Skeleton decoration of NHCs by amino groups and its sequential booster effect on the palladium-catalyzed Buchwald-Hartwig amination

Article abstract of DOI:10.1002/anie.201402301

A challenging synthetic modification of PEPPSI-type palladium pre-catalysts consisting of a stepwise incorporation of one and two amino groups onto the NHC skeleton was seen to exert a sequential enhancement of the electronic donor properties. This appears to be positively correlated with the catalytic performances of the corresponding complexes in the Buchwald-Hartwig amination. This is illustrated, for example, by the quantitative amination of 4-chloroanisole by morpholine within 2 h at 25°C with a 2 mol% catalyst/substrate ratio or by a significant reduction of catalytic loading (down to 0.005 mol%) for the coupling of aryl chlorides with anilines (max TON: 19600).

Full text of DOI:10.1002/anie.201402301

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Chemie
DOI: 10.1002/anie.201402301
Carbene Chemistry
Skeleton Decoration of NHCs by Amino Groups and its Sequential
Booster Effect on the Palladium-Catalyzed Buchwald–Hartwig
Amination**
Yin Zhang, Vincent Cꢀsar,* Golo Storch, Noꢁl Lugan, and Guy Lavigne*
Abstract: A challenging synthetic modification of PEPPSI-
type palladium pre-catalysts consisting of a stepwise incorpo-
ration of one and two amino groups onto the NHC skeleton
was seen to exert a sequential enhancement of the electronic
donor properties. This appears to be positively correlated with
the catalytic performances of the corresponding complexes in
the Buchwald–Hartwig amination. This is illustrated, for
example, by the quantitative amination of 4-chloroanisole by
morpholine within 2 h at 258C with a 2 mol% catalyst/
substrate ratio or by a significant reduction of catalytic loading
(down to 0.005 mol%) for the coupling of aryl chlorides with
anilines (max TON: 19600).
D
uring the past two decades, N-heterocyclic carbenes
(NHCs) have gained considerable significance for the
design of a variety of highly efficient transition-metal pre-
catalysts.[1] Their intrinsic interest is both due to their high
steric bulk, mainly determined by the nature of the nitrogen
substituents, and their strong electronic s-donor properties.
These donor properties are dramatically influenced by the
nature of the heterocyclic skeleton.[2] Among NHCs, 1,3-
dimesityl-2H-imidazol-2-ylidene (IMes) and 1,3-bis(2,6-diiso-
propylphenyl)-2H-imidazol-2-ylidene (IPr) are the most
widely employed in homogeneous catalysis. Hence, they
represent ideal standard archetypes from which an optimiza-
tion of stereoelectronic properties can be envisioned. Regard-
ing the sterics, excellent results have been obtained upon
formal replacement of the 2,6-diisopropylphenyl (Dipp)
nitrogen substituents by bulkier, flexible aryl groups[3] or by
C2-symmetrical chiral aryl groups.[4] Moreover, modifications
of the electronic donor properties by decoration of the
imidazolyl skeleton are highly efficient, but often remain
subject to synthetic limitations.[5] To date, relevant notable
systems studied in catalysis include the quinone- and ace-
naphthylene-annelated imidazol-2-ylidenes 3 and 4[6,7] the
Scheme 1. Target NHCs systems 1a,b and 2a,b (left) and selected
previous examples of skeleton-functionalized IMes and IPr ligands
studied in transition-metal catalysis (right). Mes=2,4,6-trimethylphe-
nyl; Dipp=2,6-diisopropylphenyl.
methyl and chloro-disubstituted carbenes 5,[8] and the borate-
substituted anionic IPr 6 (Scheme 1).[9]
In a logical continuation of our work on skeleton
functionalization of NHCs,[10] we reasoned that the construc-
tion of NHCs 1a,b and 2a,b, formally derived from the IMes
(a) and IPr (b) ligands by incorporation of one or two
dimethylamino groups on the heterocyclic skeleton,[11] would
constitute a rational strategy to increase the donor properties
of the NHC and to unveil potentially better catalysts. Herein,
we disclose for the first time an efficient and reliable synthesis
of their imidazolium precursors and provide entry into their
coordination chemistry. We also reveal the highly beneficial
effect of the addition of skeleton amino groups onto the NHC
in the benchmark palladium-catalyzed Buchwald–Hartwig
amination.
