Nickel-Catalyzed Hydroamination of Olefins with Anthranils

Article abstract of DOI:10.1021/acs.joc.1c01430

A nickel-catalyzed polarity-reversed hydroamination of olefins has been achieved with anthranils as the electrophilic aminating agents and hydrosilane as the reductant. This protocol provides a facile access to N-alkyl-2-aminobenzophenones that are versatile intermediates in organic synthesis. A wide range of olefins and anthranils are compatible in this transformation, delivering the desired amines in useful to excellent yields (38 examples, up to 92% yield). The utility of this protocol is exhibited in the late-stage functionalization of drug molecules and the valuable derivatives of the obtained amination products.

Full text of DOI:10.1021/acs.joc.1c01430

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Nickel-Catalyzed Hydroamination of Olefins with Anthranils
Yang Gao,* Yushan Cui, Yanping Huo, Jinhong Chen, Minwei She, Xianwei Li, Qian Chen,
and Xiao-Qiang Hu
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ABSTRACT: A nickel-catalyzed polarity-reversed hydroamination of olefins has been achieved with anthranils as the electrophilic
aminating agents and hydrosilane as the reductant. This protocol provides a facile access to N-alkyl-2-aminobenzophenones that are
versatile intermediates in organic synthesis. A wide range of olefins and anthranils are compatible in this transformation, delivering
the desired amines in useful to excellent yields (38 examples, up to 92% yield). The utility of this protocol is exhibited in the late-
stage functionalization of drug molecules and the valuable derivatives of the obtained amination products.
recently, a similar reaction system was extended to the
hydroamination of 2H-chromenes and 2H-thiochromenes with
anthranils.12 However, in these reactions, the in situ-generated
carbonyl group was completely reduced to benzylic alcohol
because of the high nucleophilicity of the active CuH species.
Moreover, the scope of alkenes is strictly limited to
alkenylarenes in these CuH catalytic systems, which
undoubtedly affect the application of these reactions.
N-Alkyl-2-aminophenones are privileged motifs in bio-
logically active compounds and also versatile intermediates in
organic synthesis.13 Therefore, the further development of a
mild catalytic system that can chemoselectively preserve the
carbonyl group in the hydroamination of alkenes where
anthranils serve as the aminating reagents is highly desirable.
NiH catalysis has received extensive attention as an alternative
tool for hydroamination reactions because of the mild
nucleophilicity, good compatibility, and considerable synthetic
potential in remote functionalization.8,14 We have recently
disclosed NiH-catalyzed cascade hydroamination/cyclization
of alkynes and anthranils for the synthesis of quinolines, in
which the in situ-generated carbonyl group was retained as a
handle for intramolecular cyclization (Scheme 1c).15 As a
continuous work, we herein report our recent progress on
nickel-catalyzed hydroamination of alkenes with anthranils as
INTRODUCTION
■
Given the importance of amines in pharmaceuticals, natural
products, and materials, the development of a new strategy for
the synthesis of high-value amines is an important subject of
research.1 Traditional hydroamination of olefins that refers to
the addition of a N−H unit of nucleophilic amines across a
carbon−carbon double bond has been extensively investigated
for decades as a straightforward route to valuable complex
amines (Scheme 1a, method A).2 In recent years, a polarity-
reversed strategy based on metal hydride catalysis has emerged
as a powerful means for the hydroamination reaction because
of the attractive advantages such as high efficiency, mild
condition, and high regio- and stereoselectivity (Scheme 1a,
method B).3 Buchwald,4 Miura and Hirano,5 and Hartwig et
al.6 have previously established a series of CuH-catalyzed
hydroamination of olefins with different electrophilic aminat-
ing agents to access complex amines. Of note, hydroxylamine
esters are the most commonly used electrophilic nitrogen
sources, which typically serve as alkylamine precursors in these
hydroamination reactions.3−6 Nevertheless, other aminating
reagents that are suitable for this attractive reaction have yet
been well-developed.7 In particular, effective precursors for
aromatic amines are scarce.8
Anthranils are readily available feedstocks and have been
recognized as robust aminating reagents for C−N bond
formation.9 These reagents are often regarded as polarity-
reversed 2-carbonyl anilines in metal-catalyzed (Ni, Co, Cu,
etc.) cross-coupling with organometallic reagents.10 In 2018, Li
et al. successfully employed anthranils in copper-catalyzed
hydroamination of vinylarenes for the synthesis of secondary
arylamines tethered to a benzylic alcohol (Scheme 1b).11 Very
Received: June 17, 2021
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© XXXX American Chemical Society
A

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Scheme 1. Hydroamination of Alkenes and Reaction Design
the aminating reagents for the chemoselective synthesis of N-
alkyl-2-aminophenones (Scheme 1d).
nickel catalyst and hydrosilane were essential for this reaction
(entries 17 and 18).
The scope and limitation of this transformation were then
investigated under the optimized reaction conditions. As
illustrated in Scheme 2, a wide range of vinylarenes bearing
different functional groups such as fluoro (3ab), chloro (3ac),
bromo (3ad), trifluoromethyl (3ae), cyano (3af), acetoxy
(3ag), and methoxy (3aj) are compatible in this hydro-
amination reaction, delivering the corresponding amines in
moderate to good yields (49−81%). 2-Vinylnaphthalene (1k)
and 1-vinylnaphthalene (1l) also took part in the reaction with
a high efficiency. Remarkably, different types of internal
alkenes are suitable substrates. For instance, 1,2-diphenyle-
thene (1m), 1,2-dihydronaphthalene (1n), and 3-phenylprop-
2-en-1-ol (1o) were successfully converted into the desired
amines in 49, 51, and 52% yields, respectively. Electron-
deficient alkenes such as ethyl cinnamate (1p) and ethyl 3-
(thiophen-2-yl)acrylate (1q) are also suitable for this reaction,
affording the valuable β-amino acid ester in good regiose-
lectivity. It should be mentioned that the scope of alkenes is
strictly limited to vinylarenes in the related CuH catalytic
systems.11,12 Notably, aliphatic alkenes such as allylbenzene
(1r), cyclohexene (1s), and trans-4-octene (1t) reacted
smoothly with anthranil 2a in this NiH-catalyzed system.
Significantly, this method was applied in the late-stage
modification of several pharmaceutical derivatives. The alkenes
derived from some drug molecules such as ibuprofen (1u),
RESULTS AND DISCUSSION
■
According to our previous work,15 the initial study was
commenced with styrene 1a and anthranil 2a as the model
substrates in the presence of Ni(BF4)2·6H2O (5 mol %), L1
(5.5 mol %), and Me(OEt)2SiH (2.0 equiv) in N,N-
dimethylacetamide (DMA) at room temperature (Table 1,
entry 1). To our delight, the expected hydroamination product
3aa was detected in 84% yield and only a trace amount of
isomer was detected. The high Markov selectivity in the
formation of 3aa is presumably attributed to the stabilization of
alkylnickel species by an adjacent phenyl group.11 Nickel salts
were found to have significant influence on the outcome, and
changing Ni(BF4)2·6H2O to Ni(OAc)2, NiBr2, or Ni(acac)2·
2H2O gave 3aa in low yields (entries 2−4). The screening of
reaction solvents indicated that this reaction could also
proceed in toluene, N-methyl pyrrolidone (NMP), and N,N-
dimethylformamide (DMF), and the best yield of 3aa was
detected in DMA (entries 5−7). A low yield was obtained
when the reaction was performed in the absence of ligand
(entry 8). Among the tested ligands (entries 9−12), L2 could
improve the yield of 3aa to 92%. Me(OEt)2SiH proved to be
the most efficient hydride source, and other hydrosilanes such
as Ph2SiH2, Et3SiH, PhSiH3, and PMHS result in reduced
yields (entries 13−16). Control experiments indicated that the
B
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a
Table 1. Optimization of Reaction Conditions
b
entry
[Ni]
solvent
ligand
hydrosilane
yield 3aa (%)
1
2
3
4
5
6
7
8
Ni(BF4)2·6H2O
Ni(OAc)2
NiBr2
DMA
DMA
DMA
DMA
toluene
NMP
DMF
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
L1
L1
L1
L1
L1
L1
L1
Me(OEt)2SiH
Me(OEt)2SiH
Me(OEt)2SiH
Me(OEt)2SiH
Me(OEt)2SiH
Me(OEt)2SiH
Me(OEt)2SiH
Me(OEt)2SiH
Me(OEt)2SiH
Me(OEt)2SiH
Me(OEt)2SiH
Me(OEt)2SiH
Ph2SiH2
84
23
12
8
Ni(acac)2·2H2O
Ni(BF4)2·6H2O
Ni(BF4)2·6H2O
Ni(BF4)2·6H2O
Ni(BF4)2·6H2O
Ni(BF4)2·6H2O
Ni(BF4)2·6H2O
Ni(BF4)2·6H2O
Ni(BF4)2·6H2O
Ni(BF4)2·6H2O
Ni(BF4)2·6H2O
Ni(BF4)2·6H2O
Ni(BF4)2·6H2O
74
82
67
21
92 (87)
88
61
81
85
81
71
63
0
c
9
L2
L3
L4
L5
L2
L2
L2
L2
L2
L2
10
11
12
13
14
15
16
17
18
Et3SiH
PhSiH3
PMHS
Me(OEt)2SiH
Ni(BF4)2·6H2O
0
a
Reaction conditions: 1a (0.22 mmol), 2a (0.2 mmol), Ni(BF4)2·6H2O (5 mol %), hydrosilane (2.0 equiv), ligand (5.5 mol %), and solvent (1.0
b
1
mL) under argon at room temperature for 8 h. Yields determined by H NMR spectroscopy using 1,3,5-trimethoxybenzene as the internal
standard. Isolated yield. PMHS refers to polymethylhydrosiloxane.
c
aspirin (1v), and probenecid (1w) smoothly delivered the
value-added complex amines 3au, 3av, and 3aw in good yields.
