A Structure–Activity Study of Nickel NNN Pincer Complexes for Alkyl-Alkyl Kumada and Suzuki–Miyaura Coupling Reactions

Article abstract of DOI:10.1002/hlca.201600165

A new series of Ni NNN pincer complexes were synthesized and characterized. The main difference among these complexes is the substituents on the side arm amino group(s). No major structural difference was found except for the C–N–C angle of the various substituents and the ‘pseudo bite angle’ of the complexes. Four new complexes were efficient for the alkyl-alkyl Kumada reaction of primary alkyl halides, and among them, one complex was also efficient with secondary alkyl halides. The influence of the substituents on the catalytic performance of the Ni complexes in alkyl-alkyl Kumada and Suzuki–Miyaura cross-coupling reactions was systematically investigated. No correlation was found between the catalytic activity and the key structural parameters (C–N–C angle and ‘pseudo bite angle’), redox properties or Lewis acidity of the complexes.

Full text of DOI:10.1002/hlca.201600165

Received Date: 03-Jun-2016
Revised Date: 22-Jul-2016
Accepted Date: 08-Aug-2016
Article Type: Full Paper
A Structure-Activity Study of Nickel NNN Pincer Complexes
for Alkyl-Alkyl Kumada and Suzuki-Miyaura Coupling
Reactions
Thomas Di Franco, Marko Stojanovic, Sébastien Carlos Keller, Rosario Scopelliti, and
Xile Hu*
Laboratory of Inorganic Synthesis and Catalysis, Institute of Chemical Sciences and Engineering, École Polytechnique
Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland (phone: +41-21-6939781; fax: +41-21-6939305; e-
mail: xile.hu@epfl.ch)
Abstract: A new series of nickel NNN pincer complexes were synthesized and characterized. The main difference among
these complexes is the substituents on the side arm amino group(s). No major structural difference was found except for
the C-N-C angle of the various substituents and the "pseudo bite angle" of the complexes. Four new complexes were
efficient for the alkyl-alkyl Kumada reaction of primary alkyl halides and among them, one complex was also efficient
with secondary alkyl halides. The influence of the substituents on the catalytic performance of the nickel complexes in
alkyl-alkyl Kumada and Suzuki-Miyaura cross-coupling reactions was systematically investigated. No correlation was
found between the catalytic activity and the key structural parameters (C-N-C angle and "pseudo bite angle"), redox
properties or Lewis acidity of the complexes.
Keywords: nickel • pincer ligands • cross-coupling • alkyl halides • structure-activity study
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Supporting information for this article is given via a link at the end of the document.
Introduction
There is continuous interest in developing metal complexes of pincer ligands for catalytic applications due to their many
desirable properties such as high stability, diversity, modularity, and ability to mediate unusual chemical transformations
[1-9]. A common method to vary the properties of pincer ligands is to change either the central linker or the donor groups
on the two side arms, or both. Such a change generally results in a dramatic difference in the electronic properties of the
ligands [10-15]. A complimentary approach is to vary the substituents on the donor atoms without changing the donors
themselves [16-18]. This approach is simple and straightforward from a synthetic point of view. It is especially appealing
for the optimization of already active but not yet efficient catalysts because the changes in the stereoelectronic
properties may be easy to identify and rationalize. Here we describe a structure-activity study of nickel NNN pincer
complexes where only the substituents of two N donors on the side arms are systematically changed, leading to very
different catalytic performances.
C-C cross-coupling of non-activated alkyl halides is challenging because alkyl electrophiles are less prone to oxidative
addition and metal alkyl intermediates are susceptible to β-hydride elimination [19-21].
Moreover, alkyl halides suffer from many side reactions such as hydrodehalogenation, homocoupling or base-promoted
HX elimination (X = halide) [22-23]. Despite these challenges, many efficient catalytic systems have been developed for
the coupling of non-activated alkyl halides [24-26] with various base metal such as Fe [27-31], Co [32-35], Ni [36-40] and
Cu [41-43]. However, the majority of these systems consists of a mixture of metal sources and ligands, making it difficult
to identify the active catalysts and rationally improve them. These difficulties might be alleviated by using well-defined
metal complexes as catalysts.
Our group previously reported a nickel pincer complex Nickamine ([(MeN2N)Ni−Cl], 1, see Figure 1 for the ligand
structure) as an efficient catalyst for a large number of cross-coupling reactions of non-activated alkyl halides [44-50]. A
major limitation of 1 is its low efficiency for the coupling of sterically demanding substrates such as secondary alkyl
halides.
Surprisingly, when one of the dimethylamino group in 1 was replaced by a pyrrolidino group, the resulting complex
[(PyrNMeNN)Ni−Cl] (2, see Figure 1 for the ligand structure), was able to catalyze the coupling of many secondary alkyl
halides in good yields [51]. This result indicated that a subtle change of the substituents of the side arm nitrogen atoms
in this NNN pincer system could result in a significant change and improvement of the catalytic properties.
This inspired us to conduct a systematic study of the influence of various substituents on the catalytic performance of the
Ni-NNN complexes in alkyl-alkyl Kumada and Suzuki-Miyaura cross-coupling reactions.
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Figure 1. Structure of ligands 1L-7L.
Results and Discussion
Synthesis and Characterization of New Nickel NNN Complexes.
Pro-ligands Synthesis. Five new NNN ligands 3L-7L were prepared to compare with ligands 1L and 2L which are used
in catalysts 1 and 2 (Figure 1). In the series of 1L-7L, the ligand structure and donor atoms are maintained while the
substituents on one or two of the side arm N donors are varied. The design of the five new ligands was inspired by the
surprising activity of catalyst 2. Like 2L, each of ligands 4L-7L contains a cyclic alkyl amine at one of the side arms. The
cyclic amines were varied systematically from 3-membered ring to 6-membered ring. They were abbreviated as follow:
Pyr for the pyrrolidine, Aze for the azetidine, Morph for the morpholine, Pip for the piperidine and Azi for the aziridine
(Figure 1). Ligand 3L contains two pyrrolidino side arms. The protonated forms of 3L-7L were first synthesized similar to
1H and 2H. Scheme 1 shows the synthesis of 3H, and Scheme 2 shows the synthesis of 4H-6H. Synthesis of pro-ligand
7H is shown in the supporting information (Scheme S1).
Scheme 1. Synthesis of Pro-Ligand 3H.
Scheme 2. Synthesis of the Pro-Ligands 4H-6H.
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Synthesis and Characterization of Nickel Chloride Complexes. Pro-ligands 3H-6H were deprotonated with n-butyl lithium
and then treated with NiCl2·dme (dme = dimethoxyethane) to give the resulting Ni(II) chloride complexes in good yields
(74-82 %; Scheme 3). The complexes are diamagnetic, suggesting a square planar structure. Pro-ligand 7H was
subjected to the same procedures to give the Ni(II) chloride complex 7 (Scheme S2, supporting information).
Unfortunately, the purification of 7 was difficult and this compound seemed to decompose in solution over a short period
of time. Therefore, no further studies were performed with this complex.
Scheme 3. Synthesis of Ni Pincer Complexes 3-6.
The solid-state structures of complexes 3-6 were determined by X-ray crystallography (Figure 2).
Table 1. Comparison of Key Structural Parameters of Complexes 1-6.
Entry
Complex
C-N-C Angle (°)
Ni-N(amide)
Averaged Ni-N(amine)
Bond Length (Å)
Ni-Cl Bond
Length (Å)
"Pseudo Bite
Bond Length (Å)
Angle" (°) a
105.97
101.24
95.59
)
1
2
3
4
5
1
2
3
4
108.9(2)
104.7(4)
1.835(2)
1.854(4)
1.831(2)
1.839(4)
1.958(2)
1.966(4)
1.970(2)
1.950(4)
2.203(7)
2.213(2)
2.189(4)
2.200(2)
103.5(1) and 104.6(1)
91.6(4)
98.76
5i
5j
110.4(1)
110.5(1)
1.838(2)
1.838(2)
1.959(2)
1.948(2)
2.222(6)
2.209(6)
96.21
94.37
6
6
112.1(1)
1.841(2)
1.964(2)
2.211(5)
96.04
a) The larger angle of the two bite angles for each complex is used.
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Figure 2. Crystal structure of complexes 3-6. The tw
o isomers of 5 are represented. Hydrogens atoms are omitted for clarity. The ellipsoids are
displayed at a 50% probability.
