Nickel-catalyzed coupling reaction of alkyl halides with aryl Grignard reagents in the presence of 1,3-butadiene: Mechanistic studies of four-component coupling and competing cross-coupling reactions

Article abstract of DOI:10.1039/c7sc04675h

We describe the mechanism, substituent effects, and origins of the selectivity of the nickel-catalyzed four-component coupling reactions of alkyl fluorides, aryl Grignard reagents, and two molecules of 1,3-butadiene that affords a 1,6-octadiene carbon framework bearing alkyl and aryl groups at the 3- and 8-positions, respectively, and the competing cross-coupling reaction. Both the four-component coupling reaction and the cross-coupling reaction are triggered by the formation of anionic nickel complexes, which are generated by the oxidative dimerization of two molecules of 1,3-butadiene on Ni(0) and the subsequent complexation with the aryl Grignard reagents. The C-C bond formation of the alkyl fluorides with the γ-carbon of the anionic nickel complexes leads to the four-component coupling product, whereas the cross-coupling product is yielded via nucleophilic attack of the Ni center toward the alkyl fluorides. These steps are found to be the rate-determining and selectivity-determining steps of the whole catalytic cycle, in which the C-F bond of the alkyl fluorides is activated by the Mg cation rather than a Li or Zn cation. ortho-Substituents of the aryl Grignard reagents suppressed the cross-coupling reaction leading to the selective formation of the four-component products. Such steric effects of the ortho-substituents were clearly demonstrated by crystal structure characterizations of ate complexes and DFT calculations. The electronic effects of the para-substituent of the aryl Grignard reagents on both the selectivity and reaction rates are thoroughly discussed. The present mechanistic study offers new insight into anionic complexes, which are proposed as the key intermediates in catalytic transformations even though detailed mechanisms are not established in many cases, and demonstrates their synthetic utility as promising intermediates for C-C bond forming reactions, providing useful information for developing efficient and straightforward multicomponent reactions.

Full text of DOI:10.1039/c7sc04675h

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DOI: 10.1039/C7SC04675H.
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DOI: 10.1039/C7SC04675H
Chemical Science
ARTICLE
Nickel-catalyzed coupling reaction of alkyl halides with aryl
Grignard reagents in the presence of 1,3-butadiene: Mechanistic
studies of four-component coupling and competing cross-coupling
reactions†
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
a
a
a
a
b
cde
Takanori Iwasaki,* Asuka Fukuoka, Wataru Yokoyama, Xin Min, Ichiro Hisaki, Tao Yang,*
cd
a
a
www.rsc.org/
Masahiro Ehara,* Hitoshi Kuniyasu and Nobuaki Kambe*
We describe the mechanism, substituent effects, and origins of the selectivity of nickel-catalyzed four-component coupling
reaction of alkyl fluorides, aryl Grignard reagents, and two molecules of 1,3-butadiene that affords a 1,6-octadiene carbon
framework bearing alkyl and aryl groups at 3- and 8-positions, respectively, and the competing cross-coupling reaction. Both
the four-component coupling reaction and the cross-coupling reaction are triggered by the formation of anionic nickel
complexes, which are generated by the oxidative dimerization of two molecules of 1,3-butadiene on Ni(0) and the
subsequent complexation with aryl Grignard reagents. The C–C bond formation of alkyl fluorides with the -carbon of anionic
nickel complexes leads to the four-component coupling product, whereas the cross-coupling product is yielded via
nucleophilic attack of the Ni center toward alkyl fluorides. These steps are found to be the rate-determining and selectivity-
determining steps of the whole catalytic cycle, in which the C–F bond of alkyl fluorides is activated by Mg cation rather than
Li or Zn cation. ortho-Substituent(s) of aryl Grignard reagents suppressed the cross-coupling reaction leading to the selective
formation of the four-component products. Such steric effects of the ortho-substituent(s) were clearly demonstrated by
crystal structure characterizations of ate complexes and DFT calculations. Electronic effects of para-substituent of aryl
Grignard reagents on both the selectivity and reaction rates are thoroughly discussed. The present mechanistic study offers
new insight into anionic complexes, which are proposed as the key intermediates in catalytic transformations though
detailed mechanisms are not established in many cases, and demonstrates their synthetic utility as promising intermediates
for C–C bond forming reactions, providing useful information for developing efficient and straightforward multicomponent
reactions.
2
C8 carbon frameworks.
