An Alternative Approach to PEPPSI Catalysts: From Palladium Isonitriles to Highly Active Unsymmetrically Substituted PEPPSI Catalysts

Article abstract of DOI:10.1002/chem.201500025

A series of new pyridine-enhanced precatalyst preparation, stabilization, and initiation (PEPPSI)-type complexes bearing different types of carbene ligands was prepared by the modular and convergent template synthesis strategy. Nitrogen acyclic carbenes, saturated and unsaturated five-membered NHC, saturated six-membered NHCs, and five-membered N-heterocyclic oxo-carbene (NHOC) ligands on palladium were prepared this way. These new organometallic compounds then were tested in Suzuki and Negishi cross-coupling reactions by using substrates with one or two substituents in ortho-position of the new C- C bond being formed. Both aryl chlorides and bromides were tested as coupling partners. In some cases, the new ligands gave results similar to Organ's successful IPr-based and IPent-based PEPPSI derivatives, with aryl bromides 0.05 mol % catalyst load still gave satisfactory results, with aryl chlorides 0.5 mol % were needed.

Full text of DOI:10.1002/chem.201500025

DOI: 10.1002/chem.201500025
Full Paper
&
Synthetic Methods
An Alternative Approach to PEPPSI** Catalysts: From Palladium
Isonitriles to Highly Active Unsymmetrically Substituted PEPPSI
Catalysts
Anna Zeiler,[a] Matthias Rudolph,[a] Frank Rominger,[a] and A. Stephen K. Hashmi*[a, b]
Abstract: A series of new pyridine-enhanced precatalyst
preparation, stabilization, and initiation (PEPPSI)-type com-
plexes bearing different types of carbene ligands was pre-
pared by the modular and convergent template synthesis
strategy. Nitrogen acyclic carbenes, saturated and unsaturat-
ed five-membered NHC, saturated six-membered NHCs, and
five-membered N-heterocyclic oxo-carbene (NHOC) ligands
on palladium were prepared this way. These new organo-
metallic compounds then were tested in Suzuki and Negishi
cross-coupling reactions by using substrates with one or
two substituents in ortho-position of the new CÀC bond
being formed. Both aryl chlorides and bromides were tested
as coupling partners. In some cases, the new ligands gave
results similar to Organ’s successful IPr-based and IPent-
based PEPPSI derivatives, with aryl bromides 0.05 mol%
catalyst load still gave satisfactory results, with aryl chlorides
0.5 mol% were needed.
Introduction
most approaches are based either on a free carbene or on the
in situ generation of a free carbene, which is derived from an
imidazolium salt in the presence of a palladium source and
a base.[10]
Initially regarded as a curiosity when reported in the late
1960s,[1] N-heterocyclic carbenes (NHCs) have become one of
the most important ligand classes in homogeneous
transition-metal catalysis. This rise was initiated by
Arduengo et al. who were able to isolate the first
stable NHC derivative in 1991.[2] Due to their very
strong s-donating properties combined with a weak
p-acceptor capability,[3] NHCs form stable complexes
especially with late transition metals, resulting in a di-
verse spectrum of applications.[4] One important field
is the use of NHC–Pd complexes as highly active cat-
alysts in Pd-promoted cross-coupling reactions as
was reported by groups of Herrmann,[5] Beller,[6]
Nolan,[7] Caddick and Cloke,[8] Bellemin-Laponez and
Scheme 1. First and second generation Pd–PEPPSI catalysts.
Gade,[9] and others. Among the different synthetic
strategies for the synthesis of NHC–Pd complexes,
The Organ group contributed a series of air-stable, user-
friendly NHC–PdII precatalysts, the Pd–pyridine-enhanced
precatalyst preparation, stabilization, and initiation (PEPPSI;
Scheme 1).[11] These catalysts turned out to be generally appli-
cable in nearly every field of cross-coupling reactions.[12] The 3-
chloropyridine ligand of the precatalysts functions as a “throw-
away” ligand. Pd–PEPPSI–IPr complex (1), the first-generation
of the Pd–PEPPSI catalysts, was prepared in almost quantitative
yield by heating of the corresponding imidazolium salt with
PdCl2 and K2CO3 in neat 3-chloropyridine. In the same way,
second-generation Pd–PEPPSI complexes (2) were synthe-
sized.[13] By increasing the steric bulk at the ortho positions of
the N-phenyl moieties of the NHCs, higher catalyst reactivities
could be observed.[12] Based on the aforementioned synthetic
strategy for the ligands, this approach has only been applied
[a] Dipl.-Chem. A. Zeiler, Dr. M. Rudolph, Dr. F. Rominger,+
Prof. Dr. A. S. K. Hashmi
Organisch-Chemisches Institut
Ruprecht-Karls-Universität Heidelberg
Im Neuenheimer Feld 270, 69120 Heidelberg (Germany)
Fax: (+49)6221-54-4205
E-mail: hashmi@hashmi.de
Homepage: http://www.hashmi.de
[b] Prof. Dr. A. S. K. Hashmi
Chemistry Department, Faculty of Science
King Abdulaziz University, Jeddah 21589 (Saudi Arabia)
[+] Crystallographic investigation.
