Synthesis and Characterization of a Tetradentate, N-Heterocyclic Carbene Copper(II) Complex and Its Use as a Chan-Evans-Lam Coupling Catalyst

Article abstract of DOI:10.1021/acs.organomet.0c00552

Copper N-heterocyclic carbenes (NHCs) are an emerging area of focus for catalysis and other applications. Using a straightforward methodology, a new and highly modifiable tetradentate copper(II) NHC complex was generated and characterized using X-ray crystallography, UV-vis and EPR spectroscopy, cyclic voltammetry, and ESI-MS. This copper(II) NHC complex adopted a distorted 4-coordinate coordination mode and demonstrates a unique absorption spectrum for a copper(II) species, but more interestingly, its redox properties indicate that it can readily access all three common copper oxidation states under atmospheric conditions. The tetradentate copper(II) NHC complex was used to catalytically generate new C-N bonds from a series of phenylboronic acids and amines. Once this CEL methodology was refined, moderate to high yields were achieved using catalytic amounts of the copper(II) complex to couple phenylboronic acids to a series of aniline derivatives. Substituted phenylboronic acids and anilines had minimal impact on the catalytic capabilities of this copper complex; however, there is some indication that steric interactions between catalyst and substrates may have an impact on efficient catalysis. The straightforward synthesis of this framework and the utilization of an inexpensive, first-row transition metal center in this system highlight the usefulness of copper(II) NHCs as catalyst for cross-coupling reactions.

Full text of DOI:10.1021/acs.organomet.0c00552

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Article
Synthesis and Characterization of a Tetradentate, N‑Heterocyclic
Carbene Copper(II) Complex and Its Use as a Chan−Evans−Lam
Coupling Catalyst
James D. Cope, Patrick E. Sheridan, Christopher J. Galloway, Raymond Femi Awoyemi, Sean L. Stokes,
and Joseph P. Emerson*
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ABSTRACT: Copper N-heterocyclic carbenes (NHCs) are an emerging
area of focus for catalysis and other applications. Using a straightforward
methodology, a new and highly modifiable tetradentate copper(II) NHC
complex was generated and characterized using X-ray crystallography, UV−
vis and EPR spectroscopy, cyclic voltammetry, and ESI-MS. This
copper(II) NHC complex adopted a distorted 4-coordinate coordination
mode and demonstrates a unique absorption spectrum for a copper(II)
species, but more interestingly, its redox properties indicate that it can
readily access all three common copper oxidation states under atmospheric
conditions. The tetradentate copper(II) NHC complex was used to
catalytically generate new C−N bonds from a series of phenylboronic acids
and amines. Once this CEL methodology was refined, moderate to high yields were achieved using catalytic amounts of the
copper(II) complex to couple phenylboronic acids to a series of aniline derivatives. Substituted phenylboronic acids and anilines had
minimal impact on the catalytic capabilities of this copper complex; however, there is some indication that steric interactions
between catalyst and substrates may have an impact on efficient catalysis. The straightforward synthesis of this framework and the
utilization of an inexpensive, first-row transition metal center in this system highlight the usefulness of copper(II) NHCs as catalyst
for cross-coupling reactions.
be considered more of a reagent than a catalyst. Several groups
have made dedicated progress in exploring the ligands that
support CEL reactivity, but overall, the scope of these reports
is limited.10,12−14 Previously, we reported a series of bidentate
ligands including diazafluorenone, which stabilized the Cu+
state more efficiently than phenanthroline, and this shift in
potential was linked to increased catalytic yields for the CEL
process.15 Building on these results, we set out to develop
copper complexes that could more efficiently stabilize the Cu2+
(or Cu3+) oxidation states using a novel N-heterocyclic carbene
(NHC) based ligand system, which has inspired us to explore
these strong σ donor ligands and their propensity to support
CEL reactions.
