C–N Cross-coupling Reactions of Amines with Aryl Halides Using Amide-Based Pincer Nickel(II) Catalyst

Article abstract of DOI:10.1007/s10562-019-03062-5

Abstract: An approach to C–N cross-coupling reactions of aryl halides with amines in the presence of an amide-based pincer nickel(II) catalyst (2) is described. For 3?h reactions at 110?°C with 0.2?mol% catalyst, aryl bromides gave higher turnover numbers (TON) than the corresponding chlorides or iodides. Both primary and secondary amines could be used with the former giving higher TON. However, sterically hindered amines showed lower TON. In elucidating the mechanism of this nickel complex-catalyzed C–N cross coupling reaction it was found that the rate of reaction was unchanged in the presence of radical quenchers and a plausible Ni(I)–Ni(III) pathway is proposed. Graphic Abstract: [Figure not available: see fulltext.]Nickel pincer catalyst proved to be excellent catalyst for the C-N cross-coupling reaction with the high turnover number (TON) for 1° and 2° amines and different nonactivated aryl halides under optimum conditions.

Full text of DOI:10.1007/s10562-019-03062-5

Catalysis Letters
https://doi.org/10.1007/s10562-019-03062-5
C–N Cross‑coupling Reactions of Amines with Aryl Halides Using
Amide‑Based Pincer Nickel(II) Catalyst
1
1
1
1
1
Yahya M. Albkuri · Ambar B. RanguMagar · Andrew Brandt · Hunter A. Wayland · Bijay P. Chhetri ·
1
1
1
1
Charlette M. Parnell · Peter Szwedo · Anil Parameswaran‑Thankam · Anindya Ghosh
Received: 4 June 2019 / Accepted: 30 November 2019
©
Springer Science+Business Media, LLC, part of Springer Nature 2019
Abstract
An approach to C–N cross-coupling reactions of aryl halides with amines in the presence of an amide-based pincer nickel(II)
catalyst (2) is described. For 3 h reactions at 110 °C with 0.2 mol% catalyst, aryl bromides gave higher turnover numbers
(
TON) than the corresponding chlorides or iodides. Both primary and secondary amines could be used with the former
giving higher TON. However, sterically hindered amines showed lower TON. In elucidating the mechanism of this nickel
complex-catalyzed C–N cross coupling reaction it was found that the rate of reaction was unchanged in the presence of radi-
cal quenchers and a plausible Ni(I)–Ni(III) pathway is proposed.
Electronic supplementary material The online version of this
article (https://doi.org/10.1007/s10562-019-03062-5) contains
supplementary material, which is available to authorized users.
*
Anindya Ghosh
axghosh@ualr.edu
1
Department of Chemistry, University of Arkansas At
Little Rock, 2801 South University Avenue, Little Rock,
AR 72204, USA
Vol.:(0
1
123456789)
3

Y. M. Albkuri et al.
Graphic Abstract
Nickel pincer catalyst proved to be excellent catalyst for the C-N cross-coupling reaction with the high turnover number
TON) for 1° and 2° amines and diꢀerent nonactivated aryl halides under optimum conditions.
(
Keywords Nickel catalyst · Pincer catalyst · Cross-coupling · Aryl halides · Amination
1
Introduction
success. In 1903, Ullmann and Goldberg showed that copper
salts enabled reactions of activated aryl halides with anime
nucleophiles [6, 7]. However, these reactions used stoichio-
metric copper and typically harsh reaction conditions. In
the 1990s, Buchwald [8, 9] and Hartwig [10, 11] worked
independently to successfully develop palladium catalyzed
N-arylation using phosphine ligands. Since that time the
Buchwald–Hartwig amination has brought great advances in
C–N cross-coupling reactions [12, 13]. In attempts to reduce
catalyst loading and reaction times, design of new catalysts
for eꢂcient C–N coupling reactions continues as a vigorous
research area [14]. In a recent example, aryl chlorides, bro-
mides and iodides could be eꢂciently coupled using 1 mol%
CuBr with a simple 8-oxyquinoline N-oxide ligand [15].
With a view to performing C–N coupling catalysis on
larger scales, recent interest has focused on advancing nickel
catalysis [16–18] beyond the original reports [19–21]. In
contrast to Pd and Cu catalysts, nickel catalyzed C–N bond-
forming reactions often proceed through paramagnetic Ni(I)/
Using transition metal complexes for amination of aryl hal-
ides to form arylamines has become a prevailing methodol-
ogy [1]. In this context, heterocyclic compounds containing
nitrogen atoms are of signiꢁcant importance due to their
abundance in natural products and their roles in biologi-
cal and bio-inspired reactions [2]. Carbon–nitrogen (C–N)
bond-containing aromatic and aliphatic compounds have
also found multiple applications as polymers, dyes, and
agrochemicals [3, 4]. However, one of the primary avenues
for exploration of C–N bond-containing molecules is their
value in medicinal chemistry [5]. Some prevalent pharma-
ceutical compounds containing C–N bonds are shown in
Fig. 1. Due to these and many more potential applications,
it is highly desirable to develop improved methodologies for
facile and economical generation of C–N bonds.
Development of versatile catalyzed processes for
arylamine synthesis took chemists over a century to achieve
1
3