The nickel centers in the four complexes all have a square planar coordination geometry. Two isomers were found for
complex 5 due to the two different conformations adopted by the morpholino group. In 5i, the morpholino group has a
chair conformation, while in 5j, it has a skew-boat conformation (Figure 2). The structural parameters for complexes 1-6
are very similar. The maximum difference is less than 0.033(7) Å and 0.023(4) Å for the corresponding Ni−Cl and Ni−N
bond lengths, respectively (Table 1).
Likewise, the maximum difference of the bond angles around the nickel centers is less than 2°. The most important
change in the structures of 1-6 is the C-N-C angle of the amino groups whose substituents are varied. The dimethyl
amino group in 1 has a C-N-C angle of about 109°, close to that of an ideal tetrahedron. The C-N-C angles in the
complexes with 6-membered rings, 5 and 6, are about 110° and 112°, respectively, similar to those in 1. The complexes
with 5-membered ring(s), 2 and 3, on the other hand, have a C-N-C angle of about 104°, indicating a significant
contraction. The biggest contraction was found in the complex with a 4-membered ring, 4, which has a C-N-C angle of
only about 92°. This C-N-C angle is close to that of the free azetidine (92.2°) [52].
The "pseudo bite angle" between the amino groups and the nickel center as drawn in Figure 3 and Figure S1, supporting
information, is measured from the crystal structures. Table 1 shows that the angle is largest in 1, but varies only slightly
among 2-6.
Figure 3. "Pseudo bite angle" for complexes 3 and 6.
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Figure 4. Cyclic voltammograms of complexes 8-13 (
4 mM) recorded in CH3CN solutions at a scan rate of 400 mV·s-1; the potential is referenced
to the ferrocene/ferrocenium couple. The arrows indicate the starting potential and the direction of each scan.
Synthesis and Properties of Nickel Acetonitrile Complexes. To study the electronic properties of the complexes (see
below), nickel acetonitrile complexes 9-13 were synthesized by chloride abstraction from complexes 2-6. The
corresponding acetonitrile complex from 1 was previously reported (8) [53]. Complexes 9-12 were obtained by reaction
of 2-6 with silver tetrafluroborate in CH3CN, while complex 13 was obtained by reaction of 6 with sodium tetrakis[3,5-
bis(trifluoromethyl)phenyl]borate (NaBArF ) (Scheme 4).
4
Scheme 4. Synthesis of the Acetonitrile Complexes 9-13.
+
-
+
BF4
X-
N
N
Ni
N
AgBF4
or NaBArF
2 6
-
N
Ni
N
or
N
N
MeCN
rt, 30 min
NMe2
9, Pyr, 88% (X = BF4)
10
, (Pyr)2, 86%
11
, Aze, 84% (X = BF4)
12, Morph, 66% (X = BF4)
13, Pip, 48% (X = BArF
)
4
Cyclic voltammetry was conducted on complexes 9-13 (Figure 4 and Table 2). All these complexes exhibit one
reversible oxidation peak and one reduction peak which is either reversible (for 8 and 9) or non-reversible (for 10-13).
The corresponding redox potentials are shown in Table 2. The values determined for 8 are in agreement with previous
results [53]. From Table 2, the oxidation potentials of 8-12 are very close, and the maximum difference is only 90 mV.
The peak separation between the cathodic and the anodic peaks is about 200 mV for each compound, so this small
difference of redox potentials is well within the range of experimental uncertainty. The difference in the reduction
potentials of 8-13 is more substantial, with the maximum difference of 300 mV. However, these potentials cannot be
directly compared because of the complication in determining the true redox potentials of non-reversible electron
transfer by cyclic voltammetry. Overall, the cyclic voltammogram data are indicative of similar electronic properties of this
series of nickel complexes.
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Table 2. Reductive and Oxidative Potential of the [(RNR’NN)Ni-(NCCH3)]BR”4 Complexes.
Entry
Complex
E°'1/2 red (V) a
-1.67 (rev)
-1.64 (rev)
)
E°'1/2 ox (V) a)
-0.15 (rev)
-0.09 (rev)
-0.12 (rev)
-0.06 (rev)
-0.15 (rev)
-0.15 (rev)
1
2
3
4
5
6
8
9
10
11
12
13
-1.54 (non-rev)
-1.59 (non-rev)
-1.37 (non-rev)
-1.41 (non-rev)
a) rev = reversible, non-rev = non-reversible.
By determining how tightly a Lewis base such as CH3CN is bound to a metal center, the Lewis acidity of the
corresponding complex can be evaluated [54,55]. The stronger CH3CN is coordinated to the Ni center, the more
downfield will be the proton signal, which corresponds to a more Lewis acidic metal center. Thus, comparison of the shift
in the 1H NMR of the methyl group of coordinated CH3CN allows the measurement of the relative Lewis acidity of
complexes 8-13. (D6)Acetone was chosen as the solvent in these NMR experiments because some complexes were
poorly soluble in the commonly used CDCl3 for this type of experiments. The results are shown in Table 3. According to
Table 3, the Lewis acidity of these complexes have the order of 12 > 13 > 11 > 8 > 10 ≈ 9. The complexes seem to have
quite different Lewis acidity.
Table 3. The 1H NMR Chemical Shift of Coordinated CH3CN in 8-13.
Entry
Complex
δ(H) for CH3CN
(ppm, in (D6)Acetone)
1
2
3
4
8
9
2.53
2.31
2.32
2.70
10
11
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5
6
7
12
13
-
2.90
2.83
2.05
Activity in Alkyl-Alkyl Kumada Coupling Reactions.
The catalytic activity of new nickel complexes 3-6 was examined using the coupling of (3-iodobutyl)benzene and (4-
iodobutyl)benzene with n-butylMgCl (Tables 4-5 and Figures 5-6) as test reactions. The two substrates represent
secondary and primary alkyl iodides, respectively. The previously optimized reaction conditions for complex 2 were
chosen. Thus, the reactions were conducted using 3.5 mol % of catalyst in a 1:1.5 mixture of DMA/THF at -20 °C; 1.2
equivalent of Grignard reagent was slowly added over 2 h. Control experiments using NiCl2·dme as catalyst or no
catalyst were also conducted. The results using catalysts 1 and 2 were also listed for comparison.
Coupling of (3-iodobutyl)benzene with n-BuMgCl. With Nickamine (1) as catalyst, the coupling yield was only 5%,
consistent with it being inefficient for the coupling of secondary alkyl halides (Table 4, Entry 1). The conversion was
59%, and a small amount of reduction and elimination products were also obtained. The main side product was (3-
chlorobutyl)benzene (27%), presumably formed from I-Cl exchange. As previously reported, complex 2 was efficient for
the coupling, giving a yield of 72% (Table 4, Entry 2). The conversion was complete, and the main side product was the
reduction product (6%). Complexes 3 and 4 were also efficient for this reaction, with complete conversion and high
yields (Table 4, Entries 3 and 4). Complexes 5 and 6 had modest efficiency (Table 4, Entries 5 and 6). While the
conversion was complete, a significant amount of reduction and homocoupling products were also formed. NiCl2·dme
was not efficient as catalyst (Table 4, Entry 7). Without any catalyst, no coupling occurred (Table 4, Entry 8). About 21%
of conversion was made, and the main reaction was the I-Cl exchange of (3-iodobutyl)benzene to give (3-
chlorobutyl)benzene (16%). It is noted that no elimination product was observed without a nickel catalyst, suggesting
that the elimination was metal-mediated. A graphical representation of the results in Table 4 is shown in Figure 4.
Figure 5. A graphical representation of the products distribution for the Kumada coupling with a secondary alkyl iodide. R-H = butylbenzene, R-R =
(3,4-dimethylhexane-1,6-diyl)dibenzene, R-Cl = (3-chlorobutyl)benzene and Elim. = elimination products (but-3-en-1-ylbenzene and but-2-en-1-
ylbenzene).