The success of these reactions demonstrated the synthetic
potential of this methodology in organic chemistry. In
addition, the reaction was conducted on the 5 mmol scale,
and the expected products 3aa (0.91 g) and 3ah (1.1 g) were
isolated in 80 and 78% yields, respectively, without significant
reduction in yields. Unfortunately, 1,1-disubstituted alkenes
such as ethene-1,1-diyldibenzene and prop-1-en-2-ylbenzene
were incompatible under the current conditions probably
because of the steric hindrance of these alkenes.
We next turned our attention to the scope of anthranils in
this new NiH catalytic system. As shown in Scheme 3, various
substituents including F (3ba and 3ca), Cl (3da), Br (3ea),
OMe (3fa), PhO (3ga), allyloxy (3ha), PhCOO (3ia), TsO
(3ja), and acetal (3ka) were well-tolerated, affording the
desired N-alkyl-2-aminobenzaldehydes in good yields (61−
88%). Notably, 3-aryl and alkyl-substituted anthranils could
also take part in this transformation to give the corresponding
N-aryl-2-aminobenzophenones with high efficiency (3oa, 3pa,
and 3qa).
derivative 5 was obtained via the nucleophilic addition of
nBuLi to 3ah, and compound 6 was synthesized via the
reduction of 3ah by NaBH4. N-(1-Phenylethyl)-2-vinylaniline
7 was obtained in 90% yield through the Wittig reaction of 3aa
and MePPh3Br. In addition, 2-phenylquinoline 8 was formed
through cascade oxidation/cyclization of 3aa.16
Control experiments were conducted to understand the
reaction mechanism. First, 2-aminobenzaldehyde 9 was
employed as a substrate in the reaction (Scheme 5a); however,
the desired product 3aa was not detected. This result indicated
that the detected 2-aminobenzaldehyde 9 is a byproduct rather
than an effective intermediate in this reaction. Next, an
isotope-labeling experiment was conducted with the use of
Ph2SiD2 as a reductant (Scheme 5b). As a result, >90%
deuterium incorporation of the amination product D-3aa was
observed, which indicated that a deuterium is provided by silyl
deuteride from the generated NiD species. These results
strongly support a NiH-catalyzed three-component hydro-
amination reaction of alkenes, anthranils, and hydrosilane. The
kinetic profiles were obtained by measuring the initial reaction
rates at different concentrations of the catalyst and reagents
(see Supporting Information for details). The studied reaction
exhibits a first-order dependence on Ni(BF4)2·6H2O and a
zero-order dependence on Me(OEt)2SiH, styrene 1a, and
anthranil 2a. These primary kinetic studies indicate that δ-
bond metathesis of nickel species and Me(OEt)2SiH for the
The synthetic utility of this hydroamination reaction was
then demonstrated by the derivatization of the obtained
amination products. As shown in Scheme 4, the reductive
amination of 3ah with benzylamine afforded the corresponding
diamine product 4 in 88% yield. The related benzyl alcohol
C
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a
Scheme 2. Scope of Olefins
a
Reaction conditions: 1a (0.33 mmol), 2a (0.3 mmol), Ni(BF4)2·6H2O (5 mol %), L2 (5.5 mol %), Me(OEt)2SiH (2.0 equiv), and DMA (1.0 mL)
b
under an argon atmosphere at room temperature for 8 h. Isolated yields were given. 5 mmol scale.
formation of the LNiH catalyst is likely involved in the rate-
determining step.17
scope. The asymmetric catalysis of this hydroamination
reaction and further synthetic applications of this method are
under investigation in our laboratory.
Accordingly, a plausible mechanism is proposed in Scheme
6. Initially, an active LNiH species is in situ-formed from the
reaction of Ni(BF4)2·6H2O, ligand, and Me(OEt)2SiH.14,15
Styrene is then inserted into the Ni−H bond of LNiH species
to afford alkylnickel intermediate A.13 This intermediate goes
through an oxidative insertion into the N−O bond of
anthranils, giving rise to species B and its tautomer C.10,11
Subsequently, intermediate D is formed via the reductive
elimination of B.10,11 Finally, the desired hydroamination
product 3aa is obtained via the proto-demetalation of species
D, and LNiH species is regenerated through the reaction of the
resulting nickel species and Me(OEt)2SiH.15
In conclusion, an efficient nickel-catalyzed three-component
hydroamination reaction of olefins was developed with
anthranils as the electrophilic aminating agents and hyrosilane
as the reductant. A wide range of olefins and anthranils reacted
smoothly to give the valuable N-alkyl-2-aminobenzophenone
and N-alkyl-2-aminobenzaldehyde derivatives in moderate to
good yields. This new protocol features good regioselectivity,
mild reaction conditions, simple operation, and broad substrate
EXPERIMENTAL SECTION
■
General Information. All reactions were performed in oven-dried
glassware containing a Teflon-coated stirring bar. Commercial
substrates were used as received unless otherwise stated. Anthranils
were synthesized according to the reported method and recorded in
our previous work.10,15 Solvents were purchased (puriss p.A.) from
1
commercial suppliers. H NMR spectra were recorded in CDCl3 at
400 MHz. Chemical shifts (δ) are reported in ppm from the
resonance of tetramethyl silane as the internal standard (TMS: 0.00
ppm). Data are reported as follows: chemical shift, multiplicity (s =
singlet, d = doublet, t = triplet, q = quartet, and m = multiplet),
coupling constants (Hz), and integration. 13C NMR spectra were
recorded on 100 MHz with complete proton decoupling spectropho-
tometers. Gas chromatography−mass spectrometry (GC−MS) was
obtained using electron ionization. High-resolution mass spectrom-
etry (HRMS) was carried out on a MAT 95XP (Thermo). Thin-layer
chromatography was performed using commercially prepared 100−
400 mesh silica gel plates (GF254), and visualization was affected at
254 nm.
D
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a
Scheme 3. Scope of Anthranils
a
Reaction conditions: 1 (0.33 mmol), 2 (0.3 mmol), Ni(BF4)2·6H2O (5 mol %), L2 (5.5 mol %), Me(OEt)2SiH (2.0 equiv), and DMA (1.0 mL)
under an argon atmosphere at room temperature for 8 h. Isolated yields were given.
Scheme 4. Synthetic Applications
General Procedure for the Synthesis of Compound 3. An
oven-dried 20 mL vial was charged with Ni(BF4)2·6H2O (5 mol %)
and 4,4′-di-tert-butyl-2,2′-bipyridine (5.5 mol %) and closed with a
septum cap. After it was evacuated and backfilled with argon three
times, DMA (1.0 mL), Me(OEt)2SiH (0.6 mmol), and alkene (0.33
mmol) were successively added via a syringe, and the mixture was
stirred at room temperature for 5 min. Then, anthranil (0.30 mmol)
was added, and the mixture was stirred at room temperature for 8 h
under an argon atmosphere. After completion of the reaction, the
resulting mixture was diluted with 1 M LiCl aqueous solution water
(10 mL). Following phase separation, the aqueous layer was extracted
three times with diethyl ether (5 mL). The combined organic phases
were washed with brine (10 mL), dried over anhydrous MgSO4, and
filtered, and the organic phase was evaporated under reduced pressure
(rotary evaporator). The residue was purified by column chromatog-
raphy (SiO2, ethyl acetate/petroleum ether gradient).
2-((1-Phenylethyl)amino)benzaldehyde (3aa). Purification by
column chromatography on silica gel (PE/EA = 20:1, v/v) afforded
1
3aa as yellow oil (58.7 mg, 87%). H NMR (400 MHz, chloroform-
d): δ 9.84 (s, 1H), 8.71 (s, 1H), 7.42 (dd, J = 7.7, 1.7 Hz, 1H), 7.29
E
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Scheme 5. Mechanistic Study
Scheme 6. Plausible Mechanistic Pathway
1
(d, J = 6.4 Hz, 4H), 7.18 (ddd, J = 8.7, 7.2, 1.7 Hz, 2H), 6.61 (t, J =
7.4 Hz, 1H), 6.42 (d, J = 8.6 Hz, 1H), 4.60−4.58 (m, 1H), 1.57 (d, J
= 6.8 Hz, 3H). 13C{1H} NMR (100 MHz, chloroform-d): δ 194.2,
149.8, 144.4, 136.7, 135.7, 128.8, 127.1, 125.8, 118.6, 115.2, 112.3,
52.7, 24.9. HRMS (ESI) m/z: calcd for C15H16NO [M + H]+,
226.1226; found, 226.1221.
2-((1-(4-Fluorophenyl)ethyl)amino)benzaldehyde (3ab). Purifica-
tion by column chromatography on silica gel (PE/EA = 20:1, v/v)
afforded 3ab as yellow oil (43.8 mg, 60%).1H NMR (400 MHz,
chloroform-d): δ 9.87 (s, 1H), 8.73 (d, J = 5.5 Hz, 1H), 7.48 (dd, J =
7.7, 1.7 Hz, 1H), 7.34−7.27 (m, 2H), 7.27−7.21 (m, 1H), 7.18−6.95
(m, 2H), 6.68 (ddd, J = 7.9, 7.1, 1.0 Hz, 1H), 6.43 (d, J = 8.5 Hz,
1H), 5.09−4.10 (m, 1H), 1.59 (d, J = 6.7 Hz, 3H). 13C{1H} NMR
(100 MHz, chloroform-d): δ 194.3, 161.8 (d, J = 244.9 Hz), 149.6,
140.1 (d, J = 3.1 Hz), 136.7, 135.8, 27.3 (d, J = 8.0 Hz), 118.6, 115.5
(d, J = 37.8 Hz) 115.5, 112.2, 52.0, 25.0. 19F{1H} NMR (375 MHz,
chloroform-d): δ −115.8. HRMS (ESI) m/z: calcd for C15H15FNO
[M + H]+, 244.1132; found, 244.1126.
afforded 3ac as yellow oil (63.0 mg, 81%). H NMR (400 MHz,
chloroform-d): δ 9.87 (s, 1H), 8.71 (d, J = 5.8 Hz, 1H), 7.47 (dd, J =
7.7, 1.7 Hz, 1H), 7.26 (d, J = 2.4 Hz, 3H), 7.24 (d, J = 2.9 Hz, 1H),
7.21 (d, J = 8.6 Hz, 1H), 6.66 (t, J = 7.4 Hz, 1H), 6.39 (d, J = 8.5 Hz,
1H), 5.19−4.37 (m, 1H), 1.57 (d, J = 6.7 Hz, 3H). 13C{1H} NMR
(100 MHz, chloroform-d): δ 194.3, 149.5, 143.0, 136.7, 135.7, 132.7,
129.0, 127.2, 118.7, 115.5, 112.2, 52.1, 24.9. HRMS (ESI) m/z: calcd
for C15H15ClNO [M + H]+, 260.0837; found, 260.0834.