C–N Cross-coupling Reactions of Amines with Aryl Halides Using Amide-Based Pincer Nickel(II)…
Fig. 1 Signiꢁcant pharmaceu-
tical compounds of diꢀerent
classes containing C–N bonds
(
III) intermediates via redox processes [22–24] although
received without any further puriꢁcation unless otherwise
stated. All amines were puriꢁed by passing through activated
alumina prior to use. Gas chromatography-mass spectrom-
etry (GC–MS) spectra were collected using a Shimadzu
QP2010 GC–MS, where parameters were maintained at
275 °C interface, 3 injections at 24 and 50 min. Characteri-
zation of the ligand and metal catalyst were performed by
electrospray ionization mass spectrometry (ESI–MS), Fou-
rier transform infrared spectrometer (FT/IR), and nuclear
magnetic resonance (NMR) as reported previously [26, 27].
systems have been developed recently to favor Ni(0)/(II)
[
17, 25]. Therefore, developing new nickel-based catalysts
with geometrical constraints enforced by pincer ligands
may allow for improved catalysts. We have previously used
a diamidopyridine-ligated nickel complex for cross-coupling
3
reactions of multiple C–Cl bonds [26] and activation of sp
2
and sp C–H bonds in alkylation and arylation [27]. In this
study, we show that the nickel complex aꢀects the selective
cross-coupling amination of unactivated aryl halides with
various aliphatic and aromatic amines with low catalyst
loading and short reaction times.
2.2 Synthesis of N,N′‑bis(2,6‑di‑isopropylphenyl)‑2,
6‑pyridinedicarboxamide (1)
The ligand was synthesized according to a previous synthetic
route with slight modiꢁcations [26, 27]. In a 100 mL round
bottom ꢃask with a stir bar, 2,6-pyridinedicarboxylic acid
(5 g, 0.03 mol) and 15 mL 1,2-dimethoxyethane were added
followed by addition of thionyl chloride (5 mL, 0.07 mol).
The reaction mixture was reꢃuxed for 3 h. After completion,
the excess solvent and thionyl chloride were removed under
reduced pressure to obtain a white product, followed by crys-
tallization from concentrated hexane to obtain 2,6-pyridin-
edicarbonyl dichloride. The acid chloride was then treated
with 2,6-diisopropylaniline and triethylamine of anhydrous
2
Experimental Section
2.1 Materials and Instrumentation
All reactions were carried out under an inert (Ar) atmos-
phere using oven-dried glassware. All solvents and chemi-
cals such as anhydrous dimethylsulfoxide (DMSO), amines,
t
anhydrous aryl halides, KO Bu, and all chemicals for ligand
synthesis were obtained from Sigma-Aldrich, USA, Acros
Organics, USA, and Alfa Aesar, USA and were used as
1
3

