Single-Step Synthesis of Dinuclear Neutral Gold(I) Complexes with Bridging Di(N-heterocyclic carbene) Ligands and Their Catalytic Performance in Cross Coupling Reactions and Alkyne Hydroamination

Article abstract of DOI:10.1021/acs.organomet.8b00531

We report on a single-step procedure for the synthesis of dinuclear gold(I) complexes with bridging di(N-heterocyclic carbene) (diNHC) ligands of general formula Au₂Br₂L^1-9 (L = diNHC). The obtained complexes differ in the bridging group between the carbene donors and in the terminal wingtip substituents at the imidazol-2-ylidene rings. The complexes have been characterized by means of elemental analysis, NMR spectroscopy, ESI-MS spectrometry, and single-crystal X-ray structure analysis. The dinuclear gold(I) complexes have been tested as homogeneous catalysts in technologically relevant reactions such as the cross coupling between phenylboronic acid and aryl bromides and the intermolecular hydroamination of alkynes. The catalytic performance has been compared for complexes Au₂Br₂L^1-9 and the benchmark mononuclear complex IPrAuCl.

Full text of DOI:10.1021/acs.organomet.8b00531

Article
pubs.acs.org/Organometallics
Cite This: Organometallics XXXX, XXX, XXX−XXX
Single-Step Synthesis of Dinuclear Neutral Gold(I) Complexes with
Bridging Di(N-heterocyclic carbene) Ligands and Their Catalytic
Performance in Cross Coupling Reactions and Alkyne
Hydroamination
Marco Baron,*,† Edoardo Battistel,† Cristina Tubaro,† Andrea Biffis,*,† Lidia Armelao,†,‡
Marzio Rancan,†,‡ and Claudia Graiff§
†
̀
Dipartimento di Scienze Chimiche, Universita degli Studi di Padova, Via F. Marzolo 1, 35131 Padova, Italy
‡ICMATE-CNR, Via F. Marzolo 1, 35131 Padova, Italy
§
̀
̀
Dipartimento di Scienze Chimiche, della Vita e della Sostenibilita Ambientale, Universita degli Studi di Parma, Parco Area delle
Scienze 17/A, 43124 Parma, Italy
S
* Supporting Information
ABSTRACT: We report on a single-step procedure for the
synthesis of dinuclear gold(I) complexes with bridging di(N-
heterocyclic carbene) (diNHC) ligands of general formula
Au2Br2L1−9 (L = diNHC). The obtained complexes differ in
the bridging group between the carbene donors and in the
terminal wingtip substituents at the imidazol-2-ylidene rings. The
complexes have been characterized by means of elemental
analysis, NMR spectroscopy, ESI-MS spectrometry, and single-
crystal X-ray structure analysis. The dinuclear gold(I) complexes
have been tested as homogeneous catalysts in technologically
relevant reactions such as the cross coupling between phenyl-
boronic acid and aryl bromides and the intermolecular hydro-
amination of alkynes. The catalytic performance has been
compared for complexes Au2Br2L1−9 and the benchmark mononuclear complex IPrAuCl.
reactions in which the gold catalyst changes its oxidation state
and consequently does not simply act as a Lewis acid.13,18,23
We and other researchers have been working for many years
on the synthesis of dinuclear gold(I) complexes with bridging
bidentate NHC ligands.24−26 The majority of the complexes of
this kind reported up to now are dinuclear dicationic gold(I)
complexes, of general formula [Au2(μ-L2)]2+ (L = diNHC), in
which the gold centers are linearly dicoordinated by two NHC
donors. This type of complexes is not suitable for efficient
catalysis, the two NHC ligands being strongly coordinated to
the metal center, leaving no free sites for substrate
coordination and activation. Only a few examples of dinuclear
gold(I) complexes with one bridging diNHC ligand and the
coordination sphere completed by easily removable ligands,
such as halides, have been reported.27,28 Furthermore, the
described syntheses usually involve several steps, inevitably
affecting the overall yield of the process and making the
accessibility to these compounds very limited. For this reason,
the majority of studies on dinuclear gold(I) catalysts focus on
P-donor ligands or dinuclear monocarbene complexes with μ-
INTRODUCTION
■
Gold(I) complexes with N-heterocyclic carbene ligands
(NHC) have been extensively studied in the past 15 years
for applications in homogeneous catalysis,1−4 luminescent
materials,5−7 and medicinal chemistry.8,9 In the field of organic
transformations, gold(I) NHC complexes are efficient
activators of multiple carbon−carbon bonds, promoting
cycloisomerization of enynes and ynones, activation of
propargylic esters, hydrofunctionalization of alkynes, allenes
and alkenes, and carbene transfer reactions.1,3 One aspect of
the catalytic properties of gold compounds that has emerged
only recently is dual gold catalysis. Dual gold catalysis is
defined as the ability of two gold complexes to be involved in
one catalytic cycle.10−13 Since dinuclear organogold species,
such as gem-diaurated phenyl or σ,π-diaurated acetylide
complexes, were first proposed and later identified as key
intermediates or catalyst reservoirs in gold-catalyzed reac-
tions,14−17 dinuclear gold(I) complexes have started to be
intensively investigated, with the aim of identifying dinuclear
catalysts in which cooperative effects lead to enhanced
performances.18−22 Furthermore, dinuclear gold complexes
can stabilize unusual oxidation states for gold, such as
gold(II)−gold(II) complexes, facilitating the access to catalytic
Received: July 27, 2018
© XXXX American Chemical Society
A
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Article
OH or σ,π-acetylide bridging groups (Chart 1).18−22 In this