A
well-known application is
3
Introduction
telomerization, in which bis(

-allyl)metal complexes of group
1
0 metals (Ni and Pd) generated by the oxidative dimerization
Metal-catalyzed multicomponent coupling reactions are useful
and straightforward synthetic methods, because they can
construct complex carbon frameworks from relatively simple
organic molecules through the concomitant formation of
multiple new bonds. In these transformations, the oxidative
dimerization of 1,3-butadiene on low valent group 10 metals is
a fundamental process, being often used to produce a variety of
of two molecules of 1,3-butadiene on the metals react with
heteroatom nucleophiles such as water, alcohols, and amines.
This process has been used for the industrial production of C8
chemicals including 1-octanol and 1-octene. In this context,
pioneering studies of the Ni-catalyzed multicomponent reaction
4
1
5
a,b
of two molecules of 1,3-butadiene with carbonyl compounds
and imines
5
b-d
6
2
as well as CO and CO were reported in the
1970s. Kimura and Tamaru have expanded these
multicomponent coupling reactions of 1,3-butadiene to the
bifunctionalization of the C8 carbon framework through the
combined use of ketones, aldehydes, or imines with organozinc
or organoaluminum reagents. This reaction could introduce
two different carbon moieties into the 2,6-octadiene
framework. However, in some cases, the three component
a.
Department of Applied Chemistry, Graduate School of Engineering, Osaka
University, Suita, Osaka 565-0871, Japan. E-mail: iwasaki@chem.eng.osaka-
u.ac.jp; kambe@chem.eng.osaka-u.ac.jp
Department of Material and Life Science, Graduate School of Engineering, Osaka
University, Suita, Osaka 565-0871, Japan
Department of Theoretical and Computational Molecular Science, Institute for
Molecular Science, 38 Nishigo-Naka, Myodaiji, Okazaki, Aichi 444-8585, Japan. E-
mail: ehara@ims.ac.jp
Elements Strategy Initiative for Catalysts and Batteries (ESICB), Kyoto University,
Katsura, Kyoto 615-8510, Japan
Fachbereich Chemie, Philipps-Universität Marburg, Hans-Meerwein-Strasse,
Marburg 35032, Germany. E-mail: yangt@staff.uni-marburg.de
Electronic Supplementary Information (ESI) available: Detailed experimental and
b.
7
,8
c.
d.
e.
coupling of these reagents in a 1:1:1 ratio without dimerization
7a,c,9
can occur as a competing or preferred reaction
due to the
competing oxidative cyclization of 1,3-butadiene with carbonyl
1
0
†
compounds to form oxanickelacycle intermediates.
computational results, procedures, characterization data, copies of NMR charts, and
crystallographic data. CCDC 1572238. See DOI: 10.1039/x0xx00000x
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1
6
We have reported the dimerization and silylation of 1,3- complexes ) have rarely been studied, except for the case of
View Article Online
DOI: 10.1039/C7SC04675H
1
1
17
butadiene as another application of these transformations. In cuprates, even though ate complexes have been proposed as
addition, aiming at the construction of carbon skeletons, we key intermediates in catalytic C–C bond formations.1
8-21
In
recently developed the multicomponent coupling reaction of addition, theoretical calculations of ate complexes have not
two molecules of 1,3-butadiene, aryl Grignard reagents, and been well-established because of lack of structural information
alkyl fluorides to give a 1,6-octadiene bearing an alkyl group of ate complexes (especially counter cation). Therefore,
arising from alkyl fluorides at the 3-position, and an aryl group another challenge in this study is to develop a means of
arising from aryl Grignard reagents at the 8-position (Scheme theoretical calculations of ate complexes-meditated
1
2
1
). It was also revealed that a similar multicomponent transformations.
