Ruthenium(II) Complexes of Heteroditopic N-Heterocyclic Carbene Ligands: Efficient Catalysts for C-N Bond Formation via a Hydrogen-Borrowing Strategy under Solvent-Free Conditions

Article abstract of DOI:10.1021/acs.inorgchem.9b03049

Both imidazol-2-ylidene (ImNHC) and 1,2,3-triazol-5-ylidene (tzNHC) have evolved to be elite groups of N-heterocyclic carbene (NHC) ligands for homogeneous catalysis. To develop efficient ruthenium(II)-based catalysts incorporating these ligands for C-N bond-forming reactions via hydrogen-borrowing methodology, we utilized chelating ligands integrated with ImNHC and mesoionic tzNHC donors connected via a CH₂ spacer with a diverse triazole backbone. The synthesized ruthenium(II) complexes 3 are found to be highly efficient for C-N bond formation across a wide range of primary amine and alcohol substrates under solvent-free conditions, and among all of the complexes studied here, catalyst 3a with a mesityl substituent displayed maximum activity. To our delight, catalyst 3a is also effective for the selective mono-N-methylation of various anilines utilizing methanol as a coupling partner, known to be relatively more difficult than other alcohols. Furthermore, complex 3a also delivers various substituted quinolines successfully via the reaction of 2-aminobenzyl alcohol with several secondary alcohols. Importantly, catalyst 3a exhibited the highest activity among the reported ruthenium(II) complexes for both the N-benzylation of aniline [achieving a turnover number (TON) of 50000] and the realization of quinoline 8a by reacting 2-aminobenzyl alcohol with 2-phenylethanol (attaining a TON of 30000).

Full text of DOI:10.1021/acs.inorgchem.9b03049

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Article
Ruthenium(II) Complexes of Heteroditopic N‑Heterocyclic Carbene
Ligands: Efficient Catalysts for C−N Bond Formation via a Hydrogen-
Borrowing Strategy under Solvent-Free Conditions
S. N. R. Donthireddy, Praseetha Mathoor Illam, and Arnab Rit*
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ABSTRACT: Both imidazol-2-ylidene (ImNHC) and 1,2,3-triazol-5-ylidene (tzNHC) have evolved to be elite groups of N-
heterocyclic carbene (NHC) ligands for homogeneous catalysis. To develop efficient ruthenium(II)-based catalysts incorporating
these ligands for C−N bond-forming reactions via hydrogen-borrowing methodology, we utilized chelating ligands integrated with
ImNHC and mesoionic tzNHC donors connected via a CH2 spacer with a diverse triazole backbone. The synthesized ruthenium(II)
complexes 3 are found to be highly efficient for C−N bond formation across a wide range of primary amine and alcohol substrates
under solvent-free conditions, and among all of the complexes studied here, catalyst 3a with a mesityl substituent displayed
maximum activity. To our delight, catalyst 3a is also effective for the selective mono-N-methylation of various anilines utilizing
methanol as a coupling partner, known to be relatively more difficult than other alcohols. Furthermore, complex 3a also delivers
various substituted quinolines successfully via the reaction of 2-aminobenzyl alcohol with several secondary alcohols. Importantly,
catalyst 3a exhibited the highest activity among the reported ruthenium(II) complexes for both the N-benzylation of aniline
[achieving a turnover number (TON) of 50000] and the realization of quinoline 8a by reacting 2-aminobenzyl alcohol with 2-
phenylethanol (attaining a TON of 30000).
process involving transfer dehydrogenation (I) of alcohol and
hydrogen transfer (III) to an intermediate imine, generated via
the condensation of amine and carbonyl compound (II),
leading to the desired substituted amine (Figure 1).2a,b,d
In the early 1980s, the group of Watanabe and Grigg
independently described pioneering works on the C−N bond
forming reaction utilizing homogeneous ruthenium,
[RuCl2(PPh3)3], and rhodium, [RhH(PPh3)4], catalysts.3
After these reports, several transition-metal-based homoge-
neous catalytic systems were developed, and, recently,
nonprecious-metals such as manganese, nickel, cobalt, and
iron based systems have also been receiving attention.1f,g,2,4
However, most of these metal complexes contain sensitive
phosphine ligands and require stoichiometric amounts of bases
INTRODUCTION
■
Amines are important structural motifs for various applications
such as pharmaceuticals, peptide chemistry, fine chemicals,
etc.1a,b Conventional methods to attain amines via N-alkylation
make use of expensive and/or toxic reagents, and, in addition,
they suffer from less selectivity, poor atom economy, and
stoichiometric generation of byproducts.1c−e,2a Also, the direct
coupling of alcohol with simple amines to realize substituted
amines is difficult because of the poor nucleophilicity of
commonly utilized amines and/or inadequate effectivity of
hydroxide as the leaving group.1f,g Therefore, the development
of atom-economic and environmentally benign processes for
C−N bond formation is necessary to subdue these drawbacks
and is still a challenging task for synthetic chemists. In line with
this, transition-metal-catalyzed N-alkylation of amines with
alcohols as alkylating agents utilizing a hydrogen-borrowing
methodology has gained interest in recent years because of its
higher atom economy and greener nature with generation of
water as the sole byproduct.1f,g,2 In particular, this process
evolved to be a tandem extension of the transfer hydrogenation
Received: October 17, 2019
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of advantages offered by chelating ligands for the synthesis of
more effective catalytic systems.
Chelating ligands incorporating NHCs, such as classical
symmetrical bis(NHCs),9 ImNHC with a secondary nitrogen
donor,7c,e,f,10 and ImNHC-based pincer ligands,11 are well-
known structural motifs and have been exploited for the
synthesis of various efficient catalysts.6,7,9−12 However, the use
of unsymmetrical chelating ligands incorporating different
NHC donors (such as imidazol-2-ylidene, ImNHC, and 1,2,3-
triazol-5-ylidene, tzNHC) are rather limited, although this has
the potential to yield efficient catalytic systems because of the
presence of two distinct carbene centers having varying σ-
donor/π-acceptor properties.13 In addition, the incorporation
of two carbene functionalities offers easy tunability of the
electronic (because of their distinctly different donor
strengths) and steric (due to numerous possibilities for
alteration of the substitution patterns) properties of the
resulting metal complexes and thereby, in principle, their
catalytic activity. However, previously reported transition-
metal complexes of bidentate ImNHC^tzNHC ligands are
mostly restricted to rhodium/palladium metal centers with
minimal catalytic applications.13b−e Nevertheless, Messerle et
al. have described the activity tweaking of rhodium(I)/
iridium(III) complexes of chelating ligands featuring ImNHC
coupled to a tz-N donor in a C−N bond-forming reaction by
tuning the electronics of the complexes via modification of the
triazole ring.14 Recently, we have described the stereo-
electronic fine-tuning of unsymmetrical chelating ImNHC/
tzNHC-based ruthenium(II)/iridium(III) complexes and
observed the significant impact of this tuning in transfer
hydrogenation of carbonyl and imine functionalities.13a Given
that the N-alkylation of amine via a hydrogen-borrowing
methodology also involves the transfer hydrogenation of imine,
we were optimistic that this type of catalytic system will also be
effective for the same reaction. Motivated by this justification,
we extended the utility of similar systematic electronic tuning
methods of ruthenium(II) complexes containing unsym-
metrical chelating ligands installed with ImNHC and 1,2,3-
Figure 1. General scheme for the N-alkylation reaction via a
hydrogen-borrowing pathway.
and/or longer reaction duration.2a,b,4 In the past few decades,
N-heterocyclic carbenes (NHCs) have been established as a
new genre of ancillary ligands by replacing the traditional
ligands such as phosphines.5 In 2008, the Peris group first
described the utility of IrIII-NHC complexes in amine
alkylation via a hydrogen-borrowing methodology.6 After this
report, various iridium(III) and ruthenium(II) complexes
containing chelating pyrimidine/picolyl NHC, phosphine
NHC, alkoxide- and ether-functionalized NHC ligands have
been reported that show improved catalytic activities.7
Recently, ruthenium(II) complexes containing NNN pincer
ligands have been shown to achieve the highest turnover
number (TON) value among all of the known ruthenium(II)
complexes in the formation of C−C and C−N bonds using the
same methodology.8 These findings suggest that the use of a
chelating ligand instead of a monodentate ligand is beneficial
for the production of an efficient catalyst system for these
transformations possibly because of the stability of the catalytic
intermediate species imparted by these types of ligand systems.
