Palladate Precatalysts for the Formation of C-N and C-C Bonds

Article abstract of DOI:10.1021/acs.organomet.9b00326

A series of imidazolium-based palladate precatalysts has been synthesized and the catalytic activity of these air- and moisture-stable complexes evaluated as a function of the nature of the imidazolium counterion. These precatalysts can be converted under

Full text of DOI:10.1021/acs.organomet.9b00326

Article
pubs.acs.org/Organometallics
Cite This: Organometallics XXXX, XXX, XXX−XXX
Palladate Precatalysts for the Formation of C−N and C−C Bonds
Caroline M. Zinser,† Katie G. Warren,† Fady Nahra,‡,§ Abdullah Al-Majid,∥ Assem Barakat,∥
Mohammad Shahidul Islam,∥ Steven P. Nolan,*,‡,∥ and Catherine S. J. Cazin*,‡
†School of Chemistry, University of St Andrews, St Andrews KY16 9ST, U.K.
‡Department of Chemistry and Centre for Sustainable Chemistry, Ghent University, Krijgslaan 281, S-3, 9000 Ghent, Belgium
§VITO (Flemish Institute for Technological Research), Separation and Conversion Technology, Boeretang 200, B-2400 Mol,
Belgium
∥Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia
S
* Supporting Information
ABSTRACT: A series of imidazolium-based palladate pre-
catalysts has been synthesized and the catalytic activity of
these air- and moisture-stable complexes evaluated as a
function of the nature of the imidazolium counterion. These
precatalysts can be converted under catalytic conditions to Pd-
NHC species capable of enabling the Buchwald−Hartwig aryl
amination and the α-arylation of ketones. Both reactions can
be carried out efficiently under very mild operating conditions.
The effectiveness of the protocol was tested on functionality-
laden substrates.
and little attention is paid to the steps required to generate the
precatalyst itself. In our search for increasingly user-friendly
and greener catalytic systems, we recently reported on the use
of a palladate precatalyst, [IPr·H][Pd(η3-cin)Cl2]36 (IPr =
N,N′-bis(2,6-diisopropylphenyl)imidazol-2-ylidene;37 cin =
cinnamyl), that displays, in the Suzuki−Miyaura reaction,
very high activity and a broad functional group tolerance while
making use of a mild inorganic base and a green solvent.38
Another important advantage of such systems is that they can
be synthesized on a gram scale under solvent-free conditions
and without the need for any workup. Considering the
importance of the C−N bond forming reaction and related α-
arylation of ketones, we wished to explore whether the easily
prepared palladate precatalysts could display high efficacy in
these two important reactions (Scheme 1).
INTRODUCTION
■
The formation of carbon−heteroatom bonds is central to
molecular assembly in its many incarnations.1−3 In particular
carbon−nitrogen bonds can be found in a plethora of
molecules ranging from pharmaceutical agents and natural
products to agrochemicals.4−8 The Buchwald−Hartwig aryl
amination reaction has become one of the most important
cross-coupling reactions practiced in modern chemistry to
achieve C−N bond formation. This protocol has led to a large
variety of C−N-containing molecules enabling a plethora of
applications.9−18 Due to its importance, various catalytic
systems have been devised to the specific end of generating
C−N bonds selectively.
The Buchwald−Hartwig reaction is principally mediated by
palladium catalysts and operated through rapid and straightfor-
ward activation of well-defined complexes, leading to the
putative Pd0L species.19−21 Our interest in this area has
focused mainly on the use of N-heterocyclic carbenes (NHCs)
as supporting ligands.22,23 The difference in electronic and
steric properties of NHCs in comparison to the traditionally
used tertiary phosphine ligands has generated new possibilities
and improved reaction conditions in catalysis.24 The family of
[Pd(NHC)(η3-R-allyl)Cl] precatalysts has shown high cata-
lytic activity in numerous cross-coupling reactions such as in
carbon−carbon,28,29 carbon−nitrogen,13,18,25−30 and carbon−
sulfur31,32 bond formations as well as in the arylation of the
ketones.33 A main advantage of these precatalysts is their use at
very low loadings under very mild reaction conditions and in
environmentally friendly solvents.34,35
RESULTS AND DISCUSSION
■
A number of [NHC·H][Pd(η3-R-allyl)Cl2] complexes were
synthesized using the solvent-free method consisting of
grinding the NHC salt with [Pd(η3-cin)(μ-Cl)]2.38 In this
manner, a number of palladates were obtained quantitatively in
microanalytical purity (Scheme 2). The synthetic methodology
was shown to be general, as variations of both NHC and allyl
moieties are possible.