Y. M. Albkuri et al.
Fig. 2 Structures of ligand 1
and pincer nickel(II) catalyst 2
tetrahydrofuran (THF) cooled to 0 °C and stirred for 3 h. On
warming the reaction was further stirred at room tempera-
ture for another 9 h. The reaction mixture was then ꢁltered
and THF was removed under reduced pressure to obtain the
crude ligand (1) (Fig. 2).
ethanol, and 10 μL of decane was added as an internal
standard. Turn over number (TON) was determined using
GC–MS.
3
Results and Discussion
2.3 Synthesis of Pincer Nickel(II) Complex (2)
3.1 Optimization of Reaction Solvent and Base
Our previous work has described the synthesis of pincer
nickel(II) complex (2) (Fig. 2) [26, 27]. In short, a 100 mL
Schlenk ꢃask ꢁtted with a magnetic stir bar was charged with
To best facilitate the amination, reactions conditions were
optimized by changing solvents and bases (Table 1). Many
solvents gave low TON (Entries 1–3) most likely due to
the low solubility of the catalyst and/or base. The low boil-
ing point of the solvents may also have played a role in the
product conversion. Solvents with high polarity and boiling
point, such as dimethylacetamide (DMA), produced moder-
ate results (TON 69) (Entry 6). whereas none of the desired
product was obtained using dimethylformamide (DMF)
(Entry 1), presumably due to thermal decomposition. DMSO
proved to be the most eꢀective solvent, yielding a TON of
243 (Entry 7). Therefore, DMSO was used to further opti-
mize the C–N coupling reaction conditions.
1. The ꢃask was sealed with a septum and stirred for 5 min
while purging with N . Dry THF was added using a gas tight
2
syringe, and n-butyllithium was added to the ice bath-cooled
(
0 °C) reaction mixture to deprotonate the ligand, followed
by addition of anhydrous nickel(II) chloride to yield the deep
red nickel(II) complex 2. The catalyst was characterized using
1
H-NMR, ESI–MS, FT/IR, and ultraviolet–visible (UV–Vis)
spectroscopy as described in the previous reports [26, 27].
2
.4 General Amination Procedure of Aryl Halides
Using Diꢀerent Amines
One of the requirements for many cross-coupling reac-
tions, and particularly for aminations, is the use of a base
[28, 29]. None of cesium carbonate (Cs CO ), potassium
A representative amination method using chlorobenzene,
t
pentylamine, and KO Bu in DMSO is described here. All
2
3
other amination reactions including diꢀerent aryl halides,
primary (1°) and secondary (2°) amines, solvents and bases
were performed using a similar method. A 4 mL reaction
vial containing a magnetic stir bar was charged with 1.4 mL
of anhydrous DMSO. The reaction vial, after being sealed
with a septum and paraꢁlm, was purged with Ar for 10 min.
Chlorobenzene [0.4 mL, 3.9 mmol, 2.25 equivalent (eq.)],
pentylamine (0.21 mL, 1.8 mmol, 1.0 eq.), anhydrous pow-
carbonate (K CO ), 4-dimethylaminopyridine (DMAP) or
2 3
DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) yielded any
product (Entries 8–11), while relatively stronger bases such
as KOH gave high yields (Entry 12). Results showed that
t
KO Bu was most eꢀective (Entry 7) and was thus used for
all subsequent reactions.
3.2 Optimizing Reaction Temperature and Aryl
Halide Comparison
t
dered KO Bu (70 mg, 0.63 mmol, 0.3 eq.), and 2 (2 mg,
0
.2 mol%) were added sequentially. The reaction mixture
was stirred for 5 min while continually purging with Ar. The
vial was then sealed with a Teꢃon screw cap. The reaction
mixture was stirred for 3 h at 110 °C in a preheated oil bath,
then allowed to cool to room temperature and ꢁltered by
passing through Celite to remove the base and the catalyst.
In reactions run at temperatures ranging from 70 to 120 °C,
increasing the temperature resulted in higher yields and
TONs (Fig. 3). The TON of the reaction increased slightly
from 70 to 100 °C with values of 169, 174, 181 and 195,
respectively. Similar trends were observed at 110 and
3
0 μL of the solution was then dissolved in 1 mL absolute
1
3

