Highly efficient and recyclable magnetic nanoparticles-supported gold(III)-bipy catalyst for oxidative α-cyanation of tertiary amines

Article abstract of DOI:10.1016/j.tet.2016.05.037

Oxidative α-cyanation of tertiary amines with trimethylsilyl cyanide was achieved by using a magnetic nanoparticles-supported gold(III)-bipy complex as catalyst to afford the corresponding α-aminonitriles in good to excellent yields in the presence of ter

Full text of DOI:10.1016/j.tet.2016.05.037

Tetrahedron xxx (2016) 1e9
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Highly efficient and recyclable magnetic nanoparticles-supported
gold(III)-bipy catalyst for oxidative
a-cyanation of tertiary amines
,
,
Weisen Yang a b, Li Wei a, Feiyan Yi a, Mingzhong Cai a
*
a Key Laboratory of Functional Small Organic Molecule, Ministry of Education and College of Chemistry & Chemical Engineering, Jiangxi Normal
University, Nanchang 330022, PR China
b College of Ecology and Resources Engineering, Wuyi University, Wuyishan City 354300, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Oxidative
a
-cyanation of tertiary amines with trimethylsilyl cyanide was achieved by using a magnetic
-aminonitriles in
Received 31 March 2016
Received in revised form 10 May 2016
Accepted 13 May 2016
Available online xxx
nanoparticles-supported gold(III)-bipy complex as catalyst to afford the corresponding
a
good to excellent yields in the presence of tert-butyl hydroperoxide under acid-free conditions. The new
heterogeneous gold catalyst can easily be separated from the reaction mixture by using an external
magnet and can be recycled for at least 10 times without any loss of activity.
Ó 2016 Elsevier Ltd. All rights reserved.
Keywords:
Oxidative a-cyanation
Magnetic nanoparticles
Gold(III)-bipy complex
Supported gold catalyst
Heterogeneous catalysis
1. Introduction
excellent results have been achieved, catalytic functionalization of
unactivated sp3 CeH bonds remains a challenge.7 Transition metal-
a
-Aminonitriles are extremely useful and versatile synthetic
catalyzed oxidative
tionalization of sp3 CeH bonds represents one of the most conve-
nient and straightforward methods to prepare -aminonitriles and
a-cyanation of tertiary amines via direct func-
intermediates in a variety of organic transformations and have
widely been utilized in the construction of synthetically and bi-
a
ologically important compounds such as
carbonyls,
-amino alcohols, 1,2-diamines and alkaloids.1 Many
methods have been developed for the synthesis of -aminonitriles
a
-amino acids,
a
-amino
a number of metal catalysts including Ru,8 Fe,9 V,10 Cu,11 Mo,12 Re13
etc. in the presence of stoichiometric oxidants such as m-chlor-
operbenzoic acid, tert-butyl hydroperoxide (TBHP), O2, H2O2 have
been reported. However, the use of precious metals such as ru-
thenium, rhenium and difficult recovery and non-recyclability of
the metal catalysts still leave a scope for developing an efficient and
a
a
including the Strecker reaction,2 the oxidative cyanation of sec-
ondary3 or tertiary4 amines, and anodic oxidative cyanation of
tertiary amines.5 However, most of these methods have some
drawbacks in one or another respect, such as the poor selectivity,
multistep synthesis, limited substrate scope, and/or heavy metal
oxidants and generation of huge amount of wastes, making their
utility limited. Therefore, the development of a novel and more
efficient method that employs simple and mild as well as envi-
ronmentally benign conditions is highly desirable.
improved method for the direct synthesis of
a-aminonitriles
through the oxidative -cyanation of tertiary amines.
a
Gold complexes have increasingly found uses as catalysts in
a variety of organic transformations owing to their unique reactivity
as soft and carbophilic Lewis acids.14 To date, the gold-catalyzed
carbonecarbon15 and carbon-heteroatom16 bond formation re-
actions have successfully been applied in organic synthesis. In
contrast, the gold-catalyzed oxidation reactions have received less
attention,17 which should have potential applications in synthetic
oxidation chemistry. In addition, Industrial applications of these
homogeneous gold catalysts remain a challenge because they are
quite expensive, cannot be recycled, and difficult to separate from
the product mixture, which is a particularly significant drawback for
their application in the pharmaceutical industry. To overcome these
limitations, magnetic nanoparticles-supported catalysts are a better
Transition metal-catalyzed activation of sp3 CeH bonds and
subsequent carbonecarbon bond formation which avoids the pre-
functionalization of the substrates and reduces the synthetic pro-
cedures is therefore an extremely useful and straightforward
method for constructing complex structures.6 Although some
* Corresponding author. Fax: þ86 791 8812 0388; e-mail address: mzcai@jxnu.
edu.cn (M. Cai).
http://dx.doi.org/10.1016/j.tet.2016.05.037
0040-4020/Ó 2016 Elsevier Ltd. All rights reserved.
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2
W. Yang et al. / Tetrahedron xxx (2016) 1e9
choice because their magnetic separation is an alternative to filtra-
tion or centrifugation as it prevents loss of catalyst and increases the
reusability.18 Magnetic nanoparticles-supported palladium,19 ru-
thenium,20 rhodium,21 and copper22 complexes have widely been
used in a variety of organic reactions. Recently, Sadeghzadeh23 re-
ported a recyclable gold(III) dipyridine complex immobilized on
Fe3O4 magnetic nanoparticles for the synthesis of 2,6-dihydro[2,1-a]
isoindole under mild conditions. In continuing of our efforts to de-
velop economical and eco-friendly synthetic pathways for organic
transformations,24 in this paper, we report the synthesis of a mag-
netic nanoparticles-supported gold(III)-bipy complex and its suc-
Scheme 1. Firstly, the silica-coated Fe3O4 (Fe3O4@SiO2)19f was
treated with 4,40-bis[3-(triethoxysilyl)propylaminomethyl]-2,20-
bipyridine (BTESBPY)25 in toluene under reflux for 24 h to give the
bipyridine-functionalized magnetic nanoparticles (Fe3O4@SiO2-
bipy), the nitrogen content was determined to be 2.85 mmol gꢀ1 by
elemental analysis. The latter was reacted with AuCl3 in methanol
at 65 ꢁC for 24 h to afford the magnetic nanoparticles-supported
gold(III)-bipy complex (Fe3O4@SiO2-bipy-AuCl3), the gold content
was determined to be 0.63 mmol gꢀ1 by ICP-AES.
Transmission electron microscopy (TEM) images showed that the
diameter of Fe3O4@SiO2-bipy-AuCl3 complex was approximately
30 nm (Fig. 1a). Fig. 2 shows the XRD spectra of Fe3O4@SiO2 and
Fe3O4@SiO2-bipy-AuCl3 complex. XRD measurements of Fe3O4@SiO2
exhibit diffraction peaks corresponding to the typical spinel
maghemite structure whereas the diffraction peak of the layered
amorphous silica was not obvious. XRD measurements of the
Fe3O4@SiO2-bipy-AuCl3 obviously show two sets of diffraction
peaks, the new peaks that appeared are attributed to the Au species.