2-((1-(4-Bromophenyl)ethyl)amino)benzaldehyde (3ad). Purifi-
cation by column chromatography on silica gel (PE/EA = 20:1, v/v)
1
afforded 3ad as yellow oil (49.1 mg, 54%). H NMR (400 MHz,
chloroform-d): δ 9.88 (s, 1H), 8.71 (d, J = 5.8 Hz, 1H), 7.48 (dd, J =
7.8, 1.7 Hz, 1H), 7.46−7.42 (m, 2H), 7.25−7.17 (m, 3H), 6.69 (d, J =
7.7 Hz, 1H), 6.39 (d, J = 8.5 Hz, 1H), 4.59−4.57 (m, 1H), 1.58 (d, J
= 6.7 Hz, 3H). 13C{1H} NMR (100 MHz, chloroform-d): δ 194.3,
149.5, 143.6, 136.7, 135.7, 131.9, 127.6, 120.8, 118.7, 115.5, 112.2,
52.2, 24.8. HRMS (ESI) m/z: calcd for C15H15BrNO [M + H]+,
304.0332; found, 304.0327.
2-((1-(4-Chlorophenyl)ethyl)amino)benzaldehyde (3ac). Purifica-
tion by column chromatography on silica gel (PE/EA = 20:1, v/v)
2-((1-(4-(Trifluoromethyl)phenyl)ethyl)amino)benzaldehyde
(3ae). Purification by column chromatography on silica gel (PE/EA =
F
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30:1, v/v) afforded 3ae as yellow oil (58.1 mg, 66%). 1H NMR (400
MHz, chloroform-d): δ 9.89 (s, 1H), 8.74 (d, J = 6.1 Hz, 1H), 7.57
(d, J = 8.1 Hz, 2H), 7.50 (dd, J = 7.7, 1.7 Hz, 1H), 7.44 (d, J = 8.1 Hz,
2H), 7.24−7.21 (m, 1H), 6.85−6.62 (m, 1H), 6.36 (d, J = 8.5 Hz,
1H), 4.90−4.38 (m, 1H), 1.61 (d, J = 6.8 Hz, 3H). 13C{1H} NMR
(100 MHz, chloroform-d): δ 194.4, 149.4, 148.6, 136.7, 135.7, 129.4
(q, J = 32.4 Hz), 126.1, 125.8 (q, J = 3.9 Hz), 124.2 (q, J = 273.3 Hz),
118.7, 115.6, 112.1, 52.4, 24.8. 19F NMR (375 MHz, chloroform-d): δ
−62.4. HRMS (ESI) m/z: calcd for C16H15F3NO [M + H]+,
294.1100; found, 294.1097.
194.3, 149.8, 142.0, 136.6, 135.7, 133.6, 132.8, 128.8, 127.8, 127.7,
126.2, 125.7, 124.3, 124.2, 118.6, 115.3, 112.4, 52.9, 24.9. HRMS
(ESI) m/z: calcd for C17H20NO2 [M + H]+, 276.1383; found,
276.1379.
2-((1-(Naphthalen-1-yl)ethyl)amino)benzaldehyde (3al). Purifi-
cation by column chromatography on silica gel (PE/EA = 20:1, v/v)
1
afforded 3al as a yellow solid (40.4 mg, 49%), mp 125−126 °C. H
NMR (400 MHz, chloroform-d): δ 9.92 (s, 1H), 9.12−8.59 (m, 1H),
8.16 (d, J = 8.4 Hz, 1H), 7.97−7.86 (m, 1H), 7.74 (d, J = 8.2 Hz,
1H), 7.59 (ddd, J = 8.4, 6.8, 1.5 Hz, 1H), 7.55−7.51 (m, 2H), 7.49
(dd, J = 7.8, 1.7 Hz, 1H), 7.42−7.34 (m, 1H), 7.11 (ddd, J = 8.7, 7.1,
1.7 Hz, 1H), 6.63 (ddd, J = 8.0, 7.1, 0.9 Hz, 1H), 6.28 (d, J = 8.5 Hz,
1H), 5.62−4.83 (m, 1H), 1.75 (d, J = 6.7 Hz, 3H). 13C{1H} NMR
(100 MHz, chloroform-d): δ 194.3, 149.6, 139.3, 136.6, 135.7, 134.1,
130.5, 129.3, 127.6, 126.3, 126.0, 125.6, 122.3, 122.2, 118.6, 115.2,
112.4, 48.9, 23.7. HRMS (ESI) m/z: calcd for C19H18NO [M + H]+,
276.1383; found, 276.1374.
4-(1-((2-Formylphenyl)amino)ethyl)benzonitrile (3af). Purifica-
tion by column chromatography on silica gel (PE/EA = 15:1, v/v)
afforded 3af as yellow oil (36.8 mg, 49%). 1H NMR (400 MHz,
chloroform-d): δ 9.89 (s, 1H), 8.73 (d, J = 5.8 Hz, 1H), 7.62 (d, J =
8.3 Hz, 2H), 7.51 (dd, J = 7.7, 1.7 Hz, 1H), 7.44 (d, J = 8.3 Hz, 2H),
7.23 (ddd, J = 8.7, 7.1, 1.7 Hz, 1H), 6.71 (t, J = 7.5 Hz, 1H), 6.30 (d, J
= 8.5 Hz, 1H), 5.13−4.22 (m, 1H), 1.61 (d, J = 6.8 Hz, 3H). 13C{1H}
NMR (100 MHz, chloroform-d): δ 194.4, 150.1, 149.2, 136.8, 135.8,
132.8, 126.6, 118.8, 115.9, 112.0, 111.1, 52.5, 24.6. HRMS (ESI) m/z:
calcd for C16H15N2O [M + H]+, 251.1179; found, 251.1173.
4-(1-((2-Formylphenyl)amino)ethyl)phenyl acetate (3ag). Purifi-
cation by column chromatography on silica gel (PE/EA = 10:1, v/v)
2-((1,2-Diphenylethyl)amino)benzaldehyde (3am). Purification
by column chromatography on silica gel (PE/EA = 20:1, v/v)
1
afforded 3am as yellow oil (38.0 mg, 42%). H NMR (400 MHz,
chloroform-d): δ 9.83 (s, 1H), 8.93 (d, J = 6.0 Hz, 1H), 7.43 (dd, J =
7.8, 1.7 Hz, 1H), 7.30−7.25 (m, 4H), 7.23 (d, J = 4.3 Hz, 2H), 7.20−
7.15 (m, 4H), 6.66−6.58 (m, 1H), 6.41 (d, J = 8.5 Hz, 1H), 4.70 (q, J
= 6.5 Hz, 1H), 3.16 (s, 1H), 3.14 (s, 1H). 13C{1H} NMR (100 MHz,
chloroform-d): δ 194.2, 149.8, 142.6, 137.5, 136.6, 135.6, 129.6,
129.5, 128.7, 128.4, 127.3, 126.7, 126.5, 118.8, 115.3, 112.3, 6.15,
45.2. HRMS (ESI) m/z: calcd for C21H20NO [M + H]+, 302.1539;
found, 302.1533.
2-((1,2,3,4-Tetrahydronaphthalen-1-yl)amino)benzaldehyde
(3an). Purification by column chromatography on silica gel (PE/EA =
20:1, v/v) afforded 3an as yellow oil (38.7 mg, 51%). 1H NMR (400
MHz, chloroform-d): δ 9.82 (s, 1H), 8.66 (s, 1H), 7.50 (d, J = 7.8 Hz,
1H), 7.43 (t, J = 7.0 Hz, 1H), 7.33 (d, J = 8.0 Hz, 1H), 7.24−7.19 (m,
1H), 7.16 (t, J = 7.4 Hz, 2H), 6.90 (d, J = 8.6 Hz, 1H), 6.72 (t, J = 7.4
Hz, 1H), 5.05−4.51 (m, 1H), 2.91 (dt, J = 16.8, 6.1 Hz, 1H), 2.80
(dt, J = 16.8, 6.5 Hz, 1H), 2.09 (ddt, J = 13.4, 9.1, 4.1 Hz, 1H), 2.03−
1.92 (m, 2H), 1.84 (ddd, J = 18.4, 5.8, 3.3 Hz, 1H). 13C{1H} NMR
(100 MHz, chloroform-d): δ 193.9, 150.0, 137.5, 137.1, 137.0, 135.9,
129.2, 128.6, 127.3, 126.3, 118.5, 114.8, 111.1, 50.4, 29.2, 29.2, 20.0.
HRMS (ESI) m/z: calcd for C17H18NO [M + H]+, 252.1383; found,
252.1376.
