Radical alkylation of imines with 4-alkyl-1,4-dihydropyridines enabled by photoredox/br?nsted acid cocatalysis

Article abstract of DOI:10.1021/acs.joc.7b01425

Radical alkylation of imines with 4-alkyl-1,4-dihydropyridines cocatalyzed by iridium/ruthenium complex and Br?nsted 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.

Full text of DOI:10.1021/acs.joc.7b01425

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Article
Radical Alkylation of Imines with 4-Alkyl-1,4-dihydropyridines
Enabled by Photoredox/Brønsted Acid Co-catalysis
Hong-Hao Zhang, and Shouyun Yu
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b01425 • Publication Date (Web): 21 Aug 2017
Downloaded from http://pubs.acs.org on August 22, 2017
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Radical Alkylation of Imines with 4-Alkyl-1,4-
dihydropyridines Enabled by Photoredox/Brønsted Acid Co-
catalysis
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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)
KEYWORDS: photoredox catalysis • alkylation • imines • photochemistry
ABSTRACT: Radical alkylation of imines with 4ꢀalkylꢀ1,4ꢀdihydropyridines coꢀcatalyzed by
iridium 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 stuctrually diverse amines (57 examples) have been produced with up to 98%
isolated yields using this method.
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INTRODUCTION
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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 CꢀC bond formation.2
There are two reaction modes wellꢀestablished for the alkylation of imines (Scheme 1a). One is
the direct addition of carbonꢀcentered nucleophiles,3 such as organometallic reagents, to 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 radicalꢀbased transformations
(Scheme 1a, bottom).4 Classical radicalꢀbased methods usually require organoborane reagents5 or
strong reductants6, such as an alkali metal, titanium and samarium reagents, to generate radical
species. These radical generators are also moistureꢀ or oxygenꢀsensitive.
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Visibleꢀlight photoredox catalysis, which takes advantage of the redox potential of the
photocatalyst under irradiation, has emerged as a powerful tool to promote singleꢀelectron
transfer processes.7 Recently, photoredoxꢀcatalyzed radical alkylation of imines has been
reported, which is an elegant complementary approach to classical radicalꢀbased methods
(Scheme 1b).8 Mechanistically, αꢀaminoalkyl radicals or radical anions generated from imines by
photoredox catalysis couple with another radical species to give the desired functionalized
amines. Aldimines and αꢀheteroatomꢀstabilized radicals are suitable coupling partners.8aꢀ8f
However, ketimines8g and nonfunctionalized radical9 coupling partners are challenging
substrates.
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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,
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Recently, as demonstrated by Nishibayashi,12a, 12b Cheng12c and Molander,12d 4ꢀalkylꢀ1,4ꢀ
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dihydropyridines were used as alkylation reagents to couple with aryl halides, cyanoarenes and
αꢀbromoketones under photoredox catalysis. Tang and coꢀworkers reported a Lewis acidꢀ
catalyzed alkyl transfer reactions of 4ꢀalkylꢀ1,4ꢀdihydropyridines to aldimines at elevated
temperature.13 Inspired by these works, as well as our continuing research interest on photoredox
catalysis,14 we present herein our efforts on photoredox and Brønsted acid coꢀcatalyzed radical
alkylation of aldimines and ketimines with 4ꢀalkylꢀ1,4ꢀdihydropyridines under visible light
irradiation (Scheme 1c).
Scheme 1. Profile of Alkylation of Imines
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RESULTS AND DISCUSSION
We started our investigation using aldimine 1a and 4ꢀbenzylꢀ1,4ꢀdihydropyridine 2a as the
model substrates (see Table S1 in the 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 strips for 48 h in the presence of
photocatalyst Ir(ppy)2(dtbbpy)PF6 (I, 2 mol %), the desired αꢀbranched 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 2ꢀ5). Benzoic acid showed the highest
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activity in terms of the yield (71%, entry 2). Several other photocatalysts, such as facꢀIr(ppy)3
(II), 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 8ꢀ11). It was found that CH3CN was the most
suitable solvent for this reaction with 86% GC yield (entry 11). In order 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).
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Table 1. Optimization of the Aldimine Alkylation Reactiona
entry
solvent
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
dioxane
DMF
PC
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acid
ꢀ
yield (%)b
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PhCO2H
CH3CO2H
TsOH
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I
H3PO4
I
PhCO2H
PhCO2H
PhCO2H
PhCO2H
II
III
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I
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MeOH
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
PhCO2H
PhCO2H
PhCO2H
PhCO2H
PhCO2H
PhCO2H
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12c
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98 (93e)
N. R.
N. R.
aReaction 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
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white LED strips for 48 h. GC yields. 2a (0.15 mmol, 1.5 equiv) was used. 1 mol %
photocatalyst I was used. eIsolated yield. No visible light irradiation. PMP = paraꢀ
f
methoxyphenyl.
