Highly efficient heterogeneous aerobic oxidative C-C coupling from C sp3-H bonds by a magnetic nanoparticle-immobilized bipy-gold(iii) catalyst

Article abstract of DOI:10.1039/c6cy02567f

A highly efficient heterogeneous cross-dehydrogenative coupling (CDC) of tertiary amines with nitroalkanes and various unmodified ketones was achieved by using a magnetic nanoparticle-immobilized bipy-gold(iii) complex as catalyst and air as the sole oxid

Full text of DOI:10.1039/c6cy02567f

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Highly efficient heterogeneous aerobic oxidative C–C
coupling from C –H bonds by a magnetic nanoparticles-
3
sp
immobilized bipy-gold(III) catalyst
Weisen Yang,a,b Li Wei,a Tao Yana and Mingzhong Caia*
a Key Laboratory of Functional Small Organic Molecule, Ministry of Education and
College of Chemistry & Chemical Engineering, Jiangxi Normal University, Nanchang
330022, P. R. China
b College of Ecology and Resources Engineering, Wuyi University, Wuyishan City
354300, P. R. China
Fax: (+86)ꢀ791ꢀ8812ꢀ0388; Eꢀmail: mzcai@jxnu.edu.cn
A highly efficient heterogeneous crossꢀdehydrogenative coupling (CDC) of tertiary
amines with nitroalkanes and various unmodified ketones was achieved by using a
magnetic nanoparticlesꢀimmobilized bipyꢀgold(III) complex as catalyst and air as the
sole oxidant to afford the corresponding C–C coupling products in good to excellent
yields under mild reaction conditions. The new heterogeneous gold catalyst can easily
be separated from the reaction mixture by applying an external magnet and can be
recycled for at least ten times without a significant loss of activity.
Introduction
The construction of C–C bond is a central part of many chemical syntheses, and the
development of new methods for forming C–C bonds will profoundly improve overall
synthetic efficiency. Transition metalꢀcatalyzed C–H bond activations and subsequent
C–C bond formations1 and crossꢀcoupling reactions of various reactive functional
groups2 have become powerful tools for constructing C–C bonds. From a practical
point of view, the crossꢀdehydrogenative coupling (CDC) reaction of two different
1

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C–H bonds of pronucleophiles and proelectrophiles will avoid the use of previously
functionalized substrates and thus make synthetic schemes shorter and more efficient.
Since the pioneering works on the crossꢀdehydrogenative coupling (CDC) reactions
demonstrated by Li and Murahashi through the activation of the αꢀCsp3–H bond of
tertiary amines,3 a tremendous progress has been achieved on this subject mostly
employing highꢀvalent transitionꢀmetal catalysts combined with oxidants.4 A wide
range of transitionꢀmetals including copper,5 ruthenium,6 platinum,7 palladium,8 and
vanadium9 have been utilized as the catalysts for oxidative CDC reactions between
tertiary amines and sp3 C–H compounds in the presence of a stoichiometric amount of
oxidants or pure oxygen. However, from the viewpoint of green and sustainable
chemistry, the development of recyclable supported catalysts having a high catalytic
activity for sp3 C–H functionalizations would be highly desirable.10 In spite of the
significant progress made in the homogeneous transitionꢀmetal catalysis, very few
reports on heterogeneous catalytic CDC reactions of tertiary amines have been
described thus far11 and, in most cases, these heterogeneous catalysts such as Fe3O4
nanoparticles, SBAꢀ15ꢀsupported Fe(II) terpyridine complex, and RuO2 nanoparticles
on grapheme, did not exhibit satisfactory high recyclability and high temperatures
were required for these heterogeneous reactions.
The past two decades have witnessed dramatic growth in reports on reactions
catalyzed by gold complexes owing to their unique reactivity as soft and carbophilic
Lewis acids.12 To date, the goldꢀcatalyzed carbonꢀcarbon13 and carbonꢀheteroatom14
bond formation reactions have successfully been used in organic synthesis. However,
2

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the goldꢀcatalyzed oxidative C–C coupling of sp3 C–H bonds under aerobic oxidative
conditions remains a challenge.15 In addition, the use of homogeneous gold catalysts
has seriously limited the utility of these reactions because they are quite expensive,
cannot be recovered and recycled. Although gold nanoparticles supported on different
matrices have been used as heterogeneous catalysts for some organic transformations
in recent years,16 little progress has been made on the supported gold complexesꢀ
catalyzed reactions so far.17 Recently, magnetic nanoparticlesꢀsupported catalysts have
received more and more attention because their magnetic separation is an alternative
to filtration or centrifugation as it prevents loss of catalyst and increases the reusaꢀ
bility.18 It is well known that air is a sustainable and favorable oxidant and has
received much attention in modern oxidation chemistry because of water as the only
waste product.19 To the best of our knowledge, there is no successful example of a
heterogeneous goldꢀcatalyzed αꢀCsp3–H functionalization of tertiary amines with air as
the sole oxidant. As a part of our continuing interest in the development of efficient
heterogeneous catalysts for organic synthesis,20 herein we wish to report an efficient
magnetically recoverable and reusable Fe3O4 nanoparticlesꢀimmobilized bipyꢀgold(III)
complex and its successful application to the oxidative crossꢀdehydrogenative coupꢀ
ling (CDC) of tertiary amines with nitroalkanes and various unmodified ketones with
air as the sole oxidant. The new catalyst could be easily recovered by decantation of
the reaction mixture in the presence of an external magnet and reused at least 10 times
without significant loss of its catalytic activity.
3

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Results and discussion
The magnetic nanoparticlesꢀimmobilized bipyꢀgold(III) complex (Fe3O4@SiO2ꢀbipyꢀ
AuCl2]+[AuCl4]－) was synthesized according to the procedure summarized in Scheme
1. Firstly, the treatment of bis(bromomethyl)ꢀfunctionalized bipyꢀgold(III) complex
[(BrCH2)2bipyꢀAuCl2][AuCl4]21 with 3ꢀaminopropyltriethoxysilane in THF in the preꢀ
sence of Et3N gave the triethoxysilylꢀfunctionalized [(bipy)AuCl2][AuCl4] complex.
The latter was then reacted with the silicaꢀcoated Fe3O4 (Fe3O4@SiO2)22 in toluene
under reflux for 24 h to afford the magnetic nanoparticlesꢀimmobilized bipyꢀgold(III)
complex (Fe3O4@SiO2ꢀbipyꢀAuCl2]+[AuCl4]－), the gold content was determined to be
0.23 mmol gꢀ1 by ICPꢀAES.
-
Br
[AuCl4]
Cl
Br
(EtO)
3Si
N
H
N
N
(EtO)3Si(CH2)3NH2
-
[AuCl4]
Au
Et3N, THF, 50 oC, 6 h
Cl
H
N
N
N
(EtO)
3Si
Au
Cl
Cl
-
OEt
O
[AuCl4]
Fe O
Fe O
Si
O
N
H
(Fe3O4@SiO2)
3
4
4
3
N
Cl
Cl
SiO2
Fe O
Fe O
Au
3
4
4
3
O
O
H
N
N
SiO2
Toluene, reflux, 24 h
Si
OEt
-
Fe3O4@SiO2-bipy-AuCl2]
[AuCl4]
Scheme 1 Synthesis of magnetic nanoparticlesꢀimmobilized bipyꢀgold(III) complex.
The TEM image of the Fe3O4@SiO2ꢀbipyꢀAuCl2]+[AuCl4]－complex shows slight
aggregation and the size of the particles were between 30 and 40 nm (Fig. 1a). The
XRD spectra of Fe3O4@SiO2 and Fe3O4@SiO2ꢀbipyꢀAuCl2]+[AuCl4]－ complex are
presented in Fig. 2. XRD measurements of Fe3O4@SiO2 exhibit diffraction peaks
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corresponding to the typical spinel maghemite structure whereas the diffraction peak
of the layered amorphous silica was not obvious. XRD measurements of the Fe3O4
@SiO2ꢀbipyꢀAuCl2]+[AuCl4]－obviously show two sets of diffraction peaks, the new
peaks that appeared are attributed to the Au species. The energy dispersive Xꢀray
spectroscopy (EDS) shows the elements present in the material. EDS analysis of the
fresh Fe3O4@SiO2ꢀbipyꢀAuCl2]+[AuCl4]－complex shows the presence of Si, O, C, N,
Cl, Fe, and Au elements (Fig. 3).
