Synthetic access to ring-expanded N-heterocyclic carbene (Re-NHC) copper complexes and their performance in click chemistry

Article abstract of DOI:10.1021/acs.organomet.1c00039

The facile syntheses of ring-expanded N-heterocyclic carbene (RE-NHC) copper(I) halide complexes are reported. The method makes use of a weak inorganic base in a green solvent. The reaction times can be greatly reduced by use of this weak-base route under microwave irradiation. The easy access to these complexes permits an evaluation of the catalytic activity and reaction profiling of [Cu(RE-NHC)X] complexes in the Huisgen 1,3-cycloaddition reaction.

Full text of DOI:10.1021/acs.organomet.1c00039

pubs.acs.org/Organometallics
Article
Synthetic Access to Ring-Expanded N‑Heterocyclic Carbene (RE-
NHC) Copper Complexes and Their Performance in Click Chemistry
Jonathan W. Hall, Damien Bouchet, Mary F. Mahon, Michael K. Whittlesey, and Catherine S. J. Cazin*
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ABSTRACT: The facile syntheses of ring-expanded N-heterocyclic
carbene (RE-NHC) copper(I) halide complexes are reported. The
method makes use of a weak inorganic base in a green solvent. The
reaction times can be greatly reduced by use of this weak-base route
under microwave irradiation. The easy access to these complexes
permits an evaluation of the catalytic activity and reaction profiling of
[Cu(RE-NHC)X] complexes in the Huisgen 1,3-cycloaddition
reaction.
(Scheme 1b).6 This method developed by Cazin is reminiscent
of the Lin protocol for the synthesis of [Ag(NHC)Cl] using
Ag2O.7 The more recent weak-base approach to [Cu(NHC)Cl]
where the NHC can be readily varied has become the state of
the art, as it can be carried out in air, using reagent-grade
sustainable solvents and weak inorganic bases (Scheme 1c).8
Having a general synthetic access is key to the development
of chemistry/catalysis revolving around specific compositions.
The workhorse in this area has been the complex [Cu(IPr)Cl],
which has enabled fluorination9 and carboxylation10 catalysis,
in addition to the early examples of catalytic reductions.5
The extent of ring expansion of the basic five-membered ring
NHC in copper-mediated catalysis has been much less
explored.11 The reasons for this relative paucity of studies
might be linked to the tedious routes to [Cu(RE-NHC)X]
complexes. Again, the use of the deprotonation with a strong-
base approach appears most used in this area. It is noteworthy
that simple copper complexes bearing members of the RE-
NHC class of ligands (Scheme 2) have not yet been reported
as being accessible using the weak-base method.
INTRODUCTION
■
The use of copper-NHC1 (NHC = N-heterocyclic carbene)
complexes has had a significant effect in permitting important
developments in organic synthesis.2 One class that has been a
longstanding interest of ours has been the simple [Cu(NHC)-
(halide)] system.3 The synthetic methodology leading to such
complexes has evolved significantly since the initial report of
[Cu(IPr)Cl] (IPr = N,N′-bis[2,6-(diisopropyl)phenyl]-
imidazol-2-ylidene)4 by Buchwald and Sadighi in 2003.5
From generating the free carbene in situ or using an isolated
NHC to bind CuCl (Scheme 1a), the synthetic protocol has
increased in simplicity. The reaction was initially carried out
under anaerobic and water-free conditions, where Schlenk
conditions were the norm, but the advent of a simpler method
making use of the reaction of Cu2O with an imidazolium salt
has made the [Cu(NHC)Cl] systems readily accessible
Scheme 1. Evolution of the Synthetic Route to
[Cu(NHC)Cl] Complexes
In combining our expertise and mutual interest in Cu-NHC
chemistry, we disclose here efforts in this direction and present
a practical protocol allowing access to such compounds. The
simpler synthetic access permitted here will undoubtedly allow
researchers to explore and evaluate the performance of these
[Cu(RE-NHC)X] complexes in catalysis.
The role of [Cu(NHC)Cl] and its congeners has been
explored in the copper-mediated azide−alkyne click (Huisgen)
Received: January 21, 2021
Published: April 27, 2021
https://doi.org/10.1021/acs.organomet.1c00039
© 2021 American Chemical Society
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expanded azolium chlorides, and the results of reactions
performed on a 100 mg scale of the azolium chloride are
presented in Table 1. Noteworthy are the lower yields obtained
Scheme 2. Members of the Ring-Expanded N-Heterocyclic
Carbene (RE-NHC) Family Employed in This Study
Table 1. Scope of Azolium Chlorides Used to Yield
a
[Cu(NHC)Cl] Complexes 1−7
time
(h)
NMR conversn
(%)
product (isolated yield
(%))
entry NHC·HCl
1
2
3
4
5
6
7
6Mes
6Xylyl
6Dipp
7Mes
7Xylyl
7Dipp
8Mes
1.5
1.5
1.5
2.5
2.5
2.5
6
94
99
88
94
95
54
95
1 (82)
2 (98)
3 (73)
4 (77)
5 (58)
6 (50)
7 (36)
cycloaddition reactions.12 More recently Dıez-Gonzalez has
reported a study involving some RE-NHC complexes that were
synthesized using CuBr, CuI and the free carbene, generated
by the deprotonation of the RE-NHC salt precursor using a
very strong base (KHMDS).13,14
́
́
a
Reaction conditions: NHC·HCl (100 mg), CuCl (1.2 equiv), K2CO3
(3 equiv), acetone (2 mL), microwave (MW), 80 °C.
Here, in addition to disclosing a facile and practical synthetic
route to the [Cu(RE-NHC)X] motif, our studies allow us to
probe the role of ring size and of the halide on the catalytic
activity in the ubiquitously encountered Huisgen cycloaddition
reaction.
and/or longer reaction times required when sterically more
congested substituents are present on the azolium nitrogens
(e.g., 7Dipp·HCl) and when larger ring sizes are employed
(Table 1, entries 4−7).
The role and effect of varying the identity of the counterion
associated with the azolium salt and the copper source were
also examined in small-scale reactions (Table 2). The reactivity
RESULTS AND DISCUSSION
■
The study into the synthesis [Cu(RE-NHC)Cl] chemistry
begins with exploring the compatibility of the weak-base
method with RE-NHC·HX precursors under conditions
previously employed for five-membered NHCs for copper8
and other metals.15−18
Table 2. Scope of Azolium Halides and Copper Source Used
to Yield [Cu(RE-NHC)X] Complexes 8−11
a
The 6Mes·HX ligand precursor was selected for an initial
screening, and we rapidly found that the 6Mes·HCl salt is best
used under these conditions. 6Mes·HCl is obtained from the
6Mes·HBF4 analogue by anion exchange using Amberlite resin
(see Scheme 3 and the Supporting Information for details).
