Synthesis of tetra-substituted imidazoles and 2-imidazolines by Ni(0)-catalyzed dehydrogenation of benzylic-type imines

Article abstract of DOI:10.1039/c4dt02313g

Ni(0)-catalyzed dehydrogenation of benzylic-type imines was performed to yield asymmetrical tetra-substituted imidazoles and 2-imidazolines. This was achieved with a single operational step while maintaining good selectivity and atom economy. The catalytic system shows low to moderate tolerance for fluoro-, trifluoromethyl-, methyl-, and methoxy-substituted benzylic-type imines. In addition, the substitution pattern at the N-heterocyclic products was easily controlled by the appropriate selection of R-groups in the starting organic substrates. Based on experimental observations, we propose a reaction mechanism in which benzylic C(sp³)-H bond activation and insertion steps play pivotal roles in this nickel-catalyzed organic transformation. This journal is

Full text of DOI:10.1039/c4dt02313g

Dalton
Transactions
View Article Online
View Journal | View Issue
PAPER
Synthesis of tetra-substituted imidazoles and
2-imidazolines by Ni(0)-catalyzed
dehydrogenation of benzylic-type imines†
Cite this: Dalton Trans., 2014, 43,
15997
Adrian Tlahuext-Aca, Oscar Hernández-Fajardo, Alma Arévalo and
Juventino J. García*
Ni(0)-catalyzed dehydrogenation of benzylic-type imines was performed to yield asymmetrical tetra-sub-
stituted imidazoles and 2-imidazolines. This was achieved with a single operational step while maintaining
good selectivity and atom economy. The catalytic system shows low to moderate tolerance for fluoro-,
trifluoromethyl-, methyl-, and methoxy-substituted benzylic-type imines. In addition, the substitution
pattern at the N-heterocyclic products was easily controlled by the appropriate selection of R-groups in
the starting organic substrates. Based on experimental observations, we propose a reaction mechanism in
which benzylic C(sp3)–H bond activation and insertion steps play pivotal roles in this nickel-catalyzed
organic transformation.
Received 30th July 2014,
Accepted 28th August 2014
DOI: 10.1039/c4dt02313g
www.rsc.org/dalton
thetic procedures that normally require a single operational
step and simple organic building blocks as starting materials.
Introduction
Imidazoles and 2-imidazolines are very important five-mem- In the search for complementary synthetic methodologies
bered heterocyclic compounds in natural product, pharma- involving more abundant and cheaper transition metal cata-
ceutical, and materials science. They constitute platforms for lysts, our group reported a Ni(0)-catalyzed synthesis of triaryl-
biologically active molecules1 and advanced materials.2 In imidazoles from highly available aromatic nitriles under both
addition, they have broad applications as ligands in coordi- neat and hydrogen pressure conditions using [(dippe)Ni(μ-H)]2
nation chemistry,3 and their imidazolium salts are widely used (dippe = 1,2-bis-(diisopropylphosphino)ethane) as the Ni(0)-
as N-heterocyclic carbene precursors.4 Moreover, these imida- catalyst precursor (Scheme 1a).9 To explain the formation of
zolium-type species are currently being investigated as ionic the imidazole ring, the formation of imines by a Ni(0)-cata-
liquids in the search for environmentally friendly solvents for lyzed hydrogenation pathway was postulated (Scheme 1a, step
novel organic transformations.5 Typically, polysubstituted imi- a).10 These imines would then react with nitriles to form the
dazoles and 2-imidazolines are prepared from multicompo- organic product through a Ni(0)-catalyzed dehydrogenation
nent condensation reactions between carbonyl compounds process (Scheme 1a, step b).
and nitrogen sources such as ammonia, ammonium salts, and
As a continuation of our interest in the synthesis of five-
amines, providing a plethora of synthetic methodologies membered N-heterocyclic species, we envisioned the formation
towards these valuable organic compounds. Nevertheless, such of tetra-substituted products by replacing the nitrile building
procedures usually involve harsh reaction conditions, for block by a second equivalent of imine during the Ni(0)-cata-
instance, high temperatures and the use of strong dehydration lyzed dehydrogenation step (Scheme 1b). This would lead to
or oxidizing agents.6
new atom-economical processes towards highly functionalized
In recent years, transition-metal-catalyzed organic trans- imidazoles, in which readily available starting materials
formations based on Zr, Rh, Pd, Ag, Cu, Yb, and La-complexes are used with C(sp3)–H bond activation as a key step. The
have emerged as powerful tools for obtaining both polysubsti- activation and subsequent functionalization of C–H bonds re-
tuted imidazoles7 and 2-imidazolines,8 enabling novel syn- present major challenges in homogeneous catalysis in the
search for sustainable catalytic organic transformations.