1
afforded 3ag as yellow oil (67.9 mg, 80%). H NMR (400 MHz,
chloroform-d): δ 9.86 (s, 1H), 8.71 (d, J = 6.0 Hz, 1H), 7.45 (dd, J =
7.7, 1.7 Hz, 1H), 7.32 (d, J = 8.5 Hz, 2H), 7.24−7.18 (m, 1H), 7.13−
6.92 (m, 2H), 6.77−6.58 (m, 1H), 6.43 (d, J = 8.6 Hz, 1H), 4.62−
4.60 (m, 1H), 2.26 (s, 3H), 1.58 (d, J = 6.8 Hz, 3H). 13C{1H} NMR
(100 MHz, chloroform-d): δ 194.3, 169.5, 149.6, 141.9, 136.7, 135.7,
126.8, 121.8, 118.6, 115.3, 112.3, 52.1, 24.9, 21.1. MS (EI) m/z:
C17H17NO3, 283.1 HRMS (ESI) m/z: calcd for C17H18NO3 [M +
H]+, 284.1281; found, 284.1278.
2-((1-(4-(tert-Butyl)phenyl)ethyl)amino)benzaldehyde (3ah). Pu-
rification by column chromatography on silica gel (PE/EA = 30:1, v/
1
v) afforded 3ah as yellow oil (74.2 mg, 88%). H NMR (400 MHz,
chloroform-d): δ 9.86 (s, 1H), 8.73 (d, J = 5.6 Hz, 1H), 7.46 (dd, J =
7.7, 1.5 Hz, 1H), 7.37−7.30 (m, 2H), 7.25−7.18 (m, 3H), 6.67−6.60
(m, 1H), 6.50 (d, J = 8.5 Hz, 1H), 4.97−4.45 (m, 1H), 1.59 (d, J =
6.8 Hz, 3H), 1.30 (s, 9H). 13C{1H} NMR (100 MHz, chloroform-d):
δ 194.1, 149.8, 141.1, 136.6, 135.6, 125.6, 125.3, 118.4, 114.9, 112.2,
52.1, 34.4, 31.3, 24.7. HRMS (ESI) m/z: calcd for C19H24NO [M +
H]+, 282.1852; found, 282.1844.
2-((1-(o-Tolyl)ethyl)amino)benzaldehyde (3ai). Purification by
2-((3-Hydroxy-1-phenylpropyl)amino)benzaldehyde (3ao). Puri-
column chromatography on silica gel (PE/EA = 30:1, v/v) afforded
fication by column chromatography on silica gel (PE/EA = 20:1, v/v)
1
1
3ai as yellow oil (34.4 mg, 48%), mp 108−109 °C. H NMR (400
afforded 3ao as yellow oil (26.0 mg, 34%). H NMR (400 MHz,
MHz, chloroform-d): δ 9.88 (s, 1H), 8.75 (d, J = 5.3 Hz, 1H), 7.47
(dd, J = 7.7, 1.7 Hz, 1H), 7.35−7.30 (m, 1H), 7.24−7.20 (m, 1H),
7.18−7.11 (m, 3H), 6.89−6.56 (m, 1H), 6.29 (d, J = 8.5 Hz, 1H),
5.25−4.38 (m, 1H), 2.46 (s, 3H), 1.56 (d, J = 6.7 Hz, 3H). 13C{1H}
NMR (100 MHz, chloroform-d): δ 194.2, 149.7, 142.1, 136.6, 135.7,
134.3, 130.7, 126.9, 126.8, 124.7, 118.5, 115.1, 112.0, 49.2, 22.9, 19.0.
HRMS (ESI) m/z: calcd for C16H18NO [M + H]+, 240.1383; found,
240.1378.
chloroform-d): δ 9.86 (s, 1H), 8.89 (d, J = 6.6 Hz, 1H), 7.46 (dd, J =
7.8, 1.7 Hz, 1H), 7.37−7.28 (m, 4H), 7.27−7.18 (m, 2H), 6.65 (t, J =
7.4 Hz, 1H), 6.52 (d, J = 8.5 Hz, 1H), 4.75 (q, J = 6.8 Hz, 1H), 3.89−
3.79 (m, 1H), 3.78−3.70 (m, 1H), 2.83−1.43 (m, 2H). 13C{1H}
NMR (100 MHz, chloroform-d): δ 194.3, 149.9, 142.8, 136.6, 135.7,
128.8, 127.2, 126.2, 118.7, 115.3, 112.2, 59.4, 54.1, 41.0. HRMS (ESI)
m/z: calcd for C16H18NO2 [M + H]+, 256.1332; found, 256.1324.
Ethyl 3-((2-Formylphenyl)amino)-3-phenylpropanoate (3ap).
Purification by column chromatography on silica gel (PE/EA =
2-((1-(4-Methoxy-3-methylphenyl)ethyl)amino)benzaldehyde
1
(3aj). Purification by column chromatography on silica gel (PE/EA =
20:1, v/v) afforded 3ap as yellow oil (62.4 mg, 70%). H NMR (400
1
20:1, v/v) afforded 3aj as yellow oil (49.2 mg, 61%). H NMR (400
MHz, chloroform-d): δ 9.87 (s, 1H), 8.96 (s, 1H), 7.47 (d, J = 7.8 Hz,
1H), 7.37 (d, J = 8.5 Hz, 2H), 7.32 (t, J = 7.4 Hz, 2H), 7.26 (q, J =
3.0, 2.2 Hz, 1H), 7.26−7.20 (m, 1H), 6.78−6.63 (m, 1H), 6.56 (d, J =
8.5 Hz, 1H), 5.03 (q, J = 6.1 Hz, 1H), 4.12 (q, J = 7.2 Hz, 2H), 3.25−
2.56 (m, 2H), 1.20 (t, J = 7.1 Hz, 3H). 13C{1H} NMR (100 MHz,
chloroform-d): δ 194.2, 170.6, 149.4, 141.5, 136.6, 135.7, 135.2,
128.9, 127.7, 126.3, 118.9, 116.0, 115.7, 112.1, 60.9, 54.1, 43.3, 14.1.
HRMS (ESI) m/z: calcd for C18H20NO3 [M + H]+, 298.1438; found,
298.1433.
MHz, chloroform-d): δ 9.87 (s, 1H), 8.68 (s, 1H), 7.46 (d, J = 7.7 Hz,
1H), 7.22 (d, J = 7.0 Hz, 1H), 7.11 (d, J = 9.1 Hz, 2H), 6.76 (d, J =
8.1 Hz, 1H), 6.64 (t, J = 7.4 Hz, 1H), 6.50 (d, J = 8.6 Hz, 1H), 4.55−
4.53 (m, 1H), 3.80 (s, 3H), 2.20 (s, 3H), 1.57 (d, J = 6.8 Hz, 3H).
13C{1H} NMR (100 MHz, chloroform-d): δ 194.2, 156.8, 149.9,
136.6, 136.0, 135.7, 128.1, 126.9, 123.9, 118.5, 115.0, 112.3, 110.0,
55.3, 52.1, 25.0, 16.4. HRMS (ESI) m/z: calcd for C17H20NO2 [M +
H]+, 270.1489; found, 270.1485.
2-((1-(Naphthalen-2-yl)ethyl)amino)benzaldehyde (3ak). Purifi-
Methyl 3-((2-Formylphenyl)amino)-3-(thiophen-2-yl)-
propanoate (3aq). Purification by column chromatography on silica
gel (PE/EA = 20:1, v/v) afforded 3aq as a yellow solid (44.2 mg,
cation by column chromatography on silica gel (PE/EA = 20:1, v/v)
1
afforded 3ak as a yellow solid (51.1 mg, 62%), mp 94−95 °C. H
1
NMR (400 MHz, chloroform-d): δ 9.92 (s, 1H), 8.86 (d, J = 5.7 Hz,
1H), 8.07−7.71 (m, 4H), 7.61−7.43 (m, 4H), 7.23−7.12 (m, 1H),
6.65 (t, J = 7.4 Hz, 1H), 6.51 (d, J = 8.5 Hz, 1H), 5.30−4.44 (m, 1H),
1.70 (d, J = 6.8 Hz, 3H). 13C{1H} NMR (100 MHz, chloroform-d): δ
51%) mp 53−55 °C. H NMR (400 MHz, chloroform-d): δ 9.79 (s,
1H), 8.82 (d, J = 7.3 Hz, 1H), 7.42 (dd, J = 7.9, 1.7 Hz, 1H), 7.34−
7.23 (m, 1H), 7.11 (dd, J = 5.0, 1.2 Hz, 1H), 6.93 (d, J = 3.5 Hz, 1H),
6.86 (dd, J = 5.1, 3.5 Hz, 1H), 6.67 (dd, J = 8.3, 5.8 Hz, 2H), 5.27 (q,
G
https://doi.org/10.1021/acs.joc.1c01430
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
J = 7.0 Hz, 1H), 3.62 (s, 3H), 3.20−2.52 (m, 2H). 13C{1H} NMR
(100 MHz, chloroform-d): δ 194.3, 170.7, 149.1, 145.7, 136.7, 135.8,
127.0, 124.6, 124.3, 119.0, 116.1, 111.9, 52.0, 49.8, 43.1. HRMS (ESI)
m/z: calcd for C15H16NO3S [M + H]+, 290.0845; found, 290.0842.
Mixture of 2-((1-Phenylpropan-2-yl)amino)benzaldehyde and 2-
((3-Phenylpropyl)amino)benzaldehyde (3ar). Purification by col-
umn chromatography on silica gel (PE/EA = 30:1, v/v) afforded 3ar
1H), 3.40−2.69 (m, 4H), 1.62 (d, J = 6.6 Hz, 4H), 1.56 (dt, J = 14.8,
7.5 Hz, 3H), 0.88 (t, J = 7.4 Hz, 6H). 13C{1H} NMR (100 MHz,
chloroform-d): δ 194.3, 163.9, 149.6, 149.5, 144.9, 142.5, 136.7,
135.7, 132.8, 130.1, 127.2, 127.0, 121.8, 118.6, 115.4, 112.3, 52.2,
50.0, 25.0, 22.0, 11.2. HRMS (ESI) m/z: calcd for C28H33N2O5S [M
+ H]+, 509.2105; found, 509.2093.