This new series of palladates was first tested in the
Buchwald−Hartwig arylamination reaction involving 4-chlor-
oanisole and 4-fluoroaniline. Early results revealed that
complexes bearing [IPr*·H]+ (N,N′-1,3-bis[2,6-bis-
The efficacy of the bond-forming reaction is most often the
focus of reports dealing with the Buchwald−Hartwig reaction
Received: May 15, 2019
© XXXX American Chemical Society
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Next, the conditions for precatalyst activation were
investigated (Tables S2−S4 in the Supporting Information).
As expected, the activation temperature plays a more
significant role than the operating temperature. The ideal
activation temperature appears to be 60 °C, as increasing the
temperature further results in a decrease in conversion (see the
Supporting Information for details).
Scheme 1. Palladate Complexes as Precatalysts in Cross-
Coupling Reactions
We then focused on optimizing the reaction using green
solvents.40,41 In this context, cyclopentyl methyl ether
(CPME) was chosen for its numerous advantages over other
commonly employed ether solvents such as THF, diethyl
ether, or 1,4-dioxane. Indeed, in addition to its stability under
acidic and basic conditions, CPME does not lead to the
formation of peroxides, thereby decreasing risks associated
with this reaction.42 In addition, the low miscibility of CPME
with water allows efficient purification/separation and its use is
therefore very attractive for large-scale industrial reactions.42
The scope of the newly established catalytic system was next
explored using a variation of primary amines with aryl chlorides
(Scheme 3, 4a−o). It was possible to couple substrates with
substituents at para, meta, or ortho positions without loss of
reactivity (Scheme 3). The use of sterically hindered anilines
such as 2-tolylaniline (4g), 2-isopropylaniline (4h,i), 2,6-
diisopropylaniline (4n), and 2,6-diethylaniline (4o) resulted in
excellent isolated yields.43 As all reactions proceed in high
yield, the product purification was achieved by using a simple
filtration through silica to remove impurities and catalyst
residues. The use of flash column chromatography proved
unnecessary. A series of secondary amines (aliphatic and
aromatic) was also successfully coupled using this method-
ology (Scheme 3, 5a−i).
Scheme 2. Imidazolium Palladates Used in This Study
As proof of the robustness of the procedure and of the
catalysts, three compounds were scaled to 5.5 mmol (≥1 g)
(4a and 5a,e). In all cases, no loss of reactivity was observed.
The seven-membered ring azepane (5g,h) and the four-
membered ring pyrrolidine (5f) were coupled successfully in
excellent yields.
We then turned our attention to more complex structures
and targeted a motif present in anticancer agents.44 The
specific architecture of N-ethylindolylphenylpropenone was
selected, as it brings multiple challenges in the form of
numerous functional groups (two heteroatoms and an alkene
moiety) that have the ability to inhibit catalysts (Scheme
4).12,25,45−47 Both primary and secondary amines were coupled
successfully, leading to the formation of 7a−c in good isolated
yields, after flash column chromatography. The involvement of
more complex and functionalized substrates showcases the
potential use of this simple methodology and of these simple
catalysts to enable the generation of complex molecules using a
late-functionalization strategy. This greener approach generates
molecular diversity in a very rapid and efficient manner.
The coupling of enolizable ketones and aryl chlorides finds
its importance in the synthesis of natural products and
synthetic intermediates found in pharmaceuticals. First
reported by Hartwig,48 Buchwald49 and Miura,50 the α-
arylation of ketones is now a powerful and widely used tool in
synthetic chemistry. Since the arylation of ketones and aryl
amination reactions proceed through closely related mecha-
nisms, we studied our palladate catalytic strategy in the α-
arylation of a range of ketones (Scheme 5). Conveniently by
changing the base from KOtBu to NaOtBu, the optimized
conditions were established for the present ketone function-
alization protocol (see the Supporting Information). The
(diphenylmethyl)-4-methylphenyl]imidazolium) as counter-
cation (preligand) lead to the best conversion. Furthermore,
the cinnamyl derivative [IPr*·H][Pd(η3-cin)Cl2] (1) was
determined to be the optimum precatalyst (Table S1 in the
Supporting Information). Previous reports have shown that
IndtBu-based Pd-NHC complexes exhibited higher activity in
comparison to their allyl and cinnamyl counterparts.39
Interestingly, under our conditions, this has been shown not
to be the case, as evidenced by the lower activity of [IPr*·
H][Pd(η3-IndtBu)Cl2] (only 56% conversion in comparison to
99% conversion when 1 is used).
