Gold complexes of bis-indazole-derived N-Heterocyclic carbene: Synthesis, structural characterizations, and catalysis

Article abstract of DOI:10.1016/j.molstruc.2021.130043

A novel series of bis Indy-NHC gold complexes have been developed and investigated via a mild Ag-carbene transfer route. The obtained complexes were characterized by NMR spectroscopy and X-ray diffraction analysis. The catalytic property of these gold complexes was further evaluated in the oxidation of benzylic. The gold complex E1 showed a high catalytic activity in the oxidation of various benzylic substrates, resulting in the corresponding carbonyl compounds with excellent yields using TBHP as oxidant.

Full text of DOI:10.1016/j.molstruc.2021.130043

Journal of Molecular Structure 1233 (2021) 130043
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstr
Gold complexes of bis-indazole-derived N-Heterocyclic carbene:
Synthesis, structural characterizations, and catalysis
Hua Zhanga,b,1, Ting Xub,1, Dongdong Lic, Tao Chengd, Jing Chenb,∗, Yang Zhoub,∗
a School of Materials Science and Engineering, Xi’an University of Technology, Xi’an, 710048, China
b Cixi Institute of Biomedical Engineering, Ningbo Institute of Materials Technology & Engineering, Chinese Academy of Sciences, Ningbo, 315201, China
c College of Chemical Engineering, Nanjing Forestry University, 159 Long Pan Road, Nanjing, 210037, China
d Pharmaron (Ningbo) Technology Development Co., Ltd., Hangzhou Bay New Zone, Ningbo 315366, China
a r t i c l e i n f o
a b s t r a c t
Article history:
A novel series of bis Indy-NHC gold complexes have been developed and investigated via a mild Ag-
carbene transfer route. The obtained complexes were characterized by NMR spectroscopy and X-ray
diffraction analysis. The catalytic property of these gold complexes was further evaluated in the oxida-
tion of benzylic. The gold complex E1 showed a high catalytic activity in the oxidation of various benzylic
substrates, resulting in the corresponding carbonyl compounds with excellent yields using TBHP as oxi-
dant.
Received 13 October 2020
Revised 26 January 2021
Accepted 29 January 2021
Available online 3 February 2021
Keywords:
N-Heterocyclic carbenes
bis Indy-NHC gold (I) complexes
benzylic oxidation
© 2021 Elsevier B.V. All rights reserved.
1. Introduction
NHCs with reduced heteroatom stabilization based on the indazole
backbone, shows even stronger donating capacities than the clas-
N-Heterocyclic carbenes (NHCs) have been used as ligands in
organometallic chemistry and in catalysis ever since their isola-
tion in the free state by Arduengo and coworkers in 1991 [1,2].
Comparing with most of phosphine ligands, NHC complexes have
higher catalytic activities and thermal stability, partially owing to
their strong NHC-metal bonds and high σ-donating ability of NHC
ligands [3–5].
sical NHC ligands [16]. The organic chemistry of these ligands and
a few of transition metals bearing these ligands have been studied
[17,18]. Previously, we expanded these kinds of NHCs with intro-
ducing an aryl group with different substituents on the central ni-
trogen atom of the Indy-NHCs, The electronic and steric properties
around the Indy-N-heterocyclic carbene skeleton are thus changed
[19]. The iPr Indy-NHC ligands could react with [AuCl(SMe2)] by
a silver carbene transfer method to give AuI Indy-NHC complex,
leading to high catalytic activities in the hydration of alkynes at
room temperature. As a continuation of our previous work, we
herein report on the synthesis of bis Indy-NHC gold (I) complexes
and their catalytic activity in benzylic oxidation.
Most research in the field has focused on the development of
popular diamino N-heterocyclic carbenes variants such as imida-
zole, benzimidazole, imidazoline, 1,2,4-triazole and diamido car-
benes [6-9]. However, other families of stable carbenes with re-
duced heteroatom stabilization, such as the cyclic-amino-carbenes
(CAACs) or the 1,2,3-triazole mesoionic carbenes (MICs) have also
emerged as interesting fields of study [10,11]. Notably, this is due
to removing of one or both heteroatoms from the positions next to
the ylidene carbon increasing the energy of the σ-HOMO orbital
and leading to a more strongly donating carbene center [12–14].
Fig. 1 shows representatives subclasses of stable carbenes includ-
ing those with reduced heteroatom stabilization [15].
2. Results and discussion
2.1. Synthesis of the Indy-NHC ligands
In our previous work, excess triethyl phosphate as the reduc-
tant was added for the synthesis of indazoles. In the mean time,
the reaction systems needed to be stirred at high temperature for
a long time with a favorable yield and the triethyl phosphate was
difficult to be removed in the post processing. To improve the syn-
thetic program, low-valent Ti reagents (TiCl4/Sm/Et3N) with high
reducing abilities are introduced in this work following a previous
report [20]. The synthetic routes of these novel Indy-NHC ligands
is outlined in Scheme 1.
Huynh and coworkers pioneered the design and synthesis of
indazolin-s-ylidene (Indy) carbenes in 2009. This new class of
∗
Corresponding authors.
E-mail addresses: jing.chen@nimte.ac.cn (J. Chen), zhouyang876@nimte.ac.cn (Y.
Zhou).
1
These authors contributed equally to this work
https://doi.org/10.1016/j.molstruc.2021.130043
0022-2860/© 2021 Elsevier B.V. All rights reserved.