[**] PEPPSI=Pyridine-enhanced precatalyst preparation, stabilization, and ini-
tiation.
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201500025.
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to symmetrically substituted Pd–
PEPPSI complexes due to prepa-
rative feasibility to date.
The pioneering contributions
from the groups of Minghetti
and Bonati,[14] as well as Hahn,[15]
on the synthesis of metal car-
benes starting from metal-coor-
dinated isonitriles, inspired us to
develop an alternative strategy
for the synthesis of Pd–PEPPSI
complexes. Preparing NHC li-
gands through an isonitrile strat-
egy not only offers a route to
Scheme 2. Different approaches for the formation of NHC complexes from coordinated isonitriles.
unsymmetrically
substituted
NHC ligands, but also avoids
a stepwise pre-synthesis of the
corresponding imidazolium salts.
Earlier approaches were based
on isonitriles bearing tethered
nucleophilic functionalities for
the ring closure towards the
NHC. These strategies have the
drawback that one of the NHC
nitrogen atoms remains unsub-
stituted (Scheme 2a). This can
be circumvented by an alterna-
tive approach, in which the nu-
cleophilic nitrogen atom is at-
tached to a secondary amine 5
instead of being incorporated
into the isonitrile backbone. One
condition the amine has to fulfill
is to bear a leaving group/elec-
trophilic position in an appropri-
ate distance to the nitrogen,
which allows nucleophilic ring
closure in the following step
(Scheme 2b).
Scheme 3. Synthesis of the dimeric precursor 10.
Our strategy towards an alter-
native synthesis of PEPPSI cata-
lysts used the dimeric PdII com-
plexes 10 as isonitrile precursor
for all of the isonitrile-based
PEPPSI catalyst syntheses. Com-
pound 10 could be synthesized
through the known route in
almost quantitative yield by the
treatment of [PdIICl2(CH3CN)2]
(9) with the corresponding
Pd–isonitrile
complexes
8
(Scheme 3).[16] Cleavage of the
dimer with 3-chloropyridine
gave access to the pyridine-coor-
dinated isonitrile monomers 18,
which could be converted to the
desired PEPPSI catalyst deriva-
Scheme 4. Overview of the different routes towards new Pd–PEPPSI complexes in this contribution.
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tives in a synthetically valuable one-pot fashion by
simple addition of the appropriate amine.
Table 1. NHC–Pd–PEPPSI complexes synthesized.
Scheme 4 summarizes the classes of NHC com-
plexes obtained by this route. By variation of the
tether length, as well as the electrophilic moieties at-
tached to the reacting amines, four different classes
of PEPPSI derivatives were feasible. N-Heterocyclic
oxo-carbenes (NHOCs; Scheme 4, top left) were ob-
tained by using an ester moiety as electrophile. 6-
Membered (Scheme 4, top right) and 5-membered
(Scheme 4, bottom left) NHC–PEPPSI derivatives were
obtained by the reaction with amines bearing
a chloro substituent as leaving group. Unsaturated
NHCs were prepared following a two-step procedure
(Scheme 4, bottom right). After formation of the
acetal-substituted N-acyclic carbene (NAC) com-
plexes, deprotection of the acetal with hydrochloric
acid initiates ring closure and, under elimination of
methanol, the unsaturated NHC complexes are
formed.