Therefore, current progress in this field demands the utilization
Scheme 1. (a) Synthesis of the Precursor Azolium Salts for Unsymmetrical Imidazolylidene/1,2,3-Triazolylidene-Based
Chelating Dicarbene Ligands and the Corresponding Ruthenium(II) Metal Complexes and (b) Molecular Structure of 3d with
a
Displacement Parameters at the 30% Probability Level
a
Hydrogen atoms and counterion are omitted for clarity.
B
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tzNHC donors linked by a CH2 spacer in the C−N bond-
forming reaction via a hydrogen-borrowing/acceptorless
dehydrogenation strategy.
range of 5.00−6.00 ppm with a 2JH−H coupling constant of ∼16
1
Hz) and the appearance of four different H NMR signals for
the p-cymene aromatic protons due to the loss of symmetry
around the ruthenium(II) center. Electrospray ionization mass
spectrometry (ESI-MS) spectra of the complexes that exhibit
only peaks corresponding to the [M − BF4]+ ion, with isotopic
patterns in perfect agreement with the calculated patterns,
further foster complex formation, which is validated by a
single-crystal X-ray diffraction study of a crystal of 3d
(obtained by the slow diffusion of pentane into a saturated
solution of the complex in dichloromethane). The complex
possesses a typical piano-stool structure, and the pseudoocta-
hedral geometry around the metal center is occupied by a p-
cymene ligand and one chloride ligand and the other two sites
are occupied by two carbene donors from the chelating
ligand.16
RESULTS AND DISCUSSION
■
Synthesis of the Heteroditopic Bis(azolium) Salts
[(2a−2e)-H2](BF4)2. Huisgen 1,3-cycloaddition reactions
(Click reaction) between 1-propargyl-3-methylimidazolium
bromide salt with diversely substituted aromatic azides yield
a series of imidazolium salts connected to substituted triazole
moieties via a CH2 bridge [(1a−1e)-H]Br in good-to-excellent
yields as hygroscopic solids except the mesityl-substituted
compound [1a-H]Br (Scheme 1a). Next, quaternization of the
triazole ring of these compounds by reaction with the
−
methylating agent Me3O+BF4 gave the corresponding
triazolium group containing species [(2a−2e)-H2](BF4)2
(Scheme 1a), which opens up the possibility of generating
mesoionic ligands in addition to the Arduengo-type carbene
center. Diverse substitution at the triazole ring in 2a−2e is
expected to alter the electronic as well as steric properties of
the metal complexes of these ligands, which may lead to a
substantial change in their catalytic performances, as observed
for related cyclometalated ruthenium complexes of mesoionic
monocarbene ligands.15a,b The 1H NMR spectra of the
resulting bis(azolium) compounds [(2a−2e)-H2](BF4)2 in
dimethyl sulfoxide (DMSO)-d6 show distinct signals for
imidazolium, triazolium, and tz-N-methyl protons in the
regions of 9.28−9.71, 9.18−9.24, and 5.92−5.98 ppm,
respectively. In addition, 13C{1H} NMR spectra show an
additional signal for the N-methyl group at the triazole ring
around 38 ppm.13a It is also evident from the 1H NMR spectra
that the triazolium proton is substantially downfield-shifted
compared to those of their corresponding precursor com-
pounds [(1a−1e)-H]Br (see the Supporting Information).
This means that the two most acidic azolium protons in [(2a−
2e)-H2](BF4)2 ligands (based on 1H NMR) can be
deprotonated simultaneously under suitable conditions to
obtain metal complexes with chelating ligands featuring two
different carbene donors (one of the ImNHC type and the
other of the tzNHC type). The observed mass fragments
corresponding to the monopositive ion [M − BF4]+ addition-
ally support formation of the compounds [(2a−2e)-H2]-
(BF4)2.
Next, to study the electronic properties of these bidentate
RuII-NHC complexes 3a−3d with varying substituents, we
carried out electrochemical analysis using both cyclic
voltammetry (CV) and differential-pulse voltammetry (DPV;
Figure 2) in CH2Cl2 (for details, see the Supporting
Figure 2. DPV of selected complexes.
Information). Complexes 3a−3d having CImNHC^CtzNHC
coordination mode displayed consistent variation of the
redox potentials, E1/2 [0.636 V (3a), 0.650 V (3b), 0.646 V
(3c), and 0.690 V (3d)], for the RuII/RuIII redox couple
depending on the substituents at the tz-N-phenyl ring. These
data imply that the mesityl-substituted complex 3a is the most
electron-rich (having the lowest redox potential), whereas the
CF3-substituted complex 3d is the least electron-rich. This
might have important implication(s) in their catalytic perform-
ances because previously described related complexes with tz-
N-3,5-dimethylphenyl (3f; E1/2 = 0.637 V) and tz-N-phenyl
(3g; E1/2 = 0.663 V) substituents have displayed significant
variation in their activity in the catalytic transfer hydrogenation
of unsaturated organic compounds.13a
Catalytic C−N Bond-Forming Reaction via a Hydro-
gen-Borrowing Strategy. Recently, a hydrogen autotransfer
(hydrogen-borrowing) strategy for the C−C and C−N bond-
forming reactions has attracted special interest from the green
chemistry perspective because it exploits nonhazardous
alcohols as alkylating agents and successfully overcomes the
selectivity drawbacks as well as waste generation issue
Synthesis and Characterization of Complexes 3a−3e.
After obtaining the unsymmetrical ligands [(2a−2e)-H2]-
(BF4)2, we proceeded further to synthesize the corresponding
ruthenium(II) complexes 3a−3e by treating the ligands with
[Ru(p-cymene)Cl2]2 in the presence of Cs2CO3 as the base at
65 °C (Scheme 1a). All of these complexes were isolated as air-
stable solids in good-to-excellent yields of 75−92% and well-
characterized by multinuclear NMR spectroscopy, mass
spectrometry, and elemental analysis as well as by X-ray
diffraction studies for 3d. The absence of imidazolium and
1
triazolium protons in the H NMR spectra of the complexes
indicates the successful generation of the carbene donors via
deprotonation, and binding of these carbene donors to
ruthenium(II) centers is manifested by the presence of
characteristic metal-bound carbene carbon signals in the
ranges of 173.1−173.4 ppm (for Ru−CImNHC) and 159.9−
161.2 ppm (for Ru−CtzNHC).13a,15c,d Additional support for
coordination of the ligands 2a−2e to ruthenium(II) in 3a−3e
is obtained from the diastereotopic nature of the bridging CH2
protons (evident from the presence of two doublets in the
C
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associated with other available methods.1c−g,2 To date, various
heterogeneous and homogeneous catalysts have been utilized
for this transformation. Among them, homogeneous iridium-
and ruthenium-based systems have been reported to perform
efficiently with excellent product selectivity.1f,g,2 After having
these well-characterized complexes 3a−3e, the catalytic
efficacy was tested in a C−N bond-forming reaction utilizing
the hydrogen-borrowing method. The initial studies were done
by reacting aniline with benzyl alcohol using the precatalyst 3a
and KOH as the base under neat conditions as a benchmark
reaction, and a good conversion of 78% with 90% selectivity to
N-benzylaniline (6a) was achieved after 2 h (Table S1). Then
we screened various bases to attain a maximum yield of the
product 6a, and KOtBu was found to deliver the best result
(Table S1). Using KOtBu as the base, when we increased the
reaction time to 4 h, ∼90% conversion with complete
selectivity toward amine was achieved (Table S1). Traces of
the product formation were observed when the reaction was
carried out without a ruthenium(II) precatalyst (Table 1, entry
Figure 3. Other related complexes used in this study.