However, the application of these methodologies usually
Facultad de Química, Universidad Nacional Autónoma de México, Circuito Interior,
requires stoichiometric amounts of bases and external oxi-
Ciudad Universitaria, MexicoCity, 04510, Mexico. E-mail: juvent@unam.mx
dants such as Cu or Ag salts along with quinone-derivates.11
†Electronic supplementary information (ESI) available: Figures with selected
We report the catalytic dehydrogenation of benzylic-type
GC-MS data and additional dehydrogenation experiments. See DOI: 10.1039/
imines to produce tetra-substituted imidazole rings using the
c4dt02313g
This journal is © The Royal Society of Chemistry 2014
Dalton Trans., 2014, 43, 15997–16005 | 15997

View Article Online
Paper
Dalton Transactions
Scheme 1 Reaction design.
commercially available [Ni(COD)2] (COD = 1,5-cyclooctadiene)
As shown in Table 1, the use of either mono- or diphos-
complex and organophosphorous ligands as a catalytic system, phines in combination with [Ni(COD)2] produced the expected
without the use of additives. In addition, we show that this tetra-substituted imidazole 1-benzyl-2,4,5-triphenyl-imidazole
system provides a method to prepare not only functionalized B in addition to the corresponding partially saturated hetero-
imidazoles, but also their partially saturated analogs 2-imida- cycle 1-benzyl-2,4,5-triphenyl-4,5-dihydro-imidazole A, which
zolines as a result of incomplete catalytic dehydrogenation arises from the incomplete catalytic dehydrogenation of
(Scheme 1b). This process becomes part of the Ni(II)-catalyzed NBB. Notably, phosphine ligands have important effects on
reaction between 1,2-dicarbonyl groups and benzylamines that the catalytic system in terms of both substrate conversion and
was very recently reported by Maiti12 and the Fe(II)-catalyzed selectivity, and interesting trends emerge. In the case of mono-
oxidation of benzylic-type amines that was reported by Tsuji13 phosphines, σ-donor/π-acceptor ligands such as PPh3 and
to afford tetra-substituted five-membered heterocyclic com- P(OPh)3 (Table 1, entries 4 and 5) produce higher yields of
pounds (Scheme 1c). Such reactions also involve dehydrogena- A (10–13%) and B (7–11%), along with moderate NBB conver-
tion pathways of imines, but the current reaction offers the use sions (30–37%) in comparison with those afforded by exclusive
of both catalytic amounts of Ni-complexes and a lack of toxic σ-donor ligands (Table 1, entries 1–3). Moreover, the π acceptor
reaction media such as CCl4.14
character seems to be a determining property, as PPh3 and
P(OPh)3 have almost the same effect, although their cone
angles are different.15 This could also be seen when comparing
the effect of PEt3, PtBu3, and PCy3 ligands (Table 1, entries
1–3). Another interesting feature is the sole use of [Ni(COD)2]
(Table 1, entry 12), which gave almost the same catalytic
activity as the [Ni(COD)2]/π-acceptor ligand system. Since COD
ligands are easily replaced from the Ni(0) coordination sphere,
we believe that NBB probably behaves as both ligand and
substrate in this system, and it seems to have good π acceptor
properties due to the presence of a low-energy π* C–N orbital.
Notably, opposite electronic effects were observed in the
case of diphosphines. The use of ethane-bridged σ-donor
ligands such as dippe, dtbpe, and dcype (Table 1, entries 7–9)
Results and discussion
In order to establish the best reaction conditions for the Ni(0)-
catalytic system, we assessed the reactivity of the model sub-
strate N-benzylidenebenzylamine (NBB) with catalytic amounts
(2 mol%) of [Ni(COD)2] in the presence of either mono- or
diphosphines with different steric and electronic properties
using an initial catalyst concentration of 34 mM. The metal-to-
ligand ratios shown in Table 1 were used. We investigated the
effect of these ligands in THF at 190 °C for 48 h.
15998 | Dalton Trans., 2014, 43, 15997–16005
This journal is © The Royal Society of Chemistry 2014

View Article Online
Dalton Transactions
Paper
Table 1 Ligand screeninga
Entry
Ligand
Metal : ligand ratio
NBB conv. (%)
A yield (%)
B yield (%)
1
2
3
4
5
6
7
8
PEt3
1 : 2
1 : 2
1 : 2
1 : 2
1 : 2
1 : 1
1 : 1
1 : 1
1 : 1
1 : 1
1 : 1
—
15
25
20
37
30
30
60
60
79
11
15
43
5
8
5
2
5
3
7
11
5
PtBu3
PCy3
PPh3
P(OPh)3
dppe
dippe
dtbpe
dcype
dppf
dippf
No-ligand added
13
10
6
30
38
45
10
3
6
12
20
0.5
0.5
8
9
10
11
12
13
a Chromatographic yield. Complete conversion percentage of NBB is calculated by summing A, B and additional product C. Information for
species C is included in the ESI.
afforded higher yields of products A (30–45%) and B (6–20%),
The impact of performing the reaction at temperatures
in addition to better substrate conversions (60–79%) in lower than 190 °C was assessed in toluene to establish milder
comparison with those produced by the analogous σ-donor/ reactions conditions while maintaining good catalytic activity
π-acceptor ligand dppe (Table 1, entry 6). Therefore, to gain (Table 2, entries 4 and 5). At 170 °C, there is good NBB conver-
insight into the role of the ethane scaffold, we investigated the sion (71%) and similar product yields of A (53%) and B (11%)
effect of ferrocenyl-bridged phosphines featured with isopropyl in comparison with the reaction at 190 °C, reflecting an
and phenyl groups on the phosphorous atoms (Table 1, entries increase in selectivity towards the heterocyclic compounds.