Fig. 1 TEM images of Fe3O4@SiO2ꢀbipyꢀAuCl2]+[AuCl4]－(a) and recycled Fe3O4@
SiO2ꢀbipyꢀAuCl2]+[AuCl4]－(b).
Fig. 2 XRD patterns of Fe3O4@SiO2 (a) and Fe3O4@SiO2ꢀbipyꢀAuCl2]+[AuCl4]－(b).
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Fig. 3 EDS analysis of Fe3O4@SiO2ꢀbipyꢀAuCl2]+[AuCl4]－.
The presence of magnetic iron oxide inside Fe3O4@SiO2ꢀbipyꢀAuCl2]+[AuCl4]－
prevents the analysis of organic functional groups by solid state NMR spectroscopy.
Therefore, these hybrid materials were further analyzed by FTꢀIR spectroscopy (Fig. 4)
and elemental analysis. The FTꢀIR spectrum (Fig. 4a) of Fe3O4@SiO2 shows the Fe–O
stretching absorption at 580 cmꢀ1 and a sharp band for the Si–O vibration at 1089 cmꢀ1.
In the FTꢀIR spectrum (Fig. 4b) of Fe3O4@SiO2ꢀbipyꢀAuCl2]+[AuCl4]－absorptions at
3355 cmꢀ1 (N–H), 2970 and 2884 cmꢀ1 (CH3), 2928 cmꢀ1 (CH2), and typical bipyridine
bands at 1599, 1560 and 1443 cmꢀ1 were observed indicating the presence of silylated
bipyꢀgold(III) groups. The results from FTꢀIR imply that the bipyꢀgold(III) complex
has been successfully grafted on the surface of MNPs. By determination of the nitroꢀ
gen content (C, H, N elemental analysis), a bipyꢀgold(III) complex loading of approꢀ
ximately 0.12 mmol gꢀ1 was calculated for the Fe3O4@SiO2ꢀbipyꢀAuCl2]+[AuCl4]－
complex, which is in well accordance with the Au content determined by ICPꢀAES
analysis. The N2 adsorptionꢀdesorption isotherms for Fe3O4@SiO2 and Fe3O4@SiO2ꢀ
bipyꢀAuCl2]+[AuCl4]－are illustrated in Fig. 5. The isotherms in Fig. 5 have remarkꢀ
able changes before and after grafting, but both samples exhibited type II isotherms,
characteristic of nonꢀporous materials according to the IUPAC classification. After the
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grafting the bipyꢀgold(III) complex onto Fe3O4@SiO2, the surface area and pore
volume decreased from 27.9 m2 gꢀ1 and 0.044 cm3 gꢀ1 to 11.4 m2 gꢀ1 and 0.025 cm3 gꢀ1,
respectively.
a
100
1625
b
80
1400
580
1089
60
40
20
0
1599
1560
1443
1402
3355
2970
2884
2928
570
1076
a
: Fe O @SiO
3 4
2
b
: Fe O @SiO ꢀbipyꢀAuCl ][AuCl ]
3 4 2 2 4
4000 3500 3000 2500 2000 1500 1000
500
-1)
Wavenumbers (cm
Fig. 4 FTꢀIR spectra of Fe3O4@SiO2 (a) and Fe3O4@SiO2ꢀbipyꢀAuCl2]+[AuCl4]－(b).
30
a: Fe O @SiO
3 4
2
25
20
15
10
5
b: Fe O @SiO ꢀbipyꢀAuCl ][AuCl ]
3 4 4
2
2
a
b
0
0.0
0.2
0.4
0.6
0.8
1.0
Relative pressure /P/P0
Fig. 5 N2 adsorption/desorption isotherms of Fe3O4@SiO2 (a) and Fe3O4@SiO2ꢀ
bipyꢀAuCl2]+[AuCl4]－(b).
In our initial screens, the aerobic oxidative C–C coupling of Nꢀphenyl tetrahydroꢀ
isoquinoline 1a with nitromethane 2a was selected as the model reaction to optimize
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the reaction conditions and the results are summarized in Table 1. Firstly, catalyst
effect was examined by using various heterogeneous gold complexes as catalyst in
MeOH as solvent at 60 ºC under air (Table 1, entries 1ꢀ3). When a magnetic nanoꢀ
particlesꢀsupported phosphineꢀAu(I) complex17f (Fe3O4@SiO2ꢀPꢀAuCl) was used as
catalyst, only a trace amount of the desired product 3a was formed. To our delight, the
aerobic oxidative C–C coupling reaction could proceed smoothly under the catalysis
of Fe3O4@SiO2ꢀbipyꢀAuCl2]+[AuCl4]－to afford 3a in 69% yield (entry 2). Whilst
another magnetic nanoparticlesꢀimmobilized bipyꢀgold(III) complex17e (Fe3O4@SiO2ꢀ
bipyꢀAuCl2][Cl]) was substantially less effective and gave a moderate yield (entry 3).
A control experiment demonstrated that a trace amount of the desired product 3a was
obtained in the absence of any catalyst (entry 4). When the aerobic oxidative C–C
coupling reaction was carried out in MeNO2 as the solvent at 60 ºC under air, the
desired product 3a was obtained in 80% yield after 12 h (entry 5). We were pleased to
find that the yield could be further increased to 83% within 6 h by addition of a small
amount of MeOH (entry 6). Even if the amount of the catalyst was reduced to 3 mol%,
the reaction also proceeded smoothly to afford 3a in 82% yield after 8 h (entry 7).
When the homogeneous unsupported bipyꢀgold(III) complex was used as the catalyst,
the desired product 3a was also isolated in 84% yield after 5 h (entry 8), indicating
that the catalytic activity of Fe3O4@SiO2ꢀbipyꢀAuCl2]+[AuCl4]－was comparable to
that of the homogeneous [(bipy)AuCl2][AuCl4] complex. It is noteworthy that, when
the oxidative C–C coupling reaction was performed in an argon atmosphere instead of
air, the reaction proceeded very slowly and a much lower yield was obtained (entry 9).
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Thus, the optimized reaction conditions for this transformation are the Fe3O4@SiO2ꢀ
bipyꢀAuCl2]+[AuCl4]－(3 mol%) in MeNO2 as solvent in the presence of a small
amount of MeOH at 60 °C under air for 8 h (Table 1, entry 7).
Table 1 Optimization of the heterogeneous goldꢀcatalyzed aerobic oxidative C–C
coupling of Nꢀphenyl tetrahydroisoquinoline 1a with nitromethane 2a.a
Entry Au catalyst (mol%)
Solvent Time (h) Yield(%)b
1
Fe3O4@SiO2ꢀPꢀAuCl (5)
MeOH
MeOH
MeOH
MeOH
12
12
12
12
trace
69
2
Fe3O4@SiO2ꢀbipyꢀAuCl2][ AuCl4] (5)
Fe3O4@SiO2ꢀbipyꢀAuCl2][Cl] (5)
–
3
45
4
trace
80
5
Fe3O4@SiO2ꢀbipyꢀAuCl2][AuCl4] (5)
Fe3O4@SiO2ꢀbipyꢀAuCl2][AuCl4] (5)
Fe3O4@SiO2ꢀbipyꢀAuCl2][AuCl4] (3)
[(bipy)AuCl2][AuCl4] (3)
MeNO2 12
6c
7c
8c
9c,d
MeNO2
MeNO2
MeNO2
6
8
5
83
82
84
Fe3O4@SiO2ꢀbipyꢀAuCl2][AuCl4] (3)
MeNO2 24
13
a Reaction conditions: 1a (0.1 mmol), 2a (0.2 mL), heterogeneous Au catalyst (3ꢀ5 mol%), solvent
(0.8 mL) at 60 ºC under air. b Isolated yield. c MeOH (0.1 mL) was used as coꢀsolvent. d The
reaction was performed under Ar.
