Hz, 3H), 2.51 (s, 3H). 13C NMR (DMSO-d6) δ 170.4,


Page 11 of 16

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154.9, 145.7, 140.0, 136.7, 135.0, 132.9, 131.1, 128.7, 128.6, 128.1, 126.7, 125.8, 21.3. HRMS (ESI): m/z [M+H]+ calcd for C17H15N2O : 263.1179; found: 263.1183. Methyl 6-methyl-2-phenylquinoline-3-carboxylate (4r)：： 74% yield (204 mg); Yellow crystalline; mp = 69-72 ℃; IR νmax: 1729, 1552, 1434, 1291, 1254, 1095, 1006, 820, 712 cm−1; 1H NMR (DMSO-d6) δ 8.69 (s, 1H), 7.97 (d, J = 8.4 Hz, 1H), 7.87 (s, 1H), 7.70 (d, J = 8.4 Hz, 1H), 7.58 (d, J = 6.0 Hz, 2H), 7.47 (d, J = 7.2 Hz, 3H), 3.70 (s, 3H).

13

C NMR (DMSO-d6) δ 168.0,

155.8, 146.3, 140.0, 138.2, 137.2, 134.2, 128.5, 128.2, 128.2, 127.2, 125.4, 124.9, 52.5, 21.2. HRMS (ESI): m/z [M+H]+ calcd for C18H16NO2 : 278.1176; found: 278.1176. Methyl 6-methylquinoline-3-carboxylate (4s)：： 42% yield (85 mg); White crystalline; mp = 119-121℃; IR νmax: 1714, 1442, 1341, 1282, 1248, 1233, 1102, 825, 763 cm−1; 1H NMR (DMSO-d6) δ 9.23 (s, 1H), 8.88 (s, 1H), 7.99 (d, J = 8.4 Hz, 1H), 7.94 (s, 1H), 7.76 (d, J = 8.4 Hz, 1H), 3.94 (s, 3H), 2.52 (s, 3H). 13C NMR (DMSO-d6) δ 165.4, 148.5, 147.9, 137.8, 137.4, 134.5, 128.6, 128.2, 126.5, 122.6, 52.5, 21.1. HRMS (ESI): m/z [M+H]+ calcd for C12H12NO2: 202.0868; found: 202.0863. 4-(6-methylquinolin-3-yl)phenol (4t)：： 69% yield (163 mg); Yellow crystalline; mp = 242-245 ℃; IR νmax: 1628, 1606, 1516, 1500, 1269, 1241, 838, 817, 527 cm−1; 1H NMR (DMSO-d6) δ 9.76 (s, 1H), 9.11 (s, 1H), 8.39 (s, 1H), 7.91 (d, J = 8.4 Hz, 1H), 7.75 (s, 1H), 7.69 (d, J = 8.4 Hz, 2H), 7.55 (d, J = 8.4 Hz, 1H), 6.93 (d, J = 8.4 Hz, 2H), 2.50 (s, 3H). 13C NMR (DMSO-d6) δ 157.8, 148.5, 145.0, 136.3, 132.9, 131.2, 130.7, 128.4, 127.9, 127.8, 126.8, 116.1, 21.2. HRMS (ESI): m/z [M+H]+ calcd for C16H14NO : 236.1070; found: 236.1073. 6-Methyl-2-phenyl-3-propylquinoline (4u)：： 50% yield (130 mg); Yellow oil; IR νmax: 3056, 2959, 2929, 2869, 1597, 1488, 1443, 1378, 1266, 1013, 826, 762, 700, 575 cm−1; 1H NMR (DMSO-d6) δ 8.09 (s, 1H), 7.86 (d, J = 8.4 Hz, 1H), 7.67 (s, 1H), 7.51 (d, J = 7.2 Hz, 3H), 7.49 – 7.43 (m, 3H), 2.72 – 2.63 (m, 2H), 2.47 (s, 3H), 1.45 (m, 2H), 0.74 (t, J = 7.2 Hz, 3H). 13

C NMR (DMSO-d6) δ 159.0, 144.5, 140.7, 135.8, 135.0, 133.2, 131.1, 128.7, 128.4, 128.0, 127.9, 127.2,

125.9, 34.3, 23.1, 21.2, 13.7. HRMS (ESI): m/z [M+H]+ calcd for C19H20N : 262.1590; found: 262.1600. 3-Cyclopropyl-6-methyl-2-phenylquinoline (4v)：： 65% yield (167 mg); Yellow oil; IR νmax: 1598, 1489, 1432, 1343, 1266, 1130, 1073, 823, 760, 723, 698, 575 cm−1; 1H NMR (DMSO-d6) δ 7.89 – 7.82 (m, 2H), 7.69 (d, J = 7.8 Hz, 2H), 7.63 (s, 1H), 7.49 (t, J = 7.8 Hz, 3H), 7.45 (d, J = 7.2 Hz, 1H), 2.46 (s, 3H), 1.97 – 1.90 (m, 1H), 0.91 (d, J = 7.8 Hz, 2H), 0.81 (d, J = 4.8 Hz, 2H).