10 and 11). Both ligands have similar effects on the Ni(0)- Importantly, upon lowering the reaction temperature to 150 °C
center and led to low NBB conversions and product yields. (Table 2, entry 5), the catalytic activity of the Ni(0)/dcype
This indicates that the ethane bridge in the ligands is a key system decreased. We observed not only poor NBB conversion
feature for good catalytic activity.
(30%), but also rather low yields of A (22%) and B (1%). In
After establishing that the [Ni(COD)2]/dcype system pro- addition, even under these milder reaction conditions, we
vides the best catalytic performance (Table 1, entry 9), we observed minute amounts of black metal deposits, presumably
investigated different ligand-to-metal ratios and the effect of from Ni(0)-catalyst decomposition. Considering this, we
solvents, reaction temperatures, and initial catalyst concen- assessed the effect of different metal-to-ligand ratios in avoid-
trations in improving activity (Table 2). We screened three ing Ni(0)-complex decomposition in toluene at 150 °C
different solvents with different polarities.16 Surprisingly, (Table 2, entries 5–7). There is an important effect on the cata-
despite the remarkable polarity difference between benzo- lyst performance when increasing the metal-to-ligand ratio
nitrile and mesitylene (Table 2, entries 1 and 2), they gave from 1 : 1 to 1 : 2 (Table 2, entries 5 and 6), and black Ni(0)
similar results in terms of both NBB conversion (78–81%) and deposits were not detected in such experiments.17 In addition,
product yields of A (35–37%) and B (18%). Nevertheless, the better NBB conversion and A and B yields were obtained. Inter-
catalytic activity in these solvents was low in comparison with estingly, using a 1 : 4 metal-to-ligand ratio had almost the
that in THF (Table 1, entry 9). Despite having almost the same same result as the 1 : 1 ratio (Table 2, entries 5 and 7). This
polarity as mesitylene, toluene (Table 2, entry 3) gave better could be attributed to competition between dcype and NBB for
results: 81% NBB conversion, 15% yield of B, and a notable coordination sites in the Ni(0)-catalyst.
59% yield of A. Thus, we selected the last solvent to continue
In order to increase the catalyst performance, we examined
our studies.
the effect of its initial concentration on the reaction. The
This journal is © The Royal Society of Chemistry 2014
Dalton Trans., 2014, 43, 15997–16005 | 15999

View Article Online
Paper
Dalton Transactions
Table 2 Reaction optimizationa
Metal : ligand
ratio
Initial catalyst
concentration (mM)
Reaction
time (h)
NBB conv.
(%)
A yield
(%)
B yield
(%)
Entry
Solvent
T (°C)
1
2
3
4
5
6
1 : 1
1 : 1
1 : 1
1 : 1
1 : 1
1 : 2
1 : 4
1 : 2
34
34
34
34
34
34
34
68
4.2
—
Benzonitrile
Mesitylene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
—
190
190
190
170
150
150
150
150
150
150
150
150
48
48
48
48
48
48
48
48
48
48
48
72
81
78
81
71
30
50
33
71
0
37
35
59
53
22
39
23
56
0
18
18
15
11
1
6
2
11
0
0
3
14
7
8b
9
1 : 2
No catalyst
1 : 2
10
11
12
0
51
78
0
46
63
Neat
68
1 : 2
Toluene
a Chromatographic yields. Complete conversion percentage of NBB is calculated by summing A, B, and additional product C. Information for C
species is reported in the ESI. b Mercury-drop test using the same reaction conditions resulted in no inhibition.
experiments in Table 1 and entries 1–7 in Table 2 were con- fluoro- (7–48%), trifluoromethyl- (24%), and methyl-NBB
ducted with a 34 mM initial concentration of the [Ni(COD)]/ (19–26%) substrates (S1–S8). However, imidazole-type products
dcype system. When increasing the concentration to 68 mM were not observed in any case.19 On the other hand, alkyl-,
(Table 2, entry 8), a remarkable effect on the catalyst perform- naftyl-, and pyridyl-NBB derivatives and bromo-, phenyl-, di-
ance was observed. Both good NBB conversion and A yield methylamino-, and hydroxyl-functionalized NBB substrates
were obtained (71% and 56%, respectively), but the imidazole (S9–S19, see ESI†) did not produce the corresponding hetero-
B yield remained rather low (11%) despite this improvement. cyclic products. In the particular case of alkyl-NBB derivatives,
The impact of the initial catalyst concentration turns out to be substrate conversion was not observed. This indicated that
very important. For instance, with an initial concentration of benzylic motifs at the imines play a central role in the reactiv-
4.2 mM, there is no reaction at all (Table 2, entry 9), which is ity towards dehydrogenation pathways.
the same result as running the experiment without the Ni(0)-
The results in Scheme 2 point out the remarkable features
catalyst (Table 2, entry 10). Further efforts were made to of the developed catalytic system. Since there are two different
increase the catalyst performance. We did an experiment using functionalization sites at the imine scaffold (R1 and R2), not
neat (no solvent) reaction conditions (Table 2, entry 11) and only did the use of substrates where R1 ≠ R2 lead to asymmetri-
longer reaction time (Table 2, entry 12) under the conditions cal 2-imidazoline products, but also it was possible to easily
shown in Table 2, entry 8. Unfortunately, none of these control the substitution pattern in these products by the
changes increased the reaction yields.
