Synthesis and structural characterization of 20-membered macrocyclic rings bearing: Trans -chelating bis(N-heterocyclic carbene) ligands and the catalytic activity of their palladium(ii) complexes

Article abstract of DOI:10.1039/c9dt02147g

Macrocycles consisting of a 20-membered ring containing two imidazolium salt functionalities and of the formula [PhCH₂N(CH₂CH₂CH₂)Im(CH₂CH₂CH₂)₂][Br]₂ (Im = imidazole = 3a, benzimidazole = 3b) were synthesized in 70-75% yields. These salts serve as precursors to macrocycles containing two N-heterocyclic carbene (NHC) moieties. Reaction of the macrocyclic salts 3a and 3b with silver oxide afforded macrocyclic-bis(NHC)silver(i) complexes 4a and 4b. Single-crystal X-ray diffraction studies of macrocyclic-bis(NHC)silver(i) complex 4a revealed a tetranuclear silver core with a short Ag-Ag distance (2.9328 ?). Complexes 4a and 4b serve as carbene transfer reagents to Pd. The treatment of macrocyclic-bis(NHC)silver(i) complexes 4a and 4b with one equivalent of PdCl₂(MeCN)₂ in methylene chloride afforded square-planar trans-macrocyclic-bis(NHC)Pd(ii)X₂ complexes 5a and 5b. Preliminary screening of these palladium complexes showed they are competent precatalysts for Heck and Suzuki coupling reactions.

Full text of DOI:10.1039/c9dt02147g

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Douglas W. Stephen et al.
N-Heterocyclic carbene stabilized parent sulfenyl, selenenyl,
and tellurenyl cations (XH , X = S, Se, Te)
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DOI: 10.1039/C9DT02147G
ARTICLE
Synthesis and structural characterization of 20-membered
macrocyclic rings bearing trans-chelating bis(N-heterocyclic
carbene) ligands and the catalytic activity of their palladium(II)
complexes
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
Rajesh Thapa and Stefan M. Kilyanek*a
Macrocycles consisting of a 20-membered ring containing two imidazolium salt functionalities and of the formula
[
2 2 2 2 2 2 2 2 2
PhCH N(CH CH CH )Im(CH CH CH ) ][Br] (Im = imidazole = 3a, benzimidazole = 3b) were synthesized in 70-75% yields.
These salts serve as precursors to macrocycles containing two N-heterocyclic carbene (NHC) moieties. Reaction of the
macrocyclic salts 3a and 3b with silver oxide afforded macrocyclic-bis(NHC)silver(I) complexes 4a and 4b. Single-crystal X-
ray diffraction studies of macrocyclic-bis(NHC)silver(I) complex 4a revealed a tetranuclear silver core with a short Ag-Ag
distance (2.9328 Å). Complexes 4a and 4b serve as carbene transfer reagents to Pd. The treatment of macrocyclic-
bis(NHC)silver(I) complexes 4a and 4b with one equivalent of PdCl
trans-macrocyclic-bis(NHC)Pd(II)X complexes 5a and 5b. Preliminary screening of these palladium complexes showed they
are competent precatalysts for Heck and Suzuki coupling reactions.
2 2
(MeCN) in methylene chloride afforded square-planar
2
ligand formed a mixture of cis- and trans-chelated Pd NHC
Introduction
After the isolation of the first stable, free N-heterocyclic
complexes. The cis/trans mixture is common and cannot be
separated in most cases.27, Pd complexes with bidentate
trans-chelating NHCs have been shown to be active catalysts for
31
1
carbenes (NHCs) by Arduengo, NHCs have been used widely in
3
2,18
C-C coupling reactions.
homogenous catalysis and coordination chemistry. Due to their
strong σ-donating properties, NHC ligands bind strongly to a
variety of metals and stabilize a wide range of metal oxidation
states.2 NHC complexes owe their high thermal stabilities to
their strong metal-carbon bonds, and NHC ligands are unique
Douthwaite et al. discovered flexible tridentate bis-NHC amino
ligands where the NHC moieties are connected by a flexible five-
atom linker consisting of four methylene groups and an amino
,3,4
functionality (CH
2 2 2 2
CH NRCH CH ). They showed that these
ligands bind to the Pd center as a tridentate pincer with
5
,6
due to their lack of π-accepting properties. For these reasons,
NHCs have found a wide range of applications where phosphine
ligands are not desirable.
to coordinate to most transition metals and has been used as a
supporting ligand for a wide variety of catalysts with excellent
performance in many important reactions.6
been shown to coordinate with Pd, generating competent
precatalysts for C-C bond-forming reactions.
3
2,33
coordination of the central amine.
Hazari et al. reported a
family of bidentate trans-chelating NHC ligands with flexible
propyl linkers incorporating a tertiary amine. They have shown
that these ligands easily bind to Pd in a bidentate trans-
spanning fashion with no coordination to the central amine,
7
-10
The NHC moiety has been shown
,
11-13
NHCs have
1
8
forming a 12-membered palladacycle (Chart 1, i). These Pd
complexes are active towards Heck and Suzuki
1
4-22
,
,
reactions.18 32 33
Although there has been an abundance of work on the synthesis
and reactivity of NHC-metal complexes, there is still significant
interest in the development of new macrocyclic NHC ligands.
A macrocyclic complex with a 15-membered ring and a
bidentate cyclophane geometry containing a butane linker was
3
4
reported (Chart 1, ii) by Hahn. A plethora of small 15-
2
,3,5,12,14,20,23,24
There is an abundance of research on cis-
3
1,34,35
membered macrocyclic complexes
membered macrocyclic ligands
or larger 28-38
with tridentate coordination
systems have been reported, but only a handful of
intermediate” sized macrocyclic ligands are in the literature.
bidentate-chelating NHC ligands with Pd; fewer ligands have
been reported that coordinate in a trans fashion, and still fewer
within a closed (macrocyclic) scaffold. 18
chelated bis(NHC) complexes of Pd and Ni possessing
3
6,37
,25-29
The first trans-
“
Chaplin and co-workers have synthesized a series of 19-23-
membered CNC macrocyclic pincer ligands consisting of
bis(imidazolium)-lutidine salts with octa-, deca- and dodecane
spacers (Chart 1, iii). These CNC macrocyclic pincer ligands are
converted to Ag carbene complexes that serve as
3
0
binaphthyl backbones were reported by RajanBabu. This
a. Department of Chemistry and Biochemistry, 1 University of Arkansas, Fayetteville,
AR 72701
Electronic Supplementary Information (ESI) available: [NMR and FT-MS spectra as
well as detailed descriptions of X-Ray data collection are available. CIF files transmetalating agents to produce cationic Pd(II) chloride
containing crystallographic data are also available.]. See DOI: 10.1039/x0xx00000x
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Pleas De ad l to o nn oT tr aa nd sj au cs t ti omn as rgins
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ARTICLE
Journal Name
complexes.38
Pd complexes comprised of 16-member macrocycles with a broad array of metals. We found that these
View Article Online
DOI: 10.1039/C9DT02147G
macrocycles containing two or more NHC’s have been macrocycles adopt trans-NHC configurations when coordinated
3
9
synthesized by Pöthig and Kühn (Chart 1, iv) in addition to to Pd. The flexible trans amino ligands connected to the NHCs
macrocycles containing other transition metals.4 These by propyl chains were not found to displace inner sphere halides
macrocyclic systems differ from the others discussed here of the Pd complexes in the solid state. We have characterized
because they are rigid and do not contain any available these Pd complexes and screened them for activity as
coordination sites at the metal. Other groups have synthesized precatalysts for Suzuki-Miyauri and Heck cross-coupling
macrocycles containing two or more NHC moieties of similar reactions.
0
4
1
size.
Additionally, Kühn and co-workers have synthesized
larger more flexible systems that are analogous to their
4
2
Results and Discussion
macrocyclic systems but do not consist of a closed macrocycle.
These flexible ligand systems can coordinate a variety of metals
Scheme 1 summarizes the synthesis of the bis-imidazole amine
and bis-benzimidazole amine compounds (2a-2b) that comprise
half of the target 20-member macrocycles as well as
macrocycles 3a and 3b. Bis(ester) (A) was synthesized from
commercially available benzylamine and ethyl acrylate utilizing
4
3
and some can coordinate several metal centers.