paper, we report on a novel single-step procedure for the
groups of Nolan and Gimeno for mononuclear gold(I)
complexes.29,30 The procedure was modified, because of the
lower solubility in organic solvents that characterizes the
dinuclear complexes compared to their mononuclear ana-
logues, in particular when the ligand has methyl wingtip
substituents. The products are white-yellowish solids, isolated
in good yields (>60%). The compounds with methyl wingtip
groups (Au2Br2L1−Au2Br2L3) are soluble in DMSO and
sparingly soluble in CHCl3 and CH3CN, while the compounds
with bulkier mesityl (Au2Br2L4−Au2Br2L6) or 2,6-diisopro-
pylphenyl (Au2Br2L7−Au2Br2L9) groups have a good
solubility in all three of the above-mentioned solvents. All
the products were characterized by means of elemental
Chart 1. Recently Reported Dinuclear Gold(I) Precatalysts
with Bidentate P-Donor Ligands (Left) and Monocarbene
Ligands with μ-OH or σ,π-Acetylide Bridging Groups
(Right)
1
analysis, H and 13C NMR, and ESI-MS. In the NMR spectra,
the signals expected for the functional groups present in the
molecules were found. Moreover, NMR spectra suggest a
symmetric coordination motif where the two gold centers have
the same coordination environment. The formation of the
1
NHC donor is confirmed in the H NMR spectra by the
absence of the proton in position 2 of the imidazole rings, due
to the formation of the gold-carbene bonds. In the 13C NMR
spectra, the signals relative to the carbene carbons are found in
the range 173−178 ppm, diagnostic position for NHC
coordinated to a gold(I) center with a bromide in the trans
position.29,30 ESI-MS analysis of the products present the
signal relative to the species [Au2BrL1−9]+, indicative of the
formation of the desired dinuclear complexes. The chloro-
analogues of complexes Au2Br2L3 and Au2Br2L4 (Au2Cl2L3,
and Au2Cl2L4) were already reported in the literature.13,32
However, the reported syntheses are based on multistep
procedures: transmetalation of the diNHC ligand from the
corresponding silver(I) complex in the case of Au2Cl2L3
(overall yield 55%),32 and treatment with HCl of the methyl
derivative Au2Me2L4 in the case of Au2Cl2L4 (overall yield
39%).13
X-ray Crystallography. Single crystals suitable for X-ray
diffraction analysis have been obtained by slow diffusion of n-
hexane into a chloroform solution of Au2Br2L4 and a
dichloromethane solution of Au2Br2L5 or by slow diffusion
of diethyl ether into an acetonitrile solution of Au2Br2L6.
ORTEP views of the molecular structures of Au2Br2L4−
Au2Br2L6 are reported in Figure 1; selected bond distances and
angles are listed in Table 1.
In all three cases, the expected molecular structures have
been obtained. The two gold(I) centers of the dinuclear
complexes are linearly dicoordinated by a bridging dicarbene
ligand and a bromide, the Ccarbene−Au−Br angles being close to
180°. The Ccarbene−Au and Au−Br bond distances are in
accordance with those reported for mononuclear NHC−Au−
Br complexes.33 In the crystal of Au2Br2L4, two crystallo-
graphically independent molecules of the complex are present
together with a disordered chloroform solvent molecule. One
of the molecules of the complex has a symmetric structure,
with a two-fold rotation axis passing through the bridging
methylene carbon atom. The structural parameters of the two
molecules are slightly different (Table 1), in particular, the
Ccarbene−Au−Br angle of the symmetric form deviate more
from linearity (174.2(5)°) compared to the non-symmetric
form (177.4(5) and 178.3(4)°). It is interesting to note that
the packing of the two crystallographically independent
molecules of compound Au2Br2L4 is very different. In fact,
the disposition of the symmetric form in the crystal packing
shows the molecules in an alternating arrangement without
synthesis of dinuclear neutral gold(I) complexes with diNHC
ligands of general formula Au2Br2L (L = diNHC). The
protocol is based on the one reported by Nolan and Gimeno
for mononuclear coinage metals NHC complexes,29,30 tailored
for the dinuclear case. Complexes bearing bidentate ligands
with aliphatic bridging group of different lengths, and with
different wingtip substituents, have been successfully obtained
and characterized. The catalytic performance of the dinuclear
gold(I) complexes has been evaluated in the Suzuki-type
coupling between phenylboronic acid and cinnamyl bromide,18
and in the intermolecular hydroamination of alkynes.31 The
catalytic activity of the novel dinuclear catalyst has been
compared with one another and with the benchmark
mononuclear catalyst IPrAuCl.
RESULTS AND DISCUSSION
■
Synthesis and Characterization of the Dinuclear
Gold(I) Complexes. The gold(I) diNHC complexes
Au2Br2L1−Au2Br2L9 were synthesized by reacting the ligand
precursors H2Br2L1−H2Br2L9 with AuCl(SMe2) in the
presence of K2CO3 as base and LiBr (Scheme 1).
The addition of a bromide source such as LiBr to the
reaction mixture minimizes the formation of side products due
either to halogen scrambling or to the formation of bis-cationic
complexes [Au2L2]2+. A similar procedure was reported by the
Scheme 1. Synthesis of the Gold(I) diNHC Complexes
Au2Br2L1−Au2Br2L9
B
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Figure 1. ORTEP drawing of complexes Au2Br2L4 (non-symmetric form), Au2Br2L5, and Au2Br2L6 (from left to right). Ellipsoids are drawn at the
50% probability level. Hydrogen atoms and solvent molecules have been omitted for clarity.