Inspired in part from our earlier approaches to skeleton-
decorated NHCs, the synthetic strategies employed to access
the imidazolium salts [1a,b·H](OTf) and [2a,b·H](OTf) both
relied on the incorporation of the desired unit directly onto
the corresponding formamidines 7a,b. The 4-(dimethylami-
no)imidazolium triflates [1a,b·H](OTf) were thus synthesized
in a two-step sequence consisting of the alkylation of the
formamidine 7a,b by the a-chloroacetamide 8 and a selective
triflic anhydride mediated intramolecular cyclization
(Scheme 2). However, the synthesis of the 4,5-bis(dimethyla-
mino)imidazolium salts [2a,b·H](OTf) appeared less straight-
forward, since the procedure developed by Huber, Weiss
et al.[11] using a bis(phosphonio)diaminoethene reagent led
only to either a very poor yield of [2a·H](OTf) (less than
[*] Y. Zhang, Dr. V. Cꢀsar, G. Storch, Dr. N. Lugan, Dr. G. Lavigne
CNRS, LCC (Laboratoire de Chimie de Coordination)
205 route de Narbonne, BP44099, 31077 Toulouse Cedex 4 (France)
and
Universitꢀ de Toulouse, UPS, INPT
31077 Toulouse (France)
E-mail: vincent.cesar@lcc-toulouse.fr
guy.lavigne@lcc-toulouse.fr
Homepage: http://www.lcc-toulouse.fr/lcc/spip.php?article24
[**] We thank the CNRS for financial support and the Chinese Scholar-
ship Council (CSC) for a PhD grant to Y.Z. NHCs=N-Heterocyclic
Carbenes.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201402301.
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Scheme 2. Synthesis of the imidazolium triflates [1a,b·H](OTf) and
[2a,b·H](OTf). Tf-=CF3SO2-.
19%) or to no product at all in the case of [2b·H](OTf).
Taking into account the steric bulk of the Mes and Dipp
substituents in 7a,b, we found that the in situ generated
dichlorodiaminoethene 10 constitutes an ideal reagent for this
synthesis. Indeed, its addition in slight excess to the lithiated
7a,b at room temperature gave the postulated intermediate
formamidines 11a,b. These were subsequently cyclized
Scheme 3. Synthesis of the rhodium(I) complexes 13–16 and
palladium(II) complexes 17 and 18 bearing NHCs 1a,b and 2a,b.
cod=h2-(1,5-cyclooctadiene); allyl=h3-propenyl; KHDMS= potassium
bis(trimethylsilyl)amide.
through
a transient keteneiminium species formed by
abstraction of the chloride with TMSOTf. The bis-
(amino)imidazolium triflates [2a,b·H](OTf) were isolated as
white powders in 47% and 38% yields, respectively. These
salts were all fully characterized including by X-Ray diffrac-
tion studies on single crystals (Figure 1).[12]
Having established the synthetic routes towards the
imidazolium salts, we next turned our attention to the
generation of the carbenes 1a,b and 2a,b and their coordi-
nation to transition-metal centers. Firstly, deprotonation of
[1a·H]OTf and [2a·H]OTf with KN(SiMe3)2 in the presence
of [{RhCl(COD)}2] afforded the corresponding rhodium(I)
complexes 13 and 15 in moderate to good yields
(Scheme 3).[13] Complexes 13 and 15 were then further
converted into their dicarbonyl analogues 14 and 16 upon
displacement of the COD ligand with carbon monoxide
(Scheme 3). Measuring the average IR-stretching frequency
of the carbonyl ligands in 14 and 16 allowed assessment
of the electron-donor ability of these new NHCs. A compar-
ison of their calculated Tolman electronic parameter (TEP)
values (1a: TEP = 2048.6 cmÀ1, 2a: TEP = 2046.6 cmÀ1) with
that of their non-substituted analogue IMes (TEP =
2050.8 cmÀ1),[2,14] revealed that introduction of each NMe2
group on the skeleton increments the electron-donating
ability of the carbene ligand by 2 cmÀ1, thus confirming our
working hypothesis.