13

C NMR (DMSO-d6) δ 159.1, 144.2, 140.5, 135.8, 134.6, 131.0, 130.5, 129.2, 128.3, 127.9, 127.2,

125.9, 21.2, 13.7, 9.9. HRMS (ESI): m/z [M+H]+ calcd for C19H18N :260.1434; found: 260.1438. 6-Methyl-3-((methylthio)methyl)-2-phenylquinoline (4w)：： 48% yield (134 mg); Yellow oil; IR νmax: 2915, 1617, 1494, 1439, 1262, 1015, 823, 760, 700 cm−1; 1H NMR (DMSO-d6) δ 8.25 (s, 1H), 7.88 (d, J = 8.4 Hz, 1H), 7.75 (s, 1H), 7.62 (d, J = 6.6 Hz, 2H), 7.58 (d, J = 8.4 Hz, 1H), 7.52 – 7.43 (m, 3H), 3.83 (s, 2H), 2.48 (s, 3H), 1.92 (s, 3H). 13C NMR (DMSO-d6) δ 158.6, 144.9, 140.0, 136.3, 136.1, 131.8, 129.6, 129.0, 128.4, 128.2, 128.1, 126.8, 126.1, 35.0, 21.2, 14.8. HRMS (ESI): m/z [M+H]+ calcd for C18H18NS : 280.1155; found: 280.1157.



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Page 12 of 16

6-Ethoxy-2,3-diphenylquinoline (5a)：： 77% yield (250 mg); White crystalline; mp = 147-150 ℃; IR νmax: 1618, 1489, 1473, 1379, 1229, 1207, 1180, 1041, 845, 760, 701 cm−1; 1H NMR (DMSO-d6) δ 8.21 (s, 1H), 7.96-7.96 (m, 1H), 7.39-7.23 (s, 2H), 7.28 (m, 10H), 4.14-4.15 (m, 2H), 1.41-1.39 (m, 3H). 13C NMR (DMSO-d6) δ 156.8, 154.9, 142.7, 140.3, 139.8, 136.5, 134.1, 130.2, 129.8, 129.5, 128.3, 128.0, 127.7, 127.2, 122.7, 106.0, 103.5, 63.6, 14.6. HRMS (ESI): m/z [M+H]+ calcd for C23H20NO : 326.1539; found: 326.1546. 2,3-Diphenyl-6-(trifluoromethyl)quinoline (5b)：： 68% yield (238 mg); Yellow crystalline; mp = 88-91 ℃; IR νmax: 1631, 1321, 1291, 1161, 1122, 1061, 1006, 841, 676, 699, 634 cm−1; 1H NMR (DMSO-d6) δ 8.58 (s, 1H), 8.54 (s, 1H), 8.23 (d, J = 8.4 Hz, 1H), 7.99 (d, J = 8.4 Hz, 1H), 7.37 (d, J = 6.6 Hz, 2H), 7.38- 7.24 (m, 8H). 13C NMR (DMSO-d6) δ 160.1, 147.5, 139.6, 139.0, 138.7, 135.2, 130.3, 129.9, 129.5, 128.5, 128.4, 127.9, 127.6, 126.9, 126.7, 126.4, 126.0, 125.1, 123.3. HRMS (ESI): m/z [M+H]+ calcd for C22H15F3N : 350.1151; found: 350.1156. 6-(tert-butyl)-2,3-diphenylquinoline (5c)：： 72% yield (242 mg); Red crystalline; mp = 139-142 ℃; IR νmax: 2961, 1614, 1495, 1363, 1259, 1023, 832, 818, 701 cm−1; 1H NMR (DMSO-d6) δ 8.29 (s, 1H), 8.00 (d, J = 8.4 Hz, 1H), 7.93 (s, 1H), 7.87 (d, J = 8.4 Hz, 1H), 7.34 (d, J = 6.6 Hz, 2H), 7.29-7.22 (m, 6H), 7.22 (d, J = 4.8 Hz, 2H), 1.38 (s, 9H).