With this promising result in hand, we started to investigate the scope of this
heterogeneous gold(III)ꢀcatalyzed aerobic oxidative C–C coupling reaction under the
optimized conditions. Initially, a variety of Nꢀaryltetrahydroisoquinolines 1a-h were
investigated as substrates to explore the functional group tolerance and the results are
listed in Table 2. To our delight, both electronꢀdonating and electronꢀwithdrawing
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groups on the aromatic rings were compatible under the optimized reaction conditions.
The reactions of all the substrates with nitromethane proceeded smoothly to afford the
corresponding 1ꢀnitromethylꢀsubstituted Nꢀaryltetrahydroisoquinolines 3a-h in good
to high yields. Interestingly, the less active nitroethane 2b can also be used as the
nucleophile under the optimized conditions to give the corresponding C–C coupling
products 3i-o in good yields. When a nonbenzylic tertiary amine such as N,Nꢀ
dimethylꢀ4ꢀmethylaniline was employed as substrate, the desired product 3p was also
obtained in satisfactory yield after 36 h.
Table 2 Heterogeneous gold(III)ꢀcatalyzed aerobic oxidative C–C coupling reaction
of tertiary amines with nitroalkanes.a,b
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a Reaction conditions: tertiary aniline 1 (0.1 mmol), nitroalkane 2/MeOH (v/v = 9:1, 1.0 mL),
Fe3O4@SiO2ꢀbipyꢀAuCl2][AuCl4] (3 mol%) at 60 ºC for 8 h under air. b Isolated yield. c For 36 h.
Encouraged by the above results, we then applied the heterogeneous goldꢀcatalyzed
strategy to the aerobic oxidative C–C coupling reaction of Nꢀaryltetrahydroisoquinoꢀ
lines with three unmodified ketones to further illustrate the generality of our protocol
and the results are listed in Table 3. Initially, treatment of 1b with acetone 2c in the
presence of 3 mol% of Fe3O4@SiO2ꢀbipyꢀAuCl2]+[AuCl4]－in acetone as solvent gave
the desired product 3q in only 27% yield. We were pleased to find that addition of
molecular sieves (4 Ǻ) and an acid were beneficial to the aerobic oxidative C–C
coupling reaction and the yield of 3q could be improved to 73%. Under the optimized
reaction conditions, a wide range of Nꢀaryltetrahydroisoquinolines could undergo the
oxidative C–C coupling reaction with acetone smoothly to furnish the corresponding
C–C coupling products 3q-v in good yields (73ꢀ86%). The results indicated that the
electronic effect of substituents on the aromatic rings has limited influence on this
heterogeneous goldꢀcatalyzed C–C coupling reaction. The bulky acetophenone 2d
was proved to be an active nucleophile and coupled with different Nꢀaryltetrahydroꢀ
isoquinolines effectively to afford the desired products 3w-z in good yields. Notably,
besides methyl ketones, cyclohexanone 2e was also a suitable substrate and could
undergo the aerobic oxidative C–C coupling reaction with Nꢀaryltetrahydroisoquinoꢀ
lines smoothly to give the desired products 3a' and 3b' in useful synthetic yields.
Table 3 Heterogeneous gold(III)ꢀcatalyzed aerobic oxidative C–C coupling reaction
of Nꢀaryltetrahydroisoquinolines with ketones.a,b
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a Reaction conditions: Nꢀaryltetrahydroisoquinoline 1 (0.1 mmol), ketone 2 (0.5 mL), 4 Ǻ MS (60
b
mg), HOAc (0.1 mL), Fe3O4@SiO2ꢀbipyꢀAuCl2][AuCl4] (3 mol%) at 60 ºC for 12 h under air.
Isolated yield. c MsOH (5 ꢁL) was used.
To determine whether the observed catalysis was due to the heterogeneous catalyst
Fe3O4@SiO2ꢀbipyꢀAuCl2]+[AuCl4]－or to a leached gold species in solution, the
aerobic oxidative C–C coupling reaction of Nꢀphenyl tetrahydroisoquinoline 1a with
nitromethane 2a was carried out until an approximately 50% conversion of 1a was
reached. The Fe3O4@SiO2ꢀbipyꢀAuCl2]+[AuCl4]－catalyst was then separated magꢀ
netically from the solution and the reaction solution was transferred to another
reaction tube and stirred again at 60 ºC for 6 h. If gold was leaching from the solid
surface during the reaction, the solution should contain gold. In this case, no signiꢀ
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ficant increase in conversion of 1a was observed, indicating that leached Au species
from the catalyst (if any) are not responsible for the observed activity. It was conꢀ
firmed by ICPꢀAES analysis that indicated that no gold species could be detected in
the reaction solution after the separation of Fe3O4@SiO2ꢀbipyꢀAuCl2]+[AuCl4]－.
These results rule out any contribution to the observed catalysis from a homogeneous
gold species demonstrating that the catalytic oxidative C–C coupling reaction was
intrinsically heterogeneous.
Although the exact mechanism of the goldꢀcatalyzed C–C coupling reaction is not
clear at this stage, a plausible mechanism for this heterogeneous goldꢀcatalyzed reacꢀ
tion is showed in Scheme 2. Initially, the Fe3O4@SiO2ꢀbipyꢀAuCl2]+[AuCl4]－complex
may be reduced by the solvent or substrates to a magnetic nanoparticlesꢀsupported
gold(I) species (A),13e which would coordinate to tertiary amine (1a) to produce an
intermediate (B). An electron transfer and subsequent hydrogen transfer from tertiary
amine (1a) to gold gives a magnetic nanoparticlesꢀsupported iminium gold hydride
complex (C). The AuH species (C) could form the iminium ion/AuOOH complex (D)
in the presence of air (O2) in a similar way to PdH and RuH.23 The supported iminium
ion/AuOOH complex (D) can be trapped with nitromethane (2a) quickly to afford the
desired product (3a), H2O and the supported gold(III) oxo complex (E). Subsequently,
the latter reacts with another tertiary amine (1a) to produce the supported iminium
intermediate (F) by electron and hydrogen transfer.24 Finally, the supported iminium
intermediate (F) could react with nitromethane (2a) to give the product (3a) and
regenerate the magnetic nanoparticlesꢀsupported gold(I) species (A) to complete the
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catalytic cycle.
Fe3O4@SiO2-bipy-AuCl2][AuCl4]
reduction
3a + H2O
Ph
Fe3O4@SiO2
N
(1a)
(2a)
CH3NO2
(A)
N
N
Fe3O4@SiO2
AuI
Fe3O4@SiO2
N
N
N
N
AuI
N
OH
Ph
AuI
N
(F)
(B)
Ph
1a
Fe3O4@SiO2
Fe3O4@SiO2
Fe3O4@SiO2
(E)
N
N
N
N
AuIII
AuI
N
H
Ph
(C)
O
N
N
AuI
N
OOH
Ph
3a + H2O
CH3NO2 (2a)
air
(D)
Scheme 2 Plausible mechanism for heterogeneous goldꢀcatalyzed aerobic oxidative
C–C coupling reaction.
For the practical application of a heterogeneous precious metal catalyst system, its
stability and reusability are important factors. We next investigated the recycling of
Fe3O4@SiO2ꢀbipyꢀAuCl2]+[AuCl4]－complex by using the coupling of Nꢀ(4ꢀmethoxyꢀ
phenyl)tetrahydroisoquinoline 1f with nitromethane 2a as a model reaction. Each time,
after the reaction was finished, more than 99% of the gold catalyst could simply be
recovered by fixing a magnet near to the reaction vessel. The recovered catalyst was
washed with MeOH, airꢀdried and used directly in the next run without further puriꢀ
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fication. The recovered gold catalyst was used for ten consecutive cycles using fresh
substrates and solvent under identical conditions and the results are presented in Fig. 6.
As shown in Fig. 6, the yield of the desired product 3f in all cases was found to be
almost similar which confirmed that the developed catalyst can be recycled efficiently
for at least ten times without significant loss of activity. In addition, 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 nanoparticles could be observed. The
excellent reusability 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.