INTRODUCTION
■
Developing new first-row transition metal catalysts that
support the formation of new C−C or C−heteroatom bonds
provides new and inexpensive methods for modern synthetic
chemistry.1,2 Clearly there are a number of well-behaved
catalytic systems that are based on Pd chemistry, but there is a
major cost advantage to exploring cross-coupling catalysts that
rely on abundant transition metals like Cu. Over a century ago,
Ullman and Goldberg reported copper-dependent C−C cross-
coupling chemistry,3,4 which has been found to rely upon a 2-
electron, copper(I)/copper(III) catalytic cycle.5 A more recent
copper mediated protocol for C−N bond formation was
developed by Chan, Evans, and Lam.6−8 The Chan−Evans−
Lam or CEL coupling is an oxidative “nucleophile−
nucleophile” approach, which is much more akin to the Pd-
catalyzed Suzuki coupling using phenylboronic acids as the
coupling agent. The CEL reaction, however, is much less
understood, where the reaction has been proposed to proceed
through several different copper oxidation states including Cu+,
Cu2+, and Cu3+. The mechanistic role of each of these species
is still actively debated.9−11 Another issue with adopting the
CEL coupling is that many using this reaction still employ a
large excess of aryl boronic acids and 1−2 equiv of a copper
“catalyst,” even though, under these conditions, copper should
NHCs are ubiquitous ligands that have been used since the
discovery of stable free carbenes by Arduengo in 1991.16
Several books and review articles exist highlighting the
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multitude of complexes that utilize these ligands for a variety of
different applications.17−21 Specifically, copper NHC com-
plexes have seen a surge of interest as potential catalysts and
photovoltaic molecules.17,22 Generally, these complexes are
copper(I) monodentate structures which arise from the high
stability of the soft-soft acid/base interactions that come from
the copper(I)−C(carbene) bond.23
dazole (1), achieving up to 84% yield. This was then reacted
with excess dibromomethane under reflux to generate the
tetradentate ligand bromide salt (2). The counterions were
−
then exchanged with PF6 , forming compound 3.
To generate the desired copper(II) complex, we initially set
out using the same procedure as reported for Ni and Pd.29
Compound 2 was reacted with 1 equiv of Cu(OAc)2 in DMSO
for 3 h at 50 °C. However, under these conditions, no metal-
coordinated product was generated. Upon closer investigation
of the reaction solution, 2 was found to be oxygenated. A
similar oxidized NHC compound was previously observed
when using Cu(OAc)2,30 where the acetate ion played a role in
transferring an oxygen atom to the imidazolium group after
copper coordination. Alternative solvents and coordination
conditions were attempted, including trials using MeOH and
DCM. In all efforts, either we observed no reaction or we
generated the oxygenated ligand as the only discernible
product of the reaction. This hurdle was overcome, by
That being said, Chen,23 Long,24 Singer,25 and Meyer26
recently reported copper NHC complexes bearing pyridine
groups, which formed stable, multidentate copper coordination
complexes (Figure 1). In one case, it was a tetradentate, cyclic
−
changing the bromide counterion of 2 to the PF6 salt, 3.
−
The change in counterion from bromide to PF6 did not lead
to drastically different physical properties of the compound.
Starting with complex 3 and copper(II) acetate, we were
successful in precipitating the targeted copper(II) NHC
species (Scheme 2).
Scheme 2. Synthesis of Compound 4
Figure 1. General structures of Cu+ and Cu2+ NHC complexes
bearing picolyl groups.
N-heterocyclic carbene complex that was able to stabilize
Cu3+.26 Herein, we report the synthesis and characterization of
a tetradentate pyridyl-based NHC complex using Cu(OAc)2
under atmospheric conditions. This complex adds to the
growing number of NHC complexes using Cu(OAc)2 as both
the metal source and the general base to generate Cu-NHC
complexes with good success.27,28 These complexes were
characterized and then screened as CEL coupling agents using
phenylboronic acids and various amines.
The copper(II) NHC complex (4) was generated through a
stoichiometric reaction of Cu(OAc)2 with 3 in MeOH at 50
°C for 3 h, which produced a pure orange precipitate with a
72% yield. This complex was characterized by mass
spectrometry, elemental analysis, and X-ray crystallography.
Crystals suitable for single crystal X-ray crystallography were
produced by vapor diffusion of diethyl ether into an
acetonitrile solution of 4. The X-ray crystal structure of 4 is
shown in Figure 2.