Table 1. Selected Bond Distances (Å) and Angles (deg) for the X-ray Structures of Au2Br2L4−Au2Br2L6
Au2Br2L4
Au2Br2L5
Au2Br2L6
Au−Br
2.376(2) (Au1−Br1)
2.382(2) (Au2−Br2)
2.379(3) (Au3−Br3)
2.4010(7) (Au1−Br1)
2.3966(9) (Au2−Br2)
2.3787(6) (Au1−Br1)
Au−Ccarbene
1.999(17) (Au1−C1)
1.972(18) (Au2−C7)
1.963(19) (Au3−C26)
1.974(6) (Au1−C1)
1.983(7) (Au2−C8)
1.977(4) (Au1−C1)
Ccarbene−N
1.337(19) (C1−N1)
1.370(19) (C1−N2)
1.35(2) (C7−N3)
1.36(2) (C7−N4)
1.37(2) (C26−N5)
1.35(2) (C26−N6)
1.358(8) (C1−N1)
1.350(8) (C1−N2)
1.349(9) (C8−N3)
1.350(9) (C8−N4)
1.346(6) (C1−N1)
1.349(5) (C1−N2)
Au···Au
5.9848(13) (Au1···Au2)
6.0746(16) (Au3···Au3′)
5.1449(4) (Au1···Au2)
4.0861(9) (Au1···Au1′)
Ccarbene−Au−Br
177.4(5) (C1−Au1−Br1)
178.3(4) (C7−Au2−Br2)
174.2(5) (C26−Au3−Br3)
175.56(19) (C1−Au1−Br1)
178.50(20) (C8−Au2−Br2)
177.12(13) (C1−Au1−Br1)
a
BrAuAuBr
173.27(11) (Br1Au1Au2Br2)
141.53(4) (Br1Au1Au2Br2)
93.80(4) (Br1Au1Au1′Br1′)
178.60(30) (Br3Au3Au3′Br3′)
a
Torsional angle.
appreciable interactions between them as evidenced in Figure
2 (orange), while the non-symmetric form, whose packing is
reported in Figure 2 (green) tends to pack in such a manner
that the Au atoms of two adjacent molecules are at a distance
of 3.703(1) Å and 3.804(1) Å, which is shorter than the Au···
Au intramolecular separation. Further details on the crystal
packing of Au2Br2L4 are given in Figure S24. The asymmetric
unit of Au2Br2L5 is composed of a complex and a disordered
dichloromethane solvent molecule. Finally, the asymmetric
unit of Au2Br2L6 contains half molecule. The other half is
generated by symmetry through a two-fold rotation axis
passing through the central carbon atom of the bridging group
(C5). In the crystal packing of Au2Br2L6, π−π stacking
interactions involving the mesityl groups of different dinuclear
complexes leads to the formation of a 1D supramolecular chain
(Figure 3). On the contrary, no π−π stacking interactions have
been observed for Au2Br2L4 and Au2Br2L5. The three
complexes Au2Br2L4−Au2Br2L6 differ for the length of the
aliphatic bridging linker of the bidentate diNHC ligand. From
a structural point of view this mainly influences the relative
orientation of the two linear Ccarbene−Au−Br fragments. This
can be easily evaluated considering the torsional angle between
the two Au−Br fragments. Increasing the length of the
aliphatic spacer the molecule folds reducing the BrAuAuBr
torsional angle and the Au···Au distance (Table 1). With the
shortest methylene bridging group, the two gold(I) are pretty
far away from each other; the Au···Au distance in Au2Br2L4 is
around 6 Å (5.9848(13) and 6.0746(16) Å for Au1···Au2 and
Au3···Au3′), and the BrAuAuBr torsional angle is close to 180°
(173.27(11) and 178.60(30)° for Br1Au1Au2Br2 and
Br3Au3Au3′Br3′, respectively). The same spatial arrangement
has been observed for the corresponding dichloro analogue, as
reported by Toste et al.18 By increasing the number of carbon
atoms in the alkyl bridging group this tendency is reduced,
probably because this enhances the structural degree of
freedom of the systems for which a higher number of possible
conformations are accessible. According to that, BrAuAuBr
torsional angles and the Au···Au distances values decrease as
more carbon atoms are added to the aliphatic spacer, as
confirmed by the data of Au2Br2L5 and Au2Br2L6 (141.53(4)°
C
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Table 2. Catalytic Performance of the Complexes
Au2Br2L1−Au2Br2L9 in the Cross Coupling of Cinnamyl
a
Bromide with Phenylboronic Acid
entry
cat.
yield 1 (%)
1
2
3
4
5
6
7
8
−
<1
15
23
20
19
7
11
17
23
26
30
b
IPrAuCl
Au2Br2L1
Au2Br2L2
Au2Br2L3
Au2Br2L4
Au2Br2L5
Au2Br2L6
Au2Br2L7
Au2Br2L8
Au2Br2L9
9
10
11
a
Reaction conditions: 0.123 mmol phenylboronic acid, 0.492 mmol
cinnamyl bromide, 5 mol% catalyst, 0.379 mmol Cs2CO3, 65 °C, 18 h.
b
10 mol% catalyst.
between the two carbene donors and a diisopropylphenyl
wingtip substituent. Furthermore, all dinuclear catalysts, with
the exception of Au2Br2L4 and Au2Br2L5 (Table 2, entries 6
and 7), show a better performance compared to mononuclear
IPrAuCl (Table 2, entry 2).
Figure 2. View along the a axis of the crystal packing of Au2Br2L4.
The symmetric and asymmetric forms of the complex are highlighted
in orange and green, respectively.
The catalytic performance of the dinuclear gold(I)
complexes has been screened also in another reaction, namely
the intermolecular catalytic hydroamination of alkynes.35,36
Gold(I) species are already known to be active catalysts in this
versatile organic transformation,37 and gold(I) NHC com-
plexes clearly stand out among the most efficient catalysts for
this purpose.38−45 In this study, hydroamination of phenyl-
acetylene with mesitylamine (Scheme 3) has been used as
Figure 3. π−π stacking interactions in the crystal packing of Au2Br2L6
(reported distance in Å).
Scheme 3. Employed Standard Hydroamination Reaction
and 5.1449(4) Å for Au2Br2L5 and 93.80(4)° and 4.0861(9) Å
for Au2Br2L6).