Keeping in mind Organꢀs previous report that the air-
stable, user-friendly PEPPSI complexes (pyridine-enhanced
pre-catalyst preparation, stabilization, and initiation) bearing
IPr or IPent ligands are highly active in palladium-catalyzed
cross-coupling reactions,[15] we chose to synthesize the modi-
fied palladium PEPPSI pre-catalysts 17 and 18 bearing the
IPr-derived NHCs 1b, and 2b, respectively. Complex 17 was
obtained in excellent yield (83%) using a one-pot, three-step
procedure based on the transmetalation of 1b from its silver
complex [(1b)AgCl] to [PdCl2(CH3CN)2] (Scheme 3). On the
other hand, the preparation of complex 18 involved depro-
tonation of [2b·H]OTf with nBuLi, followed by trapping of
the free carbene 2b by the dimer [{PdCl(allyl)2}] to give the p-
allyl complex [(2b)PdCl(h3-allyl)]. This species was then
protonated and treated with 3-chloropyridine. The structures
of the air- and moisture-stable complexes 17 and 18 were fully
confirmed by single-crystal X-Ray diffraction studies
(Figure 2). From these crystal structures, we also calculated
the percent buried volume (%Vbur) of carbenes 1b and
2b.[2b,16] Starting from the original PEPPSI–IPr complex 19[15]
exhibiting a %Vbur value of 34.3%, the stepwise incorporation
Figure 1. Molecular structures of imidazolium rings [1a,b·H]+ and
[2a,b·H]+. Thermal ellipsoids set at 30% probability; all hydrogen
atoms except on the carbene center are omitted for clarity.
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morpholine was chosen as a model
reaction to compare catalysts 17–
19. Complex 18 was found to be by
far the most active, giving total
conversion within two hours, fol-
lowed by complexes 17 and 19,
giving 57% and 39% conversion
respectively after 6 h (Figure 3).
These
promising
results
prompted us to evaluate 18 in the
room-temperature coupling of
a variety of (hetero)aryl chlorides
with aliphatic and aryl amines
(Scheme 4). First, the deactivated
4-(pyrrol-1-yl)- and 4-(dimethyla-
mino)phenyl chlorides were effi-
ciently coupled with morpholine
using 2 mol% of 18 to give prod-
ucts 20b and 20c in excellent yields,
whereas the use of catalysts 17 and
19 only led to modest conversions
Figure 2. Molecular structures of complexes 17 (left) and 18 (right, molecule A). Thermal ellipsoids
set at 30% probability; hydrogen atoms and solvent molecules are omitted for clarity.
of NMe2 group leads to a calculated %Vbur of 39.5% for 1b in
17, and of 39.7% and 40.0% for 2b (the two values being
associated with the two crystallographically independent
molecular units of 18 in the lattice). This result reveals that
the global effect of skeleton substituents is not only purely
electronic but also involves a detectable steric component,
albeit being already maximized after introduction of the first
NMe2.[17]
and yields under identical conditions. The reaction was shown
to be unaffected by the nature of the amine partner.
Morpholine, pyrrolidine (giving 20d), piperidine (giving
20l), N-methylaniline (giving 20h—j) and the more crowded
2,6-dimethylaniline (giving 20g) all underwent efficient
The effect of the NMe2 groups was then studied by
comparing the respective catalytic efficiencies of complexes
17, 18, and 19 in the Buchwald–Hartwig amination, a powerful
method in modern synthetic chemistry.[18] In an initial experi-
ment, performed at 258C, the amination of 4-chloroanisole by
Figure 3. Efficiency of the palladium-catalyzed amination of 4-chloro-
anisole with morpholine using PEPPSI pre-catalysts 17–19. Conver-
sions were determined by GC analysis against a calibrated internal
standard (dodecane). Reactions were performed in duplicate.
DME=1,2-dimethoxyethane.
Scheme 4. Scope of the room-temperature Buchwald–Hartwig
amination reaction catalyzed by 18. Yields refer to the average yields of
isolated product from two runs after column chromatography. [a] At
508C. [b] At 808C.
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coupling. The catalytic efficiency was found to be only slightly
affected by the steric hindrance of one of the coupling
partners, with a longer time or a slightly higher temperature
being required to obtain 20 f and 20g. Catalyst 18 was also
found to exhibit excellent activity in the case of heteroaryl
chlorides, such as 2-and 3-chloropyridines (giving 20j–m), and
even for the quite difficult case of 3-chlorothiophene (giving
20n, at 808C), for which catalysts 17 and 19 proved
completely inefficient.