appropriate selection of R-groups. For instance, the use of
Considering these results, we established that 48 h of reac- 2-fluorophenyl as R1 in S1 gives the 2-imidazoline A1 functio-
tion using the reaction conditions shown in Table 2, entry 8, nalized with these groups at the 2- and 5-positions. On the
are the optimized reaction conditions for further studies.
other hand, if 2-fluorophenyl is used instead as R2 (S7), this
Since there is a major interest, in medicinal chemistry, in yields A7 as the product, with 2-fluorophenyl at the N-CH2-
the synthesis of functionalized heterocyclic molecules,18 we and 4-positions. These changes in the substitution pattern
decided to use the optimized reactions conditions to examine could also be seen upon comparing products A2 and A8.
the reaction scope of this process with a variety of dimethyl-
What is particularly striking is the influence that fluorine
amino-, methoxy-, hydroxyl-, methyl-, phenyl-, bromo-, fluoro-, atoms at different positions in the aromatic motifs in R1 and
and trifluoromethyl-functionalized NBB substrates in addition R2 (S1 and S2, S7 and S8) have on the formation of the corres-
to pyridyl-, naftyl- and alkyl-NBB derivatives that were studied.
ponding 2-imidazolines. We speculate that 2-fluoro functiona-
As shown in Scheme 2, low to moderate reaction yields of lized substrates generally give higher product yields due to
the corresponding tetra-substituted 2-imidazoline-type pro- their stability towards feasible side reactions such as C–F acti-
ducts A1–A8 were obtained in the case of methoxy- (5%), vation. This stability may arise from the steric effects associ-
16000 | Dalton Trans., 2014, 43, 15997–16005
This journal is © The Royal Society of Chemistry 2014

View Article Online
Dalton Transactions
Paper
Scheme 2 Reaction scope (chromatographic yield).
ated with the presence of the dcype ligand coordinated at the addition, the formation of intermediate 3 accounts for the lack
metal center during such processes. of reactivity of alkyl-NBB derivatives (see ESI†). The low stabi-
A mechanistic proposal for the Ni(0)-catalyzed process is lity of [(dcype)Ni(H)(R)] (R = alkyl) intermediates would lead to
depicted in Scheme 3. We include the following considerations either decomposition of such intermediates or undesired side
for this proposal: (i) the use of a strong σ-donor ligand (dcype), reactions.
(ii) the high catalyst concentration required, and (iii) the high
selectivity towards 2-imidazoline product compared to the imi- insertion reaction by a second equivalent of NBB into the
dazole using NBB as the substrate. Ni(II)–C bond affording a new C–C bond in species 4 (step d).
Once intermediate 3 has been formed in step c, there is an
Since COD ligands are easily replaced from Ni(0)-centers by The high catalyst concentration needed for this transformation
phosphines, we postulate the formation of the catalytic active accounts for a possible bimolecular nature of such steps also
species [(dcype)2Ni] by reaction of Ni(COD)2 with two equi- showing the rather poor nucleophilic character of Ni–C bonds.
valents of dcype in step a. From there, a ligand substitution Then, the five-membered heterocyclic ring is assembled in
reaction by NBB takes place to form the 16-electron π-complex intermediate 5 by an intramolecular insertion pathway in step
2 (step b).20 This Ni(0) species undergoes benzylic C–H bond e. From this, we propose that β-hydride elimination followed
activation through oxidative addition to afford Ni(II) intermedi- by H2 reductive elimination and re-coordination of the pro-
ate 3 (step c).21 As this kind of oxidative addition process is duced 2-imidazoline species affords the Ni(0)-intermediate 6
promoted by electron-rich metal centers, we believe that it cer- (step f). Product A is then finally released in step g by a ligand
tainly accounts for the use of strong σ-donor ligands such as substitution reaction with dcype closing the catalytic cycle.
dcype.22 However, considering the ligand screening in Table 1,
In order to explain the formation of the complete unsatu-
we also believe that dcype not only increases the electron rated product B, we propose that intermediate 6 undergoes
density at the Ni-metal center, but also plays a pivotal role in C–H bond activation at the imidazoline framework yielding
stabilizing Ni(II)-intermediates throughout the catalytic cycle intermediate 7 (step h). Then, 7 releases product B in step i
through both steric effects and the ethane backbone. In though β-hydride elimination, concomitant reductive elimin-
This journal is © The Royal Society of Chemistry 2014
Dalton Trans., 2014, 43, 15997–16005 | 16001

View Article Online
Paper
Dalton Transactions
Scheme 3 Mechanistic proposal.
ation of H2, and re-coordination of dcype to the Ni(0) center, seemed to be the slow steps. Since both C–H bond activation
forming the initial [(dcype)2Ni] complex. Since the B yield was and functionalization are topical issues, we believe that the
always low starting from NBB, we believe that imidazoline C–H current contribution sheds light on the design of operationally
bond activation in step h is a very slow step in comparison simple and novel methodologies using abundant metal cata-
with the release of product A (step g), perhaps due to steric lysts towards important organic molecules.
hindrance at the oxidative addition intermediate 7 between
the cyclohexyl units of dcype and the imidazoline heterocycle.