N
N
N
R
R
N
4
4
a Michael addition. Reduction of A with LiAlH
4
produced
Cl Pd
N
N
N
N
N
2
2+
18
bis(alcohol) (B), which was converted into the bis-bromide
starting material (1) by refluxing with concentrated HBr for 24
Pd
N
4
5
hours. N-Benzylbis(3-bromopropyl)-imidazole (2a) and N-
benzylbis(3-bromopropyl)benz-imidazole (2b) were obtained
by the reaction of N-benzylbis(3-bromopropyl)amine 1, sodium
hydride and imidazole or benzimidazole, respectively, in THF
(Scheme 1). Both compounds 2a and 2b are colorless viscous
liquids.
i. Hazari 2011
ii. Hahn 2010
R = Me, Bn, tBu
N
N
N
N
N
X
N
N
2+
N
Pd
(CH2)n
Pd
N
N
N
N
N
COOEt
O
MeOH
+
NH2
iii. Chaplin 2013
X = Cl; n = 8, 10, 12
iv. Kühn 2015
OEt 25 °C
4d
Ph
N
COOEt
Br
Chart 1. Previously reported polydentate and macrocyclic (NHC)Pd(II) complexes
A
OH
HBr
As mentioned above, some of these polydentate ligands have
been observed to adopt a variety of coordination modes by
LiAlH4
Ph
N
reflux,
OH
Ph
N
THF, 24 h
3
8,32,33
displacement of inner sphere halides.
The ligands in this
1
0
- 25 °C
B
Br
study were chosen to have a larger ring structure than those of
Hahn and co-workers. These larger ring structures are
expectedly fluxional. Additionally, the larger ring structures
used in this study differ from Chaplin and Hahn’s previous work
because these macrocycles contain four possible coordination
sites, enabling these macrocycles to adopt a number of
coordination modes and stereochemistries.
N
N
Imidazole or,
CH CN
3
Benzimidazole
Ph
N
+ 1
reflux
24 h
NaH, THF
N
N
Imidazole (2a, Yield = 95%)
In this study, we examined the coordination chemistry and
reactivity of intermediate-sized 20-membered macrocyclic rings
containing two tertiary amines and two NHC moieties derived
from imidazole and benzimidazole. We synthesized and
characterized the silver(I) complexes of these macrocyclic
ligands for use as carbene transfer / transmetalating agents. We
surveyed the coordination chemistry of these ligands with Pd as
a first step toward understanding whether these intermediate-
sized rings would adopt a mixture of stereoisomers (cis / trans
Benzimidazole (2b, Yield = 94%)
2
Br
N
N
N
Ph
N
N
Ph
N
2
NHCs) or form mixtures of coordination modes to the metal (κ ,
3
κ etc.). In particular, the displacement of inner-sphere halides
to form cationic metal species is of interest for Pd and other
transition metals. This work lays the foundation for studies of
the coordination chemistry of these intermediate-sized
Imidazole (3a, Yield = 60%)
Benzimidazole (3b, Yield = 50%)
Scheme 1. Synthesis of macrocyclic ligand 3a and 3b
2
| J. Name., 2012, 00, 1-3
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ARTICLE
1
3
The cyclization reaction between 1 and N-benzylbis(3- characteristic downfield C NMR peak at δ 208 ppm
View Article Online
1
DOI: 10.1039/C9DT02147G
bromopropyl)-imidazole
2a
or
N-benzylbis(3- corresponding to a free carbene. Additionally, the H NMR
bromopropyl)benzimidazole 2b yields the corresponding signal for the imidazolium 2-position previously observed at δ
cyclophane-like 20-membered macrocyclic bisimidazolium 9.19 ppm is no longer present, implying formation of the free
1
3
bromide salts 3a and 3b (Scheme 1). The cyclization reactions carbene 3c. The free bis-NHC C NMR carbene chemical shift
were performed at low concentrations (~100 mM) to prevent observed is comparable to the isolable NHC (δ 211.43 ppm in
1
8
1
46
possible oligomerization side reactions.
6 6
C D ) reported by Arduego et al. and other NHCs.
Proligand 3a is a hygroscopic white solid, which is soluble in Attempts to isolate the free carbene furnished an intractable
polar solvents such as dichloromethane, acetonitrile, and THF viscous dark red oil consistent with the literature.32 This oil can
and insoluble in nonpolar solvents such as toluene, hexanes, be generated through deprotonation of the imidazolium salt 3a
and petroleum ether. Unlike 3a, the proligand 3b is stable in air using bases such as t-BuOK and/or NaH. However, subsequent
and is soluble in chloroform, but is insoluble in methylene work-up results in decomposition and the formation of multiple
chloride, acetonitrile, and dimethyl sulfoxide. The overall yield products. As reported previously,12 this product mixture was
of 3a-3b is 50 to 60%.
likely formed by deprotonation of the benzylic positions of the
A crystal suitable for X-ray crystallography of 3a was obtained macrocycle and deprotonation of the methylene groups
by slow diffusion of chloroform into a solution of 3a in adjacent to the imidazole rings.
dichloromethane (Figure 1). The X-ray structure confirms Direct reaction of free carbenes generated in situ by treatment
1
macrocycle formation. H NMR spectroscopy of 3a in CD
2
Cl
2
of a mixture of imidazolium salt and strong base with
4
7
shows three resonances at  4.05 (triplet),  2.49 (triplet) and  PdCl
.97 (quintet) ppm. These resonances correspond to the three Direct reaction of in situ generated 3c with PdCl
methylene groups of the four propyl chains (NCH CH CH
2
(MeCN)
2
has been shown to yield metalated product.
1
2
(MeCN)
2
2
2
2
N) yielded a mixture of products. Several bases were screened for
present in the macrocyclic proligand 3a Similarly, three direct deprotonatation and metalation of the ligand including n-
resonances were observed for the methylene protons of the BuLi, NaH, t-BuOK. All these reactions yielded a mixture of
propyl chains of 3b in CDCl
and  2.65 (quintet) ppm. These data show that the solution also yields a complex product mixture. Additionally, direct
conformations of 3a and 3b are either highly fluxional or are metalation of 3a and 3b with PdCl (MeCN) did not occur after
consistent with the symmetric structures observed in the solid refluxing 16 hours in methylene chloride.
3 2 2
at  4.64 (triplet),  2.83 (triplet) products. Reaction of 3b with t-BuOK in THF with PdCl (MeCN)
2
2
state.
Ag complexes
1
The H NMR resonances of the imidazolium 2-position protons
Several groups have used transmetalation from Ag complexes
(NCHN) for 3a and 3b appear as singlets at  10.77 ppm and
as a strategy to efficiently synthesize other metal NHC
1
3

11.33 ppm, respectively. C NMR shows the C-H resonances
Cl ) and δ
). These chemical shifts are consistent with
38,48-57
complexes.
Bis(NHC)silver(I)bromide complexes 4a and
of the imidazolium 2-position at δ 139 ppm (3a in CD
44 ppm (3b in CDCl
similar systems in the literature.
2
2
4
b were prepared as ligand transfer agents (Schemes 2 and 3)
1
3
by the reaction of imidazolium salts 3a and 3b with excess silver
oxide in methylene chloride. Upon deprotonation of 3a and 3b,
the target 20-member macrocyclic bis-NHC-bis-amino ligands
are formed and coordinate to Ag(I).
4
6
N
N
Ph
N
Ag
N
Ph
N
N
Br
Ag
Ag O
Br
2
Br
(
3a)
Br Ag
2
4 h, 25 °C
N
N
Ph
N
CH Cl
Ag
2
2
N
Ph
-
H O
N
2
N
(
4a, Yield = 86%)
Scheme 2. Synthesis of bis(NHC)Ag(I)bromide complexes 4a
2 6 3
Figure 1. Thermal ellipsoid plot of the diimidazolium salt, C32H44 Br N ∙2(CHCl ), 3a (50%
ellipsoids). Hydrogen atoms, bromide anions and solvent molecules have been omitted
for clarity. The two sides of the macrocycle were found to be equivalent by symmetry.
