Direct Installation of a Silyl Linker on Ready-Made NHC Ligands: Immobilized NHC-Pd Complex for Buchwald-Hartwig Amination

Article abstract of DOI:10.1021/acs.organomet.9b00159

An immobilized N-heterocyclic carbene (NHC)-Pd complex was prepared via direct silyl linker installation onto the imidazole backbone of commercially available 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene (IPr) ligand. The IPr backbone was lithiated and treated with Me₂SiCl₂ to afford ClMe₂Si-IPr, which reacted with [Pd(π-allyl)Cl]₂ to yield a ClMe₂Si-IPr-Pd complex, and this was immobilized on Wang resin. The immobilized NHC-Pd complex facilitated quantitative Buchwald-Hartwig amination of aryl chlorides within 10 min, even at a low Pd loading of 0.2 mol %. The catalyst could be removed from the reaction mixture by simple filtration, and Pd leaching into the reaction medium was suppressed to below 1 ppm.

Full text of DOI:10.1021/acs.organomet.9b00159

Communication
pubs.acs.org/Organometallics
Cite This: Organometallics XXXX, XXX, XXX−XXX
Direct Installation of a Silyl Linker on Ready-Made NHC Ligands:
Immobilized NHC-Pd Complex for Buchwald−Hartwig Amination
Tomoteru Mizusaki,†,‡,§ Kazuhiro Matsumoto,† Katsuhiko Takeuchi,† Norihisa Fukaya,†
Yukio Takagi,§ and Jun-Chul Choi*,†,‡
†National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba Central 5, 1-1-1 Higashi, Tsukuba 305-8565,
Ibaraki, Japan
‡Tsukuba Research Center for Energy Materials Science (TREMS), Graduate School of Pure and Applied Sciences, University of
Tsukuba, Tsukuba 305-8571, Ibaraki, Japan
§N. E. CHEMCAT Corporation, 678 Ipponmatsu, Numazu, Shizuoka 410-0314, Japan
S
* Supporting Information
ABSTRACT: An immobilized N-heterocyclic carbene
(NHC)-Pd complex was prepared via direct silyl linker
installation onto the imidazole backbone of commercially
available 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene
(IPr) ligand. The IPr backbone was lithiated and treated with
Me2SiCl2 to afford ClMe2Si-IPr, which reacted with [Pd(π-
allyl)Cl]2 to yield a ClMe2Si-IPr-Pd complex, and this was
immobilized on Wang resin. The immobilized NHC-Pd
complex facilitated quantitative Buchwald−Hartwig amination of aryl chlorides within 10 min, even at a low Pd loading of
0.2 mol %. The catalyst could be removed from the reaction mixture by simple filtration, and Pd leaching into the reaction
medium was suppressed to below 1 ppm.
arbon−nitrogen bond formation is one of the most
C
important reactions in organic synthesis because many
biologically active compounds include nitrogen functionalities
in their molecular structures. In addition, triarylamine is a
ubiquitous structural motif that is frequently utilized in
materials science.1,2 Consequently, significant effort has been
devoted to the development of efficient C−N bond formation
reactions.3 In particular, Buchwald−Hartwig amination, which
involves palladium-catalyzed cross-coupling of aryl halides and
amines, has emerged as a reliable method for C−N bond
formation from readily accessible substrates under mild
reaction conditions.4
Figure 1. Immobilization by covalent grafting onto (a) an N
substituent and (b) an imidazole backbone.
N-heterocyclic carbenes (NHCs) have been widely applied
as ligands in transition-metal catalysis. Strong metal−ligand
binding occurs, as NHCs are strong σ donors and
comparatively weak π acceptors, which contributes to
enhanced catalyst stability.5 NHCs are proven efficient ligands
for Buchwald−Hartwig amination.6,7 Commercially available
1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene (IPr), which
bears sterically bulky 2,6-diisopropylphenyl groups as N
substituents, is one of the most frequently used ligands in
Buchwald−Hartwig amination.4a To enhance the practical
utility of NHC ligands in transition-metal-catalyzed reactions,
the development of immobilized NHC-metal catalysts has
received increasing attention over the past two decades.8,9
There are two common approaches to NHC immobilization
on a supporting material such as silica or polystyrene resin, via
covalent grafting: installation of a linker on an N substituent
(Figure 1a)10,11 and addition of a linker to the imidazole
backbone (Figure 1b).12−14 Although successful immobiliza-
tion has been achieved with both approaches, synthesis of the
reported immobilized catalysts is usually laborious and requires
multiple steps. Specific synthetic routes include linker
installation, imidazolium core formation, carbene formation,
complexation, and immobilization, which are costly and time-
consuming. Thus, direct installation of a linker on ready-made
(if possible, commercially available) NHC ligands is desirable
in terms of practicality.