optimization in the present study, we also carried out the N-
alkylation reaction using our previously reported complexes of
chelating heteroditopic ligands (Table 1) in addition to the
newly synthesized complexes, and we were pleased to see that,
on the basis of different substituents and/or donors at the
ligands, these mixed-donor containing RuII-NHC complexes
displayed differences in their catalytic activity. The related
RuII-NHC complex 3f′ with a secondary tz-N donor (Figure 3)
gave a lesser yield of the product with lower selectivity than the
corresponding complex with a triazolylidene donor (3f in
Table 1). The performance of 3f′ is also inferior to those of the
complexes 3d and 3e with the most electron-withdrawing
group substituted triazolylidene donors. These might be due to
shuttle variation in the donor strength between tz-N and
triazolylidene on top of steric alteration. On a similar note, the
related symmetrical bis(ImNHC)-containing complex 5
(Figure 3)9a,16a displays activity similar to that of the secondary
nitrogen-donor containing complex 3f′, although selectivity
toward 6a is enhanced (Table 1), which is possibly expected
from the observed better imine reduction capability of 5 than
3f′.13a We previously observed that the ruthenium(II)
complexes of the heteroditopic NHC ligands are more active
than the analogues iridium(III) complexes (3f vs 3f′ and 4f vs
4f′) in the reduction of unsaturated functionalities using
transfer hydrogenation strategies.13a Therefore, we were
curious to see how these complexes will perform in our
present interest of the N-alkylation reaction of primary amines,
which also involves the reduction of imine as one of the steps.
It was interesting to see that the RuII-NHC complex 3f′ with a
secondary tz-N donor delivers a better yield and selectivity
(toward secondary amines) than the corresponding iridium-
(III) complexes with both a secondary tz-N donor (4f′) and a
triazolylidene donor (4f; Table 1 and Figure 3). Relying on
these catalytic outcomes, we further optimized the reaction
and nearly quantitative conversion of the secondary amine 6a
was attained and isolated in a good yield of 84% when the
reaction time was slightly increased to 6 h (6a in Table 2). It is
important to note that the present catalytic system displays the
highest catalytic activity among the reported ruthenium(II)-
based catalysts7d,8 by achieving a TON of 50000 (for the
synthesis of 6a employing 0.001 mol % catalyst loading).
Inspired by these catalytic results, we extended the
applicability of this reaction to a wide range of amines and
alcohols to identify the substrate scope of the present catalytic
system. Thus, under the optimized reaction conditions, diverse
Table 1. Catalyst Screening for the N-Alkylation of Amines
b
entry
catalyst
% conv (selectivity to amine 6a)
1
2
3
4
3
4
5
8
3a
3f
89 (100)
87 (98)
85 (89)
83 (94)
79 (96)
78 (95)
77 (88)
71 (84)
60 (60)
64 (84)
72 (97)
traces
3b
3c
3g
3d
3e
3f’
4f’
4f
9
10
11
12
5
a
Reagents and conditions: aniline (1.0 mmol), benzyl alcohol (1.2
b
mmol), KOtBu (0.2 mmol), catalyst (0.5 mol %), 4 h. The selectivity
of amine 6a was given in parentheses and calculated from the crude
product mixture using GC−MS analysis.
12) or in the absence of any base (Table S1), which
demonstrates that both the catalyst and base are absolutely
necessary for this catalytic transformation. Additionally, only
[Ru(p-cymene)Cl2]2 under the same reaction conditions
provided poor conversion and low selectivity toward 6a
(Table S1).
Further to study the impact of supporting NHC ligand
variation, a series of ruthenium(II) complexes were employed
for the coupling of aniline with benzyl alcohol, and the results
are summarized in Table 1. Among all of the complexes tested,
3a featuring a mesityl substituent at the triazole ring delivered
the best results (maximum yield and selectivity to 6a).
Recently, we have demonstrated the impact of stereoelectronic
tuning of the structurally similar heteroditopic NHC-based
ligands (Figure 3) in the ruthenium(II)- and iridium(III)-
catalyzed transfer hydrogenation of ketone and imine
functionalities.13a We have noticed that the electron-rich
ruthenium(II) complexes with a dicarbene donor performed
better in the reduction process compared to the complex
containing a monocarbene ligand. In order to have a systematic
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a
Table 2. Scope of the C−N Bond-Forming Reaction
a
Reagents and conditions: aniline (1.0 mmol), primary alcohol (1.2 mmol), KOtBu (0.2 mmol), catalyst 3a (0.005 mmol). Conversion was
b
c
d
obtained from GC−MS analysis. Isolated yields are given in parentheses. Time = 12 h. Time = 24 h. The yield was determined by GC−MS
analysis using mesitylene as the internal standard. A total of 0.5 equiv of base was used.
e
amines and alcohols were investigated, and the results are
summarized in Table 2. Both electron-donating and -with-
drawing substituents at the para position of aniline displayed
excellent functional group tolerance, and the corresponding
secondary amines were isolated in good yield (6a−6e in Table
2). The reaction outcome did not vary upon using p- or m-
methoxy-substituted aniline and afforded the corresponding
products in good yield (80% of 6c and 6f). The alkylation of 2-
aminopyridine is challenging because of the chelation
possibility of both the starting material and product to the
metal center and, thereby, can potentially deactivate the
catalyst by substituting any weakly coordinating supporting
ligand. However, the precatalyst 3a efficiently promotes the
alkylation of 2-aminopyridine, and the corresponding amines
(6g and 6h) were isolated in good yields of 68−78%. We were
pleased to find that the sterically hindered 3,5-dimethylaniline
and 1-naphthylamine were also smoothly alkylated and
afforded the corresponding secondary amines (6i and 6j) in
excellent isolated yields of 81−84%.
in the yield was observed in the case of p-Br-substituted
alcohol (6k and 6l vs 6m). It is worth mentioning that
halosubstitution at either the N-phenyl or C-phenyl ring did
not affect the reaction, and substituted amine products (6d/6e
and 6m/6n) were isolated in moderate-to-excellent yields
(60−86%) with no sign of dehalogenation, whereas the
previous report on the rhodium(I)-catalyzed reaction suffers
from dehalogenation.14b The relatively less reactive aliphatic
alcohols such as butyl/hexyl alcohols also served as successful
alkylating partners and delivered the corresponding amines (6o
and 6p) in decent yields (60−79%). Similarly, heteroaromatic
alcohols such as furan-2-ylmethanol and 2-pyridinemethanol
delivered the products 6q and 6r in moderate-to-good yields
(52−79%), although a longer reaction time of 24 h is required.
A further effort was also directed toward the alkylation of o-
diamine, which normally results in the formation of a
benzimidazole derivative via cyclization after first alkylation
rather than a dialkylated product.17 To our surprise, the
alkylation of o-phenylenediamine with (4-methyl)benzyl
alcohol generated the corresponding dialkylated amines 6s
and 6t instead of C2-alkylated benzimidazole derivatives in
good yields. This observation possibly points toward facile
hydride transfer from the in situ generated ruthenium hydride
Next, the substrate scope of the present protocol was
reviewed using various substituted benzyl alcohols as alkylating
partners. The electron-donating p-Me/p-OMe-substituted
alcohols gave products in good yields, while a slight decrease
E
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to the imine intermediate in the second step (Figure 1) as
opposed to the intramolecular attack of the free NH2 to the
benzylidene intermediate observed for other systems.17a,d It is
also important to note that only a few reports on the
dialkylation of o-phenylenediamine are known.18a,b Notably,
catalyst 3a is also efficient for the synthesis of some biologically
relevant molecules containing either benzylamine or 2-
phenethyl cores, which are commonly found in antiobesity
drugs14,18c,d and afforded the corresponding molecules 6u−6x
in moderate-to-excellent yields of 53−91%.
(82−95%; Table 3). This protocol also tolerates the more
challenging substrate 2-aminopyridine, capable of deactivating
the catalyst because of its chelating nature, and the product 7f
was isolated in a moderate yield of 68%. Although the substrate
scope of the present catalyst system for methylation is
reasonable, catalytic activity is low compared to the most
active ruthenium systems known.22a−c However, it should be
noted that only a very few transition-metal-NHC complexes
are reported to catalyze the N-methylation reaction, and to the
best of our knowledge, no RuII-NHC-based catalyst is known
for the same transformation with substrate scope.23
Catalytic N-Methylation of Amines Using Methanol.