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Coupling of (4-iodobutyl)benzene with n-BuMgCl. For the coupling of this primary alkyl iodide, complexes 1-4 all
exhibited high efficiency (Table 5, Entries 1-4). Complexes 5 and 6 had slightly lower efficiency, with yields of 49% and
61%, respectively (Table 5, Entries 5 and 6). The conversion using these two catalysts was complete, but a significant
amount of homocoupling was observed. NiCl2·dme again had a very low efficiency (Table 5, Entry 7). Without any
catalyst, the conversion was 38% and no product was formed (Table 5, Entry 8). The major side-product was (4-
chlorobutyl)benzene (13%), formed via a I/Cl exchange of (4-iodobutyl)benzene with the Grignard reagent. A graphical
representation of the results in Table 5 is shown in Figure 6.
Table 4. Conversion and Product Distribution for the Kumada Coupling of (3-Iodobutyl)benzene with n-BuMgCl. a) b)
Entry
Ni-cat
Conv. (%)
59
Yield (%)
R-H (%) c)
R-R (%) d)
R-Cl (%) e)
Elim (%) f)
1
2
3
4
5
6
7
8
1
5
3
6
1
1
27
0
2
3
2
> 99
> 99
> 99
> 99
> 99
96
72
65
67
35
39
14
0
3
1
0
0
0
4
4
1
0
3
5
13
8
11
11
12
0
0
5
6
0
5
NiCl2·dme
-
21
1
0
15
1
21
16
a) n-BuMgCl (1.2 equiv, 0.24 mmol) was diluted in THF (1 mL) and added dropwise via a syringe pump (2 h) to a
DMA/THF solution (0.3 and 0.2 mL) of catalyst (3.5 mol %) and alkyl iodide (0.2 mmol) at -20 °C under N2. The
reaction time was 30 min. b) Conversions and yields were determined by GC-MS relative to the alkyl halide. c) R-H =
butylbenzene. d) R-R = (3,4-dimethylhexane-1,6-diyl)dibenzene. e) R-Cl = (3-chlorobutyl)benzene. f) Elim. =
elimination products (but-3-en-1-ylbenzene and but-2-en-1-ylbenzene).
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Table 5. Conversion and Product Distribution for the Kumada Coupling of (4-Iodobutyl)benzene with n-BuMgCl. a) b)
I
n-Bu
Ni-cat (3.5 mol %)
n-Bu MgCl
+ side products
+
THF/DMA
-20 °C, 2 h
1.2 equiv
Entry
Ni-cat
Conv. (%)
> 99
> 99
> 99
89
Yield (%)
R-H (%) c)
R-R (%) d)
R-Cl (%) e)
Elim (%) f)
1
2
3
4
5
6
7
8
1
78
1
1
1
1
4
8
0
0
2
70
76
70
49
61
22
0
3
1
6
1
0
4
1
6
2
0
5
> 99
> 99
98
8
17
13
1
0
3
6
2
5
0
NiCl2·dme
-
10
0
10
13
15
0
38
0
a) Same conditions as in Table 4. b) Conversions and yields were determined by GC-MS relative to the alkyl halide.
c) R-H = butylbenzene. d) R-R = 1,8-diphenyloctane. e) R-Cl = (4-chlorobutyl)benzene. f) Elim. = elimination products
(but-3-en-1-ylbenzene and but-2-en-1-ylbenzene).
Figure 6. A graphical representation of the products distribution for the Kumada coupling with a primary alkyl iodide. R-H = butylbenzene, R-R =
1,8-diphenyloctane, R-Cl = (4-chlorobutyl)benzene and Elim. = elimination products (but-3-en-1-ylbenzene and but-2-en-1-ylbenzene).
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Activity in Alkyl-Alkyl Suzuki-Miyaura Coupling Reactions.
The reactions of (3-iodobutyl)benzene and (4-iodobutyl)benzene with 9-octyl-9-borabicyclo[3.3.1]nonane (abbreviated n-
octyl-(9-BBN)) were used as the test reactions (Tables 6-7). The previously developed conditions for complexes 1 and 2
were applied: 5 mol % of catalyst, 1.6 equivalent of sodium hydroxide, 0.5 equivalent of sodium iodide, 2 equivalent of
isopropanol, 1,4-dioxane as solvent and stirring at room temperature for 24 h.
Coupling of (3-iodobutyl)benzene with n-octyl-(9-BBN). For this reaction, only complex 2 was efficient (Table 6, Entry 2).
Complexes 1 and 4 have low conversion and yields (Table 6, Entries 1 and 4). The conversion using complexes 3, 5,
and 6 was modest, so were the yields (30-40%; Table 6, Entries 3, 5 and 6). NiCl2.dme gave low conversion and no
coupling yields (Table 6, Entry 7). Without a nickel catalyst, the conversion was about 22% and no coupling product was
made (Table 6, Entry 8). None of the new catalysts showed better efficiency than 2 for the Suzuki-Miyaura coupling with
non-activated secondary alkyl iodides.
Coupling of (4-iodobutyl)benzene with n-octyl-(9-BBN). For this reaction, complex 1 has a modest efficiency while
complex 2 is quite efficient (Table 7, Entries 1 and 2). Complexes 3-6 exhibited similar and quite low efficiency (Table 7,
Entries 3-6). The problem seemed to be related to the low conversion. No product was obtained using NiCl2·dme as
catalyst or without a nickel catalyst (Table 7, Entries 7-8). Under these conditions, nearly no conversion was made.
Table 6. Conversion and Product Distribution for the Szuki-Miyaura Coupling of (3-Iodobutyl)benzene with n-Octyl-(9-BBN). a) b)
Entry
Ni-cat
Conv. (%)
Yield (%)
R-H (%) c)
Elim (%) d)
1
2
3
4
5
6
7
1
23
96
75
38
59
61
31
9
89
42
8
8
6
6
5
6
7
6
2
0
3
2
6
2
4
2
3
4
5
6
36
30
0
NiCl2·dme
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8
-
22
0
2
2
a) NaOH (1.6 equiv), catalyst (5 mol %), NaI (0.5 equiv), i-PrOH (2 equiv), alkyl iodide (0.2 mmol)
and alkyl-(9-BBN) (1.6 equiv) in 1,4-dioxane (1 mL), at room temperature and under N2. The
reaction time was 24 h. b) Conversions and yields were determined by GC-MS relative to the alkyl
halide. c) R-H = butylbenzene. d) Elim. = elimination products (but-3-en-1-ylbenzene and but-2-en-
1-ylbenzene).
Table 7. Conversion and Product Distribution for the Szuki-Miyaura Coupling of (4-Iodobutyl)benzene with n-Octyl-(9-BBN). a) b)
Entry
Ni-cat
Conv. (%)
Yield (%)
R-H (%) c)
Elim (%) d)
1
2
3
4
5
6
7
8
1
76
73
36
27
37
27
12
3
53
70
27
25
15
23
0
5
4
2
0
3
3
4
0
0
0
1
1
7
2
0
0
2
3
4
5
6
NiCl2·dme
-
0
a) Same conditions as in Table 6. b) Conversions and yields were determined by GC-MS
relative to the alkyl halide. c) R-H = butylbenzene. d) Elim. = elimination products (but-3-en-1-
ylbenzene).
Stability of Nickel Complexes under Suzuki-Miyaura Coupling Conditions.
Complexes 3-6 exhibited in general lower activity in the Suzuki-Miyaura coupling reactions than in the Kumada coupling
reactions. A test was made to probe whether they decomposed during the Suzuki-Miyaura coupling reactions (Scheme
5).
Scheme 5. Stability Tests for the Suzuki-Miyaura Cross-Coupling Reaction.
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Thus, complexes 1-6 were subjected to the basic reaction conditions without the substrates. After the pre-mixing, the
two substrates (alkyl halide and boron reagent) were added and the reaction was stirred at room temperature for 24 h.
When the pre-mixing time was 10 min, coupling yields were similar to those obtained under conventional coupling
conditions were obtained for complexes 1 and 2, suggesting that these two complexes were stable during the pre-mixing
period. For complexes 3-6, however, the coupling yields after 10 min of pre-mixing were much lower than those obtained
under conventional coupling conditions. This result suggests that a large portion of complexes 3-6 were decomposed
during the pre-mixing period. When the pre-mixing time was extended to 4 h, even complexes 1 and 2 seemed to
decompose, leading to negligible coupling yields.
Hemilability Tests.