100
80
60
40
20
0
1
2
3
4
5
6
7
8
9
10
Recycling number
Fig. 6 Recycle of the Fe3O4@SiO2ꢀbipyꢀAuCl2]+[AuCl4]－catalyst.
Conclusions
In conclusion, we have developed a highly efficient heterogeneous aerobic oxidative
C–C coupling reaction of tertiary amines with nitroalkanes and various unmodified
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ketones by using a magnetic nanoparticlesꢀimmobilized bipyꢀgold(III) complex
(Fe3O4@SiO2ꢀbipyꢀAuCl2]+[AuCl4]－) as catalyst and air as the sole oxidant. The
reaction proceeds with high efficiency under mild conditions, generating the corresꢀ
ponding C–C coupling products in good to high yields. More importantly, this heteroꢀ
geneous gold catalyst can simply be recovered by applying an external magnet and
recycled at least ten times without significant loss of activity. The advantageous
features such as safe, convenient, and environmentally benign process, the broad subꢀ
strate scope, good yields, as well as easy recovery and recyclability of the catalyst
make the present protocol very practical.
Experimental
All reagents were obtained from commercial sources without further purification, and
commercially available solvents were purified before use. Bis(bromomethyl)ꢀfunctioꢀ
nalized bipyꢀgold complex [(BrCH2)2bipyꢀAuCl2][AuCl4],21 [(bipy)AuCl2][AuCl4],21
4,4'ꢀbis[3ꢀ(triethoxysilyl)propylaminomethyl]ꢀ2,2'ꢀbipyridine17e and the silicaꢀcoated
Fe3O4 (Fe3O4@SiO2)22 were prepared according to literature procedures. All products
1
13
were fully characterized. H and C NMR spectra were recorded at 400 or 100 MHz
with CDCl3 as the solvent and TMS as an internal standard. Chemical shifts are
reported in δ (ppm) relative to TMS. HRMS spectra were recorded on a QꢀTof
spectrometer with micromass MS software using electrospray ionization (ESI). Gold
content was determined with inductively coupled plasma atom emission spectrometry
(ICPꢀAES). TEM images were recorded in a transmission electron microscope
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operated at an accelerated voltage of 200 kV. Xꢀray diffraction (XRD) measurements
were carried out at room temperature using an Xꢀray powder diffractmeter. Xꢀray
energy dispersive spectroscopy (EDS) was performed using a microscope.
Preparation of Fe3O4@SiO2-P-AuCl complex
To a suspension of 0.75 g of Fe3O4@SiO2 in 30 mL of dry toluene was added a
solution of (EtO)3SiCH2CH2PPh2 (0.57 g) in 10 mL of dry toluene. The mixture was
stirred at 110 ºC under argon atmosphere for 24 h. Then the resulting material was
magnetically separated, washed repeatedly with toluene and CH2Cl2 to remove any
unanchored species and dried at 100 ºC under vacuum for 5 h to afford 0.85 g of the
phosphinoꢀfunctionalized Fe3O4@SiO2 (Fe3O4@SiO2ꢀP) as brown nanoparticles. The
phosphine content was found to be 0.44 mmol gꢀ1 by elemental analysis.
To a threeꢀnecked round bottom flask, AuCl (80 mg, 0.34 mmol) and MeOH (50
mL) were added. The solution was stirred at room temperature under argon
atmosphere for 10 min, and then 0.82 g of Fe3O4@SiO2ꢀP was added. The mixture
was stirred at 65 ºC for 12 h, then the solid catalyst was magnetically separated,
washed thoroughly with MeOH, and dried under vacuum at 100 ºC for 3 h to afford
0.88 g of Fe3O4@SiO2ꢀPꢀAuCl as brown nanoparticles. The gold content was
determined to be 0.39 mmol gꢀ1 by ICPꢀAES.
Preparation of Fe3O4@SiO2-bipy-AuCl2][AuCl4] complex
Et3N (0.202 g, 2 mmol) and 3ꢀaminopropyltriethoxysilane (0.442 g, 2 mmol) were
17

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added to a solution of [(BrCH2)2bipyꢀAuCl2][AuCl4] (0.190 g, 0.2 mmol) in THF (10
mL), and the mixture was stirred at 50 ºC under Ar for 6 h. After cooling the solution
to room temperature, hexane (20 mL) was added and the mixture was filtered through
a short MgSO4 column to remove the ammonium salt. The clear solution was then
concentrated and dried under vacuum at 100 ºC for 24 h to give the triethoxysilylꢀ
functionalized [(bipy)AuCl2][AuCl4] complex. The latter was added to a suspension
of Fe3O4@SiO2 (0.5 g) in 40 mL of dry toluene. The reaction mixture was stirred at
110 ºC under Ar for 24 h. Then the resulting material was magnetically separated,
washed repeatedly with toluene and CH2Cl2 to remove any unanchored species and
dried at 80 ºC under vacuum for 3 h to afford 0.621 g of the Fe3O4@SiO2ꢀbipyꢀAuCl2]
[AuCl4] complex as brown nanoparticles. The nitrogen content was found to be 0.51
mmol gꢀ1 by elemental analysis and the gold content was determined to be 0.23 mmol
gꢀ1 by ICPꢀAES.
Preparation of Fe3O4@SiO2-bipy-AuCl2][Cl] complex
To a suspension of 0.75 g of Fe3O4@SiO2 in 20 mL of dry toluene was added a
solution of 4,4'ꢀbis[3ꢀ(triethoxysilyl)propylaminomethyl]ꢀ2,2'ꢀbipyridine (0.872 g, 1.4
mmol) in 40 mL of dry toluene. The mixture was stirred at 110 ºC under argon
atmosphere for 24 h. Then the solid material was magnetically separated, washed
repeatedly with toluene and CH2Cl2 to remove any unanchored species and dried at
100 ºC under vacuum for 5 h to afford 0.86 g of the bipyridineꢀfunctionalized
Fe3O4@SiO2 (Fe3O4@SiO2ꢀbipy) as brown nanoparticles. The nitrogen content was
18

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found to be 2.85 mmol gꢀ1 by elemental analysis.
To a threeꢀnecked 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 Fe3O4@SiO2ꢀbipy was added. The mixture was stirred at
65 ºC for 24 h, then the solid catalyst was magnetically separated, washed thoroughly
with MeOH, and dried under vacuum at 60 ºC for 3 h to give 0.456 g of Fe3O4@SiO2ꢀ
bipyꢀAuCl2][Cl] as brown nanoparticles. The gold content was determined to be 0.63
mmol gꢀ1 by ICPꢀAES.
General procedure for heterogeneous gold-catalyzed aerobic oxidative C–C
coupling reaction of tertiary amines with nitroalkanes
To the mixture of Nꢀarylꢀ1,2,3,4ꢀtetrahydroisoquinoline (0.1 mmol) and Fe3O4@
SiO2ꢀbipyꢀAuCl2][AuCl4] (26 mg, 3 mol%) in nitroalkanes (0.9 mL) was added a
small amount of methanol (0.1 mL). Then the reaction mixture was stirred at 60 ºC
under air for 8 h. The reaction was monitored by TLC on silicaꢀgel plates (GF 254).
After completion of the reaction, the reaction mixture was cooled to room temperature
and the supported catalyst was magnetically separated and washed with methanol (2 ×
2 mL), airꢀdried and used directly for the next run. The reaction solution was concenꢀ
trated under reduced pressure and the residue was purified by flash chromatography
(petroleum ether : ethyl acetate = 15:1) to afford the desired product.