The results from XRD imply that the gold complex has been suc-
cessfully immobilized on the surface of MNPs. The energy dispersive
X-ray spectroscopy (EDS) shows the elements present in the mate-
rial. EDS analysis of the fresh Fe3O4@SiO2-bipy-AuCl3 complex
shows the presence of Si, O, C, N, Cl, Fe, and Au elements (Fig. 3).
cessful application to the oxidative
To the best of our knowledge, this is the first example of use of
heterogeneous gold catalyst for the direct oxidative -cyanation of
a-cyanation of tertiary amines.
a
tertiary amines with high efficiency. The catalyst could be easily
separated from the reaction mixture with the simple application of
an external magnet, and its catalytic efficiency remains unaltered
even after recycling 10 times.
2. Results and discussion
The magnetic nanoparticles-supported gold(III)-bipy complex
was synthesized according to the procedure summarized in
Scheme 1. Synthesis of magnetic nanoparticles-supported gold(III)-bipy complex.
Fig. 1. TEM images of Fe3O4@SiO2-bipy-AuCl3 (a) and recycled Fe3O4@SiO2-bipy-AuCl3 (b).
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W. Yang et al. / Tetrahedron xxx (2016) 1e9
3
fresh gold catalyst could be resolved into two chemically distinct
species corresponding to Au(I) and Au(III) (Fig. 4a). The pair at 85.3
and 89.3 eV can be assigned as the spin orbit coupling of Au 4f7/2
and Au 4f5/2, respectively, of Au(III). The presence of signals at
84.8 eV and 88.7 eV is related to the presence of Au(I). The am-
biguous detection of Au(I) can be attributed to the electron do-
nating capability of bipyridine to Au(III) and strong X-ray radiation
while recording XPS.26 The XPS of the used catalyst (Fig. 4b) after
the 10th cycle of reaction displayed the spin orbit pair at 85.2 and
89.1 eV that can be assigned to Au(III), indicating that the oxida-
tion state of supported gold catalyst did not change after the
reaction.
In our initial screens, the oxidative
a-cyanation of N,N-
dimethylaniline catalyzed by Fe3O4@SiO2-bipy-AuCl3 was se-
lected as the model reaction by using TMSCN as the cyanide
source to optimize the reaction conditions and the results are
summarized in Table 1. Among the oxidants tested, H2O2 and
molecular O2 were found to be ineffective for the reaction and
no product was detected, TBHP afforded an 89% isolated yield
(entries 1e3). Reducing the amount of TBHP could improve the
yield and 1.2 equiv of TBHP gave the best result (entries 3e5).
The effect of the solvent on the model reaction was also in-
vestigated. Although EtOH, EtOAc and MeCN also afforded good
yields (entries 6e8), MeOH was the most efficient (entry 5).
While other solvents such as toluene and 1,2-dichloroethane
were substantially less effective (entries 9 and 10). Lowering
the reaction temperature resulted in a decrease in yield (entries
11 and 12). When Bu4NCN or K3[Fe(CN)6] was used as cyanide
source, low yield was obtained (entries 13 and 14). Reducing the
amount of the catalyst to 5 mol % led to an only 76% yield and no
reaction was observed in the absence of any catalyst (entries 15
Fig. 2. XRD patterns of Fe3O4@SiO2 (a) and Fe3O4@SiO2-bipy-AuCl3 (b).
and 16). When
a homogeneous bipyridine-AuCl3 complex
([bipyAuCl2]Cl) was used as catalyst, the desired product was
also obtained in 95% yield (entry 17). Thus, the optimized re-
action conditions for this transformation are the Fe3O4@SiO2-
bipy-AuCl3 (10 mol %) in MeOH using TMSCN (2.0 equiv) as cy-
anide source and TBHP (1.2 equiv) as oxidant at 50 ꢁC under air
for 6 h (Table 1, entry 5).
Fig. 3. EDS analysis of Fe3O4@SiO2-bipy-AuCl3.
To explore the scope and the functional group tolerance of the
heterogeneous gold-catalyzed oxidative
a-cyanation reaction,
The structure of supported gold catalyst was also verified by X-
ray photoelectron spectroscopy (XPS) determination (Fig. 4). The
spectra have been background corrected using the Shirley algo-
rithm prior to curve resolution. The Au 4f core level signals of the
a variety of tertiary anilines were investigated as substrates under
the optimized reaction conditions and the results are listed in
Table 2. To our delight, all the substrates were selectively and
effectively converted to the corresponding
a-aminonitriles in
good to excellent yields. Substituted N,N-dimethylanilines bear-
ing both electron-donating and electron-withdrawing sub-
stituents afforded the corresponding cyanated products 2be2l in
86e95% yields. The results indicated that the electronic effect of
substituents on the benzene ring has limited influence on this
heterogeneous gold-catalyzed oxidative a-cyanation reaction and
a variety of functional groups such as methyl, fluoro, chloro,
bromo, cyano, nitro, phenyl, ester, alkynyl, and ketone were tol-
erated well. Bulky N,N-dimethyl-1-naphthylamine 1m also gave
the desired product 2m in 84% yield. It is noteworthy that, N-
ethyl-N-methylaniline 1n, an unsymmetrical aniline, underwent
a selective oxidative cyanation at the methyl group rather than at
the methylene carbon of the ethyl group to furnish the cyanated
product 2n in 91% yield. Similarly, the reactions of cyclic tertiary
amines such as pyrrolidine, piperidine, and tetrahydroisoquino-
line derivatives also proceeded smoothly to afford the corre-
sponding a-aminonitriles 2oe2x in good to excellent yields. The
sterically hindered N-(2-methylphenyl)pyrrolidine 1p and N-(2-
nitrophenyl)piperidine 1s could also give the corresponding
cyanated products 2p and 2s in high yields. Both electron-
donating and electron-withdrawing groups such as methyl,
methoxy, bromo, nitro, and trifluoromethyl were well tolerated.
Fig. 4. XPS of the supported gold catalysts.
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4
W. Yang et al. / Tetrahedron xxx (2016) 1e9
Table 1
Optimization of reaction conditions for heterogeneous gold-catalyzed oxidative
a
-cyanation of N,N-dimethylanilinea
Entry
Oxidant (equiv)
Solvent
Temp (ꢁC)
Yield (%)b
1
2
3
4
5
6
7
8
H2O2 (2.0)
O2
MeOH
MeOH
MeOH
MeOH
MeOH
EtOH
EtOAc
MeCN
Toluene
(CH2Cl)2
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
50
50
50
50
50
50
50
50
50
50
40
25
50
50
50
50
50
0
0
TBHP (2.0)
TBHP (1.5)
TBHP (1.2)
TBHP (1.2)
TBHP (1.2)
TBHP (1.2)
TBHP (1.2)
TBHP (1.2)
TBHP (1.2)
TBHP (1.2)
TBHP (1.2)
TBHP (1.2)
TBHP (1.2)
TBHP (1.2)
TBHP (1.2)
89
92
96
84
71
74
27
Trace
85
49
13
19
76
0
9
10
11
12
13c
14d
15e
16f
17g
95
a
Reaction conditions: N,N-dimethylaniline (0.5 mmol), TMSCN (1.0 mmol), TBHP (5e6 M in decane), Fe3O4@SiO2-bipy-AuCl3 (10 mol %), solvent (1 mL) for 6 h under air.