coupling reaction using perfluoroarenes instead of alkyl
fluorides proceeds smoothly to yield the corresponding 1,6-
octadienes with perfluoroaryl and aryl groups. In these
reactions, three-component coupling products consisting of
organo fluorides, aryl Grignard reagents, and 1,3-butadiene in a
1
3
Results and discussion
1. Reaction using aryl Grignard reagents
We first examined the reaction using n-OctF (1a) and p-
fluorophenylmagnesium bromide (2a), and the representative
results are summarized in Table 1. When the reaction was
conducted in the presence of NiBr
butadiene (3 equiv) at 40 °C for 24 h, the cross-coupling product
1:1:1 ratio were not produced due to the intermediacy of
anionic bis(allyl)nickel intermediates. In the alkylation reaction
mentioned above, the use of ortho-substituted aryl Grignard
reagents is essential for selectively forming four-component
coupling products. When unsubstituted aryl Grignard reagents
were employed instead, the competing reaction of direct cross-
coupling of alkyl fluorides with aryl Grignard reagents occurred,
resulting in a mixture of cross-coupling and four-component
2
(dme) (20 mol%) and 1,3-
4aa was obtained in 33% yield along with 3aa incorporating two
1,3-butadiene molecules in 50% yield (entry 1). The structure of
compound 3aa was fully assigned by NMR. The alkyl and aryl
groups were introduced site-selectively onto the 3- and 8-
positions of the 1,6-octadiene framework, respectively, with E-
configuration of the internal alkene moiety. The amount of Ni
catalyst could be reduced to 10 mol% (entry 2); however, a
further reduction to 5 mol% led to incomplete reaction within
1
4
coupling products (Scheme 1). In these reactions as well as our
1
5
previously reported cross-coupling reactions, an anionic nickel
complex B generated by the reaction of the bis( -allyl)nickel

complex A with Grignard reagent is likely the key intermediate,
which reacts with electrophiles at the Ni center to promote
24 h (79% conversion of 1a). We found that the selectivity of the
cross-coupling reaction (via complex D) or at the
-allyl giving rise to four-component coupling products (via
complex C).
-carbon of the
four-component coupling versus cross-coupling reactions is
temperature-dependent. When the reaction temperature was
increased to 50 °C, the selectivity decreased to almost 1:1 (entry

3). In contrast, a lower reaction temperature increased the
selectivity to 1.7:1 (entry 4), although the reaction was sluggish
at 0 °C and 41% of 1a remained after 24 h (entry 5).
6 4
Table 1 Coupling reactions of n-OctX, p-FC H
MgBr, and 1,3-butadienea
Scheme 1 Ni-catalyzed dimerization and alkylarylation of 1,3-dienes.
Entry
Catalyst (mol%)
X
F
F
F
F
T (°C)
40
40
50
30
0
30
30
30
30
25
25
25
3aa (%)b
50
48
49
63 (48)
31
2
15
6
17
n.d.
n.d.
n.d.
4aa (%)b
33
36
49
37 (37)
19
10
52
58
68
1
2
3
4
5
6
7
8
9
NiBr
NiBr
2
(dme) (20)
(dme) (10)
Herein, to understand the detailed mechanism of the four-
component coupling reaction of alkyl fluorides, aryl Grignard
reagents, and two molecules of 1,3-butadiene, we performed
mechanistic studies and theoretical calculations to clarify the
structures and chemical behaviors of the anionic nickel
intermediate B. In addition, we performed the reaction using
various aryl Grignard reagents including ortho-unsubstituted
ones to reveal not only substrate scope of the reaction but also
the origin of the selectivity of the four-component coupling
reaction over direct cross-coupling reaction. Steric and
electronic effects on the selectivity were also investigated by
theoretical calculations.
2
NiBr (dme) (10)
2
NiBr
NiBr
NiBr
NiBr
NiBr
NiBr
2
2
2
2
2
2
(dme) (10)
(dme) (10)
(dme) (10)
(dme) (10)
(dme) (10)
(dme) (10)
none
F
Cl
Br
I
OTs
F
1
1
1
0
1
2
n.d.
52
3
Pd(acac)
2
(20)
F
F
PtCl (20)
2
a
Reaction conditions: catalyst, n-OctF (1.0 mmol), p-F-C6H4MgBr (2.0 mmol), and
,3-butadiene (3.0 mmol) in THF (3 mL) for 24 h. Yields were determined by GC.
Isolated yields are in parentheses.
b
1
Notably, the structures as well as chemical characteristics of
anionic complexes of transition metals (the so-called ate
2
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DOI: 10.1039/C7SC04675H
Scheme 2 Ni-catalyzed four-component coupling reaction of alkyl fluorides, aryl Grignard reagents, and 1,3-butadiene. Isolated yields. Yields of cross-coupling products 4 are shown
in parentheses. a ca. 20% of 1g was recovered. b Reaction time was 42 h. c n.i. = not isolated. d 44% of 1g was recovered.