Scheme 3. Initial Weak-Base Reaction Conditions Leading
to [Cu(6Mes)Cl] (1)
Cu
source
time
(h)
isolated
yield (%)
a
entry
NHC·HX
product
1
2
3
4
5
6
6Mes·HCl
6Mes·HBr
6Dipp·HBr
6Mes·HBr
7Mes·HI
CuI
[Cu(6Mes)I] (8)
[Cu(6Mes)Br] (9)
[Cu(6Dipp)Br] (10)
[Cu(6Mes)I] (8)
[Cu(7Mes)I] (11)
-
6
54
77
98
37
18
-
CuCl
CuCl
CuI
CuCl
CuCl
2.5
2.5
2.5
6
7Dipp·HI
6
a
Reaction conditions: NHC·HX (100 mg), CuCl (1.2 equiv), K2CO3
(3 equiv), acetone (2 mL), MW, 80 °C.
a
Reaction conditions: (1) Amberlite IRA402 chloride resin, MeOH,
obtained is in agreement with previous observations made on
five-membered-ring carbene Cu complex formation8 and
points toward a mechanism involving a cuprate intermediate
of the type [NHC·H][CuXX′]. A combination of halide trans
effect and energy associated with KX formation (salt
precipitation) accounts for the products obtained in reactions
involving mixed halides.
As can be seen, the method proves effective to various
degrees as a function of the copper source and of the azolium
ring size and associated counterion. The larger size RE-NHC
complexes are again troublesome to form and/or isolate.
rt, 16 h; 2) CuCl (100 mg), K2CO3 (2 equiv), acetone (2 mL), 60 °C.
Under an argon atmosphere and upon heating at 60 °C in an
oil bath, the reaction proceeds to yield 61% of the desired
product 1 after 20 h in acetone. Conducting the reaction under
microwave heating (60 °C) reduces the reaction time to 2 h
and provides a 52% yield.
We viewed the microwave approach as being the most rapid
to yield material for catalytic studies. The microwave approach
using the weak base in acetone was then tested on various ring-
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In order to obtain enough of the materials synthesized using
the weak-base method and to benefit from an economy of
scale, gram-scale reactions of the azolium salts were launched.
This also served as proof of the scalability of the synthetic
route. The results of these larger-scale reactions are
summarized in Table 3. Overall, larger-scale reactions afford
the desired materials in modest to very good yields. The
poorer yield obtained for [Cu(6Mes)I] (8, entry 4) is
associated with the poor solubility of the product in the
reaction medium, necessitating extraction from benzene, which
is not a desirable solvent (carcinogen).
We had previously clearly demonstrated that five-membered
imidazole-based NHCs are initially partners in rapidly forming
an imidazolium cuprate compound via simple mixing of
solutions of the azolium and copper source in solution8 or in
the solid state by simple grinding. We have recently expanded
on these observations and confirmed in a study dealing with
mechanochemical synthesis that the weak-base route can be
simply applied using grinding by ball milling.19
Table 3. Larger-Scale Reactions Leading to [Cu(RE-
a
NHC)X] Complexes
In our initial mechanistic studies, the existence of cuprates
shed light on the intermediacy of these ionic compounds along
the weak-base-assisted synthesis. We have also found this to be
the case for the RE-NHC systems. By simple mixing of the
azolium salts and the copper source in the absence of the base,
the cuprates are readily formed. A number of these were
unambiguously characterized by single-crystal X-ray diffraction,
with four examples illustrated in Figure 1. These, all show
hydrogen bonding of the azolium C−H to the [CuCl2]− anion.
The donor (C)−acceptor (Cl) distances in [6MesH][CuCl2]
(13), [7MesH][CuCl2] (15), and [7XylylH][CuCl2] (16) are
in the range 3.4388(19)−3.476(3) Å, noticeably shorter than
that in the N-alkyl derivative [7nPent][CuCl2] (17; 3.560(3)
Å).
time
(h)
isolated yield
b
entry NHC·HX
X
product
(%)
1
2
3
4
6Mes·HCl
7Mes·HCl
6Mes·HBr
6Mes·HBr
Cl
Cl
Cl
I
[Cu(6Mes)Cl] (1)
[Cu(7Mes)Cl] (4)
[Cu(6Mes)Br] (9)
[Cu(6Mes)I] (8)
2
10
4
78
64
82
64
20
a
Reaction conditions: NHC·HX (1 g), CuX (1.2 equiv), K2CO3 (3
equiv), acetone (10 mL), MW, 80 °C. These are isolated yields and
b
are the average of two reactions.
Figure 1. Molecular structures of RE-azolium cuprates 13 and 15−17 (top left to bottom right). Ellipsoids are represented at 30% probability.
Hydrogens, with the exception of H1 (in all cases) and those on the tetrahydrodiazepin-2-ylidene ring (in 16), and the disorder in 15 have been
omitted for clarity. Symmetry operations in 16: (i) 3/2 − x, 3/2 − y, 1/2 − z; (ii) 1/2 − x, y, 1 − z.
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Figure 2. Molecular structures of [Cu(RE-NHC)Cl] complexes 1, 4, 5, and 7 (top left to bottom right). Ellipsoids are represented at 30%
probability, and in all cases hydrogens have been omitted for clarity. For 4, only one of the two molecules in the asymmetric unit of the crystal
structure is shown.
From a mechanistic perspective, the synthetic route leading
to the neutral complexes is identical with that for the five-
membered congeners. We propose the initial formation of the
cuprate azolium, which is converted into the neutral product
via a concerted metalation−deprotonation (CMD) mecha-
nism.18 When the cuprate is reacted with the weak base in
acetone or when all components are mixed together in the
MW reactor, the outcome pleasingly yields the neutral
[Cu(RE-NHC)X] complexes. Full characterization of these is
reported in the Experimental Section along with spectroscopic
and elemental analytical data. The compounds are micro-
crystalline materials that could easily produce single crystals
suitable for diffraction studies. The X-ray crystal structures of
complexes 1, 4, 5, and 7 are presented in Figure 2 (see the
Supporting Information for structures of 8 and 9). The solid-
state structures highlight one of the significant features of RE-
NHC ligands: namely, the variation of NCN angle with ring
size (e.g.: 1, 117.5(2)°;25 4, 118.7(6), 120.5(5)°; 7,
123.05(16)°).
To test the catalytic performance of these RE-NHC
complexes, the Huisgen reaction was selected, as it has been
studied extensively using five-membered imidazole-based
systems.2 Having material in hand in larger amounts allowed
us to probe numerous factors influencing the catalytic
performance of this motif and the influence of its structural
diversity. A simple synthetic access to materials is key in order
to conduct such a study. We began this section of the
investigation by a comparison of (SIMes)CuCl (18), 6Mes
complex 1 and 7Mes complex 4 in the copper-mediated
alkyne−azide cyclization (CuAAC) reaction for three different
combinations of substrates.
Initially exploring the ring-size influence on catalytic
performance of the CuAAC of azidoheptane and phenyl-
acetylene (eq 1, Figure 3a), we note that the order of reactivity
decreases with decreasing ring size and is found to be 7 > 6 > 5
within the substituted mesityl series. This order was found to
reverse when the azide was changed to phenylazide (eqs 2 and
3, Figures 3b,c). Of note was that, after a 300 min reaction
time, the coupling of phenylazide and 1-octyne produced the
product in nearly the same yield with all three catalysts (eq 3,
Figure 3c).
Reaction profiling of a series of [Cu(6Mes)X] (X= F, Cl, Br,
I) complexes permits the first study of the entire halogen group
bound to copper, following the recent disclosure of a synthetic
route to [Cu(6Mes)F] (19).3b For the CuAAC of
azidoheptane and phenylacetylene (eq 1, Figure 4a), all
complexes are fairly effective, with the exception of [Cu-
(6Mes)Cl] (1), which is more sluggish yet still active enough
to reach complete conversion to the triazole in about 300 min.