Experimental
General considerations
Conclusions
Unless otherwise noted, all experiments were carried out using
We have shown the additive-free Ni(0)-catalyzed dehydrogena- standard Schlenk techniques in a double-vacuum argon mani-
tion of benzylic-type imines to yield five-membered hetero- fold or in a glovebox (MBraun Unilab) under high-purity argon
cyclic compounds. Starting from N-benzylidenebenzylamine, (Praxair 99.998) with controlled concentrations of water and
we obtained the corresponding tetra-substituted 2-imidazoline oxygen (<1 ppm). Catalytic experiments were carried out in
and the corresponding imidazole in good and moderate yields, Schlenk tubes. All purchased liquid reagents were of reagent
respectively. On the other hand, using fluoro-, trifluoromethyl- grade and degassed before use. All solvents were dried and
, methoxy-, and methyl-substituted NBB imines, we observed deoxygenated by standard procedures. NBB and S1–S10 sub-
the sole formation of the asymmetric 2-imidazoline products strates were prepared by reported methods. [Ni(COD)2] (COD =
in low to moderate yields. We have also shown the feasibility 1,5-cyclooctadiene) was purchased from Strem and stored in
of controlling the substitution pattern in these products by the glovebox for further use. dippe (1,2-bis(diisopropylphos-
carefully selecting the substituents at the starting imine.
phino)ethane) was prepared from 1,2-bis(dichloro)ethane
We proposed a mechanistic pathway for this transformation (Aldrich) and a solution of isopropylmagnesium chloride
based on simple experimental observations. Benzylic C(sp3)–H (2.0 M, Aldrich) in THF. PEt3, dppe (1,2-bis(diphenylphos-
bond activation of the substrate through oxidative addition phino)ethane), dippf (1,1′-bis(diisopropylphosphino)ferro-
and bimolecular insertions into the Ni–C bond formed cene), and dppf (1,1′-bis-(diphenylphosphino)ferrocene) were
16002 | Dalton Trans., 2014, 43, 15997–16005
This journal is © The Royal Society of Chemistry 2014

View Article Online
Dalton Transactions
Paper
purchased from Aldrich and used without further purification.
PtBu3, PCy3, P(OPh)3, dtbpe (1,2-bis(ditertbutylphosphino)-
ethane), and dcype (1,2-bis(dicyclohexylphosphino)ethane)
were purchased from Strem Chemicals and stored in the glove-
box for further use. GC-MS determinations were performed
using an Agilent 5975C system equipped with a 30 m DB-5MS
capillary (0.32 mm i.d.) column.
H. Iwaasa, S. Mashiko, A. Gomori, R. Moriya, N. Fujino,
T. Ohe, A. Ishihara, A. Kanatani and T. Fukami, J. Med.
Chem., 2009, 52, 3385; (i) L. T. Vassilev, B. T. Vu, B. Graves,
D. Carvajal, F. Podlaski, Z. Filipovic, N. Kong, U. Kammlott,
C. Lukacs, C. Klein, N. Fotouhi and E. A. Liu, Science, 2004,
303, 844; ( j) V. Sharma, S. Peddibhotla and J. J. Tepe, J. Am.
Chem. Soc., 2006, 128, 9137; (k) V. Sharma, T. A. Lansdell,
S. Peddibhotla and J. J. Tepe, Chem. Biol., 2004, 11, 1689;
(l) S. Tsujii, K. L. Rinehart, Y. Kashman, S. S. Cross,
M. S. Lui, S. A. Pomponi and M. C. Diaz, J. Org. Chem.,
1988, 53, 5446; (m) M. R. Kuszpit, W. D. Wulff and
J. J. Tepe, J. Org. Chem., 2011, 76, 2913; (n) D. K. Kahlon,
T. A. Lansdell, J. S. Fisk and J. J. Tepe, Bioorg. Med. Chem.,
2009, 17, 3093.
2 For selected publications on imidazole-based novel
materials, see: (a) T. Iwamura and S. Nakamura, Polymer,
2013, 54, 4161; (b) M. Trojer, A. Movahedi, H. Blanck and
M. Nydén, J. Chem., 2013, 23, 1; (c) S. Yuan, Y. Deng and
D. Sun, Chem. – Eur. J., 2014, 20, 1; (d) Y. Liu, J. Wang,
Y. Yang, T. M. Brenner, S. Seifert, Y. Yan, M. W. Liberatore
and A. M. Herring, J. Phys. Chem. C, 2014, 118(28), 15136–
15145; (e) Y. Gao, J. Wu, W. Zhang, Y. Tan, J. Zhao and
B. Tang, Mater. Lett., 2014, 128, 208; (f) L. Zhang, H. Qi,
J. Hao, L. Yang, P. Yu and L. Mao, ACS Appl. Mater. Inter-
faces, 2014, 6, 5988. For selected publications on imidazo-
line-based novel materials, see: (g) F. Zhou, H. Zhang,
D. Du and W. Wang, Adv. Mater. Res., 2014, 864–867, 1342;
(h) D. Farkhani, H. Rezaei, N. Gholami, M. Sina,
A. A. Khalili and A. Mehdizadeh, J. Pet. Sci. Technol., 2013,
3, 1; (i) D. Bajpai and V. K. Tyagi, J. Oleo Sci., 2006, 55, 319.