After having success in the synthesis of diverse secondary
amines, we applied the same strategy to attain N-methylated
amines (using methanol) because they are integral compo-
nents of many agrochemicals, medicines, fine chemicals,
etc.19,20 From an environmental perspective, a greener
approach for the methylation of amines is desirable by
avoiding the use of toxic methyl halides, diazomethane, and
other reducing agents; a solvent like methanol is an
appropriate choice for this transformation.21 However, the
selective monomethylation of amines using methanol is still
challenging, and reports are much less because of the higher
activation energy for dehydrogenation compared to higher
alcohols and the possibility of dimethylation.21a,22 To explore
the wide applicability of our RuII-NHC systems, we motivated
ourselves to investigate the challenging N-methylation
reaction, and, gratifyingly, we found that the monomethylation
of various anilines can be smoothly realized by deploying the
catalyst 3a and using methanol as the methylating agent under
the hydrogen-borrowing method. After screening various
conditions, a catalyst loading of 1 mol %, KOH as the base,
and a reaction temperature of 130 °C for 24 h were found to
be optimized conditions for the methylation reaction (Table
S2).
Catalytic Synthesis of Quinolines. The same strategy
was further extended toward the synthesis of biologically
relevant heteroaromatic molecules quinolines, which are
present in several therapeutic drugs.24 Most of the efforts for
their synthesis have been directed toward the cyclization of 2-
amino alcohols with ketones.25 Relative to these, the
cyclization of amino alcohols with secondary alcohols as
coupling partners is less explored, and in most of the cases,
excess alcohol or hydrogen scavengers are typically requir-
ed.25b,26a−c Inspired by the catalytic proficiency in the N-
alkylation reaction of our present catalytic systems, we next
assessed their efficiency in the cyclization of 2-aminobenzyl
alcohol with various secondary alcohols to realize substituted
quinolines. To our delight, the complex 3a displayed excellent
activity in this reaction by displaying the highest TON of
30000 for the synthesis of 8a among the ruthenium(II)
complexes reported to date.8,26a−c Further, various electron-
withdrawing as well as -donating-group substituted 1-phenyl-
ethanol and 2-aminobenzyl alcohol were coupled with ease,
and the corresponding quinoline derivatives 8a−8d were
attained in good yields (Table 4). Satisfyingly, bulkier 1-
naphthylethanol can also be employed as a coupling partner to
deliver the quinoline derivative 8e. However, coupling between
1-phenyl-1-propanol and 2-aminobenzyl alcohol to yield 8f was
somewhat less effective and, therefore, isolated in relatively
lower yield (Table 4).
Mechanistic Studies. To probe the reaction mechanism,
various controlled experiments were carried out. We first
intended to study the kinetics of this reaction by examining the
formation of 6a as a function of time under the optimized
reaction conditions (Figure 4). At the initial stage of reaction
(up to 2 h), aniline was expeditiously consumed and converted
into 6a accompanied by the formation of N-benzylideneaniline
(6a′) as a minor product. Notably, from the start of the
reaction until 1 h, intermediate imine was observed in
considerable amount. However, as the reaction time elapsed,
the desired product 6a was exclusively obtained and reached a
maximum of 94% in 6 h. Hence, the reaction profile supports
the progress of the reaction via an imine intermediate, which
follows a one-pot tandem transfer hydrogenation strategy, as
depicted in Figure 1.
Satisfyingly, aniline is transformed to N-methylaniline (7a)
almost quantitatively under optimized conditions and isolated
in a good yield of 85% (Table 3). Notably, the methylation of
various sterically and electronically different aromatic amines
can also be attained efficiently via this protocol to afford the
corresponding products 7b−7e in good-to-excellent yields
a
Table 3. Scope of the N-Methylation of Amines
A few more controlled experiments were also carried out, as
depicted in Scheme 2. The presence of elemental mercury (3
equiv with respect to aniline) did not alter the catalytic
outcome, indicating the homogeneous nature of the reaction.
The reaction of 6a′ with benzyl alcohol under standard
conditions afforded 6a in decent yield [35% based on gas
chromatography−mass spectrometry (GC−MS) analysis],
which proposes the formation of a Ru−H intermediate during
the catalytic cycle via the dehydrogenation of benzyl alcohol.
This proposal is further strengthened by the observation of
benzaldehyde formation (49%) when the reaction was
a
Reagents and conditions: aniline (0.5 mmol), methanol (1 mL),
KOH (0.5 mmol), catalyst 3a (0.005 mmol). All are isolated yields.
b
The yield was determined by GC−MS analysis using mesitylene as
internal standard.
F
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a
Table 4. Scope for the Quinoline Synthesis
a
Reagents and conditions: 2-aminobenzyl alcohol (1.0 mmol), secondary alcohol (1.2 mmol), KOtBu (0.5 mmol), catalyst 3a (0.005 mmol). All
are isolated yields.
involves first dehydrogenation of alcohol, followed by the
coupling of free amine with the produced aldehyde to provide
the corresponding imine, and then the reduction by in situ
generated RuII-H species to yield the final secondary amine
(Figure S1). We believe that an analogous mechanism via
formaldehyde formation is operating for the N-methylation
reaction.
CONCLUSION
■
In conclusion, we have developed unsymmetrical bidentate
ligands incorporating two different carbene donors, ImNHC
and tzNHC, which upon coordination to the ruthenium(II)
center yield efficient catalysts for the N-alkylation of aniline
using alcohol under neat conditions via a hydrogen-borrowing
strategy. Satisfyingly, the catalyst 3a having a mesityl
substituent exhibited the highest activity among the reported
ruthenium(II)-based catalysts for the benzylation of aniline by
achieving a TON of 50000. Furthermore, the catalyst 3a was
also successfully employed for the selective mono-N-
methylation of various anilines utilizing the coupling partner
methanol. Importantly, the same strategy could also be
extended toward the synthesis of biologically significant
heteroaromatic quinolines via oxidative coupling, followed by
Figure 4. Course of the reaction progress for the N-benzylation of
aniline based on the conversion determined using GC−MS.
performed under standard conditions for 12 h, however, in
open air and without added aniline. All of these findings are in
line with the hydrogen-borrowing methodology, which
Scheme 2. Control Experiments
G
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methylphenyl azide (1.0 g, 7.51 mmol) and 1-propargyl-3-
methylimidazolium bromide salt (1.66 g, 8.26 mmol) and obtained
as a cream-colored hygroscopic solid. Yield: 2.31 g (6.91 mmol, 92%).
1H NMR (400 MHz, CDCl3): δ 10.28 (s, Im N−CH−N, 1H), 8.99
(s, Trz C−CH−N, 1H), 7.75 (s, 1H), 7.62 (d, 2H), 7.31 (s, 1H), 7.24
(s, 1H), 5.90 (s, CH2, 2H), 4.01 (s, Im N−CH3, 3H), 2.37 (s, Ar−
CH3, 3H). 13C{1H} NMR (101 MHz, CDCl3): δ 140.8, 139.4, 137.4,
134.3, 130.4, 123.9, 123.1, 122.8, 120.6, 44.5 (CH2), 37.0 (N−CH3),
21.2 (Ar−CH3). MS (ESI, positive ions): m/z 254.1406 (calcd for [M
− Br]+: m/z 254.1406). Consistent CHN data could not be obtained
because of the hygroscopic nature of the compound.
Synthesis of [1d-H]Br. Compound [1d-H]Br was synthesized
following the same procedure as that used for [1a-H]Br using 4-
(trifluoromethyl)phenyl azide (1 g, 5.34 mmol) and 1-propargyl-3-
methylimidazolium bromide salt (1.18 g, 5.87 mmol) and obtained as
a cream-colored hygroscopic solid. Yield: 1.88 g (4.38 mmol, 82%).