Catalytic Activity. Recently Toste et al. have reported on
the use of a dinuclear gold(I) catalyst with a bidentate
aminophosphine ligand in the Suzuki cross coupling between
allyl bromides and boronic acids.18 It was in fact demonstrated
that bimetallic gold complexes undergo accelerated oxidative
addition, due to the formation of AuII−AuII species (rather
than discrete AuIII) upon oxidation, resulting in improved
catalytic performances.34 We have thus tested our catalysts by
using the literature reported optimized conditions,18 with
phenylboronic acid and cinnamyl bromide as substrates
(Scheme 2).
model reaction. Two equivalents with respect to the complexes
of a silver salt were added as cocatalyst, in order to remove the
bromides coordinated to the gold(I) centers and generate the
catalytically competent species for substrate activation.
The initially employed reaction conditions were taken from
our recent work on the catalysis of the same reaction by Pd(II)
complexes.31 We first performed a screening of the reaction
conditions, optimizing the solvent, the temperature, and the
catalyst counteranion introduced with the silver salt using as
catalyst complex Au2Br2L9. Screening of the solvent (Table 3)
yielded results similar to those previously recorded with Pd
complexes.31 In particular, neat conditions provided the
highest yields in hydroamination product, followed by use of
an ionic liquid with a non-coordinating anion. A small amount
of acetophenone, the formal product of hydration of the
phenylacetylene substrate, was invariably obtained as cop-
roduct. Acetophenone formation was found to proceed
through both Au-catalyzed hydration of phenylacetylene and
hydrolysis of the hydroamination product by adventitious
water, most probably brought in the system with the silver salt
cocatalyst, which is quite hygroscopic. Compared to the
Scheme 2. Employed Standard Cross Coupling Reaction
The obtained results are listed in Table 2. Complexes
Au2Br2L1−9 actually produce low yields of the coupling
product, particularly with mesityl as wingtip substituent, and
appear less efficient than the dinuclear complex with a
bidentate aminophosphine ligand reported by Toste (although
reaction with the same two substrates was not described in the
latter case).18 The best result is obtained with complex
Au2Br2L9 (Table 2, entry 11), with a propylene bridging group
D
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phenylacetylene and mesitylamine. The results are reported in
Table 5.
Table 3. Screening of the Solvent for the Hydroamination
Reaction of Phenylacetylene with Mesitylamine, Promoted
a
by Catalyst Au2Br2L9
Table 5. Screening of the Gold Complexes as Catalysts for
the Hydroamination Reaction of Phenylacetylene with
Mesitylamine
solvent
time (h)
temp (°C)
yield 2a (%)
yield 3a (%)
toluene
22
22
22
22
4
80
80
80
80
80
40
33
18
75
93
81
22
3
1
9
6
6
2
a
acetonitrile
b
IL
entry
catalyst
yield 2a (%)
yield 3a (%)
Au2Br2L1
Au2Br2L2
Au2Br2L3
Au2Br2L4
Au2Br2L5
Au2Br2L6
Au2Br2L7
Au2Br2L8
Au2Br2L9
93
94
94
64
75
72
73
75
70
88
7
6
6
3
9
10
2
2
6
11
neat
1
2
3
4
5
6
7
8
9
10
c
neat
c
neat
4
a
Reaction conditions: 1 mmol mesitylamine, 1 mmol phenylacetylene,
b
0.5 mol% Au2Br2L9, 2 mol% AgOTf, 1 mL solvent, 80 °C, 22 h. IL =
1-butyl-2-methylimidazolium bis(trifluoromethylsulfonyl)imide.
c
Reaction performed with 1 mol% Au2Br2L9.
previously employed Pd complexes, the use of Au2Br2L9
allowed to significantly reduce the reaction time, while at the
same time maintaining a high reaction yield; most notably, and
at variance with the Pd case, catalytic activity was observed also
at 40 °C (last entry in Table 3).
b
IPrAuCl
a
Reaction conditions: 1 mmol amine, 1 mmol phenylacetylene, 1 mol
b
% Au catalyst, 2 mol% AgSbF6, 40 °C, 4 h. 2 mol% Au catalyst.
Screening of the silver salt cocatalyst was consequently
performed at 40 °C under neat conditions (Table 4). In stark
It is evident that all complexes bearing aryl substituents
deliver approximately the same performance in the reaction
(entries 4−9), irrespective both of the kind of aryl substituent
(mesityl or 2,6-diisopropylphenyl) and of the nature of the
bridge between the carbene units (methylene, ethylene, or
propylene). In contrast, better performances were recorded
with the N-methyl-substituted complexes, which were the only
catalysts, together with benchmark IPrAuCl (entry 10), to
reach complete alkyne conversions and very high hydro-
amination yields within the 4 h reaction time. In order to
better differentiate the performance of these complexes, we
chose to perform the reaction with only 0.2 mol% complex.
The results are reported in Table 6.
Table 4. Screening of the Silver Salt Cocatalyst for the
Hydroamination Reaction of Phenylacetylene with
a
Mesitylamine, Promoted by Catalyst Au2Br2L9
entry
cocatalyst
yield 2a (%)
yield 3a (%)
1
2
3
4
5
AgOTs
AgOTf
AgNTf2
AgPF6
2
22
59
59
70
<1
2
5
6
6
AgSbF6
a
Reaction conditions: 1 mmol mesitylamine, 1 mmol phenylacetylene,
1 mol% Au2Br2L9, 2 mol% Ag salt cocatalyst, 40 °C, 4 h.