Entry
Nucleophile
Conditions
Pd complex
Yield [%]
1
THF, rt, 4d
56
2
3
4
THF, rt, 4d
THF, rt, 1d
THF, rt, 1d
50
76
45
5
THF, rt, 1d
88
By employing these routes, we gained access to
a set of structurally diverse unsymmetrically substi-
tuted Pd–PEPPSI complexes. All of the obtained com-
plexes are bearing an aryl or alkyl group on one of
the nitrogen atoms of the NHC ring and a 12- or 15-
membered ring on the other. The installation of large
cyclic aliphatic rings was accomplished when these
substituents had a positive influence on catalytic
reactivities in previous studies of our group.[17] It is
important to note that the ratio of cis- and trans-
isomers of 18 is highly dependent on the reaction
conditions. In general, longer reaction times and
higher concentration of the reaction mixture led to
undesired isomerization reactions.
6
7
8
THF, rt, 1d
THF, rt, 1d
THF, rt, 1d
48
72
53
9
THF, rt, 1d
THF, rt, 1d
THF, rt, 2d
THF, rt, 2d
45
66
43
53
10
11
12
Table 1 summarizes the results for the complex
syntheses. After work-up, which was done by column
chromatography, the Pd–PEPPSI complexes were ob-
tained in moderate to excellent yields. The NHOC–Pd
complexes 12a and b (entries 1 and 2) were pre-
pared by treating the in situ formed isonitrile com-
plex 18 with an a-amino ester. Reaction times for the
NHOC synthesis turned out to be quite long, and
yields turned out to be only moderate, which is
partly based on the observation that the resulting
complexes were hardly soluble in all common sol-
vents, which might explain the moderate yields after
isolation by column chromatography.
13
14
15
16
20a
20b
20c
20d
HCl (4m), CH2Cl2, rt, 2d
HCl (4m), CH2Cl2, rt, 2d
HCl (4m), CH2Cl2, rt, 2d
HCl (4m), CH2Cl2, rt, 2d
100
100
97
The addition of g-substituted amines to 18 yielded
the six-membered NHC–Pd complexes 15a and
b (Table 1, entries 3 and 4). As was mentioned before,
a primary attack of the amine led to the formation of
a secondary nucleophilic center (the former isonitrile),
which enables intramolecular cyclization by the
reaction with the leaving group. Because of the easy
handling, we utilized the corresponding ammonium
salts in combination with triethylamine for the in situ
generation of the 3-(chloropropyl)amines.
98
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Figure 1. Molecular structures of the NHC–Pd–PEPPSI complexes 12a, 12b, 15b, 16a, 16c, 21a, and 21b in the solid state.
The corresponding five-membered Pd complexes 16a and
c (Table 1, entries 5 and 7) could be obtained in very good
yields by applying the same strategy with substituted 2-
(chloroethyl)ammonium salts. With secondary halides in the
amine tether, it was also possible to introduce a phenyl group
in the backbone of the NHC ligand (Table 1, entries 6, 8). An in-
Table 2 schematically illustrates the structure of the com-
plexes shown in Figure 1. The angle between the Ccarbene-Pd-N
axis and NÀCring axis (a) was determined and is listed along
with selected bond lengths. Furthermore, the percentage
buried volume (%Vbur) of the NHC ligands bound to palladium
have been calculated.[19]
1
teresting electronic effect was observed in the H NMR spectra
As was expected, the Pd–carbene bond is significantly short-
er (1.95–1.98 Š) than the Pd–pyridine distance (2.09–2.12 Š),
but variations within the series of complexes are small. The
angle between the aliphatic ring of the nitrogen and the
Ccarbene-Pd-N axis was determined to verify whether a depend-
ency to the catalytic performance exists, which was tested in
selected Suzuki and Negishi cross-coupling reactions (see
below). The studies revealed that with the exception of the
six-membered NHC complex 15b, the complexes with the
smallest angle (21b and 16c) performed best, whereas com-
of 16b and 16d. Due to the ring current of the phenyl group
in the backbone the signals corresponding to the iso-propyl
group of the aromatic moieties of the Pd complexes are
shifted significantly towards higher field (0.01 ppm instead of
the usual 1.15 ppm).
The synthesis of unsaturated NHC–Pd–PEPPSI complexes
was accomplished by the treatment of 18 with substituted
(2,2-dimethoxyethyl)amines to 20a–d. Subsequent acid-cata-
lyzed ring closure delivered the desired complexes 21a–d in
quantitative yields. By this procedure, NHC complexes bearing
different sterically bulky aliphatic groups at both nitrogen
atoms could be synthesized (21c and d).
