Heteroleptic bis(N-heterocyclic carbene)copper(I) complexes: Highly efficient systems for the [3+2] cycloaddition of azides and alkynes

Article abstract of DOI:10.1021/om3006195

The first examples of heteroleptic bis-N-heterocyclic carbene (NHC) copper(I) complexes and a mixed NHC-phosphine Cu complex are reported. These complexes are easily synthesized from the reaction of [Cu(OH)(NHC)] with various imidazol(idin)ium or phosphon

Full text of DOI:10.1021/om3006195

Article
pubs.acs.org/Organometallics
Heteroleptic Bis(N-heterocyclic carbene)Copper(I) Complexes: Highly
Efficient Systems for the [3+2] Cycloaddition of Azides and Alkynes
Faïma Lazreg, Alexandra M. Z. Slawin, and Catherine S. J. Cazin*
EaStCHEM School of Chemistry, University of St Andrews, KY16 9ST, U.K.
S
* Supporting Information
ABSTRACT: The first examples of heteroleptic bis-N-heterocyclic carbene (NHC) copper(I) complexes and a mixed NHC−
phosphine Cu complex are reported. These complexes are easily synthesized from the reaction of [Cu(OH)(NHC)] with various
imidazol(idin)ium or phosphonium tetrafluoroborate salts. These cationic heteroleptic bis-NHC Cu complexes are highly active
systems for the azide−alkyne cycloaddition leading to the formation of 1,2,3-triazoles. The mechanism of this transformation was
investigated, and information gathered suggests that only one NHC remains coordinated to the metal center during catalysis.
ium salts 2. The sole side-product formed being water, this
reaction is very straightforward and most atom economical.
In order to assess the viability of this synthetic pathway,
[Cu(OH)(IPr)] (IPr = N,N′-bis{2,6-(di-isopropyl)phenyl}-
imidazol-2-ylidene) was reacted with IPr·HBF4, and the NMR
spectra of the product of the reaction were compared with data
reported for [Cu(IPr)2]BF4.8c As NMR data indicated an
essentially quantitative conversion to the homoleptic bis-NHC
complex 3a had occurred, we tested the viability of this new
route to access heteroleptic bis-NHC Cu complexes (Scheme
1). A series of heteroleptic bis-carbene copper(I) complexes
bearing saturated and unsaturated NHCs was synthesized in
this manner. These colorless complexes (3b−f) were isolated
microanalytically pure in excellent yields (90−99%) (Scheme
1).
INTRODUCTION
■
Functionalized triazoles have rapidly become a very common
molecular construct, finding applications ranging from biology
to material science.1 The popularity of this approach has been
driven by the ease with which the basic architecture can be
assembled using “click” chemistry.2 Of the various reactions
falling under the click appellation, the 1,3 dipolar cycloaddition
of alkynes and azides (the Huisgen reaction)3 represents the
flag-bearer for the reaction class. Whether metal catalyzed4 or
not,5 it represents a very simple experimental protocol to
assemble the triazole core.
Among the most active single-component systems enabling
the Huisgen reaction,6 copper N-heterocyclic carbene (NHC)
complexes stand at the head of the class in terms of activity and
productivity.7 These copper complexes usually have a [CuX-
(NHC)] (X = halide) or the homoleptic [Cu(NHC)2]Y (e.g.,
Y = BF4 or PF6) formulation.8 As the proposed mechanism,
described by Nolan and co-workers,8b using the homoleptic
systems involves decoordination of one of the NHC ligands,8b
we reasoned that heteroleptic complexes bearing two different
ligands (with one of these being more labile than the other)
may lead to an interesting activity in the Huisgen reaction
leading to triazoles. We now report a straightforward synthetic
approach leading to the first examples of heteroleptic bis-NHC
copper complexes and examine the activity of these novel
compositions in alkyne−azide cycloaddition reactions.
1
The H NMR spectra of complexes of type 3 contain two
singlets corresponding to the imidazolylidene protons. These
are shifted to higher field for the saturated ligands (3.68−3.75
ppm) compared to the unsaturated ones (6.88−7.34 ppm).