The results obtained in these conditions (Table 6, entries
1−3) highlight the higher initial activity displayed by complex
Au2Br2L3 bearing the propylene bridge compared to the other
complexes bearing shorter bridges. Since this is also the
complex in which the two Au centers can come at closest
distance, this might be an indication of cooperativity of the two
centers in the catalytic event. Incidentally, a slight cooperative
effect in polynuclear gold(I) complexes as catalysts in alkyne
hydrohydrazinations and hydroaminations has been very
recently reported.47 Comparison of the results obtained with
the various complexes after 2 and 4 h reaction time also
indicates that complex Au2Br2L3 deactivates more rapidly than
the other two, possibly as the consequence of the easier
decomposition to Au colloids. A very similar behavior is
exhibited also by the benchmark catalyst IPrAuCl (Table 6,
entry 4). Remarkably, complex Au2Br2L3 clearly stands out as
the best catalyst also in reactions with other substituted
primary arylamines, such as 4-anisidine (Table 6, entries 5−7)
and 4-chloroaniline (Table 6, entries 8−10), which provides
additional support to the existence of a cooperative effect. On
the other hand, complex Au2Br2L3 fails altogether to effect
hydroaminations with internal alkynes or with secondary
amines, either at 40 or at 80 °C. Such a reaction scope is
largely shared also by the other complexes investigated in this
work. As shown in Table 7, reasonable conversion to the
hydroamination product is obtained at 40 °C only with
terminal alkynes and primary arylamines (Chart 2).
contrast to previously reported Pd catalysts,31 the performance
of Au2Br2L9 was found to depend heavily on the silver salt
anion: in particular, oxoanions were found to be detrimental to
the process, whereas less coordinating anions such as
bis(trifluoromethanesulfonyl)imidate, hexafluorophosphate, or
hexafluoroantimoniate enabled a much better performance,
with hexafluoroantimoniate standing out as the best choice.
This might be indicative of a different mechanism, or at least of
different rate-determining steps of the reaction with the two
metal centers. A control experiment was also performed in
order to evaluate the catalytic activity of the silver salt
cocatalyst per se, since there have been reports in the literature
that hydroamination can be also catalyzed by silver salts.46
Silver hexafluoroantimoniate (2 mol%) did indeed convert to
some extent the alkyne to the hydroamination product (16%)
and to the hydration product (7%) after 4 h at 40 °C under
neat conditions, but catalytic efficiency was much lower than in
the presence of the Au catalyst, and it should be also taken into
account that in the presence of Au2Br2L9 most of the silver
precipitates as the insoluble bromide. Consequently, it can be
safely stated that the presence of silver in the catalytic system
does not result in a significant contribution to the catalytic
event.
After having optimized the reaction conditions, the various
gold complexes were finally screened for their catalytic
performance in the model hydroamination reaction between
With internal alkynes (phenylpropyne, diphenylacetylene),
secondary arylamines (N-methylaniline), and primary/secon-
E
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this kind are not observed at all with primary arylamines using
the gold catalysts described herein. We have tried to expand
the cyclization reaction scope in our conditions by reacting N-
methyl-p-nitroaniline with phenylacetylene (Table 7). In this
reaction, however, we observed only the formation of the
hydroamination product (2h) even after 24 h. The different
reactivity in the presence of a nitro group on the aromatic ring
of the secondary amine suggests that the cascade reaction
sequence could be different in this case compared to the
literature, involving rate-determining intermolecular alkyne
hydroarylation at the aromatic amine ring (i.e., the most
electron-rich ring) followed by cyclization. More mechanistic
investigations are however needed to substantiate this
statement. We have also tried to react in the same conditions
N-methylaniline with 1-octyne and 1-hexyne, but in these cases
we did not observe the formation of the hydroamination nor of
the cyclization product. Thus, the reaction appears at present
limited to terminal arylacetylenes.
Table 6. Screening of Catalysts for the Hydroamination
Reaction at 0.2% Catalyst Loading
a
The reason for the moderate activity with less reactive
alkylamines and secondary arylamines, evidenced by Au
catalysts bearing the N-2,6-diisopropylphenyl substituent, can
in our opinion be traced back to the increased stability
imparted to the complex by this large substituent, which in
turn allows the complex to survive for sufficient time at the
reaction temperature (80 °C) to promote the reaction to some
extent. It has to be remarked that whenever successful NHC-
Au catalyzed hydroamination with these difficult substrates was
reported, high reaction temperatures (often above 100 °C)
were invariably required.5,38−44 We currently aim at further
optimizing the reaction conditions in order to improve the
efficiency of these reactions with these substrates.
CONCLUSIONS
■
In this paper we have reported on an optimized one-step
procedure for the synthesis of dinuclear neutral gold(I)
complexes with bridging diNHC ligands of general formula
Au2Br2L (L = diNHC ligand). Our single-step synthetic
protocol is tolerant toward different wingtip groups (methyl,
mesityl, and 2,6-diisopropylphenyl) and bridging groups
between the two carbene donors. The structural analysis of
complexes Au2Br2L4−6 has shown that, by elongating the
aliphatic bridge between the imidazol-2-ylidene rings from one
to three carbon atoms, the two gold(I) centers can come closer
one to another. This is in line with what we already reported
for dinuclear gold(I) diNHC complexes of general formula
[Au2L2]2+.6 The synthesized complexes have been tested as
catalysts in the cross coupling reaction between phenyl boronic
acid and cinnamyl bromide; the complexes have shown
moderate activity in this reaction. Better performances have
been recorded in the hydroamination reaction of phenyl-
acetylene with mesitylamine. Other primary arylamines can be
used with good results; however, the catalysts cannot activate
internal alkynes and aliphatic amines, with the exception of
complex Au2Br2L7 that effects sluggish hydroamination of
phenylacetylene with cyclohexylamine or morpholine at 80 °C.
