Radical Alkylation of Imines with 4-Alkyl-1,4-dihydropyridines Enabled

Aug 21, 2017 - Radical alkylation of imines with 4-alkyl-1,4-dihydropyridines cocatalyzed by iridium/ruthenium complex and Brønsted acid under visibl...
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Radical Alkylation of Imines with 4‑Alkyl-1,4-dihydropyridines Enabled by Photoredox/Brønsted Acid Cocatalysis Hong-Hao Zhang and Shouyun Yu* State Key Laboratory of Analytical Chemistry for Life Science, Jiangsu Key Laboratory of Advanced Organic Materials, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China S Supporting Information *

ABSTRACT: Radical alkylation of imines with 4-alkyl-1,4-dihydropyridines cocatalyzed by iridium/ruthenium complex and Brønsted acid under visible light irradiation has been achieved. Both aldimines and ketimines can undergo this transformation. Common functional groups, such as hydroxyl groups, ester, amide, ether, cyanide, and heterocycles, can be tolerated in this reaction. A variety of structurally diverse amines (57 examples) have been produced with up to 98% isolated yields using this method.

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INTRODUCTION Amines are one of the most important organic compounds. The development of efficient and general methods for their synthesis has long attracted the attention of the synthetic community.1 Alkylation of imines has proven to be the most powerful tool for the synthesis of structurally diverse and biologically active amines through CN bond cleavage and C−C bond formation.2 There are two reaction modes wellestablished for the alkylation of imines (Scheme 1a). One is the direct addition of carbon-centered nucleophiles,3 such as organometallic reagents, to the CN bond (Scheme 1a, top). Despite the high efficiency of this approach, harsh reaction conditions (typically low temperature and sensitive to moisture and oxygen) and low functional group tolerance restrain its application in organic synthesis. The other is radicalbased transformations (Scheme 1a, bottom).4 Classical radicalbased methods usually require organoborane reagents5 or strong reductants,6 such as an alkali metal, titanium, and samarium reagents, to generate radical species. These radical generators are also moisture- or oxygen-sensitive. Visible-light photoredox catalysis, which takes advantage of the redox potential of the photocatalyst under irradiation, has emerged as a powerful tool to promote single-electron transfer processes.7 Recently, photoredox-catalyzed radical alkylation of imines has been reported, which is an elegant complementary approach to classical radical-based methods (Scheme 1b).8 Mechanistically, α-aminoalkyl radicals or radical anions © 2017 American Chemical Society

generated from imines by photoredox catalysis couple with another radical species to give the desired functionalized amines. Aldimines and α-heteroatom-stabilized radicals are suitable coupling partners.8a−f However, ketimines8g and nonfunctionalized radical9 coupling partners are challenging substrates. Hantzsch esters are extensively used as reductants in catalytic transfer hydrogenation reactions.10 In addition, Hantzsch esters serve as terminal reductants in photoredox catalysis.11,8h,i Recently, as demonstrated by Nishibayashi,12a,b Cheng,12c and Molander,12d 4-alkyl-1,4-dihydropyridines were used as alkylation reagents to couple with aryl halides, cyanoarenes, and αbromoketones under photoredox catalysis. Tang and coworkers reported Lewis acid-catalyzed alkyl transfer reactions of 4-alkyl-1,4-dihydropyridines to aldimines at elevated temperature.13 Inspired by these works, as well as our continuing research interest in photoredox catalysis,14 we present herein our efforts on photoredox and Brønsted acid cocatalyzed radical alkylation of aldimines and ketimines with 4-alkyl-1,4dihydropyridines under visible light irradiation (Scheme 1c).

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RESULTS AND DISCUSSION

We started our investigation using aldimine 1a and 4-benzyl1,4-dihydropyridine 2a as the model substrates (see Table S1 in Received: June 9, 2017 Published: August 21, 2017 9995

DOI: 10.1021/acs.joc.7b01425 J. Org. Chem. 2017, 82, 9995−10006

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The Journal of Organic Chemistry Scheme 2. Substrate Scope of Aldiminesa,b

Scheme 1. Profile of Alkylation of Imines

a

Reaction conditions: a solution of 1 (0.10 mmol), 2a (0.15 mmol), PhCO2H (0.01 mmol, 10 mol %), and photocatalyst I (0.001 mmol, 1 mol %) in CH3CN (1.0 mL) was irradiated by white LED strips for 48 h. bThe yields were isolated yields.

Supporting Information (SI) for more details). When a solution of 1a (1 equiv) and 2a (1 equiv) in CH2Cl2 was irradiated by a 13 W white LED strip for 48 h in the presence of photocatalyst Ir(ppy)2(dtbbpy)PF6 (I, 2 mol %), the desired α-branched amine 3aa was generated in a moderate yield based on GC analysis (48%, Table 1, entry 1). Given that imines can be activated by Brønsted acids, a catalytic amount of Brønsted acid (10 mol %) was added to the reaction tentatively to improve the efficiency of this reaction. To our delight, the addition of Brønsted acid improved the yields significantly (entries 2−5). Benzoic acid showed the highest activity in terms of the yield (71%, entry 2). Several other photocatalysts, such as facIr(ppy)3 (II) and Ru(bpy)3Cl2 (III), were employed and not superior to Ir(ppy)2(dtbbpy)PF6 (I) (entries 6 and 7). The solvent effect was then examined (entries 8−11). It was found that CH3CN was the most suitable solvent for this reaction with 86% GC yield (entry 11). To improve the yield further, the dosage of 2a was explored and the use of slightly excess 2a (1.5 equiv) could give excellent GC yield (98%, entry 12). The loading of the photocatalyst I could be reduced to 1 mol % without affecting the yield (98% GC yield and 93% yield based on isolated product, entry 13). Control experiments verified the necessity of irradiation and photocatalyst. Both visible light and the photocatalyst were crucial to this reaction (entries 14 and 15). After determining the optimized conditions, we investigated the scope and limitations of this protocol, as shown in Scheme 2. Various N-aryl aldimines were alkylated with 4-benzyl-1,4dihydropyridine 2a. This protocol was applicable to a wide range of N-aryl aldimines to give products 3aa−ha in good yields (50−98%). N-Aryl aldimines with electron-neutral and -donating substituents on the N-aryl group gave the excellent yields while electron-deficient N-aryl aldimine was less reactive

in this reaction (50% yield for 3ea). Meta-substituted N-aryl aldimine could go through this transformation smoothly (93% yield for 3ga) and ortho-substituted N-aryl aldimine was less reactive substrate (76% yield for 3ha). Aldimines derived from different functionalized benzaldehydes with 4-methoxyaniline were then coupled with 4-benzyl-1,4-dihydropyridine 2a. Remarkable functional group tolerance was observed. Common functional groups, such as hydroxyl groups (3la), ester (3na), amide (3ja), ether (3ia, 3pa, and 3qa), cyanide (3ma), and heterocyles (3sa and 3ta), could be tolerated in this reaction. The success on aldimines encouraged us to explore the reactivity of more synthetically challenging ketimines, which are elusive in photoredox catalysis at this stage. We were pleased to find that our newly established conditions were amenable to ketimines (Scheme 3). A variety of ketimines derived from aryl ketones with aniline could be alkylated with 4-benzyl-1,4dihydropyridine 2a to give structurally diverse and sterically hindered amine 5aa−ia in 64−97% yields. Remarkably, amino acid derivative 5ja could be also synthesized in 71% yield by this method under slightly modified conditions (for the full condition screening, see Table S2 in the SI). Under these conditions, isatin-derived ketimines could be also alkylated with 2a to deliver the corresponding 3-aminooxindoles 5ka−na, which are privileged building blocks in the synthesis of heterocycles with potential bioactivities,15 in 84%−95% yields. For the aim to show the utility of this visible-light-promoted radical alkylation reaction, a gram scale synthesis of amines 3aa and 5ka was performed. As shown in Scheme 4, when 5 mmol of 1a and 4k was alkylated with 2a under our established 9996

DOI: 10.1021/acs.joc.7b01425 J. Org. Chem. 2017, 82, 9995−10006

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The Journal of Organic Chemistry Table 1. Optimization of the Aldimine Alkylation Reactiona

a

Reaction conditions: a solution of 1a (0.10 mmol), 2a (0.10 mmol), acid (0.01 mmol, 10 mol %), and photocatalyst (0.002 mmol, 2 mol %) in the indicated solvent (1.0 mL) was irradiated by white LED strips for 48 h. bGC yields. c2a (0.15 mmol, 1.5 equiv) was used. d1 mol % photocatalyst I was used. eIsolated yield. fNo visible light irradiation. PMP = p-methoxyphenyl.

conditions, comparative isolated yields of 3aa (80%, 1.21 g) and 5ka (82%, 1.35 g) were obtained. We next performed reactions of imines with various 4-alkyl1,4-dihydropyridines. As indicated in Scheme 5, this protocol was amenable to substrates 2b−g bearing benzyl groups with either electron-donating or electron-withdrawing substituents at different positions of the ring, affording the desired products in moderate to good yields (67−95%). Dihydropyridine 2h with a thiophenylmethyl substituent gave heterocyclic products

3ah, 5bh, and 5kh in good yield. Imines could also be alkylated with the bulkier isopropyl group and benzhydryl group. Unsymmetrical secondary alkyl radical forming from 2k could react with imines with high efficiency (84−94% yields), although no diastereoselectivity was observed. α-Heteroatomstabilized (benzyloxy)methyl radical formed from dihydropyridine 2l could also be transferred efficiently, giving the product 3al in 87% yield. 9997

DOI: 10.1021/acs.joc.7b01425 J. Org. Chem. 2017, 82, 9995−10006

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The Journal of Organic Chemistry Scheme 3. Substrate Scope of Ketiminesa,b

Scheme 5. Substrate Scope of 4-Alkylated-1,4dihydropyridinesa−c

a

Reaction conditions A: a solution of 4 (0.10 mmol), 2a (0.15 mmol), PhCO2H (0.01 mmol, 10 mol %), and photocatalyst I (0.001 mmol, 1 mol %) in CH3CN (1.0 mL) was irradiated by white LED strips for 48 h. Reaction conditions B: a solution of 4 (0.10 mmol), 2a (0.15 mmol), TFA (0.01 mmol, 10 mol %), and photocatalyst III (0.001 mmol, 1 mol %) in MeOH (1.0 mL) was irradiated by white LED strips for 12 h. bThe yields were isolated yields.