Analytically pure, light-sensitive Ag complexes 4a and 4b were
obtained in high yield as white crystalline solids. After the
reaction of silver oxide with solutions of 3a and 3b for 24 hours,
Attempts to deprotonate proligand 3a to form a macrocyclic
bis-NHC compound were not successful on large scales. An NMR
tube reaction between proligand 3a and excess sodium hydride
in DMSO-d showed the formation of free bis-NHC 3c in situ
6
under nitrogen atmosphere at room temperature. The in situ
generation of the free bis-NHC 3c was confirmed by a
1
the imidazolium 2-position H NMR resonances were no longer
1
3
present. Additionally, the characteristic C NMR signals of the
C-H 2-position of imidazolium compounds 3a and 3b were
shifted downfield from 139 and 144 ppm to 180 and 181 ppm
for the Ag complexes 4a and 4b, respectively. This downfield
1
8,46
shift is characteristic of Ag-NHC complexes.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
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2
-
2 4
View Article Online
macrocycles and the Ag atoms of the [Ag Br ] core is only is
AgBr2
DOI: 10.1039/C9DT02147G
2
.9328(18) Å, which is shorter than bond lengths reported for
N
N
N
N
Ph
Ph
N
N
Ag
N
N
Ph
Ph
18,25,58
similar Ag complexes and is indicative of Ag-Ag bonding.
This short Ag(1)-Ag(2) bond distance may explain the acute
angle observed for (C(4)-Ag(1)-C(13), as if the bonding to the
Ag O
2
(
3b)
2
4 h, 25 °C
Br Ag Br
2
-
2 4
Ag Br core is pulling the chelated Ag away from the center of
CH Cl
N
N
2
2
Ag
the macrocycle.
-
H O
2
N
N
(
4b, Yield = 73%)
Scheme 3. Synthesis of bis(NHC)Ag(I)bromide complexes 4a and 4b
1
The H NMR spectra of 4a and 4b show four methylene
resonances consistent with a benzylic methylene group and
three methylene resonances from the propyl chains of the
macrocycle. These data show that both sides of the macrocycle
and all four propyl chain linkers are equivalent, implying that
the Ag carbene macrocycle is fluxional in solution. The absence
1
3
of Ag- C coupling also suggests that 4a and 4b linkers are
fluxional and that the Ag-carbene bond is labile on the NMR
timescale.5
7,58 60
Figure 3. Thermal ellipsoid plot of silver complex 4b with thermal ellipsoids at 50%
probability. Hydrogen atoms, AgBr
2
-, and solvent molecules have been removed for
clarity. Selected bond distances (Å) and bond angles (°): Ag(1)-Br(1) = 2.450(4), Ag(1)-
Ag(2) = 3.005(3); Ag(2’)-Ag(1)-Ag(2) = 180.0, Br(1)-Ag(1)-Ag(2’) = 97.73(8), Br(1’)-Ag(1)-
Br(1) = 180.00(6).
A crystal suitable for single-crystal X-ray diffraction of 4b was
obtained by slow evaporation of a saturated dichloromethane
solution of macrocyclic-bis(NHC)silver(I) bromide 4b. In the
solid state structure of 4b (Figure 3), two structurally equivalent
cationic macrocyclic-bis(NHC)silver(I) complexes are linked
Figure 2. Thermal ellipsoid plot of silver complex 4a with thermal ellipsoids at 50%
probability. Hydrogen atoms have been removed for clarity. Selected bond distances (Å)
and bond angles (°): Ag(1)-Ag(2) = 2.9327(18), Ag(2)-Br(1) = 2.6802(19), Ag(2)-Br(2) =
2
=
-
-
2 2
through an anionic AgBr core. A second AgBr unit is found in
the unit cell; however, no close contacts are observed to the
-
.5370(19); C(4) -Ag(1)-Ag(2) = 123.0(3), Br(2)-Ag(2)-Br(1) = 126.42(6), Br(2)-Ag(2)-Ag(1) second anion. The AgBr
91.60(5)
2
unit linking the two macrocyclic Ag
complexes appears to be perfectly linear. The Br(1)-Ag(1)-Ag(2)
angle of 97.94° shows that the bridging Ag(1) atom possess a
slightly distorted square planar geometry. Unlike 4a, the Ag(1)-
Ag-NHC complexes have been shown to exhibit a variety of Ag(2) bond distance of 3.004(3) Å is consistent with literature
,
,61
61
binding modes in the solid state.18 25
In
order
to reports of Ag-Ag bond distances in similar compounds.
determine the nucleariety of the complexes, the structures Additionally, the C(14)-Ag(2)-C(1) angle was found to be
were investigated by single-crystal X-ray diffraction analysis.
170.30°, which is larger than the analogous angle in 4a. This
A colorless crystal suitable for X-ray crystallography of 4a was AgBr2- anionic core bridging between Ag-NHC complexes is
obtained by slow diffusion of chloroform into a saturated commonly seen as part of larger coordination-polymer crystal
6
1
dichloromethane solution of 4a. As shown in Figure 2, 4a exists systems in the literature. However, it does not appear to be as
6
5
as a dimer consisting of two crystallographically equivalent common for dimeric structures.
macrocyclic ligands, each chelating a single silver atom through Palladium complexes
the NHC moieties of the macrocycle. These Ag-macrocycle
Metal acetates have been used to synthesize NHC complexes
without isolation of the free carbene. Hermann et al. reported
the first structurally characterized trans-bis(NHC)Pd(II)Cl
complex that was prepared by direct deprotonation of
imidazolium salts with palladium acetate 34 64 In our hands,
the direct deprotonation of imidazolium salts 3a and 3b with
complexes are bridged by a dianionic core which consists of a
2
-
2-
[
Ag
2
Br
4
] unit. This bridging [Ag
2
Br
4
] unit is well known in the
2
1
8,25,50,59,61,62-64
literature.
The C(4)-Ag(1)-C(13) angle (NHC-Ag
NHC angle) was found to be 163.4°, showing the coordinated Ag
atom protruding from the center of the macrocycle. Notably,
the distance between the chelated Ag atoms within the
6
6,
,
4
| J. Name., 2012, 00, 1-3
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palladium(II) acetate and platinum(II) acetylacetonate at high of the pendant amines to Pd. Additionally, X-ray diffraction
View Article Online
DOI: 10.1039/C9DT02147G
temperature leads to inseparable mixtures of products.
shows that 5b exists as a mixed halide species with a
1
46 6
stoichiometry of C40H N PdCl1.57Br0.43
.
H NMR spectra of
typical preparations of 5b show only one set of peaks for 5b.
HR-FT-ICR-MS shows the monochloride mono cation
N
N
N
+
[
40 6
C H46ClN Pd] ): m/z 751.2508 (calcd) and 751.2528 (found).
PdCl (MeCN)2
2
(
4a or 4b)
Ph
N
X
Pd
Y
N
Ph
Mixtures of halomers have been previously observed as a result
of various synthetic methods to generate late metal carbene
20 h, 60 °C
CH Cl
N
68
2
2
species including transmetalation from silver salts.
The structure of 5b is comparable to the solid-state structure of
5
a (Figure 4). Both structures show nearly ideal square-planar
coordination of Pd. The stereochemistry of the Pd center is
likely related to the ring size of the macrocycle, specifically, the
number of methylene linkers in the chains between the two
Imidazole (5a, X=Y=Cl Yield = 55%)
Benzimidazole (5b, X=Cl1.57, Y=Br0.43 Yield = 58%)
Scheme 4. Synthesis of bis(NHC)Pd(II)Cl complexes 5a and 5b
2
NHC moieties. The cis isomer appears to be favored in shorter
,
Pd complexes 5a and 5b were prepared by the reaction of linkers.18 64 A minimum of six methylenes as linker is suggested
bis(NHC)silver(I) bromide complexes 4a and 4b with to favor trans coordination by DFT studies,18 consistent with
PdCl
forms silver bromide as
Bis(NHC)Pd(II)Cl
complexes 5a and 5b were obtained as white envelop the Pd center. The torsion angles between the square
solids after removal of silver bromide by filtration and planes of the Pd(II) center and the planes of the NHC rings are
2
(MeCN)
2
(Scheme 4). After 20 hours at 60 ˚C, the reaction our observations.
pale yellow precipitate. The macrocyclic ligands in 5a and 5b appear to completely
a
2
evaporation of solvent (Scheme 4).
115.5° and 108.9°, respectively. Effectively, the Pd-Cl bonds
protrude from the plane of the macrocyclic structure
surrounding the Pd center. The distances between the Pd and
amine N atoms in 5a and 5b are 3.746 Å and 3.825 Å, which are
well beyond the sum of the van der Waals radii of Pd and N (3,18
7
3,69
Å).
It is reasonable to assume that these large distances
allow ample space for reactions to occur at Pd (vide infra).
Figure 4. Thermal ellipsoid plot of 5a with thermal ellipsoids at 50% probability.