1H NMR (400 MHz, CDCl3): δ 10.29 (s, Im N−CH−N, 1H), 9.35
(s, Trz C−CH−N, 1H), 8.01 (d, J = 8.4 Hz, 2H), 7.75 (d, J = 8.5 Hz,
2H), 7.73 (s, 1H), 7.27 (s, 1H), 5.94 (s, CH2, 2H), 4.03 (s, Im N−
CH3, 3H). 13C{1H} NMR (101 MHz, CDCl3): δ 141.4, 139.1, 137.7,
127.2, 124.4, 123.1, 122.8, 120.8, 44.6 (CH2), 37.1 (N−CH3). MS
(ESI, positive ions): m/z 308.0338 (calcd for [M − Br]+: m/z
308.1123). Consistent CHN data could not be obtained because of
the hygroscopic nature of the compound.
Synthesis of [2a-H2](BF4)2. In an oven-dried pressure tube,
trimethyloxonium tetrafluoroborate (0.255 g, 1.725 mmol) and
compound [1a-H]Br (0.25 g, 0.690 mmol), followed by dry
dichloromethane (5 mL), were added under an inert atmosphere.
Then the tube was closed, and the reaction mixture was kept in a
preheated oil bath at 80 °C for 24 h. After removal of the solvent in
vacuo, methanol (4 mL) was added. The resulting mixture was stirred
at room temperature for 0.5 h in open air to decompose the excess
oxonium salt, and the volatiles were removed in vacuo. The resulting
residue was washed with diethyl ether (3 × 5 mL) and a minimal
amount of dichloromethane to yield the product as an off-white air
stable solid. Yield: 0.312 g (0.662 mmol, 96%). 1H NMR (500 MHz,
DMSO-d6): δ 9.28 (s, Im N−CH−N, 1H), 9.18 (s, Trz C−CH−N,
1H), 7.85 (s, Im H4/H5, 1H), 7.81 (s, Im H4/H5, 1H), 7.21 (s, Ar−
H, 2H), 5.92 (s, CH2, 2H), 4.44 (s, Im N−CH3, 3H), 3.90 (s, Trz N−
CH3, 3H), 2.36 (s, Ar−CH3, 3H), 2.02 (s, Ar−CH3, 6H). 13C{1H}
NMR (126 MHz, DMSO-d6): δ 142.0 (Im N−CH−N), 138.8, 137.7,
134.2, 132.6, 131.0, 129.5, 124.2, 122.6, 40.8 (CH2), 38.8 (Trz N−
CH3), 36.0 (Im N−CH3), 20.6 (Ar−CH3), 16.6 (Ar−CH3). 11B NMR
(160 MHz, DMSO-d6): δ −1.31 (s). 19F NMR (471 MHz, DMSO-
d6): δ −148.24 (s), −148.29 (s). MS (ESI, positive ions): m/z
384.1972 (calcd for [M − BF4]+: m/z 384.1816). Anal. Calcd for
C17H23N5B2F8·H2O: C, 41.75; N, 14.32; H, 5.15. Found: C, 41.06; N,
13.28; H, 4.19.
the cyclization of 2-aminobenzyl alcohol with various
secondary alcohols. Significantly, the catalyst 3a established
excellent activity in this reaction, attaining the highest TON of
30000 among all of the ruthenium(II) complexes reported for
synthesis of the quinoline 8a.
EXPERIMENTAL SECTION
■
General Considerations. All manipulations were performed
under an argon/dinitrogen atmosphere using either standard Schlenk-
line or glovebox techniques. All glassware was oven-dried at 130 °C
overnight prior to use. The solvents used were dried, distilled, and
degassed by standard methods and stored over 4 Å molecular sieves.
NMR measurements were performed on Bruker 400 and 500 MHz
FT-NMR spectrometers. The chemical shifts in the 1H NMR spectra
were referenced to the residual proton signals of the deuterated
1
solvents (CDCl3, H 7.26 ppm and 13C{1H} 77.16 ppm; DMSO-d6,
1H 2.50 ppm and 13C{1H} 39.52 ppm) and reported relative to
tetramethylsilane. The coupling constants are expressed in hertz. ESI-
MS spectra were recorded with an Agilent 6545A Q-TOF mass
spectrometer, and elemental analysis was performed using a
PerkinElmer 24000 instrument. The starting materials [Ru(p-
cymene)Cl2]2,27a 1-propargyl-3-methylimidazolium bromide salt,13a,d
ligand [1e-H]Br,27b and alcohols27c−e were prepared according to
literature procedures. All other chemicals were purchased from
commercial sources and used as received without further purification.
Synthesis of Substituted Aryl Azides. All of the substituted aryl
azides were synthesized either following or modifying the reported
procedure,27f and all spectroscopic values are in good agreement with
the reported values. Caution! Organic azides are toxic and explosive.
Therefore, these materials must be handled with appropriate safety
measures.
Synthesis of [1a-H]Br. To a round-bottomed flask containing
2,4,6-trimethylphenyl azide (1 g, 6.20 mmol) and 1-propargyl-3-
methylimidazolium bromide salt (1.37 g, 6.82 mmol) was added 50
mL of a mixture of methanol and H2O (1:1). The resulting mixture
was stirred for 10 min to make it homogeneous, and CuI (0.142 g,
0.74 mmol), followed by NEt3 (1.88 g, 18.6 mmol), was added. The
solution was then stirred overnight at room temperature, and the
reaction mixture was extracted with chloroform (3 × 20 mL). The
combined organic layer was dried over anhydrous MgSO4, and the
solvent was removed in vacuo. The obtained residue was washed with
diethyl ether (3 × 10 mL) and dried under vacuum to yield the
compound as a cream-colored air-stable solid. Yield: 2.17 g (5.98
mmol, 96%). 1H NMR (400 MHz, CDCl3): δ 10.40 (s, Im N−CH−
N, 1H), 8.44 (s, Trz C−CH−N, 1H), 7.76 (s, 1H), 7.24 (s, 1H), 6.96
(s, 2H), 5.97 (s, CH2, 2H), 4.03 (s, Im N−CH3, 3H), 2.34 (s, Ar−
CH3, 3H), 1.91 (s, Ar−CH3, 6H). 13C{1H} NMR (101 MHz,
CDCl3): δ 140.5 (Im N−CH−N), 137.5, 134.9, 133.1, 129.3, 127.4,
123.1, 122.9, 44.5 (CH2), 37.0 (N−CH3), 21.2 (Ar−CH3), 17.6 (Ar−
CH3). MS (ESI, positive ions): m/z 282.0924 (calcd for [M − Br]+:
m/z 282.1719). Anal. Calcd for C16H20N5Br·H2O: C, 50.53; N, 18.42;
H, 5.83. Found: C, 50.22; N, 17.13; H, 4.82.
Synthesis of [2b-H2](BF4)2. Compound [2b-H2](BF4)2 was
synthesized following the same procedure as that used for [2a-
H2](BF4)2 using [1b-H]Br (0.25 g, 0.714 mmol) and trimethyloxo-
nium tetrafluoroborate (0.264 g, 1.758 mmol) and obtained as a
1
cream-colored air-stable solid. Yield: 0.300 g (0.654 mmol, 92%). H
NMR (500 MHz, DMSO-d6): δ 9.45 (s, Im N−CH−N, 1H), 9.24 (s,
Trz C−CH−N, 1H), 7.89 (d, Ar−H, 2H), 7.83 (s, Im N−CH−N,
1H), 7.82 (s, Im N−CH−N, 1H), 7.29 (d, Ar−H, 2H), 5.92 (s, CH2,
2H), 4.42 (s, Im N−CH3, 3H), 3.90 (s, Ar−OCH3, 3H) 3.88 (s, Trz
N−CH3, 3H). 13C{1H} NMR (126 MHz, DMSO-d6): δ 161.6 (Im
N−CH−N), 138.2, 137.7, 128.8, 127.6, 124.2, 123.1, 122.7, 115.5,
55.9 (Ar−OCH3), 40.6 (CH2), 38.6 (Trz N−CH3), 36.1 (Im N−
CH3). 11B NMR (160 MHz, DMSO-d6): δ −1.30 (s). 19F NMR (471
MHz, DMSO-d6): δ −148.28 (s), −148.34 (s). MS (ESI, positive
ions): m/z 372.1609 (calcd for [M − BF4]+: m/z 372.1622). Anal.