Scheme 4. Gram-Scale Preparation of 3aa and 5ka

To gain insight into the mechanism of this reaction, a series of control reactions were conducted. The desired reaction could be terminated completely when TEMPO was introduced to the reaction mixture, and the TEMPO-trapped product 612a−c could be observed by high-resolution mass spectrometry (Scheme 6a), which suggested that this reaction involves a single electron-transfer (SET) pathway. When 4d was employed to react with 2a, the desired product 5da was generated in 68% isolated yield together with a small amount of byproduct 7 (24% yield, Scheme 6b). It is envisaged that byproduct 7 is generated by dimerization of α-aminoalkyl radical A.8c Stern−Volmer quenching experiments showed that a significant quenching of Ir(ppy)2(dtbbpy)PF6 fluorescence by 2a while imine 1a showed a much less pronounced effect (Figure 1). These results strongly suggest that the photoexcited catalyst I was quenched by 2a. Based on these observations, a plausible mechanism for this radical alkylation reaction is proposed. As shown in Scheme 7, an excited-state photocatalyst *Ru(bpy)32+ is formed by the absorption of visible light, which is reductively quenched by 4alkyl-1,4-dihydropyridine to give the corresponding alkyl radical 9, pyridine 8, and Ru(bpy)3+.12b,c The alkyl radical 9 adds to

a The yields were isolated yields. bReaction conditions A: a solution of 1a, 4a or 4b (0.10 mmol), 2 (0.15 mmol), PhCO2H (0.01 mmol, 10 mol %), and photocatalyst I (0.001 mmol, 1 mol %) in CH3CN (1.0 mL) was irradiated by white LED strips for 48 h. cReaction conditions B: a solution of 4k (0.10 mmol), 2 (0.15 mmol), TFA (0.01 mmol, 10 mol %), and photocatalyst III (0.001 mmol, 1 mol %) in MeOH (1.0 mL) was irradiated by white LED strips for 12 h.

the imine to give N-centered radical 10. Reduction of radical 10 by Ru(bpy)3+ with the assistance of a proton to give the final amine with the regeneration of the photocatalyst (pathway A).8e,f,9 Alternatively, imine is reduced with the assistance of a proton by Ru(bpy)3+ to give α-aminoalkyl radical 11.16 The coupling of radical 11 with 9 gives the final product (pathway B).8a−d,g−i The observation of the dimer of α-aminoalkyl radical 118c (Scheme 6b) suggests that pathway B might be the major route. However, pathway A cannot be ruled out completely at this stage. 9998

DOI: 10.1021/acs.joc.7b01425 J. Org. Chem. 2017, 82, 9995−10006

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The Journal of Organic Chemistry Scheme 6. Control Experiments

Figure 1. Luminescence quenching of Ir(ppy)2(dtbbpy)PF6 with excitation at 400 nm by 2a in CH3CN (left). The Stern−Volmer plot (right).

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CONCLUSION In summary, we have established a photoredox and Brønsted acid cocatalyzed radical alkylation of imines with 4-alkyl-1,4dihydropyridines as the alkylation reagents. Both aldimines and ketimines can be alkylated with various 4-alkyl-1,4-dihydropyridines under visible light irradiation at room temperature. A variety of stuctrually diverse amines (57 examples) have been produced with up to 98% isolated yields using this method. Common functional groups, such as hydroxyl groups, ester, amide, ether, cyanide, and heterocycles, can be tolerated in this reaction. Therefore, this method is an elegant complementary approach to the classical nucleophilic addition of imines.

Scheme 7. Mechanistic Proposal

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EXPERIMENTAL SECTION

General Information. All reagents were used without further purification. Thin layer chromatography (TLC) was performed on precoated plates (silica gel 60 F254, Art 5715) and visualized by fluorescence quenching under UV light and by staining with phosphomolybdic acid or potassium permanganate, respectively. Column chromatography was performed on silica gel 60 (300−400 Mesh) using a forced flow of 0.5−1.0 bar. 1H NMR (400 MHz), 13C NMR (100 MHz) were measured on a NMR spectrometer. Chemical shifts are expressed in parts per million (ppm) with respect to the residual solvent peak. Coupling constants are reported as hertz (Hz), and signal shapes and splitting patterns are indicated as follows: s, 9999

DOI: 10.1021/acs.joc.7b01425 J. Org. Chem. 2017, 82, 9995−10006

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The Journal of Organic Chemistry

126.9, 126.4 (q, J = 3.8 Hz), 126.3, 124.9 (q, J = 268.6 Hz), 119.04 (q, J = 32.5 Hz), 112.8, 58.8, 45.0; IR (KBr): 3418, 3029, 2924, 2854, 1615, 1529, 1492, 1453, 1317, 1273, 1186, 1157, 1102, 1060, 822, 756, 697, 638, 588 cm−1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C21H19F3N 342.1464; found 342.1466. N-(1,2-Diphenylethyl)aniline (3fa): 18 According to general procedure A, 3fa was obtained as a colorless sticky oil (25.3 mg, 93%) from imine 1f and 4-alkyl-1,4-dihydropyridine 2a. 1H NMR (400 MHz, CDCl3) δ 7.39−7.16 (m, 8H), 7.15−7.08 (m, 2H), 7.08−6.98 (m, 2H), 6.68−6.56 (m, 1H), 6.48−6.41 (m, 2H), 4.58 (dd, J = 8.2, 5.7 Hz, 1H), 4.11 (s, 1H), 3.13 (dd, J = 14.0, 5.7 Hz, 1H), 3.00 (dd, J = 14.0, 8.2 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 147.3, 143.5, 137.7, 129.2, 129.0, 128.60, 128.57, 127.1, 126.7, 126.5, 117.5, 113.7, 59.2, 45.2. N-(1,2-Diphenylethyl)-3-methoxyaniline (3ga): According to general procedure A, 3ga was obtained as a colorless sticky oil (28.3 mg, 93%) from imine 1g and 4-alkyl-1,4-dihydropyridine 2a. 1H NMR (400 MHz, CDCl3) δ 7.32−7.19 (m, 8H), 7.12−7.08 (m, 2H), 6.97− 6.91 (m, 1H), 6.24−6.14 (m, 1H), 6.10−6.07 (m, 1H), 6.02−5.99 (m, 1H), 4.57 (dd, J = 8.2, 5.8 Hz, 1H), 4.14 (s, 1H), 3.63 (s, 3H), 3.12 (dd, J = 14.0, 5.7 Hz, 1H), 3.00 (dd, J = 14.0, 8.2 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 160.6, 148.7, 143.4, 137.7, 129.8, 129.2, 128.62, 128.57, 127.1, 126.7, 126.5, 106.8, 102.7, 99.7, 59.3, 55.0, 45.1; IR (KBr): 3401, 3060, 3026, 2919, 2849, 1659, 1612, 1596, 1508, 1492, 1451, 1424, 1340, 1302, 1278, 1208, 1159, 1104, 1069, 1039, 826, 753, 697, 686, 566 cm−1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C21H22NO 304.1696; found 304.1687. N-(1,2-Diphenylethyl)-2-methoxyaniline (3ha): According to general procedure A, 3ha was obtained as a colorless sticky oil (23.2 mg, 76%) from imine 1h and 4-alkyl-1,4-dihydropyridine 2a. 1H NMR (400 MHz, CDCl3) δ 7.30−7.19 (m, 8H), 7.13−7.09 (m, 2H), 6.71 (dd, J = 7.8, 1.5 Hz, 1H), 6.68−6.63 (m, 1H), 6.60−6.54 (m, 1H), 6.31 (dd, J = 7.8, 1.6 Hz, 1H), 4.81 (s, 1H), 4.53 (t, J = 6.9 Hz, 1H), 3.79 (s, 3H), 3.10 (dd, J = 6.9, 2.3 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 146.9, 143.6, 138.0, 137.3, 129.3, 128.5, 128.4, 127.0, 126.55, 126.53, 121.1, 116.5, 111.3, 109.5, 59.5, 55.6, 45.3; IR (KBr): 3422, 3081, 3060, 2919, 2850, 1601, 1509, 1493, 1452, 1426, 1342, 1300, 1245, 1221, 1175, 1122, 1049, 1027, 756, 733, 697, 535 cm−1; HRMS (ESI- TOF) m/z: [M + H]+ Calcd for C21H22NO 304.1696; found 304.1695. N-(1-(4-Methoxyphenyl)-2-phenylethyl)aniline (3ia): 19 According to general procedure A, 3ia was obtained as a colorless sticky oil (29.4 mg, 97%) from imine 1i and 4-alkyl-1,4-dihydropyridine 2a. 1H NMR (400 MHz, CDCl3) δ 7.28−7.19 (m, 5H), 7.12−7.08 (m, 2H), 7.07− 7.02 (m, 2H), 6.86−6.80 (m, 2H), 6.64−6.59 (m, 1H), 6.49−6.42 (m, 2H), 4.53 (dd, J = 7.9, 6.0 Hz, 1H), 4.07 (s, 1H), 3.76 (s, 3H), 3.08 (dd, J = 13.9, 5.9 Hz, 1H), 2.99 (dd, J = 13.9, 7.9 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 158.6, 147.4, 137.8, 135.4, 129.3, 129.0, 128.5, 127.5, 126.7, 117.5, 114.0, 113.7, 58.7, 55.3, 45.3. N-(4-(2-Phenyl-1-(phenylamino)ethyl)phenyl)acetamide (3ja): According to general procedure A, 3ja was obtained as a white solid (32.5 mg, 98%) from imine 1j and 4-alkyl-1,4-dihydropyridine 2a. mp 157−158 °C; 1H NMR (400 MHz, CDCl3) δ 7.50−7.38 (m, 3H), 7.27−7.18 (m, 5H), 7.12−7.08 (m, 2H), 7.06−7.00 (m, 2H), 6.66− 6.57 (m, 1H), 6.45−6.41 (m, 2H), 4.54 (dd, J = 8.0, 5.8 Hz, 1H), 4.10 (s, 1H), 3.08 (dd, J = 13.9, 5.8 Hz, 1H), 2.98 (dd, J = 13.9, 8.1 Hz, 1H), 2.11 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 168.5, 147.2, 139.4, 137.6, 136.8, 129.2, 129.0, 128.6, 127.1, 126.8, 120.2, 117.5, 113.7, 58.8, 45.1, 24.5; IR (KBr): 3375, 3298, 3051, 3024, 2938, 2920, 2850, 1664, 1598, 1544, 1501, 1452, 1429, 1411, 1340, 1310, 1279, 1196, 1094, 991, 966, 937, 912, 870, 830, 817, 748, 729, 700, 690, 536 cm−1; HRMS (ESI- TOF) m/z: [M + Na]+ Calcd for C22H22N2ONa 353.1624; found 353.1634. N-(2-Phenyl-1-(p-tolyl)ethyl)aniline (3ka): 19 According to general procedure A, 3ka was obtained as a colorless sticky oil (27.6 mg, 96%) from imine 1k and 4-alkyl-1,4-dihydropyridine 2a. 1H NMR (400 MHz, CDCl3) δ 7.29−7.23 (m, 2H), 7.22−7.18 (m, 3H), 7.15−7.08 (m, 4H), 7.06−7.00 (m, 2H), 6.65−6.56 (m, 1H), 6.47−6.43 (m, 2H), 4.55 (dd, J = 8.3, 5.6 Hz, 1H), 4.08 (s, 1H), 3.11 (dd, J = 14.0, 5.6 Hz, 1H), 2.98 (dd, J = 14.0, 8.3 Hz, 1H), 2.31 (s, 3H); 13C NMR (100