13

C NMR

(DMSO-d6) δ 156.9, 149.2, 145.2, 140.3, 139.7, 137.7, 133.8, 129.8, 129.5, 128.8, 128.3, 128.3, 127.9, 127.7, 127.2, 126.5, 122.7, 34.8, 30.9. HRMS (ESI): m/z [M+H]+ calcd for C25H24N: 338.1903; found: 338.1915. 6-Cyclohexyl-2,3-diphenylquinoline (5d)：： 75% yield (271 mg); White crystalline; mp = 84-87 ℃; IR νmax: 2935, 2847, 1443, 908, 842, 768, 759, 699 cm−1; 1H NMR (DMSO-d6) δ 8.24 (s, 1H), 7.96 (d, J = 8.4 Hz, 1H), 7.77 (s, 1H), 7.63 (d, J = 8.4 Hz, 1H), 7.33 (d, J = 6.6 Hz, 2H), 7.30 – 7.22 (m, 6H), 7.20 – 7.19 (m, J = 3.2 Hz, 2H), 2.63 (t, J = 10.8 Hz, 1H), 1.83 (d, J = 10.8 Hz, 2H), 1.77 (d, J = 10.8 Hz, 2H), 1.68 (d, J = 11.4 Hz, 1H), 1.47-1.41 (m, 2H), 1.39 – 1.31 (m, 2H), 1.19-1.21 (m, 1H).

13

C NMR (DMSO-d6) δ 156.7, 146.2, 145.6, 140.3, 139.7, 137.3, 133.8, 130.0,

129.8, 129.5, 128.6, 128.3, 127.8, 127.7, 127.2, 126.9, 124.2, 43.7, 33.8, 26.3, 25.6. HRMS (ESI): m/z [M+H]+ calcd for C27H26N : 364.2060; found: 364.2088. 2,3-Diphenylbenzo[f]quinoline (5e)：： 61% yield (201 mg); Brown crystalline; mp = 186-188 ℃; IR νmax: 1600, 1472, 1399, 1068, 1025, 831, 751, 697, 590, 507 cm−1; 1H NMR (CDCl3) δ 8.91 (s, 1H), 8.62 (d, J = 7.8 Hz, 1H), 8.09 (d, J = 9.0 Hz, 1H), 7.99 (d, J = 9.0 Hz, 1H), 7.93 (d, J = 7.2 Hz, 1H), 7.68-7.62 (m, 3H), 7.50-7.49 (m, 2H), 7.33- 7.31(m, 4H), 7.30-7.29 (m, 3H).

13

C NMR (CDCl3) δ 157.4, 147.1, 140.3, 140.2, 134.3, 132.9, 132.9, 131.8, 131.0,

130.1, 129.8, 129.5, 128.7, 128.3, 128.1, 128.0, 127.2, 127.1, 124.1, 122.7. HRMS (ESI): m/z [M+H]+ calcd for C25H18N: 332.1440; found: 332.1434. 2,3-Diphenylbenzo[h]quinoline (5f)：： 66% yield (217 mg); White crystalline; mp = 127-130 ℃; IR νmax: 1400, 1022, 908, 802, 742, 699, 568 cm−1; 1

H NMR (DMSO-d6) δ 9.23 (s, 1H), 8.44 (s, 1H), 8.06 (s, 1H), 7.99-7.94 (m, 2H), 7.77 (s, 2H), 7.51 (s, 2H),

7.34 (s, 8H). 13C NMR (DMSO-d6) δ 155.7, 144.2, 140.4, 139.6, 138.0, 134.5, 133.5, 130.6, 130.1, 129.6,


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128.4, 128.2, 128.1, 127.9, 127.4, 127.3, 125.4, 124.9, 124.0. HRMS (ESI): m/z [M+H]+ calcd for C25H18N: 332.1436; found: 332.1434. 8,9-Diphenylphenaleno[1,9-gh]quinoline (5g)：： 31% yield (124 mg); Brown crystalline; mp = 102-104 ℃; IR νmax: 1649, 1026, 1000, 531, 753, 691 cm−1; 1

H NMR (CDCl3) δ 9.75 (d, J = 7.8 Hz, 1H), 8.52 (s, 1H), 8.42 (s, 1H), 8.36 (d, J = 7.8Hz, 1H), 8.27 (d, J =