[Cu(6Mes)I] (8) and the fluoro complex Cu(6Mes)F (19)
work best and reach completion in 75 min. The superior
behavior of the iodo complex had previously been noted.13,20
Both 19 and 8 demonstrate the best activity in the other
systems (eqs 2 and 3, Figures 4b,c), while Cu(6Mes)Br (9)
and 1 continued to perform more sluggishly to afford the order
F ≈ I > Br > Cl. Of note is the significantly enhanced activity
of 19 at an elevated temperature (45 °C) for the CuAAC of
phenyl azide and 1-octyne (Figure 4c). The nature of the effect
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Figure 3. Kinetic profiles of [3 + 2] cycloaddition of (a) azidoheptane
and phenylacetylene (room temperature), (b) phenyl azide and
phenylacetylene (room temperature), and (c) azidobenzene and 1-
octyne (45 °C) by 1, 4, and 18. Lines are visual aids and not curve
fits. Each point represents an average of at least two independent
reactions quenched at that time.
Figure 4. Kinetic profiles of [3 + 2] cycloaddition of (a) azidoheptane
and phenylacetylene (room temperature), (b) phenyl azide and
phenylacetylene (room temperature), and (c) azidobenzene and 1-
octyne (45 °C) by 1, 8, 9, and 19. Lines are visual aids and not curve
fits. Each point represents an average of at least two independent
reactions quenched at that time.
of the halide ligand on reaction kinetics is not yet fully
understood and is the subject of ongoing studies.
CuAAC of phenyl azide and phenylacetylene by an atmosphere
of oxygen, dry air, or compressed air had a deleterious effect on
the efficiency of the reaction when it is catalyzed by 1 (Figure
5). However, introducing even a few microliters of water into
the reaction mixture (Ar atmosphere) led to an enhancement
of the reaction. While it is known that on-water effects can
influence reactivity, the beneficial effect of such small amounts
of water as shown in Figure 5 implies that even small
Figures 3 and 4 illustrate quite clearly that catalytic
performance of the different [(RE-NHC)CuX] catalysts is a
function of the substrate. Our studies also revealed that even
relatively subtle changes to the reaction conditions affected the
activity of an individual catalyst upon a single reaction. We
note that replacing the standard blanket of argon used for the
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performed by Elemental Microanalysis Ltd., Okehampton, Devon,
U.K.
N,N′-Dimesitylformamidine, 6Mes·HBr, 6Dipp·HBr, 6Xylyl·HBr,
7Mes·HI, 7Dipp·HI, 7Xylyl·HI, and their corresponding BF4 salts
were all synthesized following procedures in the literature.21 The
synthesis of 7nPent·HI also followed procedures in the literature.22
Salt exchanges to form RE-NHC·HCl were carried out following
procedures in the literature.23
General Note. The RE-NHC·HCl salts in most cases are
extremely hygroscopic. With excessive heat (ca. 140 °C), Amberlite
IRA402 chloride resin gave a byproduct during attempted conversions
of tetrafluoroborate salts to their chloride analogues. Thus, the resin
was dried instead on a rotary evaporator until the beads fell fluidly.
Although this approach did not completely dry the beads, it allowed
for RE-NHC·HCl salts to be obtained with less difficulty.
6Mes·HCl. 1H NMR (500 MHz, CDCl3): δ 7.64 (s, 1H, NCHN),
3
6.90 (s, 4H, C6Me3H2), 4.13 (t, JHH = 5.8 Hz, 4H, NCH2), 2.61
3
(quint, JHH = 5.8 Hz, 2H, NCH2CH2), 2.30 (s, 12H, o-Me-
C6Me3H2), 2.23 (s, 6H, p-Me-C6Me3H2). 13C{1H} NMR (75 MHz,
CDCl3): δ 153.8 (NCHN), 140.6, 136.6, 134.5, 130.2, 47.2, 21.1,
19.8, 18.1.
6Xylyl·HCl. 1H NMR (300 MHz, CDCl3): δ 7.65 (s, 1H, NCHN),
7.29−7.24 (m, 2H, p-H-C6Me2H3; overlap with residual CHCl3
3
peak), 7.17−7.15 (m, 4H, m-H-C6Me2H3), 4.31 (t, JHH = 5.7 Hz,
Figure 5. Conversions (after 110 min) in the room-temperature [3 +
2] cycloaddition of phenyl azide (100 mol %) and phenylacetylene (1
mmol) catalyzed by 1 (0.5 mol %). Addition of substrates occurred
after 10 min of the catalytic run. Average of two runs.
3
4H, NCH2), 2.67 (quint, JHH = 5.7 Hz, 2H, NCH2CH2), 2.43 (s,
12H, C6Me2H3). 13C{1H} NMR (75 MHz, CDCl3): δ 153.5
(NCHN), 139.0, 135.0, 130.5, 129.7, 47.1, 19.7, 18.2.
6Dipp·HCl. 1H NMR (300 MHz, CDCl3): δ 7.54 (s, 1H, NCHN),
i
3
7.43 (m, 2H, p-H-C6 Pr2H3), 7.25 (d, JHH = 7.8 Hz, 4H, p-H-
i
C6 Pr2H3; overlaps with residual CHCl3 peak), 4.27 (t, 3JHH = 5.7 Hz,
3
4H, NCH2), 3.05 (sept, JHH = 6.7 Hz, 4H, CHMe2), 2.83 (quint,
differences in the dryness of azide and alkyne substrates could
disturb the activity, making meaningful comparisons across
different [(NHC)CuX] complexes difficult.
3JHH = 5.7 Hz, 2H, NCH2CH2), 1.38 (d, JHH = 6.7 Hz, 12H,
3
CHMe2), 1.23 (d, JHH = 6.8 Hz, 12H, CHMe2). 13C{1H} NMR (75
3
MHz, CDCl3): δ 153.0 (NCHN), 145.8, 136.0, 131.3, 125.3, 49.3,
29.0, 25.0, 24.9, 19.5.
7Mes·HCl. 1H NMR (500 MHz, CDCl3): δ 7.22 (s, 1H, NCHN),
6.94 (s, 4H, C6Me3H2), 4.67 (m, 4H, NCH2), 2.57 (quint, 3JHH = 5.6
Hz, 4H, NCH2CH2), 2.41 (s, 12H, o-Me-C6Me3H2), 2.27 (s, 6H, p-
Me-C6Me3H2). 13C{1H} NMR (75 MHz, CDCl3): δ 158.0 (NCHN),
140.3, 139.6, 133.9, 130.3, 54.8, 25.4, 21.1, 18.5.
SUMMARY AND CONCLUSIONS
■
The weak-base synthetic route leading to [Cu(NHC)X]
complexes has been shown to be fully compatible with the
[Cu(RE-NHC)X] architecture. Here the use of sustainable
reagents and green solvents is noteworthy. The simple
synthetic route will surely encourage efforts in the exploration
of chemistry mediated by these now readily accessible
complexes. The existence of imidazolium cuprate intermedi-
ates is again confirmed and mimics what has been found for
five-membered congeners. In terms of catalysis, we have
explored the CuAAC reaction, but this time investigating three
different reactions, and found that there is no universal catalyst
for the Huisgen reaction. Some generalizations can be drawn,
but realistically, ease of access not only to the final complex but
also to the azolium precursor must be considered before
finalizing the catalyst selection.