Previously we used an “inhibition” test to probe the potential hemilability of the pincer ligand in complexes 2.[51] An
analogous test was made for complexes 3-6 for the Kumada coupling reaction between (3-iodobutyl)benzene and n-
octylmagnesium chloride. With 3.5 mol % of catalyst and 10 equivalent of an exogenous ligand (2,4-lutidine, pyridine,
and PPh3; relative to the catalyst), no noticeable changes in the product yield were observed. However, with a lower
catalyst loading (1 mol %), inhibition of the coupling for certain complexes was observed (Table 8). The addition of 10
equivalent (relative to the catalyst) of an external ligand (2,4-lutidine or pyridine) to the reaction mixture decreased
significantly the yields for complexes 2 and 4-6. Addition of 10 equivalent of PPh3 had no effect on the catalysis of 4 and
6 while yield decreased for 2 and 5. It was reported that for some nickel complexes with bidentate NN ligands, PPh3
binds less strongly than pyridine and 2,4-lutidine [56]. Thus, complexes 2 and 5 seem more "hemilabile" than complexes
4 and 6. For complex 3, no inhibition was observed with 10 mol % of an external ligand.
Table 8. Effect of the Addition of Exogenous Ligands on Kumada Coupling. a) b)
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Entry
Ligand
Yield
Yield
Yield
Yield
Yield
2 (%)
3 (%)
4 (%)
5 (%)
6 (%)
1
2
-
70
22
64
65
29
18
18
3
24
5
2,4-
Lutidine
3
4
Pyridine
PPh3
24
36
64
82
14
32
5
7
13
20
a) Same conditions as in Table 4 with 10 mol % of the exogenous
ligand. b) Yields determined by GC-MS relative to the alkyl halide.
Discussion.
The synthesis of complexes 3-6 allows us to conduct a structure-activity study of this series of nickel pincer complexes
in Kumada and Suzuki-Miyaura coupling reactions of alkyl halides. The new complexes 3-6 exhibited lower efficiency for
the Suzuki-Miyaura coupling than for the Kumada coupling.
The pre-mixing experiments shown in Scheme 5 suggest that complexes 3-6 are not stable under the conditions of
Suzuki-Miyaura, possibly due to reactions with NaOH. Complexes 1 and 2 are more stable under these conditions. But
in the absence of substrates, they seem to be unstable as well over a longer period of pre-mixing. It is possible that
when the substrates are present, the stability of the complexes 1-6 is higher than when the substrates are absent.
Nevertheless, the low yields of 3-6 in Suzuki-Miyaura reactions might be attributed to their lower stability under the
reaction conditions.
For alkyl-alkyl Kumada coupling of a primary alkyl iodide, complexes 3-6 all exhibited good to excellent efficienc. For the
coupling of a secondary alkyl iodide, complexes 3 and 4 were efficient, complexes 5 and 6 gave low coupling yields. For
complexes 1-6, there is a substantial difference in their catalytic activity in the Kumada coupling reactions. We attempted
1
to correlate their activity with four different parameters: the Lewis acidity represented by the H NMR chemical shift of
the methyl group of [Ni]-NCMe complexes; the electronic property represented by the oxidation potential of the [Ni]-
NCMe complexes; the C-N-C angle of the substituents of the side arm amino groups; the “pseudo bite angles”.
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Figure 7. Correlation plots between electronic properties (Lewis acidity, A; and oxidative potential, B) or structural parameters (C-N-C angle of the
varying amino group, C; and "pseudo bite angle", D) and product yields for the Kumada reactions catalyzed by 1-6 (coupling of primary alkyl iodide
♦ and secondary alkyl iodide ■ ).
Figure 7 shows that there is no obvious correlation between the activity and these parameters for the coupling of both a
primary and a secondary alkyl iodide. Thus, two empirical parameters of the electronic properties of the catalysts, redox
potential and Lewis acidity, are not good descriptors of the catalytic activity of these structurally similar complexes. The
structural differences, represented by the C-N-C angles of the side arm amino groups and the “pesudo bite angles“, also
have no direct translation to the activity.
This result is probably not surprising because the efficiency of a catalyst in a multiple-step reaction depends on many
factors such as stability, reaction barriers, mechanism, etc. Considering the previous and current studies of this nickel
pincer system, we hypothesize the following reasons for the observed trend in catalytic activity. For Kumada coupling of
primary alkyl halides, most Ni-NNN complexes should be electronically rich enough to activate the alkyl halide by a
single-electron-transfer [57], so complexes 1-6 all have good to excellent efficiency, with a modest difference in yields for
certain reactions. For Kumada coupling of secondary alkyl halides, the main problem is the access of the nickel center
by the substrate. For a rigid [Ni]-NNN complex such as 1, the access is blocked; if one of the amino groups is
"hemilabile" like in 2, then the alkyl halide can be activated. Complexes 2, 4-6 all showed a certain level of hemilability
according to the test in Table 8, so they should be active for the coupling of secondary alkyl halides. This was indeed
observed. No inhibition was found for complex 3. However, this does not mean that 3 is not "hemilabile". There are two
"hemilabile" pyrolidino groups in 3, so when one arm dissociates and binds to an exogenous ligand, the other arm can
also dissociate and allow the access of the secondary alkyl halide. The detailed difference in the efficiency of active
catalysts is not easily explained due to the complexity mentioned above.
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Conclusion
In summary, a series of nickel NNN pincer complexes with difference only in the substituents of the side arm amino
groups were synthesized and characterized. A structure-activity study of these complexes in alkyl-alkyl Kumada and
Suzuki-Miyaura coupling reactions was conducted. The catalytic activity shows no obvious correlation with the redox
potential, Lewis acidity, or a key structural parameter (C-N-C angle) of the complexes. The study underlines the
complexity of catalyst design even on a well-defined metal-ligand system.
Subtle changes of the substituents of the side arm amino groups of this pincer NNN ligand framework resulted in a
significant difference in catalytic activity. Through this work, four new nickel pincer complexes (complexes 3-6) with good
to excellent efficiency in alkyl-alkyl Kumada coupling of primary alkyl halides were prepared. Among these four, one
(complex 3) was also efficient for the coupling of secondary alkyl halides.
Acknowledgements
This work is supported by the Swiss National Science Foundation (no. 200020_144393/1).
Author Contribution Statement
Thomas Di Franco performed the majority of synthesis, characterization, and catalysis tests; Marko Stojanovic
contributed to the synthesis and characterization of complexes 3 and 5; Sébastien C. Keller contributed to the synthesis
of 5 and preliminary catalysis tests of 3 and 5; Rosario Scopelliti performed the X-ray crystallographic analysis; Xile Hu
designed and directed the project. Thomas Di Franco and Xile Hu wrote the paper.
Supplementary Data
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HocanhrObdairMtgaelOs,aNannBddOLtoUtaMl O
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siacnuhvfpaoriprlgomaebratliteniogfrne.eTohfis is
vhwitiatlpet:yh//.eocnoinlmitne.renliebtratry.
Ogicsoeoponmtmtirmeiebritsuzr,ieteiadostonomsfoicf
HocanhrObdairMtgaelOs,aNannBddOLtoUtaMl O
rtbheeleafmtoiuvoneldeecniunelretghsieecsanof
siacnuhvfpaoriprlgomaebratliteniogfrne.eTohfis is
vhwitiatlpet:yh//.eocnoinlmitne.renliebtratry.
1H and 13C NMR spectra, X-ray crystal details, tables giving additional experimental details and crystallographic data can
be found in the supporting information. This is available free of charge via the internet at http://onlinelibrary.wiley.com.
This article is protected by copyright. All rights reserved.

Experimental Part
Chemicals and Reagents.
All manipulations were carried out under an inert N2(g) atmosphere using standard Schlenk or glovebox techniques.
Solvents were purified using a two-column solid-state purification system (Innovative Technology, NJ, USA) and
transferred to the glovebox without exposure to air. Deuterated solvents were purchased from Cambridge Isotope
Laboratories, Inc., and were degassed and stored over activated 3 Å molecular sieves. Unless otherwise noted, all other
reagents and starting materials were purchased from commercial sources and used without further purification. Liquid
compounds were degassed by standard freeze-pump-thaw procedures prior to use. The following chemicals were
prepared according to literature procedures: Nickamine (complex 1) [58], complex 2 [51], 2-bromo-N,N-dimethylaniline
[58], (4-iodobutyl)benzene [59] and (3-iodobutyl)benzene [60].
Physical Methods.