1-(Nitromethyl)-2-phenyl-1,2,3,4-tetrahydroisoquinoline (3a).5a Yellow solid. Mp
1
89–90 ºC. H NMR (400 MHz, CDCl3): δ 7.30ꢀ7.11 (m, 6H), 6.99ꢀ6.95 (m, 2H),
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6.86ꢀ6.82 (m, 1H), 5.54 (t, J = 7.2 Hz, 1H), 4.87ꢀ4.82 (m, 1H), 4.58ꢀ4.53 (m, 1H),
3.68ꢀ3.55 (m, 2H), 3.13ꢀ3.02 (m, 1H), 2.82ꢀ2.74 (m, 1H); 13C NMR (100 MHz,
CDCl3): δ 148.5, 135.3, 133.0, 129.5, 129.2, 128.1, 127.0, 126.7, 119.5, 115.2, 78.8,
58.2, 42.1, 26.5.
2-(4-Methylphenyl)-1-(nitromethyl)-1,2,3,4-tetrahydroisoquinoline (3b).6 Yellow
1
solid. Mp 95–96 ºC. H NMR (400 MHz, CDCl3): δ 7.25ꢀ7.10 (m, 4H), 7.06 (d, J =
8.6 Hz, 2H), 6.88 (d, J = 8.6 Hz, 2H), 5.51ꢀ5.45 (m, 1H), 4.87ꢀ4.80 (m, 1H),
4.58ꢀ4.53 (m, 1H), 3.68ꢀ3.51 (m, 2H), 3.11ꢀ2.99 (m, 1H), 2.77ꢀ2.70 (m, 1H), 2.25 (s,
3H); 13C NMR (100 MHz, CDCl3): δ 146.4, 135.4, 133.0, 130.0, 129.3, 129.1, 128.0,
127.0, 126.7, 115.9, 78.9, 58.4, 42.3, 26.2, 20.4.
2-(4-Chlorophenyl)-1-(nitromethyl)-1,2,3,4-tetrahydroisoquinoline (3c).6 Yellow
1
solid. Mp 99–100 ºC. H NMR (400 MHz, CDCl3): δ 7.32ꢀ7.08 (m, 6H), 6.88 (d, J =
8.8 Hz, 2H), 5.48 (t, J = 7.4 Hz, 1H), 4.87ꢀ4.80 (m, 1H), 4.59ꢀ4.54 (m, 1H), 3.69ꢀ3.51
(m, 2H), 3.14ꢀ2.98 (m, 1H), 2.81ꢀ2.71 (m, 1H); 13C NMR (100 MHz, CDCl3): δ 147.1,
135.1, 132.5, 129.3, 128.3, 127.0, 126.9, 124.4, 116.5, 78.7, 58.2, 42.2, 26.2.
2-(4-Bromophenyl)-1-(nitromethyl)-1,2,3,4-tetrahydroisoquinoline (3d).15d Yellow
1
solid. Mp 105–106 ºC. H NMR (400 MHz, CDCl3): δ 7.36ꢀ7.27 (m, 2H), 7.26ꢀ7.10
(m, 4H), 6.84 (d, J = 8.8 Hz, 2H), 5.48 (t, J = 7.2 Hz, 1H), 4.86ꢀ4.80 (m, 1H),
4.59ꢀ4.53 (m, 1H), 3.71ꢀ3.51 (m, 2H), 3.11ꢀ2.98 (m, 1H), 2.83ꢀ2.73 (m, 1H); 13C
NMR (100 MHz, CDCl3): δ 147.5, 135.1, 132.5, 132.3, 129.3, 128.3, 127.0, 126.9,
116.8, 111.6, 78.7, 58.1, 42.2, 26.2.
2-(4-Fluorophenyl)-1-(nitromethyl)-1,2,3,4-tetrahydroisoquinoline (3e). Yellow
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1
oil. H NMR (400 MHz, CDCl3): δ 7.29ꢀ7.11 (m, 4H), 6.99ꢀ6.85 (m, 4H), 5.46ꢀ5.36
(m, 1H), 4.84ꢀ4.79 (m, 1H), 4.59ꢀ4.52 (m, 1H), 3.70ꢀ3.50 (m, 2H), 3.08ꢀ2.97 (m, 1H),
2.75ꢀ2.66 (m, 1H); 13C NMR (100 MHz, CDCl3): δ 157.2 (d, J = 237.7 Hz), 145.34 (d,
J = 2.2 Hz), 135.3, 132.6, 129.5, 128.1, 127.0, 126.8, 118.0 (d, J = 7.6 Hz), 115.9 (d, J
= 22.2 Hz), 78.9, 58.8, 42.9, 25.8. HRꢀMS (ESI) m/z calcd for C16H15FN2O2 [M+]
+
286.1118, found 286.1113.
2-(4-Methoxyphenyl)-1-(nitromethyl)-1,2,3,4-tetrahydroisoquinoline(3f).5a Yellow
solid. Mp 103–104 ºC. 1H NMR (400 MHz, CDCl3): δ 7.21ꢀ7.02 (m, 4H), 6.84 (d, J =
8.8 Hz, 2H), 6.74 (d, J = 8.8 Hz, 2H), 5.34ꢀ5.28 (m, 1H), 4.78ꢀ4.71 (m, 1H),
4.52ꢀ4.44 (m, 1H), 3.67 (s, 3H), 3.48 (d, J = 4.4 Hz, 2H), 3.00ꢀ2.86 (m, 1H),
2.66ꢀ2.58 (m, 1H); 13C NMR (100 MHz, CDCl3): δ 154.0, 143.1, 135.4, 132.9, 129.5,
127.9, 126.9, 126.6, 118.9, 114.7, 79.0, 58.9, 55.6, 43.2, 25.9.
2-(2-Methoxyphenyl)-1-(nitromethyl)-1,2,3,4-tetrahydroisoquinoline
(3g).5a
1
Yellow solid. Mp 101–102 ºC. H NMR (400 MHz, CDCl3): δ 7.27ꢀ7.13 (m, 4H),
7.02 (t, J = 7.6 Hz, 1H), 6.91ꢀ6.80 (m, 3H), 5.53ꢀ5.44 (m, 1H), 4.84ꢀ4.76 (m, 1H),
4.57ꢀ4.49 (m, 1H), 3.82 (s, 3H), 3.60ꢀ3.54 (m, 1H), 3.52ꢀ3.43 (m, 1H), 3.04ꢀ2.90 (m,
1H), 2.75ꢀ2.64 (m, 1H); 13C NMR (100 MHz, CDCl3): δ 153.2, 139.0, 135.4, 133.7,
129.6, 127.6, 126.8, 126.4, 124.1, 122.0, 121.1, 112.6, 79.2, 58.2, 55.8, 43.0, 26.9.
1-(Nitromethyl)-2-(4-nitrophenyl)-1,2,3,4-tetrahydroisoquinoline (3h).25 Yellow
oil. 1H NMR (400 MHz, CDCl3): δ 8.15 (d, J = 9.2 Hz, 2H), 7.32ꢀ7.14 (m, 4H), 6.96
(d, J = 9.2 Hz, 2H), 5.71 (t, J = 7.0 Hz, 1H), 4.89ꢀ4.84 (m, 1H), 4.66ꢀ4.60 (m, 1H),
3.74 (t, J = 6.0 Hz, 2H), 3.19ꢀ3.11 (m, 1H), 3.01ꢀ2.92 (m, 1H); 13C NMR (100 MHz,
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CDCl3): δ 152.6, 138.9, 134.5, 132.0, 129.1, 128.9, 127.3, 127.1, 126.3, 112.0, 78.1,
57.5, 42.3, 27.0.
1-(1-Nitroethyl)-2-phenyl-1,2,3,4-tetrahydroisoquinoline (3i).5a Yellow oil. dr = 2:1.
1H NMR (400 MHz, CDCl3): δ 7.31ꢀ7.07 (m, 6H), 7.02ꢀ6.96 (m, 2H), 6.85ꢀ6.78 (m,
1H), 5.27ꢀ5.20 (m, 1H), 5.08ꢀ4.85 (m, 1H), 3.87ꢀ3.50 (m, 2H), 3.10ꢀ2.85 (m, 2H),
[1.70 (d, J = 6.6 Hz), 1.54 (d, J = 6.6 Hz), 3H]; 13C NMR (100 MHz, CDCl3): δ 149.2,
148.9, 135.6, 134.8, 133.8, 132.1, 129.5, 129.3, 129.1, 128.9, 128.7, 128.4, 128.2,
127.3, 126.6, 126.2, 119.4, 118.8, 115.5, 114.5, 89.0, 85.5, 62.8, 61.2, 43.6, 42.7, 26.8,
26.4, 17.5, 16.4.