3 For publications on imidazole coordination chemistry, see:
(a) Y. Sunatsuki, Y. Motoda and N. Matsumoto, Coord.
Chem. Rev., 2002, 226, 199; (b) Y. Sunatsuki, R. Kawamoto,
K. Fujita, H. Maruyama, T. Suzuki, H. Ishida, M. Kojima,
S. Iijima and N. Matsumoto, Coord. Chem. Rev., 2010, 254,
1871; (c) K. M. Lancaster, J. B. Gerken, A. C. Durrell,
J. H. Palmer and H. B. Gray, Coord. Chem. Rev., 2010, 254,
1803. For publications on imidazoline coordination chemi-
stry, see: (d) S. Haneda, C. Ueba, K. Eda and M. Hayashi,
Adv. Synth. Catal., 2007, 349, 833; (e) H. Liu and D. Due,
Adv. Synth. Catal., 2009, 351, 489; (f) J. P. Roth and
J. M. Mayer, Inorg. Chem., 1999, 38, 2760.
General procedure
In a typical experiment, [Ni(COD)2] (2.8 mg, 0.010 mmol), NBB
(0.1 g, 0.512 mmol) and the corresponding amounts of the
ligand and the solvent were placed in a Schlenk tube. The tube
was then closed and taken out from the glovebox. Using an oil
bath, the tube was heated to the required temperature for 48 h.
After this time, the reaction mixture was cooled down to room
temperature, exposed to air, and analyzed by GC-MS.
Reaction scope
In a typical experiment, [Ni(COD)2] (2.8 mg, 0.010 mmol),
dcype (8.6 mg, 0.020 mmol), 0.512 mmol of a given substrate,
and 0.15 ml of toluene were place in a Schlenk tube. The tube
was then closed and taken out of the glovebox. Using an oil
bath, the tube was heated to 150 °C for 48 h. After this time,
the reaction mixture was cooled down to room temperature,
exposed to air, and analyzed by GC-MS.
Acknowledgements
We thank PAPIIT-DGAPA-UNAM (IN-210613) and CONACYT
(0178265) for their financial support of this work. A. T. A. also
thanks CONACYT (270971) for a scholarship for graduate
studies.
References
1 For the biological application of imidazoles, see:
(a) G. J. Atwell, J. Fan, K. Tan and W. A. Denny, J. Med.
Chem., 1998, 41, 4744; (b) Y. Iinuma, S. Kozawa,
H. Ishiyama, M. Tsuda, E. Fukushi, J. Kawabata, J. Fromont
and J. Kobayashi, J. Nat. Prod., 2005, 68, 1109;
(c) P. B. Koswatta and C. H. Lovely, Nat. Prod. Rep., 2011,
28, 511; (d) F. V. Lali, A. E. Hunt, S. J. Turner and
B. M. J. Foxwell, J. Biol. Chem., 2000, 275, 7395;
(e) P. R. Young, M. M. McLaughlin, S. Kumar, S. Kassis,
M. L. Doyle, D. McNulty, T. F. Gallagher, S. Fisher,
P. C. McDonnell, S. A. Carr, M. J. Huddleston, G. Seibel,
T. G. Porter, G. P. Livi, J. L. Adams and J. C. Lee, J. Biol.
Chem., 1997, 272, 12116; (f) R. R. Wexler, W. J. Greenlee,
J. D. Irvin, M. R. Goldberg, K. Prendergast, R. D. Smith and
P. B. M. W. M. Timmermans, J. Med. Chem., 1996, 39(3),
625; (g) S. Riduan and Y. Zhang, Chem. Soc. Rev., 2013, 42,
9055. For the biological application of 2-imidazolines, see:
(h) N. Sato, M. Ando, S. Ishikawa, M. Jitsuoka, K. Nagai,
H. Takahashi, A. Sakuraba, H. Tsuge, H. Kitazawa,
4 (a) F. Ekkehardt Hahn and M. C. Jahnke, Angew. Chem., Int.
Ed., 2008, 47, 3122; (b) W. A. Herrmann, Angew. Chem., Int.
Ed., 2002, 41, 1290; (c) T. Dröge and F. Glorius, Angew.
Chem., Int. Ed., 2010, 49, 6940; (d) H. D. Velazquez and
F. Verpoort, Chem. Soc. Rev., 2012, 41, 7032; (e) L. Schaper,
S. J. Hock, W. A. Herrmann and F. E. Kühn, Angew. Chem.,
Int. Ed., 2013, 52, 270; (f) W. A. Herrmann, Angew. Chem.,
Int. Ed., 2002, 41, 1290; (g) W. A. Herrmann and C. Kocher,
Angew. Chem., Int. Ed. Engl., 1997, 36, 2162.