7Xylyl·HCl. 1H NMR (500 MHz, CDCl3): δ 7.27 (s, 1H, NCHN),
7.22 (dd, 3JHH = 8.7, 6.3 Hz, 2H, p-H-C6Me2H3), 7.17−7.11 (m, 4H,
m-H-C6Me2H3), 4.71 (m, 4H, NCH2), 2.59 (m, 4H, NCH2CH2),
2.47 (s, 12H, C6Me2H3). 13C{1H} NMR (75 MHz, CDCl3): δ 157.8
(NCHN), 141.8, 134.3, 130.3, 129.8, 54.8, 25.5, 18.6.
7Dipp·HCl. 1H NMR (300 MHz, CDCl3): δ 7.40 (dd, J = 8.4, 7.2
i
i
Hz, 2H, p-H-C6 Pr2H3), 7.25−7.22 (m, 5H, m−H-C6 Pr2H3
+
3
NCHN), 4.74 (m, 4H, NCH2), 3.23 (sept, JHH = 6.8 Hz, 4H,
3
CHMe2), 2.64 (m, 4H, NCH2CH2), 1.39 (d, JHH = 6.8 Hz, 12H,
CHMe2), 1.24 (d, JHH = 6.8 Hz, 12H, CHMe2). 13C{1H} NMR (75
3
MHz, CDCl3): δ 157.1 (NCHN), 145.0, 139.1, 131.0, 125.4, 56.2,
29.1, 25.2, 25.1, 24.8.
7nPent·HCl. 1H NMR (500 MHz, CDCl3): δ 9.37 (s, 1H,
NCHN), 3.75 (m, 4H, NCH2CH2), 3.65 (s, 4H, NCH2CMe3), 2.19
(m, 4H, NCH2CH2), 1.06 (s, 18H, NCH2CMe3). 13C{1H} NMR
(126 MHz, CDCl3): 162.7 (NCHN), 69.6, 52.7, 33.4, 27.8, 25.4.
8Mes·HCl. 1H NMR (300 MHz, CDCl3): δ 7.38 (s, 1H, NCHN),
6.93 (s, 4H, C6Me3H2), 4.86 (br s, 4H, NCH2), 2.41 (s, 12H, o-Me-
C6Me3H2), 2.35−2.21 (s, 10H, p-Me-C6Me3H2 + NCH2CH2), 2.17−
2.06 (m, 2H, NCH2CH2CH2). 13C{1H} NMR (75 MHz, CDCl3): δ
158.1 (NCHN), 142.0, 140.1, 133.7, 130.4, 53.8, 28.4, 21.0, 18.8.
Synthesis of 8Mes·HBr. 1,5-Dibromopentane (486 μL, 3.57
mmol), N,N′-dimesitylformamidene (1.00 g, 3.57 mmol), K2CO3
(493 mg, 3.57 mmol), and MeCN (10 mL) were placed in a 10−20
mL microwave vial, which was sealed and heated in a microwave
reactor at 110 °C for 12 h. The suspension was then filtered, washed
with MeCN (2 × 5 mL), and dried under vacuum to afford an oil.
Et2O was added with vigorous stirring to the oil to yield a white
precipitate. This was recrystallized from CH2Cl2/pentane to give an
off-white powder (843 mg, 55% yield). 1H NMR (500 MHz, CDCl3):
EXPERIMENTAL SECTION
■
General Considerations. All manipulations were carried out
using standard Schlenk, high-vacuum and glovebox techniques unless
otherwise stated. Reagent-grade K2CO3 was used after being left at
140 °C overnight and ground in the glovebox to a fine powder.
Solvents were purified using an MBraun SPS solvent system (hexane,
Et2O, pentane), under a nitrogen atmosphere from sodium
benzophenone ketyl (benzene), with Drierite (acetone) or standing
over activated 3 Å molecular sieves (MeCN). For catalytic studies,
reagent-grade acetone (Sigma-Aldrich) was used as received. NMR
solvents were dried and vacuum-transferred (C6D6 from K, CD2Cl2/
CDCl3 from CaH2). NMR spectra were recorded at 298 K on Bruker
Avance 300, 400, and 500 and Agilent 500 MHz NMR spectrometers
and referenced to solvent signals as follows: benzene (1H, δ 7.16;
13C{1H}, δ 128.0), CD2Cl2 (δ 5.32; δ 54.0), CDCl3 (δ 7.24; δ 77.2).
All 13C{1H} resonances were singlets. Elemental analyses were
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Article
δ 7.38 (s, 1H, NCHN), 6.93 (s, 4H, C6Me3H2), 4.85 (br s, 4H,
NCH2CH2), 2.41 (s, 12H, o-Me-C6Me3H2), 2.30−2.26 (m, 10H, p-
Me-C6Me3H2 + NCH2CH2), 2.15−2.10 (m, 2H, NCH2CH2CH2).
ESI-TOF MS: [M]+ m/z 349.2643 (theoretical m/z 349.2644).24
General Synthetic Procedure for [Cu(RE-NHC)X]. In a
glovebox, NHC·HX (0.3 mmol), CuCl (0.36 mmol, 1.2 equiv), and
acetone (2 mL) were loaded into a 2−5 mL microwave vial. The
mixture was stirred for 5 min before the addition of K2CO3 (3 equiv),
and then the vial was sealed/capped. For larger-scale reactions, the
same procedure was adopted using NHC·HX (1.00 g), CuCl (1.1
equiv), and acetone (10 mL) in a 10−20 mL microwave vial. The
vials were then heated in a microwave reactor for the allocated time
and reloaded into the glovebox, whereupon the suspension was
filtered through Celite. The filtrate was reduced to dryness, the
residue was extracted into CH2Cl2, and the solution was filtered
through a silica plug to afford, upon concentration in vacuo, a white
precipitate. Crystalline samples of all [Cu(RE-NHC)X] complexes
were obtained from CH2Cl2/pentane unless otherwise stated.
[(6Mes)CuI] (8) and [(7Mes)CuI] (11) were extracted with C6H6
before filtering through silica with CH2Cl2. Once they were purified,
these compounds only redissolved into solution at elevated temper-
atures.
C21H26N2ClCu: C, 62.21; H, 6.46; N, 6.19. Found: C, 62.02; H,
6.36; N, 6.87.