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a
Scheme 3. Aryl Amination of Primary and Secondary
Amines with Aryl Chlorides
Scheme 4. Aryl Amination of More Elaborated Substrates
a
a
Reaction conditions: [IPr*·H][Pd(η3-cin)Cl2] (12 mg, 2 mol %),
KOtBu (62 mg, 0.55 mmol), CPME (1 mL); 1 h at 60 °C; then amine
and aryl halide in CPME (1 mL) added; 2 h at 80 °C. Isolated yields,
as the average of two reactions, are given in parentheses.
a
Scheme 5. Scope of the Ketone Arylation Reaction
a
Reaction conditions: [IPr*·H][η3-cin)Cl2] (1) (1.2 mg, 0.2 mol %),
a
Reaction conditions: [IPr*·H][Pd(η3-cin)Cl2] (1.2 mg, 0.2 mol %),
NaOtBu (53 mg, 0.55 mmol), CPME (1 mL); 1 h at 60 °C; then
ketone and aryl chloride in CPME (1 mL) added; 1 h (*3 h) at 80
°C. Isolated yields, as the average of two reactions, are given in
parentheses.
KOtBu (62 mg, 0.55 mmol), CPME (1 mL); 1 h at 60 °C; then amine
and aryl chloride in CPME (1 mL) added; 2 h at 80 °C. Isolated
yields, as the average of two reactions, are given in parentheses.
for both reactions using low catalyst loading and a green
solvent (CPME). Highly functionalized and biologically
relevant substrates have been coupled using the aryl amination
reaction protocol, highlighting the compatibility of the present
protocol with late-stage functionalization synthetic strategies.
Ongoing studies aimed at expanding the role of these
palladates in related reactions are currently being examined
in our laboratories.
reaction was carried out in air with no need for dry solvent
using a low catalyst loading (0.2 mol % Pd). Propiophenone
was successfully coupled with neutral (10a), electron-donating
(10b), and electron-withdrawing (10c) aryl chlorides, in high
isolated yields. Sterically hindered aryl chlorides were
successfully coupled with the more challenging α-tetralone
(10e) and acetophenone (10g,h).
CONCLUSIONS
■
EXPERIMENTAL SECTION
■
A range of palladate precatalysts was synthesized following a
facile and environmentally friendly synthetic protocol. The
precatalysts were tested in the aryl amination and ketone α-
arylation reactions. A highly efficient protocol was established
General Procedure for the Synthesis of [NHC·H][Pd(η3-R-
allyl)Cl2] Complexes. In air, NHC·HCl and [Pd(η3-R-allyl)(μ-Cl)]2
were placed in a mortar. The two solids were mixed and ground using
a pestle for 5 min. A crystalline solid was obtained.