Next, we investigated the effect of the leaving group in the yields of the direct cross-coupling product 4 are given in
entries 6–9. The reaction of n-OctCl was sluggish (entry 6). Alkyl parentheses. Alkyl fluorides carrying various functional groups
bromides, iodides, and tosylates (which are good coupling produced mixtures of 3 and 4 in 1.5:1 to 1:1 ratio. It should be
1
5,20a-c
partners in alkyl-alkyl cross-coupling reaction)
the major product in 52 to 68% yields along with small amounts and the aliphatic C–F bonds were cleaved exclusively. The
of 3aa (entries 7–9), where the product ratios 3aa/4aa were reaction of -branched alkyl fluoride 1g resulted in better
.20:1 (Cl), 0.29:1 (Br), 0.10:1 (I), and 0.25:1 (OTs). These results selectivity (3ga:4ga = 5.2:1) although the reaction was slow and
imply the usefulness of alkyl fluorides as promising alkylating did not complete within 24 h (80% conv.). This result may
gave 4aa as noted that the aromatic C–F and C–Cl bonds remained intact,

0
2
2,23
reagents toward 1,3-butadiene.
coupling nor cross-coupling reactions could proceed without component coupling reaction to give 3 rather than the cross-
the Ni catalyst (entry 10). It is known that other group 10 metals coupling reaction. However, the reaction of
(fluoromethyl)cyclohexane (1h) resulted in a low yield, and no
Neither four-component suggest that sterically hindered alkyl fluorides prefer the four-
3
,20a
also promote the oxidative dimerization of 1,3-dienes.
However, no desired four-component coupling product 3aa was reaction took place with fluorocyclohexane (1i). Next, we ran
yielded by Pd and Pt catalysts, while the cross-coupling product the reactions using different aryl Grignard reagents (2b–i).
4
aa was obtained in 52% and 3% yields, respectively (entries 11 PhMgBr (2b) afforded the corresponding products 3ab and 4ab
and 12). in 40% and 55% yields, respectively, (95% total yield with 0.7:1
In order to improve the selectivity of 3aa over 4aa, we ratio). The introduction of electron-donating groups such as Me,
tested the reaction using various ligands, additives, and solvents. MeO, and Me N led to the preferential formation of the cross-
However, these attempts were not fruitful. For instance, the coupling product 4. On the other hand, para-chlorophenyl
addition of PPh slightly affected the reaction efficiency without Grignard reagent (2e) gave a 1:1 mixture of 3ae and 4ae in 44%
2
3
appreciable change in the selectivity. The addition of Mg and Li total yield. Substituents at the meta-position showed a similar
salts, on the other hand, decreased the selectivity to 1:1 and tendency. The reaction of 1g with phenyl and para- and meta-
0
.6:1, respectively. The reactions in mixed solvents of toluene- tolyl Grignard reagents afforded four-component coupling
2
4
THF or hexane-THF depressed both the yields and selectivity.
products 3gb, 3gc, and 3gg as the major product. Thienyl
Scheme 2 summarizes the results of the four-component Grignard reagent 2i underwent cross-coupling reaction
coupling reaction with various aryl Grignard reagents and alkyl exclusively to give 4gi in 23% yield.
fluorides under the same conditions as entry 4 in Table 1, where
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2
. Reaction using ortho-substituted aryl Grignard reagents
Table 3 Four-component coupling reaction of alkyl (pseudo)halides
DOI: 10.1039/C7SC04675H
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We found a remarkable effect of the ortho-substituent in the
aryl Grignard reagents, as shown in eqn (1). When o-
tolylmagnesium bromide (2j) was employed in the reaction with
1
2
1g, four-component coupling product 3gj was obtained as the
sole product in 85% yield, and no 4gj was observed.
Entry
Alkyl–X
n-Oct–F
n-Oct–Cl
n-Non–Br
n-Oct–I
Conv. (%)a
3 (%)a
87
4
64
45
4 (%)a
3
2
1
2
3
4
5
98
8
>99
>99
47
2
trace
18
n-Oct–OMs
16
a
Determined by GC.
Using 1a and 2j under the previously optimized conditions
the cross-coupling, giving rise to the selective formation of the
four-component coupling product albeit only in moderate
yields (entries 3 and 4). Alkyl mesylate was found to be
ineffective as an alkylating reagent in the present reaction
(
Table 1, entry 4), the reaction smoothly proceeded to give 3aj
in 92% GC yield within 10 h (Table 2, entry 1). The addition of
PPh or a bidentate phosphine (dppf) hindered the reaction
entries 2 and 3). Other Ni salts such as NiCl and Ni(acac)
2
3
(
2
(entry 5).