singlet; d, doublet; t, triplet; q, quartet; m, multiplet. Infrared (IR) spectra were recorded on an IR spectrophotometer and are reported as wavenumber (cm−1). All imines were synthesized according to the literature procedure.17 The 4-alkyl-1,4-dihydropyridines (2) were prepared according to the literature procedure.8 General Procedure A. A 10.0 mL microwave tube equipped with magnetic stir bar was charged with imine 1a (0.1 mmol, 21.1 mg), 4benzyl-1,4-dihydropyridine 2a (0.15 mmol, 51.5 mg), PhCO2H (0.01 mmol, 1.2 mg), and Ir(ppy)2(dtbbpy)PF6 (I, 0.001 mmol, 1.0 mg) under air. The tube was evacuated and backfilled with N2 for 3 times (3 × 5 min). Degassed CH3CN (1.0 mL) was added by syringe under N2. The mixture was then irradiated by a 13 W white LED strips and stirred at room temperature for 48 h. Upon completion, the reaction mixture was concentrated under vacuum, and the residue was purified by column chromatography (petroleum ether/EtOAc = 20:1) to give the desired product 3aa (28.3 mg, 93%) as a colorless sticky oil. General Procedure B. A 10.0 mL microwave tube equipped with magnetic stir bar was charged with imine 4k (0.1 mmol, 23.6 mg), 4benzyl-1,4-dihydropyridine 2a (0.15 mmol, 51.5 mg), and Ru(bpy)3Cl2 (III, 0.001 mmol, 0.7 mg) under air. The tube was evacuated and backfilled with N2 three times (3 × 5 min). Trifluoroacetic acid (100 μL, 0.1 M methanol solution) and degassed MeOH (0.9 mL) were added by syringe under N2. The mixture was then irradiated by a 13 W white LED strips and stirred at room temperature for 12 h. Upon completion, the reaction mixture was concentrated under vacuum and the residue was purified by column chromatography (petroleum ether/EtOAc = 10:1) to give the desired product 5ka (30.9 mg, 94%) as a white solid. N-(1,2-Diphenylethyl)-4-methoxyaniline (3aa): 18 According to general procedure A, 3aa was obtained as a colorless sticky oil (28.3 mg, 93%) from imine 1a and 4-alkyl-1,4-dihydropyridine 2a. 1H NMR (400 MHz, CDCl3) δ 7.37−7.18 (m, 8H), 7.17−7.09 (m, 2H), 6.70− 6.60 (m, 2H), 6.43−6.37 (m, 2H), 4.50 (dd, J = 8.3, 5.6 Hz, 1H), 3.87 (s, 1H), 3.66 (s, 3H), 3.11 (dd, J = 13.9, 5.6 Hz, 1H), 2.99 (dd, J = 14.0, 8.3 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 152.1, 143.7, 141.6, 137.8, 129.2, 128.6, 128.5, 127.0, 126.7, 126.5, 114.9, 114.7, 60.1, 55.7, 45.3. N-(1,2-Diphenylethyl)-4-methylaniline (3ba): 18 According to general procedure A, 3ba was obtained as a colorless sticky oil (27.8 mg, 97%) from imine 1b and 4-alkyl-1,4-dihydropyridine 2a. 1H NMR (400 MHz, CDCl3) δ 7.33−7.18 (m, 8H), 7.14−7.08 (m, 2H), 6.93− 6.80 (m, 2H), 6.39−6.35 (m, 2H), 4.54 (dd, J = 8.3, 5.6 Hz, 1H), 3.99 (s, 1H), 3.11 (dd, J = 14.0, 5.6 Hz, 1H), 2.99 (dd, J = 14.0, 8.3 Hz, 1H), 2.15 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 145.1, 143.7, 137.8, 129.6, 129.2, 128.6, 127.0, 126.7, 126.5, 113.8, 59.5, 45.2, 20.4. N-(4-((1,2-Diphenylethyl)amino)phenyl)acetamide (3ca): 18 According to general procedure A, 3ca was obtained as a white solid (32.3 mg, 98%) from imine 1c and 4-alkyl-1,4-dihydropyridine 2a. mp 145−146 °C; 1H NMR (400 MHz, acetone-d6) δ 8.71 (s, 1H), 7.41− 7.37 (m, 2H), 7.33−7.08 (m, 10H), 6.50−6.47 (m, 2H), 5.28 (s, 1H), 4.66 (t, J = 7.2 Hz, 1H), 3.12 (dd, J = 13.8, 8.1 Hz, 1H), 3.04 (dd, J = 13.7, 6.2 Hz, 1H), 1.95 (s, 3H); 13C NMR (100 MHz, acetone-d6) δ 167.0, 144.4, 144.2, 138.9, 129.6, 129.3, 128.2, 128.1, 126.72, 126.65, 126.1, 120.6, 113.1, 59.5, 44.7, 23.1. N-(1,2-Diphenylethyl)-4-fluoroaniline (3da): 18 According to general procedure A, 3da was obtained as a colorless sticky oil (27.0 mg, 93%) from imine 1d and 4-alkyl-1,4-dihydropyridine 2a. 1H NMR (400 MHz, CDCl3) δ 7.36−7.17 (m, 8H), 7.15−7.07 (m, 2H), 6.82− 6.68 (m, 2H), 6.38−6.33 (m, 2H), 4.52−4.48 (m, 1H), 3.99 (s, 1H), 3.12 (dd, J = 14.0, 5.6 Hz, 1H), 2.98 (dd, J = 14.0, 8.3 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 155.8 (d, J = 233.8 Hz), 143.6 (d, J = 1.9 Hz), 143.3, 137.6, 129.2, 128.64, 128.60, 127.2, 126.8, 126.5, 115.4 (d, J = 22.2 Hz), 114.5 (d, J = 7.3 Hz), 59.8, 45.2. N-(1,2-Diphenylethyl)-4-(trifluoromethyl)aniline (3ea): According to general procedure A, 3ea was obtained as a colorless sticky oil (17.1 mg, 50%) from imine 1e and 4-alkyl-1,4-dihydropyridine 2a. 1H NMR (400 MHz, CDCl3) δ 7.41−7.17 (m, 10H), 7.17−7.04 (m, 2H), 6.45 (d, J = 8.5 Hz, 2H), 4.65−4.60 (m, 1H), 4.43 (s, 1H), 3.16 (dd, J = 14.0, 5.7 Hz, 1H), 3.02 (dd, J = 14.1, 8.2 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 149.6, 142.4, 137.2, 129.1, 128.74, 128.66, 127.4, 10000

DOI: 10.1021/acs.joc.7b01425 J. Org. Chem. 2017, 82, 9995−10006

Article

The Journal of Organic Chemistry MHz, CDCl3) δ 147.4, 140.5, 137.9, 136.6, 129.3, 129.2, 129.0, 128.6, 126.7, 126.4, 117.4, 113.7, 59.0, 45.2, 21.2. 4-(2-Phenyl-1-(phenylamino)ethyl)phenol (3la): According to general procedure A, 3la was obtained as a colorless sticky oil (20.3 mg, 70%) from imine 1l and 4-alkyl-1,4-dihydropyridine 2a. 1H NMR (400 MHz, CDCl3) δ 7.28−7.24 (m, 2H), 7.23−7.20 (m, 1H), 7.18− 7.14 (m, 2H), 7.12−7.02 (m, 4H), 6.79−6.71 (m, 2H), 6.67−6.59 (m, 1H), 6.51−6.42 (m, 2H), 4.74 (s, 1H), 4.52 (dd, J = 7.9, 6.0 Hz, 1H), 4.08 (s, 1H), 3.08 (dd, J = 13.9, 6.0 Hz, 1H), 3.00 (dd, J = 13.9, 7.8 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 154.5, 147.3, 137.7, 135.6, 129.3, 129.0, 128.5, 127.7, 126.7, 117.5, 115.4, 113.7, 58.7, 45.2; IR (KBr): 3392, 3052, 2920, 2850, 1598, 1501, 1452, 1353, 1315, 1226, 1168, 1094, 960, 907, 867, 819, 748, 691, 535 cm−1; HRMS (ESITOF) m/z: [M + H]+ Calcd for C20H20NO 290.1539; found 290.1534. 4-(2-Phenyl-1-(phenylamino)ethyl)benzonitrile (3ma): According to general procedure A, 3ma was obtained as a colorless sticky oil (22.7 mg, 76%) from imine 1m and 4-alkyl-1,4-dihydropyridine 2a. 1H NMR (400 MHz, CDCl3) δ 7.60−7.55 (m, 2H), 7.42−7.38 (m, 2H), 7.30−7.22 (m, 3H), 7.09−7.02 (m, 4H), 6.71−6.60 (m, 1H), 6.41− 6.36 (m, 2H), 4.61 (dd, J = 7.8, 6.1 Hz, 1H), 4.16 (s, 1H), 3.08 (dd, J = 13.9, 6.1 Hz, 1H), 3.02 (dd, J = 13.9, 7.9 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 149.2, 146.6, 136.6, 132.5, 129.19, 129.17, 128.8, 127.3, 127.2, 118.9, 118.2, 113.6, 111.0, 59.1, 44.8; IR (KBr): 3378, 2952, 2920, 2849, 1600, 1495, 1315, 1287, 1255, 1177, 837, 750, 732, 693, 559 cm−1; HRMS (ESI- TOF) m/z: [M + H]+ Calcd for C21H19N2 299.1543; found 299.1549. Methyl 4-(2-Phenyl-1-(phenylamino)ethyl)benzoate (3na): According to general procedure A, 3na was obtained as a white solid (30.1 mg, 91%) from imine 1n and 4-alkyl-1,4-dihydropyridine 2a. mp 102−103 °C; 1H NMR (400 MHz, CDCl3) δ 8.00−7.93 (m, 2H), 7.39−7.35 (m, 2H), 7.29−7.20 (m, 3H), 7.11−7.07 (m, 2H), 7.06− 7.01 (m, 2H), 6.66−6.60 (m, 1H), 6.45−6.39 (m, 2H), 4.63 (dd, J = 7.9, 5.9 Hz, 1H), 4.15 (s, 1H), 3.89 (s, 3H), 3.11 (dd, J = 13.9, 5.9 Hz, 1H), 3.02 (dd, J = 13.9, 8.0 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 167.0, 148.9, 146.9, 137.1, 130.0, 129.2, 129.1, 128.7, 127.0, 126.6, 117.8, 113.7, 59.2, 52.1, 44.9; IR (KBr): 3360, 3026, 2954, 2920, 2901, 2849, 1704, 1601, 1513, 1513, 1496, 1429, 1341, 1313, 1282, 1266, 1182, 1112, 1083, 1013, 870, 767, 742, 702, 689, 578 cm−1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C22H21NO2Na 354.1465; found 354.1463. N-(2-Phenyl-1-(4-(trifluoromethyl)phenyl)ethyl)aniline (3oa): According to general procedure A, 3oa was obtained as a colorless sticky oil (30.7 mg, 90%) from imine 1o and 4-alkyl-1,4-dihydropyridine 2a. 1 H NMR (400 MHz, CDCl3) δ 7.55 (d, J = 8.1 Hz, 2H), 7.42 (d, J = 8.1 Hz, 2H), 7.31−7.21 (m, 3H), 7.12−7.08 (m, 2H), 7.08−7.02 (m, 2H), 6.69−6.60 (m, 1H), 6.43−6.39 (m, 2H), 4.63 (dd, J = 8.2, 5.8 Hz, 1H), 4.14 (s, 1H), 3.11 (dd, J = 14.0, 5.8 Hz, 1H), 3.00 (dd, J = 14.0, 8.2 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 147.7, 146.8, 137.0, 129.4 (q, J = 32.1 Hz), 129.2, 129.1, 128.7, 127.0, 126.8, 125.6 (q, J = 3.7 Hz), 124.2 (q, J = 270.2 Hz), 118.0, 113.7, 59.0, 45.0; IR (KBr): 3412, 3054, 3027, 2921, 2852, 1618, 1600, 1502, 1418, 1321, 1262, 1161, 1115, 1064, 1015, 868, 834, 747, 733, 691, 608, 525 cm−1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C21H19F3N 342.1464; found 342.1457. N-(1-(3-Methoxyphenyl)-2-phenylethyl)aniline (3pa): According to general procedure A, 3pa was obtained as a colorless sticky oil (27.5 mg, 91%) from imine 1p and 4-alkyl-1,4-dihydropyridine 2a. 1H NMR (400 MHz, CDCl3) δ 7.29−7.19 (m, 4H), 7.14−7.11 (m, 2H), 7.06− 7.02 (m, 2H), 6.94−6.90 (m, 1H), 6.87−6.85 (m, 1H), 6.81−6.72 (m, 1H), 6.65−6.59 (m, 1H), 6.48−6.44 (m, 2H), 4.54 (dd, J = 8.2, 5.7 Hz, 1H), 4.09 (s, 1H), 3.74 (s, 3H), 3.12 (dd, J = 14.0, 5.7 Hz, 1H), 2.99 (dd, J = 14.0, 8.3 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 159.9, 147.3, 145.4, 137.7, 129.6, 129.2, 129.0, 128.6, 126.8, 118.8, 117.5, 113.7, 112.4, 112.1, 59.3, 55.2, 45.1; IR (KBr): 3404, 3051, 3024, 2918, 2833, 1598, 1502, 1452, 1430, 1313, 1251, 1150, 1042, 993, 868, 779, 747, 691, 505 cm−1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C21H22NO 304.1696; found 304.1686. N-(1-(2-Methoxyphenyl)-2-phenylethyl)aniline (3qa): According to general procedure A, 3qa was obtained as a colorless sticky oil (29.3