5 (a) S. Zhang, J. Sun, X. Zhang, J. Xin, Q. Miao and J. Wang,
Chem. Soc. Rev., 2014, DOI: 10.1039/c3cs60409h;
(b) J. Dupont, R. F. de Souza and P. A. Z. Suarez,
Chem. Rev., 2002, 102, 3667; (c) T. L. Greaves and
C. J. Drummond, Chem. Rev., 2008, 108, 206;
This journal is © The Royal Society of Chemistry 2014
Dalton Trans., 2014, 43, 15997–16005 | 16003

View Article Online
Paper
Dalton Transactions
(d) M. A. P. Martins, C. P. Frizzo, D. N. Moreira, N. Zanatta 14 (a) W. F. Seifer, A. Bosma, A. Brouwer, H. F. J. Hendriks,
and H. G. Bonacorso, Chem. Rev., 2008, 108, 2015;
(e) T. Welton, Chem. Rev., 1999, 99, 2071; (f) J. P. Hallett
and T. Welton, Chem. Rev., 2011, 111, 3508.
6 (a) J. Revuelta, F. Machetti and S. Cicchi, in Modern Hetero-
cyclic Chemistry, ed. J. Alvaréz-Builla, J. J. Vaquero and
P. J. M. Roholl, R. E. W. van Leeuwen, G. C. F. T. Ruitner,
I. Seifer-Bock and D. L. Knook, Hepatology, 1994, 19, 193;
(b) K. Liu, Y. Kato, M. Yamazaki, O. Higuchi, T. Nakamura
and Y. Sugiyama, Hepatology, 1993, 17, 651;
(c) R. O. Recknagel, E. A. Glende, J. J. A. Dolak and
R. L. Waller, Pharmacol. Ther., 1989, 43, 139;
(d) R. O. Recknagel, Pharmacol. Rev., 1967, 19, 145.
J. Barluenga, Wiley-VCH Verlag Gmbh
& Co. KGaA,
Germany, 2011, vol. 2, pp. 809–925; (b) R. J. Ferw and
J. L. Riebsomer, Chem. Rev., 1954, 54, 593; 15 (a) J. Hartwig, in Organotransition Metal Chemistry From
(c) M. R. Grimmet, in Imidazol and benzimidazol synthesis,
Academic Press, USA, 1997, pp. 1–247; (d) H. Fujioka,
K. Murai, K. Ozora, Y. Ohba and Y. Kita, Tetrahedron, 2007,
63, 638; (e) A. Mirjafari, Environ. Chem. Lett., 2014, 12, 177;
(f) S. E. Wolkenberg, D. D. Wisnoski, W. H. Leister,
Bonding to Catalysis, University Science Books, USA, 2010;
(b) C. A. Tolman, Chem. Rev., 1977, 77, 313; (c) P. W. N.
M. van Leeuwen, in Homogeneus Catalysis Understanding
the Art, Kluwer Academic Publishers, The Netherlands,
2004.
Y. Wang, Z. Zhao and C. W. Lindsley, Org. Lett., 2004, 6, 16 Dielectric constants (ε): mesitylene (2.28), THF (7.32),
1453; (g) R. D. Crouch, Tetrahedron, 2009, 65, 2387;
(h) D. Kumar, D. N. Kommi, N. Bollineni, A. R. Patel and
A. K. Chakraborti, Green Chem., 2012, 14, 2038.
toluene (2.38), benzonitrile (25.2). Values are from: The
Chemist’s companion a handbook of practical data, techniques
and references, ed. A. J. Gordon and R. A. Ford, Wiley-Inter-
science, Germany, 1972.
7 (a) S. Kamijo and Y. Yamamoto, Chem. – Asian J., 2007, 2,
568; (b) A. V. Gulevich, A. S. Dudnik, N. Chernyak and 17 Similar effects on the catalyst performance due to such
V. Gevorgyan, Chem. Rev., 2013, 113, 3084; (c) D. Tang,
X. Li, X. Guo, P. Wu, J. Li, K. Wang, H. Jing and B. Chen,
Tetrahedron, 2014, 70, 4038; (d) D. Tang, P. Wu, X. Liu,
ligand to metal ratios have been recently reported in the
Ni(0)/Ni(II)-catalytic system, see: K. Muto, J. Yamaguchi,
A. Lei and K. Itami, J. Am. Chem. Soc., 2013, 135, 16384.
Y. Chen, S. Guo, W. Chen, J. Li and B. Chen, J. Org. Chem., 18 (a) P. Anbarasan, H. Neumann and M. Beller, Angew.
2013, 78, 2746; (e) S. Li, Z. Li, Y. Yuan, D. Peng, Y. Li,
L. Zhang and Y. Wu, Org. Lett., 2012, 14, 1131; (f) J. Li and
L. Neuville, Org. Lett., 2013, 15, 1752; (g) Z. Cai, S. Wang
and S. Ji, Org. Lett., 2012, 14, 6068; (h) Z. Jiang, P. Lu and
Y. Wang, Org. Lett., 2012, 14, 6267.
8 (a) K. Worrall, B. Xu, S. Bontemps and B. A. Arndtsen,
J. Org. Chem., 2011, 76, 170; (b) Q. Li, L. Wei, X. Chen and
C. Wang, Chem. Commun., 2013, 49, 6277; (c) H. Liu and
D. Du, Adv. Synth. Catal., 2009, 351, 489; (d) S. Bontemps,
J. S. Quesnel, K. Worrall and B. A. Arndtsen, Angew. Chem.,
Chem., Int. Ed., 2010, 49, 2219; (b) T. Liang, C. N. Neumann
and T. Ritter, Angew. Chem., Int. Ed., 2013, 52, 8214;
(c) M. Shimizu and T. Hiyama, Angew. Chem., Int. Ed., 2005,
44, 214; (d) M. Tredwell and V. Gouverneur, Angew. Chem.,
Int. Ed., 2012, 51, 11426; (e) J. C. Lee, J. T. Laydon,
P. C. McDonnell, T. F. Gallagher, S. Kumar, D. McNully,
M. Blumenthal and J. R. Heys, Nature, 1994, 372, 739;
(f) J. Wang, M. Sánchez-Roselló, J. L. Aceña, C. del Pozo,
A. E. Sorochinsky, S. Fustero, V. A. Soloshonok and H. Liu,
Chem. Rev., 2014, 114, 2432.