C–N Cross-coupling Reactions of Amines with Aryl Halides Using Amide-Based Pincer Nickel(II)…
Table 1 Amination of chlorobenzene using varies of solvents and bases
Entry
Solvent
Base
TON
t
1
2
3
4
5
6
7
8
9
DMF
KO Bu
NR
t
MTBE
Dioxane
THF
Toluene
DMA
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
KO Bu
3± 1
25± 2
36± 7
68± 14
69± 5
243± 29
NR
NR
NR
NR
20
t
KO Bu
t
KO Bu
t
KO Bu
t
KO Bu
t
KO Bu
Cs CO
K CO
DMAP
DBU
KOH
2
3
2
3
1
1
1
0
1
2
Yields represents an average of two runs. TON was measured in GC by using decane as an internal standard
MTBE methyl tert-butyl ether
1
20 °C, with values of 212 and 219, respectively, with maxi-
reaction times, all reactions were heated at 110 °C for 3 h
under argon (Table 2). Bromobenzene yielded the desired
product with highest TON of 484 (Entry 3) compared to
chlorobenzene (361, Entry 2) and iodobenzene (317, Entry
1). Note that 484 turnovers amount to 97% conversion of
the bromobenzene limiting reagent with a selectivity of
mum TON observed at 120 °C.
After identifying the optimal amination conditions
using 2, we investigated the amination of chloro-, bromo-
t
and iodobenzene with morpholine in DMSO with KO Bu.
In order to focus on low catalyst loadings and short
9
5% due to a small amount of biphenyl formation. None-
theless, aryl chlorides were chosen as the major focus of
this work as they are less expensive and more widely avail-
able than their bromo and iodo analogs.
2
2
2
2
1
1
1
1
1
30
20
10
00
90
80
70
60
50
Table 2 Evaluation of various electrophiles
Entry
X
TON
1
2
3
I
Cl
Br
316.9± 3.8
361.3± 0.07
484.1± 1.1
6
5
75
85
95
105
115
125
°
Temperature ( C)
Yields represent an average of two runs. TON was measured in GC
by using decane as an internal standard
Fig. 3 Eꢀect of temperature (70 °C to 120 °C) on the amination reac-
t
tion using 2 and KO Bu in DMSO. Yields represent an average of two
runs after 3 h
1
3

Y. M. Albkuri et al.
Scheme 1 Pincer nickel cata-
lyzed amination of chloroben-
zene with 1° amines. Yields
represents an average of two
runs. TON was measured in GC
by using decane as an internal
standard. The GC–MS spectra
of the products are given in the
Supporting Information
3
.3 Amination Scope of Chlorobenzene
TON). Octyl- and decyl-amines yielded high TONs of 331
and 365, respectively (7f, h). The steric bulk of the amines
was found to negatively inꢃuence the outcome of the desired
products, as t-butylamine produced low TON of 55 (7i).
Similarly, other sterically bulky amines also showed dim-
ished activities (7j, k). Two of the amine products (7l, m)
were isolated from the reaction mixture for the purpose of
with Aliphatic/Aromatic Amines
A series of 1° amines were tested for cross-coupling reac-
tions using chlorobenzene under the same conditions as pre-
viously stated (Scheme 1). Good TONs were obtained for
most 1° amines tested. Among the series of linear aliphatic
amines (7a–h), there was no clear-cut trend for the smaller
compounds (7a–c). However, as the amine chain lenth
increased, a rise in TON (from 173 to 365) was observed
1
13
H and C NMR analysis and these characterizations are
included in supplementary information (Fig. S1).
Reactions of chlorobenzene with alkyl and aromatic 2°
amines with varying degrees of steric bulk and nucleo-
philicity were also investigated (Scheme 2). Alkyl amines
(
7d–h). All linear aliphatic amines were found to react with
chlorobenzene to produce the desired products (143–365
1
3