After determining the optimized conditions, we investigated the scope and limitations of this
protocol, as shown in Scheme 2. Various Nꢀaryl aldimines were alkylated with 4ꢀbenzylꢀ1,4ꢀ
dihydropyridine 2a. This protocol was applicable to a wide range of Nꢀaryl aldimines to give
products 3aa-3ha in good yields (50–98%). Nꢀaryl aldimines with electronꢀneutral and ꢀdonating
substituents on Nꢀaryl group gave the excellent yields while electronꢀdeficient Nꢀaryl aldimine
was less reactive in this reaction (50% yield for 3ea). Metaꢀsubstituted Nꢀaryl aldimine could go
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through this transformation smoothly (93% yield for 3ga) and orthoꢀsubstituted Nꢀaryl aldimine
was less reactive substrate (76% yield for 3ha). Aldimines derived from different functionalized
benzaldehydes with 4ꢀmethoxyaniline were then coupled with 4ꢀbenzylꢀ1,4ꢀdihydropyridine 2a.
Remarkable functional group tolerance was observed. Common functional groups, such as
hydroxyl groups (3la), ester (3na), amide (3ja), ether (3ia, 3pa and 3qa), cynide (3ma), and
heterocyles (3sa and 3ta), could be tolerated in this reaction.
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Scheme 2. Substrate Scope of Aldiminesa,b
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aReaction 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.
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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 newlyꢀestablished conditions were amenable to ketimines (Scheme 3). A variety
of ketimines derived from aryl ketones with 4ꢀmethoxyaniline could be alkylated with 4ꢀbenzylꢀ
1,4ꢀdihydropyridine 2a to give structurally diverse and sterically hindered amine 5aaꢀ5ia in 64ꢀ
98% 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, isatinꢀderived ketimines could be also alkylated with 2a to
deliver the corresponding 3ꢀaminooxindoles 5kaꢀ5na, which are privileged building blocks in
the synthesis of heterocycles with potential bioactivities,15 in 84%ꢀ95% yields.
Scheme 3. Substrate Scope of Ketiminesa,b
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aReaction 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.
For the aim to show the utility of this visibleꢀlightꢀpromoted 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 conditions, comparative isolated
yields of 3aa (80%, 1.21 g) and 5ka (82%, 1.35 g) were obtained.
Scheme 4. Gram-Scale Preparation of 3aa and 5ka.
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We next performed reactions of imines with various 4ꢀalkylꢀ1,4ꢀdihydropyridines. As
indicated in Scheme 5, this protocol was amenable to substrates 2bꢀ2g bearing benzyl groups
with either electronꢀdonating or electronꢀwithdrawing 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. αꢀHeteroatomꢀ
stabilized (benzyloxy)methyl radical formed from dihydropyridine 2l could also be transfered
efficiently, giving the product 3al in 87% yield.
Scheme 5. Substrate Scope of 4-Alkylated-1,4-Dihydropyridinesa
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aThe 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.
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 TEMPOꢀtrapped product 612aꢀ12c could be observed by highꢀ
resolution mass spectrometry (Scheme 6a), which suggested that this reaction involves a single
electronꢀtransfer (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 byꢀproduct 7 (24%
yield, Scheme 6b). It is envisaged that byꢀproduct 7 is generated by dimerization of αꢀaminoalkyl
radical A.8c
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Scheme 6. Control Experiments
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Stern–Volmer quenching experiments showed that
a
significant quenching of
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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.
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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).
Based on these observations, a plausible mechanism for this radical alkylation reaction is
2+
proposed. As shown in Scheme 7, an excitedꢀstate photocatalyst *Ru(bpy)3 is formed by the
absorption of visible light, which is reductively quenched by 4ꢀalkylꢀ1,4ꢀdihydropyridine to give
the corresponding alkyl radical 9, pyridine 8 and Ru(bpy)3+.12b, 12c The alkyl radical 9 adds to the
+
imine to give Nꢀcentered 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, 8f , 9
+
Alternatively, imine is reduced with the assistance of a proton by Ru(bpy)3 to give αꢀaminoalkyl
radical 11.16 The coupling of radical 11 with 9 gives the final product (pathway B).8aꢀ8d, 8gꢀ8i The
observation of the dimer of αꢀaminoalkyl radical 118c (Scheme 6b) suggests that pathway B
might be the major route. However, pathway A cannot be ruled out completely at this stage.