From the catalytic studies, we have also gained important
insights on the structure/activity relationship in the gold(I)
complexes. Complexes with bulkier wingtip substituents, such
as 2,6-diisopropylphenyl, present higher stability under
catalytic conditions, whereas complexes with small methyl
substituents are more reactive. Complexes with the more
flexible propylene bridging group display in general a better
catalytic performance compared to the complexes with shorter
a
Reaction conditions: 5 mmol amine, 5 mmol phenylacetylene, 0.2
b
mol% Au catalyst, 0.4 mol% AgSbF6, 40 °C. 0.4 mol% Au catalyst.
dary alkylamines (cyclohexylamine, morpholine) no formation
of hydroamination product is generally observed, neither at 40
°C nor at 80 °C, with the exception of complexes bearing the
N-2,6-diisopropylphenyl substituent, such as Au2Br2L7, which
beside efficiently catalyzing the reaction with differently ring
substituted primary anilines at 40 °C, also effects sluggish
hydroamination of phenylacetylene with cyclohexylamine or
morpholine at 80 °C (Table 7). Furthermore, complex
Au2Br2L7 is also able to effect hydroaminations of phenyl-
acetylene with a secondary aromatic amine such as N-
methylaniline at 80 °C in up to moderate yield (Table 7 and
Scheme 4). However, the enamine hydroamination product is
not stable under the reaction conditions and tends to undergo
further Au-catalyzed reaction with an additional molecule of
phenylacetylene through a cascade reaction sequence, leading
to the bicyclic product reported in Scheme 4. Under the same
conditions IPrAuCl produces the substituted 1,2-dihydroqui-
noline 4 exclusively without intermediate accumulation of the
hydroamination product (last entry of Table 7).
The possible onset of this reaction has been observed
previously with a few catalytic systems, including gold(I) NHC
complexes, and mechanistically interpreted in terms of a
nucleophilic addition/intramolecular hydroarylation se-
quence.48−52 It has to be remarked that cascade reactions of
F
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Article
a
Table 7. Substrate Screening for the Hydroamination Reaction with the Gold Catalysts
a
b
c
Reaction conditions: 1 mmol amine, 1 mmol alkyne, 1 mol% Au catalyst, 2 mol% AgSbF6. Reaction performed with 2 mmol phenylacetylene. 2
mol% Au catalyst.
Chart 2. Scope of the Alkyne Hydroamination Reaction
will be, however, necessary to rationalize the presence of
cooperative effects in the studied catalytic reactions.
EXPERIMENTAL SECTION
■
All manipulations were carried out using standard Schlenk techniques
under an atmosphere of argon or dinitrogen. The reagents were
purchased by Aldrich as high-purity products and generally used as
received; all solvents were used as received as technical grade solvents.
The diimidazolium salts H2Br2L1−H2Br2L9 were synthesized
according to literature procedure.53 NMR spectra were recorded on
a Bruker Avance 300 MHz (300.1 MHz for H and 75.5 for 13C);
1
chemical shifts (δ) are reported in units of parts per million (ppm)
relative to the residual solvent signals. ESI mass spectra were recorded
on a Finnigan Thermo LCQ-Duo ESI mass spectrometer. Elemental
analyses were carried out by the microanalytical laboratory of
Chemical Sciences Department (University of Padova) with a
Thermo Scientific FLASH 2000 instrument.
General Procedure for the Synthesis of the Gold(I)
Complexes Au2Br2L1−Au2Br2L9. A mixture of the diimidazolium
salt (0.50 mmol), AuCl(SMe2) (1.00 mmol), potassium carbonate
(11.00 mmol), and LiBr (2.50 mmol) in acetonitrile (50 mL) was
and less flexible linkers, which we attribute to the fact that the
two gold(I) centers can come more easily close one to another,
thus enabling cooperative catalysis. Further mechanistic studies
G
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1
Au2Br2L5. Yield 88%. H NMR (300.1 MHz, CDCl3, 25 °C) δ =
2.01 (s, 12H, CH3), 2.33 (s, 6H, CH3), 4.87 (s, 4H, CH2), 6.94 (m,
6H, CH), 7.34 ppm (d, 3J(H,H) = 1.8 Hz, 2H, CH). 13C NMR (75.5
MHz, CDCl3, 25 °C) δ = 18.7 (CH3), 21.3 (CH3), 51.1 (CH2), 121.4
(CH imidazole), 123.6 (CH imidazole), 129.6 (C aromatic), 134.4
(CH aromatic), 134.7 (C aromatic), 140.0 (C aromatic), 175.7 ppm
(NCN). ESI-MS (m/z): 871.21 ([M−Br]+, expected 871.10).
Elemental analysis calcd (%) for C26H30N4Br2Au2: C 32.79, H 3.18,
N 5.88; found: C 32.45, H 3.25, N 5.97.
Scheme 4. Cascade Reaction Involving Alkyne
Hydroamination with N-Methylaniline and Subsequent
Reaction of the Hydroamination Product with
Phenylacetylene
1
Au2Br2L6. Yield 91%. H NMR (300.1 MHz, CDCl3, 25 °C) δ =
3
2.03 (s, 12H, CH3), 2.33 (s, 6H, CH3), 2.68 (quint., J(H,H) = 7.2
Hz, 2H, CH2CH2CH2), 4.41 (t, 3J(H,H) = 7.2 Hz, 4H,
3
CH2CH2CH2), 6.96 (m, 6H, CH), 7.35 ppm (d, J(H,H) = 1.8 Hz,
2H, CH). 13C NMR (75.5 MHz, CDCl3, 25 °C) δ = 18.1 (CH3), 21.3
(CH3), 32.8 (CH2CH2CH2), 48.3 (CH2CH2CH2), 121.0 (CH
imidazole), 123.3 (CH imidazole), 129.6 (C aromatic), 134.7 (CH
aromatic), 134.8 (C aromatic), 139.9 (C aromatic), 175.4 ppm
(NCN). ESI-MS (m/z): 887.11 ([M−Br]+, expected 887.11).
Elemental analysis calcd (%) for C27H32N4Br2Au2: C 33.56, H 3.34,
N 5.80; found: C 32.47, H 3.19, N 5.27.