7.8 Hz, 1H), 8.16 (d, J = 7.2 Hz, 1H), 8.10 (d, J = 6.6 Hz, 2H), 8.00 (d, J = 9.6 Hz, 2H), 7.71 (d, J = 6.0 Hz, 2H), 7.55 (s, 1H), 7.39 (m, 2H), 7.36 (m, 4H). 13C NMR (CDCl3) δ 156.5, 141.6, 140.7, 140.4, 137.8, 134.6, 132.2, 131.5, 131.3, 130.6, 130.6, 129.9, 129.0, 128.9, 128.7, 128.5, 128.4, 128.1, 127.9, 127.7, 127.6, 127.2, 126.5, 126.1, 125.5, 125.0, 124.9, 124.6, 123.9, 122.7. HRMS (ESI): m/z [M+H]+ calcd for C31H20N: 406.1590; found: 406.1593. 7-Ethyl-2,3-diphenyl-7H-pyrido[2,3-c]carbazole (5h)：： 74% yield (296 mg); Red crystalline; mp = 133-135 ℃; IR νmax: 1631, 1613, 1491, 1468, 1378, 1024, 1001, 827, 780, 769, 739, 701 cm−1; 1H NMR (DMSO-d6) δ 9.00 (s, 1H), 8.55 (d, J = 7.2 Hz, 1H), 8.22 (d, J = 7.8 Hz, 1H), 8.13 (d, J = 8.4 Hz, 1H), 7.81 (d, J = 7.2 Hz, 1H), 7.52 (s, 1H), 7.47 – 7.23 (m, 11H), 4.64 (d, J = 6.0 Hz, 2H), 1.38 (s, 3H).

13

C NMR (DMSO-d6) δ 153.6, 143.1, 140.5, 140.0, 138.9, 137.0, 134.1, 132.2,

129.9, 128.4, 127.9, 127.8, 127.3, 124.8, 123.0, 122.6, 121.9, 120.2, 115.3, 113.2, 110.3, 37.3, 14.4. HRMS (ESI): m/z [M+H]+ calcd for C29H23N2: 399.1856; found: 399.1860. 10,10-Dimethyl-2,3-diphenyl-10H-indeno[1,2-g]quinoline (5i)：： 65% yield (258 mg); Brown oil; IR νmax: 1654, 1475, 1437, 1052, 1026, 1006, 825, 731, 626 cm−1; 1H NMR (DMSO-d6) δ 8.42 (s, 1H), 8.38 (s, 1H), 8.22 (s, 1H), 7.98 (d, J = 4.8 Hz, 1H), 7.64 (d, J = 4.2 Hz, 1H), 7.45 – 7.37 (m, 4H), 7.36 – 7.25 (m, 8H), 1.57 (s, 6H). 13C NMR (DMSO-d6) δ 156.7, 156.0, 153.9, 146.9, 140.3, 139.7, 138.6, 137.6, 137.3, 133.4, 129.8, 129.6, 128.8, 128.3, 127.9, 127.7, 127.5, 127.2, 126.6, 123.3, 122.3, 121.0, 117.8, 46.4, 27.7. HRMS (ESI): m/z [M+H]+ calcd for C30H24N: 398.1908; found: 398.1903. 2,3,10,10-Tetraphenyl-10H-indeno[1,2-g]quinoline (5j)：： 44% yield (230 mg); Orange crystalline; mp = 280-282 ℃; IR νmax: 1631, 1596, 1490, 1445, 1379, 911, 764, 747, 726, 700, 687 cm−1; 1H NMR (CDCl3) δ 8.23 (s, 1H), 8.19 (d, J = 7.2 Hz, 2H), 7.93 (d, J = 7.2 Hz, 1H), 7.50 (d, J = 7.2 Hz, 1H), 7.42 (d, J = 7.2 Hz, 3H), 7.37 – 7.33 (m, 1H), 7.28 (s, 7H), 7.25 (d, J = 5.4 Hz, 6H), 7.21 (d, J = 7.8 Hz, 5H). 13C NMR (CDCl3) δ 157.8, 153.5, 151.6, 147.4, 146.0, 140.3, 140.0, 139.8, 138.8, 137.5, 134.4, 129.9, 129.7, 128.9, 128.3, 128.2, 127.9, 127.8, 127.2, 127.0, 126.9, 126.7, 126.6, 120.9, 117.4, 65.3. HRMS (ESI): m/z [M+H]+ calcd for C40H28N: 522.2216; found: 522.2220. 3-Methyl-5,6-diphenyl-2H-pyrazolo[3,4-b]pyridine (5k)：： 70% yield (201 mg); White crystalline; mp = 216-217 ℃; IR νmax:1615, 1488, 1440, 1384, 1215, 1134, 762, 698, 631, 562 cm−1; 1H NMR (DMSO-d6) δ 13.31 (s, 1H), 8.20 (s, 1H), 7.34 – 7.21 (m, 8H), 7.19- 7.17(m, 2H), 2.54 (s, 3H).