[Cu(7Dipp)Cl] (6). This complex was prepared as for 1 with 7Dipp·
HCl (100 mg, 0.22 mmol), CuCl (26 mg, 0.26 mmol), and K2CO3
(91 mg, 0.66 mmol) to give 6 as a white powder in 50% yield (57
1
mg). H NMR (500 MHz, CD2Cl2): δ 7.37 (t, J = 7.7 Hz, 2H, p-H-
i
i
C6 Pr2H3), 7.24 (d, 3JHH = 7.7 Hz, 4H, m-H-C6 Pr2H3), 3.97 (m, 4H,
3
3
NCH2), 3.27 (sept, JHH = 6.9 Hz, 4H, CHMe2), 2.33 (quint, JHH
=
2.7 Hz, 4H, NCH2CH2), 1.35 (d, 3JHH = 6.9 Hz, 12H, CHMe2), 1.33
(d, JHH = 6.9 Hz, 12H, CHMe2). 13C{1H} NMR (126 MHz,
3
CD2Cl2): δ 210.3 (NCN), 145.6, 144.6, 129.2, 125.1, 54.4, 29.2, 25.6,
24.9, 24.7. 1H NMR (500 MHz, C6D6): δ 7.17−7.14 (m, p-H-
i
3
C6 Pr2H3, 2H; partially obscured by C6D5H), 7.05 (d, JHH = 7.8 Hz,
i
4H, m-H-C6 Pr2H3), 3.26 (m, 4H, NCH2), 3.18 (sept, 3JHH = 6.9 Hz,
4H, CHMe2), 1.61 (m, 4H, NCH2CH2), 1.48 (d, 3JHH = 6.9 Hz, 12H,
3
CHMe2), 1.18 (d, JHH = 6.9 Hz, 12H, CHMe2). Data match those
found in the literature.26
[Cu(8Mes)Cl] (7). This complex was prepared as for 1 with 8Mes·
HCl (100 mg, 0.26 mmol), CuCl (31 mg, 0.31 mmol), and K2CO3
(108 mg, 0.78 mmol) to give 7 as a white powder in 36% yield (42
1
mg). H NMR (500 MHz, CD2Cl2): δ 6.96 (s, 4H, C6Me3H2), 4.04
(t, 3JHH = 6.4 Hz, 4H, NCH2), 2.37 (s, 12H, o-Me-C6Me3H2), 2.29 (s,
6H, p-Me-C6Me3H2), 2.12−1.96 (m, 8H, NCH2CH2CH2). 13C{1H}
NMR (126 MHz, CD2Cl2): δ 208.4 (NCN; via HMBC), 147.2, 137.9,
134.4, 130.2, 52.2, 29.4, 22.0, 21.1, 19.2. Anal. Calcd for
C24H32N2ClCu: C, 64.41; H, 7.42; N, 6.25. Found: C, 63.76; H,
7.21; N, 6.24.
[Cu(6Mes)Cl] (1). This complex was prepared by the general
synthetic procedure with 6Mes·HCl (100 mg, 0.28 mmol), CuCl (33
mg, 0.34 mmol) and K2CO3 (116 mg, 0.84 mmol) to afford 1 as a
white powder in 82% yield (96 mg). 1H NMR (500 MHz, CD2Cl2): δ
7.00 (s, 4H, C6Me3H2), 3.35 (t, J = 5.9 Hz, 6H, NCH2), 2.32−2.29
1
[Cu(6Mes)I] (8). This complex was prepared as for 1 with 6Mes·
HCl (100 mg, 0.28 mmol), CuI (64 mg, 0.34 mmol), and K2CO3
(116 mg, 0.84 mmol) to give 8 as a white powder in 54% yield (77
mg). 1H NMR (500 MHz, CDCl3): δ 6.93 (s, 4H, C6Me3H2), 3.36 (t,
(m, 20H, C6Me3H2 + NCH2CH2). H NMR (500 MHz, CDCl3): δ
6.93 (s, 4H, C6Me3H2), 3.36 (m, 4H, NCH2), 2.31 (m, 2H,
NCH2CH2), 2.29−2.26 (m, 18H, C6Me3H2). 13C{1H} NMR (126
MHz, CDCl3): δ 201.0 (NCN), 142.1, 138.2, 134.6, 130.0, 44.3, 21.2,
18.1. Anal. Calcd for C22H28ClCuN2: C, 62.99; H, 6.73; N, 6.68.
Found: C, 62.32; H, 6.69; N, 6.56. Data match those found in the
literature.25
[Cu(6Xylyl)Cl] (2). This complex was prepared as for 1 with 6Xylyl·
HCl (100 mg, 0.31 mmol), CuCl (36 mg, 0.37 mmol), and K2CO3
(126 mg, 0.92 mmol) to give 2 as a white powder in 98% yield (117
3
3JHH = 5.9 Hz, 4H, NCH2), 2.32 (quint, JHH = 6.1 Hz, 2H,
NCH2CH2), 2.28 (s, 18H, C6Me3H2). 13C{1H} NMR (126 MHz,
CDCl3): δ 202.9 (NCN), 141.7, 138.3, 134.7, 129.9, 44.4, 21.2, 21.0,
18.2. 1H NMR (500 MHz, C6D6): δ 6.75 (s, 4H, C6Me3H2), 2.48 (m,
4H, NCH2), 2.12 (s, 12H, o-Me-C6Me3H2), 2.08 (s, 6H, p-Me-
C6Me3H2), 1.38−1.27 (m, 2H, NCH2CH2). 13C NMR (126 MHz,
C6D6): δ 203.6 (NCN; via HMBC), 142.1, 138.2, 134.7, 130.1, 43.8,
21.1, 20.6, 18.1. Anal. Calcd for C22H28N2ICu: C, 51.72; H, 5.52; N,
5.48. Found: C, 51.70; H, 5.52; N, 5.54. Data match those found in
the literature.13
1
3
mg). H NMR (500 MHz, CD2Cl2): δ 7.24 (dd, JHH = 8.6, 6.3 Hz,
2H, p-H-C6Me2H3), 7.19 (d, 3JHH = 7.4 Hz, 4H, m-H-C6Me2H3), 3.41
3
(t, JHH = 5.9 Hz, 4H, NCH2), 2.39−2.34 (m, 14H, C6Me2H3
+
NCH2CH2). 13C{1H} NMR (126 MHz, CD2Cl2): δ 200.7 (NCN),
144.9, 135.6, 129.3, 128.7, 44.5, 21.1, 18.3. Anal. Calcd for
C20H24ClN2Cu: C, 61.37; H, 6.18; N, 7.16. Found: C, 61.48; H,
6.14; N, 7.27.
[Cu(6Mes)Br] (9). This complex was prepared as for 1 with 6Mes·
HBr (100 mg, 0.25 mmol), CuCl (30 mg, 0.30 mmol), and K2CO3
(103 mg, 0.75 mmol) to give 9 as a white powder in 77% yield (89
1
mg). H NMR (500 MHz, CD2Cl2): δ 6.99 (s, 4H, C6Me3H2), 3.35
[Cu(6Dipp)Cl] (3). This complex was prepared as for 1 with 6Dipp·
HCl (100 mg, 0.25 mmol), CuCl (29 mg, 0.30 mmol), and K2CO3
(102 mg, 0.74 mmol) to give 3 as a white powder in 73% yield (90
mg). 1H NMR (500 MHz, CDCl3): δ 7.36 (t, 3JHH = 7.7 Hz, 2H, p-H-
(m, 4H, NCH2), 2.34−2.27 (m, 20H, C6Me3H2 + NCH2CH2).