1
Au2Br2L7. Yield 71%. H NMR (300.1 MHz, CDCl3, 25 °C) δ =
3
3
1.12 (d, J(H,H) = 6.9 Hz, 12H, CH3), 1.27 (d, J(H,H) = 6.9 Hz,
3
12H, CH3), 2.27 (sept, J(H,H) = 6.9 Hz, 4H, CH), 6.71 (s, 2H,
3
3
CH2), 7.03 (d, J(H,H) = 1.8, 2H, CH), 7.28 (d, J(H,H) = 7.8 Hz,
4H, CH), 7.51 (t, 3J(H,H) = 7.8 Hz, 2H, CH), 8.22 ppm (d, 3J(H,H)
= 1.8 Hz, 2H, CH). 13C NMR (75.5 MHz, CDCl3, 25 °C) δ = 24.3
(CH3), 24.5 (CH3), 28.8 (CH), 62.5 (CH2), 121.1 (CH imidazole),
124.3 (CH imidazole), 124.6 (CH aromatic), 131.3 (CH aromatic),
133.6 (C aromatic), 145.4 (C aromatic), 177.5 ppm (NCN). ESI-MS
(m/z): 943.21 ([M−Br]+, expected 943.18). Elemental analysis calcd
(%) for C31H40N4Br2Au2: C 36.41, H 3.94, N 5.48; found: C 36.23, H
4.09, N 5.32.
heated and maintained at 60 °C for 16 h. The obtained suspension
was then filtered over a PTFE Millipore syringe filter (polytetrafluoro-
ethylene, 0.45 μm). The solvent was removed at reduced pressure
from the filtrate, obtaining a brown/yellow solid. The crude product
was recrystallized from acetonitrile/diethyl ether (Au2Br2L1−3) or
dichloromethane/n-hexane (Au2Br2L4−9) to obtain a white/yellow
solid. Complexes Au2Br2L4, Au2Br2L7, and Au2Br2L8 were further
purified by recrystallization from acetone/n-hexane. Purity of the
isolated complexes has been established by elemental analysis.
Although the elemental analysis results are in few cases outside the
range viewed as establishing analytical purity, they are provided to
illustrate the best values obtained to date.
1
Au2Br2L8. Yield 84%. H NMR (300.1 MHz, CDCl3, 25 °C) δ =
3
3
1.11 (d, J(H,H) = 6.6 Hz, 12H, CH3), 1.32 (d, J(H,H) = 6.9 Hz,
3
12H, CH3), 2.31 (sept., J(H,H) = 6.9 Hz, 4H, CH), 4.95 (s, 4H,
3
CH2), 6.93 (d, J(H,H) = 1.5 Hz, 2H, CH), 7.28 (m, 6H, CH), 7.50
3
ppm (t, J(H,H) = 7.8 Hz, 2H, CH). 13C NMR (75.5 MHz, CDCl3,
Au2Br2L1. Yield 83%. 1H NMR (300.1 MHz, [D6]DMSO, 25 °C) δ
= 3.77 (s, 6H, CH3), 6.43 (s, 2H, CH2), 7.53 (s, 2H, CH), 7.66 ppm
(s, 2H, CH). 13C NMR (75.5 MHz, [D6]DMSO, 25 °C) δ = 38.1
(CH3), 62.3 (CH2), 121.4 (CH), 123.4 (CH), 173.6 ppm (NCN).
ESI-MS (m/z): 649.12 ([M−Br]+, expected 648.98). Elemental
analysis calcd (%) for C9H12N4Br2Au2: C 14.81, H 1.66, N 7.68;
found: C 14.86, H 1.74, N 7.74.
25 °C) δ = 24.4 (CH3), 24.6 (CH3), 28.6 (CH), 51.0 (CH2), 121.9
(CH imidazole), 123.2 (CH imidazole), 124.5 (CH aromatic), 131.1
(CH aromatic), 133.8 (C aromatic), 145.5 (C aromatic), 176.3 ppm
(NCN). ESI-MS (m/z): 955.21 ([M−Br]+, expected 955.19).
Elemental analysis calcd (%) for C32H42N4Br2Au2: C 37.08, H 4.08,
N 5.41; found: C 36.84, H 4.21, N 5.27.
1
Au2Br2L9. Yield 90%. H NMR (300.1 MHz, CDCl3, 25 °C) δ =
Au2Br2L2. Yield 75%. 1H NMR (300.1 MHz, [D6]DMSO, 25 °C) δ
= 3.69 (s, 6H, CH3), 4.48 (s, 4H, CH2), 7.30 (d, 3J(H,H) = 3 Hz, 2H,
CH), 7.40 ppm (d, 3J(H,H) = 3 Hz, 2H, CH). 13C NMR (75.5 MHz,
[D6]DMSO, 25 °C) δ = 37.6 (CH3), 51.0 (CH2), 121.4 (CH), 123.3
(CH), 172.3 ppm (NCN). ESI-MS (m/ z): 665.10 ([M−Br]+,
expected 664.97). Elemental analysis calcd (%) for C10H14N4Br2Au2:
C 16.14, H 1.90, N 7.53; found: C 16.09, H 2.14, N 6.92.