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Scheme 7. Mechanistic Proposal
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CONCLUSION
In summary, we have established a photoredox and Brønsted acid coꢀcatalyzed radical
alkylation of imines with 4ꢀalkylꢀ1,4ꢀdihydropyridines as the alkylation reagents. Both aldimines
and ketimines can be alkylated with various 4ꢀalkylꢀ1,4ꢀdihydropyridines 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.
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Experimental Section
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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),
signal shapes and splitting patterns are indicated as follows: s, 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 4ꢀalkylꢀ1,4ꢀdihydropyridines (2) were prepared according to the literature
procedure.8
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General Procedure A: A 10.0 mL microwave tube equipped with magnetic stir bar was charged
with imine 1a (0.1 mmol, 22.1 mg), 4ꢀbenzylꢀ1,4ꢀdihydropyridine 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 hours. Upon completion, the reaction mixture was
concentrated under vacuum and the residue was purified by column chromatography (petrol
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, 22.1 mg), 4ꢀbenzylꢀ1,4ꢀdihydropyridine 2a (0.15 mmol, 51.5 mg) and
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Ru(bpy)3Cl2 (III, 0.001 mmol, 0.7 mg) under air. The tube was evacuated and backfilled with N2
for 3 times (3 × 5 min). Trifluoroacetic acid 100 µL (0.1 M methanol solution) and degassed
MeOH (0.9 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 12 hours. Upon completion, the reaction
mixture was concentrated under vacuum and the residue was purified by column
chromatography (petrol ether/EtOAc = 10:1) to give the desired product 5ka (30.9 mg, 94%) as a
white solid.
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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 4ꢀalkylꢀ1,4ꢀdihydropyridine
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 4ꢀalkylꢀ1,4ꢀdihydropyridine
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 4ꢀalkylꢀ1,4ꢀ
o
dihydropyridine 2a. m.p. 145ꢀ146 C; 1H NMR (400 MHz, Acetoneꢀd6) 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),
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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, Acetoneꢀd6) 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.
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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 4ꢀalkylꢀ1,4ꢀdihydropyridine
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,
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J = 14.0, 8.3 Hz, 1H); C 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 4ꢀalkylꢀ1,4ꢀ
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
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(dd, J = 14.1, 8.2 Hz, 1H); C NMR (100 MHz, CDCl3) δ 149.6, 142.4, 137.2, 129.1, 128.74,
128.66, 127.4, 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 cmꢀ1; HRMS (ESIꢀTOF) 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 4ꢀalkylꢀ1,4ꢀdihydropyridine 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
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Hz, 1H), 3.00 (dd, J = 14.0, 8.2 Hz, 1H); C NMR (100 MHz, CDCl3) δ 147.3, 143.5, 137.7,
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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 4ꢀalkylꢀ1,4ꢀdihydropyridine
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),
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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); C
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 cmꢀ1; HRMS (ESIꢀTOF) 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 4ꢀalkylꢀ1,4ꢀdihydropyridine
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,
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1H), 4.53 (t, J = 6.9 Hz, 1H), 3.79 (s, 3H), 3.10 (dd, J = 6.9, 2.3 Hz, 2H); C 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 cmꢀ1; HRMS (ESIꢀ
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 4ꢀalkylꢀ1,4ꢀ
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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.
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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 4ꢀalkylꢀ1,4ꢀ
dihydropyridine 2a. m.p. 157ꢀ158 oC; 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 cmꢀ1; HRMS (ESIꢀ 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 4ꢀalkylꢀ1,4ꢀdihydropyridine
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),
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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); C
NMR (100 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.
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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 4ꢀalkylꢀ1,4ꢀdihydropyridine
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 cmꢀ1; HRMS (ESIꢀ TOF)
m/z: [M+H]+ Calcd for C20H20NO 290.1539; Found 290.1534.
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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 4ꢀalkylꢀ1,4ꢀ
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 cmꢀ1; HRMS (ESIꢀ 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 4ꢀalkylꢀ1,4ꢀ
dihydropyridine 2a. m.p. 102ꢀ103 oC; 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 =
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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 cmꢀ1; HRMS (ESIꢀTOF) m/z:
[M+Na]+ Calcd for C22H21NO2Na 354.1465; Found 354.1463.