13

C NMR (DMSO-d6) δ 156.1, 151.7, 141.3, 140.6, 140.5, 131.6, 129.9, 128.9, 128.2,

127.8, 127.7, 126.7, 113.0, 12.4. HRMS (ESI): m/z [M+H]+ calcd for C19H16N3: 286.1339; found: 286.1341. 2,3,7,8-Tetraphenylpyrido[2,3-g]quinoline (5l)：： 36% yield (87 mg); Orange crystalline; mp = 77-80 ℃; IR νmax: 1632, 1404, 1073, 1024, 831, 762, 698, 591 cm−1; 1H NMR (CDCl3) δ 8.90 (s, 2H), 8.36 (s, 2H), 7.53 (m, 4H), 7.33 (m, 16H). 13C NMR (CDCl3) δ 158.1,



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

146.8, 139.9, 139.9, 134.9, 132.9, 132.2, 130.1, 129.8, 128.4, 128.2, 128.0, 127.5, 123.4. HRMS (ESI): m/z [M+H]+ calcd for C36H25N2: 485.2012; found: 485.2015. 2,2',3,3'-Tetraphenyl-6,6'-biquinoline (5m)：： 41% yield (115 mg); White crystalline; mp = 245-247 ℃; IR νmax: 1475, 1444, 1356, 1023, 1003, 907, 833, 763, 698, 591 cm−1; 1H NMR (DMSO-d6) δ 8.58 (s, 2H), 8.51 (s, 2H), 8.33 (d, J = 8.4 Hz, 2H), 8.24 (d, J = 8.4 Hz, 2H), 7.42 (d, J = 6.0 Hz, 4H), 7.36-7.31 (m, 16H).

13

C NMR (DMSO-d6) δ 157.9, 146.2, 140.1,

139.6, 138.1, 137.5, 134.5, 129.9, 129.6, 129.2, 128.4, 128.2, 127.8, 127.4, 127.2, 125.9. HRMS (ESI): m/z [M+H]+ calcd for C42H29N2: 561.2325; found: 561.2326. Bis(2,3-diphenylquinolin-6-yl)methane (5n): 64% yield (184 mg); Yellow crystalline; mp = 94-97 ℃; IR νmax: 2923, 1632, 1489, 1263, 1074, 1024, 800, 764, 698 cm−1; 1H NMR (DMSO-d6) δ 8.31 (s, 2H), 8.03 (d, J = 7.8 Hz, 2H), 7.94 (s, 2H), 7.72 (d, J = 7.2 Hz, 2H), 7.35 (s, 4H), 7.29 (m, 12H), 7.24 (s, 4H), 4.40 (s, 2H). 13C NMR (DMSO-d6) δ 157.1, 145.6, 140.2, 139.6, 137.3, 134.1, 131.7, 129.8, 129.5, 129.0, 128.3, 127.9, 127.7, 127.2, 126.9. HRMS (ESI): m/z [M+H]+ calcd for C43H31N2: 575.2482; found: 575.2473. 4-Methyl-8,9-diphenyl-2H-pyrano[2,3-f]quinolin-2-one (5o): 31% yield (112 mg); Yellow crystalline; mp = 203-205 ℃; IR νmax: 1725, 1631, 1604, 1378, 1276, 1157, 846, 699 cm−1;

1

H NMR (DMSO-d6) δ 8.58 (s, 1H), 8.07 (d, J = 9.0 Hz, 1H), 7.99 (d, J = 9.0 Hz, 1H), 7.43