1
1
The H and 13C NMR spectra were recorded at 293 K on a Bruker Avance 400 spectrometer. H NMR chemical shifts
were referenced to residual solvent as determined relative to Me4Si (δ = 0 ppm). The 13C{1H} chemical shifts were
reported in ppm relative to the carbon resonance of CDCl3 (77.0 ppm). GC-MS measurements were conducted on a
Perkin-Elmer Clarus 600 GC equipped with Clarus 600T MS. HRESI-MS measurements were conducted at the EPFL
ISIC Mass Spectrometry Service with a Micro Mass QTOF Ultima spectrometer. Cyclic voltammetric measurements
were recorded in a glovebox by a CHI760E electrochemical workstation that was connected to a glassy carbon working
electrode (surface area = 0.07 cm2), a platinum wire auxiliary electrode, and an Ag/AgNO3 (0.01 M) reference electrode
filled with acetonitrile and [n-Bu4] [PF6] (0.1 M). All potentials were referenced to Fc/Fc+ as internal standard. The
temperature of reactions below room temperature was regulated by a Julabo FT-902 chiller. Elemental analyses were
performed on a Carlo Erba EA 1110 CHN instrument at EPFL. X-ray diffraction studies were carried out in the EPFL
Crystallographic Facility. Data collections were performed at low temperature by two four-circle kappa diffractometers
equipped with CCD detectors and a marresearch marmx system equipped S3 with mar345 imaging plate scanner. Data
were reduced and corrected for absorption only in the case of crystals measured by means of CCD detectors [61].
Solution, refinement and geometrical calculations for all crystal structures were performed by SHELXTL [62].
Experimental Details
Synthesis of 1-(2-nitrophenyl)pyrrolidine (3a). 1-Fluoro-2-nitrobenzene (1 equiv, 43 mmol, 4.5 mL) was dissolved with
K2CO3 (0.6 equiv, 26 mmol, 3.59 g) in 40 mL of acetonitrile. Pyrrolidine (1 equiv, 43 mmol, 3.06 g) was added under
stirring to the resulting mixture. The reaction was then heated under reflux during 3 h. 40 mL of water were added to the
reaction mixture and the product was extracted with DCM (3 × 50 mL). The organic phase was washed with brine (2 ×
50 mL) and with distilled water (50 mL). The organic phase was then dried over Na2SO4, filtered and the solvent was
evaporated under vacuum to give the product as orange oil. Yield: 8.26 g (99%). 1H-NMR (400 MHz, CDCl3): 7.73 (d, J =
8.2 Hz, 1H), 7.36 (t, J = 8.2 Hz, 1H), 6.90 (d, J = 8.6 Hz, 1H), 6.70 (t, J = 7.6 Hz, 1H), 3.21 (t, J = 6.4 Hz, 4H), 1.98 (t, J =
6.5 Hz, 4H). 13C-NMR (101 MHz, CDCl3): 142.9, 137.2, 133.1, 126.9, 116.0, 115.6, 50.5, 25.9. HRMS (ESI) for ([M+H]+:
+
C10H13N2O2 ), calculated: 193.0977, found: 193.0979.
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Synthesis of 1-(2-nitrophenyl)azetidine (4a). It was synthesized in a procedure similar to the one described for 3a
1
except that azetidine (15.8 mmol, 1.67 mL) was used instead of pyrrolidine. Yield: 2.79 g (99%). H-NMR (400 MHz,
CDCl3): 7.80 (d, J = 8.4 Hz, 1H), 7.38 (dd, J = 8.4, 7.1 Hz, 1H), 6.72 (dd, J = 8.4, 7.1 Hz, 1H), 6.60 (d, J = 8.4 Hz, 1H),
3.98 (t, J = 7.6 Hz, 4H), 2.38 (quint., J = 7.5 Hz, 2H). 13C-NMR (101 MHz, CDCl3): 145.9, 135.7, 133.5, 126.6, 116.5,
115.7, 53.7, 16.4. HRMS (ESI) for ([M+H]+: C9H11N2O2 ), calculated: 179.0820, found: 179.0825.
+
Synthesis of 4-(2-nitrophenyl)morpholine (5a). It was synthesized in a procedure similar to the one described for 3a
except that morpholine (1.74 g, 20 mmol) was used instead of pyrrolidine. Yield: 3.96 g (95%). 1H-NMR (400 MHz,
CDCl3): 7.77 (dd, J = 8.1, 1.6 Hz, 1H), 7.50 (ddd, J = 8.4, 7.4, 1.6 Hz, 1H), 7.15 (dd, J = 8.3, 1.1 Hz, 1H), 7.12-7.01 (m,
1H), 3.92-3.76 (m, 4H), 3.14-2.97 (m, 4H). 13C-NMR (101 MHz, CDCl3): 146.0, 143.9, 133.7, 126.0, 122.4, 121.1, 67.0,
52.2. HRMS (ESI) for ([M+H]+: C10H13N2O3 ), calculated: 209.0926, found: 209.0932.
+
Synthesis of 1-(2-nitrophenyl)piperidine (6a). It was synthesized in a procedure similar to the one described for 3a
except that piperidine (2.82 g, 20 mmol) was used instead of pyrrolidine. Yield: 4.31 g (99%). 1H-NMR (400 MHz,
CDCl3): 7.74 (d, J = 8.1 Hz, 1H), 7.43 (t, J = 7.8 Hz, 1H), 7.11 (d, J = 8.3 Hz, 1H), 6.95 (t, J = 7.7 Hz, 1H), 3.10-2.92 (m,
4H), 1.78-1.66 (m, 4H), 1.66- 1.46 (m, 2H). 13C-NMR (101 MHz, CDCl3): 147.2, 142.8, 133.4, 126.1, 121.0, 120.7, 53.1,
26.1, 24.2. HRMS (ESI) for ([M+H]+: C11H15N2O2 ), calculated: 207.1134, found: 207.1132.
+
Synthesis of 2-(pyrrolidin-1-yl)aniline (3b). 1-(2-Nitrophenyl)pyrrolidine 3b (8.0 g, 42 mmol) was dissolved in 40 mL of
methanol and 400 mg of Pd/C (5 %/weight of Pd) was added. The reaction flask was degassed and flushed with
hydrogen twice. It was then stirred for 14 h under hydrogen (2 bar) at room temperature. The Pd catalyst was filtered off
on silica, and the solvent was removed under reduced pressure. The pure compound was obtained as dark yellow oil.
1
Yield: 6.66 g (98%). H-NMR (400 MHz, CDCl3): 7.00 (dd, J = 8.2, 1.3 Hz, 1H), 6.96-6.81 (m, 1H), 6.74 (ddd, J = 7.9,
6.1, 1.5 Hz, 2H), 3.86 (s, 2H), 3.14-2.93 (m, 4H), 2.00-1.83 (m, 4H). 13C-NMR (101 MHz, CDCl3): 141.4, 137.8, 123.5,
118.8, 118.7, 115.5, 51.0, 24.2. HRMS (ESI) for ([M+H]+: C10H15N2 ), calculated: 163.1235, found: 163.1240.
+
Synthesis of 2-(azetidin-1-yl)aniline (4b). It was synthesized in a procedure similar to the one described for 3b except
that 1-(2-nitrophenyl)azetidine (2.78 g, 15.6 mmol) was used instead of 1-(2-nitrophenyl)pyrrolidine. Yield: 2.19 g (95%).
1H-NMR (400 MHz, CDCl3): 6.84-6.75 (m, 2H), 6.70-6.60 (m, 2H), 3.84 (t, J = 7.1 Hz, 4H), 3.51 (s, 2H), 2.37-2.16 (m,
2H). 13C-NMR (101 MHz, CDCl3): 139.9, 137.4, 121.4, 119.2, 116.0, 114.4, 53.4, 17.6. HRMS (ESI) for ([M+H]+:
+
C9H13N2 ), calculated: 149.1079, found: 149.1085.
Synthesis of 2-morpholinoaniline (5b). It was synthesized in a procedure similar to the one described for 3b except
that 4-(2-nitrophenyl)morpholine (3.94 g, 18.9 mmol) was used instead of 1-(2-nitrophenyl)pyrrolidine. Yield: 2.75 g
(82%). 1H-NMR (400 MHz, CDCl3): 7.01 (d, J = 7.7 Hz, 1H), 6.96 (t, J = 7.6 Hz, 1H), 6.76 (t, J = 8.4 Hz, 2H), 4.09-3.91
(m, 2H), 3.91-3.79 (m, 4H), 3.01-2.84 (m, 4H). 13C-NMR (101 MHz, CDCl3): 141.6, 139.1, 125.0, 120.0, 118.8, 115.4,
67.8, 51.6. HRMS (ESI) for ([M+H]+: C10H15N2O +), calculated: 179.1184, found: 179.1193.