mg, 97%) from imine 1q and 4-alkyl-1,4-dihydropyridine 2a. 1H NMR (400 MHz, CDCl3) δ 7.27−7.17 (m, 5H), 7.16−7.12 (m, 2H), 7.06− 7.00 (m, 2H), 6.91−6.87 (m, 1H), 6.87−6.82 (m, 1H), 6.64−6.54 (m, 1H), 6.47−6.43 (m, 2H), 4.99 (dd, J = 8.2, 5.1 Hz, 1H), 4.18 (s, 1H), 3.87 (s, 3H), 3.21 (dd, J = 13.9, 5.1 Hz, 1H), 2.88 (dd, J = 13.9, 8.2 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 156.8, 147.4, 138.6, 130.9, 129.2, 129.0, 128.4, 127.9, 127.2, 126.4, 120.7, 117.2, 113.5, 110.5, 55.4, 53.7, 42.7; IR (KBr): 3420, 3026, 2920, 2830, 1598, 1504, 1487, 1453, 1424, 1312, 1264, 1236, 1184, 1159, 1124, 1087, 1071, 1023, 993, 810, 744, 692, 504 cm−1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C21H21NONa 326.1515; found 326.1521. N-(1-(Naphthalen-2-yl)-2-phenylethyl)aniline (3ra): According to general procedure A, 3ra was obtained as a green solid (30.1 mg, 93%) from imine 1r and 4-alkyl-1,4-dihydropyridine 2a. mp 99−100 °C; 1H NMR (400 MHz, CDCl3) δ 7.83−7.73 (m, 4H), 7.50−7.39 (m, 3H), 7.28−7.19 (m, 3H), 7.16−7.12 (m, 2H), 7.05−6.99 (m, 2H), 6.64− 6.57 (m, 1H), 6.51−6.46 (m, 2H), 4.74 (dd, J = 8.3, 5.6 Hz, 1H), 4.19 (s, 1H), 3.22 (dd, J = 14.0, 5.6 Hz, 1H), 3.07 (dd, J = 14.0, 8.3 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 147.3, 141.1, 137.6, 133.6, 132.9, 129.3, 129.1, 128.6, 128.4, 127.9, 127.7, 126.8, 126.0, 125.6, 125.2, 124.8, 117.6, 113.8, 59.5, 45.2; IR (KBr): 3393, 2998, 2921, 2907, 2820, 1599, 1501, 1452, 1424, 1371, 1311, 1262, 1183, 1155, 1125, 1093, 1081, 962, 871, 810, 748, 723, 692, 506 cm−1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C24H21NNa 346.1566; found 346.1563. N-(2-Phenyl-1-(pyridin-4-yl)ethyl)aniline (3sa): 20 According to general procedure A, 3sa was obtained as a colorless sticky oil (20.3 mg, 74%) from imine 1s and 4-alkyl-1,4-dihydropyridine 2a. 1H NMR (400 MHz, CDCl3) δ 8.54−8.50 (m, 2H), 7.31−7.22 (m, 5H), 7.11− 7.03 (m, 4H), 6.73−6.60 (m, 1H), 6.42−6.38 (m, 2H), 4.59−4.54 (m, 1H), 4.13 (s, 1H), 3.11 (dd, J = 13.9, 5.9 Hz, 1H), 3.02 (dd, J = 13.9, 8.0 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 152.6, 150.1, 146.6, 136.6, 129.20, 129.16, 128.8, 127.1, 121.8, 118.1, 113.6, 58.4, 44.4. N-(2-Phenyl-1-(thiophen-3-yl)ethyl)aniline (3ta): According to general procedure A, 3ta was obtained as a colorless sticky oil (20.3 mg, 73%) from imine 1t and 4-alkyl-1,4-dihydropyridine 2a. 1H NMR (400 MHz, CDCl3) δ 7.28−7.19 (m, 4H), 7.12−7.06 (m, 4H), 7.04− 6.96 (m, 2H), 6.69−6.61 (m, 1H), 6.54−6.49 (m, 2H), 4.73 (t, J = 6.7 Hz, 1H), 4.03 (s, 1H), 3.17−3.06 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 147.2, 144.6, 137.6, 129.3, 129.1, 128.5, 126.7, 126.2, 126.0, 121.0, 117.6, 113.6, 55.2, 43.9; IR (KBr): 3404, 3053, 3024, 2919, 2851, 1599, 1499, 1452, 1428, 1312, 1252, 1179, 1096, 1075, 1029, 843, 778, 746, 690, 655, 506 cm−1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C18H18NS 280.1154; found 280.1152. 4-Methoxy-N-(2-(4-methoxyphenyl)-1-phenylethyl)aniline (3ab): According to general procedure A, 3ab was obtained as a colorless sticky oil (26.7 mg, 80%) from imine 1a and 4-alkyl-1,4dihydropyridine 2b. 1H NMR (400 MHz, CDCl3) δ 7.34−7.26 (m, 4H), 7.24−7.20 (m, 1H), 7.05−7.00 (m, 2H), 6.84−6.76 (m, 2H), 6.69−6.59 (m, 2H), 6.43−6.38 (m, 2H), 4.45 (dd, J = 8.2, 5.6 Hz, 1H), 3.86 (s, 1H), 3.77 (s, 3H), 3.65 (s, 3H), 3.05 (dd, J = 14.0, 5.6 Hz, 1H), 2.92 (dd, J = 14.0, 8.2 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 158.4, 152.1, 143.8, 141.6, 130.2, 129.8, 128.5, 127.0, 126.5, 114.9, 114.7, 113.9, 60.2, 55.7, 55.3, 44.4; IR (KBr): 3375, 3001, 2922, 2829, 1725, 1508, 1452, 1437, 1298, 1285, 1244, 1229, 1172, 1098, 1029, 835, 816, 760, 735, 699, 613, 563, 522 cm−1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C22H24NO2 334.1802; found 334.1804. N-(2-(4-Fluorophenyl)-1-phenylethyl)-4-methoxyaniline (3ac): 21 According to general procedure A, 3ac was obtained as a colorless sticky oil (21.6 mg, 67%) from imine 1a and 4-alkyl-1,4dihydropyridine 2c. 1H NMR (400 MHz, CDCl3) δ 7.31−7.25 (m, 4H), 7.24−7.20 (m, 1H), 7.06−7.00 (m, 2H), 6.97−6.90 (m, 2H), 6.69−6.61 (m, 2H), 6.44−6.40 (m, 2H), 4.47 (dd, J = 7.7, 6.1 Hz, 1H), 3.83 (s, 1H), 3.66 (s, 3H), 3.06 (dd, J = 14.0, 6.1 Hz, 1H), 2.99 (dd, J = 13.9, 7.7 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 161.7 (d, J = 243.3 Hz), 152.2, 143.3, 141.4, 133.5 (d, J = 3.2 Hz), 130.7 (d, J = 7.8 Hz), 128.6, 127.1, 126.5, 115.3 (d, J = 20.9 Hz), 114.9, 114.7, 60.2, 55.7, 44.3. 4-Methoxy-N-(1-phenyl-2-(m-tolyl)ethyl)aniline (3ad): According to general procedure A, 3ad was obtained as a colorless sticky oil (30.0 10001