Isolated yield.
Bu4NCN (2 equiv) as cyanide source.
K3[Fe(CN)6] (2 equiv) as cyanide source.
5 mol % gold catalyst was used. .
Without gold catalyst.
b
c
d
e
f
g
[bipyAuCl2]Cl (10 mol %) was used.
We also performed the oxidative
a
-cyanation reaction of alkyl-
next investigated the recycling of the Fe3O4@SiO2-bipy-AuCl3 by
using N,N-dimethylaniline 1a as a model substrate. Each time,
after completion of the reaction, more than 99% of the catalyst
could simply be recovered by fixing a magnet near to the reaction
vessel (Fig. 5b and c). The recovered catalyst was washed with
MeOH, air-dried and used directly in the next run without further
purification. The recovered catalyst was used for 10 runs using
fresh substrates and oxidant under identical conditions and the
results are presented in Fig. 5a. As shown in Fig. 5a, the yield of
the desired product 2a in all cases was found to be almost similar
which confirmed that the developed catalyst can be reused effi-
ciently for at least 10 times without any loss of activity. In addi-
tion, from the TEM images of the recovered catalyst (Fig. 1b) and
the fresh one (Fig. 1a), no obvious differences in the morphology
and dispersion of particles could be observed. The excellent re-
usability of the catalyst should result from the chelating action of
bidentate bipyridine ligand on gold and the magnetic separation.
The result is important from industrial and environmental points
of view.
amines such as n-Bu3N, unfortunately, the reaction did not occur
under the optimized reaction conditions. Thus, the protocol de-
veloped represents a simple and practical methodology for the
preparation of a-aminonitriles, which are versatile synthetic in-
termediates, and have widely been used in the synthesis of
a wide range of synthetically, as well as biologically important
compounds.
To verify whether the observed catalysis was due to the het-
erogeneous Fe3O4@SiO2-bipy-AuCl3 or to a leached gold species
in solution, the oxidative cyanation reaction of N,N-dimethyla-
niline 1a was carried out until an approximately 50% conversion
of 1a. Then the Fe3O4@SiO2-bipy-AuCl3 catalyst was separated
magnetically from the solution and the solution was transferred
to another reaction tube and stirred again at 50 ꢁC for 4 h. If gold
was leaching from the solid surface during the reaction, the so-
lution should contain gold. ICP analysis of the solution indicated
that any detectable gold was absent in the reaction mixture. Si-
multaneously the cyanation reaction did not proceed further after
the separation of Fe3O4@SiO2-bipy-AuCl3. It was further noted
that gold was also not detected in the liquid phase after the
completion of reaction. These results suggest that the Au is not
being leached out from the solid surface of the catalyst during the
reaction.
3. Conclusion
In conclusion, we have developed a highly efficient and
easily recoverable magnetic nanoparticles-supported gold(III)-
Although the exact mechanism of the reaction is not clear at this
stage, a plausible mechanism for this heterogeneous gold-catalyzed
reaction is showed in Scheme 2. First, the reaction of Fe3O4@SiO2-
bipy-AuCl3 complex with TBHP gives a magnetic nanoparticles-
supported oxo-gold(V) species17d,e [Fe3O4@SiO2-(bipyCl2AuV¼O)
Cl] (A). The latter undergoes the reaction with tertiary amine (1) to
produce an iminium ion intermediate (B) by electron transfer and
subsequent hydrogen transfer. Finally, the nucleophilic attack by
TMSCN on the iminium ion intermediate (B) affords the corre-
bipy catalyst for the oxidative a-cyanation reaction of tertiary
amines using TBHP as oxidant and TMSCN as cyanide source.
The reaction proceeds with high efficiency under acid-free and
mild conditions, generating
a variety of valuable a-amino-
nitriles compounds in good to excellent yields. More impor-
tantly, this heterogeneous gold catalyst can simply be
recovered by applying an external magnet and recycled at least
10 times without any loss of activity. The advantageous fea-
tures of the present protocol such as easy recovery of the
catalyst and its recyclability without any loss of activity and
leaching, and excellent product yields make this a superior tool
sponding a-cyanated product (2) and regenerates the Fe3O4@SiO2-
bipy-AuCl3 complex to complete the catalytic cycle.
For a supported precious metal catalyst, it is very important to
know its ease of separation, recoverability and reusability. We
for the oxidative
methods.
a-cyanation reaction than existing literature
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W. Yang et al. / Tetrahedron xxx (2016) 1e9
5
Table 2
Heterogeneous gold-catalyzed oxidative a
-cyanation of tertiary anilinesa,b
a Reaction conditions: tertiary aniline (0.5 mmol), TMSCN (1.0 mmol), TBHP (0.6 mmol, 5-6 M
b
in decane), Fe3O4@SiO2-bipy-AuCl3 (10 mol%), MeOH (1 mL) at 50 ºC for 6 h under air.
Isolated yield.
4. Experimental
inductively coupled plasma atom emission spectrometry (ICP-
AES). TEM images were recorded in a transmission electron mi-
croscope operated at an accelerated voltage of 200 kV. X-ray dif-
fraction (XRD) measurements were carried out at room
temperature using an X-ray powder diffractmeter. X-ray energy
dispersive spectroscopy (EDS) was performed using a microscope
X-ray photoelectron spectra (XPS) were recorded on XSAM 800
(Kratos).
4.1. Physical measurements and materials
All reagents were obtained from commercial sources without
further purification, and commercially available solvents were
purified before use. The silica-coated Fe3O4 (Fe3O4@SiO2)19f and
4,40-bis[3-(triethoxysilyl)propylaminomethyl]-2,20-bipyridine
(BTESBPY)25 were prepared according to literature procedures.
The reaction was carried out at 50 ꢁC without exclusion of air from
the reaction mixture. All compounds were fully characterized. 1H
and 13C NMR spectra were recorded at 400 or 100 MHz with CDCl3
as the solvent and TMS as an internal standard. Chemical shifts are
4.2. Preparation of Fe3O4@SiO2-bipy
To a suspension of 0.75 g of Fe3O4@SiO2 in 20 mL of dry tol-
uene was added a solution of 4,40-bis[3-(triethoxysilyl)propyla-
minomethyl]-2,20-bipyridine (BTESBPY) (0.872 g, 1.4 mmol) in
40 mL of dry toluene. The mixture was stirred at 110 ꢁC under
argon atmosphere for 24 h. Then the solid material was
reported in
d (ppm) relative to TMS. HRMS spectra were recorded
on a Q-Tof spectrometer with micromass MS software using
electrospray ionization (ESI). Gold content was determined with
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6
W. Yang et al. / Tetrahedron xxx (2016) 1e9
Scheme 2. Plausible mechanism for heterogeneous gold-catalyzed oxidative cyanation reaction.