2-((1-(4-tert-Butyl)phenyl)ethyl)amino)-5-fluorobenzaldehyde
1
as yellow oil (62.0 mg, 86%). H NMR (400 MHz, chloroform-d): δ
(3ba). Purification by column chromatography on silica gel (PE/EA =
1
9.80 (s, 1H), 9.77 (s, 1H), 7.44−7.41 (m, 1H), 7.34 (t, J = 7.8 Hz,
1H), 7.27 (t, J = 7.5 Hz, 2H), 7.23−7.17 (m, 3H), 6.73−6.59 (m,
2H), 3.83 (dt, J = 12.9, 6.5 Hz, 1H), 3.21 (t, J = 7.0 Hz, 1H), 2.98
(dd, J = 13.5, 5.7 Hz, 1H), 2.77−2.68 (m, 2H), 2.04−1.94 (m, 1H),
1.22 (d, J = 6.4 Hz, 3H). 13C{1H} NMR (100 MHz, chloroform-d): δ
193.9, 193.8, 150.7, 149.7, 141.2, 138.3, 136.9, 136.6, 135.7, 129.3,
128.4, 128.3, 126.4, 125.9, 118.3, 114.7, 114.6, 111.1, 110.8, 49.1,
42.7, 41.6, 33.1, 30.4, 20.0. HRMS (ESI) m/z: calcd for C16H18NO
[M + H]+, 240.1383; found, 240.1376.
20:1, v/v) afforded 3ba as yellow oil (64.6 mg, 72%). H NMR (400
MHz, chloroform-d): δ 9.79 (s, 1H), 8.56 (d, J = 6.0 Hz, 1H), 7.32
(d, J = 8.4 Hz, 2H), 7.27−7.19 (m, 2H), 7.14 (dd, J = 8.4, 3.1 Hz,
1H), 6.98 (ddd, J = 9.2, 8.0, 3.1 Hz, 1H), 6.43 (dd, J = 9.3, 4.1 Hz,
1H), 4.62−4.48 (m, 1H), 1.57 (d, J = 6.8 Hz, 3H), 1.29 (s, 9H).
13C{1H} NMR (100 MHz, chloroform-d): δ 192.9 (d, J = 2.5 Hz),
153.3 (d, J = 234.7 Hz), 150.0, 146.8, 141.1, 125.7, 125.4, 123.8 (d, J
= 23.2 Hz), 120.3 (d, J = 21.2 Hz), 117.7 (d, J = 5.1 Hz), 113.8 (d, J =
6.5 Hz), 52.6, 34.5, 31.4, 24.9. 19F{1H} NMR (375 MHz, chloroform-
d): δ −130.6. HRMS (ESI) m/z: calcd for C19H23FNO [M + H]+,
300.1758; found, 300.1754.
2-((1-(4-Bromophenyl)ethyl)amino)-5-fluorobenzaldehyde
(3ca). Purification by column chromatography on silica gel (PE/EA =
20:1, v/v) afforded 3ca as yellow oil (55.9 mg, 58%). 1H NMR (400
MHz, chloroform-d): δ 9.81 (s, 1H), 8.54 (d, J = 5.7 Hz, 1H), 7.44
(d, J = 8.6 Hz, 2H), 7.18 (d, J = 8.3 Hz, 3H), 7.00 (t, J = 8.5 Hz, 1H),
6.33 (dd, J = 9.3, 4.1 Hz, 1H), 4.55−4.51 (m, 1H), 1.57 (d, J = 6.7
Hz, 3H). 13C{1H} NMR (100 MHz, chloroform-d): δ 193.0 (d, J =
2.4 Hz), 153.5 (d, J = 235.7 Hz), 146.3, 143.4, 132.0, 127.5, 123.7 (d,
J = 23.1 Hz), 120.9, 120.5 (d, J = 21.3 Hz), 118.0 (d, J = 5.1 Hz),
113.6 (d, J = 6.5 Hz), 52.6, 24.9. 19F{1H} NMR (375 MHz,
chloroform-d): δ −129.8. HRMS (ESI) m/z: calcd for C15H14BrFNO
[M + H]+, 322.0237; found, 322.0232.
2-(Cyclohexylamino)benzaldehyde (3as). Purification by column
chromatography on silica gel (PE/EA = 20:1, v/v) afforded 3as as
1
yellow oil (42.7 mg, 70%). H NMR (400 MHz, chloroform-d): δ
9.79 (s, 1H), 8.39 (s, 1H), 7.43 (dd, J = 7.7, 1.7 Hz, 1H), 7.38−7.30
(m, 1H), 6.70 (d, J = 8.6 Hz, 1H), 6.63 (t, J = 7.4 Hz, 1H), 3.43 (tt, J
= 8.8, 4.0 Hz, 1H), 2.20−1.95 (m, 2H), 1.79 (dd, J = 13.2, 3.8 Hz,
2H), 1.71−1.53 (m, 1H), 1.52−1.24 (m, 5H). 13C{1H} NMR (100
MHz, chloroform-d): δ 193.8, 150.0, 136.9, 135.7, 118.1, 114.3, 111.2,
50.4, 32.7, 25.8, 24.6. HRMS (ESI) m/z: calcd for C13H18NO [M +
H]+, 204.1383; found, 204.1386.
2-(Octan-4-ylamino)benzaldehyde (3at). Purification by column
chromatography on silica gel (PE/EA = 20:1, v/v) afforded 3at as
1
yellow oil (39.2 mg, 56%). H NMR (400 MHz, chloroform-d): δ
9.79 (s, 1H), 8.30 (s, 1H), 7.43 (dd, J = 7.7, 1.7 Hz, 1H), 7.34 (t, J =
7.0 Hz, 1H), 6.69 (d, J = 8.6 Hz, 1H), 6.62 (t, J = 7.4 Hz, 1H), 3.51
(m, J = 12.2, 6.4 Hz, 1H), 1.70−1.51 (m, 4H), 1.44−1.23 (m, 6H),
0.90 (m, J = 10.9, 7.3 Hz, 6H). 13C {1H} NMR (100 MHz,
chloroform-d): δ 193.8, 150.9, 136.9, 135.7, 118.0, 114.0, 111.0, 51.8,
37.1, 34.5, 28.0, 22.8, 19.1, 14.1, 14.0. HRMS (ESI) m/z: calcd for
C15H24NO [M + H]+, 234.1852; found, 234.1849.
4-(1-((2-Formylphenyl)amino)ethyl)phenyl 2-(4-isobutylphenyl)-
propanoate (3au). Purification by column chromatography on silica
gel (PE/EA = 20:1, v/v) afforded 3au as yellow oil (109.4 mg, 85%).
1H NMR (400 MHz, chloroform-d): δ 9.86 (s, 1H), 8.70 (d, J = 5.9
Hz, 1H), 7.46 (dd, J = 7.7, 1.7 Hz, 1H), 7.33−7.25 (m, 4H), 7.24−
7.17 (m, 1H), 7.13 (d, J = 8.0 Hz, 2H), 6.95 (d, J = 8.6 Hz, 2H), 6.65
(t, J = 7.4 Hz, 1H), 6.40 (d, J = 8.5 Hz, 1H), 4.62−4.58 (m, 1H), 3.92
(q, J = 7.1 Hz, 1H), 2.47 (d, J = 7.1 Hz, 2H), 1.86 (dt, J = 13.5, 6.7
Hz, 1H), 1.58 (dd, J = 8.7, 6.9 Hz, 6H), 0.91 (d, J = 6.6 Hz, 6H).
13C{1H} NMR (100 MHz, chloroform-d): δ 194.3, 173.3, 149.8,
149.6, 141.8, 140.8, 137.2, 136.6, 135.7, 129.5, 127.2, 126.6, 121.7,
118.6, 115.3, 112.3, 52.2, 45.3, 45.1, 30.2, 24.9, 22.4, 18.5. HRMS
(ESI) m/z: calcd for C28H32NO3 [M + H]+, 430.2377; found,
430.2364.
5-Chloro-2-((1-phenylethyl)amino)benzaldehyde (3da). Purifica-
tion by column chromatography on silica gel (PE/EA = 20:1, v/v)
1
afforded 3da as yellow oil (58.3 mg, 75%). H NMR (400 MHz,
chloroform-d): δ 9.81 (s, 1H), 8.71 (s, 1H), 7.42 (d, J = 2.5 Hz, 1H),
7.38−7.28 (m, 5H), 7.14 (dd, J = 9.1, 2.6 Hz, 1H), 6.41 (d, J = 9.1
Hz, 1H), 4.85−4.19 (m, 1H), 1.60 (d, J = 6.8 Hz, 3H). 13C{1H}
NMR (100 MHz, chloroform-d): δ 193.1, 148.3, 143.9, 135.6, 135.1,
128.9, 127.3, 125.7, 119.7, 119.1, 114.1, 52.9, 24.9. HRMS (ESI) m/z:
calcd for C15H15ClNO [M + H]+, 260.0837; found, 260.0833.
5-Bromo-2-((1-phenylethyl)amino)benzaldehyde (3ea). Purifica-
tion by column chromatography on silica gel (PE/EA = 20:1, v/v)
1
afforded 3ea as yellow oil (69.1 mg, 76%). H NMR (400 MHz,
chloroform-d): δ 9.80 (s, 1H), 8.72 (d, J = 6.0 Hz, 1H), 7.56 (d, J =
2.4 Hz, 1H), 7.36−7.27 (m, 5H), 7.25 (d, J = 2.7 Hz, 1H), 6.36 (d, J
= 9.1 Hz, 1H), 4.59−4.57 (m, 1H), 1.60 (d, J = 6.8 Hz, 3H). 13C{1H}
NMR (100 MHz, chloroform-d): δ 193.0, 148.6, 143.9, 138.2, 128.9,
127.3, 125.7, 119.8, 114.5, 106.3, 52.9, 24.8. HRMS (ESI) m/z: calcd
for C15H15BrNO [M + H]+, 304.0332; found, 304.0328.