Hydrogen atoms have been removed for clarity. Selected bond distances (Å) and bond
angles (°): Pd(1)-Cl(1)= 2.3387(9), Pd(1)-C(1) = 2.031(3), C(1)-N(1) = 1.352(4); Cl(1)-Pd(1)-
Cl(1’) = 180.00(2), C(1)-Pd(1)-Cl(1) = 90.05(9), C(1)-Pd(1)-C(1’) = 180.0
A crystal of 5a suitable for X-ray crystallography was obtained
by slow diffusion of pentane into a saturated dichloromethane
solution of the Pd compound. The X-ray structure (Figure 4)
confirms that the NHC moieties of the macrocycle coordinate in
2
a trans fashion. 5a was found to possess a C -symmetric
structure. Additionally, no coordination is observed from the
pendant amines in the macrocycle to the Pd center. The [C(1)-
Pd-C(1’)] angle was found to be 180.00˚, and the Pd center has
a nearly ideal square-planar geometry, in contrast to Hazari’s Figure 5. Thermal ellipsoid plot of carbene complex 5b with thermal ellipsoids at 50%
probability. Hydrogen atoms, a disordered phenyl group and a partially occupied Br have
been omitted for clarity. Selected bond distances (Å) and bond angles (°): Pd-Cl(1)=
similar complexes.18 Additionally, the observed bite angle of
the ligand is larger than that of many Pd complexes with trans-
2
.241(16), Pd-C(1) = 2.027(12), C(1)-N(1) = 1.343(15); Cl(1)-Pd(1)-Cl(1’) = 180.0, C(1)-
6
7
spanning phosphine ligands. The two pendant amine groups
within the macrocycle are positioned directly above and below
the Pd-NHC coordination plane, as if approaching the Pd along
the idealized z-axis of the square-planar complex. The amine N-
Pd distance was found to be 3.746(2) Å.
Pd(1)-Cl(1) = 89.3(6).
Pd-catalyzed coupling reactions
The Suzuki reaction, the coupling of an aryl halide with
phenylboronic acid, is one of the most widely known cross-
X-ray diffraction of 5b (Figure 5) shows a trans configuration for
the NHC moieties of the macrocyclic ligand with no coordination
7
0
coupling reactions.
The macrocyclic-trans-bis(NHC)PdCl
2
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Journal Name
complexes 5a and 5b were screened for activity as precatalysts than similar reported non-macrocyclic catalysts.1V8iewDAureticlteoOntlhinee
for Suzuki and Heck cross-coupling reactions. The reaction apparently quantitative coupling of DaOryI:l10b.1r0o3m9/iCd9eDsT02u1s4in7Gg
conditions for the Suzuki and Heck reactions are described in precatalyst 5a and 5b, the couplings of 4-bromonitrobenzene
the experimental procedures and were modified from the and 4-bromotoluene with phenylboronic acid were selected for
literature.1
8,71
The products were detected by gas further investigations at lower precatalyst loads (0.1 mol %). At
chromatography-mass spectroscopy (GC/MS) and the 0.1 mol % precatalyst loading, 4-bromotoluene was found to
percentage yield was calculated by comparing the proton afford appreciable yield (Table 1, Entry 17) but 4-
resonance of the product with the known proton resonance of bromonitrobenzene gave poor yield (Table 1, Entries 18-19).
an internal standard (1,3,5-trimethoxybenzene).
2
Next, the macrocyclic-trans-bis(NHC)PdCl complexes were
The Suzuki coupling of aryl halides with phenylboronic acid screened as precatalysts for the Heck coupling reaction
(Scheme 5) was performed using 1 mol % of the Pd precatalyst (Scheme 6). Initially, 4-iodoacetophenone was combined with
(
Table 1).
n-butyl acrylate in the presence of 0.1 to 0.02 mol % of
Cs CO
R
2
3
precatalysts 5a and 5b.
5
a or, 5b
,4-dioxane
00 °C
R
+
B(OH)2
R
Na CO3
O
2
1
X
O
n-Bu
5
a or 5b
1
+
O
n-Bu
DMA
O
X = Cl, Br, I
R = H, CH , -COCH , -OCH , -NO
140 “C
R
3
3
3
2
X
Scheme 5. Suzuki coupling reaction between aryl halides and phenylboronic acid
X = Cl, Br, I
R = H, CH , -COCH , -OCH , -NO
2
3
3
3
The bidentate macrocyclic-trans-bis(NHC)PdCl
2
complexes 5a
Scheme 6. Heck coupling reaction between aryl halides and n-butyl acrylate
and 5b were demonstrated to be competent precatalysts for
Suzuki cross-coupling reactions. Various aryl halides, including
aryl chlorides, bromides and iodides, were coupled with phenyl
boronic acid in moderate to excellent yields (Table 1).
Our data shows that 5b generates a more active catalyst than
a, showing 10-16% higher yields for the Heck coupling reaction
Table 2). A possible explanation for this observation could be
5
(
the absence of vinylic imidazole protons on the benzimidazole
heterocycle. Imidazole C-H protons have been postulated to be
acidic enough to react with bases during catalysis and serve as
Table 1 Suzuki coupling of aryl halides with phenylboronic acid using (5a-5b)
Entry
Substrate
4-bromonitrobenzene
4-bromonitrobenzene
bromobenzene
bromobenzene
bromobenzene
4-iodoanisole
4-iodoanisole
4-bromotoluene
4-bromotoluene
Time (h)
Cat.
5a
5b
5a
5b
5a
5a
5b
5a
5b
5a
5b
5a
5b
5a
Yield (%)a
>99
>99
61
1
2
3
4
5
6
7
8
9
.
.
.
.
.
.
.
.
.
3
3
3
3
6
16
10
3
72
an additional route to catalyst decomposition.
Table 2. Heck reaction between n-butyl acrylate and 4-iodoacetophenone
50
96
96
>99
97
70
37
9
52
>99
70
>99
>99
Entry
Cat. (mol%)
5a (0.1)
5a (0.1)
5a (0.1)
5a (0.02)
5b (0.1)
5b (0.1)
5b (0.1)
5b (0.02)
time (h)
Yield (%)a
TOFb
510
400
670
2037
660
567
1025
2378
1
2
3
4
5
6
7
8
.
.
.
.
.
.
.
.
1
1.5
4
1
1
1.5
4
1
50
60
70
38
66
85
82
46
3
1
1
1
1
1
1
1
1
1
1
2
0.
1.
2.
3.
4.
5.
6.
7.
8.
9.
0.
4-chlorotoluene
4-chlorotoluene
24
24
8
8
17
3
3
7
7
7
4-chloroacetophenone
4-chloroacetophenone
4-chloroacetophenone
4-bromoacetophenone
4-bromoacetophenone
4-bromotoluene
4-bromonitrobenzene
4-bromonitrobenzene
4-bromonitrobenzene
a
1
Yield determined by H NMR using an internal standard; only the trans isomer was
b
5a
5b
5a
5b
5a
none
observed. Turnover frequency (TOF) = (mol of product)/((mol of Pd) h).
2 3
Conditions: All reactions used 4-iodoacetophenone (0.2 mmol), Na CO (0.24
mmol), tetra-n-butylammonium bromide (0.02 mmol), n-butyl acrylate (0.4 mmol,
2 equivalents), dimethyl-acetamide (1.5 mL), 140 ˚C.
b
64
9
4
b
b
Table 3 summarizes a survey of substrates for the coupling of
aryl halides with n-butyl acrylate in the presence of precatalyst
24
0
a
1
The average of two runs determined by H NMR using an internal standard. No
increase in yield was observed if the reaction time was increased. Conditions: 1
mol % of precatalyst, Cs CO (0.90 mmol), substrate (0.20 mmol), phenylboronic
acid (0.45 mmol) and 1,4-dioxane (1.5 mL) at 100 °C under N
.1 mol %.
5
b (Scheme 6). Various aryl iodides and aryl bromides can be
coupled with n-butyl acrylate efficiently using 5b; however, in
contrast to the Suzuki coupling reaction, aryl chlorides show low
reactivity.