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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 4ꢀ
alkylꢀ1,4ꢀdihydropyridine 2a. 1H 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,
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1H), 3.00 (dd, J = 14.0, 8.2 Hz, 1H); C 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 cmꢀ1; HRMS (ESIꢀTOF)
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 4ꢀalkylꢀ1,4ꢀ
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,
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J = 14.0, 5.7 Hz, 1H), 2.99 (dd, J = 14.0, 8.3 Hz, 1H); C 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,
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1042, 993, 868, 779, 747, 691, 505 cmꢀ1; HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd for C21H22NO
304.1696; Found 304.1686.
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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 4ꢀalkylꢀ1,4ꢀ
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 cmꢀ1; HRMS (ESIꢀTOF) m/z: [M+Na]+ Calcd for
C21H21NONa 326.1515; Found 326.1521.
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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 4ꢀalkylꢀ1,4ꢀdihydropyridine 2a.
m.p. 99ꢀ100 oC; 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 cmꢀ1; HRMS (ESIꢀTOF) m/z: [M+Na]+
Calcd for C24H21NNa 346.1566; Found 346.1563.
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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 4ꢀalkylꢀ1,4ꢀdihydropyridine
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.
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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 4ꢀalkylꢀ1,4ꢀdihydropyridine
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 cmꢀ1; HRMS
(ESIꢀTOF) 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 4ꢀ
alkylꢀ1,4ꢀdihydropyridine 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,
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760, 735, 699, 613, 563, 522 cmꢀ1; HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd for C22H24NO2
334.1802; Found 334.1804.
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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 4ꢀ
alkylꢀ1,4ꢀdihydropyridine 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 =
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13.9, 7.7 Hz, 1H); C 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 mg, 95%) from imine 1a and 4ꢀalkylꢀ1,4ꢀ
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 cmꢀ1.
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 4ꢀ
alkylꢀ1,4ꢀdihydropyridine 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
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(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,
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1H); C NMR (100 MHz, CDCl3) δ 162.8 (d, J = 244.5 Hz), 152.2, 143.2, 141.2, 140.4 (d, J =
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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 cmꢀ1.
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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 4ꢀalkylꢀ1,4ꢀ
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 cmꢀ1.
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 4ꢀ
alkylꢀ1,4ꢀdihydropyridine 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,
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1H), 3.66 (s, 3H), 3.13 – 3.02 (m, 2H); C 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 cmꢀ1.
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 4ꢀ
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alkylꢀ1,4ꢀdihydropyridine 2d. 1H 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 cmꢀ1; HRMS (ESIꢀTOF) m/z: [M+H]+
Calcd for C19H20NOS 310.1260; Found 310.1264.
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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 4ꢀalkylꢀ1,4ꢀ
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 4ꢀalkylꢀ1,4ꢀdihydropyridine
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,
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J = 8.8 Hz, 1H), 3.92 (s, 1H), 3.66 (s, 3H); C 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 cmꢀ1; HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd for C27H26NO
380.2009; Found 380.2009.
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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 4ꢀalkylꢀ1,4ꢀdihydropyridine 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 cmꢀ1; HRMS (ESIꢀTOF) m/z:
[M+H]+ Calcd for C22H24NO 318.1852; Found 318.1850.
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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 4ꢀalkylꢀ1,4ꢀ
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
cmꢀ1.
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 4ꢀalkylꢀ1,4ꢀdihydropyridine
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),
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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 cmꢀ1; HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd for C21H22N 288.1747;
Found 288.1748.
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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 4ꢀ
alkylꢀ1,4ꢀdihydropyridine 2a. 1H 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 cmꢀ1; HRMS (ESIꢀTOF) 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 4ꢀalkylꢀ1,4ꢀ
dihydropyridine 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, 1094, 1082, 1030, 1013,
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994, 834, 815, 747, 724, 694, 547, 514 cmꢀ1; HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd for
C21H21FN 306.1653; Found 306.1659.
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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 4ꢀ
alkylꢀ1,4ꢀdihydropyridine 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,
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1H), 3.27 (d, J = 12.9 Hz, 1H), 3.09 (d, J = 13.0 Hz, 1H), 1.59 (s, 3H); C 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 cmꢀ1; HRMS (ESIꢀTOF) 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 4ꢀalkylꢀ1,4ꢀ
dihydropyridine 2a. 1H 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 cmꢀ1; HRMS (ESIꢀTOF) m/z: [M+Na]+ Calcd for
C22H23NONa 340.1672; Found 340.1670.
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