The isopropyl groups of the IPr ligand are seen as two doublets
(CH3 groups) and a septet (CH proton), with a coupling
constant near 7 Hz. In the 13C-{1H} NMR spectrum, the
backbone carbon atoms are seen as two singlets, one per
imidazolylidene carbon atoms, while the most characteristic
peaks, corresponding to the carbene carbon atoms, are shifted
to lower field, between 171.6 and 200.8 ppm. As expected, the
saturated NHCs give rise to the lowest field signals (200
ppm).10,11
RESULTS AND DISCUSSION
■
Synthesis and Characterization of [Cu(NHC)(NHC′)]-
BF4 Complexes. Heteroleptic bis-NHC complexes of copper
were obtained by reaction of a hydroxide complex of the type
[Cu(OH)(NHC)], 1,9 with tetrafluororoborate imidazol(idin)-
Special Issue: Copper Organometallic Chemistry
Received: July 4, 2012
Published: October 31, 2012
© 2012 American Chemical Society
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lie in the range 1.897(6) to 1.908(7) Å, which is shorter than
the Cu−Ccarbene length measured for the homoleptic analogue
3a (1.938(18) and 1.926(19) Å).8c This is in agreement with
the steric hindrance of IPr (%VBur IPr of 3a is 36.9). The steric
bulk of the NHC ligands of complexes 3b−f was assessed using
the SambVca application.13 The %VBur values obtained show
that ItBu is the most sterically demanding NHC in the study,
ICy the less congested, and the saturated SIMes more hindered
than its unsaturated analogue. This is in accordance with
previous observations made for these ligands.8d Complexes
bearing two aryl-N-substituted NHCs (complexes 3b, 3c, 3f)
display a twist between the NHCs five-membered rings (Table
1). In contrast, complexes 3d and 3e, which bear a NHC with
N-alkyl substituents, do not present such a twist. This shows
the flexibility of alkyl groups compared to aryl ones, the former
having the ability to modulate its bulkiness in response to the
steric requirement of IPr.
Scheme 1. [Cu(IPr)(NHC)]BF4 Complexes Synthesized in
This Study
Catalysis. The catalytic activity of this novel series of
cationic copper complexes was first examined for the [3+2]
cycloaddition of heptyl azide and phenylacetylene. At room
temperature, in neat substrate, with a catalyst loading of 0.5 mol
%, all complexes of type 3 permitted complete conversion to
the triazole product.14 However, a divergence between the
complexes in terms of rate of reaction is observed, 3d and 3e
reaching completion within 2 h (Table 2, entries 4 and 5),
while 3a−c and 3f require between 20 and 36 h to attain
quantitative conversion (Table 2, entries 1−3 and 6). This
observation cannot be rationalized using steric arguments alone
based on %VBur, as the two fastest systems, 3d and 3e, bear the
smallest and the largest NHC of the study (ICy and ItBu)
(Table 1). However, a common feature of the two N-alkyl-
Crystallographic studies were carried out to unambiguously
establish the structural features of these complexes (Figure 1).12
All complexes present a linear geometry with C(IPr)−Cu-
C(NHC) angles between 178.55(19)° and 180.0(2)° (Table 1).
The Cu−Ccarbene bond lengths for the heteroleptic complexes
Figure 1. ORTEP plots of [Cu(IPr)(IMes)]BF4, 3b, [Cu(IPr)(SIMes)]BF4, 3c, [Cu(IPr)(ICy)]BF4, 3d, [Cu(IPr)(ItBu)]BF4, 3e, and
[Cu(IPr)(NHC′)]BF4, 3f.12 (NHC′ = N,N′-bis[2,6-(diethyl)phenyl]imidazolidin-2-ylidene.) Ellipsoids are represented at the 50% probability level.
Hydrogen atoms and anion are omitted for clarity. Selected bond lengths (Å) and angles (deg) (esd): 3b: Cu(1)−C(1) 1.905(5), Cu(1)−C(21)
1.902(5), C(1)−Cu(1)−C(21) 180.0(2); 3c: Cu(1)−C(1) 1.899(5), Cu(1)−C(31) 1.900(4), C(1)−Cu(1)−C(31) 178.55(19); 3d: Cu(1)−C(1)
1.898(6), Cu(1)−C(11) 1.897(6), C(1)−Cu(1)−C(11) 180.0(1); 3e: Cu(1)−C(1) 1.906(6), Cu(1)−C(21) 1.903(6), C(1)−Cu(1)−C(21)
178.8(3); 3f: Cu(1)−C(1) 1.906(7), Cu(1)−C(21) 1.908(7), C(1)−Cu(1)−C(21) 180.0(1).