C
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[IHept·H][Pd(η3-cin)Cl2]. Following the general procedure from
IHept·HCl (50.0 mg, 0.08 mmol) and [Pd(η3-cin)(μ-Cl)]2(20.0 mg,
0.04 mmol), the product was obtained as a yellow powder in 96%
yield (67.0 mg). 1H NMR (400 MHz, CDCl3): δ (ppm) 8.51 (s, 2H,
CHImid), 7.95 (s, 1H, CNCHN), 7.60 (t, J = 7.8 Hz, 2H, CHAr), 7.49 (d,
J = 9.1 Hz, 2H, CHAr(cin)), 7.27−7.25 (m, 4H, CHAr), 7.21−7.19 (m,
3H, CHAr(cin)), 5.68 (br s, 1H, CH(cin)), 4.47 (br s, 1H, CH2(cin)), 3.88
(d, J = 6.0 Hz, 1H, CH2(cin)), 2.94 (d, J = 11.6 Hz, 1H, CH(cin)), 2.08
(m, 4H, CH(IHept)), 1.65−1.49 (m, 16H, CH2(IPent)), 1.34−1.25 (m,
4H, CH2(IHept)), 1.11−0.95 (m, 12H, CH2(IHept)), 0.89−0.81 (m, 24H,
CH3(IHept)). 13C{1H} NMR (100 MHz, CDCl3): δ (ppm) 143.1
(CAr), 134.2 (CHNCN), 132.0 (CHAr + CAr), 129.3 (CHimid), 128.6
(CHcin), 128.0 (CHcin), 125.3 (CHAr), 105.1 (CHcin), 68.9 (CHcin),
58.1 (CH2(cin)), 40.5 (CH(IHept)), 39.5 (CH2(IHept)), 38.3 (CH2(IHept)),
21.4 (CH2(IHept)), 21.0 (CH2(IHept)), 14.5 (CH3(IHept)), 14.2
(CH3(IHept)). Anal. Calcd for C52H78Cl2N2Pd: C, 68.75; H, 8.65; N,
3.08. Found: C, 68.75; H, 9.03; N, 2.96.
C
NCHN), 7.30−7.27 (m, 16H, CHAr), 7.16−7.10 (m, 16H, CHAr),
6.79−6.77 (m, 12H, CHAr), 5.43 (s, 6HIPr*,), 5.04 (br s. 1H, CHcrotyl),
3.71 (m, 2H, CH2(crotyl)), 2.56 (br s, 1H, CHcrotyl), 2.14 (s, 6H,
CH3(IPr*)), 1.29 (d, J = 5.6 Hz, 3H, CH3(crotyl)). 13C{1H} NMR (100
MHz, CDCl3): δ (ppm) 142.6 (CAr), 142.2 (CHNCN), 141.4 (CAr),
141.0 (CAr), 130.9 (CAr), 130.3 (CHAr), 129.2 (CHAr), 128.6 (CHAr),
128.5 (CHAr), 126.9 (CHAr), 126.7 (CHAr), 110.3 (CHimid), 79.6
(CHcrotyl), 57.3.0 (CHcrotyl), 51.1 (CH2(crotyl)), 21.8 (CH3(IPr*)), 18.1
(CH3(crotyl)). Anal. Calcd for C73H64Cl2N2Pd: C, 76.47; H, 5.63; N,
2.44. Found: C, 76.23; H, 5.49; N, 2.42.
[IPr*·H][Pd(η3-2-Me-allyl)Cl2]. Following the general procedure
from IPr*·HCl (50.0 mg, 0.05 mmol) and [Pd(η3-2-Me-allyl)(μ-
Cl)]2(10.3 mg, 0.03 mmol), the product was obtained as a yellow
1
powder in 99% yield (61.0 mg). H NMR (400 MHz, CDCl3): δ
(ppm) 11.89 (s, 1H, CNCHN), 7.29−7.03 (m, 32H, CHAr), 6.77−6.76
(m, 8H, CHAr), 6.71 (s, 4H, CHAr), 5.44 (s, 4H, CH(IPr*)), 5.37 (s,
2H, CHImid), 3.85 (br s, 2H, CH2(allyl)), 2.81 (br s, 1H, CHallyl), 2.53
(br s, 1H, CHallyl), 2.16 (s, 6H, CH3(IPr*)), 2.08 (br s, 3H, CH3(allyl)).
13C{1H} NMR (100 MHz, CDCl3): δ (ppm) 142.9 (CAr), 142.3
(CNCN), 141.9 (CAr), 141.1 (CAr), 140.7 (CAr), 131.1 (CHAr), 130.5
(CHAr), 129.4 (CHAr), 128.7 (CHAr), 128.2 (CHAr), 126.9 (CHAr),
126.8 (CHAr), 123.3 (CHimid), 105.9 (CHallyl), 60.5 (CHallyl), 59.5
(CHallyl), 51.3 (CH(IPr*)), 22.0 (CH3(IPr*)), 14.3 (CH3(allyl)). Anal.
Calcd for C73H64Cl2N2Pd: C, 76.47; H, 5.63; N, 2.44. Found: C,
76.32; H, 5.54; N, 2.42.