Robinson and colleagues recently reported the direct
lithiation of the imidazole backbone of IPr with n-butyllithium
Received: March 10, 2019
© XXXX American Chemical Society
A
DOI: 10.1021/acs.organomet.9b00159
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Communication
(n-BuLi) and subsequent treatment with trimethylsilyl chloride
to yield 4-Me3Si-IPr without masking the carbene.15,16 This
report inspired us to attempt postfunctionalization of
commercially available IPr. We synthesized an array of 4-
silylated IPr ligands and revealed that the postfunctionalized
IPr ligands bearing electron-donating silyl groups showed
better catalytic performance for Buchwald−Hartwig amination
than did the parent IPr ligand under homogeneous
conditions.17 In this study, we used the postfunctionalization
method for the direct installation of a silyl linker onto
commercially available IPr for immobilization. Herein, we
report heterogeneous catalysis of an immobilized NHC-Pd
complex in Buchwald−Hartwig amination of aryl chlorides
with amines.
NHC-PdCl2 species.7a Thus, the immobilized NHC-Pd
complex 3 would include NHC-Pd(allyl)Cl and NHC-PdCl2
species, both of which can participate in the Buchwald−
Hartwig amination through the formation of the same NHC-
Pd0 active species. In the 29Si{1H} cross-polarized magic angle
spinning (CPMAS) NMR spectrum of immobilized NHC-Pd
3, a peak was observed around 1.5 ppm (Figure S2a in the
Supporting Information). In contrast, the 29Si{1H} NMR
spectrum of the precursor 2 showed a peak at 11.8 ppm
(Figure S2b in the Supporting Information). The significant
peak shift (Δ = 10 ppm) indicated conversion of the Si−Cl
bond to Si−O, which meant that immobilization on the resin
occurred. The nitrogen and palladium contents were
determined to be 0.98% (0.70 mmol N/g cat.) and 3.94%
(0.37 mmol Pd/g cat.), respectively, by elemental analysis and
ICP-AES. The approximate N to Pd molar ratio of 2:1
indicated that 1:1 coordination of NHC to the Pd center was
maintained during immobilization.
Scheme 1 illustrates the direct installation of a silyl linker
onto the IPr backbone before complexation with palladium
Scheme 1. Direct Installation of a Silyl Linker on IPr and
Immobilization of the NHC-Pd Complex on Wang Resin
The catalytic performance of the immobilized NHC-Pd
complex 3 was investigated by using it in the Buchwald−
Hartwig amination of aryl chlorides and amines with 1.2 equiv
of potassium tert-butoxide (KOtBu) as the base in THF at 70
°C (Chart 1). Chlorobenzene underwent amination by
Chart 1. Buchwald−Hartwig Amination of Aryl Chlorides
Catalyzed by the Immobilized NHC-Pd Complex 3
and immobilization on polystyrene resin. IPr-Li, which was
generated from commercial IPr following a slightly modified
Robinson protocol, was initially treated with Me2SiCl2 at −20
°C to produce 4-ClMe2Si-IPr (1) with a yield of 85%.
Immobilization precursor 2 was subsequently synthesized in a
52% yield by reacting 1 with [Pd(π-allyl)Cl]2. Finally,
precursor 2 was immobilized on Wang resin to afford the
novel immobilized NHC-Pd complex 3. NHC-Pd complex 3
was thus obtained from IPr in four steps.
The chemical structure of the immobilized NHC-Pd
complex 3 was characterized by X-ray photoelectron spectros-
copy (XPS), solid-state nuclear magnetic resonance (NMR)
spectroscopy, elemental analysis, and inductively coupled
plasma atomic emission spectroscopy (ICP-AES). XPS analysis
of 3 showed that the electronic state of the immobilized Pd
species was mainly Pd(II), along with a small amount of Pd(0)
(Figure S1 in the Supporting Information). Coproduction of
propylene was observed during the immobilization step.