Calcd for C15H19N5B2F8O: C, 39.25; N, 15.26; H, 4.17. Found: C,
39.19; N, 14.33; H, 3.47.
Synthesis of [1b-H]Br. Compound [1b-H]Br was synthesized
following a procedure similar to that used for [1a-H]Br using 4-
methoxyphenyl azide (1 g, 6.70 mmol) and 1-propargyl-3-
methylimidazolium bromide salt (1.48 g, 7.37 mmol) and obtained
as a cream-colored hygroscopic solid. Yield: 2.10 g (6.01 mmol,
1
89.7%). H NMR (500 MHz, CDCl3): δ 10.30 (s, Im N−CH−N,
1H), 8.94 (s, Trz C−CH−N, 1H), 7.77 (s, Im H4/H5, 1H), 7.65 (d, J
= 9.0 Hz, Ar−H, 2H), 7.34 (s, Im H4/H5, 1H), 6.95 (d, J = 9.0 Hz,
Ar−H, 2H), 5.89 (s, CH2, 2H), 4.01 (s, Im N−CH3, 3H), 3.81 (s,
Ar−OCH3, 3H). 13C{1H} NMR (126 MHz, CDCl3): δ 160.1, 140.7
(Im N−CH−N), 137.4, 130.0, 124.0, 123.2, 122.9, 122.3, 114.9, 55.7
(Ar−OCH3), 44.5 (CH2), 37.0 (Im N−CH3). MS (ESI, positive
ions): m/z 270.1354 (calcd for [M − Br]+: m/z 270.1355).
Consistent CHN data could not be obtained because of the
hygroscopic nature of the compound.
Synthesis of [2c-H2](BF4)2. Compound [2c-H2](BF4)2 was
synthesized following the same procedure as that used for [2a-
H2](BF4)2 using [1c-H]Br (0.25 g, 0.748 mmol) and trimethyloxo-
nium tetrafluoroborate (0.277 g, 1.870 mmol) and obtained as a
Synthesis of [1c-H]Br. Compound [1c-H]Br was synthesized
following the same procedure as that used for [1a-H]Br using 4-
1
cream-colored air-stable solid. Yield: 0.292 g (0.659 mmol, 88%). H
H
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1
NMR (500 MHz, DMSO-d6): δ 9.50 (s, Im N−CH−N, 1H), 9.24 (s,
Trz C−CH−N, 1H), 7.86 (s, Ar−H, 2H), 7.83 (s, Im N−CH−N,
1H), 7.82 (s, Im N−CH−N, 1H), 7.56 (d, Ar−H, 2H), 5.93 (s, CH2,
2H), 4.43 (s, Im N−CH3, 3H), 3.90 (s, Trz N−CH3, 3H), 2.44 (s,
Ar−CH3, 3H). 13C{1H} NMR (101 MHz, DMSO-d6): δ 142.3 (Im
N−CH−N), 138.4, 137.7, 132.3, 130.9, 128.9, 124.2, 122.7, 121.1,
40.6 (CH2), 38.7 (Trz N−CH3), 36.1 (Im N−CH3), 20.7 (Ar−CH3).
11B NMR (160 MHz, DMSO-d6): δ −1.30 (s). 19F NMR (471 MHz,
DMSO-d6): δ −148.31 (s), −148.31 (s). MS (ESI, positive ions): m/z
356.1669 (calcd for [M − BF4]+: m/z 356.1672).
Synthesis of [2d-H2](BF4)2. Compound [2d-H2](BF4)2 was
synthesized following the same procedure as that used for [2a-
H2](BF4)2 using [1d-H]Br (0.25 g, 0.685 mmol) and trimethyloxo-
nium tetrafluoroborate (0.253 g, 1.712 mmol) and obtained as a
brownish air-stable solid. Yield: 0.260 g (0.523 mmol, 76%). 1H NMR
(400 MHz, DMSO-d6): δ 9.65 (s, Im N−CH−N, 1H), 9.24 (s, Trz
C−CH−N, 1H), 8.20 (s, 4H), 7.82 (s, 2H), 5.96 (s, CH2, 2H), 4.48
(s, Im N−CH3, 3H), 3.90 (s, Trz N−CH3, 3H). 13C{1H} NMR (101
MHz, DMSO-d6): δ 138.5 (Im N−CH−N), 137.5, 137.2, 129.5,
127.7, 124.0, 122.5, 122.3, 40.4 (CH2), 38.8 (Trz N−CH3), 35.9 (Im
N−CH3). 11B NMR (160 MHz, DMSO-d6) δ −1.30 (s). 19F NMR
(471 MHz, DMSO-d6): δ −61.41 (s), −148.28 (s), −148.34 (s). MS
(ESI, positive ions): m/z 410.1390 (calcd for [M − BF4]+: m/z
410.1390). Anal. Calcd for C15H16N5B2F11·CH2Cl2: C, 33.02; N,
12.04; H, 3.12. Found: C, 34.25; N, 12.60; H, 3.01.
0.058 g (0.09 mmol, 83%). H NMR (500 MHz, CDCl3): δ 8.00 (d,
3JH−H = 8.9 Hz, Ar−H, 2H), 7.42 (d, Im N−CH−C, 1H), 7.14 (d, Im
N−CH−C, 1H), 7.08 (d, 3JH−H = 9.0 Hz, Ar−H, 2H), 5.70 (d, 2JH−H
2
= 16.7 Hz, CH2, 1H), 5.43 (d, JH−H = 16.7 Hz, CH2, 1H), 5.38 (d,
3JH−H = 6.2 Hz, p-cymene−Ph, 1H), 5.35 (d, JH−H = 6.2 Hz, p-
3
3
cymene−Ph, 1H), 5.21 (d, JH−H = 5.9 Hz, p-cymene−Ph, 1H), 4.80
3
(d, JH−H = 5.8 Hz, p-cymene−Ph, 1H), 4.31 (s, Trz N−CH3, 3H),
4.10 (s, Im N−CH3, 3H), 3.91 (s, Ar−OCH3, 3H), 2.24−2.15 (sept,
3JH−H = 7.0 Hz, p-cymene−iPr, 1H), 1.80 (s, p-cymene−Me, 3H),
1.01 (d, 3JH−H = 6.9 Hz, 3H), 0.72 (d, 3JH−H = 6.9 Hz, 3H). 13C{1H}
NMR (126 MHz, CDCl3): δ 173.2 (Im Ccarbene), 161.2 (Trz Ccarbene),
160.0, 137.5, 132.1, 129.0, 123.9, 123.2, 114.2, 104.8 (Car−
CH3(cym), 104.0 (Car−iPr(cym)), 91.0 (Car−H(cym)), 90.8 (Car−
H(cym)), 88.5 (Car−H(cym)), 85.8 (Car−H(cym)), 55.9 (Ar−
OCH3), 44.4 (CH2), 39.0 (Trz−NCH3), 37.0 (Im N−CH3), 31.1
(CH(CH3)2), 24.8 (CH(CH3)2), 20.6 (Ar−CH3), 18.5 (CH3−
Car(cym)). 11B NMR (160 MHz, CDCl3): δ −1.04 (s). 19F NMR
(471 MHz, CDCl3): δ −152.49 (s), −152.54 (s). MS (ESI, positive
ions): m/z 554.1261 (calcd for [M − BF4]+: m/z 554.1264). Anal.
Calcd for C25H31N5ORuClBF4: C, 46.85; N, 10.93; H, 4.88. Found:
C, 46.91; N, 11.32; H, 4.19.