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Table 1. %VBur and Selected Bond Lengths (Å) and Angles (deg) (esd) for Complexes 3a−f
a
IPr/IPr
IPr/IMes
IPr/SIMes
IPr/ICy
3d
IPr/ItBu
3e
IPr/NHC′
3a8c
3b
3c
3f
%VBur
36.9
45.7/32.3
1.905(5)
1.902(5)
180.0(2)
136(1)
44.2/35.1
1.899(5)
1.900(4)
178.55(19)
55(1)
42/25.5
1.898(6)
1.897(6)
180.0(1)
0(1)
38.9/37.2
1.903(6)
1.906(6)
178.8(3)
2(1)
43.6/33.2
1.908(7)
1.906(7)
180.0(1)
47(1)
Cu−CIPr
Cu−CNHC
CIPr−Cu−CNHC
1.938(18)
1926(19)
177.1(9)
49.72
b
NHC−NHC′
a
b
NHC′ = N,N′-bis[2,6-(diethyl)phenyl]imidazolidin-2-ylidene. Angle between five-membered rings.
a
catalyst loadings further highlight the high efficiency of the
heteroleptic bis-NHC system 3d. All substrates proved to lead
to the desired product with the exception of 6j, which proved
difficult to form at low catalyst loading. All other compounds
could be obtained in excellent yields using loading below 500
ppm. At 40 °C, most products could be obtained using only
100−200 ppm of catalyst. The exceptional catalytic activity of
3d was further revealed in the formation of 6m, 6n, and 6o.
Compounds 6m and 6n were obtained with a turnover number
of 28 400 and 32 400, respectively, and for 6o, an outstanding
TON of 194 000 was achieved!
Comparing the hetero- with the homoleptic system leads to
the observation of some differing reactivity trends. Most
notably, for 6b, 6m, 6o, 6p, and 6q at 0.5 mol % catalyst, less
than 3 h is required to reach complete conversion, whereas the
system described by Nolan required 5 to 9 h.8b For 6a and 6b,
the same reaction time at 0.5 mol % is observed to reach full
conversion, whereas the homoleptic systems require 5 min for
6a but 9 h for 6b. The methoxy group in the para position does
not change the reactivity at high catalyst loading. Even if for
“easy” substrates the homoleptic systems present high
reactivity, the heteroleptic system shows very high activity
especially at low catalyst loadings.
Table 2. Catalyst Optimization
c
cat loading
(mol %)
time
(h)
d
entry
complex
conv (%)
1
[Cu(IPr)2]BF4, 3a
0.5
20
25
24
2.1
1.8
36
100 (97)
100 (97)
100 (95)
100 (98)
100 (97)
100 (96)
100 (97)
100 (97)
100 (98)
100 (98)
2
[Cu(IPr)(IMes)]BF4, 3b
[Cu(IPr)(SIMes)]BF4, 3c
[Cu(IPr)(ICy)]BF4, 3d
[Cu(IPr)(ItBu)]BF4, 3e
0.5
3
0.5
4
0.5
5
0.5
b
6
[Cu(IPr)(NHC′)]BF4, 3f
[Cu(IPr)(ICy)]BF4, 3d
[Cu(IPr)(ItBu)]BF4, 3e
[Cu(IPr)(ICy)]BF4, 3d
[Cu(IPr)(ItBu)]BF4, 3e
[Cu(IPr)(ICy)]BF4, 3d
[Cu(IPr)(ItBu)]BF4, 3e
0.5
7
0.25
0.25
0.1
2.25
2
8
9
3
10
11
12
0.1
2.5
e
0.02
0.02
16
24
100 (97)
71 (65)
a
Reaction conditions: azide (1.00 mmol), alkyne (1.05 mmol), catalyst
(0.5 mol %), RT, neat. NHC′ = N,N′-bis[2,6-(diethyl)phenyl]-
imidazolidin-2-ylidene. Optimized reaction time; see Supporting
Information for kinetic profiles of entries 4, 5, 11, and 12. Conversion
determined by GC, based on azide, minimum average of 4 reactions.
Isolated yields are given in parentheses. Turnover number (TON) =
b
c
d
e
Mechanistic Considerations. A catalytic cycle was
proposed by Nolan for homoleptic bis-NHC complexes.8b
The complex is believed to react with the azide to form a
copper-acetylide. One NHC is released and an imidazolium salt
is formed. To understand if the heteroleptic and homoleptic
complexes presented the same activation, simple stoichiometric
reactions were conducted. The copper complex [Cu(IPr)-
(ICy)]BF4, 3d, was exposed to phenylacetylene and heated
overnight at 80 °C. The formation of two new species was
observed. The new products were separated and identified as
[Cu(IPr)(CCPh)] and ICy·HBF4. The same reaction was
performed at RT, and the same products were isolated,
highlighting a low activation pathway for click using these
heteroleptic complexes. Using the Cu-acetylide intermediate
[Cu(IPr)(CCPh)], a stoichiometric reaction was conducted
on an NMR tube scale in CD3CN with 1 equiv of heptyl azide.