Immobilization through Si−O bond formation concomitantly
forms HCl, which is known to react with NHC-Pd(allyl)Cl
species to generate propylene along with the corresponding
morpholine to give N-phenylmorpholine (4aa) in a 96%
yield. Reactions with aryl chlorides bearing electron-donating
methyl and methoxy groups or an electron-withdrawing
trifluoromethyl group proceeded smoothly to generate the
amination products 4ba−4da in excellent yields. A heterocycle,
2-chloropyridine, was also aminated by morpholine in 97%
yield. Other amines, such as dibutylamine and N-methylani-
line, were also suitable for the amination and furnished the
corresponding products 4ab (98%) and 4ac (98%). Notably,
all of the reactions proceeded to completion within 10 min
even when only 0.2 mol % Pd was used.
The immobilized NHC-Pd complex 3 can be employed in
the synthesis of triphenylamine, a key motif in materials
science,2 by Buchwald−Hartwig amination of chlorobenzene
with diphenylamine (Scheme 2). While a very low yield of 3%
was obtained with the previously described reaction con-
B
DOI: 10.1021/acs.organomet.9b00159
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Communication
Scheme 2. Triphenylamine Synthesis
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.organo-
met.9b00159.
■
S
Experimental procedures and spectral data (PDF)
AUTHOR INFORMATION
Corresponding Author
*E-mail for J.-C.C.: junchul.choi@aist.go.jp.
■
a
(IPr)Pd(π-allyl)Cl in place of immobilized NHC-Pd 3.
ORCID
Kazuhiro Matsumoto: 0000-0003-1580-8822
Katsuhiko Takeuchi: 0000-0002-2720-5394
Norihisa Fukaya: 0000-0001-8319-803X
Jun-Chul Choi: 0000-0002-7049-5032
ditions, the desired triphenylamine 4ad was obtained in a high
yield of 97% with 1 mol % Pd when NaOtBu was used as the
base in toluene. It was worth noting that the parent IPr ligand
produced an inferior yield of 47% under these conditions,
demonstrating the accelerating effect of immobilization.
Although the details are unclear at present, formation of single
sites that prevented unfavorable interactions between the
palladium complexes and the electron-donating effect of the
silyl group may have contributed to the better catalytic
performance of immobilized NHC-Pd 3.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank Dr. Hiroshi Igarashi and Dr. Yasuhiro Seki (N. E.
CHEMCAT Corporation) for helpful discussions. We also
thank Dr. Toshikazu Takahashi for assistance with solid-state
NMR spectroscopy.
The immobilized catalyst 3 was recovered via filtration
under a nitrogen atmosphere after the amination of
chlorobenzene with diphenylamine. The catalyst 3 exhibited
a drastic color change from orange to black, indicating the
formation of Pd black. Analysis of the recovered 3 by scanning
transmission electron microscopy (STEM) revealed that fine
nanoparticles were widely dispersed on the resin (Figure S3 in
the Supporting Information). Energy-dispersive X-ray (EDX)
analysis confirmed that the nanoparticles consisted of Pd
(Figure S4 in the Supporting Information). Since the
recovered 3 exhibited no catalytic activity during amination,
we concluded the Pd nanoparticles were not the active species.
On the other hand, ICP-AES analysis of the filtrate following
amination showed that <1 ppm Pd had leached into the
reaction medium. Thus, contamination of the products by Pd
and the NHC component during amination with 3 was
effectively suppressed without the use of any scavengers.18
The practical efficiency of the immobilized NHC-Pd
complex 3 was confirmed in a gram-scale synthesis of N,N-
dibutylaniline 4ab. A 3.86 g amount (94% yield) of 4ab was
isolated in high purity by a simple and facile procedure without
use of standard chromatographic and distillation techniques.
The reaction was complete within 10 min, following which the
reaction mixture was filtered and extracted with ethyl acetate.
Contamination of the products by Pd species was determined
to be <1 ppm by ICP analysis.
REFERENCES
■
(1) (a) Vitaku, E.; Smith, D. T.; Njardarson, J. T. Analysis of the
Structural Diversity, Substitution Patterns, and Frequency of Nitrogen
Heterocycles among U.S. FDA Approved Pharmaceuticals. J. Med.
Chem. 2014, 57, 10257−10274. (b) Roughley, S. D.; Jordan, A. M.
The Medicinal Chemist’s Toolbox: An Analysis of Reactions Used in
the Pursuit of Drug Candidates. J. Med. Chem. 2011, 54, 3451−3479.