5-Methoxy-2-((1-phenylethyl)amino)benzaldehyde (3fa). Purifi-
cation by column chromatography on silica gel (PE/EA = 15:1, v/v)
afforded 3fa as yellow oil (63.5 mg, 83%). 1H NMR (400 MHz,
chloroform-d): δ 9.86 (s, 1H), 8.71 (d, J = 5.9 Hz, 1H), 7.46 (dd, J =
7.7, 1.7 Hz, 1H), 7.32−7.14 (m, 3H), 6.86 (d, J = 8.5 Hz, 2H), 6.70−
6.60 (m, 1H), 6.48 (d, J = 8.5 Hz, 1H), 4.90−4.27 (m, 1H), 3.77 (s,
3H), 1.58 (d, J = 6.7 Hz, 3H). 13C{1H} NMR (100 MHz, chloroform-
d): δ 194.2, 158.6, 149.8, 136.6, 136.4, 135.6, 126.8, 118.5, 115.1,
114.2, 112.3, 55.3, 52.0, 25.0. HRMS (ESI) m/z: calcd for
C16H18NO2 [M + H]+, 256.1332; found, 256.1329.
4-(1-((2-Formylphenyl)amino)ethyl)phenyl 2-Acetoxybenzoate
(3av). Purification by column chromatography on silica gel (PE/EA
1
= 10:1, v/v) afforded 3av as yellow oil (100.4 mg, 83%). H NMR
(400 MHz, chloroform-d): δ 9.87 (s, 1H), 8.73 (d, J = 6.0 Hz, 1H),
8.19 (dd, J = 7.9, 1.7 Hz, 1H), 7.62 (td, J = 7.7, 1.7 Hz, 1H), 7.47 (dd,
J = 7.7, 1.7 Hz, 1H), 7.42−7.36 (m, 3H), 7.31−7.21 (m, 1H), 7.14
(dd, J = 10.3, 8.3 Hz, 3H), 6.67 (t, J = 7.5 Hz, 1H), 6.45 (d, J = 8.5
Hz, 1H), 4.63 (q, J = 6.5 Hz, 1H), 2.29 (s, 3H), 1.60 (d, J = 6.7 Hz,
3H). 13C{1H} NMR (100 MHz, chloroform-d): δ 194.3, 169.7, 164.0,
151.2, 149.6, 149.5, 142.2, 136.7, 135.8, 134.6, 132.2, 126.9, 126.2,
124.1, 122.6, 122.0, 118.6, 115.4, 112.3, 52.2, 24.9, 21.1. HRMS (ESI)
m/z: calcd for C28H32NO3 [M + H]+, 404.1492; found, 404.1487.
4-(1-((2-Formylphenyl)amino)ethyl)phenyl 4-(N,N-
Dipropylsulfamoyl)benzoate(3aw). Purification by column chroma-
tography on silica gel (PE/EA = 20:1, v/v) afforded 3aw as yellow oil
(108.2 mg, 71%). 1H NMR (400 MHz, chloroform-d): δ 9.88 (s, 1H),
8.74 (d, J = 5.9 Hz, 1H), 8.29 (d, J = 8.5 Hz, 2H), 7.94 (d, J = 8.5 Hz,
2H), 7.49 (dd, J = 7.8, 1.7 Hz, 1H), 7.40 (d, J = 8.6 Hz, 2H), 7.17 (s,
2H), 6.68 (t, J = 7.4 Hz, 1H), 6.45 (d, J = 8.5 Hz, 1H), 5.03−4.44 (m,
5-Phenoxy-2-((1-phenylethyl)amino)benzaldehyde (3ga). Purifi-
cation by column chromatography on silica gel (PE/EA = 15:1, v/v)
1
afforded 3ga as a yellow solid (83.7 mg, 88%), mp 101−103 °C. H
NMR (400 MHz, chloroform-d): δ 9.78 (s, 1H), 8.62 (d, J = 5.9 Hz,
1H), 7.32 (d, J = 5.0 Hz, 4H), 7.28 (s, 1H), 7.26 (s, 2H), 7.16 (d, J =
2.9 Hz, 1H), 7.06−6.96 (m, 2H), 6.88 (d, J = 7.9 Hz, 2H), 6.45 (d, J
= 9.1 Hz, 1H), 4.86−4.21 (m, 1H), 1.60 (d, J = 6.8 Hz, 3H). 13C{1H}
NMR (100 MHz, chloroform-d): δ 193.4, 158.5, 146.9, 145.5, 144.4,
129.7, 129.1, 128.9, 127.2, 126.3, 125.8, 122.5, 118.5, 117.2, 113.8,
53.0, 25.0. HRMS (ESI) m/z: calcd for C21H20NO2 [M + H]+,
318.1489; found, 318.1480.
H
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5-(Allyloxy)-2-((1-phenylethyl)amino)benzaldehyde (3ha). Puri-
fication by column chromatography on silica gel(PE/EA = 15:1, v/v)
afforded 3ha as yellow oil (48.9 mg, 58%). H NMR (400 MHz,
Hz, 1H), 6.47 (s, 1H), 4.60−4.56 (m, 1H), 1.60 (d, J = 6.8 Hz, 3H).
13C{1H} NMR (100 MHz, chloroform-d): δ 193.2, 150.3, 143.6,
142.3, 137.8, 128.9, 127.4, 125.7, 117.2, 115.8, 112.0, 52.7, 24.7.
HRMS (ESI) m/z: calcd for C15H15ClNO [M + H]+, 260.0837;
found, 260.0829.
1
chloroform-d): δ 9.83 (s, 1H), 8.46 (s, 1H), 7.31 (d, J = 4.3 Hz, 4H),
7.25−7.20 (m, 1H), 7.00 (d, J = 3.0 Hz, 1H), 6.93 (dd, J = 9.1, 3.0
Hz, 1H), 6.41 (d, J = 9.1 Hz, 1H), 6.02 (ddd, J = 22.6, 10.5, 5.3 Hz,
1H), 5.37 (d, J = 17.2 Hz, 1H), 5.26 (d, J = 10.5 Hz, 1H), 4.58 (d, J =
6.3 Hz, 1H), 4.45 (d, J = 5.4 Hz, 2H), 1.58 (d, J = 6.7 Hz, 3H).
13C{1H} NMR (100 MHz, chloroform-d): δ 193.5, 148.7, 145.3,
144.7, 133.5, 128.8, 127.0, 125.7, 119.8, 118.1, 117.7, 113.8, 69.9,
52.9, 25.0. HRMS (ESI) m/z: calcd for C18H20NO2 [M + H]+,
282.1489; found, 282.1485.
3-Formyl-4-((1-phenylethyl)amino)phenyl benzoate (3ia). Puri-
fication by column chromatography on silica gel (PE/EA = 15:1, v/v)
afforded 3ia as yellow oil (51.8 mg, 50%). 1H NMR (400 MHz,
chloroform-d): δ 9.86 (s, 1H), 8.74 (d, J = 5.9 Hz, 1H), 8.38−8.06
(m, 2H), 7.63 (t, J = 7.4 Hz, 1H), 7.50 (dd, J = 8.3, 7.1 Hz, 2H),
7.39−7.32 (m, 5H), 7.25 (s, 1H), 7.10 (dd, J = 9.1, 2.8 Hz, 1H), 6.51
(d, J = 9.1 Hz, 1H), 4.65−4.62 (m, 1H), 1.62 (d, J = 6.8 Hz, 3H).
13C{1H} NMR (100 MHz, chloroform-d): δ 193.3, 165.7, 147.9,
1-(2-((1-Phenylethyl)amino)phenyl)ethan-1-one (3oa). Purifica-
tion by column chromatography on silica gel (PE/EA = 20:1, v/v)
1
afforded 3oa as a yellow solid (49.5 mg, 69%), mp 52−54 °C. H
NMR (400 MHz, chloroform-d): δ 9.34 (s, 1H), 7.72 (d, J = 9.7 Hz,
1H), 7.35−7.27 (m, 4H), 7.20 (d, J = 9.0 Hz, 1H), 7.15 (t, J = 7.6 Hz,
1H), 6.52 (d, J = 15.1 Hz, 1H), 6.45 (d, J = 8.6 Hz, 1H), 4.76−4.45
(m, 1H), 2.59 (s, 3H), 1.56 (d, J = 6.7 Hz, 3H). 13C{1H} NMR (100
MHz, chloroform-d): δ 201.1, 150.1, 144.9, 134.9, 132.7, 128.8, 127.0,
125.8, 117.7, 114.3, 113.2, 52.7, 28.1, 25.1. HRMS (ESI) m/z: calcd
for C16H18NO [M + H]+, 240.1383; found, 240.1373.
Phenyl(2-((1-phenylethyl)amino)phenyl)methanone (3pa). Puri-
fication by column chromatography on silica gel (PE/EA = 20:1, v/v)
1
afforded 3pa as yellow oil (56.9 mg, 63%). H NMR (400 MHz,
chloroform-d): δ 9.05 (s, 1H), 7.68−7.57 (m, 2H), 7.57−7.47 (m,
3H), 7.45 (s, 1H), 7.38 (d, J = 6.8 Hz, 2H), 7.33 (t, J = 7.6 Hz, 2H),
7.24−7.16 (m, 2H), 6.54 (d, J = 8.5 Hz, 1H), 6.48 (ddd, J = 8.0, 7.0,
1.1 Hz, 1H), 4.66−4.64 (p, J = 6.6 Hz, 1H), 1.62 (d, J = 6.8 Hz, 3H).
13C{1H} NMR (100 MHz, chloroform-d): δ 199.6, 150.9, 144.8,
144.2, 140.0, 133.6, 130.1, 129.7, 129.4, 128.9, 128.6, 128.0, 127.2,
125.7, 118.1, 113.3, 52.9, 24.9. HRMS (ESI) m/z: calcd for
C22H20NO3 [M + H]+, 346.1438; found, 346.1428.