100
80
60
40
20
0
1
2
3
4
5
6
7
8
9
10
Recycling Number
(a)
(b)
(c)
Fig. 5. Recycle of the Fe3O4@SiO2-bipy-AuCl3 catalyst.
magnetically separated, washed repeatedly with toluene and
CH2Cl2 to remove any unanchored species and dried at 100 ꢁC
under vacuum for 5 h to afford 0.86 g of the bipyridine-
functionalized Fe3O4@SiO2 (Fe3O4@SiO2-bipy) as brown nano-
particles. The nitrogen content was found to be 2.85 mmol gꢀ1 by
elemental analysis.
complex (Fe3O4@SiO2-bipy-AuCl3) as brown nanoparticles. The
gold content was determined to be 0.63 mmol gꢀ1 by ICP-AES.
4.4. General procedure for heterogeneous gold-catalyzed ox-
idative a-cyanation of tertiary anilines
Fe3O4@SiO2-bipy-AuCl3 (80 mg, 0.05 mmol) and MeOH (1 mL)
were added to a screw-capped test tube with a Teflon-lined sep-
tum. Tertiary amine (0.5 mmol), TMSCN (1.0 mmol), and 0.1 mL of
TBHP (5e6 M in decane) were added at room temperature. The
reaction mixture was stirred at 50 ꢁC under air atmosphere for 6 h.
The reaction was monitored by TLC on silica-gel plates (GF 254).
After the reaction was completed, the supported catalyst was
magnetically separated and the reaction mixture was added into
aqueous NaHCO3 (5 mL) and extracted with ethyl acetate
(2ꢂ10 mL). The combined organic layer was washed with brine,
dried over anhydrous MgSO4 and concentrated under reduced
4.3. Synthesis of Fe3O4@SiO2-bipy-AuCl3
To a three-necked bottom flask, AuCl3 (98 mg, 0.32 mmol) and
MeOH (50 mL) were added. The solution was stirred at room
temperature under argon atmosphere for 10 min, and then 0.421 g
of the bipyridine-functionalized magnetic nanoparticles (Fe3O4@-
SiO2-bipy) was added. The mixture was stirred at 65 ꢁC for 24 h,
then the solid catalyst was magnetically separated, washed thor-
oughly with methanol, and dried under vacuum at 60 ꢁC for 3 h to
give 0.456 g of magnetic nanoparticles-supported gold(III)-bipy
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W. Yang et al. / Tetrahedron xxx (2016) 1e9
7
pressure. The residue was purified by flash chromatography (pe-
troleum ether: ethyl acetate¼10:1) to afford the corresponding
product. The recovered catalyst was washed with MeOH (2ꢂ2 mL),
air-dried and used directly for the next run.
d
7.53e7.44 (m, 4H), 7.36e7.28 (m, 3H), 6.78 (dd, J¼7.2, 2.0 Hz,
2H), 4.15 (s, 2H), 3.01 (s, 3H); 13C NMR (100 MHz, CDCl3)
d
147.4,
133.0, 131.5, 128.4, 128.0, 123.7, 115.3, 114.2, 114.1, 89.5, 88.4, 41.7,
39.1. HRMS (ESI) m/z calcd for C17H14Nþ2 [Mþ] 246.1157, found
246.1162.
4.4.1. 2-(Methyl(phenyl)amino)acetonitrile (2a).9a Colorless oil. 1H
NMR (400 MHz, CDCl3)
d
7.32 (t, J¼7.6 Hz, 2H), 6.92 (t, J¼7.4 Hz, 1H),
4.4.12. 2-((4-Benzoylphenyl)methylamino)acetonitrile (2l).30 Yellow
6.87 (d, J¼8.4 Hz, 2H), 4.17 (s, 2H), 3.01 (s, 3H); 13C NMR (100 MHz,
solid, mp 94e95 ꢁC. 1H NMR (400 MHz, CDCl3)
d
7.84 (d, J¼8.8 Hz,
CDCl3)
d
147.4, 129.1, 119.6, 115.4, 114.3, 41.6, 38.7.
2H), 7.77e7.72 (m, 2H), 7.55 (t, J¼7.2 Hz, 1H), 7.47 (t, J¼7.4 Hz, 2H),
6.84 (d, J¼9.2 Hz, 2H), 4.29 (s, 2H), 3.14 (s, 3H); 13C NMR (100 MHz,
4.4.2. 2-(Methyl(p-tolyl)amino)acetonitrile (2b).9a Colorless oil. 1H
NMR (400 MHz, CDCl3)
7.12 (d, J¼8.0 Hz, 2H), 6.80 (d, J¼8.4 Hz,
2H), 4.13 (s, 2H), 2.96 (s, 3H), 2.29 (s, 3H); 13C NMR (100 MHz,
CDCl3) 145.3, 129.5, 129.4, 127.5, 115.0, 42.4, 39.0, 19.9.
CDCl3) d 195.3, 150.8, 138.4, 132.7, 132.6, 129.7, 128.3, 128.2, 115.1,
d
112.6, 41.2, 39.1.
d
4.4.13. 2-(Methyl(naphthalen-1-yl)amino)acetonitrile
(2m).30
Yellow solid, mp 91e93 ꢁC. 1H NMR (400 MHz, CDCl3)
d
8.10 (d,
4.4.3. 2-(Methyl(m-tolyl)amino)acetonitrile (2c).9a Colorless oil. 1H
NMR (400 MHz, CDCl3)
7.27e7.11 (m, 1H), 6.74 (d, J¼7.6 Hz, 1H),
6.70e6.66 (m, 2H), 4.14 (s, 2H), 2.98 (s, 3H), 2.34 (s, 3H); 13C NMR
J¼8.4 Hz,1H), 7.86 (d, J¼7.2 Hz,1H), 7.65 (d, J¼8.0 Hz,1H), 7.55e7.47
d
(m, 2H), 7.44 (t, J¼7.8 Hz,1H), 7.33 (d, J¼7.6 Hz,1H), 4.10 (s, 2H), 3.04
(s, 3H); 13C NMR (100 MHz, CDCl3)
d 146.6, 128.2, 127.5, 125.7, 125.5,
(100 MHz, CDCl3)
38.8, 21.3.
d
147.4, 138.8, 128.8, 124.4,120.6, 115.2, 111.6, 41.8,
125.2, 124.9, 124.6, 122.2, 117.0, 116.7, 45.6, 40.9.
4.4.14. 2-(Ethyl(phenyl)amino)acetonitrile (2n).31 Colorless oil. 1H
4.4.4. 2-((4-Bromophenyl)methylamino)acetonitrile
(2d).9a
NMR (400 MHz, CDCl3)
d
7.31 (t, J¼8.0 Hz, 2H), 6.92 (t, J¼7.2 Hz,1H),
Colorless oil. 1H NMR (400 MHz, CDCl3)
d
7.39 (dd, J¼7.2, 2.0 Hz,
6.86 (d, J¼8.0 Hz, 2H), 4.14 (s, 2H), 3.44 (q, J¼7.2 Hz, 2H), 1.24 (t,
2H), 6.73 (dd, J¼8.8, 2.0 Hz, 2H), 4.14 (s, 2H), 2.99 (s, 3H); 13C NMR
J¼7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d 146.4, 129.1, 119.3, 115.9,
(100 MHz, CDCl3)
d
146.3, 131.8, 115.9, 114.7, 112.0, 41.7, 38.9.
114.5, 45.8, 39.0, 11.8.