RESULTS AND DISCUSSION
■
The crystal structure indicates that the complex is a
copper(II) NHC species due to the two hexafluorophosphate
The tetradentate ligand was synthesized in a two-step process,
based on a procedure previously reported by Chiu and co-
workers, which is outlined in Scheme 1.29 Benzimidazole was
reacted with picolyl chloride stoichiometrically under basic
conditions to produce the monosubstituted picolyl-benzimi-
1
counterions per copper ion, which is further supported by H
NMR which shows broadened peaks, indicative of a para-
magnetic copper(II) species. The complex is distinctively four
coordinate and adopts a distorted seesaw like geometry (τ4 ≈
́
0.29, τ4 = 0.26) rather than the more commonly observed
Scheme 1. Synthesis of Compounds 1−3
square planar or tetrahedral geometries.31 Perhaps somewhat
surprisingly, this system did not adopt a 5-coordinate
coordination mode with a labile or solvent derived species
occupying the axial coordination site as is the case for other
tetradentate ligands forming pseudo-square-pyramidal copper-
(II) complexes.32 We expect this stabilized geometry results
from destabilizing steric interactions between the picolyl
groups and from the intrinsic flexibility of the methylene
spacer groups between the heterocyclic rings of this structure.
These −CH2− groups afford some structural flexibility which
allows for the ligand to adopt conformations that alleviate
steric interactions. The Cu1−C1 and Cu1−C9 bonds lengths
are 1.956(2) and 1.962(2) Å, respectively. These bond lengths
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(∼260 nm) and deeper into the UV region at ∼200 nm with ε
= 10 000 and 43 000 M−1 cm−1, respectively. Due to the low
number of copper(II) NHC complexes that have been
reported, most of which do not include a spectroscopic
study, direct comparisons are limited. The d-to-d transitions
occur at higher energy than those reported by van Koten and
Albrecht, who reported a series of copper(II) imidazolylidene
based complexes with d-to-d transitions between 660 and 990
nm.28 Similar transitions in the UV have been observed for
related copper(I) NHC complexes.34,35 The X-band EPR
spectrum of 4 shows an axial signal with no resolved hyperfine
structure (Figure 3 inset). The unresolved hyperfine structure
associated with this copper(II) feature is consistent with an
ensemble of copper(II) species in solution arising from a
flexibility coordination geometry in 4. This suggests that the
structure shown in Figure 2 cannot be singularly considered as
the copper(II) coordination mode in solution.
The redox potentials for this complex were investigated
using cyclic voltammetry (CV); the voltammograms of
complex 4 at different scan rates are shown in Figure 4A.
Between the potential window of 0.000 and −0.750 V, the data
show an anodic oxidation and cathodic reduction peaks at
−0.257 and −0.475 V against Fc+/Fc, respectively. The
observed peaks correspond to the Cu2+/+ couple, and it can be
Figure 2. An ORTEP diagram at 50% thermal ellipsoids of the
molecular structure with selected bond lengths and angles of 4.
Selected bond lengths (Å): Cu1−C1 = 1.956(2); Cu1−C9 =
1.962(2); Cu1−N5 = 2.056(2); Cu1−N6 = 2.058(2). Angles
(deg): C1−Cu1−N5 = 154.36(8); C9−Cu1−N6 = 164.61(9);
C1−Cu1−C9 = 90.00(10); N5−Cu1−N6 = 95.02(9); C1−Cu1−
N6 = 90.72(9); C9−Cu1−N5 = 90.93(9).
fall in the range for previously reported copper(II)-NHC
complexes, but they are slightly longer than that of the
structurally similar tridentate copper(II) NHC complex
reported by Singer.25,33
UV−vis absorption spectroscopy of complex 4 was
performed in MeCN, shown in Figure 3. The complex is
Figure 3. UV−vis absorption spectrum of copper(II) complex 4 run
in MeCN at room temperature. Inset in this figure is the X-band EPR
spectrum of complex.
intensely orange in color, which in solution appears red. The
spectrum contains several distinct electronic transitions. There
are at least two low intensity transitions, consistent with d-to-d
transition of the d9 copper(II) complex. There is a broad band
λmax at 505 nm (ε = 333 M−1 cm−1) and a sharper band around
401 nm (ε = 700 M−1 cm−1). These transitions account for the
distinctive color of this complex, compared to more common
d-to-d transitions in copper(II) complexes that are typically
observed in the 600−800 nm region. Additionally, there is a
well-defined transition at 313 nm (ε = 3200 M−1 cm−1) which
could correspond to a charge transfer transition. Finally, we
propose that this complex has π-to-π* transitions in the UV
Figure 4. (A) Cyclic voltammetry data associated with 100 mM
complex 4 in MeCN vs Fc+/Fc. Several scan rates of 50, 75, 100, 125,
150, and 200 mV/s are shown as black, cyan, blue, green, red, and
violet traces, respectively. Voltage values are normalized vs the Fc+/Fc
standard. (B) Cyclic voltammetry data over a wider potential window
for 100 mM complex 4 in MeCN. A background scan (dashed black
trace), complex 4 (blue), and complex 4 with Fc (red) are plotted
against Fc+/Fc. All scans were collected with a scan rate of 0.1 V/s.