2
3
b
2
. Precatalyst loading:
0
The Heck coupling reaction using 0.1 mol % of precatalyst 5b
shows high yield with trans selectivity for 4-bromonitrobenzene
Precatalysts 5a and 5b both facilitate coupling of the less
reactive unactivated aryl chlorides with phenylboronic acid
(Table 3, Entry 1). 4-Bromobenzene appears sluggish compared
(Table 1, Entries 10, 11) in low to moderate yields. Activated
to 4-bromoacetophenone, but still gives moderate yield at
longer reaction times using 0.1 mol % precatalyst (Table 3,
Entries 2-5). 4-Bromoacetophenone affords a yield of 32 % using
aryl-chlorides show moderate to excellent yields (Table 1,
Entries 12-14). In these data, 5a and 5b exhibit higher activity
6
| J. Name., 2012, 00, 1-3
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Pleas De ad l to o nn oT tr aa nd sj au cs t ti omn as rgins
Journal Name
ARTICLE
0
.02 mol % 5b, which is comparable to literature reports at reactivity of these macrocyclic ligands; to combat ligand de-
View Article Online
3
DOI: 10.1039/C9DT02147G
3
2
similar catalyst loadings. 4-Chlorotoluene does not show coordination, we plan to explore metals that will favour κ and
appreciable yield of product, and 4-chloroacetophenone only higher coordination numbers for the macrocyclic ligands.
R
shows low yield at 0.1 mol % precatalyst (Table 3, Entries 7-8).
Overall, precatalysts 5a and 5b show comparable catalytic
N
N
N X Pd
N
N
X
N
N
X
N
performance for the Heck reaction with a broader substrate
scope than similar macrocyclic Pd(II) systems reported in the
X
R
R
N
N
Pd
N
N
Pd
N
3
6
literature. We must note that the performance of 5a and 5b is
poor when compared to state-of-the-art Pd C-C coupling
systems. State-of-the-art systems currently can afford near
complete conversion at catalyst loadings of 100 mol ppm or
R
R
X
X
N
N
N
N
N
trans
pseudorotation
R
cis
lower. Additionally, some reports of TOF values are several Scheme 7. cis / trans isomerisation promoted by pendant amine groups via 5-coordinate
7
3
rearrangement.
orders of magnitude greater than those found here. Other
analogous compounds in the literature also show poor
performance compared to state-of-the-art systems.
1
8,36
Conclusions
In conclusion, we have synthesized 20-membered macrocyclic
bis(NHC)-imidazolium proligands 3a and 3b derived from
imidazole and benzimidazole, Ag complexes 4a and 4b, and
The competence of complexes 5a and 5b as precatalysts for C-
C bond forming reactions implies that an active molecular
catalyst species could be capable of facile cis / trans
isomerization of the NHC moieties through intramolecular five-
coordinate rearrangement assisted by the pendant amines
2
novel macrocyclic-trans-bis(NHC)Pd(II)Cl complexes 5a and 5b.
7
4
present in the macrocycle (Scheme 7).
Interestingly, solid-state samples of 4a and 4b are dimeric and
show different coordination environments for the Ag(I)-anionic
core of dimeric structures. Ag complexes 4a and 4b were
competent transmetalation agents to bis(acetonitrile)-
dichloropalladium(II). Complexes 5a and 5b were found to be
stable towards air, moisture and heat. The molecular structures
of proligand 3a and 3b, Ag carbene complexes 4a and 4b, and
macrocyclic-trans-bis(NHC)Pd(II)Cl complexes 5a and 5b were
2
determined by single-crystal X-ray crystallography. 5a and 5b
possess a square-planar metal center, and the 20-membered
macrocyclic-bis(NHC)-imidazolium/benzimidazolium
Table 3 Heck coupling of aryl halides with n-butyl acrylate using 5b
Entry
substrate
4-bromonitrobenzene
4-bromoacetophenone
4-bromoacetophenone
4-bromotoluene
bromobenzene
4-iodoanisole
4-chlorotoluene
4-chlomoacetophenone
4-bromonitrobenzene
mol% time (h) Yield (%)a
1
2
3
4
5
6
7
8
9
.
.
.
.
.
.
.
.
.
0.1
0.1
0.02
0.1
0.1
0.1
4
1
1
7
8
>99
51
32
47
42
50
0
1
0.1
16
16
24
0.1
4
moiety
none
0
acts as a bidentate ligand. The coordination modes of the ligand
have been observed to consistently be κ in the solid state and
at no point is formation of cationic metal complexes by
2
a
1
Yield determined by H NMR using an internal standard. Only the trans isomers
were observed. Conditions: All reactions used 0.1 mol % of precatalyst 5a and 5b,
aryl halide (0.2 mmol), Na
(
mL), 140 ˚C.
2
CO
3
(0.24 mmol), tetra-n-butylammonium bromide displacement of an inner-sphere halide observed. Additionally,
0.02 mmol), n-butyl acrylate (0.4 mmol, 2 equivalents), dimethylacetamide (1.5 cis / trans mixtures of the NHC moieties are not observed in the
solid state for the Pd systems synthesized. The exploration of
the transmetalation behaviour of 4a and 4b with other metals
and the resultant coordination geometries of these macrocyclic
ligands will be reported elsewhere.
The formation of colloidal palladium clusters that serve as a
reservoir for the actual catalytic species is common in Pd
catalysis.7
5-77
Douthwaite and co-workers reported the
The macrocyclic-trans-bis(NHC)palladium(II) complexes 5a and
possibility of ligand de-coordination from the metal during a
catalytic reaction and concluded that the reaction might be
catalyzed by colloidal palladium because they observed an
increase in turnover frequency at lower catalyst loading. In this
work, 5a and 5b also show an increase in activity at lower
5
b were demonstrated to be active precatalysts for Heck and
Suzuki cross-coupling reactions. Unactivated aryl-Cl bonds can
undergo Suzuki coupling in modest yield by 5a. Notably, we
observed near quantitative yield for Suzuki coupling of the
activated substrate 4-chloroacetophenone catalyzed by 5b. This
result is comparable to state-of-the-art catalyst systems
capable of coupling aryl-Cl bonds, which are generally
0
catalyst loading, which is a common feature of Pd catalyzed
reactions.32 This observation is inconsistent with the previous
1
8
report of similar Pd systems,
and we infer that loss of ligand
8
0
considered to be less reactive than heavier aryl halides. We
have shown that complexes 5a and 5b can catalyze Suzuki and
Heck coupling reactions in the presence of the steric bulk of our
macrocyclic ligands encompassing the Pd center. Although our
catalysts are not as active as current state-of-the-art Pd
coupling systems, our results show improved yield at shorter
reaction times compared to macrocyclic and analogous Pd
from the metal and formation of colloidal Pd is indeed possible.
Recent work by Ananikov demonstrates that Pd-based “cocktail
7
8
systems” in fact contain several dominant catalytic species.
Furthermore, studies have shown that the popular Hg drop test
in fact seems to be deficient in distinguishing between possible
catalytic species.79 Further detailed mechanistic studies are
underway and will be reported elsewhere. These Pd systems are
our first step into exploring the coordination chemistry and
,
compounds in the literature.36 18
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Journal Name
Compounds A, B and 1 were synthesized according to literature
procedures.
N-benzylbis(3-imidazolpropyl)amine (2a).
Experimental Methods
General Procedures
View Article Online
DOI: 10.1039/C9DT02147G
5
,6
Oxygen- and water-sensitive reactions and manipulations were Imidazole (0.86 g, 12.6 mmol) in THF (10 mL) was added
performed using glove box and Schlenk techniques under dropwise to NaH (0.30 g, 12.6 mmol) while stirring at ambient
nitrogen atmosphere. All solvents were purchased anhydrous temperature. Stirring was continued for 16 hours. To this slurry,
and were stored over molecular sieves in the glove box. All N-benzylbis(3-bromopropyl)amine (1.2 g, 3.44 mmol) in THF (10
2 2
reagents were used as supplied (Aldrich). [PdCl (MeCN) ] was mL) solution was added, and the resulting solution was stirred
8
1
prepared using the literature procedure. High-resolution mass for an additional 16 hours. The solution was filtered and the
spectra were recorded using a Bruker APEX-II FTMS instrument volatile material was removed under reduced pressure to yield
with an electrospray ionization source. Standard ESI-MS spectra N-benzylbis(3-imidazolpropyl)amine as an pale yellow viscous
were recorded on a Shimadzu 8040 triple quadrupole-MS liquid (1.76 g, 95 %).
system. X-ray crystallographic data were collected on a Bruker C H ), 7.02 (s, 2H, imi), 6.78 (s, 2H, imi), 3.94 (t, J = 6.72, 4H, -
1
3
H NMR (CDCl ): δ 7.37-7.02 (m, 5H of
6
5
1
13
APEX CCD-based X-ray diffractometer. H and C NMR spectra NCH ), 3.52 (s, 2H, PhCH ), 2.42 (t, J = 4H), 1.87 (pen, J = 6.72,
were recorded at probe temperature on 300 MHz and Bruker 4H). 13C NMR (CDCl ): δ 139, 137.1, 129.5, 128.8, 128.5, 127.4,
2
2
3
Avance DPX 400 spectrometers. Chemical shifts are reported in 118.6, 58.7, 50.8, 44.6, 28.6. HR FT-ICR MS calcd for
parts per million downfield shift from SiMe
4
; coupling constants [C H N +H]: m/z [M+H]
: 324.2183; found 324.2803.