C–N Cross-coupling Reactions of Amines with Aryl Halides Using Amide-Based Pincer Nickel(II)…
Scheme 2 Pincer nickel cata-
lyzed amination of chloroben-
zene with 2° amines. Yields
represent an average of two
runs. TON was measured in GC
by using decane as an internal
standard. The GC–MS spectra
of the products are provided in
the Supporting Information
with relatively less steric hindrance furnished the desired
products with TONs in the range of 156–215 (8a–d, f),
while more hindered amines showed lower activity, as in
the case of diisopropylamine (8e).
3.5 Kinetic Study of Aryl Chloride Amination Using
Nickel Pincer Catalyst 2
Initial rates of chlorobenzene amination using aniline and
KOtBu in DMSO at 110 °C were measured with respect to
catalyst, aryl chloride, amine and base. Plots of concentra-
tions of diphenylamine versus time at various concentrations
of amine, catalyst, base, and aryl chloride along with their
reaction schemes are shown in the Supporting Information
(Figs. S2–S5 and Tables S1–S4). The ꢁrst observation of note
was that no reaction was observed for the ꢁrst 20–30 min
depending on the ratio of base to catalyst precursor, suggesting
that the active catalyst is slow to form, even at 110 °C. Plots
of the initial amination rate versus time at various concentra-
tions of amine, catalyst, base, and aryl chloride are shown in
the supporting information (Fig. S6). The results are consist-
ent with a ꢁrst order rate dependence on the concentrations
of catalyst and aryl chloride and zero order for the bae and
amine. Similar observations have been reported previously
with other Ni catalysts [17]. At high concentrations of aryl
chloride using 2, however, the rate is suppressed, likely due to
catalyst deactivation.
3
.4 Amination Scope of Substituted Aryl Halides
with Aliphatic/Aromatic Amines
Establishing optimal conditions for nickel-catalyzed amina-
tion of substituted aryl bromides has proved challenging,
generally requiring complicated catalyst systems and often
giving low yields [28, 29]. Indeed, using complex 2 with
t
varying ratios of KO Bu gave insigniꢁcant conversions.
However, using 1 eq. of LiHMDS as a base, the desired
coupling products were obtained from aniline and several
substituted aryl bromides in poor to fair yields (3–30% 9a–c,
Scheme 3).
Applying a similar protocol (but using 2 eq. of LiHMDS)
to the amination of several substituted aryl chlorides cata-
lyzed by 2 gave fair to moderate yields of the coupled prod-
ucts (7, 21% 10a, b).
1
3

Y. M. Albkuri et al.
Scheme 3 Pincer nickel-cata-
lyzed amination of substituted
aryl bromides and chlorides
with 1° amine. Yields represents
an average of two runs. TON
was measured in GC by using
decane as an internal stand-
ard. 10a and 10b LiHMDS
,
(
0.66 mL, 2 equiv. to substrate).
The GC–MS spectra of the
products are given in the Sup-
porting Information
3
.6 Proposed Reaction Pathway of Pincer Nickel
Complex‑Catalyzed Amination of Aryl Halides
with Amines
the long induction period whereas rate-limiting oxidative
addition of the aryl halide is consistent with the ꢁrst order
rate dependence on both catalyst and aryl halide.
The reaction was also performed in the presence of a radi-
cal quencher, namely 2,2,6,6-tetramethyl-1-piperidinyloxy
(TEMPO) assess its eꢀect on the rate. The rate of reaction
was found to be unaꢀected in the presence of TEMPO.
Therefore, it can be inferred that organic radicals are not
involved in the catalyst cycle.
As mentioned in the literature for diꢀerent Ni- and Pd-
complexes, reactions usually occur via oxidative addition
of aryl halides followed by reductive elimination from a
metal-amido intermediate [16]. While catalysts have been
designed to accomplish these steps exclusively through
Ni(0–II) intermediates [17], many Ni(II) catalysts are pro-
posed instead to involve paramagnetic Ni(I–III) intermedi-
ates in which the base serves as the initial reductant [30,
4 Conclusion
3
1]. We propose a similar scheme using anionic catalyst 2.
In our reaction system, loss of chloride from 2 is likely
Nickel pincer-based catalyst 2 was used for the ꢁrst time in
C–N cross coupling amination of aryl halides with amines.
The catalyst is stable and relatively easy to handle under
atmospheric conditions and after an induction period, low
catalyst loading (0.2 mol%) and short reaction times aꢀord
signiꢁcant product yields for both 1° and 2° amines with a
variety of substituted aryl halides. Various amines and aryl
halides were examined, and the catalyst demonstrated mod-
erate to high TONs (up to 400). Kinetic studies revealed that
the reaction proceeds with ꢁrst-order kinetics with respect
to catalyst and aryl halide concentrations while amine and
base concentrations did not aꢀect the overall reaction rate.
required before the complex can be reduced to the Ni(I)
t
anion, where either amines or KO Bu can reduce the
metal by singlet electron transfer process [30, 31], likely
present as the amine complex A (Fig. 4). Following aryl
halide oxidative addition, halide elimination would again
be required to recoordinate the amine in intermediate
B. Deprotonation of the coordinated amine will also be
favored from the neutral Ni(III) intermediate B and sub-
sequent reductive elimination of the product and recoor-
dination of the amine regenerates the active Ni(I) catalyst
A. The slow reduction of 2 to A presumably gives rise to
1
3