The scope of the Buchwald–Hartwig amination was then
explored in terms of catalyst loading. Excellent catalytic
activities were obtained for various substrates using 0.005–
0.1 mol% of pre-catalyst 18 in dioxane at 808C in the
presence of KOtBu (Scheme 5). Typically, non-activated aryl
palladium/phosphine systems for similar substrates.[20,21] The
high efficiency of catalyst 18 can be reasonably attributed to
its enhanced electron-donating ability and also in part to the
increased steric shielding of carbene 2b compared to its IPr
reference. These two complementary features are known to
be beneficial in palladium-catalyzed cross-coupling reactions.
To date, the most significant advances in the design of
palladium–NHC catalysts for the Buchwald–Hartwig amina-
tion have mainly focused on the incorporation of bulky N-aryl
wings bearing flexible substituents. By employing a rational
synthetic approach, we have now demonstrated that a further
and complementary optimization can be achieved through
a “simple” skeleton modification of IMes- and IPr-type
NHCs, leading to a sequential enhancement of their catalytic
efficiency. In this case study, a possible synergism between
steric and electronic effects is evident. Incorporation of one
skeleton amino group led to an improvement of the electron
donation and a maximization of the steric bulk, leading to
a notable enhancement of the catalytic activity. Incorporation
of a second skeleton amino group, whose effect appears to be
essentially “electronic”, was seen to exert a major doping
effect on the catalytic performances. Such a key modification
allowed both a significant decrease of the catalyst loading and
the development of extended applications to challenging
reaction partners. Further studies on the possible transposi-
tion of these benefits to other types of transition-metal-
catalyzed reactions are underway in our laboratory.
Received: February 11, 2014
Published online: && &&, &&&&
Keywords: amination reactions · amines ·
.
N-heterocyclic carbenes · homogeneous catalysis · palladium
[1] For a recent book on NHCs, see: a) RSC catalysis series N-
Heterocyclic Carbenes (Ed.: S. Dꢁez-Gonzꢂlez), RSC Publishing,
Cambridge, 2011; For selected Reviews on NHCs as ligands in
TM catalysis, see: b) D. Bꢃzier, J.-B. Sortais, C. Darcel, Adv.
Synth. Catal. 2013, 355, 19; c) C. Valente, S. C¸ alimsiz, K. H. Hoi,
D. Mallik, M. Sayah, M. G. Organ, Angew. Chem. 2012, 124,
3370; Angew. Chem. Int. Ed. 2012, 51, 3314; d) G. C. Vougiou-
kalakis, R. H. Grubbs, Chem. Rev. 2010, 110, 1746; e) S. Dꢁez-
Gonzꢂlez, N. Marion, S. P. Nolan, Chem. Rev. 2009, 109, 3612.
[2] Recent Reviews on the stereoelectronic properties of NHCs:
a) D. J. Nelson, S. P. Nolan, Chem. Soc. Rev. 2013, 42, 6723; b) T.
Drçge, F. Glorius, Angew. Chem. 2010, 122, 7094; Angew. Chem.
Int. Ed. 2010, 49, 6940.
Scheme 5. Scope of the Buchwald–Hartwig amination reaction cata-
lyzed by 18 at low catalyst loading. Yields refer to the average yields of
isolated product from two runs after column chromatography. [a] At
1008C.
chlorides and pyridinyl chlorides were successfully coupled
with morpholine or N-methylaniline (to give 21a–e) at low
catalyst loading (0.005–0.1 mol%) and remarkable turn-over
numbers were observed (TON up to 19600 for 21e). Anilines
were also found to be suitable coupling partners, as illustrated
by a 100% selectivity in the monoarylation of ArNH2 (to give
21 f in 98% yield). A total absence of bisarylation product
was evident in the preparation of molecules 21g—j. Note,
very good yields were obtained for electron-rich aryl chlor-
ides and electron-deficient anilines (giving 21g,j), which are
considered to be very challenging coupling partners.[19] These
performances place pre-catalyst 18 among the best NHC-
systems known for the arylamination reaction,[3g,19b] with
performances matching those obtained with the superior
[3] a) M. G. Organ, S. C¸ alimsiz, M. Sayah, K. H. Hoi, A. J. Lough,
Angew. Chem. 2009, 121, 2419; Angew. Chem. Int. Ed. 2009, 48,
2383; b) see Ref. [1c]; c) A. Chartoire, X. Frogneux, S. P. Nolan,
Adv. Synth. Catal. 2012, 354, 1897; d) S. Meiries, A. Chartoire,
A. M. Z. Slawin, S. P. Nolan, Organometallics 2012, 31, 3402;
e) A. Chartoire, X. Frogneux, A. Boreux, A. M. Z. Slawin, S. P.