+
1
9 25 5
1
are reported in Hz. H NMR spectra were referenced internally N-benzylbis(3-benzimidazolpropyl)amine (2b).
to the residual proton solvent resonance of CDCl
3
( 7.26), Benzimidazole (0.75 g, 6.30 mmol) in THF (10 mL) was added
( 2.50). C NMR spectra were dropwise to NaH (151 mg, 6.30 mmol) while stirring at ambient
( 77.0), CH Cl ( 53.84), DMSO-d ( temperature. Stirring was continued for 16 hours. To this slurry,
9.51). H COSY, C HSQC, NOESY experiments were performed N-benzylbis(3-bromopropyl)amine (1 g, 2.86 mmol) was added
1
3
CD
2 2 6
Cl ( 5.32), DMSO-d
referenced to CDCl
3
3
2
2
6
1
13
using standard Bruker pulse sequences. Microanalysis were and the resulting solution was stirred for an additional 16 hours.
performed by Midwest Microlab (Indianapolis, Indiana) or at The solution was filtered, and the volatile material was removed
the University of Rochester CENTC facility where microanalysis under reduced pressure to yield N-benzylbis(3-benzimidazol-
samples were weighed with a PerkinElmer Model AD-6 propyl)amine as an colorless viscous liquid (1.13 g, 94 %).
Autobalance and their compositions were determined with a NMR (CDCl ): δ 7.82-7.78 (ortho, 2H of –CH C H ), 7.58 (s, 2H,
1
H
3
2 6 5
PerkinElmer 2400 Series II Analyzer. Air-sensitive samples were benzimi-NCHN-), 7.34-7.27 (m, 8H, benzimi and 3H, -CH C H ),
2
6 5
handled in a VAC Atmospheres glovebox at the CENTC facility. 4.12 (t, J = 6.8, 4H, -NCH ), 3.52 (s, 2H, PhCH ), 2.42 (t, J = 6.4,
2
2
Gas chromatography was performed on an Agilent 6890/5973N 4H), 1.87 (pen, J = 6.8, 4H, PhCH CH CH ). 13C NMR (CDCl ): δ
2
2
2
3
in positive ion CI mode with a flow rate of 1 mL/min constant 144, 143, 139, 133.7, 129, 128.7, 127.6, 122.9, 122.2, 120.6,
flow He, inlet temperature of 250°C, column temperature of 109.6, 58.7, 51.2, 43, 27. HR FT-ICR MS calcd for C H N ): m/z
2
7 29 5
8
0°C, 20°C/min increase to 250°C (held for 2 min) for a total [M+H]
+
: 424.2183; found 424.2496.
[L1][Br ] (3a).
time of 16 min.
2
A solution of N-benzylbis(3-imidazolpropyl) amine 2a (1.1 g, 3.4
mmol) and N-benzylbis(3-bromopropyl)amine (1 g, 2.9 mmol) in
X-ray crystallography
A crystal of suitable shape and dimensions was selected for acetonitrile (200 mL) was refluxed for 48 hours. Removal of the
structural analysis. Intensity data were collected using a solvent and dissolving in CHCl at -40 ˚C gave the desired cyclic
3
8
2
diffractometer with a Bruker APEX CCD area detector and diimidazolium bromide salt 3a as a white hygroscopic powder
graphite-monochromated radiation. The data were corrected in 60 % yield (1.3 g).
H NMR (CD Cl ): δ 10.77 (s, 2H of –NCHN-
for absorption by the empirical method, giving minimum and ), 7.40-7.32 (m, 10H, -C H and 4H, J = 1.5, imi-CH=CH), 4.32 (t, J
1
2
2
8
3
6
5
maximum transmission factors. The space group was = 9.20, 8H, -NCH ), 3.59 (s, 4H, PhCH ), 2.57 (t, J = 8.8, 8H,
2
2
determined by systematic absences and statistical tests and was PhCH CH CH ), 2.18 (pen, J = 9.20, 8H, PhCH CH CH ).
H NMR
1
2
2
2
2
2
2
verified by subsequent refinement. The structure was solved by (DMSO-d ): δ 9.20 (s, 2H of –NCHN-), 7.77 (d, 4H, J = 1.5, imi-
6
direct methods and was refined by full-matrix least-squares CH=CH), 7.32 (m, 10H, -C H ), 4.08 (t, J = 6.90, 8H, -NCH ), 3.51
6
5
2
8
4
2
methods on F . The positions of hydrogens bonded to carbons (s, 4H, PhCH ), 2.25 (t, J = 6.6, 8H, PhCH CH CH ), 1.85 (pen, J =
were initially determined by geometry and were refined using a 7.10, 8H, PhCH CH CH ). 13C NMR (CD Cl ): δ 139, 137, 129.4,
2
2
2
2
2
2
2
2
2
riding model. Non-hydrogen atoms were refined with 128., 127, 122, 59, 50, 48, 27. HR FT-ICR MS calcd for
anisotropic displacement parameters. Hydrogen atom [C H N B ]
): m/z [M-Br] : 591.2805; found 591.2803. Calcd
): m/z [M-2Br] : 511.3544; found 511.3546.
+
+
3
2 44 6 r
displacement parameters were set to 1.2 times the isotropic for [C H N ]
+
+
3
2 43 6
equivalent displacement parameters of the bonded atoms. A [L2][Br ] (3b).
2
summary of refinement parameters can be found in Table 4. A solution of N-benzylbis(3-imidazolpropyl)amine 2b (1 g, 2.36
Further description and details of the refinement of each mmol) and N-benzylbis(3-bromopropyl)amine (823 mg, 2.36
structure can be found in the supporting information.
mmol) in acetonitrile (120 mL) was refluxed for 24 hours.
Concentration of the solution and cooling to -40 ˚C gave the
Synthesis and Characterization of Compounds.
desired cyclophane bis(NHC) ligand 3b as a white powder in 50
1
%
yield (910 mg). H NMR (CDCl
3
): δ 11.31 (s, 2H of –NCHN-),
8
| J. Name., 2012, 00, 1-3
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Page 9 of 14
Pleas De ad l to o nn oT tr aa nd sj au cs t ti omn as rgins
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ARTICLE
7
7
=
6
.57-7.54 (d, 4H, -CH
.35 (t, J = 7.32, 4H, -CH
7.2, 8H, benzimidazole -NCH
.4, 8H, PhCH CH CH ), 2.65 (pen, J = 7.2, 8H, PhCH
2
C
6
H
5
), 7.46 (d, 4H, benzimidazole -C
), 7.27 (d, 4H, -CH ), 4.64 (t, J for [C40
), 3.69 (s, 4H, PhCH
6 4
View Article Online
H ), 128.8, 127, 124, 119, 58.6, 54.3, 46.3, 28.5. HR FT-ICR MS calcd
+
DOI: 10.1039/C9DT02147G
2
C
6
H
5
2 6
C
H
5
H
46AgN
6
] : m/z [M-AgBr
2
] 717.2829, 719.2828; found
+
2
2
), 2.83 (t, J = 717.2829, 719.2828. Calcd for [C40
46 6
H N +H] : m/z (M-2AgBr)
1
3
2
2
2
2
CH
2
CH
2
). C 611.3857;
Br
), 51.6, 45.7, 27. HR FT-ICR MS calcd 50.16, H 5.21, N 8.16%. Analysis was attempted several times
: m/z [M-Br+H]: 693.3101, 691.3208; found and the best analysis obtained matched the above results with
: C 62.33, H solvent remaining in the bulk solid.
trans-bis(NHC)Pd(II)Cl (5a).