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said to be electrochemically quasi-reversible as the peak-to-
peak separation is given as 218 mV. There is a shift in peak-to-
peak separation especially for lower scan rates (20−50 mV/s),
whereas there is no shift in peaks for fast scan rates (50−200
mV/s). See Figure S1 in the Supporting Information for
additional CV scans of 4. When the potential window is
expanded to 1.8 V to −1.5 V, an additional set of anodic
oxidation and cathodic reduction peaks are observed at 0.714
and 1.005 V, with respect to Fc+/Fc. We have assigned this
event to a quasi-reversible Cu3+/2+ couple with a separation of
859 mV (Figure 4B), which is consistent with other literature
values.36,37 With these relatively low redox potentials, 4 can
readily access the copper(I), copper(II), and copper(III) states
under atmospheric conditions, where the neutral donor
properties of the ligand insulate the coordinated copper from
charge stabilization through solvent effects.
Once characterized, we then turned our attention to
investigating 4’s ability to catalyze Chan−Evans−Lam coupling
(CEL) between aniline and phenylboronic acid. Initially, we
set out using the following reaction conditions: 8 mol %
catalyst in 0.5 mL of MeOH, with a 2:1 ratio of phenylboronic
acid to aniline under aerobic conditions. The diphenylamine
product was obtained with an isolated yield of 47% (Table 1,
entry 1). As expected, repeating this reaction but under an
atmosphere of argon or without a source of copper produced
only trace amounts of product as observed by GC-MS.
relationships between solvent, solubility, and catalysis remain
poorly understood, where our results suggest that catalyst
solubility is not the most important factor in driving reactivity.
As noted previously, complex 4 is not readily soluble in MeOH
and does not appear to be soluble in water, but both of these
solvents support significantly higher turnover than aprotic
solvents (such as DMF or MeCN) where 4 is readily soluble.
Catalyst loading of the CEL process was investigated as the
amount of copper used in these reactions varies across reports
with excess Cu(OAc)2 often employed under ligand free
conditions. This need for excess copper has been attributed to
a copper disproportionation step in the CEL mechanism,
which increases the amount of copper needed for catalytic
turnover.9,39 Trials using between 1 and 50 mol % of catalyst
for the CEL coupling of phenylbornic acid to aniline were
conducted. The results indicate that decreasing the catalyst
loading from 8 mol % to 1 mol % saw the isolated yield drop
significantly to 23% (Table 1, entry 8), and 2 mol % of catalyst
saw a slight rise to 37% (Table 1, entry 9). A 5 mol % catalyst
loading saw a yield of 44% (Table 1, entry 10), which is very
similar to that which was observed for 8 mol %. When this was
increased to 25 and 50 mol %, the yield increased to 86% and
to completion in 24 h (Table 1, entries 11 and 12). While we
see significant gains in yield when an increased mol % of
catalyst is used, we continued to use 8 mol % catalyst loading
for further optimization since this gave us modest yields, while
still allowing for other factors to impact C−N bond formation.
The effects of temperature were also studied, and since we
were using MeOH, the temperature range that was explored
was limited to trials set between 0 and 65 °C. When the
temperature was lowered, the yield dropped to 21% (Table 1,
entry 13), but when heated to 35 °C, 45 °C, or reflux, the yield
was increased to 59, 72, and 99%, respectively (Table 1, entries
14−16).