DOI: 10.1021/acs.joc.7b01425 J. Org. Chem. 2017, 82, 9995−10006

Article

The Journal of Organic Chemistry mg, 95%) from imine 1a and 4-alkyl-1,4-dihydropyridine 2d. 1H NMR (400 MHz, CDCl3) δ 7.41−7.26 (m, 4H), 7.24−7.20 (m, 1H), 7.18− 7.13 (m, 1H), 7.06−7.00 (m, 1H), 6.99−6.89 (m, 2H), 6.68−6.59 (m, 2H), 6.43−6.37 (m, 2H), 4.48 (dd, J = 8.6, 5.3 Hz, 1H), 3.65 (s, 3H), 3.08 (dd, J = 13.9, 5.3 Hz, 1H), 2.91 (dd, J = 13.9, 8.6 Hz, 1H), 2.30 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 152.1, 143.9, 141.6, 138.2, 137.8, 130.0, 128.6, 128.5, 127.5, 127.0, 126.5, 126.2, 115.0, 114.6, 60.1, 55.7, 45.4, 21.5; IR (KBr): 3341, 3058, 3026, 1696, 1609, 1597, 1468, 1376, 1317, 1266, 1225, 1123, 1087, 793, 765, 744, 731, 689, 574 cm−1. N-(2-(3-Fluorophenyl)-1-phenylethyl)-4-methoxyaniline (3ae): According to general procedure A, 3ae was obtained as a colorless sticky oil (22.8 mg, 71%) from imine 1a and 4-alkyl-1,4dihydropyridine 2e. 1H NMR (400 MHz, CDCl3) δ 7.39−7.27 (m, 4H), 7.27−7.18 (m, 2H), 6.96−6.85 (m, 2H), 6.84−6.76 (m, 1H), 6.72−6.59 (m, 2H), 6.53−6.37 (m, 2H), 4.50 (dd, J = 8.0, 5.9 Hz, 1H), 3.66 (s, 3H), 3.09 (dd, J = 13.9, 5.9 Hz, 1H), 3.00 (dd, J = 13.9, 8.0 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 162.8 (d, J = 244.5 Hz), 152.2, 143.2, 141.2, 140.4 (d, J = 7.3 Hz), 129.9 (d, J = 8.2 Hz), 128.6, 127.2, 126.5, 124.9 (d, J = 3.1 Hz), 116.1 (d, J = 20.9 Hz), 115.0, 114.7, 113.6 (d, J = 20.9 Hz), 60.0, 55.7, 44.8; IR (KBr): 3401, 3028, 2928, 2831, 1601, 1506, 1452, 1293, 1232, 1219, 1034, 816, 742, 698, 519 cm−1. 4-Methoxy-N-(1-phenyl-2-(o-tolyl)ethyl)aniline (3af): According to general procedure A, 3af was obtained as a colorless sticky oil (28.9 mg, 91%) from imine 1a and 4-alkyl-1,4-dihydropyridine 2f. 1H NMR (400 MHz, CDCl3) δ 7.35−7.26 (m, 4H), 7.24−7.20 (m, 1H), 7.19−7.06 (m, 4H), 6.72−6.59 (m, 2H), 6.46−6.37 (m, 2H), 4.49 (dd, J = 8.5, 5.7 Hz, 1H), 3.65 (s, 3H), 3.07 (dd, J = 14.3, 5.7 Hz, 1H), 2.99 (dd, J = 14.3, 8.5 Hz, 1H), 2.23 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 152.1, 144.1, 141.6, 136.8, 136.2, 130.6, 129.6, 128.6, 127.1, 126.8, 126.4, 126.1, 114.9, 114.7, 59.0, 55.7, 42.8, 19.6; IR (KBr): 3348, 3029, 1695, 1620, 1577, 1379, 1325, 1286, 1232, 1123, 1078, 785, 755, 749, 731, 689, 576 cm−1. N-(2-(2-Fluorophenyl)-1-phenylethyl)-4-methoxyaniline (3ag): According to general procedure A, 3ag was obtained as a colorless sticky oil (21.4 mg, 67%) from imine 1a and 4-alkyl-1,4dihydropyridine 2g. 1H NMR (400 MHz, CDCl3) δ 7.37−7.26 (m, 4H), 7.25−7.15 (m, 2H), 7.14−6.95 (m, 3H), 6.71−6.58 (m, 2H), 6.46−6.40 (m, 2H), 4.52 (dd, J = 8.1, 6.0 Hz, 1H), 3.66 (s, 3H), 3.13− 3.02 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 161.4 (d, J = 242.8 Hz), 152.0, 143.6, 141.5, 131.4 (d, J = 4.6 Hz), 128.6, 128.4 (d, J = 8.2 Hz), 127.2, 126.4, 124.1 (d, J = 3.6 Hz), 115.4 (d, J = 22.2 Hz), 114.7, 59.5, 55.7, 38.6; IR (KBr): 3403, 3038, 2924, 2831, 1524, 1438, 1291, 1241, 1223, 1035, 819, 732, 691, 523 cm−1. 4-Methoxy-N-(1-phenyl-2-(thiophen-2-yl)ethyl)aniline (3ah): According to general procedure A, 3ad was obtained as a colorless sticky oil (30.0 mg, 97%) from imine 1a and 4-alkyl-1,4-dihydropyridine 2d. 1 H NMR (400 MHz, CDCl3) δ 7.43−7.21 (m, 5H), 7.12 (dd, J = 5.1, 1.2 Hz, 1H), 6.90 (dd, J = 5.1, 3.4 Hz, 1H), 6.77 (d, J = 3.4 Hz, 1H), 6.72−6.57 (m, 2H), 6.53−6.38 (m, 2H), 4.50 (dd, J = 8.2, 5.4 Hz, 1H), 3.66 (s, 3H), 3.30 (dd, J = 15.0, 5.3 Hz, 1H), 3.22 (dd, J = 15.0, 8.2 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 152.3, 143.2, 141.4, 140.2, 128.7, 127.3, 126.8, 126.5, 126.2, 124.4, 115.1, 114.7, 60.3, 55.7, 39.1; IR (KBr): 3361, 2918, 2848, 1631, 1508, 1463, 1232, 1177, 1033, 816, 753, 518 cm−1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C19H20NOS 310.1260; found 310.1264. 4-Methoxy-N-(2-methyl-1-phenylpropyl)aniline (3ai): 22 According to general procedure A, 3ae was obtained as a colorless sticky oil (21.0 mg, 82%) from imine 1a and 4-alkyl-1,4-dihydropyridine 2e. 1H NMR (400 MHz, CDCl3) δ 7.31 (d, J = 4.3 Hz, 4H), 7.25−7.19 (m, 1H), 6.71−6.66 (m, 2H), 6.49−6.45 (m, 2H), 4.06 (d, J = 5.8 Hz, 1H), 3.88 (s, 1H), 3.69 (s, 3H), 2.03 (td, J = 6.9, 6.0 Hz, 1H), 1.00 (d, J = 6.8 Hz, 3H), 0.93 (d, J = 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 151.7, 142.8, 142.1, 128.2, 127.3, 126.7, 114.8, 114.4, 64.7, 55.8, 34.9, 19.7, 18.7. 4-Methoxy-N-(1,2,2-triphenylethyl)aniline (3aj): According to general procedure A, 3af was obtained as a colorless sticky oil (22.8 mg, 60%) from imine 1a and 4-alkyl-1,4-dihydropyridine 2f. 1H NMR (400 MHz, CDCl3) δ 7.32−7.27 (m, 2H), 7.26−7.22 (m, 3H), 7.15−

7.07 (m, 8H), 7.04−7.01 (m, 2H), 6.66−6.60 (m, 2H), 6.39−6.35 (m, 2H), 4.90 (d, J = 8.8 Hz, 1H), 4.21 (d, J = 8.8 Hz, 1H), 3.92 (s, 1H), 3.66 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 152.1, 142.6, 142.0, 141.5, 140.7, 129.0, 128.7, 128.2, 128.1, 127.5, 127.0, 126.9, 126.4, 62.4, 59.7, 55.7; IR (KBr): 3406, 3022, 2921, 2873, 2849, 1509, 1491, 1449, 1404, 1292, 1276, 1199, 1152, 1029, 1001, 760, 737, 695, 617, 536, 521 cm−1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C27H26NO 380.2009; found 380.2009. N-(1,2-Diphenylpropyl)-4-methoxyaniline (3ak): According to general procedure A, 3ag was obtained as a colorless sticky oil (26.7 mg, 84%, inseparable diastereoisomers 1:1 dr) from imine 1a and 4alkyl-1,4-dihydropyridine 2g. 1H NMR (400 MHz, CDCl3) δ 7.37− 7.29 (m, 6H), 7.26−7.16 (m, 10H), 7.14−7.08 (m, 4H), 6.65−6.61 (m, 2H), 6.61−6.54 (m, 2H), 6.42−6.39 (m, 2H), 6.33−6.29 (m, 2H), 4.45 (d, J = 5.5 Hz, 1H), 4.26 (d, J = 8.5 Hz, 1H), 3.83 (s, 2H), 3.65 (s, 3H), 3.63 (s, 3H), 3.27−3.18 (m, 1H), 3.04−2.93 (m, 1H), 1.33 (d, J = 7.2 Hz, 3H), 1.15 (d, J = 7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 152.0, 151.9, 143.5, 143.1, 142.9, 141.9, 141.8, 141.5, 128.7, 128.3, 128.2, 128.1, 128.0, 127.8, 127.6, 127.5, 127.1, 126.9, 126.8, 126.6, 114.9, 114.8, 114.7, 114.5, 65.0, 64.0, 55.72, 55.69, 47.5, 45.9, 19.7, 16.2; IR (KBr): 3390, 3026, 2962, 2929, 2830, 1508, 1450, 1235, 1177, 1032, 816, 756, 698, 518 cm−1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C22H24NO 318.1852; found 318.1850. N-(2-(Benzyloxy)-1-phenylethyl)-4-methoxyaniline (3al): According to general procedure A, 3al was obtained as a colorless sticky oil (29.1 mg, 87%) from imine 1a and 4-alkyl-1,4-dihydropyridine 2l. 1H NMR (400 MHz, CDCl3) δ 7.41−7.38 (m, 2H), 7.37−7.26 (m, 7H), 7.26−7.22 (m, 1H), 6.69−6.64 (m, 2H), 6.49−6.45 (m, 2H), 4.57 (d, J = 12.0 Hz, 1H), 4.52 (d, J = 12.0 Hz, 1H), 4.47 (dd, J = 8.7, 4.0 Hz, 1H), 3.70 (dd, J = 10.0, 4.0 Hz, 1H), 3.67 (s, 3H), 3.56 (dd, J = 9.9, 8.8 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 152.2, 141.9, 140.9, 137.8, 128.7, 128.5, 127.9, 127.8, 127.4, 126.9, 115.2, 114.6, 74.6, 73.0, 59.0, 55.7; IR (KBr): 3395, 2942, 2831, 1735, 1551, 1449, 1431, 1295, 1282, 1239, 1176, 1098, 845, 827, 758, 745, 689, 643, 542 cm−1. N-(1,2-Diphenylpropan-2-yl)aniline (5aa): According to general procedure A, 5aa was obtained as a colorless sticky oil (23.6 mg, 82%) from imine 4a and 4-alkyl-1,4-dihydropyridine 2a. 1H NMR (400 MHz, CDCl3) δ 7.50−7.43 (m, 2H), 7.36−7.28 (m, 2H), 7.28−7.17 (m, 4H), 7.05−6.96 (m, 2H), 6.96−6.87 (m, 2H), 6.65−6.55 (m, 1H), 6.35−6.23 (m, 2H), 4.05 (s, 1H), 3.27 (d, J = 13.0 Hz, 1H), 3.10 (d, J = 12.9 Hz, 1H), 1.56 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 146.3, 145.9, 136.8, 130.9, 128.8, 128.5, 127.9, 126.7, 126.6, 126.3, 117.1, 115.5, 58.6, 48.4, 26.5; IR (KBr): 3403, 3054, 3025, 2974, 1598, 1493, 1444, 1304, 1257, 1180, 1082, 1028, 994, 911, 873, 766, 746, 551 cm−1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C21H22N 288.1747; found 288.1748. N-(2-(4-Methoxyphenyl)-1-phenylpropan-2-yl)aniline (5ba): According to general procedure A, 5ba was obtained as a colorless sticky oil (19.1 mg, 60%) from imine 4b and 4-alkyl-1,4-dihydropyridine 2a. 1 H NMR (400 MHz, CDCl3) δ 7.39−7.34 (m, 2H), 7.26−7.20 (m, 3H), 7.04−6.98 (m, 2H), 6.96−6.91 (m, 2H), 6.91−6.84 (m, 2H), 6.67−6.58 (m, 1H), 6.36−6.30 (m, 2H), 4.05 (s, 1H), 3.83 (s, 3H), 3.26 (d, J = 12.9 Hz, 1H), 3.09 (d, J = 12.9 Hz, 1H), 1.56 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 158.2, 146.0, 138.3, 136.9, 130.9, 128.7, 127.9, 127.5, 126.6, 117.1, 115.5, 113.7, 58.2, 55.2, 48.7, 26.4; IR (KBr): 3398, 3026, 2926, 2851, 2834, 1599, 1582, 1494, 1453, 1304, 1245, 1176, 1101, 1030, 994, 829, 800, 748, 729, 694, 553, 514 cm−1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C22H23NONa 340.1672; found 340.1667. N-(2-(4-Fluorophenyl)-1-phenylpropan-2-yl)aniline (5ca): According to general procedure A, 5ca was obtained as a colorless sticky oil (21.4 mg, 70%) from imine 4c and 4-alkyl-1,4dihydropyridine 2a. 1H NMR (400 MHz, CDCl3) δ 7.43−7.38 (m, 2H), 7.26−7.21 (m, 3H), 7.07−6.97 (m, 4H), 6.93−6.89 (m, 2H), 6.71−6.56 (m, 1H), 6.32−6.28 (m, 2H), 4.07 (s, 1H), 3.25 (d, J = 12.9 Hz, 1H), 3.08 (d, J = 12.8 Hz, 1H), 1.59 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 161.6 (d, J = 243.5 Hz), 145.7, 141.8 (d, J = 3.3 Hz), 136.4, 130.9, 128.8, 128.04 (d, J = 7.7 Hz), 128.0, 126.8, 117.3, 115.5, 115.2 (d, J = 20.9 Hz), 58.4, 49.0, 26.2; IR (KBr): 3409, 3056, 3026, 2973, 2923, 2850, 1598, 1494, 1453, 1427, 1305, 1257, 1222, 1158, 10002