13C{1H} NMR (126 MHz, CD2Cl2): δ 201.6 (NCN; via HMBC),
142.5, 138.6, 135.2, 130.0, 44.7, 21.2, 21.2, 18.2. 1H NMR (500 MHz,
i
3
i
3
C6 Pr2H3), 7.21 (d, JHH = 7.7 Hz, 4H, m-H-C6 Pr2H3), 3.42 (m, 4H,
CDCl3): δ 6.93 (s, 4H, C6Me3H2), 3.36 (t, JHH = 5.9 Hz, 4H,
3
NCH2), 3.06 (sept, JHH = 6.9 Hz, 4H, CHMe2), 2.37 (m, 2H,
NCH2), 2.35−2.29 (m, 2H, NCH2CH2), 2.28 (s, 12H, o-Me-
C6Me3H2), 2.27 (s, 6H, p-Me-C6Me3H2). 13C{1H} NMR (126
MHz, CDCl3): δ 201.5 (NCN), 142.0, 138.2, 134.6, 130.0, 44.3, 21.2,
21.0, 18.1. Anal. Calcd for C22H28N2BrCu: C, 56.96; H, 6.08; N, 6.04.
Found: C, 57.09; H, 6.10; N, 5.96. Data match those found in the
literature.13
[Cu(6Dipp)Br] (10). This complex was prepared as for 1 with
6Dipp·HBr (100 mg, 0.21 mmol), CuCl (25 mg, 0.25 mmol), and
K2CO3 (86 mg, 0.62 mmol) to give 10 as a white powder in 89% yield
3
3
NCH2CH2), 1.35 (d, JHH = 6.9 Hz, 12H, CHMe2), 1.31 (d, JHH
=
6.9 Hz, 12H, CHMe2). 13C{1H} NMR (126 MHz, CDCl3): δ 201.0
(NCN), 145.6, 141.6, 129.6, 124.9, 46.4, 28.8, 25.0, 24.8, 20.7. Data
match those found in the literature.26
[Cu(7Mes)Cl] (4). This complex was prepared as for 1 with7Mes·
HCl (100 mg, 0.27 mmol), CuCl (32 mg, 0.32 mmol), and K2CO3
(112 mg, 0.81 mmol) to give 4 as a white powder in 77% yield (90
1
mg). H NMR (500 MHz, CD2Cl2): δ 6.98 (s, 4H, C6Me3H2), 3.86
1
3
(m, 4H, NCH2), 2.37 (s, 12H, o-Me-C6Me3H2), 2.32−2.26 (m, 10H,
p-Me-C6Me3H2 + NCH2CH2). 13C{1H} NMR (126 MHz, CD2Cl2): δ
210.2 (NCN), 144.9, 138.2, 134.8, 130.0, 52.9, 26.0, 21.1, 18.7. Anal.
Calcd for C23H30ClCuN2: C, 63.73; H, 6.98; N, 6.46. Found: C,
63.65; H, 7.05; N, 6.55.
[Cu(7Xylyl)Cl] (5). This complex was prepared as for 1 with 7Xylyl·
HCl (100 mg, 0.29 mmol), CuCl (35 mg, 0.30 mmol), and K2CO3
(121 mg, 0.88 mmol) to give 5 as a white powder in 58% yield (69
mg). 1H NMR (500 MHz, CD2Cl2): δ 7.25−7.12 (m, 6H, C6Me2H3),
3.91 (m, 4H, NCH2), 2.42 (s, 12H, C6Me2H3), 2.32 (m, 4H,
NCH2CH2) 13C{1H} NMR (126 MHz, CD2Cl2): δ 210.7 (NCN),
147.3, 135.2, 129.5, 128.5, 52.8, 26.1, 18.9. Anal. Calcd for
(100 mg). H NMR (500 MHz, CD2Cl2): δ 7.41 (t, JHH = 7.7 Hz,
i
i
2H, p-H-C6 Pr2H3), 7.25 (d, 3JHH = 7.8 Hz, 4H, m-H-C6 Pr2H3), 3.42
3
(m, 4H, NCH2), 3.08 (sept, JHH = 6.9 Hz, 4H, CHMe2), 2.36 (m,
2H, NCH2CH2), 1.33 (d, 3JHH = 6.9 Hz, 12H, CHMe2), 1.31 (d, 3JHH
= 7.0 Hz, 12H, CHMe2). 13C{1H} NMR (126 MHz, CD2Cl2): δ
201.3 (NCN), 146.2, 142.0, 129.6, 125.0, 46.7, 29.0, 25.0, 24.7, 20.8.
Anal. Calcd for C28H40N2BrCu·CH2Cl2: C, 55.03 H, 6.69; N, 4.43.
Found: C, 55.54; H, 6.74; N, 4.41.
[Cu(7Mes)I] (11). This complex was prepared as for 1 with 7Mes·
HCl (100 mg, 0.23 mmol), CuI (53 mg, 0.28 mmol), and K2CO3 (96
mg, 0.69 mmol) to give 11 as a white powder in 18% yield (22 mg).
1H NMR (500 MHz, CDCl3): δ 6.92 (s, 4H, C6Me3H2), 3.87 (m, 4H,
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NCH2), 2.35 (s, 12H, o-Me-C6Me3H2), 2.31 (m, 4H, NCH2CH2),
2.27 (s, 6H, p-Me-C6Me3H2). 1H NMR (300 MHz, C6D6): δ 6.78 (s,
4H, C6Me3H2), 3.05 (m, 4H, NCH2), 2.22 (s, 12H, o-Me-C6Me3H2),
2.11 (s, 6H, p-Me-C6Me3H2), 1.49 (quint, J = 2.9 Hz, 4H,
NCH2CH2). Data match those found in the literature.13
was sonicated before a 0.3 mL sample was taken and diluted with
CH2Cl2 (0.9 mL) for GC analysis.
1-Azidoheptane. 1-Bromoheptane (6.2 mL, 39.2 mmol) was
added to a solution of NaN3 (2.8 g in 86 mL of DMSO, 43.0 mmol).
The reaction mixture was stirred at room temperature for 5 h to
obtain full conversion by NMR spectroscopy. The solution was
cooled to 0 °C, and water (150 mL) was introduced to quench the
reaction. The mixture was extracted with Et2O (3 × 100 mL), and the
combined organic phases were washed with water (4 × 150 mL) and
brine (2 × 150 mL), dried with MgSO4, filtered, and concentrated in
vacuo to afford the product as a colorless oil (4.93 g, 89%). 1H NMR
(300 MHz, CDCl3): δ 3.26 (t, J = 7.0 Hz, 2H), 1.70−1.49 (m, 2H),
1.46−1.16 (m, 8H), 1.01−0.78 (m, 3H). Data match those found in
the literature.23,27
[Cu(7nPent)Cl] (12). This complex was prepared as for 1 with
[7nPent]HCl (100 mg, 0.364 mmol), CuCl (43.2 mg, 0.437 mmol),
and K2CO3 (151 mg, 1.09 mmol) to give 12 as a white powder in 19%
yield (22 mg). 1H NMR (500 MHz, CD2Cl2): δ 3.75 (s, 4H,
NCH2CMe3), 3.58 (m, 4H, NCH2CH2), 1.92 (m, 4H, NCH2CH2),
1.03 (s, 18H, NCH2CMe3). 13C{1H} NMR (126 MHz, CD2Cl2): δ
212.5 (NCN), 75.3, 54.2, 33.0, 28.0, 25.1. Anal. Calcd for
C15H30N2ClCu: C, 53.40; H, 8.96; N, 8.30. Found: C, 53.14; H,
8.73; H, 7.95.