The reaction leads to the formation of an unstable complex,
presumably a copper-triazolyl intermediate, as diagnosed by the
characteristic CH2 group bound to azide. Finally, to confirm the
catalytic relevancy of the [Cu(IPr)(CCPh)], it was used as
catalyst (1 mol %) in a reaction involving heptylazide (1.00
mmol) and phenylacetylene (1.05 mmol) without solvent. The
reaction was stirred at RT, and after 130 min, complete
conversion was reached and the desired product was isolated in
95% yield, confirming the active role of [Cu(IPr)(CCPh)] in
the catalytic cycle. It is essential to release a carbene ligand for
catalytic activity, as shown by an experiment in which
ICy·HBF4 was added to the catalyst system. This inhibited
the catalyst, as, at room temperature, with 0.5 mol % of
5000.
substituted ligands ICy and ItBu is the fact that, in complexes of
type 3, the planes containing the two five-membered NHC
rings are nearly parallel, which is in contrast with all N-aryl
analogues (Table 1, NHC−NHC′ angle). In terms of
electronics, both NHCs are better donors than the N-aryl-
substituted NHCs studied here.15 Therefore, it appears that the
key to catalytic activity within the series is to ally strong donor
ability with ligand flexibility.
At lower catalyst loadings (0.25 and 0.1 mol %), the system
based on ItBu (3e) reached completion faster than the system
based on ICy (3d) (Table 2, entries 7−10). However, lowering
the catalyst loading showed that complex 3d is more active than
its ItBu analogue (Table 2, entries 11 and 12), and at 0.02 mol
% Cu, quantitative conversion to the triazole is obtained within
16 h. Of note is the fact that the homoleptic complex
[Cu(ICy2)]PF6, under the same reaction conditions, led to only
72% of product after 20 h.8b
The scope of the reaction was next examined using 3d
(Scheme 2). Alkyl-/Aryl-substituted and functionalized azides
and alkynes were successfully reacted, leading to a range of 1,4-
disubstitued-1,2,3-triazoles in high yields. The range of
functionalities tolerated is very broad and includes amines,
esters, alcohols, ketones, and halides. At room temperature
using 0.5 mol % catalyst loading, the reaction reached
completion within 20 min to 7 h, with isolated yields of
triazoles in the 97−99% range. Studies performed at low
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a
Scheme 2. Scope of the Reaction at RT and at Low Catalyst Loading
a
Reaction conditions: azide (1.00 mmol), alkyne (1.05 mmol), 3d (5 ppm−0.5 mol %), neat, RT to 60 °C, 20 min to 48 h. Isolated yield (average of
a
b
c
reactions): 40 °C; 50 °C; 60 °C.
[Cu(IPr)(ICy)]BF4 (3d) and 1 mol % of ICy·HBF4, after 7 h,
no conversion was observed. This system required 16 h to
reach quantitative conversion, which is in contrast with the
performance observed with 3d (Table 2, entry 4). The catalytic
cycle is therefore likely to proceed as in the case of the
homoleptic system [Cu(ICy)2]BF4 (Scheme 3).8b,16
The fact that the leaving NHC is ICy and not IPr is
counterintuitive. Indeed, ICy is less sterically demanding, is a
better donor,15 and has been shown to bind more strongly than
IPr.17 However, it should be kept in mind that the simple
difference in bond dissociation energies of Cu−ICy and Cu−
IPr is not the only thermodynamic term to be considered, as
the formation of a stronger ICy−H vs IPr−H bonds in
formation of the imidazolium salt product also contributes to
the overall reaction enthalpy.
which might enable a better understanding of the catalytic
manifold. For this reason, complex 3g, bearing PtBu3, was
synthesized. The synthetic route makes use of the general route
developed above for NHC-based systems and requires the use
of the phosphonium salt [HPtBu3]BF4. The reaction of the
latter with [Cu(OH)(IPr)] (1) at room temperature leads to
the formation of [Cu(IPr)(PtBu3)]BF4, 3g, in quantitative
yield. The structure of 3g was confirmed by X-ray diffraction on
single crystals (Figure 2).