Int. Ed., 2011, 50, 8948; (e) J. V. Geden, A. K. Pancholi and 19 We believe that the rather low yields of products A1–A8
M. Shipman, J. Org. Chem., 2013, 78, 4158.
using the examined imines arise from the well known
capacity of Ni(0)-complexes to activate C–X bonds (X = F,
OR) which could led to either catalyst decomposition or
side reactions, see for example: (a) E. Clot, O. Eisenstein,
N. Jasim, S. A. Macgregor, J. E. Mcgrady and R. N. Perutz,
Acc. Chem. Res., 2011, 44, 333; (b) M. Tobisu, T. Xu,
T. Shimasaka and N. Chatani, J. Am. Chem. Soc., 2011, 133,
19505; (c) A. Corre, T. León and R. Martin, J. Am. Chem.
Soc., 2014, 136, 1062; (d) P. Álvarez-Bercedo and R. Martin,
J. Am. Chem. Soc., 2010, 132, 17352.
9 J. J. García, P. Zerecero-Silva, G. Reyes-Rios, M. G. Crestani,
A. Arévalo and R. Barrios-Francisco, Chem. Commun., 2011,
47, 10121.
10 Imines have been selectively obtained in a similar catalytic
process by our group, see: P. Zerecero-Silva, I. Jimenez-
Solar, M. G. Crestani, A. Arévalo, R. Barrios-Francisco and
J. J. García, Appl. Catal., A, 2009, 363, 230.
11 (a) J. Li, C. Kornhaaß and L. Ackermann, Chem. Commun.,
2012, 48, 11343; (b) G. Rouquet and N. Chatani, Angew.
Chem., Int. Ed., 2013, 52, 11726; (c) K. M. Engle, T. Mei, 20 This type of [(phosphine)Ni(η2-C,N-imine)] complex has
M. Wasa and J. Yu, Acc. Chem. Res., 2012, 45, 788;
(d) M. Deponti, S. I. Kozhushkov, D. S. Yufit and
L. Ackermann, Org. Biomol. Chem., 2013, 11, 142;
(e) L. Ackermann, Chem. Rev., 2011, 111, 1315;
(f) L. Ackermann, A. V. Lygin and N. Hofmann, Org. Lett.,
2011, 13, 3278.
been described, see: (a) A. L. Iglesias, M. Muñoz-Hernán-
dez and J. J. García, J. Organomet. Chem., 2007, 692, 3498;
(b) S. Ogoshi, H. Ikeda and H. Kurosawa, Pure Appl. Chem.,
2008, 80, 1115; (c) I. Matas, J. Campora, P. Palma and
E. Alvarez, Organometallics, 2009, 28, 6515; (d) J. Cámpora,
I. Matas, P. Palma, E. Álvarez, C. Graiff and A. Tiripicchio,
Organometallics, 2007, 26, 3840.
12 S. Samanta, D. Roy, S. Khamarui and D. K. Maiti, Chem.
Commun., 2014, 50, 2477.
13 J. Tsuji, K. Sakai, H. Nemoto and H. Nagashima, J. Mol.
Catal., 1983, 18, 169.
21 For selected articles proposing the formation of key Ni(II)-
intermediates of the type [(L)Ni(H)X] (L, X = ligand)
through oxidative addition during the catalytic process,
16004 | Dalton Trans., 2014, 43, 15997–16005
This journal is © The Royal Society of Chemistry 2014

View Article Online
Dalton Transactions
Paper
see: (a) H. Shiota, Y. Ano, Y. Aihara, Y. Fukumoto and
N. Chatani, J. Am. Chem. Soc., 2011, 133, 14952;
(b) P. Kumar and J. Louie, Angew. Chem., Int. Ed., 2011, 50,
10768.
Y. Kamada, K. Muto, J. Yamaguchi and K. Itami, Angew.
Chem., Int. Ed., 2013, 52, 10048; (b) K. Muto, J. Yamaguchi
and K. Itami, J. Am. Chem. Soc., 2012, 134, 169;
(c) K. Amaike, K. Muto, J. Yamaguchi and K. Itami, J. Am.
Chem. Soc., 2012, 134, 13573; (d) K. Muto, J. Yamaguchi,
A. Lei and K. Itami, J. Am. Chem. Soc., 2013, 135, 16384.
22 For recent references pointing out the key role that dcype
plays in Ni(0)/Ni(II) catalytic systems, see: (a) L. Meng,
This journal is © The Royal Society of Chemistry 2014
Dalton Trans., 2014, 43, 15997–16005 | 16005