2-(4-Methylphenyl)-1-(1-nitroethyl)-1,2,3,4-tetrahydroisoquinoline (3j).15d Yellow
1
oil. dr = 2:1. H NMR (400 MHz, CDCl3): δ 7.26ꢀ6.99 (m, 6H), 6.89 (d, J = 8.4 Hz,
2H), 5.20ꢀ5.11 (m, 1H), 5.09ꢀ4.82 (m, 1H), 3.85ꢀ3.49 (m, 2H), 3.08ꢀ2.77 (m, 2H),
[2.25 (s), 2.23 (s), 3H], [1.68 (d, J = 6.6 Hz), 1.53 (d, J = 6.6 Hz), 3H]; 13C NMR (100
MHz, CDCl3): δ 147.2, 146.8, 135.8, 134.9, 133.8, 132.1, 130.9, 129.9, 129.8, 129.2,
128.9, 128.8, 128.4, 128.1, 127.3, 126.6, 126.1, 116.1, 115.2, 89.0, 85.6, 62.9, 61.5,
43.9, 43.1, 26.6, 26.3, 20.4, 20.3, 17.4, 16.5.
2-(4-Chlorophenyl)-1-(1-nitroethyl)-1,2,3,4-tetrahydroisoquinoline (3k). Yellow
1
oil. dr = 2:1. H NMR (400 MHz, CDCl3): δ 7.30ꢀ6.99 (m, 6H), 6.89 (d, J = 7.6 Hz,
2H), 5.21ꢀ5.11 (m, 1H), 5.05ꢀ4.81 (m, 1H), 3.86ꢀ3.44 (m, 2H), 3.09ꢀ2.83 (m, 2H),
[1.67 (d, J = 6.6 Hz), 1.55 (d, J = 6.6 Hz), 3H]; 13C NMR (100 MHz, CDCl3): δ 147.8,
147.5, 135.4, 134.6, 133.5, 131.8, 129.3, 129.2, 129.1, 128.8, 128.5, 128.4, 128.3,
127.3, 126.8, 126.3, 124.2, 123.7, 116.7, 115.7, 88.8, 85.5, 62.9, 61.2, 43.9, 42.9, 26.7,
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+
26.2, 17.4, 16.7. HRꢀMS (ESI) m/z calcd for C17H17ClN2O2 [M+] 316.0979, found
316.0981.
2-(4-Bromophenyl)-1-(1-nitroethyl)-1,2,3,4-tetrahydroisoquinoline (3l).15d Yellow
1
oil. dr = 2:1. H NMR (400 MHz, CDCl3): δ 7.36ꢀ7.01 (m, 6H), 6.88ꢀ6.81 (m, 2H),
5.22ꢀ5.12 (m, 1H), 5.03ꢀ4.81 (m, 1H), 3.82ꢀ3.47 (m, 2H), 3.06ꢀ2.85 (m, 2H), [1.67 (d,
J = 6.6 Hz), 1.54 (d, J = 6.6 Hz), 3H]; 13C NMR (100 MHz, CDCl3): δ 148.2, 147.9,
135.3, 134.5, 133.5, 132.2, 132.0, 131.8, 129.2, 128.7, 128.5, 128.4, 128.3, 127.3,
126.8, 126.3, 117.0, 116.1, 111.5, 110.8, 88.8, 85.4, 62.8, 61.1, 43.8, 42.8, 26.7, 26.2,
17.4, 16.6.
2-(4-Fluorophenyl)-1-(1-nitroethyl)-1,2,3,4-tetrahydroisoquinoline (3m). Yellow
1
oil. dr = 2:1. H NMR (400 MHz, CDCl3): δ 7.27ꢀ7.06 (m, 4H), 7.04ꢀ6.84 (m, 4H),
5.15ꢀ4.80 (m, 2H), 3.87ꢀ3.76 (m, 1H), 3.61ꢀ3.42 (m, 1H), 3.14ꢀ2.76 (m, 2H), [1.67 (d,
J = 6.6 Hz), 1.55 (d, J = 6.6 Hz), 3H]; 13C NMR (100 MHz, CDCl3): δ 157.1 (d, J =
237.5 Hz), 156.8 (d, J = 237.2 Hz), 146.1 (d, J = 2.2 Hz), 145.7 (d, J = 2.2 Hz), 135.6,
134.8, 133.5, 131.9, 129.3, 129.0, 128.4, 128.3, 128.2, 127.2, 126.7, 126.2, 118.0 (d, J
= 7.6 Hz), 117.2 (d, J = 7.6 Hz), 115.8 (d, J = 22.2 Hz), 115.7 (d, J = 22.2 Hz), 88.8,
85.7, 63.4, 61.9, 44.7, 43.6, 26.4, 26.0, 17.2, 16.8. HRꢀMS (ESI) m/z calcd for
+
C17H17FN2O2 [M+] 300.1274, found 300.1280.
2-(4-Methoxyphenyl)-1-(1-nitroethyl)-1,2,3,4-tetrahydroisoquinoline
(3n).5a
1
Yellow oil. dr = 1.3:1. H NMR (400 MHz, CDCl3): δ 7.27ꢀ7.11 (m, 4H), 7.09ꢀ6.86
(m, 2H), 6.83ꢀ6.74 (m, 2H), 5.09ꢀ4.77 (m, 2H), 3.82ꢀ3.44 (m, 5H), 3.05ꢀ2.73 (m, 2H),
[1.67 (d, J = 6.6 Hz), 1.53 (d, J = 6.6 Hz), 3H]; 13C NMR (100 MHz, CDCl3): δ 153.8,
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153.6, 143.9, 143.5, 135.9, 135.1, 133.7, 132.1, 129.3, 129.0, 128.4, 128.1, 128.0,
127.2, 126.5, 126.1, 118.9, 118.3, 114.7, 114.6, 88.8, 85.8, 63.5, 62.2, 45.0, 44.0, 26.3,
26.1, 17.1, 16.6.
1-(1-Nitroethyl)-2-(4-nitrophenyl)-1,2,3,4-tetrahydroisoquinoline (3o). Yellow oil.
1
dr = 4:1. H NMR (400 MHz, CDCl3): δ 8.20ꢀ8.09 (m, 2H), 7.34ꢀ7.05 (m, 4H),
6.99ꢀ6.91 (m, 2H), 5.50ꢀ5.39 (m, 1H), 5.03ꢀ4.85 (m, 1H), 3.95ꢀ3.88 (m, 1H),
3.65ꢀ3.57 (m, 1H), 3.22ꢀ3.01 (m, 2H), [1.68 (d, J = 6.6 Hz), 1.58 (d, J = 6.6 Hz), 3H];
13C NMR (100 MHz, CDCl3): δ 153.3, 153.0, 138.8, 138.6, 134.7, 134.0, 133.0, 131.6,
129.1, 129.0, 128.8, 128.6, 128.2, 127.3, 127.2, 126.8, 126.2, 125.9, 112.1, 111.7,
88.4, 85.1, 62.2, 60.5, 44.0, 43.0, 27.3, 26.9, 17.4, 16.7. HRꢀMS (ESI) m/z calcd for
+
C17H18N3O4 [M+H+] 328.1297, found 328.1294.
N,4-Dimethyl-N-(2-nitroethyl)aniline (3p).5a Yellow oil. 1H NMR (400 MHz,
CDCl3): δ 7.07 (d, J = 8.6 Hz, 2H), 6.66 (d, J = 8.6 Hz, 2H), 4.55 (t, J = 6.2 Hz, 2H),
3.96 (t, J = 6.2 Hz, 2H), 2.94 (s, 3H), 2.26 (s, 3H); 13C NMR (100 MHz, CDCl3): δ
145.9, 130.0, 127.5, 113.2, 72.6, 51.0, 39.0, 20.2.