Azidobenzene. A suspension of distilled aniline (6.0 mL, 66.4
mmol) in water (50 mL) was cooled to 0 °C. Concentrated 96%
sulfuric acid (14.0 mL, 263 mmol) was carefully added to the mixture
followed by the dropwise introduction of a sodium nitrite aqueous
solution (5.3 g in 31 mL of water, 76.1 mmol). The reaction mixture
was warmed to room temperature, and n-hexane (100 mL) was
added. After a slow and portionwise introduction of NaN3 (4.6 g, 70.8
mmol), the biphasic mixture was vigorously stirred at room
temperature for 3 h (NMR monitoring). The organic layer was
then collected, dried with Na2SO4, filtered, and concentrated in vacuo
[6MesH][CuCl2] (13). 6Mes·HCl (100 mg, 0.28 mmol) and CuCl
(31 mg, 0.31 mmol) were placed in a vial in the glovebox, and 1 mL
acetone was added. The mixture was stirred for 1 h and then filtered
through Celite. The filtrate was reduced to dryness to afford 13 as a
white powder in 75% yield (96 mg). Crystalline material was isolated
1
from CH2Cl2/pentane. H NMR (500 MHz, CDCl3): δ 7.70 (s, 1H,
NCHN), 6.98 (s, 4H, C6Me3H2), 4.00 (t, 3JHH = 5.7 Hz, 4H, NCH2),
3
2.64 (quint, JHH = 5.8 Hz, 2H, NCH2CH2), 2.34 (s, 12H, o-Me-
C6Me3H2), 2.30 (s, 6H, p-Me-C6Me3H2). 13C{1H} NMR (126 MHz,
CDCl3): δ 154.4 (NCHN), 141.0, 136.3, 134.3, 130.5, 46.8, 21.2,
19.7, 18.1. Anal. Calcd for C22H29Cl2CuN2: C, 57.96; H, 6.41; N,
6.14. Found: C, 57.52; H, 6.47; N, 6.14.
1
to afford the product as a dark red oil (6.02 g, 76%). H NMR (400
MHz, CDCl3): δ 7.41−7.32 (m, 2H), 7.19−7.10 (m, 1H), 7.07−7.01
(m, 2H). EI-MS: m/z 119 [M]+. Data match those found in the
literature.28
[6XylylH][CuCl2] (14). This complex was prepared as for 13 with
6Xylyl·HCl (100 mg, 0.34 mmol) and CuCl (30 mg, 0.31 mmol) to
give 14 as a white powder in 31% yield (23 mg). 1H NMR (500 MHz,
CDCl3): δ 7.80 (s, 1H, NCHN), 7.32−7.26 (m, 2H, p-H-C6Me2H3),
1,4-Diphenyl-1H-1,2,3-triazole. The typical catalytic procedure
was applied to phenylacetylene (110 μL) and azidobenzene (110 μL).
The crude reaction mixture was dissolved in CH2Cl2, filtered through
a silica plug, and recrystallized from CH2Cl2/pentane to yield an off-
white solid. 1H NMR (300 MHz, CDCl3): δ 8.20 (s, 1H), 7.97−7.87
(m, 2H), 7.85−7.76 (m, 2H), 7.61−7.51 (m, 2H), 7.52−7.42 (m,
3H), 7.42−7.33 (m, 1H). 13C{1H} NMR: (101 MHz, CDCl3) δ
148.6, 137.2, 130.4, 129.9, 129.1, 128.9, 128.6, 126.0, 120.7, 117.7.
Data match those found in the literature.29
4-Hexyl-1-phenyl-1H-1,2,3-triazole. The typical catalytic proce-
dure was applied to oct-1-yne (150 μL) and azidobenzene (110 μL)
at 45 °C. The crude reaction mixture was dissolved in CH2Cl2, filtered
through a silica plug, and recrystallized from CH2Cl2/pentane at −30
°C to yield an off-white solid, which liquified at room temperature. 1H
NMR (400 MHz, CDCl3): δ 7.77−7.68 (m, 3H), 7.55−7.46 (m, 2H),
7.45−7.37 (m, 1H), 2.79 (t, J = 7.6 Hz, 2H), 1.73 (quint, J = 7.6 Hz,
2H), 1.49−1.22 (m, 6H), 0.89 (t, J = 7.1 Hz, 3H). 13C{1H} NMR
(101 MHz, CDCl3): δ 149.3, 137.4, 129.8, 128.6, 120.6, 118.9, 31.7,
29.5, 29.1, 25.8, 22.7, 14.2. Data match those found in the literature.30
1-Heptyl-4-phenyl-1H-1,2,3-triazole. The typical catalytic proce-
dure was applied to phenylacetylene (110 μL) and 1-azidoheptane
(160 μL) at room temperature. The crude reaction mixture was
dissolved in CH2Cl2, filtered through a silica plug, and concentrated
to yield an off-white solid. 1H NMR (400 MHz, CDCl3): δ 7.87−7.79
(m, 2H), 7.74 (s, 1H), 7.47−7.38 (m, 2H), 7.37−7.29 (m, 1H), 4.39
(t, J = 7.2 Hz, 2H), 1.94 (m, 2H), 1.42−1.20 (m, 8H), 0.88 (t, J = 7.0
Hz, 3H). 13C{1H} NMR (101 MHz, CDCl3): δ 147.8, 130.8, 128.9,
128.2, 125.8, 119.5, 50.6, 31.7, 30.5, 28.8, 26.6, 22.6, 14.1. Data match
those found in the literature.28
X-ray Crystallography. Data for all crystallographic studies were
obtained using an Agilent Xcalibur diffractometer and a Mo Kα
source. All experiments were conducted at 150 K, solved using
SHELXT,31 and refined using SHELXL32 via the Olex233 interface.
Aside from the following points of note, the refinements were
generally unremarkable. The asymmetric unit in 16 was seen to
contain one cation and two crystallographically independent
[CuCl2]− halves. There is evidence for C−H···Cl interactions in the
gross structure. H1 (attached to C1) was located and refined without
restraints in the structure of 17. There is also evidence for C−H···Cl
interactions in the asymmetric unit in this structure. The asymmetric
unit in 4 was noted to comprise two independent molecules. While
this latter structure determination is unambiguous, twinning of the
3
3
7.19 (d, JHH = 7.7 Hz, 4H, m-H-C6Me3H2), 4.05 (t, JHH = 5.7 Hz,
3
4H, NCH2), 2.67 (quint, JHH = 5.8 Hz, 2H, NCH2CH2), 2.40 (s,
12H, C6Me2H3). 13C{1H} NMR (126 MHz, CDCl3): δ 154.2
(NCHN), 138.6, 134.7, 130.8, 129.9, 46.7, 19.7, 18.2. Anal. Calcd for
C20H25N2ClCu: C, 56.14; H, 5.89; N, 6.55. Found: C, 55.64; H, 5.89;
N, 6.44.
[7MesH][CuCl2] (15). This complex was prepared as for 13 with
7Mes·HCl (100 mg, 0.27 mmol) and CuCl (30 mg, 0.31 mmol), to
give 15 as a while powder in 74% yield (93 mg). Crystalline material
1
was isolated from CH2Cl2/pentane. H NMR (500 MHz, CDCl3): δ
7.38 (s, 1H, NCHN), 6.97 (s, 4H, m-H-C6Me3H2), 4.33 (br s, 4H,
NCH2), 2.58 (br s, 4H, NCH2CH2), 2.39 (s, 12H, o-Me-C6Me3H2),
2.28 (s, 6H, p-Me-C6Me3H2). 13C{1H} NMR (126 MHz, CDCl3): δ
158.7 (NCHN), 140.7, 139.3, 133.6, 130.6, 55.1, 25.6, 21.1, 18.4.