The 31P-{1H} NMR spectrum of 3g displays a singlet at 66.9
1
ppm, corresponding to the phosphine ligand. In the H NMR
spectrum, the protons of the latter are seen as a doublet shifted
at δH 1.06 ppm (3JHP = 13.3 Hz). The iPr groups of the NHC
are seen as two doublets and a septuplet (3JHH = 6.9 Hz), and
the NHC backbone protons as a singlet at 7.39 ppm. In the
13C-{1H} NMR, the most characteristic peaks for the NHC are
a singlet at 124.6 ppm (backbone carbon atoms) and a doublet
Finally, the mechanistic study directed us toward the
examination of a mixed ligand system, NHC/phosphine,
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entries 2 and 3).18 Increasing the temperature shows that
[Cu(IPr)(PtBu3)]BF4, 3g, is a high-performance catalyst, as
5000 TONs can be reached (Table 3, entry 5); however, this
result can be compared to the performance of [Cu(IPr)(ICy)]-
BF4, 3d, which performs equally well but at room temperature.
This appears to indicate that [Cu(IPr)(ICy)]BF4, 3d, bears
ligands that have the right balance in terms of electronic and
steric effects to ensure optimum performance under click
conditions, i.e., at room temperature and under solvent-free (or
neat) conditions.
Scheme 3. Catalytic Cycle Leading to the Formation of
1,2,3-Triazole
In order to find out which of the NHC or phosphine is
released in the course of catalysis, simple stoichiometric
reactions were conducted. The copper complex [Cu(IPr)-
(PtBu3)]BF4, 3g, was exposed to phenylacetylene and heated
overnight at 80 °C. The formation of two new species was
observed. The new products were separated and identified as
[Cu(PtBu3)(CCPh)] and IPr·HBF4. The same reaction was
performed at RT, and the same products were isolated,
indicating the facile nature of the reaction. This catalytic step
hints at the importance of the basicity of the NHC (or of that
of the other ligand) attached to the metal center. This might
indicate that the NHC that is released acts as a base to the
alkyne substrate to initiate the catalytic cycle, while the less
basic NHC or PR3 species remains coordinated to copper. This
highlights the interest of having heteroleptic or mixed ligand
complexes, as each ligand can be separately tuned to reach
optimum catalytic performance.
CONCLUSION
■
A novel and straightforward synthetic route leading to
moisture- and air-stable homoleptic and (the first isolation
of) heteroleptic bis-NHC copper(I) complexes has been
developed. This versatile synthetic methodology also allows
access to a mixed NHC/PR3 complex. The structural studies of
a number of these complexes indicate the presence of
significant torsion angles of ligands about the copper center
that, in essence, encapsulate the metal, rendering it less
accessible. Catalytic studies with these complexes highlight a
very good catalytic activity in the Huisgen cycloaddition
reaction. The structure−activity relationship within this series
appears to be guided by a flexibility of the coligand. With
[Cu(IPr)(ICy)]BF4, 3d, reactions can reach completion with
only a few ppm of catalyst. The access to the metal clearly
appears important, and mechanistic studies suggest that only
one NHC remains on copper during the catalytic trans-
formation.
Figure 2. Crystal structure of [Cu(IPr)(PtBu3)]BF4, 3g.12 Ellipsoids
are represented at the 50% probability level. Hydrogen atoms are
omitted for clarity. Selected bond lengths (Å) and angles (deg) (esd):
Cu(1)−C(1) 1.918(5), Cu(1)−P(1) 2.2147(15), C(1)−Cu(1)−P(1)
178.38(17).
at 178.6 ppm with a C−P coupling constant of 61.0 Hz,
corresponding to the carbene carbon atom. Doublets at 32.2
and 37.3 ppm were assigned to the tBu carbon atoms.
Catalytic testing was performed on the model reaction (1-
azidoheptane, phenylacetylene, neat) and shows that [Cu(IPr)-
(PtBu3)]BF4, 3g, at 0.5 mol % loading, leads to a catalytic
system faster than all heteroleptic bis-NHC complexes, with the
exception of [Cu(IPr)(ICy)]BF4, 3d (Table 2, entries 1−6, and
Table 3, entry 1). At lower catalyst loading, [Cu(IPr)(ICy)]-
BF4, 3d, still displays a catalytic activity superior to that of
[Cu(IPr)(PtBu3)]BF4, 3g (Table 2, entry 11, and Table 3,
EXPERIMENTAL SECTION
■
General Procedure. For the synthesis of heteroleptic bis-carbene
complexes of type 3, a vial was charged with [Cu(OH)(IPr)]9 (200
mg, 0.426 mmol), the appropriate imidazol(idin)ium salt (0.426
mmol), and acetonitrile (2 mL). The reaction mixture was heated at
80 °C in a microwave oven for 30 min. The reaction mixture was
concentrated in vacuo (1 mL), and diethyl ether (2 mL) was added.