3-Formyl-4-((1-phenylethyl)amino)phenyl 4-Methylbenzenesul-
fonate (3ja). Purification by column chromatography on silica gel
(PE/EA = 10:1, v/v) afforded 3ja as a yellow solid (93.6 mg, 79%),
mp 102−104 °C. 1H NMR (400 MHz, chloroform-d): δ 9.69 (s, 1H),
8.72 (d, J = 5.9 Hz, 1H), 7.82−7.60 (m, 2H), 7.45−7.28 (m, 6H),
7.28−7.21 (m, 1H), 7.08 (d, J = 2.8 Hz, 1H), 6.80 (dd, J = 9.2, 2.8
Hz, 1H), 6.32 (d, J = 9.2 Hz, 1H), 4.97−4.28 (m, 1H), 2.43 (s, 3H),
1.58 (d, J = 6.8 Hz, 3H). 13C{1H} NMR (100 MHz, chloroform-d): δ
193.0, 148.5, 145.4, 143.8, 138.5, 132.2, 130.2, 129.8, 129.1, 128.9,
128.6, 127.3, 125.7, 117.9, 113.3, 52.9, 24.8, 21.7. HRMS (ESI) m/z:
calcd for C22H22NO4S [M + H]+, 396.1264; found, 396.1257.
6-((1-Phenylethyl)amino)benzo[d][1,3]dioxole-5-carbaldehyde
(3ka). Purification by column chromatography on silica gel (PE/EA =
15:1, v/v) afforded 3ka as yellow oil (62.2 mg, 77%). 1H NMR (400
MHz, chloroform-d): δ 9.59 (s, 1H), 9.23 (s, 1H), 7.32 (d, J = 5.6 Hz,
4H), 7.26−7.20 (m, 1H), 6.81 (s, 1H), 5.97 (s, 1H), 5.83 (d, J = 19.2
Hz, 2H), 5.05−4.25 (m, 1H), 1.59 (d, J = 6.8 Hz, 3H). 13C{1H}
NMR (100 MHz, chloroform-d): δ 190.6, 154.5, 149.7, 144.3, 138.3,
128.9, 127.2, 125.7, 112.5, 111.5, 101.3, 92.8, 53.1, 24.9. HRMS (ESI)
m/z: calcd for C16H16NO3 [M + H]+, 270.1125; found, 270.1116.
4,5-Dimethoxy-2-((1-phenylethyl)amino)benzaldehyde (3la).
Purification by column chromatography on silica gel (PE/EA =
140.6, 135.5, 134.8, 130.9, 129.1, 128.8, 128.1, 127.0, 125.8, 117.4,
114.0, 113.0, 52.9, 25.1. HRMS (ESI) m/z: calcd for C21H20NO [M +
H]+, 302.1539; found, 302.1536.
(5-Chloro-2-((1-phenylethyl)amino)phenyl) (phenyl)methanone
(3qa). Purification by column chromatography on silica gel (PE/EA =
10:1, v/v) afforded 3qa as a yellow solid (67.4 mg, 67%), mp 109−
111 °C 1H NMR (400 MHz, chloroform-d): δ 8.98 (s, 1H), 7.66 (dd,
J = 6.9, 1.8 Hz, 2H), 7.57 (t, J = 7.5 Hz, 1H), 7.53−7.46 (m, 3H),
7.42−7.32 (m, 4H), 7.27 (d, J = 7.9 Hz, 1H), 7.15 (dd, J = 9.1, 2.6
Hz, 1H), 6.51 (d, J = 9.1 Hz, 1H), 4.65−4.62 (p, J = 6.6 Hz, 1H),
1.63 (d, J = 6.7 Hz, 3H). 13C{1H} NMR (100 MHz, chloroform-d): δ
198.6, 149.3, 144.3, 139.8, 134.7, 134.0, 131.3, 129.1, 128.9, 128.3,
127.2, 125.8, 118.7, 118.1, 114.7, 53.1, 25.1. HRMS (ESI) m/z: calcd
for C21H19ClNO [M + H]+, 336.1150; found, 336.1145.
General Procedure for the Synthesis of Compound 4. To a
solution of 3ah (0.1 mmol) in EtOH (1.0 mL), benzylamine (0.12
mmol) was added. The resulting mixture was stirred at room
temperature for 10 min, and then, NaBH4 (0.2 mmol) was added
stepwise within 30 min. After further reaction for 30 min, the reaction
was quenched with saturated NH4Cl aqueous solution (5 mL).
Following phase separation, the aqueous layer was extracted three
times with diethyl ether (5 mL). The combined organic phases were
washed with brine (10 mL), dried over anhydrous MgSO4, and
filtered, and the organic phase was evaporated under reduced pressure
(rotary evaporator).
1
10:1, v/v) afforded 3la as yellow oil (77.0 mg, 90%). H NMR (400
MHz, chloroform-d): δ 9.67 (s, 1H), 9.35−8.78 (m, 1H), 7.32 (d, J =
6.7 Hz, 4H), 7.23 (dd, J = 6.1, 2.7 Hz, 1H), 6.87 (s, 1H), 5.88 (s,
1H), 4.88−4.35 (m, 1H), 3.80 (s, 3H), 3.60 (s, 3H), 1.61 (d, J = 6.8
Hz, 3H). 13C{1H} NMR (100 MHz, chloroform-d): δ 191.2, 156.4,
147.6, 144.7, 140.0, 128.9, 127.2, 125.7, 117.1, 111.0, 95.4, 56.6, 55.6,
53.3, 24.9. HRMS (ESI) m/z: calcd for C17H20NO3 [M + H]+,
286.1438; found, 286.1434.
2-((Benzylamino)methyl)-N-(1-(4-(tert-butyl)phenyl)ethyl)aniline
(4). Purification by column chromatography on silica gel (PE/EA =
1
10:1, v/v) afforded 4 as yellow oil (68.0 mg, 88%). H NMR (400
MHz, chloroform-d): δ 7.26 (d, J = 4.6 Hz, 4H), 7.21 (s, 3H), 7.19 (s,
2H), 6.94 (t, J = 7.5 Hz, 2H), 6.48 (t, J = 6.7 Hz, 1H), 6.34 (d, J = 7.9
Hz, 1H), 4.42 (q, J = 6.7 Hz, 1H), 3.82 (d, J = 3.1 Hz, 2H), 3.76 (d, J
= 1.2 Hz, 2H), 1.44 (d, J = 6.7 Hz, 3H), 1.22 (s, 9H). 13C{1H} NMR
(100 MHz, chloroform-d): δ 149.3, 147.5, 142.8, 140.2, 129.7, 128.5,
128.3, 127.1, 125.6, 125.4, 123.1, 115.8, 111.5, 53.4, 53.1, 52.4, 34.4,
31.4, 25.2. HRMS (ESI) m/z: calcd for C26H33N2 [M + H]+,
373.2638; found, 373.2635.
General Procedure for the Synthesis of Compound 5. To a
solution of 3ah (0.1 mmol) in dry THF (1.0 mL), nBuLi (0.2 mmol)
was added at −20 °C under an argon atmosphere. After stirring at
−20 °C for 2 h, the reaction mixture was warmed to room
temperature and reacted for another 3 h. The reaction was quenched
with saturated NH4Cl aqueous solution (5 mL). Following phase
separation, the aqueous layer was extracted three times with diethyl
ether (5 mL). The combined organic phases were washed with brine
(10 mL), dried over anhydrous MgSO4, and filtered, and the organic
phase was evaporated under reduced pressure (rotary evaporator).
4′-Fluoro-3-((1-phenylethyl)amino)-[1,1′-biphenyl]-4-carbalde-
hyde (3ma). Purification by column chromatography on silica gel
1
(PE/EA = 20:1, v/v) afforded 3ma as yellow oil (80.4 mg, 84%). H
NMR (400 MHz, chloroform-d): δ 9.96 (s, 1H), 8.78 (d, J = 6.0 Hz,
1H), 7.64 (d, J = 2.3 Hz, 1H), 7.49−7.39 (m, 3H), 7.38−7.30 (m,
4H), 7.08 (t, J = 8.7 Hz, 2H), 6.55 (d, J = 8.8 Hz, 1H), 4.68−4.65 (m,
1H), 1.64 (d, J = 6.7 Hz, 3H). 13C{1H} NMR (100 MHz, chloroform-
d): δ 194.3, 162.0 (d, J = 245.7 Hz), 149.0, 144.3, 136.1 (d, J = 3.2
Hz), 134.4 (d, J = 29.4 Hz), 128.9, 127.6 (d, J = 7.9 Hz), 127.4, 127.2,
125.8, 118.7, 115.8, 115.6, 113.0, 52.8, 24.9. 19F NMR (375 MHz,
chloroform-d): δ −116.60. HRMS (ESI) m/z: calcd for C21H19FNO
[M + H]+, 320.1445; found, 320.1442.
4-Chloro-2-((1-phenylethyl)amino)benzaldehyde (3na). Purifica-
tion by column chromatography on silica gel (PE/EA = 20:1, v/v)
1
afforded 3na as yellow oil (66.1 mg, 85%). H NMR (400 MHz,
chloroform-d): δ 9.82 (s, 1H), 8.86 (s, 1H), 7.37 (d, J = 8.4 Hz, 1H),
7.35−7.30 (m, 4H), 7.27 (d, J = 2.0 Hz, 1H), 6.61 (dd, J = 8.3, 1.9
I
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1-(2-((1-(4-(tert-Butyl)phenyl)ethyl)amino)phenyl)pentan-1-ol
(5). Purification by column chromatography on silica gel (PE/EA =
5:1, v/v) afforded 5 as yellow oil (51.6 mg, 76%), dr = 1:1. 1H NMR
(400 MHz, chloroform-d): δ 7.28−7.09 (m, 4H), 6.90 (dd, J = 14.9,
7.6 Hz, 2H), 6.48 (td, J = 7.3, 2.7 Hz, 1H), 6.35 (dd, J = 15.6, 8.2 Hz,
1H), 4.62 (t, J = 7.0 Hz, 1H), 4.39 (dq, J = 20.3, 6.7 Hz, 1H), 1.89
(dt, J = 21.5, 7.3 Hz, 2H), 1.42 (dd, J = 6.8, 3.8 Hz, 3H), 1.33−1.27
(m, 4H), 1.20 (d, J = 2.9 Hz, 9H), 0.83 (t, J = 7.0 Hz, 3H). 13C{1H}
NMR (100 MHz, chloroform-d): δ 149.4, 145.9, 145.8, 142.4, 142.3,
128.6, 127.5, 127.0, 126.6, 126.4, 125.4, 125.4, 116.0, 115.9, 112.3,
112.3, 74.8, 52.7, 52.5, 34.7, 34.4, 34.4, 31.4, 28.6, 25.1, 25.1, 22.6,
14.0. HRMS (ESI) m/z: calcd for C23H34NO [M + H]+, 340.2635;
found, 340.2631.