(2) (a) Wang, J.; Liu, K.; Ma, L.; Zhan, X. Triarylamine: Versatile
Platform for Organic, Dye-Sensitized, and Perovskite Solar Cells.
Chem. Rev. 2016, 116, 14675−14725. (b) Ning, Z.; Tian, H.
Triarylamine: a Promising Core Unit for Efficient Photovoltaic
Materials. Chem. Commun. 2009, 5483−5495.
(3) (a) Zhao, Y.; Xia, W. Recent Advances in Radical-Based C−N
Bond Formation via Photo-/Electrochemistry. Chem. Soc. Rev. 2018,
47, 2591−2608. (b) Louillat, M.-L.; Patureau, F. W. Oxidative C−H
amination reactions. Chem. Soc. Rev. 2014, 43, 901−910. (c) Bariwal,
J.; Van der Eycken, E. C−N Bond Forming Cross-Coupling
Reactions: an Overview. Chem. Soc. Rev. 2013, 42, 9283−9303.
(4) (a) Ruiz-Castillo, P.; Buchwald, S. L. Applications of Palladium-
Catalyzed C−N Cross-Coupling Reactions. Chem. Rev. 2016, 116,
12564−12649. (b) Hartwig, J. F. Evolution of a Fourth Generation
Catalyst for the Amination and Thioetherification of Aryl Halides.
Acc. Chem. Res. 2008, 41, 1534−1544. (c) Surry, D. S.; Buchwald, S.
L. Biaryl Phosphane Ligands in Palladium-Catalyzed Amination.
Angew. Chem., Int. Ed. 2008, 47, 6338−6361.
In summary, we have developed a novel and facile method
for the synthesis of immobilized NHC complexes via direct
installation of a silyl linker onto the carbon backbone of
commercially available NHC ligands. The immobilized NHC-
Pd complex 3 shows excellent catalytic activity in the
Buchwald−Hartwig amination of aryl chlorides and amines.
The desired amination products can be obtained in high yields
within 10 min in the presence of only 0.2 mol % Pd. Although
the immobilized catalyst cannot be reused due to the
formation of Pd nanoparticles, Pd contamination of the
amination products can be suppressed without the use of a
scavenger. The feasibility of applying the immobilized NHC-
Pd catalyst in other reactions and the direct installation
method for the preparation of other immobilized NHC-metal
complexes are being investigated in our laboratory.
(5) (a) Huynh, H. V. Electronic Properties of N-Heterocyclic
Carbenes and Their Experimental Determination. Chem. Rev. 2018,
118, 9457−9492. (b) Hopkinson, M. N.; Richter, C.; Schedler, M.;
Glorius, F. An Overview of N-Heterocyclic Carbenes. Nature 2014,
510, 485−496. (c) Hock, S. J.; Schaper, L.-A.; Herrmann, W. A.;
Kuhn, F. E. Group 7 Transition Metal Complexes with N-
̈
Heterocyclic Carbenes. Chem. Soc. Rev. 2013, 42, 5073−5089.
(d) Fortman, G. C.; Nolan, S. P. N-Heterocyclic Carbene (NHC)
Ligands and Palladium in Homogeneous Cross-Coupling Catalysis: a
Perfect Union. Chem. Soc. Rev. 2011, 40, 5151−5169. (e) Díez-
́
Gonzalez, S.; Marion, N.; Nolan, S. P. N-Heterocyclic Carbenes in
Late Transition Metal Catalysis. Chem. Rev. 2009, 109, 3612−3676.
(f) Lin, J. C. Y.; Huang, R. T. W.; Lee, C. S.; Bhattacharyya, A.;
Hwang, W. S.; Lin, I. J. B. Coinage Metal−N-Heterocyclic Carbene
Complexes. Chem. Rev. 2009, 109, 3561−3598. (g) Kantchev, E. A.
B.; O’Brien, C. J.; Organ, M. G. Palladium Complexes of N-
C
DOI: 10.1021/acs.organomet.9b00159
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Communication
Heterocyclic Carbenes as Catalysts for Cross-Coupling Reactions−A
Synthetic Chemist’s Perspective. Angew. Chem., Int. Ed. 2007, 46,
2768−2813.
Oro, L. A. Heterogeneous Catalysts Based on Supported Rh−NHC
Complexes: Synthesis of High Molecular Weight Poly(silyl ether)s by
Catalytic Hydrosilylation. Catal. Sci. Technol. 2014, 4, 62−70.