C–N Cross-coupling Reactions of Amines with Aryl Halides Using Amide-Based Pincer Nickel(II)…
3
.
Xu S, Kim EH, Wei A et al (2014) Pd-and Ni-catalyzed cross-
coupling reactions in the synthesis of organic electronic materials.
Sci Technol Adv Mater 15(4):044201
4
5
6
7
8
.
.
.
.
.
Hili R, Yudin AK (2006) Making carbon-nitrogen bonds in bio-
logical and chemical synthesis. Nat Chem Biol 2(6):284
Taylor RD, MacCoss M, Lawson ADG (2014) Rings in drugs:
miniperspective. J Med Chem 57(14):5845–5859
Ullmann F (1903) Ueber eine neue bildungsweise von diphe-
nylaminderivaten. Ber Dtsch Chem Ges 36(2):2382–2384
Goldberg I (1906) Ueber phenylirungen bei gegenwart von kup-
fer als katalysator. Ber Dtsch Chem Ges 39(2):1691–1692
Wolfe JP, Wagaw S, Marcoux J-F et al (1998) Rational develop-
ment of practical catalysts for aromatic carbon−nitrogen bond
formation. Acc Chem Res 31(12):805–818
9
.
Yang BH, Buchwald SL (1999) Palladium-catalyzed ami-
nation of aryl halides and sulfonates. J Organomet Chem
5
76(1–2):125–146
1
1
0. Hartwig JF (2002) In: Negishi EI (ed.) Handbook of organopalla-
dium chemistry for organic synthesis. Wiley, Hoboken
1. Hartwig JF (1998) Transition metal catalyzed synthesis of ary-
lamines and aryl ethers from aryl halides and triꢃates: scope and
mechanism. Angew Chem Int Ed 37(15):2046–2067
1
1
2. Heravi MM, Kheilkordi Z, Zadsirjan V et al (2018) Buchwald–
Hartwig reaction: an overview. J Organomet Chem 861:17–104
3. Forero-Cortés PA, Haydl AM (2019) The 25th anniversary of the
Buchwald–Hartwig amination: development, applications, and
outlook. Org Proc Res Dev 23(8):1478–1483
1
1
1
1
4. Balcells D, Nova A (2018) Designing Pd and Ni catalysts for
cross-coupling reactions by minimizing oꢀ-cycle species. ACS
Catal 8(4):3499–3515
5. Yang K, Qiu Y, Li Z et al (2011) Ligands for copper-catalyzed
C−N bond forming reactions with 1 Mol% CuBr as catalyst. J Org
Chem 76(9):3151–3159
6. Desmarets C, Schneider R, Fort Y (2002) Nickel (0)/dihydroimi-
dazol-2-ylidene complex catalyzed coupling of aryl chlorides and
amines. J Org Chem 67(9):3029–3036
Fig. 4 Proposed mechanism for the nickel catalyzed amination of aryl
halides with amines using catalyst 2
7. Ge S, Green RA, Hartwig JF (2014) Controlling first-row
catalysts: Amination of aryl and heteroaryl chlorides and bro-
mides with primary aliphatic amines catalyzed by a BINAP-
ligated single-component Ni (0) complex. J Am Chem Soc
136(4):1617–1627
The proposed reaction pathway involves the oxidative addi-
tion of aryl halides to the anionic Ni(I) catalyst A and loss
of halide to give a neutral Ni(III) amine intermediate B.
Deprotonation of the coordinated amine in B is followed by
reductive elimination of the N-arylamine product. The reac-
tion does not proceed through organic radical intermediates
as revealed by radical quencher studies. In future studies,
generation, isolation and reactivity of the reduced version
of 2 will likely be informative.
1
8. Park NH, Teverovskiy G, Buchwald SL (2014) Development of
an air-stable nickel precatalyst for the amination of aryl chlorides,
sulfamates, mesylates, and triꢃates. Org Lett 16(1):220–223
19. Hidai M, Kashiwagi T, Ikeuchi T et al (1971) Oxidative addi-
tions to nickel (0): preparation and properties of a new series of
arylnickel(II) complexes. J Organomet Chem 30(2):279–282
2
0. Wolfe JP, Buchwald SL (1997) Nickel-catalyzed amination of aryl
chlorides. J Am Chem Soc 119(26):6054–6058
21. Brenner E, Fort Y (1998) New eꢂcient nickel(0) catalysed amina-
tion of aryl chlorides. Tetrahedron Lett 39(30):5359–5362
2
2. Tasker SZ, Standley EA, Jamison TF (2014) Recent advances in
homogeneous nickel catalysis. Nature 509(7500):299
Acknowledgements This research was ꢁnancially supported by the
National Science Foundation (Grant No. IIA-1457888) and the Arkan-
sas EPSCoR Program, ASSET III (CASE).
2
3. Li C, Kawamata Y, Nakamura H et al (2017) Electrochemi-
cally enabled, nickel-catalyzed amination. Angew Chem Int Ed
5
6(42):13088–13093
2
2
4. Kawamata Y, Vantourout JC, Hickey DP et al (2019) Electrochem-
ically driven, Ni-catalyzed aryl amination: scope, mechanism, and
applications. J Am Chem Soc 141(15):6392–6402
5. Rull SG, Funes-Ardoiz I, Maya C et al (2018) Elucidating the
mechanism of aryl aminations mediated by NHC-supported nickel
complexes: evidence for a nonradical Ni(0)/Ni(II) pathway. ACS
Catal 8(5):3733–3742
References
1
2
.
.
Ricci A (2000) Modern amination methods. Wiley, Weinheim
Garella D, Borretto E, Di Stilo A et al (2013) (2013) Microwave-
assisted synthesis of N-heterocycles in medicinal chemistry. Med-
ChemComm. 4(10):1323–1343
2
6. Gartia Y, Biswas A, Stadler M et al (2012) Cross coupling reac-
tions of multiple CCl bonds of polychlorinated solvents with
1
3