Nolan, Organometallics 2012, 31, 6947; f) A. Chartoire, M.
Lesieur, L. Falivene, A. M. Z. Slawin, L. Cavallo, C. S. J. Cazin,
S. P. Nolan, Chem. Eur. J. 2012, 18, 4517; g) S. Meiries, G.
Le Duc, A. Chartoire, A. Collado, K. Speck, K. S. A. Arach-
chige, A. M. Z. Slawin, S. P. Nolan, Chem. Eur. J. 2013, 19, 17358.
[4] A. Albright, R. E. Gawley, J. Am. Chem. Soc. 2011, 133, 19680.
[5] Review on the synthetic routes to NHC precursors: L. Benha-
mou, E. Chardon, G. Lavigne, S. Bellemin-Laponnaz, V. Cꢃsar,
Chem. Rev. 2011, 111, 2705.
4
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[6] a) A. G. Tennyson, V. M. Lynch, C. W. Bielawski, J. Am. Chem.
Soc. 2010, 132, 9420; b) M. D. Sanderson, J. W. Kamplain, C. W.
Bielawski, J. Am. Chem. Soc. 2006, 128, 16514.
[7] a) T. Tu, Z. Sun, W. Fang, M. Xu, Y. Zhou, Org. Lett. 2012, 14,
4250; b) T. Tu, W. Fang, J. Jiang, Chem. Commun. 2011, 47,
12358; c) a bis-NHC system derived from this structure has been
recently studied in catalysis, see: G. Guisado-Barrios, J. Hiller, E.
Peris, Chem. Eur. J. 2013, 19, 10405.
Clavier, S. Giudice, N. M. Scott, E. D. Stevens, J. Bordner, I.
Samardjiev, C. D. Hoff, L. Cavallo, S. P. Nolan, Organometallics
2008, 27, 202; b) S. Wolf, H. Plenio, J. Organomet. Chem. 2009,
694, 1487. For a pioneering work, see: c) A. R. Chianese, X. Li,
M. C. Jansen, J. W. Faller, R. H. Crabtree, Organometallics 2003,
22, 1663.
[15] PEPPSI: a) see Ref. [8a]; b) see Ref. [8b]; c) see Ref. [1c], and
references therein.
[8] a) K. H. Hoi, J. A. Coggan, M. G. Organ, Chem. Eur. J. 2013, 19,
843; b) M. Pompeo, R. D. J. Froese, N. Hadei, M. G. Organ,
Angew. Chem. 2012, 124, 11516; Angew. Chem. Int. Ed. 2012, 51,
11354; c) C. A. Urbina-Blanco, X. Bantreil, H. Clavier, A. M. Z.
Slawin, S. P. Nolan, Beilstein J. Org. Chem. 2010, 6, 1120.
[9] a) E. L. Kolychev, S. Kronig, K. Brandhorst, M. Freytag, P. G.
Jones, M. Tamm, J. Am. Chem. Soc. 2013, 135, 12448; b) S.
Kronig, E. Theuergarten, C. G. Daniliuc, P. G. Jones, M. Tamm,
Angew. Chem. 2012, 124, 3294; Angew. Chem. Int. Ed. 2012, 51,
3240.
[16] For a Review, see: a) H. Clavier, S. P. Nolan, Chem. Commun.
2010, 46, 841; See also: b) A. Poater, B. Cosenza, A. Correa, S.
Giudice, F. Ragone, V. Scarano, L. Cavallo, Eur. J. Inorg. Chem.
2009, 1759; c) L. Cavallo, A. Correa, C. Costabile, H. Jacobsen, J.
Organomet. Chem. 2005, 690, 5407.
[17] Vbur were calculated using the SambVca web application (https://
www.molnac.unisa.it/OMtools/sambvca.php) with the following
parameters: sphere radius: 3.5 ꢄ, distance from the center of the
sphere: 2.00 ꢄ, mesh spacing: 0.05 ꢄ, hydrogen atoms not
included.