(d, J = 6.6 Hz, 2H), 7.38 – 7.29 (m, 8H), 6.57 (s, 1H), 2.57 (s, 3H). 13C NMR (CDCl3) δ 160.5, 160.4, 153.2, 149.9, 148.0, 139.6, 139.0, 135.5, 132.5, 129.9, 129.7, 128.5, 128.3, 128.0, 127.6, 125.4, 123.9, 117.4, 115.6, 114.6, 19.2. HRMS (ESI): m/z [M+H]+ calcd for C25H18NO2: 364.1332; found: 364.1331. 4-Methyl-7,8-diphenyl-2H-pyrano[3,2-g]quinolin-2-one (5p): 43% yield (156 mg); Yellow crystalline; mp = 235-237 ℃; IR νmax: 1731, 1630, 1447, 1210, 1061, 1023, 767, 701 cm−1; 1H NMR (DMSO-d6) δ 8.52 (s, 2H), 7.88 (s, 1H), 7.39 (d, J = 7.2 Hz, 2H), 7.39-7.30 (m, 6H), 7.27-7.26 (m, 2H), 6.51 (s, 1H), 2.53 (s, 3H).

13

C NMR (DMSO-d6) δ 160.0, 159.4, 152.6, 152.4, 147.2,

139.7, 139.2, 138.3, 133.7, 129.8, 129.5, 128.4, 128.4, 127.8, 127.5, 126.0, 123.6, 120.5, 115.5, 112.9, 18.2. HRMS (ESI): m/z [M+H]+ calcd for C25H18NO2: 364.1332; found: 364.1332. 3-(2,3-Diphenylquinolin-6-yl)-3-ethylpiperidine-2,6-dione (5q): 67% yield (282 mg); White oil; IR νmax: 1700, 1345, 1267, 1205, 1052, 1026, 1005, 841, 767, 706, 595, 582 cm−1; 1H NMR (DMSO-d6) δ 11.03 (s, 1H), 8.38 (s, 1H), 8.10 (d, J = 8.4 Hz, 1H), 7.92 (s, 1H), 7.80 (d, J = 8.4 Hz, 1H), 7.39 – 7.20 (m, 10H), 2.55-2.52 (m, 2H), 2.28-2.23 (m, 2H), 1.98 (m, 2H), 0.81 (m, 3H). 13C NMR (DMSO-d6) δ 175.6, 172.8, 157.9, 145.7, 140.1, 139.5, 138.5, 137.9, 134.3, 129.8, 129.6, 129.3, 128.4, 128.3, 128.1, 127.8, 127.3, 126.6, 125.5, 50.5, 31.9, 29.2, 26.3, 9.1. HRMS (ESI): m/z [M+H]+ calcd for C28H25N2O2:421.1911; found: 421.1915. (1S,4R)-N-(2,3-diphenylquinolin-6-yl)-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carboxamid e (5r): 53% yield (252 mg); Brown oil; IR νmax: 1791, 1682, 1625, 1533, 1487, 1377, 1183, 1124, 1097, 1055, 1013, 923, 761, 698, 583 cm−1; 1H NMR (DMSO-d6) δ 10.25 (s, 1H), 8.55 (s, 1H), 8.28 (s, 1H), 8.13 – 8.07 (m, 1H), 8.07 – 7.99 (m, 1H), 7.36 (s, 2H), 7.29-7.25 (m, 8H), 2.53 (s, 1H), 2.06 – 1.94 (m, 2H), 1.61-1.60 (m,


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1H), 1.06 (d, J = 16.9 Hz, 6H), 0.95 (s, 3H). 13C NMR (DMSO-d6) δ 178.0, 165.9, 156.5, 144.0, 140.2, 139.6, 137.3, 136.2, 134.2, 129.8, 129.6, 129.0, 128.3, 127.9, 127.7, 127.3, 127.0, 125.2, 117.2, 91.9, 54.7, 53.8, 30.2, 28.5, 16.6, 16.4, 9.6. HRMS (ESI): m/z [M+H]+ calcd for C31H29N2O3: 477.2173; found: 477.2176.

ASSOCIATED CONTENT Supporting Information Crystallographic data and copies of the 1H and 13C NMR spectra are involved. This material is available free of charge via the Internet at http://pubs.acs.org.

AUTHOR INFORMATION Corresponding Author E-mail: [email protected].

Notes The authors declare no competing ﬁnancial interest.

ACKNOWLEDGMENT We are grateful to the National Natural Science Foundation of China (Grant Nos. 21472056 and 21602070) and the Fundamental Research Funds for the Central Universities (CCNU15ZX002 and CCNU16A05002) for financial support. This work was also supported by the 111 Project B17019. We acknowledge an Excellent Doctoral Dissertation Cultivation Grant from Central China Normal University (2015YBYB089).

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Divergent Synthesis of Functionalized Quinolines from Aniline and

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