Table 2. Comparison of structural parameters in Pd–PEPPSI complexes
In summary, the broad scope of the isonitrile-based method-
ology was underlined by the synthesis of these new NHC–Pd–
PEPPSI complexes that were accomplished in an one-pot pro-
cedure involving the in situ formation of isonitrile complexes
18 and its direct reaction with different ammonium salts and
secondary amines. We not only succeeded in the synthesis of
different saturated and unsaturated NHC–Pd complexes, but
were also able to prepare NHOCs 12 and six-membered NHC
complexes 15.
synthesized.
[a]
Complex
PdÀCcarbene
PdÀNpyridine
a [8]
%Vbur
12a
12b
15b
16a
16c
21a
21b
1.954(2)
1.954(3)
1.984(3)
1.956(4)
1.958(3)
1.966(6)
1.962(3)
2.092(2)
2.098(3)
2.117(3)
2.106(3)
2.121(3)
2.109(5)
2.114(3)
71.0
69.0
59.8
68.2
67.2
74.5
67.8
38.1
38.0
42.2
37.7
39.1
40.7
38.1
Fortunately, most of the structures of the synthesized com-
plexes could be unambiguously proven by X-ray structure
analysis (Figure 1).[18] Crystals were obtained by vapor diffusion
of n-pentane into a saturated dichloromethane solution of the
Pd complexes. All of the shown complexes possess a trans-
configuration bearing the 3-chloropyridine ligand opposite to
the NHC ligand in a square planar environment around the
metal center.
[a] NHC geometries from DFT-optimized [IrCl(CO)2(NHC)] complexes, bond
radii scaled by 1.17, sphere radius R=3.5 Š, MÀNHC distance d=2.10 Š,
which leads to the %Vbur values given in Table 2.[20]
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plexes 12a and b showed a low level of activity. Besides, the
angle for the complexes with a twelve-membered ring is great-
er than for the corresponding complexes with a fifteen-mem-
bered ring (compare 12a and b, 16a and c, 21a and b), which
is also linked to the catalytic performance. This observation is
attributed to the fact that a better shielding of the catalytic
active center is associated to a higher catalytic performance.
The calculated %Vbur as a modular descriptor of the steric
properties of the NHC ligands ranged between 37.7 and 42.2.
In comparison, the %Vbur value of the commercially available
Pd–PEPPSI–IPr is slightly smaller (34.3) than for the values for
the herein reported complexes.[21]
As was already mentioned, all synthesized complexes were
tested in Suzuki–Miyaura cross-coupling reactions by using
chlorobenzene or bromobenzene in combination with 2,5-di-
methylphenylboronic acid as coupling partner. Herein, we
were interested in the structure–performance relationship of
the different catalysts. In addition, the catalytic activity of
these complexes was compared with the commercially avail-
able Pd–PEPPSI–IPr catalyst. To have robust and user-friendly
conditions, all reactions were performed at room temperature
by using typical laboratory preparations without the need for
handling in a glovebox. All of the reactions proceeded
smoothly in technical-grade ethanol without prior degassing,
and potassium tert-butoxide was found to be the optimal base
to ensure high formation of product. The results of these
experiments are listed in Figure 2.
Figure 2. Suzuki–Miyaura cross-coupling of chlorobenzene and 2,5-dimethyl-
phenylboronic acid catalyzed by the new NHC–Pd–PEPPSI complexes.
Average of two runs. Reaction conditions: 1.00 mmol of chlorobenzene,
1.20 mmol of boronic acid, 1.20 mmol of KOtBu, 0.5 mol% [Pd], 2.00 mL of
EtOH, 12 h, rt. The yield was determined by GC, using n-dodecane as
internal standard.
compared to complexes with five-membered saturated and
unsaturated NHC ligands.
The highest yields for the Suzuki cross-coupling reaction
with chlorobenzene were obtained with the commercially
available Pd–PEPPSI–IPr and the saturated and unsaturated
NHC-complexes bearing a 15-membered ring (16c and 21b).
On the contrary, NHOC complexes (12a and b), as well as NHC
complexes bearing two aliphatic groups at both nitrogen
atoms (21c and d), showed only low activity. With all other
complexes, good to moderate yields (52–85%) could be
achieved.
Furthermore, all of the synthesized complexes were tested
in a Suzuki cross-coupling reaction using bromobenzene. Be-
cause bromobenzenes are more reactive, the amount of cata-
lyst was reduced (0.05 mol%) to obtain distinguishable results.