Silver carbene 4a (210 mg, 0.237 mmol) was dissolved in
A grey suspension of sodium hydride (25 mg, 0.037 mmol) in 1 dichloromethane (15 mL) and PdCl (MeCN) (61.5 mg, 0.237
mL of DMSO-d was added to 3a (22 mg, 0.91 mmol) at room mmol) was added. The reaction was stirred at 25 ˚C for 30
found
611.3857.
Anal.
Found
for
NMR (CDCl
1
for C40H48BrN
6
6
6
3
): δ 144 (–NCHN-), 139.5, 131.7, 129, 128.6, 127,
40
C H46Ag
2
2 6
N (0.6C
5
H12): C 50.46, H 4.94, N 8.52%; Calcd, C
26, 113, 60.4 (4H, PhCH
2
+
91.3118, 693.3099. Anal. Found for C40
2 6
H48Br N
.21, N 11.052%; Calcd, C 62.18, H 6.26, N 10.88%.
2
Generation of free carbene in situ (3c).
2
2
6
temperature. The reaction mixture turned red in color and minutes and at 60 ˚C for 20 hours. A pale yellow precipitate
effervesced immediately. The reaction mixture was stirred for 2 formed. The solution was cooled to room temperature and
minutes. The reaction mixture was filtered and transferred to a filtered, and the volatiles were removed from the filtrate under
1
J. Young tube. H NMR (DMSO-d
6
): δ 9.20 (s, 2H of –NCHN-), reduced pressure to give a white solid. Crude white solid was
), 3.81 (m, 8H, -NCH ), 3.51 (s, 4H, dissolved in a minimal amount of methylene chloride and
CH CH ), 1.71 (m, 8H, PhCH CH CH ). excess pentane was added to precipitate the product. The
): δ 208.4, 140.0, 128.5, 128.0, 126.1, 119.0, product was isolated by filtration and was washed with excess
7
.33-7.23 (m, 10H, -C
), 2.27 (m, 8H, PhCH
3C NMR (DMSO-d
H
6 5
2
PhCH
1
2
2
2
2
2
2
2
6
5
8.0, 50.2, 48.0, 28.0.
pentane to give 5a as white solid. Yield: 90 mg, 55 %. Crystals
[
(L1)Ag] (Ag Br ) (4a).
2
2
4
suitable for X-ray diffraction were grown at room temperature
3
a (218 mg, 0.32 mmol) was dissolved in dichloromethane (20 under nitrogen by slow vapor diffusion of pentane into a
1
mL), and Ag
vessel was covered with aluminium foil, and the mixture was 7.47 (d, J = 7.6, 4H, ortho-C
stirred for 24 hours. The reaction mixture was then filtered 7.23 (t, J = 7.2, 2H, para-C
through Celite, and the filtrate was dried under reduced 4.59 (t, J = 5.6, 8H, imidazole-NCH
pressure to give 4a as a white solid. Yield: 247 mg, 86 %. Crystals J = 5.6, 8H, PhCH CH CH ), 2.18 (t, J = 6, 8H, PhCH
2
O (150 mg, 0.64 mmol) was added. The reaction saturated dichloromethane solution of 5a. H NMR (CD
2
Cl
2
):
),
), 6.82 (s, 4H, imidazole –CHCH-),
), 3.68 (s, 4H, PhCH ), 3.00 (t,
CH
6 5 6 5
H ), 7.35 (t, J = 7.6, 4H, meta-C H
6 5
H
2
2
1
3
2
2
2
2
2 2
CH ). C
suitable for X-ray diffraction studies were grown at room NMR (CD
2
Cl
2
): δ 170.7, 141, 129, 128.6, 127, 121, 59.8, 33.8,
+
temperature under nitrogen by slow diffusion of pentane into 47.8, 31. HR FT-ICR MS calcd for [C32
6
H42ClN Pd] ): m/z [M-Cl]
1
the saturated dichloromethane solution of 4a. H NMR (CD
2
Cl
2
): 651.2194;
found
Pdˑ(CH Cl
651.2186.
Anal.
found
for
δ 7.40 -7.25 (m, 10H, -C
6 5
H ), 7.05 (s, 4H, imi-CH=CH), 4.25 (t, J =
32
C H42Cl
2
N
6
2
2
): C 51.62, H 5.36, N 10.52%;. Calcd, C
6
, 8H, -NCH ), 3.63 (s, 4H, PhCH
2
2
), 2.62 (t, J = 5.4, 8H, 51.28, H 5.74, N 10.87 %. Analysis was attempted several times
1
PhCH
CDCl
2
CH
): δ 7.36 (m, 10H, -C
), 3.60 (s, 4H, PhCH
), 1.94 (pen, J = 11.4, 8H, PhCH
): δ 180, 139.7, 129.5, 128.5, 128.3, 126.9, 121.4, 58.2 dichloromethane (10 mL), and PdCl
2
CH
2
), 1.96 (pen, J = 11.4, 8H, PhCH
2
CH
2
CH
2
). H NMR and the best analysis obtained matched the above results with
(
3
6 5
H
), 7.02 (s, 4H, imi-CH=CH), 4.28 (t, solvent remaining in the bulk solid.
), 2.60 (t, J = 5.2, 8H, trans-bis(NHC)Pd(II)X (5b).
). C NMR Silver carbene 4b (150 mg, 0.152 mmol) was dissolved in
(MeCN) (40 mg, 0.155
J = 6, 8H, -NCH
PhCH CH CH
Cl
PhCH
21, 59 (PhCH
m/z (M-AgBr ) 617.2516; found 617.2. Calcd for [C32
M-2AgBr+H) 511.3549; found 511.3. Anal. Found for filtered, and the volatiles were removed from the filtrate under
2
2
2
1
3
2
2
2
2 2 2
CH CH
(CD
2
2
2
2
1
3
(
1
2
N), 48.6, 30.1. C NMR (CDCl
3
): δ 181, 139, 129, 127, mmol) was added. The reaction was stirred at 25 ˚C for 30
+
2
N), 53, 49, 30. ESI-MS calcd for [C32
H
42AgN
6
] ): minutes and at 60 ˚C for 20 hours. A pale yellow precipitate
2
42 6
H N
+H]+: formed. The solution was cooled to room temperature and
(
C
32
H
42Ag
2
Br
2
N
6.: C, 43.09; H, 4.75; N, 9.12%. Calcd for reduced pressure and were washed with pentane to give 5b as
: C 43.36, H 4.78, N 9.48%. a white solid. Yield: 72 mg, 58 % based on C40
(4b). (MW = 807.24). Crystals suitable for X-ray diffraction were
b (100 mg, 0.13 mmol) was dissolved in dichloromethane (20 grown at room temperature under nitrogen by slow vapor
C
32
H42Ag
2
Br
2
N
6
46 6
H N PdCl1.47Br0.43
[
2 2 2
(L2)Ag] (AgBr )
3
mL), and Ag
2
O (60 mg, 0.26 mmol) was added. The reaction diffusion of pentane into a saturated dichloromethane solution
1
vessel was covered with aluminium foil, and the mixture was of 5b. H NMR (CD
stirred for 24 hours. The reaction mixture was then filtered 4H, imi-CH=CH), 5.02 (bs, 8H, benzimidazole-NCH
through Celite, and the filtrate was dried under reduced PhCH
pressure to give 4b as a white solid. Yield: 116 mg, 91 %. Crystals PhCH
2
Cl
2
): δ 7.56 -7.25 (m, aromatic 18H, -C
), 3.76 (s, 4H,
), 2.18 (t, J = 5.6, 8H,
): δ 182.6, 141.2, 134.8, 128.9,
6 5
H and
2
2
), 3.09 (bs, 8H, PhCH
2
CH
2 2
CH
1
3
2
CH
2
CH
2
). C NMR (CD
2
Cl
2
suitable for X-ray diffraction studies were grown at room 128.7, 127, 123, 110, 59, 44.5, 30.1, 28.7. HR FT-ICR MS calcd
+
temperature under nitrogen by slow diffusion of pentane into for [C40
H46Cl
2 6
N
Pd] ): m/z [M-Cl] 751.2507; found 751.2518.
1
the saturated dichloromethane solution of 4b. H NMR (CD
2
Cl
), 7.29 N 9.42%; Calcd, C 55.39, H 5.47, N 9.40%. Analysis was
), 3.72 (s, attempted several times and the best analysis obtained
), 2.05 (m, 8H, matched the above results with solvent remaining in the bulk
): δ 181, 144, 140, 134, 129, solid.