a
Table 1. Initial CEL Reactivity Data
b
entry
solvent
cat. load. (mol %)
temp. (°C)
yield (%)
1
2
3
4
5
MeOH
EtOH
H2O
MeCN
DCM
8
8
8
8
8
20
20
20
20
20
47
32
38
21
8
The addition of base has also been shown improve these
reactions; however, base is not always a requirement for
reactivity.40 Due to our modest yields without base, we
investigated the addition of different organic and inorganic
bases to determine if these proton scavengers could drive the
reaction to completion, the results of which are shown in Table
2. Initially, we explored 1 equiv of base and found that
carbonates such as K2CO3 and Cs2CO3 were the most reactive,
leading to 90% and 71% yields of our targeted product,
respectively (Table 2, entries 1 and 3). When using
triethylamine, no discernible difference was observed com-
6
DMF
8
20
0
7
8
9
10
11
12
13
14
15
16
hexanes
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
8
1
2
5
25
50
8
8
8
20
20
20
20
20
20
0
35
9
23
37
44
86
>99
21
59
72
99
a
Table 2. Impact of Base on CEL Reactivity
45
reflux
8
a
Reaction conditions: aniline (0.1 mmol), phenylboronic acid (0.2
mmol), 4 (8 mol %), MeOH (0.5 mL), ca. 20 °C for 24 h in air unless
b
b
entry
solvent
base
base equiv
yield (%)
otherwise noted. Isolated yields.
1
2
3
4
5
6
7
8
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
H2O
K2CO3
K2CO3
Cs2CO3
N(Et)3
KOH
Na3PO4
K2CO3
K2CO3
1
4
1
1
1
1
1
4
90
74
71
47
23
26
51
74
Next, we set out to find the best reaction medium for these
reactions. It is well established that CEL coupling using simple
copper salts gives the best turnover numbers in small protic
solvents such as alcohols;38 in some cases, DCM is successfully
employed in these trials too. A variety of different solvents
were investigated (Table 1, entries 2−7). EtOH and water gave
32% and 38% yields, respectively, which are slightly lower
yields than those measured in MeOH. MeCN gave a yield of
21%. Trials in DCM, DMF, and hexanes all gave less than 10%
yields, and there was no reactivity observed at all in DMF. The
H2O
a
Reaction conditions: aniline (0.1 mmol), phenylboronic acid (0.2
mmol), 4 (8 mol %), solvent (0.5 mL), base (0.1−0.4 mmol), ca. 20
°C for 24 h in air unless otherwise noted. Isolated yields.
b
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pared to the base free reaction, obtaining a 47% yield (Table 2,
entry 4). KOH and Na3PO4 saw decreased yields of 23% and
26%, respectively (Table 2, entries 5 and 6). A decreased yield
was also observed when using 4 equiv of K2CO3, obtaining a
yield of 74% (Table 2, entry 2), compared to the higher yields
associated with 1 equiv of K2CO3. This reaction was also
attempted in water, where we also saw a slight reduction in
yield, compared to the corresponding MeOH study (Table 2,
entry 7). However, upon adding more base, we noted higher
product formation, where 4 equiv of K2CO3 with 8 mol %
catalyst in water generated a yield of 74% (Table 2, entry 8).
Together, these data indicated that CEL reactions are strongly
little impact on the rate-limiting steps associated with the CEL
coupling reactions. When attempting to couple 2,6-diethylani-
line with phenylboronic acid, we only recovered a 3% yield,
possibility indicating steric interactions are remarkably
impactful to this process. This trend continues when we
moved on to coupling imidazole and benzimidazole to
phenylboronic acid. These reactions produced surprisingly
low yields, compared to the same coupling reactions catalyzed
by copper(II)-phen based systems.15 Once again, it seems that
steric interactions may be playing a significant role in how 4
turns over during the CEL process. Finally, methylbenzylamine
and benzamide were also coupled to phenylboronic acid to
generate C−N bonds with 43% and 12% yields, respectively.
This poorly activated amine and amide highlight alternative
C−N bonds that 4 can generate and new directions for future
reaction optimization. Together, these data show that, over this
relatively simple range of compounds, substituents on either
the boronic acid or aniline have little impact on the overall
reaction yields, but steric interactions and the type of amine
used might play a significant role in this CEL coupling.
Alternatively, this observation could also suggest the electronic
structure of the activated copper NHC complex or donor
properties of the supporting ligand may play more distinctive
roles in promoting CEL coupling. In this situation, the donor
capabilities of the NHC ligand in 4 need to be more fully
explored to dissect their impact on the CEL coupling reaction.
Although we have regularly observed high yields for
diphenylamine from the CEL reactions studied here, there
are also two side products that are regularly identified in our
trials, namely, biphenyl and anisole. Monitoring the reaction of
phenylboronic acid with aniline by GC (Figure 6), we can
2−
supported in protic solvents, and CO3 serves well as an
inexpensive base to move this chemistry forward. That being
said, we suspect ion solubility in MeOH and H2O has an
impact on the measured reactivity in these systems when using
excess base. It seems, under our optimized conditions, the CEL
coupling system is at a “sweet spot” in MeOH, where high
yields are dependent on both reactivity and perhaps solubility.