(6) (a) Bastug, G.; Nolan, S. P. [Pd(IPr*OMe)(cin)Cl] (cin =
Cinnamyl): A Versatile Catalyst for C−N and C−C Bond Formation.
Organometallics 2014, 33, 1253−1258. (b) Krinsky, J. L.; Martínez,
́
(b) Villaverde, G.; Corma, A.; Iglesias, M.; Sanchez, F. Chiral
NHC-Complexes with Dioxolane Backbone Heterogenized on MCM-
41. Catalytic Activity. ChemCatChem 2011, 3, 1320−1328. (c) Hou,
Y.; Ji, X.; Liu, G.; Tang, J.; Zheng, J.; Liu, Y.; Zhang, W.; Jia, M.
Immobilization of Palladium in N-Heterocyclic Carbene Function-
alized SBA-15 for the Catalytic Application in Aerobic Oxidation of
Benzyl Alcohol. Catal. Commun. 2009, 10, 1459−1462. (d) Lee, D.-
H.; Kim, J.-H.; Jun, B.-H.; Kang, H.; Park, J.; Lee, Y.-S. Macroporous
Polystyrene-Supported Palladium Catalyst Containing a Bulky N-
Heterocyclic Carbene Ligand for Suzuki Reaction of Aryl Chlorides.
Org. Lett. 2008, 10, 1609−1612. (e) Wang, M.; Li, P.; Wang, L. Silica-
Immobilized NHC−CuI Complex: An Efficient and Reusable Catalyst
for A3-Coupling (Aldehyde−Alkyne−Amine) under Solventless
Reaction Conditions. Eur. J. Org. Chem. 2008, 2008, 2255−2261.
́
A.; Godard, C.; Castillon, S.; Claver, C. Modular Synthesis of
Functionalisable Alkoxy-Tethered N-Heterocyclic Carbene Ligands
and an Active Catalyst for Buchwald−Hartwig Aminations. Adv.
Synth. Catal. 2014, 356, 460−474. (c) Wheaton, C. A.; Bow, J.-P. J.;
Stradiotto, M. New Phosphine-Functionalized NHC Ligands:
Discovery of an Effective Catalyst for the Room-Temperature
Amination of Aryl Chlorides with Primary and Secondary Amines.
Organometallics 2013, 32, 6148−6161. (d) Meiries, S.; Speck, K.;
Cordes, D. B.; Slawin, A. M. Z.; Nolan, S. P. [Pd(IPr*OMe)(acac)Cl]:
Tuning the N-Heterocyclic Carbene in Catalytic C−N Bond
Formation. Organometallics 2013, 32, 330−339. (e) Broggi, J.;
Clavier, H.; Nolan, S. P. N-Heterocyclic Carbenes (NHCs)
Containing N-C-Palladacycle Complexes: Synthesis and Reactivity
in Aryl Amination Reactions. Organometallics 2008, 27, 5525−5531.
(f) Organ, M. G.; Abdel-Hadi, M.; Avola, S.; Dubovyk, I.; Hadei, N.;
Kantchev, E. A. B.; O’Brien, C. J.; Sayah, M.; Valente, C. Pd-Catalyzed
Aryl Amination Mediated by Well Defined, N-Heterocyclic Carbene
(NHC) − Pd Precatalysts, PEPPSI. Chem. - Eur. J. 2008, 14, 2443−
2452. (g) Marion, N.; Navarro, O.; Mei, J.; Stevens, E. D.; Scott, N.
M.; Nolan, S. P. Modified (NHC)Pd(allyl)Cl (NHC = N-
Heterocyclic Carbene) Complexes for Room-Temperature Suzuki−
Miyaura and Buchwald−Hartwig Reactions. J. Am. Chem. Soc. 2006,
128, 4101−4111. (h) Huang, J.; Grasa, G.; Nolan, S. P. General and
Efficient Catalytic Amination of Aryl Chlorides Using a Palladium/
Bulky Nucleophilic Carbene System. Org. Lett. 1999, 1, 1307−1309.
̈
(f) Schwarz, J.; Bohm, V. P. W.; Gardiner, M. G.; Grosche, M.;
Herrmann, W. A.; Hieringer, W.; Raudaschl-Sieber, G. Polymer-
Supported Carbene Complexes of Palladium: Well-Defined, Air-
Stable, Recyclable Catalysts for the Heck Reaction. Chem. - Eur. J.