2 6 2 2
): Anal. found for C40H46Cl1.57Br0.43N Pdˑ(CH Cl ): C 55.19, H 5.42,
7
(
4
.50-7.39 (m, 8H, -CH
d, 2H, para-C ), 4.72 (m, 8H, benzimidazole-NCH
), 2.73 (t, J = 4.80, 8H, PhCH CH CH
2 6 5 6 4
C H and 8H, benzimidazole -C H
6
H
5
2
H, PhCH
CH
2
2
2
2
1
3
PhCH
2
2
CH
2
). C NMR (CD
2
Cl
2
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 9
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Pleas De ad l to o nn oT tr aa nd sj au cs t ti omn as rgins
Page 10 of 14
ARTICLE
Journal Name
General procedure for Suzuki coupling reactions.
A 15 mL Teflon-sealed pressure tube with a magnetic stir bar
was charged with aryl halide (0.20 mmol), n-butyl acrylate (51.3
mg, 0.40 mmol), n-butyl ammonium bromide (6.5 mg, 0.02
mmol), and 1,3,5-trimethoxybenzene (20-30 mg) as an internal
standard. A solution of precatalyst (0.02 mol %, 50 L, 4 mM
View Article Online
DOI: 10.1039/C9DT02147G
A 15 mL Teflon-sealed pressure tube with a magnetic stir bar
was charged with aryl halide (0.2 mmol), phenylboronic acid (36
mg, 0.45 mmol), cesium carbonate (196 mg, 0.90 mmol), and
1
,3,5-trimethoxybenzene (20-30 mg) as an internal standard.
Then, 1,4-dioxane (1.50 mL) and a solution of the precatalyst in
CH Cl (0.1 mol %, 50 µL, 0.04 M) were added in the glove box.
solution) in CH
Na CO (24 mg, 0.23 mmol) and N,N-dimethylacetamide (2 mL)
were added, and the tube was flushed with N . The reaction
2 2
Cl was added in the glove box. Anhydrous
2
3
2
2
2
The reaction mixture was heated to 100 °C in an oil bath with
vigorous stirring. The reaction mixture was filtered through a
mixture was heated in an oil bath at 140 °C for the desired time
1
period. The reaction mixture was cooled and filtered through a
2
short pad of SiO , and the filtrate was analyzed by GC and H
NMR.
1
short pad of SiO
2
. The filtrate was analyzed by H NMR.
General procedure for Heck coupling reactions.
Conflicts of interest
The authors declare no conflicts of interest.
Table 4. Crystal data and structure refinement for silver carbene complexes 4a, 4b , 5a and 5b
3
a
4a
4b
5a
5b
Empirical formula
Formula weight
Crystal system
Space group
a (Å)
C
34
H
46Br
2
Cl
6
N
6
C
65
H
86Ag
4
4
Br Cl
N
2 12
C
82
H
96Ag
4
4
Br Cl
N
4 12
C
32
H
42Cl
2
N
6
Pd
C
40
H
6
46Br0.43Cl1.57N Pd
911.29
orthorhombic
Pbca
9.350(3)
16.797(6)
25.649(8)
90
90
90
4028(2)
4, 0.5
1.503
1857.47
monoclinic
P2 /c
9.840(4)
22.482(8)
15.732(6)
90
93.172(5)
90
3475(2)
2, 0.5
2142.62
monoclinic
C2/c
31.67(4)
10.719(17)
25.17(4)
90
105.24(2)
90
8244(21)
4, 0.5
1.726
0.71073
100(2)
4272
688.01
monoclinic
P2 /c
11.612(4)
8.505(2)
16.280(5)
90
94.685(4)
90
1602.4(8)
2, 0.5
807.24
monoclinic
P2 /n
1
1
1
12.462(17)
10.751(15)
14.335(19)
90
103.665(19)
90
1866(4)
2, 0.5
1.437
b (Å)
c (Å)



(deg)
(deg)
(deg)
3
Volume (Å )
Z, Z’
3
Density (calcd) (Mg/m )
Wavelength (Mg/m3)
Temperature (K)
F(000)
1.775
1.426
0.71073
100(2)
1856
0.71073
100(2)
1844
0.71073
100(2)
712
0.71073
100(2)
831
-
1
Absorption coeff. (mm )
2.443
3.536
3.056
0.777
1.107
Semi-emp. from
equiv.
Semi-emp. from
equiv.
Semi-emp. from
equiv.
Semi-emp. from
equiv.
Semi-emp. from
equiv.
Absorption correction
Max. & min. transmission 0.775 and 0.509
0.869 and 0.373
1.581 to 27.723
49788
0.3766 and 0.2313
1.333 to 22.721
17622
0.812 and 0.757
1.760 to 27.581
81927
0.3782 and 0.2597
1.950 to 22.722°
14735

range /°
1.588 to 27.569
149026
Reflection collected
Independent reflection
Data / restraints/ param.
wR(F all data)
11335 [R(int)=0.0759] 11151 [R(int)=0.0427] 5545 [R(int)=0.0990]
14455 [R(int)=0.0474] 2508 [R(int)=0.1061]
11335 / 0 / 218
wR2 = 0.1750
R1 = 0.0597
1.006
11151 / 321 / 380
wR2 = 0.1415
R1 = 0.0579
1.007
5545 / 588 / 529
wR2 = 0.2256
R1 = 0.0835
1.009
14455 / 0 / 189
wR2 = 0.2326
R1 = 0.0751
1.004
2508 / 660 / 333
wR2 = 0.2636
R1 = 0.0879
1.007
2
R(F obsd. data)
Goodness-of-fit on F
2
Observed data [l>2 (l)]
Largest & mean shift /
s.u.
Largest diff peak and
hole e/Å3
7787
7804
3917
9254
1897
0
3
.001, 0.000
0.001, 0.000
0.001, 0.000
0.000, 0.000
0.035, 0.003
.282 and -0.783
2.592 and -0.912
1.485 and -1.066
3.153 and -1.415
0.000
0.779 and -0.853
0.038
τ
4
2
2 2
2 2 1/2
wR2 = {  [w(F - F ) ] /  [w(F ) ] }
, R1 =  ||F | - |F || /  |F
o
c
o
o
c
o
The X-ray structures were determined by Douglas R. Powell at
the University of Oklahoma small molecule lab. SMK thanks
Prof. Nathan D. Schley for useful discussions. The authors thank
the National Science Foundation (grant CHE-0130835) and the
Acknowledgements
1
0 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
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Journal Name
ARTICLE
1
1
1
1
1
5 McGuinness, D. S.; Cavell, K. J., Donor-fVuienwcAtiroticnleaOlinzleinde
University of Oklahoma for funds to purchase the X-ray
instrument and computers. The authors thank the Arkansas
Biosciences Institute for funding the NMR facility at the
University of Arkansas and the University of Arkansas for start-
up funding and financial support. The authors thank the
Arkansas Statewide MS facility for FTMS (COBRE Grant Number:
NIH P30 GM103450). Some elemental analysis analytical data
were obtained by the CENTC Elemental Analysis Facility at the
University of Rochester, funded by NSF CHE-0650456.
heterocyclic carbene complexes of palladium(II): Efficient
DOI: 10.1039/C9DT02147G
catalysts for C-C coupling reactions. Organometallics 2000, 19
(5), 741-748.
6 Peris, E.; Loch, J. A.; Mata, J.; Crabtree, R. H., A Pd complex of
a tridentate pincer CNC bis-carbene ligand as a robust
homogenous Heck catalyst. Chemical Communications 2001,
(2), 201-202.
7 Hahn, F. E.; Jahnke, M. C.; Gomez-Benitez, V.; Morales-
Morales, D.; Pape, T., Synthesis and catalytic activity of pincer-
type bis(benzimidazolin-2-ylidene) palladium complexes.
Organometallics 2005, 24 (26), 6458-6463.
8 Blakemore, J. D.; Chalkley, M. J.; Farnaby, J. H.; Guard, L. M.;
Hazari, N.; Incarvito, C. D.; Luzik, E. D.; Suh, H. W., New
bidentate trans-chelating N-heterocyclic carbene ligands for
palladium. Organometallics 2011, 30 (7), 1818-1829.
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ARTICLE
alkoxybenzimidazolin-2-ylidenes:
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DOI: 10.1039/C9DT02147G
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0‐member macrocyclic rings containing NHCs and amines were synthesized, and their late metal
coordination chemistry explored.