General procedure for heterogeneous gold-catalyzed aerobic oxidative C–C
coupling reaction of tertiary amines with ketones
To the mixture of Nꢀarylꢀ1,2,3,4ꢀtetrahydroisoquinoline (0.1 mmol) and Fe3O4@
SiO2ꢀbipyꢀAuCl2][AuCl4] (26 mg, 3 mol%) and 4Å MS (60 mg) in ketone (0.5 mL)
was injected a small amount of HOAc (0.1 mL). Subsequently, the reaction mixture
was stirred at 60 ºC under air for 12 h. When the reaction was completed, the reaction
mixture was cooled to room temperature and the supported catalyst was magnetically
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separated. The reaction mixture was poured into saturated Na2CO3 solution (5 mL)
and extracted with ethyl acetate (3 × 10 mL). The combined organic layer was dried
over MgSO4 and concentrated under reduced pressure. The residue was purified by
flash chromatography (petroleum ether : ethyl acetate = 15:1) to afford the desired
product. The recovered catalyst was washed with methanol (2 × 2 mL), airꢀdried and
used directly for the next run.
1-(2-(4-Methylphenyl)-1,2,3,4-tetrahydroisoquinolin-1-yl)propan-2-one (3q).15d
1
Colorless oil. H NMR (400 MHz, CDCl3): δ 7.20ꢀ7.10 (m, 4H), 7.05 (d, J = 8.6 Hz,
2H), 6.86 (d, J = 8.6 Hz, 2H), 5.34 (t, J = 6.4 Hz, 1H), 3.67ꢀ3.45 (m, 2H), 3.11ꢀ2.98
(m, 2H), 2.85ꢀ2.74 (m, 2H), 2.25 (s, 3H), 2.07 (s, 3H); 13C NMR (100 MHz, CDCl3):
δ 207.3, 147.0, 138.3, 134.4, 129.8, 128.8, 128.0, 126.9, 126.7, 126.2, 115.8, 55.2,
50.1, 42.3, 31.0, 27.0, 20.3.
1-(2-(4-Chlorophenyl)-1,2,3,4-tetrahydroisoquinolin-1-yl)propan-2-one
(3r).15d
1
Yellow oil. H NMR (400 MHz, CDCl3): δ 7.23ꢀ7.08 (m, 6H), 6.85 (d, J = 8.8 Hz,
2H), 5.34 (t, J = 6.2 Hz, 1H), 3.68ꢀ3.43 (m, 2H), 3.05ꢀ2.97 (m, 2H), 2.86ꢀ2.80 (m,
13
2H), 2.08 (s, 3H); C NMR (100 MHz, CDCl3): δ 207.1, 147.5, 137.9, 134.2, 129.2,
128.7, 127.0, 126.8, 126.4, 123.0, 115.8, 54.8, 50.2, 42.2, 31.2, 27.0.
1-(2-(4-Bromophenyl)-1,2,3,4-tetrahydroisoquinolin-1-yl)propan-2-one
(3s).15d
1
Colorless oil. H NMR (400 MHz, CDCl3): δ 7.30 (d, J = 8.8 Hz, 2H), 7.18ꢀ7.11 (m,
4H), 6.80 (d, J = 8.8 Hz, 2H), 5.33 (t, J = 6.0 Hz, 1H), 3.62ꢀ3.44 (m, 2H), 3.06ꢀ2.96
(m, 2H), 2.87ꢀ2.81 (m, 2H), 2.07 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 207.0,
147.9, 137.9, 134.2, 132.1, 128.7, 127.0, 126.8, 126.4, 116.2, 110.1, 54.7, 50.2, 42.2,
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31.1, 27.1.
1-(2-(4-Fluorophenyl)-1,2,3,4-tetrahydroisoquinolin-1-yl)propan-2-one
(3t).
1
Colorless oil. H NMR (400 MHz, CDCl3): δ 7.19ꢀ7.09 (m, 4H), 6.97ꢀ6.85 (m, 4H),
5.28 (t, J = 6.2 Hz, 1H), 3.64ꢀ3.44 (m, 2H), 3.10ꢀ2.94 (m, 2H), 2.85ꢀ2.73 (m, 2H),
2.07 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 207.3, 156.5 (d, J = 236.3 Hz), 145.8,
138.0, 134.2, 128.9, 126.9, 126.8, 126.4, 117.2 (d, J = 7.4 Hz), 115.7 (d, J = 21.9 Hz),
55.6, 50.1, 42.7, 31.1, 26.7. HRꢀMS (ESI) m/z calcd for C18H18FNO+ [M+] 283.1372,
found 283.1365.
1-(2-(4-Methoxyphenyl)-1,2,3,4-tetrahydroisoquinolin-1-yl)propan-2-one (3u).15d
1
Colorless oil. H NMR (400 MHz, CDCl3): δ 7.19ꢀ7.06 (m, 4H), 6.90 (d, J = 8.8 Hz,
2H), 6.81 (d, J = 8.8 Hz, 2H), 5.23 (t, J = 6.4 Hz, 1H), 3.74 (s, 3H), 3.58ꢀ3.41 (m, 2H),
3.06ꢀ2.93 (m, 2H), 2.81ꢀ2.70 (m, 2H), 2.05 (s, 3H); 13C NMR (100 MHz, CDCl3): δ
207.3, 153.4, 143.7, 138.3, 134.3, 128.9, 126.8, 126.6, 126.2, 118.4, 114.7, 56.0, 55.6,
50.0, 43.0, 30.8, 26.8.
1-(2-(4-Nitrophenyl)-1,2,3,4-tetrahydroisoquinolin-1-yl)propan-2-one
(3v).
1
Yellow oil. H NMR (400 MHz, CDCl3): δ 8.13 (d, J = 9.4 Hz, 2H), 7.24ꢀ7.15 (m,
4H), 6.85 (d, J = 9.4 Hz, 2H), 5.57ꢀ5.52 (m, 1H), 3.75ꢀ3.59 (m, 2H), 3.12ꢀ2.90 (m,
13
4H), 2.11 (s, 3H); C NMR (100 MHz, CDCl3): δ 206.0, 152.7, 137.9, 137.3, 133.9,
128.4, 127.6, 126.9, 126.8, 126.2, 111.2, 54.0, 50.1, 43.0, 31.0, 27.8. HRꢀMS (ESI)
+
m/z calcd for C18H19N2O3 [M+H+] 311.1396, found 311.1394.
2-(2-(4-Chlorophenyl)-1,2,3,4-tetrahydroisoquinolin-1-yl)-1-phenylethanone (3w).
1
White solid. Mp 67–68 ºC. H NMR (400 MHz, CDCl3): δ 7.85 (d, J = 7.6 Hz, 2H),
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7.53 (t, J = 7.2 Hz, 1H), 7.41 (t, J = 7.8 Hz, 2H), 7.24ꢀ7.08 (m, 6H), 6.88 (d, J = 9.2
Hz, 2H), 5.60 (t, J = 6.2 Hz, 1H), 3.65ꢀ3.49 (m, 3H), 3.42ꢀ3.34 (m, 1H), 3.14ꢀ3.04 (m,
1H), 2.95ꢀ2.85 (m, 1H); 13C NMR (100 MHz, CDCl3): δ 198.5, 147.4, 138.2, 137.2,
134.3, 133.2, 129.1, 128.6, 128.5, 128.1, 127.1, 127.0, 126.4, 122.8, 115.6, 55.2, 45.3,
42.3, 27.3. HRꢀMS (ESI) m/z calcd for C23H21ClNO+ [M+H+] 362.1312, found
362.1317.
2-(2-(4-Bromophenyl)-1,2,3,4-tetrahydroisoquinolin-1-yl)-1-phenylethanone (3x).