For this transformation, NHC complex 21b showed an even
higher yield than the original Pd–PEPPSI–IPr catalyst, whereas
most of the other complexes delivered the desired product 24
in moderate to good yields (54–87%). Once more, the ring size
of the attached aliphatic moiety at one of the nitrogen atoms
To study the reaction kinetics,
ReactIR in situ measurements
were conducted. Figure 3 shows
the kinetics of the Suzuki–
Miyaura
cross-coupling
of
chlorobenzene and 2,5-dimethyl-
phenylboronic acid using com-
plexes 12a, 15b, 16c, and 21a
as catalysts. After a short induc-
tion time of a few minutes, 16c
and 21a permitted the comple-
tion of the reaction in approxi-
mately 1 h. Complexes 12a and
15a showed lower reaction rates
and due to catalyst deactivation
(that was visible by a fast forma-
tion of palladium black), only
poor conversions were obtained
after 12 h (25 and 52%). This fur-
ther demonstrates the worse sta-
Figure 3. Suzuki–Miyaura cross-coupling of chlorobenzene and 2,5-dimethylphenylboronic acid monitored by
bility issues of these complexes ReactIR using complexes 12a, 15a, 16c, and 21a.
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played a key role and an increas-
ing ring size led to an increased
yield.
Due to the excellent function-
al group tolerance and high ac-
tivity of organozinc reagents, the
complexes, which performed
best in the Suzuki cross-cou-
plings, were also tested in Ne-
gishi reactions and compared
with the commercially available
catalysts PEPPSI–IPr and PEPPSI–
IPent. Herein,
a sterically de-
manding arylzinc reagent, which
was generated in situ by trans-
metalation of mesitylmagnesium
bromide to zinc chloride, was ef-
fectively coupled with different
aryl chlorides and bromides (Fig-
ures 4 and 5). All reactions were
performed in a THF/N-methyl-2-
pyrrolidone (NMP) cosolvent
system at 708C, and the yields
were determined by GC by
using n-dodecane as internal
standard.[11b]
Figure 4. Negishi cross-coupling of chloro- or bromobenzene and mesitylmagnesium bromide by the new
NHC–Pd–PEPPSI complexes. Average of two runs. Reaction conditions: 250 mmol of halide, 300 mmol of mesityl-
magnesium bromide (1m in THF), 350 mmol ZnCl2 (0.7m in THF), 0.4 mL NMP, 2 mol% [Pd], 18 h, 708C. The yield
was determined by GC, using n-dodecane as internal standard.
As depicted in Figure 4, the saturated complexes
16c and d performed better than the corresponding
unsaturated analogues (21b). An inconsistent effect
of the phenyl substituent in the backbone of the
ligand was observed. Although in the case of chloro-
benzene, the phenyl substituent in the backbone en-
hanced the catalytic performance in the Negishi
cross-coupling reaction, a reverse behavior was ob-
served for bromobenzene. In the case of the Negishi
reaction, the commercially available catalysts turned
out to be more active for chlorobenzene, but it is
noteworthy that complex 16c gave the same high
yield as Pd–PEPPSI–IPent in the reaction with bromo-
benzene.
Encouraged by these results, the same complexes
were tested in another Negishi cross-coupling reac-
tion by using 1-bromonaphthalene and mesitylzinc
halide as coupling partner. For this transformation,
the desired product 31 could be obtained in good to
excellent yields (83–96%). It is clear that a high
substrate dependency of the catalyst exists. This is
underlined by the observation that in this case, the
unsaturated complex 21b showed superior results.
Figure 5. Negishi cross-coupling of 1-bromonaphtalene and mesitylmagnesium bromide
by the new NHC-Pd-PEPPSI complexes. Average of two runs. Reaction conditions:
250 mmol of 2-bromonaphthalene, 300 mmol of mesitylmagnesium bromide (1m in THF),
350 mmol ZnCl2 (0.7m in THF), 0.4 mL NMP, 2 mol% [Pd], 18 h, 708C. The yield was
determined by GC, using n-dodecane as internal standard.