Synthesis of [Ru(2c)(p-cymene)Cl]BF4 (3c). Compound 3c was
synthesized following a procedure similar to that used for compound
3a using Cs2CO3 (0.108 g, 0.33 mmol), [2c-H2](BF4)2 (0.05 g, 0.11
mmol), and [Ru(p-cymene)Cl2]2 (0.034 g, 0.055 mmol). Yield: 0.055
g (0.088 mmol, 80%). 1H NMR (400 MHz, CDCl3): δ 7.95 (d, 3JH−H
Synthesis of [2e-H2](BF4)2. Compound [2e-H2](BF4)2 was
synthesized following the same procedure as that used for [2a-
H2](BF4)2 using [1e-H]Br (0.25 g, 0.685 mmol) and trimethyloxo-
nium tetrafluoroborate (0.253 g, 1.712 mmol) and obtained as a
brownish air-stable solid. Yield: 0.278 g (0.587 mmol, 86%). 1H NMR
(500 MHz, DMSO-d6): δ 9.71 (s, Im N−CH−N, 1H), 9.25 (s, Trz
C−CH−N, 1H), 8.62 (d, J = 9.1 Hz, 2H), 8.26 (d, J = 9.1 Hz, 2H),
7.85−7.81 (m, 2H), 5.98 (s, CH2, 2H), 4.50 (s, Im N−CH3, 3H),
3.91 (s, Trz N−CH3, 3H). 13C{1H} NMR (126 MHz, DMSO-d6): δ
148.9 (Im N−CH−N), 138.6, 138.3, 137.6, 129.8, 125.8, 124.1,
3
= 8.1 Hz, Ar−H, 2H), 7.39 (d, JH−H = 8.1 Hz, Ar−H, 2H), 7.32 (s,
Im N−CH−C, 1H), 7.14 (s, Im N−CH−C, 1H), 5.44 (d, J = 16.7
3
Hz, CH2, 1H), 5.35 (m, J = 17.7, 7.7 Hz, 3H), 5.20 (d, JH−H = 5.7
Hz, p-cymene−Ph, 1H), 4.78 (d, 3JH−H = 5.7 Hz, p-cymene−Ph, 1H),
4.25 (s, Trz N−CH3, 3H), 4.10 (s, Im N−CH3, 3H), 2.50 (s, Ar−
CH3, 3H), 2.28−2.01 (sept, 3JH−H = 7.0 Hz, p-cymene−iPr, 1H), 1.76
(s, p-cymene−Me, 3H), 1.02 (d, 3JH−H = 6.9 Hz, 3H), 0.69 (d, 3JH−H
= 6.9 Hz, 3H). 13C{1H} NMR (126 MHz, CDCl3): δ 173.3 (Im
Ccarbene), 159.9 (Trz Ccarbene), 140.9, 137.5, 129.7, 127.5, 123.9, 123.2,
105.0 (Car−CH3(cym), 103.9 (Car−iPr(cym)), 91.0 (Car−H(cym)),
90.9 (Car−H(cym)), 88.5 (Car−H(cym)), 85.7 (Car−H(cym)), 44.5
(CH2), 39.1 (Trz−NCH3), 37.1 (Im N−CH3), 31.1 (CH(CH3)2),
24.7 (CH(CH3)2), 21.5(Ar−CH3), 20.6 (Ar−CH3), 18.5 (CH3−
Car(cym)). 11B NMR (160 MHz, CDCl3): δ −1.08 (s). 19F NMR
(471 MHz, CDCl3): δ −152.1 (s), −152.2 (s). MS (ESI, positive
ions): m/z 538.1311 (calcd for [M − BF4]+: m/z 538.1315). Anal.
Calcd for C25H31N5RuClBF4: C, 48.05; N, 11.21; H, 5.00. Found: C,
48.67; N, 11.52; H, 4.89.
122.7, 122.6, 40.5 (CH2), 38.9 (Trz N−CH3), 36.0 (Im N−CH3). 11
B
NMR (160 MHz, DMSO-d6): δ −1.31 (s). 19F NMR (471 MHz,
DMSO-d6): δ −148.36 (s), −148.42 (s). MS (ESI, positive ions): m/z
387.1356 (calcd for [M − BF4]+: m/z 387.1367).
Synthesis of [Ru(2a)(p-cymene)Cl]BF4 (3a). In an oven-dried
pressure tube, Cs2CO3 (0.104 g, 0.318 mmol), compound [2a-
H2](BF4)2 (0.05 g, 0.106 mmol), and [Ru(p-cymene)Cl2]2 (0.032 g,
0.053 mmol) were added under an argon atmosphere. Then
dichloromethane was added to the tube, and the reaction mixture
was stirred for 36 h at 65 °C. The solution was filtered off using
Celite, and the filtrate was concentrated. The compound was
precipitated using hexane and the obtained solid was dried in vacuo
to isolate the compound as a dark-yellow solid. Yield: 0.064 g (0.098
Synthesis of [Ru(2d)(p-cymene)Cl]BF4 (3d). Compound 3d was
synthesized following a procedure similar to that used for compound
3a using Cs2CO3 (0.099 g, 0.303 mmol), [2d-H2](BF4)2(0.05 g,
0.101 mmol), and [Ru(p-cymene)Cl2]2 (0.031 g, 0.051 mmol). Yield:
0.054 g (0.079 mmol, 79%). 1H NMR (500 MHz, CDCl3): δ 8.34 (d,
1
mmol, 92%). H NMR (500 MHz, CDCl3): δ 7.48 (s, Ar−H, 1H),
7.09 (s, Ar−H, 2H), 6.99 (s, Ar−H, 1H), 5.73 (d, J = 16.5 Hz, CH2,
3
2
3JH−H = 7.2 Hz, Ar−H, 2H), 7.87 (d, JH−H = 6.8 Hz, Ar−H, 2H),
1H), 5.46 (m, p-cymene−Ph, 2H), 5.39 (d, JH−H = 16.6 Hz, CH2,
3
3
7.43 (s, Im N−CH−C, 1H), 7.16 (s, Im N−CH−C, 1H), 5.65 (d, J =
1H), 5.25 (d, JH−H = 5.8 Hz, p-cymene−Ph, 1H), 5.20 (d, JH−H
=
15.7 Hz, CH2, 1H), 5.47 (d, J = 16.3 Hz, CH2, 1H), 5.37 (s, 2H), 5.32
5.6 Hz, p-cymene−Ph, 1H), 4.34 (s, Trz N−CH3, 3H), 4.04 (s, Im
N−CH3, 3H), 2.36 (s, Ar−CH3, 3H), 2.35−2.24 (sept, JH−H = 7.0
3
3
3
(d, JH−H = 5.7 Hz, p-cymene−Ph, 1H), 4.85 (d, JH−H = 5.7 Hz, p-
cymene−Ph, 1H), 4.34 (s, Trz N−CH3, 3H), 4.10 (s, Im N−CH3,
3H), 2.17 (m, p-cymene−iPr, 1H), 1.74 (s, p-cymene-Me, 3H), 1.03
(d, 3JH−H = 6.7 Hz, 3H), 0.67 (d, 3JH−H = 6.7 Hz, 3H). 13C{1H} NMR
(126 MHz, CDCl3): δ 173.1 (Im Ccarbene), 160.7 (Trz Ccarbene), 141.9,
138.2, 128.5, 126.3, 124.0, 123.3, 106.5 (Car−CH3(cym), 103.0 (Car−
iPr(cym)), 91.3 (Car−H(cym)), 90.6 (Car−H(cym)), 88.6 (Car−
H(cym)), 85.8 (Car−H(cym)), 44.7 (CH2), 39.1 (Trz−NCH3), 37.5
(Im N−CH3), 31.2 (CH(CH3)2), 24.7 (CH(CH3)2), 20.5 (Ar−CH3),
18.4 (CH3−Car(cym)). 11B NMR (160 MHz, CDCl3): δ −1.15 (s).
19F NMR (471 MHz, CDCl3): δ −62.75 (s), −152.12 (s), −152.15
(s). MS (ESI, positive ions): m/z 592.1038 (calcd for [M − BF4]+:
m/z 592.1032). Anal. Calcd for C25H28N5RuClBF7: C, 44.23; N,
10.32; H, 4.16. Found: C, 44.39; N, 11.13; H, 3.18.