1
White solid. Mp 72–73 ºC. H NMR (400 MHz, CDCl3): δ 7.89ꢀ7.80 (m, 2H),
7.56ꢀ7.50 (m, 1H), 7.44ꢀ7.38 (m, 2H), 7.34ꢀ7.26 (m, 2H), 7.24ꢀ7.08 (m, 4H),
6.88ꢀ6.77 (m, 2H), 5.60 (t, J = 6.0 Hz, 1H), 3.64ꢀ3.51 (m, 3H), 3.42ꢀ3.34 (m, 1H),
3.13ꢀ3.04 (m, 1H), 2.96ꢀ2.87 (m, 1H); 13C NMR (100 MHz, CDCl3): δ 198.4, 147.8,
138.2, 137.2, 134.3, 133.2, 132.0, 128.6, 128.5, 128.1, 127.1, 127.0, 126.4, 115.9,
109.9, 55.1, 45.3, 42.2, 27.3. HRꢀMS (ESI) m/z calcd for C23H21BrNO+ [M+H+]
406.0807, found 406.0804.
2-(2-(4-Nitrophenyl)-1,2,3,4-tetrahydroisoquinolin-1-yl)-1-phenylethanone (3y).
Yellow solid. Mp 87–88 ºC. 1H NMR (400 MHz, CDCl3): δ 8.12 (d, J = 9.6 Hz, 2H),
7.85 (d, J = 7.6 Hz, 2H), 7.55 (t, J = 7.4 Hz, 1H), 7.42 (t, J = 7.4 Hz, 2H), 7.29ꢀ7.13
(m, 4H), 6.89 (d, J = 9.6 Hz, 2H), 5.79 (t, J = 6.0 Hz, 1H), 3.82ꢀ3.63 (m, 2H), 3.52 (d,
J = 6.0 Hz, 2H), 3.16ꢀ3.07 (m, 2H); 13C NMR (100 MHz, CDCl3): δ 197.6, 152.7,
137.9, 137.4, 136.8, 133.9, 133.5, 128.7, 128.4, 128.1, 127.6, 127.1, 126.9, 126.2,
+
111.2, 54.6, 45.4, 43.0, 27.8. HRꢀMS (ESI) m/z calcd for C23H20N2O3 [M+] 372.1474,
found 372.1482.
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2-(2-(4-Methoxyphenyl)-1,2,3,4-tetrahydroisoquinolin-1-yl)-1-phenylethanone
(3z).15d Colorless oil. 1H NMR (400 MHz, CDCl3): δ 7.82 (d, J = 7.6 Hz, 2H), 7.50 (t,
J = 7.4 Hz, 1H), 7.38 (t, J = 7.6 Hz, 2H), 7.20ꢀ7.06 (m, 4H), 6.95ꢀ6.88 (m, 2H),
6.83ꢀ6.74 (m, 2H), 5.51 (t, J = 6.0 Hz, 1H), 3.72 (s, 3H), 3.59ꢀ3.49 (m, 3H), 3.33ꢀ3.25
(m, 1H), 3.11ꢀ3.02 (m, 1H), 2.87ꢀ2.77 (m, 1H); 13C NMR (100 MHz, CDCl3): δ 198.8,
153.1, 143.7, 138.6, 137.4, 134.3, 132.9, 128.8, 128.5, 128.1, 127.1, 126.7, 126.1,
117.9, 114.7, 56.3, 55.7, 45.0, 42.8, 27.3.
2-(2-(4-Chlorophenyl)-1,2,3,4-tetrahydroisoquinolin-1-yl)cyclohexanone
(3a').
1
Yellow oil. dr = 1.2:1. H NMR (400 MHz, CDCl3): δ 7.35ꢀ7.08 (m, 6H), 6.87ꢀ6.68
(m, 2H), [5.61 (d, J = 8.4 Hz), 5.54 (d, J = 4.8 Hz), 1H], 3.73ꢀ3.42 (m, 2H), 3.07ꢀ2.64
(m, 3H), 2.51ꢀ2.40 (m, 1H), 2.37ꢀ2.02 (m, 2H), 1.96ꢀ1.76 (m, 2H), 1.74ꢀ1.51 (m, 3H);
13C NMR (100 MHz, CDCl3): δ 211.8, 147.9, 147.8, 140.1, 135.6, 134.8, 134.3, 129.1,
129.0, 128.7, 128.0, 127.9, 127.2, 126.9, 126.8, 126.5, 125.9, 122.9, 121.1, 116.1,
113.3, 59.3, 56.4, 55.2, 54.1, 43.8, 43.2, 42.7, 41.5, 32.9, 30.3, 28.7, 27.7, 27.3, 27.1,
25.7, 24.0. HRꢀMS (ESI) m/z calcd for C21H22ClNO+ [M+] 339.1390, found 339.1395.
2-(2-(4-Fluorophenyl)-1,2,3,4-tetrahydroisoquinolin-1-yl)cyclohexanone
(3b').
Yellow oil. dr = 12:1. 1H NMR (400 MHz, CDCl3): δ 7.23ꢀ7.08 (m, 4H), 6.97ꢀ6.79 (m,
4H), 5.42 (d, J = 5.6 Hz, 1H), 3.73ꢀ3.63 (m, 1H), 3.54ꢀ3.47 (m, 1H), 2.99ꢀ2.73 (m,
13
3H), 2.49ꢀ2.26 (m, 2H), 1.96ꢀ1.62 (m, 5H), 1.50ꢀ1.43 (m, 1H); C NMR (100 MHz,
CDCl3): δ 211.9, 156.4 (d, J = 237.1 Hz), 146.1 (d, J = 2.0 Hz), 135.8, 134.9, 128.9,
127.9, 126.8, 125.8, 117.3 (d, J = 7.3 Hz), 115.7 (d, J = 21.8 Hz), 56.4, 55.8, 43.5,
41.3, 30.4, 27.5, 26.7, 23.7. HRꢀMS (ESI) m/z calcd for C21H23FNO+ [M+H+]
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324.1764, found 324.1763.
Acknowledgements
We thank the National Natural Science Foundation of China (No. 21462021), the
Natural Science Foundation of Jiangxi Province of China (No. 20161BAB203086)
and Key Laboratory of Functional Small Organic Molecule, Ministry of Education
(No. KLFSꢀKFꢀ201409) for financial support.
Notes and references
1
(a) G. Dyker, Angew. Chem. Int. Ed., 1999, 38, 1698–1712; (b) V. Ritleng, C.
Sirlin and M. Pfeffer, Chem. Rev., 2002, 102, 1731–1770; (c) R. H. Crabtree, J.
Organomet. Chem., 2004, 689, 4083–4091; (d) F. Kakiuchi and N. Chatani, Adv.
Synth. Catal., 2003, 345, 1077–1101; (e) K. R. Campos, Chem. Soc. Rev., 2007,
36, 1069–1084; (f) J. J. Li, T. S. Mei and J. Q. Yu, Angew. Chem. Int. Ed., 2008,
47, 6452–6455.
2
(a) F. Diederich and P. J. Stang, Eds. MetalꢀCatalyzed CrossꢀCoupling Reactions;
WileyꢀVCH: New York, 1998; (b) A. de Meijere and F. Diederich, Metalꢀ
Catalyzed CrossꢀCoupling Reactions; 2nd ed.; WileyꢀVCH: Weinheim, 2008.
(a) C.ꢀJ. Li, Acc. Chem. Res., 2009, 42, 335–344; (b) S.ꢀI. Murahashi, Angew.
Chem. Int. Ed., 1995, 34, 2443–2465.
3
4
(a) S.ꢀI. Murahashi and D. Zhang, Chem. Soc. Rev., 2008, 37, 1490–1501; (b) A.
E. Wendlandt, A. M. Suess and S. S. Stahl, Angew. Chem. Int. Ed., 2011, 50,
11062–11087; (c) C. S. Yeung and V. M. Dong, Chem. Rev., 2011, 111,
1215–1292; (d) C. Liu, H. Zhang, W. Shi and A. Lei, Chem. Rev., 2011, 111,
1780–1824; (e) S. A. Girard and C.ꢀJ. Li, Angew. Chem. Int. Ed., 2014, 53,
74–100.
5
(a) Z. Li and C.ꢀJ. Li, J. Am. Chem. Soc., 2005, 127, 3672–3673; (b) O. Basle
and C.ꢀJ. Li, Green Chem., 2007, 9, 1047–1050; (c) Z. Li and C.ꢀJ. Li, Eur. J.
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