This article is protected by copyright. All rights reserved.

Synthesis of 2-(piperidin-1-yl)aniline (6b). It was synthesized in a procedure similar to the one described for 3b except
that 1-(2-nitrophenyl)piperidine (4.31 g, 21 mmol) was used instead of 1-(2-nitrophenyl)pyrrolidine. Yield: 3.65 g (99%).
1H-NMR (400 MHz, CDCl3): 7.00 (d, J = 8.0 Hz, 1H), 6.92 (t, J = 7.5 Hz, 1H), 6.75 (t, J = 7.1 Hz, 2H), 3.98 (s, 2H), 2.84
(s, 4H), 1.71 (quint., J = 5.3 Hz, 4H), 1.58 (s, 2H). 13C-NMR (101 MHz, CDCl3): 141.7, 140.9, 124.3, 119.9, 118.6, 115.1,
52.8, 27.0, 24.5. HRMS (ESI) for ([M+H]+: C11H17N2 ), calculated: 177.1392, found: 177.1395.
+
Synthesis of 1-(2-bromophenyl)pyrrolidine (3c). 1,4-Dibromobutane (1 equiv., 17.4 mmol, 2.1 mL) and N,N-
diisopropylethylamine (2.4 equiv., 41.9 mmol, 7.3 mL) were added to a solution of 2-bromoaniline (1 equiv., 17.4 mmol,
3.01 g) in toluene (20 mL). The reaction was heated at 100°C for 96 h. The product was then purified by column
1
chromatography (on SiO2, Hexane) to afford the pure compound 3c as yellow oil. Yield: 2.86 g (72%). H-NMR (400
MHz, CDCl3): 7.51 (d, J = 7.9 Hz, 1H), 7.20 (t, J = 7.4 Hz, 1H), 6.93 (d, J = 8.1 Hz, 1H), 6.74 (t, J = 7.5 Hz, 1H), 3.36 (t, J
= 6.2 Hz, 4H), 1.95 (t, J = 6.3 Hz, 4H). 13C-NMR (101 MHz, CDCl3): 148.9, 134.7, 127.9, 121.4, 118.0, 114.0, 51.4, 25.2.
HRMS (ESI) for ([M+H]+: C10H13BrN +), calculated: 226.0231, found: 226.0233.
Synthesis of N1-(2-(azetidin-1-yl)phenyl)-N2,N2-dimethylbenzene-1,2-diamine (4H). A 100 mL reaction vessel was
charged with Pd2(dba)3 (0.02 equiv., 0.27 mmol, 0.25 g), bis(diphenylphosphino)-ferrocene (dppf) (0.04 equiv., 0.54
mmol, 0.30 g), NaOt-Bu (1.3 equiv., 17.6 mmol, 1.69 g) and toluene (50 mL) under a N2 atmosphere. 2-Bromo-N,N-
dimethylaniline (1.1 equiv., 14.9 mmol, 2.98 g) and 2-(azetidin-1-yl)aniline 4b (13.5 mmol, 2.0 g) were added to the
reaction mixture. The resulting brown solution was vigorously stirred for 16 h at 110 °C. The solution was then cooled to
room temperature and filtered through Celite. Removal of the solvent yielded a black liquid which was then dissolved in
dichloromethane and filtered through silica. The solvent was evaporated and the crude product was purified by column
chromatography (on SiO2, Hexane/Ethyl Acetate 9:1) to afford the pure compound 4H as a brown oil. Yield: 2.54 g
(84%). 1H-NMR (400 MHz, CDCl3): 7.30-7.21 (m, 1H), 7.13 (d, J = 7.7 Hz, 1H), 7.05 (t, J = 7.6 Hz, 1H), 6.98 (quint., J =
9.1, 8.4 Hz, 2H), 6.82 (dt, J = 22.8, 7.4 Hz, 2H), 6.66 (d, J = 7.9 Hz, 1H), 6.26 (s, 1H), 3.85 (t, J = 7.1 Hz, 4H), 2.73 (s,
6H), 2.31-2.14 (m, 2H). 13C-NMR (101 MHz, CDCl3): 146.2, 141.1, 140.3, 130.4, 124.5, 123.7, 123.6, 119.6, 119.5,
118.3, 114.1, 112.7, 53.9, 44.3, 17.6. HRMS (ESI) for ([M+H]+: C17H22N3 ), calculated: 268.1814, found: 268.1812.
+
Synthesis of bis(2-(pyrrolidin-1-yl)phenyl)amine (3H). It was synthesized in a procedure similar to the one described
for 4H except that 1-(2-bromophenyl)pyrrolidine 3c (1 equiv., 27 mmol, 6.24 g) was used instead of 2-bromo-N,N-
dimethylaniline and 2-(pyrrolidin-1-yl)aniline 3b (1.2 equiv., 32.4 mmol, 5.26 g) was used instead of 2-(azetidin-1-
yl)aniline. Yield: 6.81 g (82%). 1H-NMR (400 MHz, CDCl3): 7.22 (d, J = 7.9 Hz, 2H), 7.05 (d, J = 7.6 Hz, 2H), 6.93 (t, J =
7.3 Hz, 2H), 6.87 (t, J = 7.5 Hz, 2H), 6.68 (s, 1H), 3.09 (t, J = 6.0 Hz, 8H), 1.90 (quint., J = 3.2 Hz, 8H). 13C-NMR (101
MHz, CDCl3): 140.8, 137.3, 122.6, 120.6, 118.4, 117.3, 51.3, 24.7. HRMS (ESI) for ([M+H]+: C20H26N3 ), calculated:
+
308.2127, found: 308.2124.
Synthesis of N1,N1-dimethyl-N2-(2-morpholinophenyl)benzene-1,2-diamine (5H). It was synthesized in a procedure
similar to the one described for 4H except that 2-morpholinoaniline 5b (2.75 g, 15.4 mmol) was used instead of 2-
(azetidin-1-yl)aniline. Yield: 3.67 g (80%). 1H-NMR (400 MHz, CDCl3): 7.63 (s, 1H), 7.52-7.37 (m, 2H), 7.17-6.97 (m, 4H),
6.96-6.82 (m, 2H), 3.96-3.77 (m, 4H), 3.06-2.91 (m, 4H), 2.72 (s, 6H). 13C-NMR (101 MHz, CDCl3): 142.9, 141.4, 137.7,
137.6, 124.6, 124.1, 120.1, 120.0, 119.9, 119.8, 115.6, 114.2, 67.9, 52.0, 44.3. HRMS (ESI) for ([M+H]+: C18H23N3O +),
calculated: 298.1919, found: 298.1921.
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Synthesis of N1,N1-dimethyl-N2-(2-(piperidin-1-yl)phenyl)benzene-1,2-diamine (6H). It was synthesized in a
procedure similar to the one described for 4H except that 2-(piperidin-1-yl)aniline 6b (1.72 g, 10 mmol) was used instead
of 2-(azetidin-1-yl)aniline. Yield: 2.37 g (80%). 1H-NMR (400 MHz, CDCl3): 7.69 (s, 1H), 7.52-7.41 (m, 2H), 7.16-6.96 (m,
4H), 6.87 (t, J = 7.4 Hz, 2H), 2.86 (s, 4H), 2.73 (s, 6H), 1.79-1.69 (m, 4H), 1.63-1.56 (m, 2H). 13C-NMR (101 MHz,
CDCl3): 143.0, 143.0, 137.8, 137.7, 124.0, 123.9, 120.2, 119.7, 119.6, 114.8, 114.3, 53.2, 44.1, 27.0, 24.6. HRMS (ESI)
for ([M+H]+: C20H25N3 ), calculated: 296.2121, found: 296.2126.