[10] Selected references: a) V. Cꢃsar, S. Labat, K. Miqueu, J.-M.
Sotiropoulos, R. Brousses, N. Lugan, G. Lavigne, Chem. Eur. J.
2013, 19, 17113; b) V. Cꢃsar, J. C. Tourneux, N. Vujkovic, R.
Brousses, N. Lugan, G. Lavigne, Chem. Commun. 2012, 48, 2349;
c) N. Vujkovic, V. Cꢃsar, N. Lugan, G. Lavigne, Chem. Eur. J.
2011, 17, 13151; d) V. Cꢃsar, N. Lugan, G. Lavigne, Chem. Eur. J.
2010, 16, 11432; e) L. Benhamou, V. Cꢃsar, H. Gornitzka, N.
Lugan, G. Lavigne, Chem. Commun. 2009, 4720; f) V. Cꢃsar, N.
Lugan, G. Lavigne, J. Am. Chem. Soc. 2008, 130, 11286.
[11] 4,5-bis(dimethylamino)imidazol-2-ylidenes have been reported
but only with non-hindered aryl groups as nitrogen arms. See:
S. M. Huber, F. W. Heinemann, P. Audebert, R. Weiss, Chem.
Eur. J. 2011, 17, 13078.
[12] CCDC 984192, 984193, 984194, 984195, 984196, 984197, 984198
contain the supplementary crystallographic data for this paper.
These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_
request/cif.
[13] The molecular structure of 15 is depicted in the Supporting
Information.
[14] The TEP value was calculated using the linear correlations
developed by Nolan and Plenio, see: a) R. A. Kelly III, H.
[18] a) J. F. Hartwig in Modern Amination Methods, Wiley-VCH,
Weinheim, 2000, p. 195; b) J. F. Hartwig in Handbook of
Organopalladium Chemistry for Organic Synthesis, Wiley, New
York, 2002, p. 1051; c) L. Jiang, S. L. Buchwald in Metal-
Catalyzed Cross-Coupling Reactions, Wiley-VCH, Weinheim,
2004, p. 699; d) D. S. Surry, S. L. Buchwald, Angew. Chem. 2008,
120, 6438; Angew. Chem. Int. Ed. 2008, 47, 6338.
[19] a) K. H. Hoi, S. C¸ alimsiz, R. D. J. Froese, A. C. Hopkinson,
M. G. Organ, Chem. Eur. J. 2012, 18, 145; b) G. Le Duc, S.
Meiries, S. P. Nolan, Organometallics 2013, 32, 7547.
[20] a) R. J. Lundgren, M. Stradiotto, Aldrichimica Acta 2012, 45, 59;
b) R. J. Lundgren, A. Sappong-Kumankumah, M. Stradiotto,
Chem. Eur. J. 2010, 16, 1983; c) B. P. Fors, S. L. Buchwald, J. Am.
Chem. Soc. 2010, 132, 15914; d) Q. Shen, T. Ogata, J. F. Hartwig,
J. Am. Chem. Soc. 2008, 130, 6586.
[21] During the refereeing process of the present manuscript, the
room-temperature coupling of deactivated anilines with aryl
chlorides using a PEPPSI pre-catalyst and a mild base was
reported: M. Pompeo, J. L. Farmer, R. D. J. Froese, M. G. Organ,
Angew. Chem. 2014, 126, 3287; Angew. Chem. Int. Ed. 2014, 53,
3223.
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Communications
Carbene Chemistry
Y. Zhang, V. Cꢁsar,* G. Storch, N. Lugan,
G. Lavigne*
&&&& — &&&&
Skeleton Decoration of NHCs by Amino
Groups and its Sequential Booster Effect
on the Palladium-Catalyzed Buchwald–
Hartwig Amination
Boosting the PEPPSI: A sequential en-
hancement of the activity of the PEPPSI
NHC-based palladium pre-catalyst in the
Buchwald–Hartwig amination was
obtained by a rational modification of its
standard N-heterocyclic carbene (IMes or
IPr), consisting of a “simple” incorpora-
tion of one, and then two, dimethylamino
groups as substituents. These results
highlight the valuable benefits of NHC-
skeleton decoration in C–N cross-cou-
pling.
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