Conclusion
We have presented a short and efficient route to new unsym-
metrically substituted NHC–Pd–PEPPSI complexes based on
isonitrile precursors. This methodology allowed the prepara-
tion of a diverse set of different catalyst classes, namely,
NHOCs, saturated, unsaturated, and six-membered NHC com-
plexes. The modular approach enabled an easy synthesis of dif-
ferent structural motifs concerning the N-termini of the car-
bene complexes. The solid-state molecular structure of most of
the synthesized complexes could be determined by X-ray crys-
tallographic analysis. Furthermore, the catalytic activity of the
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1482; c) O. Navarro, N. Marion, N. M. Scott, J. Gonzalez, D. Amoroso, A.
Bell, S. P. Nolan, Tetrahedron 2005, 61, 9716–9722; d) N. Marion, O. Nav-
arro, J. Mei, E. D. Stevens, N. M. Scott, S. P. Nolan, J. Am. Chem. Soc.
2006, 128, 4101–4111.
obtained Pd–PEPPSI complexes was tested and compared in
a number of cross-coupling reactions. All reactions were per-
formed by using typical laboratory techniques without the
need for glovebox handling. We could show that the catalytic
performance depends not only on the catalyst class but also
on the ring size of adjacent aliphatic ring. An increasing ring
size is associated with a higher degree of conformational free-
dom of this side group, which might facilitate transmetalation/
oxidative addition. The improved stability of the complexes
bearing the cyclic aliphatic systems might also be based on
the ability of shielding the metal center, which can prevent
from catalyst deactivation (this effect is also visible in the solid-
state molecular structures, in which the aliphatic moieties
point towards the palladium center). On the other hand, the
high flexibility can enable a high reactivity, as was mentioned
above. In addition, it was shown that a sterically demanding
aromatic group at the N-termini of the carbene showed
a better catalytic performance than the corresponding com-
plexes with an aliphatic group. We also found that a high sub-
strate dependency of the catalysts exists. This fact underlines
even more the necessity for modular ligand synthesis like the
[8] L. R. Titcomb, S. Caddick, F. G. N. Cloke, D. J. Wilson, D. MCKerrecher,
Chem. Commun. 2001, 1388–1389.
[9] V. CØsar, S. Bellemin-Laponnez, L. H. Gade, Organometallics 2002, 21,
5204–5208.
[10] a) W. A. Herrmann, M. Elison, J. Fischer, C. Kocher, G. R. J. Artus, Angew.
Chem. Int. Ed. Engl. 1995, 34, 2371–2374; Angew. Chem. 1995, 107,
2602–2605; b) C. Zhang, J. Huang, M. L. Trudell, S. P. Nolan, J. Org.
Chem. 1999, 64, 3804–3805.
[11] a) C. J. O’Brien, E. A. B. Kantchev, C. Valente, N. Hadei, G. A. Chass, A.
Lough, A. C. Hopkinson, M. G. Organ, Chem. Eur. J. 2006, 12, 4743–
4748; b) M. G. Organ, S. Avola, I. Dubovyk, N. Hadei, E. A. B. Kantchev,
C. J. O’Brien, C. Valente, Chem. Eur. J. 2006, 12, 4749–4755; c) M. G.
Organ, M. Abdel-Hadi, S. Avola, N. Hadei, J. Nasielski, C. J. O’Brien, C. Val-
ente, Chem. Eur. J. 2007, 13, 150–157; d) M. G. Organ, M. Abdel-Hadi, S.
Avola, I. Dubovyk, N. Hadei, E. A. B. Kantchev, C. J. O’Brien, C. Valente,
Chem. Eur. J. 2008, 14, 2443–2452; e) C. Valente, S. Baglione, D. Candito,
C. J. O’Brien, M. G. Organ, Chem. Commun. 2008, 735–737; f) M. G.
Organ, G. A. Chass, D.-C. Fang, A. C. Hopkinson, C. Valente, Synthesis
2008, 2776–2797.
[12] C. Valente, S. C¸alimsiz, K. H. Hoi, D. Mallik, M. Sayah, M. G. Organ,
Angew. Chem. Int. Ed. 2012, 51, 3314–3332; Angew. Chem. 2012, 124,
3370–3388.
[13] M. G. Organ, S. Calimsiz, M. Sayah, K. H. Hoi, A. J. Lough, Angew. Chem.
Int. Ed. 2009, 48, 2383–2387; Angew. Chem. 2009, 121, 2419–2423.
[14] G. Minghetti, F. Bonati, A Gold(I) Carbene Complex, Synthesis and Reactiv-
ity in Inorganic and Metal–Organic Chemistry 1971, 1:4, 299–302.