Y. M. Albkuri et al.
Grignard reagent using a pincer nickel complex. J Mol Catal A
63–364:322–327
30. Zheng B, Tang F, Luo J et al (2014) Organometallic nickel(III)
complexes relevant to cross-coupling and carbon–heteroatom
bond formation reactions. J Am Chem Soc 136(17):6499–6504
3
2
7. Gartia Y, Ramidi P, Jones DE et al (2014) Nickel complex cata-
3 2
t
lyzed eꢂcient activation of sp and sp C–H bonds for alkylation
and arylation of oxygen containing heterocyclic molecules. Catal
Lett 144(3):507–515
31. Barham JP, Coulthard G, Emery KJ et al (2016) KO Bu: a privi-
leged reagent for electron transfer reactions? J Am Chem Soc
138(23):7402–7410
2
2
8. Lavoie CM, MacQueen PM, Rotta-Loria NL et al (2016) Chal-
lenging nickel-catalysed amine arylations enabled by tailored
ancillary ligand design. Nat Commun 7:1–11073
Publisher’s Note Springer Nature remains neutral with regard to
jurisdictional claims in published maps and institutional aꢂliations.
9. Tassone JP, England EV, MacQueen PM et al (2019) PhPAd-Dal-
Phos: ligand-enabled, nickel-catalyzed cross-coupling of (hetero)
aryl electrophiles with bulky primary alkylamines. Angew Chem
Int Ed 58(8):2485–2489
1
3