+
Synthesis of bis(2-(pyrrolidin-1-yl)phenyl)amine nickel(II) chloride (3). n-BuLi (1 equiv, 1.6 M in hexane, 10.5 mmol,
6.6 mL) was slowly added to a THF solution (80 mL) of the bis(2-(pyrrolidin-1-yl)phenyl)amine 3H (3.22 g, 10.5 mmol) at
room temperature. The reaction mixture was stirred for 2 h at room temperature, and then NiCl2·dme (1 equiv, 10.5
mmol, 2.31 g, dme = dimethoxyethane) was added at room temperature. The resulting solution was stirred for 5 h and
then evaporated under vacuum. The residue was extracted with toluene, filtered through a PTFE filter (0.22 µm pore
size) and concentrated to ca. 5 mL. Addition of pentane (20 mL) afforded a brown precipitate which was filtered, washed
with additional pentane and dried under vacuum. Yield: 3.45 g (82%). Diffusion of pentane into a toluene solution of 3 at
room temperature afforded brown crystals suitable for X-ray analysis. CCDC-1482732 contain(s) the supplementary
crystallographic data for this work. These data can be obtained free of charge from The Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/data_request/cif. 1H-NMR (400 MHz, CDCl3): 7.32 (d, J = 9.1 Hz, 2H), 6.93 (t, J =
8.4 Hz, 2H), 6.67 (d, J = 9.1 Hz, 2H), 6.37 (t, J = 8.1 Hz, 2H), 4.51-4.30 (m, 4H), 3.24-3.10 (m, 4H), 1.91 (t, J = 7.0 Hz,
8H). 13C-NMR (101 MHz, CDCl3): 150.4, 147.5, 127.3, 121.5, 116.0, 113.6, 61.9, 24.7. Anal. calc. for C20H24ClN3Ni
(400.58): C 59.97, H 6.04, N 10.49; found: C 60.05, H 6.06, N 10.34.
Synthesis of N1-(2-(azetidin-1-yl)phenyl)-N2,N2-dimethylbenzene-1,2-diamine nickel(II) chloride (4). It was
synthesized in a procedure similar to the one described for 3 except that N1-(2-(azetidin-1-yl)phenyl)-N2,N2-
dimethylbenzene-1,2-diamine 4H (1.53 g, 5.7 mmol) was used instead of bis(2-(pyrrolidin-1-yl)phenyl)amine. Yield: 1.64
g (80%). Single crystals suitable for X-ray crystallography were obtained by diffusion of pentane into a toluene solution
of 4 at room temperature. CCDC-1482731 contain(s) the supplementary crystallographic data for this work. These data
can
be
obtained
free
of
charge
from
The
Cambridge
Crystallographic
Data
Centre
via
www.ccdc.cam.ac.uk/data_request/cif. 1H-NMR (400 MHz, CDCl3): 7.47-7.30 (m, 3H), 7.08-6.89 (m, 3H), 6.57 (t, J = 7.5
Hz, 1H), 6.47 (t, J = 7.4 Hz, 1H), 5.08 (quint., J = 9.7 Hz, 2H), 3.64 (q, J = 9.8 Hz, 2H), 2.91 (s, 6H), 2.43 (tt, J = 17.4, 7.6
Hz, 2H). 13C-NMR (101 MHz, CDCl3): 149.4, 148.1, 147.6, 146.7, 128.3, 128.1, 120.9, 120.3, 116.7, 116.0, 114.0, 113.7,
64.8, 51.3, 18.0. Anal. calc. for C17H20ClN3Ni (360.51): C 56.64, H 5.59, N 11.66; found: C 56.66, H 5.57, N 11.57.
Synthesis of N1,N1-dimethyl-N2-(2-morpholinophenyl)benzene-1,2-diamine nickel(II) chloride (5). It was
synthesized in
a
procedure similar to the one described for
3
except that N1,N1-dimethyl-N2-(2-
morpholinophenyl)benzene-1,2-diamine 5H (2.58 g, 8.7 mmol) was used instead of bis(2-(pyrrolidin-1-yl)phenyl)amine.
Yield: 2.51 g (74%). Single crystals suitable for X-ray crystallography were obtained by diffusion of pentane into a
toluene solution of 5 at room temperature. CCDC-1482733 contain(s) the supplementary crystallographic data for this
work. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif. 1H-NMR (400 MHz, CDCl3): 7.36 (d, J = 7.7 Hz, 1H), 7.23 (dd, J = 12.8, 8.1 Hz,
2H), 7.07-6.90 (m, 3H), 6.42 (dt, J = 21.8, 6.8 Hz, 2H), 4.44 (s, 2H), 4.11 (s, 2H), 3.94 (s, 2H), 3.22 (d, J = 11.8 Hz, 2H),
2.91 (s, 6H). 13C-NMR (101 MHz, CDCl3): 147.1, 147.0, 146.9, 145.8, 128.0, 127.7, 121.7, 120.1, 117.0, 116.1, 115.2,
113.9, 63.3, 54.9, 51.6. Anal. calc. for C18H22ClN3NiO (390.54): C 55.36, H 5.68, N 10.76; found: C 55.35, H 5.64, N
10.68.
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Synthesis of N1,N1-dimethyl-N2-(2-(piperidin-1-yl)phenyl)benzene-1,2-diamine nickel(II) chloride (6). It was
synthesized in a procedure similar to the one described for 3 except that N1,N1-dimethyl-N2-(2-(piperidin-1-
yl)phenyl)benzene-1,2-diamine 6H (1 g, 3.4 mmol) was used instead of bis(2-(pyrrolidin-1-yl)phenyl)amine. Yield: 0.99 g
(75%). Single crystals suitable for X-ray crystallography were obtained by diffusion of pentane into a toluene solution of
6 at room temperature. CCDC-1482734 contain(s) the supplementary crystallographic data for this work. These data can
be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
1H-NMR (400 MHz, CDCl3): 7.39 (t, J = 7.3 Hz, 2H), 7.32 (d, J = 8.3 Hz, 1H), 6.96 (t, J = 8.1 Hz, 3H), 6.40 (dt, J = 28.8,
7.6 Hz, 2H), 4.39-4.21 (m, 2H), 3.47 (d, J = 13.1 Hz, 2H), 2.90 (s, 6H), 1.91 (q, J = 10.1, 7.5 Hz, 2H), 1.83-1.67 (m, 2H),
1.60 (d, J = 14.1 Hz, 2H). 13C-NMR (101 MHz, CDCl3): 147.9, 147.2, 147.0, 146.6, 128.0, 127.4, 123.4, 120.1, 116.4,
115.4, 114.7, 114.0, 55.8, 51.6, 22.3, 22.3. Anal. calc. for C19H24ClN3Ni (388.57): C 58.73, H 6.23, N 10.81; found: C
58.68, H 6.26, N 10.72.
Synthesis of [(MeN2N)Ni(NCCH3)]BF4 (8). A solution of silver tetrafluoroborate AgBF4 (1 equiv, 0.4 mmol, 78 mg) in
CH3CN (2 mL) was added to a solution of 1 (0.4 mmol, 139 mg) in CH3CN (2 mL). The resulting green solution was
stirred for 30 min and then the white precipitate of AgCl was isolated by filtration. The filtrate was evaporated and the
solid was washed with toluene (1 mL) and pentane (2 mL), then dried under vacuum to afford a green solid.
Recrystallized at room temperature from a 1:5 MeCN/Et2O mixture. Yield: 159 mg (90%). 1H-NMR (400 MHz,
(D6)Acetone): 7.47 (d, J = 8.3 Hz, 2H), 7.35 (d, J = 7.9 Hz, 2H), 7.08 (t, J = 7.6 Hz, 2H), 6.59 (t, J = 7.5 Hz, 2H), 3.06 (s,
12H), 2.53 (s, 3H, CH3CN). 13C-NMR (101 MHz, (D6)Acetone): 147.9, 146.3, 129.6, 121.6, 117.8, 115.3, 51.3. Anal. calc.
for C18H23N4NiBF4 (440.91): C 49.03, H 5.26, N 12.71; found: C 48.97, H 5.34, N 12.26.