Using our optimized reaction conditions, we also studied
other phenylboronic acids and amines to demonstrate the
breadth of substituents on the boronic acid and on amine that
can impact CEL coupling (Figure 5). Four different 4-
Figure 5. Products generated from various phenylboronic acids
(shown in black) and amines (shown in blue) illustrating the
substrate scope associated with 4. Yields reported here are isolated
yields from reactions of amine (0.1 mmol), phenylboronic acid (0.2
mmol), K2CO3 (0.1 mmol), and 8 mol % 4 in MeOH at 20 °C under
an aerobic atmosphere.
Figure 6. Relative concentrations of limiting reactants and products
over time for the reaction of aniline (0.1 mmol), phenylboronic acid
(0.2 mmol), K2CO3 (0.1 mmol), and 8 mol % 4 in MeOH at 20 °C
under an aerobic atmosphere over a 24 h period. Concentrations
estimated from GC peak areas normalized to a toluene internal
standard.
substituted phenylboronic acid derivatives (4-cyanophenylbor-
onic acid, 4-chlorophenylboronic acid, 4-methoxyphenylbor-
onic acid, and 4-methylboronic acid) were coupled to aniline
with good yields (85−91%) that compare well with data from
phenylboronic acid trials discussed earlier (Table 2, entry 1)
This indicates that the substituent on the phenylboronic acid
has little impact to the catalytic efficiency of this process, where
activation of the phenylboronic acid is not the rate-
determining step in this catalytic system. Similarly, aniline
derivatives (2-nitroaniline, 3,5-methoxyaniline, and 4-nitroani-
line) coupled to phenylboronic acid well, giving yields of 79,
88, and 84%, respectively. Once again, the data indicate that
inductive and resonance effects associated with the amine have
track aniline consumption and diphenylamine production over
a 24 h time period. Individual GC traces are shown in Figure
S2 in the Supporting Information. On the basis of GC peak
areas, diphenylamine production occurs at two different rates;
the initial rate appears to form ∼40% of the product within the
first 5 h and then slowly forms the next 40% of product
formation over the course of the remaining 19 h. Side product
formation of anisole and biphenyl occurs primarily within the
first hour of the reaction, where their relative concentrations
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do not increase substantially beyond that time point. Product
formation seems to correlate well with the aniline con-
sumption; however, a more systematic and detailed study is
needed to better correlate catalytic efficiency or kinetic
information regarding this process.
The initial catalytic observations made above are consistent
with the proposed mechanism associated with the CEL
coupling (Figure 7). In this case, however, there seems to be
C−N bonds. Similar types of metal-carbene complexes have
been developed previous by Chen and others;24,27,35 however,
to our knowledge, this is the first time that a tetradentate
copper(II) complex has been described that shows good
stability in protic solvents like water and MeOH.38 A series of
catalytic trials were completed with 4, which demonstrate the
capabilities of this catalyst for C−N bond formation through
the aerobic CEL mechanism proposed by a number of
independent research groups.9,14,39−43 Complex 4 also showed
good utility against a range of phenylboronic acid and aniline
derivatives, indicating that resonance and inductive effects play
a small role in this catalytic process. However, when more
sterically hindered amines are used, we see a dramatic decrease
in reactivity, which may be due to the accessibility of the metal
ion during turnover. Overall, complex 4 shows good promise as
a CEL coupling catalyst, but the impact of the coordination
mode and donor ability of this carbene ligand on the electronic
state of the copper(II) ion, the lability of the pyridine ligands,
and the general accessibility of the metal site needed for
catalytic formation of C−N bonds requires further systematic
study.
EXPERIMENTAL SECTION
■
All solvents and reagents were obtained from commercial sources and
were used as received. NMR spectra were obtained using a Bruker
AVANCE III 300 MHz spectrometer at room temperature. 1H
chemical shifts are reported vs TMS and are referenced to the residual
solvent peaks. Mass spectra were obtained using a Bruker UHPLC
microTOF-Q II High Resolution MS system operating in ESI
ionization mode. UV−vis spectroscopy was obtained using an Olis14
UV/vis/NIR spectrophotometer. Single crystal X-ray crystallography
was obtained using a Bruker Venture D8 with an IμS microfocus
source. CCDC 2018628 for compound 4 contains the supplementary
crystallographic data for this paper. This data can be obtained free of
charge from The Cambridge Crystallographic Data Centre. EPR data
were collected on an X-band Varian E-12 at 4 K at the University of
Alabama EPR facility. All electrochemical measurements were
performed on a Solartron SI1287 potentiostat. The supporting
electrolyte was 0.1 M tetraethylammounium hexafluorophosphate
(TEAPF6) in acetonitrile (MeCN) as the solvent. The working
electrode was a 3 mm glassy carbon disk with a platinum wire counter
and Ag/Ag+ ion reference.