The product was collected by filtration.
a
Table 3. Catalysis Using [Cu(IPr)(PtBu3)]BF4, 3g
b
entry cat loading (mol %) temp (°C) time (h) conversion (%)
N,N′-Bis{2,6-(di-isopropyl)phenyl}imidazol-2-ylidene-{N,N′-bis-
(2,4,6-trimethylphenyl)imidazol-2-ylidene}copper(I) Tetrafluorobo-
rate, [Cu(IPr)(IMes)]BF4, 3b. Colorless solid, 320.7 mg, 90%. 1H
1
2
3
4
5
0.5
RT
RT
RT
40
<4
20
100
90
0.05
0.02
0.02
0.02
3
20
48
NMR (400 MHz, CD2Cl2, 298 K): δ 0.82 (d, 12H, JHH = 6.9 Hz,
3
24
88
CHCH3), 1.10 (d, 12H, JHH = 6.9 Hz, CHCH3), 1.66 (s, 12H, CH3
3
50
<15
100
Mes), 2.31 (septet, 4H, JHH = 6.9 Hz, CHCH3), 2.39 (s, 6H, CH3
Mes), 6.80 (s, 4H, Ar IMes), 6.88 (s, 2H, H4 and H5), 7.11 (s, 2H, H4′
a
3
Reaction conditions: azide (1.00 mmol), alkyne (1.05 mmol), neat.
Conversion determined by GC, minimum average of 4 reactions.
and H5′), 7.20 (d, 4H, 3JHH = 7.8 Hz, Ar IPr), 7.57 (t, 2H, JHH = 7.8
b
Hz, Ar IPr). 13C{1H} NMR (75 MHz, CD2Cl2, 298 K): δ 17.3 (s, CH3
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Mes), 21.3 (s, CH3 Mes), 23.6 (s, CHCH3), 24.5 (s, CHCH3), 28.9 (s,
CHCH3), 123.9 (s, C4 and C5), 124.3 (s, C4′ and C5′), 124.5 (s, Ar
IPr), 130.1 (s, Ar IMes), 131.0 (s, Ar IPr), 134.5 (s, CIV), 134.6 (s,
CIV), 134.8 (s, CIV), 139.6 (s, CIV), 145.4 (s, CIV), 176.2 (s, C2
carbene), 179.3 (s, C2 carbene). Anal. Calcd for C48H60BCuF4N4: C,
68.36; H, 7.17; N, 6.64. Found: C, 68.09; H, 7.24; N, 6.61.
3g. A vial was charged with [Cu(OH)(IPr)]9 (200 mg, 0.426 mmol),
the phosphonium salt (124 mg, 0.426 mmol), and THF (2 mL). The
reaction mixture was stirred at RT for 12 h. The solution was
concentrate in vacuo (1 mL), and diethyl ether (2 mL) was added. The
product was collected by filtration and obtained as a colorless solid
(294 mg, 99%). 1H NMR (400 MHz, CD2Cl2, 298 K): δ 1.06 (d, 27H,
3JHP = 13.3 Hz, C(CH3)3), 1.23 (d, 12H, 3JHH = 6.9 Hz, CHCH3), 1.28
N,N′-Bis{2,6-(di-isopropyl)phenyl}imidazol-2-ylidene-N,N′-bis-
{2,4,6-(trimethyl)phenyl}imidazolidin-2-ylidene Copper(I) Tetra-
fluoroborate, [Cu(IPr)(SIMes)]BF4, 3c. Colorless solid, 320 mg, 90%.
1H NMR (400 MHz, CD2Cl2, 298 K): δ 0.81 (d, 12H, 3JHH = 6.9 Hz,
3
3
(d, 12H, JHH = 6.9 Hz, CHCH3), 2.61 (septet, 4H, JHH = 6.9 Hz,
3
CHCH3), 7.35 (d, 4H, JHH = 7.9 Hz, CH Ar), 7.39 (s, 2H, H4 and
H5), 7.54 (t, 2H, 3JHH = 7.9 Hz, CH Ar). 13C{1H} NMR (CD2Cl2, 75
MHz, 298 K): δ 24.3 (s, CHCH3), 24.8 (s, CHCH3), 29.2 (s,
3
CHCH3), 1.08 (d, 12H, JHH = 6.9 Hz, CHCH3), 1.86 (s, 12H, CH3
Mes), 2.28 (septet, 4H, 3JHH = 6.9 Hz, CHCH3) overlapping with 2.33
(s, 6H, CH3 Mes), 3.68 (s, 4H, H4 and H5 SIMes), 6.74 (s, 4H, Ar
SIMes), 7.07 (s, 2H, H4′ and H5′ IPr), 7.21 (d, 4H, 3JHH = 7.8 Hz, Ar
2
1
CHCH3), 32.2 (d, JCP = 5.2 Hz, CH3 tert-butyl), 37.3 (d, JCP = 12.6
Hz, CCH3 tert-butyl), 124.6 (s, C4 and C5) 124.8 (s, Ar), 131.3 (s, Ar),
134.7 (s, CIV), 145.8 (s, CIV), 178.6 (d, JCP = 61.0 Hz, C2 carbene).