[INon·H][Pd(η3-cin)Cl2]. Following the general procedure from
INon·HCl (50.0 mg, 0.06 mmol) and [Pd(η3-cin)(μ-Cl)]2(17.0 mg,
0.03 mmol), the product was obtained as a yellow powder in 99%
1
yield (70.0 mg). H NMR (400 MHz, CDCl3): δ (ppm) = 8.45 (s,
2H, CHImid), 7.94 (s, 1H, CNCHN), 7.61 (t, J = 7.8 Hz, 2H, CHAr),
7.47 (d, J = 7.6 Hz, 2H, CHAr(cin)), 7.27 (d, J = 7.9 Hz, 4H, CHAr),
7.20 (d, J = 7.2 Hz, 3H, CHAr(cin)), 5.65 (br s, 1H, CH(cin)), 4.46 (br s,
1H, CH(cin)), 3.84 (br s, 1H, CH(cin)), 2.88 (br s, 1H, CH(cin)), 2.03
(m, 4H, CH(INon)), 1.67−1.52 (m, 16H, CH2(INon)), 1.28 (m, 20H,
CH2(INon)), 1.10−0.91 (m, 12H, CH2(INon)), 0.87 (t, J = 7.1 Hz, 12H,
CH3(INon)), 0.79 (t, J = 7.3 Hz, 12H, CH3(INon)). 13C{1H} NMR (100
MHz, CDCl3): δ (ppm) 143.1 (CAr), 134.3 (CHNCN), 132.2 (CHAr),
132.0 (CAr), 129.1 (CHimid), 128.6 (CHcin), 128.0 (CHcin), 125.4
(CHAr), 105.2 (CHcin), 68.9 (CHcin), 58.0 (CH2(cin)), 40.7 (CHcin),
37.0 (CH2(INon)), 35.6 (CH2(INon)), 30.2 (CH2(INon)), 30.0
(CH2(INon)), 23.1 (CH2(INon)), 22.8 (CH2(INon)), 14.1 (CH3(INon)),
13.9 (CH3(INon)). Anal. Calcd for C60H94Cl2N2Pd: C, 70.60; H, 9.28;
N, 2.74. Found: C, 70.42; H, 9.48; N, 2.81.
[IPr*·H][Pd(IndtBu)Cl2]. Following the general procedure from IPr*·
HCl (50.0 mg, 0.05 mmol) and [Pd(IndtBu)(μ-Cl)]2 (16.3 mg, 0.03
mmol), the product was obtained as a brown powder in 99% yield
(67.0 mg). 1H NMR (400 MHz, CDCl3): δ (ppm) 12.02 (s,
1H,CNCHN), 7.26−7.09 (m, 34H, CHAr), 6.91−6.75 (m, 15H, 10
CHAr+ 5 CHInd), 5.53 (m, 1H, CHInd), 5.42 (s, 2H, CHImid), 5.38 (s,
4, CH(IPr*)) 2.16 (s, 6H, CH3(IPr*)), 1.39−1.27 (m, 9H, CH3(Ind)).
13C{1H} NMR (100 MHz, CDCl3): δ (ppm) = 142.0 (CAr), 142.3
(CHNCN), 142.1 (CAr), 141.1 (CAr), 140.6 (CAr), 131.1 (CHAr), 130.4
(CHAr), 129.4 (CHAr), 128.6 (CHAr), 127.6 (CHInd), 127.3 (CHInd),
126.9 (CHAr), 126.8 (CHAr), 125.4 (CHInd), 123.2 (CHimid), 120.2
(CHInd), 118.8 (CHInd), 118.7 (CHInd), 107.6 (CHInd), 73.4 (CHInd),
51.2 (CH2), 34.3 (CH(Ind)), 29.0 (CH3(Ind)), 28.8 (CH3(Ind)), 22.0
(CH3(IPr*)). Anal. Calcd for C82H72Cl2N2Pd: C, 77.99; H, 5.75; N,
2.22. Found: C, 77.86; H, 5.60; N, 2.42.
General Procedure for the Buchwald−Hartwig Reactions. A
vial was charged with [IPr*·H][Pd(η3-cin)Cl2] (1.2 mg, 0.2 mol %),
KOtBu (62 mg, 0.55 mmol), CPME (1 mL), and a magnetic stir bar
and sealed with a screw cap. The mixture was stirred at 60 °C for 1 h.