H. Zhang, T. Xu, D. Li et al.
Journal of Molecular Structure 1233 (2021) 130043
2.2. Synthesis and structure of bis (Indy-NHC) Au complexes
In an initial attempt, the steric bulky bis iPr Indy-NHC ligands
(C1) with iodine or chloride as an anion are not able to pro-
duce their bis carbene Au complex by the Ag2O method [21]. It
is found that NHC ligands with non-coordinating anions, such as
BF4—/PF6—could obtain the bis(carbene) complexes in good yields
—
[22-24]. After replacing the anion with BF4 by reacting with
NaBF4 in acetone, the bis(Indy-NHC) Au complex E1 was suc-
cessfully obtained without the isolation of the presumed silver
(Scheme 2). Subsequently, complex E1 was isolated and character-
ized by NMR spectroscopy, and the signal of the ylidene carbon
atom was observed at 185.34 ppm in the 13C NMR.
Fig. 1. Representative classes of stable carbenes. . Adapted with permission from
[15]. Copyright (2009) American Chemical Society.
The effect of the different substitutes of the phenyl group on
the coordination process was further surveyed. The para-position
group of benzene ring with non-substituent (D2) or substituted by
electron-donating group methyl (D3) affected neither the rate nor
the yield of the chelation of Au and NHC. While the para-position
group was substituted with electron-withdrawing groups (D4, D5),
leading to unstable bis (carbene) Au complexes. The NHC precursor
D6 failed to give a stable bis Indy-NHC Au complex by using the
same route. The steric hindrance with two groups of R1/R2 on the
ortho-positions and the electronic effect of substituents on benzene
ring were both needed to promote the formation of stable bis car-
bene Au complexes.
1H NMR spectrums of bis(carbene) Au complexes and monocar-
bene complexes are very similar, pointing out the chemical enviro-
ments of the hydrogen atoms are not deeply affected by the coor-
dination of an additional NHC ligands to the gold(I) center. The car-
bene carbon chemical shift value belonging to compounds E were
observed around at δ 185 ppm.This is significantly more downfield
than the signals of any of the corresponding monocarbene com-
plexes around at δ 172 ppm. This indicates the Lewis acidity of the
metal cente are reduced by coordination of an additional strong σ-
donating carbene ligand nd cause the observed downfield shift of
the carbene carbon [25, 26].
Fig. 2. The molecular structure of Complex E1. Hydrogen atoms, hydrogen atoms,
−
BF4 anion have been omitted for clarity. Selected geometrical parameters of
complex were as follows:Au1-C24
=
2.031(7), Au1-C24b
=
2.031(7), C24-Au1-
C24b = 180.000(2).
The molecular structure of complex E1 was confirmed by sin-
gle crystal X-ray analysis (Fig. 2). The geometry is essentially lin-
ear about the gold(I) center, and the average Au−C bond length of
The Ar group bearing no substitution or just o-tolyl with low
steric bulkiness is not able to form stable silver complexes in the
previous work [19], neither two NHC ligands were not synthe-
sized in this work. Compounds A were prepared by a condensation
reaction of 2-nitrobenzaldehyde and aniline with excellent yield
(87–93%). Then, by Ti reagents, intramolecular cyclization was per-
formed after adding THF at the condition of pH 8, and refluxing for
4 h under an inert atmosphere to give the indazole compounds B
with 65–71% yield. Finally, the NHC ligands C were conveniently
synthesized by reacting indazoles with CH3I in CH3CN at 80 °C
(yield = 79–90%) (Scheme 1). The synthetic details and ligands’
characterization data are shown in the Supporting Information.
˚
2.031 A is within the expected range for gold(I) carbene complexes
[27].
2.3. The catalytic application of bis (Indy-NHC) Au complexes
It has been proven that Aryl ketone is a useful building block in
a plethora of significant molecules, including natural products, ac-
tive pharmaceutical ingredients, agrochemicals and advanced ma-
terials (Fig. 3) [28]. However, the classical methods to assemble
Scheme 1. Synthesis of indazole N-Heterocyclic carbene ligands.
2