Synthesis of 1-(Pyridin-2-ylmethyl)-1H-benzimidazole (1). A
mixture of 2-picolyl chloride hydrochloride (4.17 g, 25.4 mmol),
benzimidazole (3.00 g, 25.4 mmol), and potassium hydroxide (5.75 g,
101.6 mmol) in 60 mL of THF was refluxed for 36 h. The solvent was
removed completely under reduced pressure. Dichloromethane (60
mL) and water (60 mL) were added. The organic layer was extracted
and washed twice with 30 mL portions of H2O. The organic layer was
dried with anhydrous Na2SO4. The solution was filtered, and the
solvent was removed under reduced pressure, giving an off-white solid
(4.48 g, 84%). Compound synthesis was based on a previously
reported method.29 1H NMR (CDCl3, 300 MHz): δ 8.79 (s, 1H),
8.61 (d, 1H, J = 4.5 Hz), 7.90 (d, 1H, J = 8.0 Hz), 7.66 (t, 1H, J = 7.8
Hz), 7.49 (m, 1H), 7.37 (m, 2H), 7.26 (t, 1H, J = 7.0 Hz), 7.16 (d,
2H, J = 7.8 Hz), 5.64 (s, 2H).
Figure 7. Generalized CEL mechanism for C−N bond forming from
aniline and a phenylboronic acid catalyzed by 4.
reasonable evidence that there is an equilibrium between
multiple copper(II) species in solution. We are proposing that
there is an equilibrium between the 4-coordinate complex 4
and a related 5-coordinate species (4′). In the next step of the
mechanism, the phenylboronic acid is activated, replacing the
labile solvent derived ligand in 4′. We expect that one of the
pyridines shows some hemilability, where one of these pyridyl
ligands can slip to afford a 4-coordinate complex (5′).9,39,40
This 4-coordinate complex can then bind and, with the help of
a base, deprotonate the amine, shifting the potential of the
copper(II) complexes where it can be readily oxidized to afford
the oxidation to the copper(III) state (7). Some propose this
oxidation occurs through a disproportionation of two copper-
(II) states.9,11 Complex 7 can go through a reductive
elimination to generate 8, a copper(I) species, which can be
reoxidized to 4 by molecular O2. Considering the catalytic data
reported above, it seems some sterically hindered amines have
poor turnover where aniline and other more accessible amines
can be easily utilized in this system, which suggests there may
be steric clashes between 5′ and some sterically hindered
amines that impact the formation of complex 6, where we
expect this step becomes the rate-determining step of the C−N
bond forming reactions catalyzed by 4. It is easy to imagine
that complex 5′ could also interact with another boronic acid
or solvent molecule in this open coordination site, setting
alternative mechanistic pathways toward side products such as
anisole. Although these side products are not the aim of this
study, these alternative pathways suggest 4 also could be
adapted to target C−O bond forming reactions too.
1,1′-Di(2-picolyl)-3,3′-methylenedibenzimidazolium Dibro-
mide (2). 1-(Pyridin-2-ylmethyl)-1H-benzimidazole (750 mg, 3.6
mmol) in a 10-fold excess of dibromomethane (1.25 mL, 18 mmol)
was heated at reflux for 12 h. The solvent was concentrated, and the
residue was washed several times with THF. The hygroscopic off-
white solid was filtered on a frit and dried under vacuum (996 mg,
94%). Compound synthesis was based on a previously reported
method.29 1H NMR (DMSO-d6, 300 MHz): 10.50 (s, 2H), 8.33 (d,
2H, J = 4.7 Hz), 8.25 (d, 2H, J = 8.2 Hz), 7.91 (d, 2H, J = 8.2 Hz),
7.79 (dt, 2H, J = 1.7 and 7.7 Hz), 7.68−7.55 (m, 6H), 7.46 (s, 2H),
7.29−7.25 (m, 2H), 5.91 (s, 4H).