3
3
1.13 (d, J(H,H) = 6.9 Hz, 12H, CH3), 1.28 (d, J = 6.9 Hz, 12H,
CH3), 2.41 (sept., 3J(H,H) = 6.9 Hz, 4H, CH), 2.72 (quint., 3J(H,H)
= 7.5 Hz, 2H, CH2CH2CH2), 4.43 (t, 3J(H,H) = 7.2 Hz, 4H,
CH2CH2CH2), 7.02 (d, 2J(H,H)= 1.8 Hz, 2H, CH), 7.25 (d, 3J(H,H)
3
= 7.8 Hz, 4H, CH), 7.36 (d, J(H,H) = 1.8 Hz, 2H, CH), 7.47 ppm
(t, 3J(H,H) = 7.8 Hz, 2H, CH). 13C NMR (75.5 MHz, CDCl3, 25 °C)
δ = 24.4 (CH3), 24.6 (CH3), 28.6 (CH), 32.8 (CH2CH2CH2), 48.4
(CH2CH2CH2), 121.0 (CH imidazole), 124.4 (CH aromatic), 124.6
(CH imidazole), 130.8 (CH aromatic), 134.0 (C aromatic), 145.7 (C
aromatic), 176.2 ppm (NCN). ESI-MS (m/z): 969.22 ([M−Br]+,
expected 969.21). Elemental analysis calcd (%) for C33H44N4Br2Au2:
C 37.73, H 4.22, N 5.33; found: C 38.61, H 4.45, N 5.15.
Au2Br2L3. Yield 81%. 1H NMR (300.1 MHz, [D6]DMSO, 25 °C) δ
= 2.45 (m, 2H, CH2), 3.78 (s, 6H, CH3), 4.02 (m, 4H, CH2), 7.50 (s,
1
2H, CH), 7.57 ppm (s, 2H, CH). H NMR (300.1 MHz, CDCl3, 25
°C) δ = 2.45 (quint, 3J(H,H) = 6.3 Hz, 2H, CH2), 3.90 (s, 6H, CH3),
3
4.22 (t, J(H,H) = 6.3 Hz, 4H, CH2), 7.04 (s, 4H, CH). 13C NMR
(75.5 MHz, [D6]DMSO, 25 °C) δ = 28.7 (CH2), 37.7 (CH3), 45.9
(CH2), 119.9 (CH), 123.5 (CH), 172.8 ppm (NCN). ESI-MS (m/z):
677.01 ([M−Br]+, expected 676.99). Elemental analysis calcd (%) for
C11H16N4Br2Au2·1/2CH3CN: C 18.51, H 2.27, N 8.10; found: C
18.82, H 2.24, N 8.07.
X-ray Crystal Structure Determination of Complexes
Au2Br2L4, Au2Br2L5, and Au2Br2L6. X-ray crystallographic data of
complex Au2Br2L4 were obtained by mounting a crystal on a glass
fiber and transferring it to a APEX 2 Bruker CCD platform
diffractometer. The APEX 3 program package54 was used to
determine the unit-cell parameters and for the data collection (30
s/frame scan time for a sphere of diffraction data). The raw frame data
were processed using SAINT54 and SADABS55 to yield the reflection
data file. The structure was solved using SHELXT56 by Intrinsic
Phasing method in the APEX 3 program. Subsequent calculations
were carried out using the SHELXTL-2014/7 program56 in the
WinGX suite v.2014.1.57 The refinement was carried out based on F2
by full-matrix least-squares techniques. The hydrogen atoms were
1
Au2Br2L4. Yield 67%. H NMR (300.1 MHz, CDCl3, 25 °C) δ =
1.97 (s, 12H, CH3), 2.34 (s, 6H, CH3), 6.67 (s, 2H, CH2), 6.98 (s,
6H, CH), 8.11 ppm (s, 2H, CH). 13C NMR (75.5 MHz, CDCl3, 25
°C) δ = 18.7 (CH3), 21.3 (CH3), 62.8 (CH2), 125.2 (CH imidazole),
126.8 (CH imidazole), 130.3 (C aromatic), 132.1 (CH aromatic),
135.2 (C aromatic), 141.8 (C aromatic), NCN not detected. ESI-MS
(m/z): 857.28 ([M−Br]+, expected 857.08). Elemental analysis calcd
(%) for C25H28N4Br2Au2: C 32.00, H 3.01, N 5.97; found: C 31.52, H
3.12, N 5.66.
H
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included in the refinement at idealized geometry and refined “riding”
on the corresponding parent atoms.
AUTHOR INFORMATION
■
Crystal data of complexes Au2Br2L5 and Au2Br2L6 were collected
using an Oxford Diffraction Gemini E diffractometer, equipped with a
2K × 2K EOS CCD area detector and sealed-tube Enhance (Mo) and
(Cu) X-ray sources. Mo Kα (λ = 0.71073 Å) radiation was used. Data
collection, reduction, and finalization were carried out through the
CrysAlisPro software. Using Olex2,58 Au2Br2L5 and Au2Br2L6
structures were solved in the P21/c and C2/c space groups,
respectively, with the ShelXT56 structure solution program by
Intrinsic Phasing and refined with the ShelXL59 refinement package
using least-squares minimization. Au2Br2L5 crystallizes with a CH2Cl2
molecule that has been split in two parts the occupancies of which
were constrained to sum to 1.0. SADI and RIGU restrains have been
used to better model the two parts. In the last cycles of refinement,
non-hydrogen atoms were refined anisotropically. Hydrogen atoms
were included in calculated positions, and a riding model was used for
their refinement. Crystallographic data have been deposited with the
Cambridge Crystallographic Data Centre (CCDC 1839490 for
complex Au2Br2L4, 1828633 for complex Au2Br2L5, and 1828632
for complex Au2Br2L6). Crystal data and refinement parameters are
reported in Table S1.
Corresponding Authors
*E-mail: marco.baron@unipd.it.
*E-mail: andrea.biffis@unipd.it.
ORCID
Marco Baron: 0000-0001-6762-2240
Cristina Tubaro: 0000-0001-7724-735X
Andrea Biffis: 0000-0002-7762-8280
Marzio Rancan: 0000-0001-9967-5283
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
University of Padova is gratefully acknowledged for the
financial support (Assegno di Ricerca Senior GRIC15V47A).
REFERENCES
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S
* Supporting Information
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Accession Codes
CCDC 1828632, 1828633, and 1839490 contain 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.
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Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44
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