H. Zhang, T. Xu, D. Li et al.
Journal of Molecular Structure 1233 (2021) 130043
Scheme 2. Synthesis of bis Indy-NHC Au complexes.
Table 1
Reaction condition optimizationa.
Entry
Cat.
Amt of cat. (mol%)
Solvent
T( °C)
Yield(%)b
1
E1
5
5
5
5
5
4
3
5
5
5
-
H2O
90
90
90
100
110
90
90
90
90
90
90
30
37
99
65
42
58
43
80
77
31
<5
2
E1
Toluene
Pyridine
Pyridine
Pyridine
Pyridine
Pyridine
Pyridine
Pyridine
Pyridine
Pyridine
3
E1
4
E1
5
E1
6
E1
7
E1
8
E2
9
10c
E3
iPr NHC-Au-Cl
11
-
a
All the reactions were carried out in the scale of 0.5 mmol of F1.
b
c
GC yield.
The synthesis of iPr NHC-Au Cl followed our previous work19
.
3

H. Zhang, T. Xu, D. Li et al.
Journal of Molecular Structure 1233 (2021) 130043
Table 2
Bis iPr NHC gold complex catalyzed benzylic oxidationa,b
.
To optimize the reaction conditions, solvents, catalyst loadings and
reaction temperature were all screened (Table 1). Five mol% of E1
was employed as the catalyst in our primary attempt, with TBHP
(2eq.) as the oxidant. Pyridine as the best solvent for this reac-
tion, offered the desired carbonyl compounds with highest yield
(99%, entry 1–3). Whereas, the yields were declined to 42% with
increasing the reaction temperature from 90 to 110 °C, indicating
that the gold catalyst was sensitive to the reaction temperature.
The higher temperature (> 90 °C) costed the catalyst E1 unstable,
and the catalytic efficiency was reduced (Entry 3–5). Further in-
vestigation revealed that the amount of the catalyst E1 is crucial
to the reaction outcome, the optimal amount was 5 mol% and the
lower catalyst loadings would lead to lower yield (Entry 3; 6, 7).
Comparing the catalytic activities of E1, E2 and E3 at the same re-
action condition, the gold complex E1 achieved the best yield. We
thought the iPr-Indy-NHC ligand was a stronger donor than other
ligands, which would provide a stronger donating ability, mean-
while the bulk group iPr might help to facilitate the generation of
the oxidative intermediate, and improve catalytic activity of gold
[19]. It is worth to mention the important role of bis iPr NHC lig-
ands in the gold-catalyzed benzylic oxidation, while the single iPr
NHC ligand gold complex showed extremely lower activity.
With these optimized reaction condition in hand, an explo-
ration of the substrate scope was further explored. The results
revealed in Table 2. The bis iPr-NHC gold complex E1 showed
highly effective for such oxidation. Interestingly, the electronic ef-
fect of the substituents on the aromatic ring of diarymethylene
was not evident. The substituents bearing electron donating-group
CH3(F3) or these different electron-withdrawing groups (F4-F7)
all produced products with 89–94% yields. Next, the less active
substrates cyclic alkylarenes (F8, F9) were employed to give tar-
get ketone products in slightly lower yields in 83% and 81% re-
spectively. Furthermore, E1 gold-catalyzed benzylic C–H oxidation
transformation could smoothly convert alkylarenes to the corre-
sponding aryl ketones with good yields ranging between 78 to
85%.
Fig. 3. Selected aryl ketones.
such motifs are one of the most difficult reactions to perform, be-
cause it requires harsh reaction conditions and corrosive chemi-
cal reagents such as potassium permanganate, potassium dichro-
mate or ammonium cerium nitrate [29, 30]. Transition metal cat-
alyzed oxidation is an environmentally friendly and cost-effective
synthetic method. Transition metal catalyzed oxidation is an en-
vironmentally friendly and cost-effective synthetic method, and
many impressive achievements have been accomplished in metal
complexes (Ni, Cu, Ru, Pd et al.) [31-34]. Among them, some re-
searches reported the Au NPs or Au (III) to promote such benzylic
oxidations [35–37]. Impovement of Au(I) as catalysts are have been
rarely reported, although Shi group showed the AuCl supported by
neocuproine could catalyze the benzylic oxidations with maximum
yield of 46%, which was much lower than Au(III) [38]. Herein, we
report the prepared air-stable bis Indy-NHC gold complex was used
to achieve an excellent catalytic benzylic oxidation with tert-butyl
hydroperoxide (TBHP) as oxidant.
We initiated this investigation on the reaction of hydration of
diphenylmethane (F1) with bis NHC complex E1 as the catalyst.
4

H. Zhang, T. Xu, D. Li et al.
Journal of Molecular Structure 1233 (2021) 130043
3. Conclusion
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alytic activities in the benzylic oxidation with TBHP as oxidant. Es-
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group catalyzed various benzylic substrates, resulting in the corre-
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Declaration of Competing Interest
The authors declare that they have no known competing finan-
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Ting Xu: Conceptualization, Methodology. Dongdong Li: Data cur-
tion, Validation. Tao Cheng: Investigation, Formal analysis. Jing
Chen: Supervision, Writing – original draft. Yang Zhou: Writing –
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This work was supported by the Zhejiang Provincial Natural Sci-
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