[15] F. E. Hahn, Angew. Chem. Int. Ed. Engl. 1993, 32, 650–665; Angew. Chem.
1993, 105, 681–696.
demonstrated isonitrile route, which enables
a
fast
synthesis of a set of catalysts for screening purposes. Further
investigations of this ligand concept and applications in
catalysis are part of our ongoing research.
[16] A. S. K. Hashmi, C. Lothschütz, C. Bçhling, T. Hengst, C. Hubbert, F. Ro-
minger, Adv. Synth. Catal. 2010, 352, 3001–3012.
Acknowledgements
[17] a) A. S. K. Hashmi, C. Lothschütz, C. Bçhling, F. Rominger, Organometal-
lics 2011, 30, 2411–2417; b) C. Hubbert, M. Breunig, K. J. Carroll, F. Ro-
minger, A. S. K. Hashmi, Aust. J. Chem. 2014, 67, 469–474; c) A. S. K.
Hashmi, D. Riedel, M. Rudolph, F. Rominger, T. Oeser, Chem. Eur. J. 2012,
18, 3827–3830; d) D. Riedel, T. Wurm, K. Graf, M. Rudolph, F. Rominger,
A. S. K. Hashmi, Adv. Synth. Catal. 2015, 357, 1515–1523; e) A. Zeiler, M.
Ziegler, M. Rudolph, F. Rominger, A. S. K. Hashmi, Adv. Synth. Catal.
2015, 357, 1507–1514.
The authors thank Umicore AG & Co. KG for the generous
donation of palladium salts.
Keywords: amines · carbenes · cross-coupling · isonitriles ·
palladium
[18] CCDC 1021057 (12a), 1021058 (12b), 1021059 (15b) and 1021060
(16a), 1021061 (16c), 1021062 (21a), 1021063 (21b) contain the sup-
plementary crystallographic data for this paper. These data can be ob-
tained free of charge from The Cambridge Crystallographic Data Centre
via www.ccdc.cam.ac.uk/data_request/cif..
[19] Based on solid state structures, the percentage buried volume have
been calculated using the “SambVca” software on a web application at
the URL http://www.molnac.unisa.it/OMtools.php.
[20] a) A. Poater, B. Cosenza, A. Correa, S. Giudice, F. Ragone, V. Scarano, L.
Cavallo, Eur. J. Inorg. Chem. 2009, 1759–1766; b) H. Clavier, S. P. Nolan,
Chem. Commun. 2010, 46, 841–861.
[21] A. Chartoire, X. Frogneux, A. Boreux, A. M. Z. Slawin, S. P. Nolan, Organo-
metallics 2012, 31, 6947–6951.
[1] a) K. Öfele, J. Organomet. Chem. 1968, 12, 42–43; b) H.-W. Wanzlick,
H. J. Schçnherr, Angew. Chem. Int. Ed. Engl. 1968, 7, 141–142; Angew.
Chem. 1968, 80, 154–154.
[2] A. J. Arduengo, R. L. Harlow, M. J. Kline, J. Am. Chem. Soc. 1991, 113,
361–363.
[3] S. Díez-Gonzµlez, S. P. Nolan, Coord. Chem. Rev. 2007, 251, 874–883.
[4] For a review in LTM-NHC catalysis, see: S. Díez-Gonzµlez, N. Marion, S. P.
Nolan, Chem. Rev. 2009, 109, 3612–3676.
[5] S. K. Schneider, W. A. Herrmann, E. Herdtweck, J. Mol. Catal. A 2006,
245, 248–254.
[6] R. Jackstell, M. G. Andreu, A. Frisch, K. Selvakumar, A. Zapf, H. Klein, A.
Spannenberg, D. Rçttger, O. Briel, R. Karch, M. Beller, Angew. Chem. Int.
Ed. 2002, 41, 986–989; Angew. Chem. 2002, 114, 1028–1031.
[7] a) M. S. Viciu, R. F. Germaneau, O. Navarro-Fernandez, E. D. Stevens, S. P.
Nolan, Organometallics 2002, 21, 5470–5472; b) M. S. Viciu, R. A. Kelly,
E. D. Stevens, F. Naud, M. Studer, S. P. Nolan, Org. Lett. 2003, 5, 1479–
Received: January 4, 2015
Published online on June 19, 2015
Chem. Eur. J. 2015, 21, 11065 – 11071
www.chemeurj.org
11071
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