2000, 6, 1773−1780.
(11) (a) Price, G. A.; Hassan, A.; Chandrasoma, N.; Bogdan, A. R.;
Djuric, S. W.; Organ, M. G. Pd-PEPPSI-IPent-SiO2: A Supported
Catalyst for Challenging Negishi Coupling Reactions in Flow. Angew.
Chem., Int. Ed. 2017, 56, 13347−13350. (b) Price, G. A.; Bogdan, A.
R.; Aguirre, A. L.; Iwai, T.; Djuric, S. W.; Organ, M. G. C. Continuous
flow Negishi cross-couplings employing silica-supported Pd-PEPPSI−
IPr precatalyst. Catal. Sci. Technol. 2016, 6, 4733−4742. (c) Martínez,
́
A.; Krinsky, J. L.; Penafiel, I.; Castillon, S.; Loponov, K.; Lapkin, A.;
̃
Godard, C.; Claver, C. Heterogenization of Pd−NHC Complexes
onto a Silica Support and Their Application in Suzuki−Miyaura
Coupling under Batch and Continuous Flow Conditions. Catal. Sci.
Technol. 2015, 5, 310−319.
́
(7) (a) Zhang, Y.; Lavigne, G.; Lugan, N.; Cesar, V. Buttressing
Effect as a Key Design Principle towards Highly Efficient Palladium/
N-Heterocyclic Carbene Buchwald−Hartwig Amination Catalysts.
Chem. - Eur. J. 2017, 23, 13792−13801. (b) Sharif, S.; Rucker, R. P.;
Chandrasoma, N.; Mitchell, D.; Rodriguez, M. J.; Froese, R. D. J.;
Organ, M. G. Selective Monoarylation of Primary Amines Using the
Pd-PEPPSI-IPentCl Precatalyst. Angew. Chem., Int. Ed. 2015, 54,
(12) (a) Li, P.; Herrmann, W. A.; Kuhn, F. E. Unsaturated NHC
̈
Complexes Immobilized by the Backbone: Synthesis and Application.
ChemCatChem 2013, 5, 3324−3329. (b) Collinson, J.-M.; Wilton-Ely,
́
J. D. E. T.; Díez-Gonzalez, S. Reusable and highly active supported
́
9507−9511. (c) Zhang, Y.; Cesar, V.; Lavigne, G. Efficient and
copper(I)−NHC catalysts for Click chemistry. Chem. Commun. 2013,
49, 11358−11360. (c) Mayr, M.; Buchmeiser, M. R.; Wurst, K.
Synthesis of a Silica-Based Heterogeneous Second Generation Grubbs
Versatile Buchwald−Hartwig Amination of (Hetero)aryl Chlorides
Using the Pd−PEPPSI-IPr(NMe2)2 Precatalyst in the Presence of
Carbonate Base. Eur. J. Org. Chem. 2015, 2015, 2042−2050.
Catalyst. Adv. Synth. Catal. 2002, 344, 712−719. (d) Schurer, S. C.;
̈
́
(d) Zhang, Y.; Cesar, V.; Storch, G.; Lugan, N.; Lavigne, G. Skeleton
Gessler, S.; Buschmann, N.; Blechert, S. Synthesis and Application of
a Permanently Immobilized Olefin-Metathesis Catalyst. Angew. Chem.,
Int. Ed. 2000, 39, 3898−3901.
Decoration of NHCs by Amino Groups and its Sequential Booster
Effect on the Palladium-Catalyzed Buchwald−Hartwig Amination.
Angew. Chem., Int. Ed. 2014, 53, 6482−6486. (e) Pompeo, M.;
Farmer, J. L.; Froese, R. D. J.; Organ, M. G. Room-Temperature
Amination of Deactivated Aniline and Aryl Halide Partners with
Carbonate Base Using a Pd-PEPPSI-IPentCl-o-Picoline Catalyst.
Angew. Chem., Int. Ed. 2014, 53, 3223−3226. (f) Tu, T.; Fang, W.;
Jiang, J. A Highly Efficient Precatalyst for Amination of Aryl
Chlorides: Synthesis, Structure and Application of a Robust
Acenaphthoimidazolylidene Palladium Complex. Chem. Commun.
2011, 47, 12358−12360.