DOI: 10.1021/acs.joc.7b01425 J. Org. Chem. 2017, 82, 9995−10006

Article

The Journal of Organic Chemistry 1094, 1082, 1030, 1013, 994, 834, 815, 747, 724, 694, 547, 514 cm−1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C21H21FN 306.1653; found 306.1659. N-(1-Phenyl-2-(4-(trifluoromethyl)phenyl)propan-2-yl)aniline (5da): According to general procedure A, 5da was obtained as a colorless sticky oil (24.3 mg, 68%) from imine 4d and 4-alkyl-1,4dihydropyridine 2a. 1H NMR (400 MHz, CDCl3) δ 7.60−7.54 (m, 4H), 7.25−7.21 (m, 3H), 7.04−6.98 (m, 2H), 6.93−6.88 (m, 2H), 6.70−6.60 (m, 1H), 6.28−6.24 (m, 2H), 4.09 (s, 1H), 3.27 (d, J = 12.9 Hz, 1H), 3.09 (d, J = 13.0 Hz, 1H), 1.59 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 150.5, 145.4, 136.1, 130.8, 128.87, 128.86 (q, J = 32.3 Hz),128.1, 126.9, 126.8, 125.5 (q, J = 125.5 Hz), 124.3 (q, J = 270.3 Hz), 117.6, 115.5, 58.7, 48.4, 26.3; IR (KBr): 3410, 3028, 2928, 2854, 1600, 1496, 1454, 1407, 1323, 1257, 1162, 1110, 1083, 1068, 1014, 842, 747, 693, 653, 603, 511 cm−1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C22H21F3N 356.1621; found 356.1628. N-(2-(3-Methoxyphenyl)-1-phenylpropan-2-yl)aniline (5ea): According to general procedure A, 5ea was obtained as a colorless sticky oil (20.2 mg, 64%) from imine 4e and 4-alkyl-1,4-dihydropyridine 2a. 1 H NMR (400 MHz, CDCl3) δ 7.25−7.19 (m, 4H), 7.07−7.04 (m, 1H), 7.03−7.02 (m, 1H), 7.01−6.96 (m, 2H), 6.95−6.91 (m, 2H), 6.84−6.76 (m, 1H), 6.66−6.52 (m, 1H), 6.32−6.28 (m, 2H), 4.03 (s, 1H), 3.74 (s, 3H), 3.26 (d, J = 12.9 Hz, 1H), 3.08 (d, J = 12.9 Hz, 1H), 1.54 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 159.8, 148.3, 145.9, 136.7, 130.9, 129.4, 128.7, 127.9, 126.7, 118.7, 117.2, 115.6, 112.5, 111.6, 58.6, 55.2, 48.3, 26.4; IR (KBr): 3383, 3057, 3024, 2970, 2920, 2850, 1599, 1518, 1488, 1454, 1430, 1305, 1288, 1252, 1170, 1099, 1044, 993, 876, 773, 754, 696, 520 cm−1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C22H23NONa 340.1672; found 340.1670. N-(2-(3-Fluorophenyl)-1-phenylpropan-2-yl)aniline (5fa): According to general procedure A, 5fa was obtained as a colorless sticky oil (25.8 mg, 85%) from imine 4f and 4-alkyl-1,4-dihydropyridine 2a. 1H NMR (400 MHz, CDCl3) δ 7.31−7.21 (m, 5H), 7.20−7.16 (m, 1H), 7.03−6.98 (m, 2H), 6.97−6.90 (m, 3H), 6.70−6.57 (m, 1H), 6.30− 6.27 (m, 2H), 4.05 (s, 1H), 3.25 (d, J = 12.9 Hz, 1H), 3.06 (d, J = 12.9 Hz, 1H), 1.56 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 163.3 (d, J = 243.5 Hz), 149.4 (d, J = 6.2 Hz), 145.6, 136.3, 130.9, 129.9 (d, J = 8.1 Hz), 128.8, 128.0, 126.8, 121.9 (d, J = 2.7 Hz), 117.4, 115.5, 113.6 (d, J = 21.3 Hz), 113.5 (d, J = 21.1 Hz), 58.5 (d, J = 1.9 Hz), 48.5, 26.2; IR (KBr): 3383, 3057, 3026, 2973, 2922, 2850, 1599, 1494, 1453, 1429, 1305, 1254, 1171, 1154, 1084, 1030, 994, 874, 783, 748, 695, 518 cm−1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C21H21FN 306.1653; found 306.1659. N-(1-Phenyl-2-(o-tolyl)propan-2-yl)aniline (5ga): According to general procedure A, 5ga was obtained as a colorless sticky oil (24.4 mg, 81%) from imine 4g and 4-alkyl-1,4-dihydropyridine 2a. 1H NMR (400 MHz, CDCl3) δ 7.32−7.29 (m, 1H), 7.24−7.20 (m, 3H), 7.19− 7.14 (m, 2H), 7.13−7.09 (m, 1H), 6.98−6.93 (m, 4H), 6.63−6.51 (m, 1H), 6.28−6.24 (m, 2H), 3.88 (s, 1H), 3.31 (d, J = 12.8 Hz, 1H), 3.22 (d, J = 12.8 Hz, 1H), 2.55 (s, 3H), 1.65 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 146.2, 143.3, 136.83, 136.77, 133.1, 131.1, 128.9, 127.9, 127.0, 126.9, 126.7, 126.2, 116.9, 114.3, 59.2, 47.0, 26.1, 22.5; IR (KBr): 3410, 3055, 3023, 2972, 2925, 2851, 1598, 1495, 1453, 1426, 1319, 1303, 1257, 1119, 1079, 1030, 993, 907, 746, 725, 692, 509 cm−1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C22H24N 302.1903; found 302.1899. N-(1,2-Diphenylbutan-2-yl)aniline (5ha): According to general procedure A, 5ha was obtained as a colorless sticky oil (26.0 mg, 86%) from imine 4h and 4-alkyl-1,4-dihydropyridine 2a. 1H NMR (400 MHz, CDCl3) δ 7.43−7.38 (m, 2H), 7.33−7.28 (m, 2H), 7.26−7.22 (m, 1H), 7.20−7.13 (m, 3H), 7.04−6.97 (m, 2H), 6.87−6.80 (m, 2H), 6.65−6.57 (m, 1H), 6.35−6.28 (m, 2H), 3.91 (s, 1H), 3.46 (d, J = 13.0 Hz, 1H), 3.19 (d, J = 13.1 Hz, 1H), 1.88 (dt, J = 14.6, 7.3 Hz, 1H), 1.73 (dt, J = 14.4, 7.4 Hz, 1H), 0.80 (t, J = 7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 146.0, 144.6, 137.0, 130.9, 128.8, 128.3, 127.7, 127.0, 126.5, 126.4, 116.8, 115.1, 61.5, 41.0, 31.5, 8.1; IR (KBr): 3413, 3052, 3023, 2970, 2922, 2857, 1597, 1504, 1494, 1453, 1320, 1308, 1257, 1222, 1158, 1083, 1030, 834, 814, 748, 695, 549, 515 cm−1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C22H24N 302.1903; found 302.1899.