4.4.5. 2-((3-Chlorophenyl)methylamino)acetonitrile (2e).27 Yellow
oil. 1H NMR (400 MHz, CDCl3)
7.18e7.12 (m, 1H), 6.80 (dd, J¼8.0,
4.4.15. 1-Phenylpyrrolidine-2-carbonitrile (2o).9a Colorless oil. 1H
NMR (400 MHz, CDCl3)
d
d
7.30 (t, J¼8.0 Hz, 2H), 6.83 (t, J¼7.2 Hz,1H),
2.0 Hz,1H), 6.74 (t, J¼2.2 Hz,1H), 6.64 (dd, J¼8.4, 2.8 Hz,1H), 4.08 (s,
6.69 (d, J¼8.4 Hz, 2H), 4.43 (d, J¼7.2 Hz, 1H), 3.49e3.41 (m, 1H),
2H), 2.92 (s, 3H); 13C NMR (100 MHz, CDCl3)
118.9, 114.2, 113.7, 111.6, 40.9, 38.1.
d
147.8, 134.3, 129.4,
3.39e3.33 (m, 1H), 2.44e2.37 (m, 1H), 2.34e2.14 (m, 3H); 13C NMR
(100 MHz, CDCl3)
24.0.
d 145.3, 129.5, 119.3, 118.3, 112.7, 49.1, 47.5, 31.6,
4.4.6. 4-((Cyanomethyl)methylamino)benzonitrile
(2f).28 Yellow
7.58 (d, J¼8.4 Hz,
solid, mp 105e106 ꢁC. 1H NMR (400 MHz, CDCl3)
d
4.4.16. 1-o-Tolylpyrrolidine-2-carbonitrile (2p).32 Brown oil. 1H
NMR (400 MHz, CDCl3)
2H), 6.82 (d, J¼8.8 Hz, 2H), 4.26 (s, 2H), 3.13 (s, 3H); 13C NMR
d
7.20e7.12 (m, 3H), 7.03 (t, J¼7.2 Hz, 1H),
(100 MHz, CDCl3)
d
149.8, 144.4, 133.3, 117.7, 114.0, 112.9, 40.5, 38.5.
4.38 (dd, J¼7.6, 3.6 Hz, 1H), 3.49e3.42 (m, 1H), 3.17e3.12 (m, 1H),
2.42e2.35 (m, 1H), 2.31 (s, 3H), 2.29e1.97 (m, 3H); 13C NMR
4.4.7. 2-(Methyl(3-nitrophenyl)amino)acetonitrile
solid, mp 98e99 ꢁC. 1H NMR (400 MHz, CDCl3)
(2g).9a Yellow
7.75 (d, J¼8.4 Hz,
(100 MHz, CDCl3) d 144.9, 132.2,131.5, 126.8,124.2, 119.8,119.1, 52.0,
50.0, 30.7, 22.8, 18.8.
d
1H), 7.68 (s, 1H), 7.47 (t, J¼8.0 Hz, 1H), 7.13 (d, J¼8.0 Hz, 1H), 4.28 (s,
2H), 3.13 (s, 3H); 13C NMR (100 MHz, CDCl3)
119.2, 114.3, 113.9, 108.2, 41.2, 38.8.
d
148.9, 147.9, 129.8,
4.4.17. 1-Phenylpiperidine-2-carbonitrile (2q).9a Colorless oil. 1H
NMR (400 MHz, CDCl3)
d
7.31 (t, J¼7.2 Hz, 2H), 7.02e6.97 (m, 3H),
4.64e4.61 (m, 1H), 3.47e3.41 (m, 1H), 3.07e2.97 (m, 1H), 2.04e1.99
4.4.8. 2-(Biphenyl-4-yl(methyl)amino)acetonitrile (2h). White solid,
mp 103e104 ꢁC. 1H NMR (400 MHz, CDCl3)
7.57e7.52 (m, 4H), 7.41
(t, J¼7.8 Hz, 2H), 7.32e7.28 (m, 1H), 6.92 (d, J¼8.8 Hz, 2H), 4.18 (s,
2H), 3.03 (s, 3H); 13C NMR (100 MHz, CDCl3)
147.1, 140.6, 133.0,
(m, 2H), 1.86e1.82 (m, 2H), 1.71e1.66 (m, 2H); 13C NMR (100 MHz,
d
CDCl3) d 149.8, 129.5, 122.3, 118.5, 117.2, 52.1, 46.6, 29.3, 25.2, 20.2.
d
4.4.18. 1-(4-Nitrophenyl)piperidine-2-carbonitrile
(2r).33 Yellow
8.19 (d, J¼9.2 Hz,
128.8, 128.1, 126.7, 126.6, 115.5, 115.1, 42.2, 39.3. HRMS (ESI) m/z
solid, mp 109e110 ꢁC. 1H NMR (400 MHz, CDCl3)
d
calcd for C15H14Nþ2 [Mþ] 222.1157, found 222.1164.
2H), 6.98 (d, J¼9.2 Hz, 2H), 4.86e4.82 (m, 1H), 3.79e3.73 (m, 1H),
3.15e3.08 (m, 1H), 1.96e1.88 (m, 2H), 1.85e1.61 (m, 4H); 13C NMR
4.4.9. 2-((40-Fluorobiphenyl-4-yl)(methyl)amino)acetonitrile
(100 MHz, CDCl3)
24.7, 19.9.
d 154.1, 141.0, 125.7, 116.6, 115.6, 49.2, 45.8, 28.9,
(2i). White solid, mp 121e123 ꢁC. 1H NMR (400 MHz, CDCl3)
d
7.51e7.46 (m, 4H), 7.12e7.06 (m, 2H), 6.91 (d, J¼8.8 Hz, 2H), 4.19
(s, 2H), 3.03 (s, 3H); 13C NMR (100 MHz, CDCl3)
d
162.1 (d,
4.4.19. 1-(2-Nitrophenyl)piperidine-2-carbonitrile
solid, mp 55e56 ꢁC. 1H NMR (400 MHz, CDCl3)
1H), 7.60 (t, J¼7.0 Hz, 1H), 7.48 (d, J¼7.6 Hz, 1H), 7.29 (t, J¼7.4 Hz,
1H), 4.52e4.49 (m, 1H), 3.38e3.31 (m, 1H), 3.01e2.95 (m, 1H),
2.13e2.07 (m, 1H), 1.99e1.94 (m, 1H), 1.86e1.68 (m, 4H); 13C NMR
(2s).34 Yellow
7.80 (d, J¼7.2 Hz,
1JCeF¼244.1 Hz), 147.0, 136.7 (d, JCeF¼3.2 Hz), 132.1, 128.1 (d,
3JCeF¼7.9 Hz), 128.0, 115.6 (d, 2JCeF¼21.2 Hz), 115.4, 115.1, 42.2, 39.3.
HRMS (ESI) m/z calcd for C15H13FNþ2 [Mþ] 240.1063, found 240.1051.
d
4
4.4.10. Methyl
4-((cyanomethyl)methylamino)benzoate
(2j).29
(100 MHz, CDCl3) d 146.5, 144.1, 133.7, 125.6, 125.2, 124.4, 117.1, 54.3,
48.7, 28.9, 25.3, 19.9.