The vial was removed from the heating block, and the corresponding
solution of aniline and aryl chloride in CPME (1 mL) was added. The
reaction was stirred (910 rpm) for 2 h at 80 °C. After this time, the
crude mixture was purified by filtration through silica gel and the
product isolated by removal of volatiles under reduced pressure.
General Procedure for the α-Arylation of Ketones. A vial was
charged with [IPr*·H][Pd(η3-cin)Cl2] (1.2 mg, 0.2 mol %), NaOtBu
(53 mg, 0.55 mmol), CPME (1 mL), and a magnetic stir bar and
sealed with a screw cap. The mixture was stirred at 60 °C for 1 h. The
vial was removed from the heating block, and the corresponding
solution of aryl ketone and aryl chloride in CPME (1 mL) was added.
The reaction was stirred (910 rpm) for 2 h at 80 °C. Volatiles were
removed under reduced pressure, and the crude product was purified
using flash chromatography (5/95 ethyl acetate/petroleum ether).
[Pr*OMe·H][Pd(η3-cin)Cl2]. Following the general procedure from
IPr*OMe·HCl (50.0 mg, 0.05 mmol) and [Pd(η3-cin)(μ-Cl)]2(13.0
mg, 0.02 mmol), the product was obtained as a yellow powder in 99%
yield (63.0 mg). 1H NMR (400 MHz, CDCl3): δ (ppm) 12.29 (s, 1H,
CNCHN), 7.34−7.08 (m, 35H, CHAr), 6.79 (d, J = 7.2 Hz, 10H, CHAr),
6.46 (s, 4H, CHAr), 5.80−5.60 (br m, 1H, CH(cin)), 5.45 (s, 4H,
CH(IPr*OMe)), 5.23 (s, 2H, CHImid), 3.85 (br s, 1H, CH(cin)), 3.76 (br
s, 1H, CH(cin)), 3.51 (s, 6H, CH3(IPr*OMe)), 2.87 (br s, 1H, CH(cin)).
13C{1H} NMR (100 MHz, CDCl3): δ (ppm) 160.5 (CAr), 143.2
(CHNCN), 143.0 (CAr), 142.7 (CAr), 142.2 (CAr), 130.4 (CHAr), 129.3
(CHAr), 128.6 (CHAr), 128.6 (CHAr), 128.2 (CHAr), 127.0 (CHAr),
126.9 (CHAr), 125.8 (CH), 123.1 (CHimid), 115.7 (CHAr), 105.7
(CHcin), 69.0 (CHcin), 55.2 (OCH3(IPr*OMe)), 51.5 (CH(IPr*OMe)).
Anal. Calcd for C78H66Cl2N2O2Pd: C, 75.51; H, 5.36; N, 2.26. Found:
C, 75.33; H, 5.64; N, 2.32.
[IPentCl·H][Pd(η3-cin)Cl2]. Following the general procedure from
IPentCl·HCl (50.0 mg, 0.08 mmol) and [Pd(η3-cin)(μ-Cl)]2(21.0 mg,
0.04 mmol), the product was obtained as a yellow powder in 99%
yield (71.0 mg). 1H NMR (400 MHz, CDCl3): δ (ppm) 12.41 (s, 1H,
CNCHN), 7.60 (t, J = 7.7 Hz, 2H, CHAr), 7.48 (d, J = 7.3 Hz, 2H,
CHAr(cin)), 7.29 (d, J = 7.7 Hz, 4H), 7.24−7.23 (m, 3H, CHAr(cin)),
5.74 (br s, 1H, CH(cin)), 4.56 (br s, 1H, CH2(cin)), 3.92 (br s, 1H,
CH2(cin)), 2.97 (br s, 1H, CH(cin)), 1.96−1.95 (m, 4H, CH(IPentCl)),
1.86−1.78 (m, 8H, CH2(IPentCl)), 1.69−1.63 (m, 8H, CH2(IPentCl)),
0.89−0.84 (m, 24H, CH3(IPentCl)). 13C{1H} NMR (100 MHz,
CDCl3): δ (ppm) 143.4 (CAr), 142.8 (CClimid), 137.3 (CHNCN),
132.2 (CHAr), 129.6 (CHAr), 128.1 (CHAr), 126.1 (CHAr), 121.1
(CAr), 105.9 (CHcin), 81.9 (CHcin), 59.2 (CH2(cin)), 43.4 (CH(IPentCl)),
29.3 (CH2(IPentCl)), 27.2 (CH2(IPentCl)), 12.4 (CH3(IPentCl)), 11.9
(CH3(IPentCl)). Anal. Calcd for C44H60Cl4N2Pd: C, 61.08; H, 6.99;
N, 3.24. Found: C, 60.90; H, 6.78; N, 3.14.