(13) Chartoire, A.; Claver, C.; Corpet, M.; Krinsky, J.; Mayen, J.;
Nelson, D.; Nolan, S. P.; Penafiel, I.; Woodward, R.; Meadows, R. E.
̃
Recyclable NHC Catalyst for the Development of a Generalized
Approach to Continuous Buchwald−Hartwig Reaction and Workup.
Org. Process Res. Dev. 2016, 20, 551−557.
(14) (a) Leyva, A.; García, H.; Corma, A. A Soluble
Polyethyleneglycol-Anchored Phosphine as a Highly Active, Reusable
Ligand for Pd-Catalyzed Couplings of Aryl Chlorides: Comparison
with Cross and Non-Cross-Linked Polystyrene and Silica Supports.
Tetrahedron 2007, 63, 7097−7111. (b) Parrish, C. A.; Buchwald, S. L.
Use of Polymer-Supported Dialkylphosphinobiphenyl Ligands for
Palladium-Catalyzed Amination and Suzuki Reactions. J. Org. Chem.
2001, 66, 3820−3827.
(8) (a) Hubner, S.; de Vries, J. G.; Farina, V. Why Does Industry
̈
Not Use Immobilized Transition Metal Complexes as Catalysts? Adv.
Synth. Catal. 2016, 358, 3−25. (b) Leadbeater, N. E.; Marco, M.
Preparation of Polymer-Supported Ligands and Metal Complexes for
Use in Catalysis. Chem. Rev. 2002, 102, 3217−3274.
(15) Wang, Y.; Xie, Y.; Abraham, M. Y.; Wei, P.; Schaefer, H. F.;
Schleyer, P. v. R.; Robinson, G. H. A Viable Anionic N-Heterocyclic
Dicarbene. J. Am. Chem. Soc. 2010, 132, 14370−14372.
(9) (a) Wang, W.; Cui, L.; Sun, P.; Shi, L.; Yue, C.; Li, F. Reusable
N-Heterocyclic Carbene Complex Catalysts and Beyond: A
Perspective on Recycling Strategies. Chem. Rev. 2018, 118, 9843−
(16) Mendoza-Espinosa, D.; Donnadieu, B.; Bertrand, G. Synthesis
of 4- and 4,5-Functionalized Imidazol-2-ylidenes from a Single 4,5-
Unsubstituted Imidazol-2-ylidene. J. Am. Chem. Soc. 2010, 132,
7264−7265.
9929. (b) Zhong, R.; Lindhorst, A. C.; Groche, F. J.; Kuhn, F. E.
̈
Immobilization of N-Heterocyclic Carbene Compounds: A Synthetic
Perspective. Chem. Rev. 2017, 117, 1970−2058. (c) Sommer, W. J.;
Weck, M. Supported N-Heterocyclic Carbene Complexes in Catalysis.
Coord. Chem. Rev. 2007, 251, 860−873.
(17) Fukaya, N.; Mizusaki, T.; Hatakeyama, K.; Seo, Y.; Inaba, Y.;
Matsumoto, K.; Lee, V. Y.; Takagi, Y.; Kuwabara, J.; Kanbara, T.;
Choe, Y.-K.; Choi, J.-C. [Pd(4-R3Si-IPr)(allyl)Cl], a Family of Silyl-
́
́
(10) (a) Lazaro, G.; Fernandez-Alvarez, F. J.; Iglesias, M.; Horna, C.;
́
Vispe, E.; Sancho, R.; Lahoz, F. J.; Iglesias, M.; Perez-Torrente, J. J.;
D
DOI: 10.1021/acs.organomet.9b00159
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Communication
Substituted Pd−NHC Complexes: Catalytic Systems for the
Buchwald−Hartwig Amination. Organometallics 2019, 38, 375−384.
(18) (a) Reginato, G.; Sadler, P.; Wilkes, R. D. Scaling up Metal
Scavenging Operations for Pharmaceutical Pilot Plant Manufactures.
Org. Process Res. Dev. 2011, 15, 1396−1405. (b) Galaffu, N.; Man, S.
P.; Wilkes, R. D.; Wilson, J. R. H. Highly Functionalised Sulfur-Based
Silica Scavengers for the Efficient Removal of Palladium Species from
Active Pharmaceutical Ingredients. Org. Process Res. Dev. 2007, 11,
406−413.
E
DOI: 10.1021/acs.organomet.9b00159
Organometallics XXXX, XXX, XXX−XXX