White solid, mp 80e81 ꢁC. 1H NMR (400 MHz, CDCl3)
d
7.98 (dd,
J¼7.2, 2.0 Hz, 2H), 6.80 (dd, J¼7.2, 2.0 Hz, 2H), 4.25 (s, 2H), 3.88 (s,
3H), 3.10 (s, 3H); 13C NMR (100 MHz, CDCl3)
120.8, 115.2, 112.8, 51.8, 41.2, 39.0.
d
166.9, 150.9, 131.5,
4.4.20. 2-Phenyl-1,2,3,4,-tetrahydroisoquinoline-1-carbonitrile
(2t).9a Colorless oil. 1H NMR (400 MHz, CDCl3)
d
7.36 (t, J¼7.6 Hz,
2H), 7.30e7.21 (m, 4H), 7.08 (d, J¼7.6 Hz, 2H), 7.01 (t, J¼7.0 Hz,
4.4.11. 2-(Methyl(4-(phenylethynyl)phenyl)amino)acetonitrile
1H), 5.51 (s, 1H), 3.78e3.72 (m, 1H), 3.51e3.43 (m, 1H), 3.21e3.13
(2k). Yellow solid, mp 107e109 ꢁC. 1H NMR (400 MHz, CDCl3)
(m, 1H), 2.99e2.93 (m, 1H); 13C NMR (100 MHz, CDCl3)
d 148.4,
Please cite this article in press as: Yang, W.; et al., Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.05.037

8
W. Yang et al. / Tetrahedron xxx (2016) 1e9
2012, 14, 5692e5695; (g) Wagner, A.; Ofial, A. R. J. Org. Chem. 2015, 80,
2848e2854.
134.7, 129.7, 129.6, 129.4, 128.8, 127.1, 126.9, 121.9, 117.8, 117.6,
53.2, 44.2, 28.6.
5. (a) Andreades, S.; Zahnow, E. W. J. Am. Chem. Soc. 1969, 91, 4181e4190; (b)
Chiba, T.; Takata, Y. J. Org. Chem. 1977, 42, 2973e2977; (c) Le Gall, E.; Hurvois, J.-
P.; Renaud, T.; Moinet, C.; Tallec, A.; Uriac, P.; Sindbandhit, S.; Toupet, L. Liebigs
Ann. 1997, 2089e2101; (d) Tajima, T.; Nakajima, A. J. Am. Chem. Soc. 2008, 130,
10496e10502; (e) Vu, V. H.; Louafi, F.; Girard, N.; Marion, R.; Roisnel, T.; Dorcet,
V.; Hurvois, J.-P. J. Org. Chem. 2014, 79, 3358e3373.
6. (a) Li, C.-J. Acc. Chem. Res. 2009, 42, 335e344; (b) Li, J. J.; Mei, T. S.; Yu, J. Q.
Angew. Chem., Int. Ed. 2008, 47, 6452e6455; (c) Wang, D. H.; Was, M.; Giri, R.;
Yu, J. Q. J. Am. Chem. Soc. 2008, 130, 7190e7191; (d) Campos, K. R. Chem. Soc.
Res. 2007, 36, 1069e1084; (e) Tobisu, M.; Chatani, N. Angew. Chem., Int. Ed.
2006, 45, 1683e1684; (f) Kakiuchi, F.; Chatani, N. Adv. Synth. Catal. 2003, 345,
1077e1101.
4.4.21. 2-(3-Methylphenyl)-1,2,3,4,-tetrahydroisoquinoline-1-
carbonitrile (2u).11c Yellow oil. 1H NMR (400 MHz, CDCl3)
d
7.31e7.18 (m, 5H), 6.89e6.85 (m, 2H), 6.82 (d, J¼7.2 Hz, 1H), 5.49
(s, 1H), 3.80e3.69 (m, 1H), 3.48e3.39 (m, 1H), 3.13e3.07 (m, 1H),
2.97e2.89 (m, 1H), 2.35 (s, 3H); 13C NMR (100 MHz, CDCl3)
148.5,
d
139.4, 134.7, 129.8, 129.4, 128.7, 127.1, 126.8, 122.8, 118.4, 117.8, 114.7,
53.3, 44.2, 28.6, 21.7.
7. (a) Murahashi, S.-I.; Zhang, D. Chem. Soc. Rev. 2008, 37, 1490e1501; (b) Rao
Volla, C. M.; Vogel, P. Org. Lett. 2009, 11, 1701e1704; (c) Wasa, M.; Engle, K. M.;
Yu, J. Q. J. Am. Chem. Soc. 2009, 131, 9886e9887; (d) Zhang, Y. H.; Shi, B. F.; Yu, J.
Q. Angew. Chem., Int. Ed. 2009, 48, 6097e6100; (e) Liu, C.; Zhang, H.; Shi, W.; Lei,
A. Chem. Rev. 2011, 111, 1780e1824.
8. (a) Murahashi, S.-I.; Komiya, N.; Terai, H.; Nakae, T. J. Am. Chem. Soc. 2003, 125,
15312e15313; (b) Murahashi, S.-I.; Komiya, N.; Terai, H. Angew. Chem., Int. Ed.
2005, 44, 6931e6933; (c) Murahashi, S.-I.; Nakae, T.; Terai, H.; Komiya, N. J. Am.
Chem. Soc. 2008, 130, 11005e11012; (d) Verma, S.; Jain, S. L.; Sain, B. Chem-
CatChem 2011, 3, 1329e1332.
4.4.22. 2-(4-Bromophenyl)-1,2,3,4,-tetrahydroisoquinoline-1-
carbonitrile (2v).11c Yellow solid, mp 155e156 ꢁC. 1H NMR
(400 MHz, CDCl3)
d 7.47e7.41 (m, 2H), 7.34e7.19 (m, 4H), 6.94 (d,
J¼8.8 Hz, 2H), 5.45 (s, 1H), 3.75e3.64 (m, 1H), 3.52e3.41 (m, 1H),
3.19e3.11 (m, 1H), 3.02e2.89 (m, 1H); 13C NMR (100 MHz, CDCl3)
d
147.4, 134.4, 132.5, 129.4, 129.3, 128.9, 127.1, 127.0, 119.1, 117.5,
114.4, 52.9, 44.3, 28.4.
9. (a) Han, W.; Ofial, A. R. Chem. Commun. 2009, 5024e5026; (b) Singhal, S.; Jain,
S. L.; Sain, B. Adv. Synth. Catal. 2010, 352, 1338e1344; (c) Liu, P.; Liu, Y.; Wong, E.
L.; Xiang, S.; Che, C.-M. Chem. Sci. 2011, 2, 2187e2195.
10. Singhal, S.; Jain, S. L.; Sain, B. Chem. Commun. 2009, 2371e2373.
11. (a) Li, Z.; Li, C.-J. Eur. J. Org. Chem. 2005, 3173e3176; (b) Boess, E.; Schmitz, C.;
Klussmann, M. J. Am. Chem. Soc. 2012, 134, 5317e5325; (c) Zhang, G.; Ma, Y.;
Cheng, G.; Liu, D.; Wang, R. Org. Lett. 2014, 16, 656e659.