2
3
IPr), 7.58 (t, 2H, JHH = 7.8 Hz, Ar IPr). 13C{1H} NMR (CD2Cl2, 75
31P{1H} NMR (400 MHz, CD2Cl2, 298 K): δ 66.9 ppm. Anal. Calcd
for C39H63BCuF4N4: C, 63.19; H, 8.57; N, 3.78. Found: C, 63.12; H,
8.71; N, 3.66.
MHz, 298 K): δ 17.6 (s, CH3 Mes), 21.2 (s, CH3 Mes), 23.6 (s,
CHCH3), 24.4 (s, CHCH3), 28.9 (s, CHCH3), 51.8 (s, C4 and C5
SIMes), 124.3 (s, C4′ and C5′ IPr), 124.6 (s, Ar IPr), 130.4 (s, Ar
SIMes), 131.0 (s, Ar IPr), 134.4 (s, CIV), 134.7 (s, CIV), 135.4 (s, CIV),
138.7 (s, CIV), 145.3 (s, CIV), 179.0 (s, C2 carbene), 200.2 (s, C2
carbene). Anal. Calcd for C48H62BCuF4N4: C, 68.20; H, 7.39; N, 6.63.
Found: C, 68.19; H, 7.53; N, 6.71.
General Procedure for Catalytic Testing. A vial was charged
with the azide (1.00 mmol), the alkyne (1.05 mmol), and the
appropriate amount of catalyst. The reaction mixture was stirred
without solvent (when substrates were liquids) at the indicated
temperature for the specified amount of time. The progress of the
reaction was monitored by GC, and when completion was reached, the
product was collected by filtration and washed with pentane (2 × 3
mL). For low catalyst loading experiments, in a vial, the required
amount of a freshly prepared stock solution (4 mg of [Cu(IPr)(ICy)]
in 1 mL of CH2Cl2) was introduced, and the solvent was evaporated in
vacuo. Azide (1.00 mmol) and alkyne (1.05 mmol) were then charged
in turn into the vial. The reaction mixture was stirred without added
solvent at the indicated temperature for the specified amount of time.
Once the reaction reached completion, the product was collected by
filtration and washed with pentane (2 × 3 mL).
N,N′-Bis{2,6-(di-isopropyl)phenyl}imidazol-2-ylidene-N,N′-
(dicyclohexyl)imidazol-2-ylidene Copper(I) Tetrafluoroborate, [Cu-
(IPr)(ICy)]BF4, 3d. Colorless solid, 306 mg, 99%. 1H NMR (400 MHz,
CD2Cl2, 298 K): δ 0.89−1.12 (m, 6H, CH2 cyclohexyl), 1.24 (d, 12H,
3JHH = 6.8 Hz, CHCH3), 1.29 (d, 12H, 3JHH = 6.8 Hz, CHCH3), 1.31−
1.42 (m, 4H, CH23cyclohexyl), 1.56−1.71 (m, 10H, CH2 cyclohexyl),
3
2.59 (septet, 4H, JHH = 6.8 Hz, CHCH3), 3.10 (tt, 2H, JHH = 12.2
Hz, 3JHH = 4 Hz, CH cyclohexyl), 6.89 (s, 2H, H4 and H5), 7.29 (s, 2H,
H4′ and H5′), 7.44 (d, 4H, 3JHH = 7.8 Hz, Ar), 7.64 (t, 2H, 3JHH = 7.8
Hz, Ar). 13C{1H} NMR (CD2Cl2, 75 MHz, 298 K): δ 23.5 (s,
CHCH3), 24.9 (s, CH2 cyclohexyl), 25.1 (s, CH2 cyclohexyl), 25.7 (s,
CHCH3), 29.2 (s, CHCH3), 34.5 (s, CH2 cyclohexyl), 61.3 (s, CH
cyclohexyl), 118.6 (s, C4 and C5), 124.3 (s, C4′ and C5′), 125.0 (s, Ar),
131.6 (s, Ar), 134.6 (s, CIV), 146.4 (s, CIV), 171.7 (s, C2 carbene),
179.3 (s, C2 carbene). Anal. Calcd for C42H60BCuF4N4: C, 65.40; H,
7.84; N, 7.26. Found: C, 65.37; H, 7.84; N, 7.17.