Hz, p-cymene−iPr, 1H), 2.21 (s, Ar−CH3, 3H), 2.01 (s, Ar−CH3,
3H), 1.67 (s, p-cymene−Me, 3H), 1.07 (d, 3JH−H = 6.8 Hz, 3H), 0.46
(d, 3JH−H = 6.6 Hz, 3H). 13C{1H} NMR (126 MHz, CDCl3): δ 173.4
(Im Ccarbene), 161.0 (Trz Ccarbene), 140.6, 139.3, 138.2, 135.9, 135.2,
129.9, 128.3, 123.9, 123.2, 44.3 (CH2), 38.7 (Trz−NCH3), 37.4 (Im
N−CH3), 31.0 (CH(CH3)2), 25.2 (CH(CH3)2), 21.2 (Ar−CH3),
19.4 (Ar−CH3), 18.4 (Ar−CH3), 18.1 (CH3−Car(cym)). 11B NMR
(160 MHz, CDCl3): δ −1.01 (s). 19F NMR (471 MHz, CDCl3): δ
−152.04 (s), −152.09 (s). MS (ESI, positive ions): m/z 566.1406
(calcd for [M − BF4]+: m/z 566.1629). Anal. Calcd for
C27H35N5RuClBF4·H2O: C, 45.58; N, 9.49; H, 5.05. Found: C,
45.81; N, 9.19; H, 4.58.
Synthesis of [Ru(2b)(p-cymene)Cl]BF4 (3b). Compound 3b was
synthesized following a procedure similar to that used for compound
3a using Cs2CO3 (0.107 g, 0.327 mmol), [2b-H2](BF4)2 (0.05 g,
0.109 mmol), and [Ru(p-cymene)Cl2]2 (0.034 g, 0.055 mmol). Yield:
Synthesis of [Ru(2e)(p-cymene)Cl]BF4 (3e). Compound 3e was
synthesized following a procedure similar to that used for compound
3a using Cs2CO3 (0.103 g, 0.315 mmol), [2e-H2](BF4)2 (0.05 g,
I
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Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
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Article
0.105 mmol), and [Ru(p-cymene)Cl2]2 (0.033 g, 0.053 mmol). Yield:
0.052 g (0.079 mmol, 75%). 1H NMR (500 MHz, CDCl3): δ 8.48 (d,
Full characterization data for compounds 1−3 and NMR
data of isolated compounds from the catalytic run
(PDF)
3
3JH−H = 9.1 Hz, Ar−H, 1H), 8.45 (d, JH−H = 9.1 Hz, Ar−H, 1H),
7.37 (d, J = 1.9 Hz, Im N−CH−C, 1H), 7.16 (d, J = 1.9 Hz, Im N−
CH−C, 1H), 5.47 (d, J = 16.6 Hz, CH2, 1H), 5.43 (d, 3JH−H = 6.3 Hz,
Accession Codes
3
CCDC 1957541 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
via www.ccdc.cam.ac.uk/data_request/cif, or by emailing
data_request@ccdc.cam.ac.uk, or by contacting The Cam-
bridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
p-cymene−Ph, 1H), 5.40 (d, JH−H = 5.7 Hz, p-cymene−Ph, 1H),
3
5.37−5.32 (m, 1H), 4.84 (d, JH−H = 5.8 Hz, p-cymene−Ph, 1H),
4.28 (s, 1H), 4.12 (s, 1H), 2.24−2.14 (m, 1H), 1.77 (s, 3H), 1.04 (d,
3
3JH−H = 6.9 Hz, 1H), 0.68 (d, JH−H = 6.9 Hz, 1H). 13C{1H} NMR
(126 MHz, CDCl3): δ 173.2 (Im Ccarbene), 161.0 (Trz Ccarbene), 149.0,
143.9, 138.2, 129.2, 124.4, 124.1, 123.2, 105.8 (Car−CH3(cym), 103.9
(Car−iPr(cym)), 91.3 (Car−H(cym)), 91.2 (Car−H(cym)), 88.9
(Car−H(cym)), 85.3 (Car−H(cym)), 44.4 (CH2), 39.1 (Trz−
NCH3), 37.2 (Im N−CH3), 31.2 (CH(CH3)2), 25.0 (CH(CH3)2),
20.3 (Ar−CH3), 18.5 (CH3−Car(cym)). 11B NMR (160 MHz,
CDCl3): δ −1.10. 19F NMR (471 MHz, CDCl3): δ −152.23 (s),
−152.28 (s). MS (ESI, positive ions): m/z 569.0809 (calcd for [M −
BF4]+: m/z 569.1009). Anal. Calcd for C24H28N6RuClBF4O2: C,
43.95; N, 12.82; H, 4.30. Found: C, 43.90; N, 12.06; H, 3.70.
General Procedure for the N-Alkylation of Amines. To an oven-
dried Schlenk tube (5 mL) inside an argon-filled glovebox was added
KOtBu (0.2 mmol). To this were added catalyst (0.5 mol %), amine
(1 mmol), and alcohol (1.2 mmol) using standard Schlenk
techniques. Then the reaction mixture was kept in a preheated oil
bath at 120 °C. After a specific reaction time, the Schlenk tube was
taken out and cooled to room temperature. The reaction mixture was
diluted with methanol, small portions of aliquot were taken for GC−
MS analysis, and the pure products were obtained after column
chromatography using ethyl acetate and hexane as eluents.
General Procedure for the N-Methylation of Amines. To an oven-
dried pressure tube (25 mL) were added KOH (0.5 mmol), catalyst
(1 mol %), amine (0.5 mmol), and methanol (1 mL). Then the
reaction mixture was kept in a preheated oil bath at 130 °C. After a
specific reaction time, the pressure tube was cooled to room
temperature. The reaction mixture was then diluted with methanol,
and an aliquot was taken for GC−MS analysis. For isolation of the
products, the residue obtained after removal of all of the volatiles was
purified via column chromatography using ethyl acetate and hexane as
eluents.
General Procedure for the Synthesis of Quinoline Derivatives.
To an oven-dried Schlenk tube (5 mL) inside an argon-filled glovebox
was added KOtBu (0.5 mmol). To this catalyst (0.5 mol %) were
added 2-amino alcohol (1 mmol) and a secondary alcohol (1.2 mmol)
using standard Schlenk techniques. Then the reaction mixture was
kept in a preheated oil bath at 120 °C. After a specific reaction time,
the Schlenk tube was cooled to room temperature. The pure product
was obtained after column chromatography using ethyl acetate and
hexane as eluents.
Single-Crystal X-ray Crystallography. X-ray data were collected
on a Bruker AXS Kappa APEX-III CMOS diffractometer equipped
with graphite-monochromated Mo Kα radiation (λ = 0.71073 Å).28a
The crystal was fixed at the tip of a glass fiber loop, and after being
mounted on the goniometer head, it was optically centered. The
APEX3 and APEX3-SAINT programs were used for the data
collection and unit cell determination, respectively. Processing of
the raw frame data was performed using SAINT/XPREP.28b,c The
structures were solved by SHELXT-2014/528d and refined against F2
using all reflections with the SHELXL-2018/3 (WinGX) program.28e,f
Non-hydrogen atoms were refined anisotropically. All hydrogen
atoms were placed in calculated positions. The crystal data (CCDC
1957541) and refinement details are summarized in Tables S3. The
graphical representations were performed using the program
Mercury.28g
AUTHOR INFORMATION
Corresponding Author
■
Arnab Rit − Indian Institute of Technology (IIT) Madras,
Chennai, India; orcid.org/0000-0003-0224-8387;
Email: arnab.rit@iitm.ac.in
Other Authors
S. N. R. Donthireddy − Indian Institute of Technology
(IIT) Madras, Chennai, India
Praseetha Mathoor Illam − Indian Institute of
Technology (IIT) Madras, Chennai, India
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.inorgchem.9b03049
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We gratefully acknowledge SERB, India (Grant ECR/2016/
001272), and IIT Madras (seed grant) for financial support.
S.N.R.D. and P.M.I. acknowledge UGC and IIT Madras,
respectively, for fellowships. We gratefully acknowledge the
NMR and ESI-MS (DST-FIST funded) facility at the
Department of Chemistry, single-crystal X-ray diffractometer
facility at SAIF, IIT Madras, and Dr. K.R.R.’s laboratory for CV
and DPV measurements.
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ASSOCIATED CONTENT
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sı
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.inorgchem.9b03049.
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