General Procedure for the Synthesis of Compound 6. To a
solution of 3ah (0.1 mmol) in EtOH (1.0 mL), NaBH4 (0.2 mmol)
was added stepwise within 30 min. After further reaction for 1 h, the
reaction was quenched with saturated NH4Cl aqueous solution (5
mL). Following phase separation, the aqueous layer was extracted
three times with diethyl ether (5 mL). The combined organic phases
were washed with brine (10 mL), dried over anhydrous MgSO4, and
filtered, and the organic phase was evaporated under reduced pressure
(rotary evaporator).
7.86 (d, J = 8.6 Hz, 1H), 7.81 (d, J = 8.1 Hz, 1H), 7.75 (t, J = 7.6 Hz,
1H), 7.54−7.52 (m, 4H). Spectral data matched those reported in the
literature.15
Control Experiment in Scheme 5a. An oven-dried 20 mL vial
was charged with Ni(BF4)2·6H2O (5 mol %) and 4,4′-di-tert-butyl-
2,2′-bipyridine (5.5 mol %) and closed with a septum cap. After it was
evacuated and backfilled with argon three times, DMA (1.0 mL),
Me(OEt)2SiH (0.6 mmol), and styrene 1a (0.33 mmol) were
successively added via a syringe, and the mixture was stirred at room
temperature for 5 min. Then, 2-aminobenzaldehyde 9 (0.30 mmol)
was added, and the mixture was stirred at room temperature for 8 h
under an argon atmosphere. The reaction was diluted with 1 M LiCl
aqueous solution water (10 mL). Following phase separation, the
aqueous layer was extracted three times with diethyl ether (5 mL).
The combined organic phases were washed with brine (10 mL), dried
over anhydrous MgSO4, and filtered, and the organic phase was
evaporated under reduced pressure (rotary evaporator). The residue
was analyzed by 1H NMR and GC−MS, and the desired product 3aa
was not detected.
Control Experiment in Scheme 5b. An isotope-labeling
experiment was conducted with Ph2SiD2 under the standard reaction
conditions. An oven-dried 20 mL vial was charged with Ni(BF4)2·
6H2O (5 mol %) and 4,4′-di-tert-butyl-2,2′-bipyridine (5.5 mol %)
and closed with a septum cap. After it was evacuated and backfilled
with argon three times, DMA (1.0 mL), Ph2SiD2 (0.45 mmol, 1.5
equiv), and 1-(tert-butyl)-4-vinylbenzene 1h (0.33 mmol) were
successively added. After stirring at room temperature for 5 min,
anthranil 2a (0.3 mmol) was added via a syringe, and the mixture was
stirred under an argon atmosphere at room temperature for 8 h. After
completion of the reaction, the resulting mixture was diluted with 1 M
LiCl aqueous solution water (10 mL). Following phase separation, the
aqueous layer was extracted three times with diethyl ether (5 mL).
The combined organic phases were washed with brine (10 mL), dried
over anhydrous MgSO4, and filtered, and the organic phase was
evaporated under reduced pressure (rotary evaporator). The residue
was purified by column chromatography on silica gel (PE/EA = 20:1,
v/v). Deuterated D-3ah was obtained in 80% yield with 90%
deuterium incorporation.
(2-((1-(4-(tert-Butyl)phenyl)ethyl)amino)phenyl)methanol (6).
Purification by column chromatography on silica gel (PE/EA = 5:1,
1
v/v) afforded 6 as yellow oil (53.8 mg, 95%). H NMR (400 MHz,
chloroform-d): δ 7.29−7.17 (m, 4H), 7.18 (s, 1H), 7.09−6.89 (m,
2H), 6.52 (td, J = 7.4, 1.1 Hz, 1H), 6.44−6.37 (m, 1H), 4.66 (d, J =
3.0 Hz, 2H), 4.46 (q, J = 6.7 Hz, 1H), 1.47 (d, J = 6.7 Hz, 3H), 1.22
(s, 9H). 13C{1H} NMR (100 MHz, chloroform-d): δ 149.6, 146.8,
142.2, 129.6, 129.0, 125.5, 124.1, 116.2, 112.0, 65.0, 52.5, 34.5, 31.4,
25.1. HRMS (ESI) m/z: calcd for C19H26NO [M + H]+, 284.2009;
found, 284.2000.
General Procedure for the Synthesis of Compound 7. To a
solution of MePPh3Br (0.12 mmol) in dry THF (3 mL), n-BuLi (0.2
mmol) was added at −20 °C dropwise within 5 min under an argon
atmosphere. After further reaction for another 20 min, a solution of
3aa in 1 mL of dry THF was added via a syringe. The resulting
mixture was warmed to room temperature and reacted for another 10
h. The reaction was quenched with saturated NH4Cl aqueous solution
(5 mL). Following phase separation, the aqueous layer was extracted
three times with diethyl ether (5 mL). The combined organic phases
were washed with brine (10 mL), dried over anhydrous MgSO4, and
filtered, and the organic phase was evaporated under reduced pressure
(rotary evaporator). The residue was purified by column chromatog-
raphy on silica gel (PE/EA = 20:1, v/v).
ASSOCIATED CONTENT
■
sı
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.1c01430.
1H and 13C NMR spectra for all compounds (PDF)
N-(1-Phenylethyl)-2-vinylaniline (7). Purification by column
chromatography on silica gel (PE/EA = 50:1, v/v) afforded 7 as
1
yellow oil (40.2 mg, 90%). H NMR (400 MHz, chloroform-d): δ
AUTHOR INFORMATION
7.37−7.25 (m, 2H), 7.22 (t, J = 7.6 Hz, 2H), 7.19−7.10 (m, 2H),
6.91 (t, J = 7.0 Hz, 1H), 6.76 (dd, J = 17.3, 11.0 Hz, 1H), 6.57 (t, J =
7.4 Hz, 1H), 6.30 (d, J = 8.2 Hz, 1H), 5.56 (d, J = 17.4 Hz, 1H), 5.27
(dd, J = 11.0, 1.6 Hz, 1H), 4.43 (q, J = 6.7 Hz, 1H), 1.45 (d, J = 6.7
Hz, 3H). 13C{1H} NMR (100 MHz, chloroform-d): δ 145.1, 144.2,
133.1, 128.8, 128.7, 127.4, 126.9, 125.8, 124.1, 117.3, 116.4, 112.1,
53.5, 25.3. HRMS (ESI) m/z: calcd for C16H18N [M + H]+,
224.1434; found, 224.1431.
■
Corresponding Author
Yang Gao − School of Chemical Engineering and Light
Industry, Guangdong University of Technology, Guangzhou
510006, China; orcid.org/0000-0001-9513-6899;
Email: gaoyang@gdut.edu.cn
General Procedure for the Synthesis of Compound 8.17 To a
long tube (toluene can reflux in the tube), Pd(OAc)2 (10 mol %),
Cu(OAc)2 (10 mol %), and DDQ (0.2 mmol) were added. Then, a
solution of 3aa (0.1 mmol) in toluene (2.0 mL) was added. The
resulting mixture was reacted at 180 °C for 2 h. After consumption of
the starting material, the reaction was quenched with saturated NaCl
aqueous solution (5 mL). Following phase separation, the aqueous
layer was extracted three times with diethyl ether (5 mL). The
combined organic phases were washed with brine (10 mL), dried over
anhydrous MgSO4, and filtered, and the organic phase was evaporated
under reduced pressure (rotary evaporator).
Authors
Yushan Cui − School of Chemical Engineering and Light
Industry, Guangdong University of Technology, Guangzhou
510006, China
Yanping Huo − School of Chemical Engineering and Light
Industry, Guangdong University of Technology, Guangzhou
510006, China
Jinhong Chen − School of Chemical Engineering and Light
Industry, Guangdong University of Technology, Guangzhou
510006, China
Minwei She − School of Chemical Engineering and Light
Industry, Guangdong University of Technology, Guangzhou
510006, China
2-Phenylquinoline (8). Purification by column chromatography on
silica gel (PE/EA = 10:1, v/v) afforded 8 as a white solid (10.7 mg,
1
52%). H NMR (400 MHz, chloroform-d): δ 8.22−8.19 (m, 4H),
J
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Article
Copper-Catalyzed Enantioselective Hydroamination. J. Am. Chem.
Soc. 2015, 137, 15620−15623.
Xianwei Li − School of Chemical Engineering and Light
Industry, Guangdong University of Technology, Guangzhou
510006, China; orcid.org/0000-0002-4014-6712
Qian Chen − School of Chemical Engineering and Light
Industry, Guangdong University of Technology, Guangzhou
510006, China; orcid.org/0000-0002-0818-6028
Xiao-Qiang Hu − Key Laboratory of Catalysis and Energy
Materials Chemistry of Ministry of Education & Hubei Key
Laboratory of Catalysis and Materials Science, School of
Chemistry and Materials Science, South-Central University
for Nationalities, Wuhan 430074, China; orcid.org/
0000-0001-9094-2357
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Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.1c01430
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Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The authors thank the National Natural Science Foundation of
China (21901045 and 21901258) and the Technology Plan of
Guangdong Province (2018A030310570) for financial support.
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