ASSOCIATED CONTENT
■
S
* Supporting Information
Crystallographic data for 3b−g, procedure for the preparation
of azides, mechanistic studies, spectroscopic data, and NMR
spectra for all complexes and compounds. This material is
available free of charge via the Internet at http://pubs.acs.org.
N,N′-Bis{2,6-(di-isopropyl)phenyl}imidazol-2-ylidene-N,N′-(di-
tert-butyl)imidazol-2-ylidene copper(I) Tetrafluoroborate, [Cu(IPr)-
1
(ItBu)]BF4, 3e. Colorless solid, 274 mg, 95%. H NMR (400 MHz,
CD2Cl2, 298 K): δ 1.19 (s, 18H, CH3 tert-butyl), 1.22 (d, 12H, 3JHH
=
3
7.1 Hz, CHCH3) overlapping with 1.24 (d, 12H, JHH = 7.1 Hz,
AUTHOR INFORMATION
3
CHCH3), 2.71 (septet, 4H, JHH = 7.1 Hz, CHCH3), 6.98 (s, 2H, H4
■
and H5), 7.34 (s, 2H, H4 and H5), 7.36 (d, 4H, 3JHH = 7.5 Hz, Ar IPr),
7.54 (t, 2H, 3JHH = 7.5 Hz, Ar IPr). 13C{1H} NMR (CD2Cl2, 75 MHz,
298 K): δ 24.0 (s, CHCH3), 25.0 (s, CHCH3), 29.1 (s, CHCH3), 29.9
(s, CIV), 31.9 (s, CH3 tert-butyl), 57.3 (s, CIV mesityl), 117.6 (s, C4 and
C5), 124.9 (s, C4 and C5), 125.2 (s, Ar), 131.3 (s, Ar), 135.1 (s, CIV
phenyl), 145.8 (s, CIV phenyl), 171.6 (s, C2 carbene), 179.6 (s, C2
carbene). Anal. Calcd for C38H56BCuF4N4: C, 63.46; H, 7.85; N, 7.79.
Found: C, 63.55; H, 7.74; N, 7.82.
Corresponding Author
*Fax: +44 (0) 1334 463808. E-mail: cc111@st-andrews.ac.uk.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The authors gratefully acknowledge the Royal Society
(University Research Fellowship to C.S.J.C.) and the EaSt-
CHEM School of Chemistry for funding. We also thank Marc
R. L. Furst for early efforts on this project.
N,N′-Bis{2,6-(di-isopropyl)phenyl}imidazol-2-ylidene-N,N′-bis-
{2,6-(diethyl)phenyl}imidazolidin-2-ylidene Copper(I) Tetrafluoro-
borate, [Cu(IPr)(NHC′)]BF4, 3f. Colorless solid, 346 mg, 99%. 1H
3
NMR (400 MHz, CD2Cl2, 298 K): δ 0.78 (d, 12H, JHH = 7.2 Hz,
3
3
CHCH3), 1.05 (d, 12H, JHH = 7.2 Hz, CHCH3), 1.13 (t, 12H, JHH
3
=7.6 Hz, CH2CH3 ethyl), 2.12 (dq, 4H, JHH = 7.6 Hz, CH2CH3
ethyl), 2.25 (septet, 4H, JHH = 7.2 Hz, CHCH3) overlapping with
REFERENCES
3
■
2.33 (dq, 4H, 3JHH = 7.6 Hz, CH2CH3 ethyl), 3.75 (s, 4H, H4 and H5),
7.00 (d, 4H, 3JHH = 7.7 Hz, Ar), overlapping with 7.02 (s, 2H, H4′ and
H5′), 7.19 (d, 4H, 3JHH = 7.8 Hz, Ar), 7.29 (t, 2H, 3JHH = 7.7 Hz, Ar),
7.57 (t, 2H, 3JHH = 7.8 Hz, Ar). 13C{1H} NMR (CD2Cl2, 75 MHz, 298
K): δ 14.6 (s, CH2CH3 ethyl), 23.7 (s, CHCH3), 24.0 (s, CHCH3),
24.4 (s, CH2CH3), 28.9 (s, CHCH3), 53.1 (s, C4 and C5), 124.6 (s, C4′
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C2 carbene), 200.8 (s, C2 carbene). Anal. Calcd for C50H66BCuF4N4:
C, 68.76; H, 7.62; N, 6.4. Found: C, 68.83; H, 7.71; N, 6.37.
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We have not had any issue performing the reactions on a small scale.
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7975
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