N-(1,1,2-Triphenylethyl)aniline (5ia): According to general procedure A, 5ia was obtained as a white solid (33.8 mg, 97%) from imine 4i and 4-alkyl-1,4-dihydropyridine 2a. mp 139−140 °C; 1H NMR (400 MHz, CDCl3) δ 7.46−7.42 (m, 4H), 7.31−7.25 (m, 4H), 7.23− 7.18 (m, 2H), 7.13−7.09 (m, 1H), 7.06−7.00 (m, 2H), 7.00−6.93 (m, 2H), 6.65−6.56 (m, 3H), 6.35−6.31 (m, 2H), 4.55 (s, 1H), 3.81 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 145.8, 145.2, 136.5, 130.9, 128.8, 128.3, 127.7, 127.4, 126.7, 126.6, 117.5, 115.8, 65.3, 44.9; IR (KBr): 3409, 3384, 3054, 3023, 2924, 2851, 1598, 1494, 1453, 1425, 1303, 1256, 1180, 1154, 1079, 1030, 993, 747, 725, 693, 644, 507 cm−1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C26H23NNa 372.1723; found 372.1726. Methyl 2-((4-Methoxyphenyl)amino)-2,3-diphenylpropanoate (5ja): According to general procedure B, 5ja was obtained as a white solid (25.8 mg, 71%) from imine 4j and 4-alkyl-1,4dihydropyridine 2a. mp 100−101 °C; 1H NMR (400 MHz, CDCl3) δ 7.69−7.64 (m, 2H), 7.41−7.36 (m, 2H), 7.34−7.30 (m, 1H), 7.22− 7.17 (m, 3H), 6.93−6.88 (m, 2H), 6.70−6.62 (m, 2H), 6.32−6.27 (m, 2H), 4.93 (s, 1H), 3.84 (d, J = 13.2 Hz, 1H), 3.78 (d, J = 13.1 Hz, 1H), 3.70 (s, 3H), 3.65 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 173.4, 151.7, 140.6, 138.3, 136.0, 130.2, 128.8, 128.0, 127.7, 127.1, 126.9, 116.0, 114.6, 67.5, 55.6, 52.8, 38.2; IR (KBr): 3417, 2991, 2955, 2919, 2849, 1724, 1512, 1494, 1446, 1304, 1254, 1236, 1201, 1180, 1030, 818, 759, 729, 698, 545, 524 cm−1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C23H23NO3Na 384.1570; found 384.1565. 3-Benzyl-1-methyl-3-(phenylamino)indolin-2-one (5ka): According to general procedure B, 5ka was obtained as a white solid (30.9 mg, 94%) from imine 4k and 4-alkyl-1,4-dihydropyridine 2a. mp 144− 146 °C; 1H NMR (400 MHz, CDCl3) δ 7.25−7.21 (m, 2H), 7.14− 7.09 (m, 1H), 7.09−7.01 (m, 3H), 6.97−6.92 (m, 2H), 6.82−6.77 (m, 2H), 6.68−6.55 (m, 2H), 6.25−6.18 (m, 2H), 4.49 (s, 1H), 3.28−3.18 (m, 2H), 2.92 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 177.1, 145.1, 142.8, 133.1, 129.0, 128.9, 127.6, 127.1, 124.0, 122.8, 119.0, 114.9, 108.2, 66.0, 46.7, 26.0; IR (KBr): 3341, 3058, 3026, 1696, 1069, 1597, 1523, 1496, 1468, 1376, 1317, 1225, 1123, 1087, 1017, 913, 866, 793, 765, 744, 731, 698, 689, 672, 574 cm−1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C22H20N2ONa 351.1468; found 351.1470. 1,3-Dibenzyl-3-(phenylamino)indolin-2-one (5la): According to general procedure B, 5la was obtained as a white solid (38.4 mg, 95%) from imine 4l and 4-alkyl-1,4-dihydropyridine 2a. mp 145−146 °C; 1H NMR (400 MHz, CDCl3) δ 7.35 (dd, J = 7.3, 1.3 Hz, 1H), 7.22−7.15 (m, 4H), 7.14−6.99 (m, 4H), 6.99−6.93 (m, 2H), 6.92−6.83 (m, 4H), 6.74−6.65 (m, 1H), 6.46 (d, J = 7.6 Hz, 1H), 6.32−6.24 (m, 2H), 4.81 (d, J = 15.7 Hz, 1H), 4.55−4.45 (m, 2H), 3.38 (d, J = 12.2 Hz, 1H), 3.31 (d, J = 12.2 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 177.2, 145.2, 142.3, 135.3, 133.2, 130.4, 129.1, 129.0, 128.6, 127.9, 127.4, 127.2, 124.2, 122.8, 119.5, 115.8, 109.6, 66.2, 46.4, 43.9; IR (KBr): 3351, 3031, 2920, 2850, 1715, 1599, 1495, 1485, 1453, 1434, 1362, 1319, 1266, 1130, 1028, 969, 792, 746, 728, 514 cm−1; HRMS (ESITOF) m/z: [M + H]+ Calcd for C28H25N2O 405.1961; found 405.1951. 3-Benzyl-5-chloro-1-methyl-3-(phenylamino)indolin-2-one (5ma): According to general procedure B, 5ma was obtained as a white solid (30.4 mg, 84%) from imine 4m and 4-alkyl-1,4dihydropyridine 2a. mp 184−185 °C; 1H NMR (400 MHz, CDCl3) δ 7.26−7.20 (m, 2H), 7.14−7.08 (m, 3H), 7.00−6.96 (m, 2H), 6.83− 6.80 (m, 2H), 6.70−6.65 (m, 1H), 6.51 (d, J = 8.2 Hz, 1H), 6.23−6.19 (m, 2H), 4.47 (s, 1H), 3.23 (s, 2H), 2.91 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 176.6, 144.84, 144.77, 141.6, 141.3, 130.9, 130.14, 130.1, 129.1, 129.0, 128.3, 127.7, 127.4, 124.3, 119.3, 114.7, 109.2, 66.1, 46.7, 26.1; IR (KBr): 3338, 3059, 3027, 2920, 2850, 1696, 1597, 1496, 1485, 1455, 1313, 1265, 1125, 1098, 992, 823, 736, 689, 640, 591, 541, 512 cm−1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C22H19ClN2ONa 385.1078; found 385.1081. 3-Benzyl-1,5-dimethyl-3-(phenylamino)indolin-2-one (5na): According to general procedure B, 5na was obtained as a white solid (30.0 mg, 88%) from imine 4n and 4-alkyl-1,4-dihydropyridine 2a. mp 171−173 °C; 1H NMR (400 MHz, CDCl3) δ 7.14−7.06 (m, 4H), 7.06−7.02 (m, 1H), 6.99−6.94 (m, 2H), 6.83−6.79 (m, 2H), 6.69− 6.60 (m, 1H), 6.50 (d, J = 7.8 Hz, 1H), 6.25−6.20 (m, 2H), 4.48 (s, 10003

DOI: 10.1021/acs.joc.7b01425 J. Org. Chem. 2017, 82, 9995−10006

Article

The Journal of Organic Chemistry

N-(2,3-Diphenylbutan-2-yl)aniline (5ak): According to general procedure A, 5ak was obtained as a colorless sticky oil (28.4 mg, 94%, inseparable diastereoisomers 1:1 dr) from imine 4a and 4-alkyl-1,4dihydropyridine 2k. 1H NMR (400 MHz, CDCl3) δ 7.52−7.49 (m, 2H), 7.36−7.31 (m, 4H), 7.31−7.24 (m, 6H), 7.24−7.20 (m, 6H), 7.02−6.99 (m, 2H), 6.98−6.92 (m, 2H), 6.91−6.86 (m, 2H), 6.61− 6.50 (m, 2H), 6.30−6.26 (m, 2H), 6.14−6.11 (m, 2H), 4.30 (s, 1H), 4.13 (s, 1H), 3.07−3.01 (m, 2H), 1.70 (s, 3H), 1.64 (s, 3H), 1.25 (d, J = 7.2 Hz, 3H), 1.12 (d, J = 7.3 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 146.0, 145.9, 145.4, 143.8, 141.9, 129.6, 129.3, 128.55, 128.53, 128.3, 128.2, 127.9, 127.8, 127.7, 127.4, 127.2, 126.9, 126.6, 126.4, 117.3, 117.0, 115.9, 115.6, 61.2, 61.0, 53.0, 52.8, 22.6, 18.5, 16.0, 15.9; IR (KBr): 3390, 3054, 3023, 2978, 2919, 2849, 1598, 1493, 1445, 1302, 1254, 1079, 1028, 768, 747, 692, 559 cm−1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C22H24N 302.1903; found 302.1909. 3-(4-Methoxybenzyl)-1-methyl-3-(phenylamino)indolin-2-one (5kb): According to general procedure B, 5kb was obtained as a white solid (28.9 mg, 81%) from imine 4k and 4-alkyl-1,4-dihydropyridine 2b. mp 163−164 °C; 1H NMR (400 MHz, CDCl3) δ 7.26−7.21 (m, 2H), 7.07−7.02 (m, 1H), 6.98−6.91 (m, 2H), 6.75−6.70 (m, 2H), 6.68−6.56 (m, 4H), 6.27−6.16 (m, 2H), 4.47 (s, 1H), 3.71 (s, 3H), 3.33−3.04 (m, 2H), 2.96 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 177.2, 158.7, 145.2, 142.8, 131.2, 129.01, 128.99, 125.2, 123.9, 122.7, 118.9, 114.8, 113.0, 108.3, 66.0, 55.2, 45.9, 26.1; IR (KBr): 3401, 3028, 2928, 2831, 1601, 1506, 1463, 1452, 1293, 1232, 1219, 1178, 1157, 1034, 816, 742, 698, 519 cm−1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C23H22N2O2Na 381.1573; found 381.1563. 3-(4-Fluorobenzyl)-1-methyl-3-(phenylamino)indolin-2-one (5kc): According to general procedure B, 5kc was obtained as a white solid (27.6 mg, 80%) from imine 4k and 4-alkyl-1,4-dihydropyridine 2c. mp 198−199 °C; 1H NMR (400 MHz, CDCl3) δ 7.30−7.23 (m, 2H), 7.09−7.04 (m, 1H), 6.99−6.93 (m, 2H), 6.79−6.70 (m, 4H), 6.70−6.56 (m, 2H), 6.28−6.18 (m, 2H), 4.45 (s, 1H), 3.22 (s, 2H), 2.93 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 176.9, 162.0 (d, J = 244.3 Hz), 145.0, 142.8, 131.6 (d, J = 8.0 Hz), 129.2, 129.0, 128.8 (d, J = 3.2 Hz), 123.9, 122.9, 119.2, 115.0, 114.4 (d, J = 21.0 Hz), 108.3, 66.0, 45.8, 26.0; IR (KBr): 3333, 3021, 2918, 2850, 1702, 1599, 1507, 1490, 1463, 1438, 1368, 1309, 1218, 1181, 1156, 1117, 1096, 1082, 1018, 873, 838, 816, 745, 691, 671, 573, 537 cm−1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C22H19FN2ONa 369.1374; found 369.1378. 1-Methyl-3-(phenylamino)-3-(thiophen-2-ylmethyl)indolin-2-one (5kh): According to general procedure B, 5kh was obtained as a white solid (26.5 mg, 79%) from imine 4k and 4-alkyl-1,4-dihydropyridine 2h. mp 142−144 °C; 1H NMR (400 MHz, CDCl3) δ 7.35−7.27 (m, 1H), 7.26−7.21 (m, 1H), 7.13−7.01 (m, 2H), 6.99−6.94 (m, 2H), 6.83−6.78 (m, 1H), 6.74 (d, J = 7.8 Hz, 1H), 6.70−6.58 (m, 2H), 6.28−6.23 (m, 2H), 4.49 (s, 1H), 3.49 (d, J = 13.6 Hz, 1H), 3.43 (d, J = 13.6 Hz, 1H), 3.06 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 177.0, 145.0, 143.3, 134.7, 129.4, 129.0, 128.8, 128.0, 126.3, 125.2, 124.2, 123.0, 119.3, 115.3, 108.4, 65.5, 40.6, 26.2; IR (KBr): 3400, 2928, 2833, 1599, 1496, 1461, 1303, 1246, 1177, 1029, 830, 799, 747, 692, 552, 513 cm−1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C20H19N2OS 335.1213; found 335.1216. 3-Isopropyl-1-methyl-3-(phenylamino)indolin-2-one (5ki): According to general procedure B, 5ki was obtained as a white solid (16.9 mg, 60%) from imine 4k and 4-alkyl-1,4-dihydropyridine 2i. mp 172.1−173.0 °C; 1H NMR (400 MHz, CDCl3) δ 7.38−7.33 (m, 1H), 7.30−7.26 (m, 1H), 7.09−7.04 (m, 1H), 6.96−6.90 (m, 3H), 6.69− 6.58 (m, 1H), 6.21−6.15 (m, 2H), 4.25 (s, 1H), 3.24 (s, 3H), 2.30− 2.23 (m, 1H), 1.15 (d, J = 6.8 Hz, 3H), 0.69 (d, J = 6.7 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 178.3, 145.8, 143.6, 129.02, 129.0, 128.0, 124.9, 122.6, 118.9, 114.9, 108.2, 68.0, 37.4, 26.1, 16.44, 16.38; IR (KBr): 3363, 3054, 3028, 2973, 2926, 1709, 1599, 1494, 1465, 1452, 1317, 1252, 1121, 1072, 1028, 992, 746, 690, 528, 504 cm−1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C18H20N2ONa 303.1468; found 303.1478. 3-Benzhydryl-1-methyl-3-(phenylamino)indolin-2-one (5kj): According to general procedure B, 5kj was obtained as a yellow solid (37.9 mg, 94%) from imine 4k and 4-alkyl-1,4-dihydropyridine 2f. mp 85−86 °C; 1H NMR (400 MHz, CDCl3) δ 7.44−7.39 (m, 2H), 7.32−