CONCLUSIONS
In summary, we have reported a new tetradentate NHC
copper(II) complex, which shows good reactivity in generating
■
F
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Organometallics XXXX, XXX, XXX−XXX

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pubs.acs.org/Organometallics
Article
1,1′-Di(2-picolyl)-3,3′-methylenedibenzimidazolium Dihex-
afluorophosphate (3). 1,1′-Di(2-picolyl)-3,3′-methylenedibenzimi-
dazolium dibromide (200 mg, 0.34 mmol) was dissolved in a
minimum amount of water, to which was added 5 equiv of NH4PF6. A
white solid precipitated out of solution and was left for a few minutes
before the solid was collected and dried under vacuum, obtaining 3 as
an off-white solid (227 mg, 93%). Compound synthesis was based on
a previously reported method.29 1H NMR (DMSO-d6, 300 MHz):
10.50 (s, 2H), 8.34 (d, 2H, J = 4.7 Hz), 8.25 (d, 2H, J = 8.2 Hz), 7.91
(d, 2H, J = 8.2 Hz), 7.75 (dt, 2H, J = 1.7 and 7.7 Hz), 7.68−7.55 (m,
6H), 7.46 (s, 2H), 7.29−7.25 (m, 2H), 5.91 (s, 4H).
Patrick E. Sheridan − Department of Chemistry, Mississippi
State University, Mississippi State, Mississippi 39762, United
States
Christopher J. Galloway − Department of Chemistry,
Mississippi State University, Mississippi State, Mississippi
39762, United States
Raymond Femi Awoyemi − Department of Chemistry,
Mississippi State University, Mississippi State, Mississippi
39762, United States
Sean L. Stokes − Department of Chemistry, Mississippi State
University, Mississippi State, Mississippi 39762, United
States
Copper(II)(1,1′-di(2-picolyl)-3,3′-methylenedibenzimidazo-
́
lium) Dihexafluorophosphate (4). 1,1′-Di(2-picolyl)-3,3-methyl-
enedibenzimidazolium dihexafluorophosphate (100 mg, 0.14 mmol)
and Cu(OAc)2·2H2O (27.5 mg, 0.14 mmol) were combined in
MeOH (1 mL) and heated at 50 °C for 3 h, forming a bright orange
precipitate that was filtered and washed with a minimum amount of
MeOH (59 mg, 54%). Crystals suitable for X-ray diffraction were
grown via vapor diffusion of a solution of 4 in CH3CN with Et2O. The
EPR spectra associated with 4 were collected in a 1 mM sample in
CH3CN at 4 K which yielded an axial signal (g = 2.1239). ESI-HRMS
(m/z): observed 246.5598 for [M − 2PF6]2+; calcd 246.5595 for
(C27H22CuN6)2+; observed 493.1224 for [M − 2PF6]+; calcd
493.1196 for (C27H22CuN6)+. Elem. Anal. Calcd for
C27H22CuF12N6P2: C, 41.36; H, 2.83; N, 10.72. Found C, 41.26; H
3.08; N, 11.01
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.organomet.0c00552
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank Bruno Donnadieu and David O. Wipf for helpful
discussion regarding the X-ray crystallography and cyclic
voltammetry, respectively. We also thank B. Pierce and M.
Lockart from the University of Alabama for supporting our
EPR data collection required for this study.
General Procedure for Copper Catalyzed C−N Coupling. A 4
mL scintillation vial with a magnetic stirring bar was charged with
aniline (0.1 mmol), boronic acid (0.2 mmol), and copper complex (8
mol %). Solvent (0.5 mL) was added and stirred for the desired time
and temperature open to air. After completion, the reaction was
purified using silica column chromatography using 9:1 hexane:EtOAc.
All isolated yields reported here are based on mg quantities of product
recovered, where we estimate the level of detection to be ∼1 mg of
complex. 1H NMR data for all complexes are reported in the
Supporting Information (Figures S3−S8). All reported yields should
be considered to 5% of the value reported.
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ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.organomet.0c00552.
■
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CCDC 2018628 contains the supplementary crystallographic
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AUTHOR INFORMATION
Corresponding Author
Joseph P. Emerson − Department of Chemistry, Mississippi
State University, Mississippi State, Mississippi 39762, United
States; orcid.org/0000-0002-7556-1393;
Email: jemerson@chemistry.msstate.edu
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