Synthesis of [(PyrNMeNN)Ni(NCCH3)]BF4 (9). It was synthesized in a procedure similar to the one described for
[(MeN2N)Ni(NCCH3)]BF4 (8) except that complex 2 (0.4 mmol, 150 mg) was used instead of complex 1. Green crystals
recrystallized at room temperature from a 1:5 MeCN/Et2O mixture. Yield: 164 mg (88%). 1H-NMR (400 MHz,
(D6)Acetone): 7.48-7.38 (m, 2H), 7.34 (d, J = 8.0 Hz, 1H), 7.02 (d, J = 7.9 Hz, 3H), 6.58 (t, J = 7.6 Hz, 1H), 6.52 (t, J =
7.5 Hz, 1H), 4.39 (dt, J = 11.5, 6.1 Hz, 2H), 3.44-3.32 (m, 2H), 3.06 (s, 6H), 2.31 (s, 3H, CH3CN), 2.25-2.11 (m, 4H). 13C-
NMR (101 MHz, (D6)Acetone): 149.5, 147.9, 147.5, 146.2, 129.6, 129.4, 128.7, 122.4, 121.4, 117.7, 115.1, 114.7, 62.9,
51.2, 25.5. Anal. calc. for C20H25N4NiBF4 (466.95): C 51.44, H 5.40, N 12.00; found: C 51.40, H 5.44, N 12.09.
Synthesis of [(PyrN2N)Ni(NCCH3)]BF4 (10). It was synthesized in a procedure similar to the one described for
[(MeN2N)Ni(NCCH3)]BF4 (8) except that complex 3 (0.4 mmol, 160 mg) was used instead of complex 1. Green crystals
recrystallized at room temperature from a 1:5 MeCN/Et2O mixture. Yield: 170 mg (86%). 1H-NMR (400 MHz,
(D6)Acetone): 7.45-7.30 (m, 2H), 7.01 (d, J = 6.8 Hz, 4H), 6.51 (m, 2H), 4.47-4.34 (m, 4H), 3.43-3.33 (m, 4H), 2.32 (s,
3H, CH3CN), 2.18 (m, 8H). 13C-NMR (101 MHz, (D6)Acetone): 149.4, 147.5, 128.4, 122.1, 117.6, 114.3, 62.8, 25.3. Anal.
calc. for C22H27N4NiBF4 (492.98): C 53.60, H 5.52, N 11.37; found: C 53.65, H 5.54, N 11.45.
Synthesis of [(AzeNMeNN)Ni(NCCH3)]BF4 (11). It was synthesized in a procedure similar to the one described for
[(MeN2N)Ni(NCCH3)]BF4 (8) except that complex 4 (0.4 mmol, 144 mg) was used instead of complex 1. Green crystals
recrystallized at room temperature from a 1:5 MeCN/Et2O mixture. Yield: 152 mg (84%). 1H-NMR (400 MHz,
(D6)Acetone): 7.74-7.58 (m, 1H), 7.45-7.28 (m, 3H), 7.10-6.97 (m, 2H), 6.67 (t, J = 7.4 Hz, 1H), 6.57 (t, J = 7.3 Hz, 1H),
5.00 (q, J = 10.1 Hz, 2H), 4.00 (q, J = 10.0 Hz, 2H), 3.07 (s, 6H), 2.70 (s, 3H, CH3CN), 2.43 (d, J = 9.4 Hz, 2H). 13C-NMR
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(101 MHz, (D6)Acetone): 148.5, 148.4, 148.0, 146.2, 129.5, 129.3, 122.2, 121.5, 118.3, 117.6, 114.9, 114.6, 64.9, 51.2,
17.7. Anal. calc. for C19H23N4NiBF4 (452.92): C 50.39, H 5.12, N 12.37; found: C 50.36, H 5.16, N 12.44.
Synthesis of [(MorphNMeNN)Ni(NCCH3)]BF4 (12). It was synthesized in a procedure similar to the one described for
[(MeN2N)Ni(NCCH3)]BF4 (8) except that complex 5 (0.4 mmol, 160 mg) was used instead of complex 1. Blue crystals
recrystallized at room temperature from a 1:5 MeCN/Et2O mixture. Yield: 127 mg (66%). 1H-NMR (400 MHz,
(D6)Acetone): 7.43 (dd, J = 12.2, 8.2 Hz, 2H), 7.23-7.11 (m, 2H), 7.11-7.00 (m, 2H), 6.88 (dt, J = 12.8, 7.3 Hz, 2H), 4.13
(d, J = 9.0 Hz, 2H), 3.96-3.71 (m, 6H), 2.90 (s, 3H, CH3CN), 2.73 (s, 6H). 13C-NMR (101 MHz, (D6)Acetone): 144.5,
143.9, 141.9, 140.6, 127.0, 126.5, 123.6, 123.1, 120.1, 119.3, 119.0, 114.3, 63.8, 53.2, 47.6. Anal. calc. for
C20H25N4NiOBF4 (482.94): C 49.74, H 5.22, N 11.60; found: C 49.86, H 5.26, N 11.51.
Synthesis of [(PipNMeNN)Ni(NCCH3)]BArF (13). A solution of sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate
4
NaBArF (1 equiv, 0.4 mmol, 354 mg) in CH3CN (2 mL) was added to a solution of 6 (0.4 mmol, 155 mg) in CH3CN (2
4
mL). The resulting green solution was stirred for 30 min and then filtred through PTFE filter (0.22 µm pore size). The
filtrate was evaporated and the solid was washed with cold pentane (2 mL), then dried under vacuum to afford a green
1
solid, which was directly used for NMR and electrochemical measurements in solution.Yield: 241 mg (48%). H NMR
(400 MHz, Acetone-d6): 7.82 (s, 8H), 7.70 (s, 4H), 7.41 (d, J = 7.7 Hz, 2H), 7.31-7.25 (m, 2H), 7.15 (dd, J = 13.0, 6.4 Hz,
4H), 4.16 (d, J = 34.6 Hz, 4H), 3.54 (s, 6H), 2.83 (s, 3H, CH3CN), 2.70 (m, 6H). 13C NMR (101 MHz, Acetone-d6): 163.1,
162.6, 162.1, 161.7, 135.4, 130.3, 130.0, 130.0, 129.7, 129.4, 129.3, 128.8, 128.6, 126.5, 123.8, 121.3, 121.1, 118.3,
56.7, 50.5, 23.7, 22.5.
General procedure for the alkyl-alkyl Kumada reactions. A 2 M solution of alkyl-MgCl (commercially available, 1.2
equiv, 0.6 mmol) was diluted to 1 mL with THF. The solution was then slowly added by a syringe pump over 2 h to a
solution containing the catalyst (3.5 mol %, 0.007 mmol), 0.3 mL of DMA, 0.2 mL of THF and the halide (0.2 mmol) at -
20°C. After the addition, the solution was stirred for 30 min at -20°C. It was then quenched by the addition of 5 mL water.
The organic phase in the resulting solution mixture was extracted with 20 mL of ether, and subjected to GC-MS analysis.
60 μL of decane (0.31 mmol) were used as an internal standard.
General procedure for the alkyl-alkyl Suzuki-Miyaura reactions. To a solution of sodium hydroxide (1.6 equiv, 0.32
mmol, 13 mg), catalyst (5 mol %, 0.01 mmol), sodium iodide (0.5 equiv, 0.1 mmol, 15 mg), isopropanol (2 equiv, 0.4
mmol, 30 μL) in 1 mL of dry 1,4-dioxane, were added alkyl halide (0.2 mmol) and the 9-octyl-9-borabicyclo[3.3.1]nonane
(1.6 equiv, 0.32 mmol, 0.64 mL of a 0.5 M stock solution in 1,4-dioxane) under a N2 atmosphere. The reaction mixture
was stirred at room temperature for 24 h. The solution was diluted in ether (20 mL) and subjected to GC-MS analysis. 60
μL of decane (0.31 mmol) were used as an internal standard.
Inhibition experiments for Kumada coupling. Following the general procedure used for the alkyl-alkyl Kumada
reactions, the inhibition experiments were conducted with 1 mol % of catalyst (0.002 mmol) and 10 mol % of extra ligand
(10 equivalent relative to catalyst, 0.02 mmol) in the starting reaction mixture. Amount of 10 mol % of extra ligand were:
2.3 µL of 2,4-lutidine, 1.6 µL of pyridine and 5.2 mg of PPh3.
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Stability experiments for Suzuki-Miyaura cross-coupling reactions. Following the general procedure used for the
alkyl-alkyl Suzuki-Miyaura reactions, the reaction mixtures were stirred at room temperature for a defined pre-stirring
time before the simultaneous addition of (4-iodobutyl)benzene and 9-octyl-9-borabicyclo[3.3.1]nonane (n-octyl-(9-BBN)).
Reaction mixture was then stirred for 24 h at room temperature.
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