1H), 3.24 (d, J = 12.0 Hz, 1H), 3.20 (d, J = 12.1 Hz, 1H), 2.91 (s, 3H), 2.32 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 177.0, 145.2, 140.4, 133.2, 132.3, 130.2, 129.3, 129.0, 128.9, 127.5, 127.1, 124.7, 118.9, 114.7, 108.0, 65.9, 46.8, 26.0, 21.2; IR (KBr): 3332, 3058, 3025, 2919, 2851, 1693, 1597, 1525, 1494, 1315, 1262, 1122, 1091, 910, 821, 742, 724, 689, 652, 549, 512 cm−1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C23H22N2ONa 365.1624; found 365.1632. N-(1-(4-Methoxyphenyl)-2-phenylpropan-2-yl)aniline (5ab): According to general procedure A, 5ab was obtained as a colorless sticky oil (21.6 mg, 68%) from imine 4a and 4-alkyl-1,4-dihydropyridine 2b. 1 H NMR (400 MHz, CDCl3) δ 7.46−7.43 (m, 2H), 7.35−7.29 (m, 2H), 7.27−7.22 (m, 1H), 7.02−6.96 (m, 2H), 6.84−6.81 (m, 2H), 6.79−6.73 (m, 2H), 6.65−6.56 (m, 1H), 6.31−6.27 (m, 2H), 4.05 (s, 1H), 3.78 (s, 3H), 3.20 (d, J = 13.2 Hz, 1H), 3.03 (d, J = 13.2 Hz, 1H), 1.56 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 158.4, 146.3, 145.9, 131.8, 128.7, 128.4, 126.5, 126.3, 117.0, 115.5, 113.3, 58.6, 55.2, 47.8, 26.2; IR (KBr): 3413, 2964, 2921, 2850, 2831, 1597, 1506, 1442, 1310, 1248, 1226, 1175, 1113, 1028, 852, 810, 766, 738, 703, 691, 555, 524, 513 cm−1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C22H24NO 318.1852; found 318.1843. N-(1-(4-Fluorophenyl)-2-(4-methoxyphenyl)propan-2-yl)aniline (5bc): According to general procedure A, 5bc was obtained as a colorless sticky oil (23.0 mg, 69%) from imine 4b and 4-alkyl-1,4dihydropyridine 2c. 1H NMR (400 MHz, CDCl3) δ 7.35−7.30 (m, 2H), 7.04−6.98 (m, 2H), 6.94−6.78 (m, 6H), 6.66−6.59 (m, 1H), 6.34−6.29 (m, 2H), 3.97 (s, 1H), 3.82 (s, 3H), 3.24 (d, J = 13.0 Hz, 1H), 3.07 (d, J = 13.0 Hz, 1H), 1.52 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 161.8 (d, J = 243.3 Hz), 158.2, 145.9, 137.8, 132.5 (d, J = 3.4 Hz), 132.3 (d, J = 7.9 Hz), 128.8, 127.5, 117.2, 115.4, 114.6 (d, J = 20.9 Hz), 113.7, 58.2, 55.2, 47.5, 26.6; IR (KBr): 3397, 2955, 2921, 2850, 1600, 1505, 1462, 1304, 1245, 1220, 1177, 1157, 1104, 1030, 829, 747, 693 cm−1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C22H22FNONa 358.1578; found 358.1575. N-(2-(4-Methoxyphenyl)-1-(thiophen-2-yl)propan-2-yl)aniline (5bh): According to general procedure A, 5bh was obtained as a colorless sticky oil (18.0 mg, 56%) from imine 4b and 4-alkyl-1,4dihydropyridine 2h. 1H NMR (400 MHz, CDCl3) δ 7.44−7.40 (m, 2H), 7.16 (dd, J = 5.2, 1.2 Hz, 1H), 7.05−7.00 (m, 2H), 6.93 (dd, J = 5.1, 3.4 Hz, 1H), 6.91−6.86 (m, 2H), 6.69 (dd, J = 3.4, 1.1 Hz, 1H), 6.66−6.61 (m, 1H), 6.38−6.34 (m, 2H), 4.15 (s, 1H), 3.83 (s, 3H), 3.51 (d, J = 14.3 Hz, 1H), 3.32 (d, J = 14.3 Hz, 1H), 1.60 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 158.3, 145.7, 138.5, 138.1, 128.7, 127.7, 127.4, 126.6, 124.6, 117.3, 115.6, 113.9, 57.9, 55.2, 42.4, 26.9; IR (KBr): 3328, 2921, 2850, 1712, 1602, 1535, 1499, 1468, 1374, 1309, 1258, 1127, 1018, 835, 752, 691, 506 cm−1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C20H22NOS 324.1417; found 324.1417. N-(3-Methyl-2-phenylbutan-2-yl)aniline (5ai): According to general procedure A, 5ai was obtained as a colorless sticky oil (15.0 mg, 63%) from imine 4a and 4-alkyl-1,4-dihydropyridine 2i. 1H NMR (400 MHz, CDCl3) δ 7.45−7.40 (m, 2H), 7.34−7.28 (m, 2H), 7.26−7.18 (m, 1H), 7.04−6.95 (m, 2H), 6.65−6.56 (m, 1H), 6.35−6.29 (m, 2H), 4.06 (s, 1H), 1.94−1.87 (m, 1H), 1.67 (s, 3H), 0.94 (d, J = 6.8 Hz, 3H), 0.82 (d, J = 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 146.2, 144.7, 128.6, 127.9, 127.2, 126.2, 116.8, 115.4, 61.0, 41.2, 20.3, 17.52, 17.48; IR (KBr): 3426, 3053, 2960, 2924, 2874, 1598, 1497, 1445, 1308, 1255, 1222, 1025, 802, 747, 693, 586 cm−1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C17H22N 240.1747; found 240.1755. N-(2-(4-Methoxyphenyl)-1,1-diphenylpropan-2-yl)aniline (5bj): According to general procedure A, 5bj was obtained as a colorless sticky oil (30.8 mg, 78%) from imine 4b and 4-alkyl-1,4dihydropyridine 2j. 1H NMR (400 MHz, CDCl3) δ 7.28−7.25 (m, 2H), 7.24−7.14 (m, 8H), 7.10−7.07 (m, 2H), 7.00−6.92 (m, 2H), 6.80−6.70 (m, 2H), 6.64−6.52 (m, 1H), 6.34−6.24 (m, 2H), 4.43 (s, 1H), 4.23 (s, 1H), 3.79 (s, 3H), 1.87 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 158.2, 145.6, 140.3, 140.0, 136.9, 130.44, 130.40, 129.0, 128.6, 128.2, 128.0, 126.9, 126.7, 117.3, 115.9, 113.0, 67.0, 61.4, 55.2, 23.4; IR (KBr): 3399, 3050, 2924, 2835, 1600, 1505, 1462, 1304, 1245, 1220, 1177, 1157, 1030, 829, 748, 693 cm−1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C28H27NONa 416.1985; found 416.1983. 10004

DOI: 10.1021/acs.joc.7b01425 J. Org. Chem. 2017, 82, 9995−10006

Article

The Journal of Organic Chemistry

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7.27 (m, 2H), 7.24−7.17 (m, 8H), 7.10−7.05 (m, 1H), 6.93−6.87 (m, 2H), 6.65−6.54 (m, 2H), 6.12−6.08 (m, 2H), 4.54 (s, 1H), 4.48 (s, 1H), 2.77 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 176.9, 144.8, 143.8, 137.9, 137.6, 130.1, 129.9, 129.4, 128.9, 128.7, 128.3, 128.1, 127.5, 127.4, 124.8, 122.6, 118.8, 114.8, 108.1, 68.2, 61.9, 25.9; IR (KBr): 3392, 3054, 3026, 2923, 1711, 1599, 1492, 1468, 1450, 1340, 1312, 1250, 1117, 1084, 1031, 745, 689, 630, 586, 534 cm−1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C28H24N2ONa 427.1781; found 427.1777. 1-Methyl-3-(phenylamino)-3-(1-phenylethyl)indolin-2-one (5kk): According to general procedure B, 5kk was obtained as a white solid (30.4 mg, 89%, inseparable diastereoisomers 1:1 dr) from imine 4k and 4-alkyl-1,4-dihydropyridine 2k. mp 124−125 °C; 1H NMR (400 MHz, CDCl3) δ 7.47−7.42 (m, 1H), 7.35−7.27 (m, 5H), 7.17−7.09 (m, 4H), 7.08−7.03 (m, 2H), 6.98−6.88 (m, 5H), 6.85−6.79 (m, 2H), 6.74−6.69 (m, 2H), 6.66−6.62 (m, 1H), 6.61−6.55 (m, 2H), 6.24− 6.19 (m, 2H), 6.13−6.08 (m, 2H), 4.43 (s, 1H), 4.38 (s, 1H), 3.46− 3.36 (m, 2H), 3.24 (s, 3H), 2.70 (s, 3H), 1.56 (d, J = 7.2 Hz, 3H), 1.19 (d, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 177.7, 177.3, 145.6, 144.9, 143.7, 143.5, 139.5, 138.7, 129.3, 129.2, 129.1, 129.0, 128.9, 128.5, 128.1, 127.7, 127.43, 127.37, 127.27, 125.5, 124.8, 122.33, 122.30, 119.0, 118.8, 115.0, 114.7, 108.2, 108.0, 68.7, 67.4, 48.7, 47.8, 26.3, 25.6, 14.7, 14.4; IR (KBr): 3356, 3084, 3054, 3026, 2975, 2933, 1708, 1598, 1493, 1451, 1315, 1253, 1121, 1029, 769, 692, 562, 530 cm−1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C23H22N2ONa 365.1624; found 365.1632. N2,N3-Diphenyl-2,3-bis(4-(trifluoromethyl)phenyl)butane-2,3-diamine (7): According to general procedure B, 7 was obtained as colorless sticky oil (6.4 mg, 24%) from imine 4d. 1H NMR (400 MHz, acetone-d6) δ 7.53−7.46 (m, 4H), 7.39−7.20 (m, 4H), 6.96−6.91 (m, 4H), 6.61−6.55 (m, 2H), 6.36 (d, J = 8.1 Hz, 4H), 5.42 (s, 2H), 2.81 (s, 6H); 13C NMR (100 MHz, acetone-d6) δ 145.8, 145.5, 135.9, 129.9, 128.6 (q, J = 31.7 Hz), 128.3, 124.5 (q, J = 269.8 Hz) 123.9 (q, J = 3.5 Hz), 117.7, 116.5, 65.7, 18.9.; IR (KBr): 3377, 3000, 2919, 2850, 1715, 1631, 1599, 1468, 1408, 1324, 1162, 1121, 1094, 1070, 1012, 859, 842, 753, 718, 697, 613, 584 cm−1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C30H27F6N2 529.2073; found 529.2068.

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ASSOCIATED CONTENT

* Supporting Information S

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.7b01425. Copies of NMR spectra (PDF)

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Shouyun Yu: 0000-0003-4292-4714 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We thank the National Natural Science Foundation of China (21472084, 21672098, and 81421091) for supporting this research.

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REFERENCES

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