4.4.23. 2-(4-Methoxyphenyl)-1,2,3,4,-tetrahydroisoquinoline-1-
carbonitrile (2w).11c Yellow oil. 1H NMR (400 MHz, CDCl3)
d
7.32e7.21 (m, 4H), 7.11e7.06 (m, 2H), 6.94e6.87 (m, 2H), 5.36 (s,
1H), 3.79 (s, 3H), 3.60e3.54 (m, 1H), 3.46e3.38 (m, 1H), 3.19e3.11
(m, 1H), 2.96e2.88 (m, 1H); 13C NMR (100 MHz, CDCl3)
155.7,
d
12. Alagiri, K.; Prabhu, K. R. Org. Biomol. Chem. 2012, 10, 835e842.
13. Lin, A.; Peng, H.; Abdukader, A.; Zhu, C. Eur. J. Org. Chem. 2013, 7286e7290.
14. For selected reviews, see: (a) Modern Gold Catalyzed Synthesis; Hashmi, A.
S. K., Toste, F. D., Eds.; Wiley-VCH: Weinheim, 2012; (b) Li, Z.; Brouwer, C.;
He, C. Chem. Rev. 2008, 108, 3239e3265; (c) Hashmi, A. S. K. Chem. Rev.
2007, 107, 3180e3211; (d) Rudolph, M.; Hashmi, A. S. K. Chem. Soc. Rev.
2012, 41, 2448e2462; (e) Hashmi, A. S. K. Angew. Chem., Int. Ed. 2010, 49,
5232e5241; (f) Wegner, H. A.; Auzias, M. Angew. Chem., Int. Ed. 2011, 50,
8236e8247; (g) Corma, A.; Leyva-Perez, A.; Sabater, M. J. Chem. Rev. 2011,
111, 1657e1712.
15. For selected examples, see: (a) Hashmi, A. S. K.; Schwarz, L.; Choi, J. H.; Frost, T.
M. Angew. Chem., Int. Ed. 2000, 39, 2285e2288; (b) Wang, S.; Zhang, L. J. Am.
Chem. Soc. 2006, 128, 14274e14275; (c) Brand, J. P.; Waser, J. Angew. Chem., Int.
Ed. 2010, 49, 7304e7307; (d) Shi, Z.; He, C. J. Org. Chem. 2004, 69, 3669e3671;
(e) Yao, X.-Q.; Li, C.-J. J. Am. Chem. Soc. 2004, 126, 6884e6885; (f) Kennedy-
Smith, J.-J.; Staben, S.-T.; Toste, F. D. J. Am. Chem. Soc. 2004, 126, 4526e4527; (g)
Chen, Y.; Chen, M.; Liu, Y. Angew. Chem., Int. Ed. 2012, 51, 6181e6186; (h) Wei, C.;
Li, C.-J. J. Am. Chem. Soc. 2003, 125, 9584e9585; (i) Chen, Y.; Lu, Y.; Li, G.; Liu, Y.
Org. Lett. 2009, 11, 3838e3841; (j) de Haro, T.; Nevado, C. J. Am. Chem. Soc. 2010,
132, 1512e1513.
16. For selected examples, see: (a) Yang, C. G.; He, C. J. Am. Chem. Soc. 2005, 127,
6966e6967; (b) Mo, F.; Yan, J. M.; Qiu, D.; Li, F.; Zhang, Y.; Wang, J. Angew. Chem.
, Int. Ed. 2010, 49, 2028e2032; (c) Zhang, J.; Yang, C.-G.; He, C. J. Am. Chem. Soc.
2006, 128, 1798e1799; (d) Liu, Y.; Song, F.; Guo, S. J. Am. Chem. Soc. 2006, 128,
11332e11333; (e) Ye, L.; Cui, L.; Zhang, G.; Zhang, L. J. Am. Chem. Soc. 2010, 132,
3258e3259; (f) Brouwer, C.; He, C. Angew. Chem., Int. Ed. 2006, 45, 1744e1747;
(g) Hesp, K. D.; Stradiotto, M. J. Am. Chem. Soc. 2010, 132, 18026e18027; (h) Yan,
B.; Liu, Y. Org. Lett. 2007, 9, 4323e4326.
17. (a) Guan, B.; Xing, D.; Cai, G.; Wan, X.; Yu, N.; Fang, Z.; Yang, L.; Shi, Z. J. Am.
Chem. Soc. 2005, 127, 18004e18005; (b) Hashmi, A. S. K.; Lothschutz, C.; Ac-
kermann, M.; Doepp, R.; Anantharaman, S.; Marchetti, B.; Bertagnolli, H.; Ro-
minger, F. Chem.dEur. J. 2010, 16, 8012e8019; (c) Xu, C.-F.; Xu, M.; Jia, Y.-X.; Li,
C.-Y. Org. Lett. 2011, 13, 1556e1559; (d) Zhang, Y.; Peng, H.; Zhang, M.; Cheng, Y.;
Zhu, C. Chem. Commun. 2011, 2354e2356; (e) Cinellu, M. A.; Minghetti, G.;
Cocco, F.; Stoccoro, S.; Zucca, A.; Manassero, M. Angew. Chem., Int. Ed. 2005, 44,
6892e6895; (f) Wang, L.; Xie, X.; Liu, Y. Angew. Chem., Int. Ed. 2013, 52,
13302e13306; (g) Chen, M.; Chen, Y.; Sun, N.; Zhao, J.; Liu, Y.; Li, Y. Angew. Chem.
, Int. Ed. 2015, 54, 1200e1204.
18. For selected reviews, see: (a) Polshettiwar, V.; Luque, R.; Fihri, A.; Zhu, H.;
Bouhrara, M.; Basset, J. M. Chem. Rev. 2011, 111, 3036e3075; (b) Nasir Baig, R. B.;
Varma, R. S. Chem. Commun. 2013, 752e770; (c) Wang, D.; Astruc, D. Chem. Rev.
2014, 114, 6949e6985.
19. For selected examples, see: (a) Stevens, P. D.; Li, G.; Fan, J.; Yen, M.; Gao, Y.
Chem. Commun. 2005, 4435e4437; (b) Liu, J.; Peng, X.; Sun, W.; Zhao, Y.; Xia, C.
Org. Lett. 2008, 10, 3933e3936; (c) Baruwati, B.; Guin, D.; Manorama, S. V. Org.
Lett. 2007, 90, 5377e5380; (d) Jin, M.-J.; Lee, D.-H. Angew. Chem., Int. Ed. 2010,
49, 1119e1123; (e) Shylesh, S.; Wang, L.; Thiel, W. R. Adv. Synth. Catal. 2010, 352,
425e432; (f) Li, P.; Wang, L.; Zhang, L.; Wang, G. W. Adv. Synth. Catal. 2012, 354,
1307e1318.
20. (a) Kotani, M.; Koike, T.; Yamaguchi, K.; Mizuno, N. Green Chem. 2006, 8,
735e741; (b) Hu, A.; Yee, G. T.; Lin, W. J. Am. Chem. Soc. 2005, 127,
12486e12487; (c) Polshettiwar, V.; Varma, R. S. Chem.dEur. J. 2009, 15,
1582e1586.