[7XylylH][CuCl2] (16). This complex was prepared as for 13 with
7Xylyl·HCl (100 mg, 0.29 mmol) and CuCl (32 mg, 0.32 mmol) to
give 16 as a white powder in 12% yield (15 mg). Crystalline material
1
was isolated from CH2Cl2/pentane. H NMR (500 MHz, CDCl3): δ
7.43 (s, 1H, NCHN), 7.30−7.25 (m, 2H, p-H-C6Me2H3), 7.18 (d,
3JHH = 7.7 Hz, 4H, m-H-C6Me2H3), 4.39 (m, 4H, NCH2), 2.61 (m,
4H, NCH2CH2), 2.46 (s, 12H, o-Me-C6Me2H3). 13C{1H} NMR (126
MHz, CDCl3): δ 158.5 (NCHN), 141.6, 134.0, 130.1, 55.1, 25.6, 18.5.
Anal. Calcd. for C21H27N2Cl2Cu: C, 57.08; H, 6.16, N, 6.34. Found:
C, 55.33; H, 5.83; N, 6.07.
[7nPentH][CuCl2] (17). This complex was prepared as for 13 with
7nPent·HCl (100 mg, 0.37 mmol) and CuCl (40 mg, 0.40 mmol) to
1
give 17 as a white powder in 91% yield (123 mg). H NMR (500
MHz, CDCl3): δ 7.85 (s, 1H, NCHN), 3.86 (m, 4H, NCH2CH2),
3.47 (s, 4H, NCH2CMe3), 2.24 (m, 4H, NCH2CH2), 1.03 (s, 18H,
NCH2CMe3) 13C{1H} NMR (126 MHz, CDCl3): δ 160.6 (NCHN),
70.6, 53.1, 33.5, 27.8, 25.2. Anal. Calcd for C15H31N2Cl2Cu: C, 48.19;
H, 8.36; N, 7.49. Found: C, 46.60; H, 7.91; N, 7.06.
General Procedure for Catalytic Experiments. In a dry argon
glovebox [Cu(NHC)X] (5 × 10−3 mmol) was weighed into a 4 mL
screw-cap vial. To this was added the alkyne (1 mmol) followed by
the azide (1 mmol) to start the reaction. The vial was closed, removed
from the glovebox, and remained sealed while the contents were
stirred at the designated temperature for the appropriate time, after
which it was quenched with CH2Cl2 (3 mL) in air. The suspension
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sample (although resolved) compromised the raw data to a degree.
This legacy is evidenced in the R(int) value and the estimated
standard deviations pertaining to the unit cell parameters.
Crystallographic data for all compounds have been deposited with
the Cambridge Crystallographic Data Centre as supplementary
publications CCDC 2016583 (compound 13), 2016584 (15),
2016585 (16), 2016586 (17), 2016587 (1), 2016588 (4), 2016589
(5), 2016590 (1), 2016591 (9; see the Accession Codes paragraph)
and 2016592 (8; see the Accession Codes paragraph), respectively.
Copper N-heterocyclic carbene complexes in catalysis. Catal. Sci.
Technol. 2013, 3, 912−926. (c) Lazreg, F.; Nahra, F.; Cazin, C. S. J.
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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.1c00039.
■
sı
Experimental details and multinuclear NMR spectra of
all complexes (PDF)
Accession Codes
CCDC 2016583−2016592 contain the supplementary crys-
tallographic 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
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
AUTHOR INFORMATION
Corresponding Author
■
Catherine S. J. Cazin − Department of Chemistry and Center
for Sustainable Chemistry, Ghent University, Ghent 9000,
Belgium; orcid.org/0000-0002-9094-8131;
Email: catherine.cazin@ugent.be
Authors
Jonathan W. Hall − Department of Chemistry, University of
Bath, Bath BA2 7AY, U.K.
Damien Bouchet − Department of Chemistry and Center for
Sustainable Chemistry, Ghent University, Ghent 9000,
Belgium
Mary F. Mahon − Department of Chemistry, University of
Bath, Bath BA2 7AY, U.K.
Michael K. Whittlesey − Department of Chemistry, University
of Bath, Bath BA2 7AY, U.K.; orcid.org/0000-0002-
5082-3203
(10) (a) Zhang, L.; Hou, Z. N-Heterocyclic carbene (NHC)-copper-
catalysed transformations of carbon dioxide. Chem. Sci. 2013, 4,
3395−3403. (b) Boogaerts, I. F. F.; Fortman, G. C.; Furst, M. R. L.;
Cazin, C. S. J; Nolan, S. P. Carboxylation of N-H/C-H Bonds Using
N-Heterocyclic Carbene Copper(I) Complexes. Angew. Chem., Int.
Ed. 2010, 49, 8674−8677.
Complete contact information is available at:
(11) For recent contributions, see ref 3b and: Hall, J. W.; Unson, D.
M. L.; Brunel, P.; Collins, L. R.; Cybulski, M. K.; Mahon, M. F.;
Whittlesey, M. K. Copper-NHC-Mediated Semi-hydrogenation and
Hydroboration of Alkynes: Enhanced Catalytic Activity Using Ring-
Expanded Carbenes. Organometallics 2018, 37, 3102−3110.
(12) See for example: (a) Díez-González, S.; Correa, A.; Cavallo, L.;
Nolan, S. P. (NHC)Copper(I)-Catalyzed [3 + 2]-Cycloaddition of
Azides and Mono- or Disubstituted Alkynes (NHC = N-Heterocyclic
Carbene). Chem. - Eur. J. 2006, 12, 7558−7564. (b) Díez-González,
S.; Nolan, S. P. [(NHC)2Cu]X Complexes as Efficient Catalysts for
Azide-Alkyne Click Chemistry at Low Catalyst Loadings. Angew.
Chem., Int. Ed. 2008, 47, 8881−8884.
(13) Sebest, F.; Dunsford, J. J.; Adams, M.; Pivot, J.; Newman, P. D.;
Díez-González, S. Ring-Expanded N-Heterocyclic Carbenes for
Copper-Mediated Azide−Alkyne Click Cycloaddition Reactions.
ChemCatChem 2018, 10, 2041−2045.
(14) During the assembly of this manuscript, the Hashmi group
described the Ag transfer route to prepare RE-NHC copper
complexes: Cervantes-Reyes, A.; Rominger, F.; Hashmi, A. S. K.
Sterically Demanding AgI and CuI N-Heterocyclic Carbene
Complexes: Synthesis, Structures, Steric Parameters, and Catalytic
Activity. Chem. - Eur. J. 2020, 26, 5530−5540.
https://pubs.acs.org/10.1021/acs.organomet.1c00039
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We acknowledge financial support from the EPSRC Centre for
Doctoral Training in Catalysis (EP/L016443/1) for J.W.H.
and the Erasmus Programme for D.B. For work performed in
Ghent, the UGent BOF and FWO are gratefully acknowledged
for support.
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