ASSOCIATED CONTENT
■
S
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.organo-
met.9b00326.
[IPr*·H][Pd(η3-crotyl)Cl2]. Following the general procedure from
IPr*·HCl (50.0 mg, 0.05 mmol) and [Pd(η3-crotyl)(μ-Cl)]2(10.3 mg,
0.03 mmol), the product was obtained as a yellow powder in 99%
yield (60.0 mg). 1H NMR (400 MHz, CDCl3): δ (ppm) 11.60 (s, 1H,
Materials, methods, optimization data, detailed synthetic
procedures, and spectroscopic data and spectra (PDF)
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(14) Chartoire, A.; Boreux, A.; Martin, A. R.; Nolan, S. P. Solvent-
free aryl amination catalysed by [Pd(NHC)] complexes. RSC Adv.
2013, 3, 3840−3843.
AUTHOR INFORMATION
■
Corresponding Authors
*E-mail for S.P.N.: Steven.nolan@ugent.be.
*E-mail for C.S.J.C.: Catherine.cazin@ugent.be.
(15) Sunesson, Y.; Lime, E.; Lill, S. O. N.; Meadows, R. E.; Norrby,
P. Role of the Base in Buchwald−Hartwig Amination. J. Org. Chem.
2014, 79, 11961−11969.
ORCID
́
(16) Zhang, Y.; Cesar, V.; Storch, G.; Lugan, N.; Lavigne, G.
Fady Nahra: 0000-0002-1115-9725
Assem Barakat: 0000-0002-7885-3201
Steven P. Nolan: 0000-0001-9024-2035
Catherine S. J. Cazin: 0000-0002-9094-8131
Skeleton 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.
(17) Le Duc, G.; Meiries, S.; Nolan, S. P. Effect of Electronic
Enrichment of NHCs on the Catalytic Activity of [Pd(NHC)(acac)-
Cl] in Buchwald−Hartwig Coupling. Organometallics 2013, 32,
7547−7551.
Notes
The authors declare no competing financial interest.
(18) Marelli, E.; Chartoire, A.; Le Duc, G.; Nolan, S. P. Arylation of
Amines in Alkane Solvents by using Well-Defined Palladium−N-
Heterocyclic Carbene Complexes. ChemCatChem 2015, 7, 4021−
4024.
(19) 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.
ACKNOWLEDGMENTS
■
The authors gratefully acknowledge support from the Royal
Society (University Research Fellowship to C.S.J.C.), Astra-
Zeneca (Studentship to C.M.Z.), the Distinguished Scientist
Fellowship Program (DSFP) at KSU, and the VLAIO
(Co2perate) for support. Mr. Nikolaos Tzouras is gratefully
thanked for technical contributions.
(20) Marion, N.; Navarro, O.; Stevens, E. D.; Ecarnot, E. C.; Bell, A.;
Amoroso, D.; Nolan, S. P. Modified [(IPr)Pd(R-acac)Cl] Complexes:
Influence of the acac Substitution on the Catalytic Activity in Aryl
Amination. Chem. - Asian J. 2010, 5, 841−846.
(21) Cawley, M. J.; Cloke, F. G. N.; Fitzmaurice, R. J.; Pearson, S. E.;
Scott, J. S.; Caddick, S. Development of a practical Buchwald−
Hartwig amine arylation protocol using a conveniently prepared
[Pd(NHC)(R-allyl)Cl] catalyst. Org. Biomol. Chem. 2008, 6, 2820−
2825.
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DOI: 10.1021/acs.organomet.9b00326
Organometallics XXXX, XXX, XXX−XXX

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F
DOI: 10.1021/acs.organomet.9b00326
Organometallics XXXX, XXX, XXX−XXX