21. Abu-Reziq, R.; Alper, H.; Wang, D.; Post, M. L. J. Am. Chem. Soc. 2006, 128,
5279e5282.
142.6, 134.4, 129.7, 129.5, 128.7, 127.1, 126.7, 121.0, 117.7, 114.8, 55.6,
51.2, 44.9, 28.7.
4.4.24. 2-(4-Trifluoromethylphenyl)-1,2,3,4,-tetrahydroisoquinoline-
1-carbonitrile (2x).35 White solid, mp 101e102 ꢁC. 1H NMR
(400 MHz, CDCl3)
d
7.58 (d, J¼8.4 Hz, 2H), 7.35e7.21 (m, 4H), 7.07 (d,
J¼8.8 Hz, 2H), 5.57 (s, 1H), 3.88e3.79 (m, 1H), 3.59e3.49 (m, 1H),
3.18e3.12 (m, 1H), 3.10e2.96 (m, 1H); 13C NMR (100 MHz, DMSO)
d
150.4, 134.5, 129.3, 129.0, 128.7, 126.8, 126.6, 126.5, 126.4, 124.7 (q,
1JCeF¼269.0 Hz), 118.4, 115.2, 49.4, 42.8, 27.5.
Acknowledgements
We thank the National Natural Science Foundation of China (No.
21462021) and Key Laboratory of Functional Small Organic Mole-
cule, Ministry of Education (No. KLFS-KF-201409) for financial
support.
Supplementary data
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2016.05.037.
References and notes
1. (a) Dyker, G. Angew. Chem., Int. Ed. 1997, 36, 1700e1702; (b) Martinez, E. J.;
Corey, E. J. Org. Lett. 1999, 1, 75e78; (c) Enders, D.; Shilvock, J. P. Chem. Soc.
Rev. 2000, 29, 359e373; (d) North, M. Angew. Chem., Int. Ed. 2004, 43,
4126e4128; (e) En, D.; Zou, G.-F.; Guo, Y.; Liao, W.-W. J. Org. Chem. 2014, 79,
4456e4462.
2. (a) North, M. In Comprehensive Organic Functional Group Transformations; Ka-
tritzky, A. R., Meth-Cohn, O., Rees, C. W., Pattenden, G., Eds.; Pergamon, Oxford:
1995; Vol. 3, pp 611e617; (b) Fukuda, Y.; Kondo, K.; Aoyama, T. Synthesis 2006,
2649e2652; (c) Ishitani, H.; Komiyama, S.; Kobayashi, S. Angew. Chem., Int. Ed.
1998, 37, 3186e3188; (d) Wiles, C.; Watts, P. Eur. J. Org. Chem. 2008, 5597e5613;
(e) Surendra, K.; Krishnaveni, N. S.; Mahesh, A.; Rao, K. R. J. Org. Chem. 2006, 71,
2532e2534; (f) Heydari, A.; Khaksar, S.; Pourayoubi, M.; Mahjoub, A. R. Tetra-
hedron Lett. 2007, 48, 4059e4060.
3. (a) Barton, D. H. R.; Billion, A.; Boivin, J. Tetrahedron Lett. 1985, 26, 1229e1232;
(b) Stock, G.; Jacobsen, R. M.; Levitz, R. Tetrahedron Lett. 1979, 20, 771e773.
4. (a) Chen, C.-K.; Hortmann, A. G.; Marzabadi, M. R. J. Am. Chem. Soc. 1988, 110,
4829e4831; (b) Groutas, W. C.; Essawi, M.; Portoghese, P. S. Synth. Commun.
1980, 10, 495e499; (c) Koskinen, A.; Lounasmaa, M. Tetrahedron 1983, 39,
1627e1633; (d) Leonard, N. J.; Hay, A. S. J. Am. Chem. Soc. 1956, 78, 1984e1987;
(e) Shu, X.-Z.; Xia, X.-F.; Yang, Y.-F.; Ji, K.-G.; Liu, X.-Y.; Liang, Y.-M. J. Org.
Chem. 2009, 74, 7464e7469; (f) Liu, L.; Wang, Z.; Fu, X.; Yan, C.-H. Org. Lett.
Please cite this article in press as: Yang, W.; et al., Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.05.037

W. Yang et al. / Tetrahedron xxx (2016) 1e9
9
22. (a) Wang, D.; Etienne, L.; Echeverria, M.; Moya, S.; Astruc, D. Chem.dEur. J.
2014, 20, 4047e4054; (b) Nasir Baig, R. B.; Varma, R. S. Green Chem. 2012, 14,
625e632; (c) Nasir Baig, R. B.; Varma, R. S. Chem. Commun. 2012, 2582e2584;
(d) Zeng, T.; Yang, L.; Hudson, R.; Song, G.; Moores, A. R.; Li, C.-J. Org. Lett. 2011,
13, 442e445.
28. Harsha, K.; Reddy, V.; Satish, G.; Prakash Reddy, V.; Anil Kumar, B. S. P.; Na-
geswar, Y. V. D. RSC Adv. 2012, 2, 11084e11088.
29. Temple, C., Jr.; Kussner, C. L.; Montgomery, J. A. J. Org. Chem. 1974, 39,
2866e2871.
30. Wagner, A.; Han, W.; Mayer, P.; Ofial, A. R. Adv. Synth. Catal. 2013, 355,
3058e3070.
23. Sadeghzadeh, S. M. RSC Adv. 2014, 4, 43315e43320.
24. (a) Cai, M.; Zheng, G.; Ding, G. Green Chem. 2009, 11, 1687e1693; (b) Cai, M.;
Peng, J.; Hao, W.; Ding, G. Green Chem. 2011, 13, 190e196; (c) Zhao, H.; Cheng,
M.; Zhang, J.; Cai, M. Green Chem. 2014, 16, 2515e2522; (d) Zhao, H.; He, W.;
Yao, R.; Cai, M. Adv. Synth. Catal. 2014, 356, 3092e3098.
25. Tsai, F.-Y.; Lin, B.-N.; Chen, M.-J.; Mou, C.-Y.; Liu, S.-T. Tetrahedron 2007, 63,
4304e4309.
31. Panwar, V.; Kumar, P.; Bansal, A.; Ray, S. S.; Jain, S. L. Appl. Catal. A Gen. 2015,
498, 25e31.
32. Liu, W.; Ma, Y.; Yin, Y.; Zhao, Y. Bull. Chem. Soc. Jpn. 2006, 79, 577e579.
33. Patil, M.; Kapdi, A. R.; Vijay Kumar, A. RSC Adv. 2015, 5, 54505e54509.
34. Renaud, T.; Hurvois, J.-P.; Uriac, P. Eur. J. Org. Chem. 2001, 987e996.
35. Yang, R.; Ruan, Q.; Zhang, B.-Y.; Zheng, Z.-L.; Miao, F.; Zhou, L.; Geng, H.-L.
Molecules 2014, 19, 8051e8066.
26. Singh, S.; Prasad, B. L. V. J. Phys. Chem. C 2007, 111, 14348e14352.
27. Zhang, C.; Liu, C.; Shao, Y.; Bao, X.; Wan, X. Chem.dEur. J. 2013, 19, 17917e17925.
Please cite this article in press as: Yang, W.; et al., Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.05.037