showed a comparable reactivity (entries 4 and 5). The amount
of Grignard reagent 2j could be reduced to 1.5 equiv without
significant loss of yield (entry 6). Although the reaction did not
Under the optimized conditions shown in entry 8 of Table 2,
the scope and limitations of the aryl Grignard reagents and alkyl
fluorides were further examined, and the results are
2
complete within 10 h with 5 mol% of NiBr (dme) (entry 7, 88%
1
2
summarized in Scheme 3. Sterically hindered aryl Grignard
reagents such as 2-ethyl-, 2-isopropyl-, and 2,6-dimethylphenyl
Grignard reagents (2k–m) underwent the four-component
coupling reaction to produce 3ak–am in good yields. On the
other hand, the introduction of methoxy group at the ortho-
position (2n) completely suppressed the reaction (3an). When
o-tolyl Grignard reagents bearing electron-withdrawing groups
at the para-position (2o and 2p) were employed, the yields
were slightly reduced (3ao and 3ap). The reaction of 2,4-
dimethylphenyl Grignard reagent (2q) resulted in an excellent
yield (3aq) although the p-methoxy substituent led to a
somewhat lower yield (3ar). The thienyl Grignard reagent (2t)
was less effective, and the naphthyl Grignard reagent (2s)
afforded 3as in 81% yield.
conv. of 1a), the four-component coupling product 3aj was
obtained in 87% yield by elevating the reaction temperature to
40 °C (entry 8).
The results using various alkyl (pseudo)halides are
3
summarized in Table 3. While the C(sp )–Cl bond is weaker than
3
the C(sp )–F bond, n-OctCl was less reactive and mostly
recovered unreacted (entry 2). Although alkyl bromides and
iodides afforded the cross-coupling product predominantly
with p-fluorophenyl Grignard reagent 2a, as shown in Table 1,
introducing ortho-substituent into ArMgBr largely suppressed
Table 2 Four-component coupling reaction of n-Oct–F, o-TolMgBr, and 1,3-butadiene
Alkyl fluorides (2b–m) carrying various functionalities
including acetal, silyl ether, N-tosyl, and N-Boc protecting
groups afforded the four-component coupling products in good
yields. A terminal olefin moiety in 1j remained intact to give 3jm
in 91% yield under the selective oxidative dimerization
conditions of 1,3-dienes. Alkyl fluoride 1d bearing an acidic
Entry
Catalyst (mol%)
NiBr (dme) (10)
(PPh (10)
(dppf) (10)
(10)
Ni(acac) (10)
NiBr (dme) (10)
2j
Temp. (°C)
3aj (%)a
92
43
8
90
95
88
79
87(86)
1
2
3
4
5
6
7
8
2
2.0 equiv
2.0 equiv
2.0 equiv
2.0 equiv
2.0 equiv
1.5 equiv
1.5 equiv
1.5 equiv
30
30
30
30
30
30
30
40
NiCl
NiCl
2
3
)
2
2
hydrogen at the -position of thiophene also gave 3dm in an
excellent yield (93%). It is well known that low-valent Ni
NiCl
2
2
2
22
intermediates can cleave C(sp )–X bonds including C–F bond.
2
2
NiBr
NiBr
2
(dme) (5)
(dme) (5)
However, under the reaction conditions, both C(sp )–Cl and
C(sp )–F bonds remained unchanged, and the C(sp )–F bond
was selectively cleaved to give 3em, 3eo, 3fm, and 3fs. In
addition, 1-chloro-6-fluorohexane (1m) reacted at the C(sp )–F
bond rather than the C(sp )–Cl bond to exclusively give 3mm
2
3
2
a
Determined by GC (isolated yield is in parentheses). In all cases, ca. 5% of 4aj was
observed in GC analysis.
3
3
and 3mo.
4
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DOI: 10.1039/C7SC04675H
Scheme 3 Scope and limitations of the four-component coupling reaction. a Reaction was conducted in 0.1 M concentration of
1 for 20 h.
When isoprene was employed as the conjugated diene of the thus-formed complex C (step D). Alternatively, the Ni
under the optimized conditions, the corresponding four- center in complex B can react with alkyl fluorides to give cross-
component coupling product 3aj’ was obtained as a mixture of coupling product 4 through complex D (steps E and F).25
inseparable four regioisomers in 1:1.3:1.4:1.5 ratio in 76% total Therefore, the reaction courses of four-component coupling vs.
yield (eqn (2)). In contrast, the reaction of 1,3-pentadiene was cross-coupling are determined by the reaction of alkyl fluorides
sluggish, and no desired four-component coupling products with complex B (step C vs. step E).
were observed.
3. Mechanistic studies
The mechanistic studies include the observation and isolation
of catalytic intermediates, kinetic parameters, electronic effects
of the Grignard reagents, and theoretical calculations. Based on
the results, plausible catalytic cycles of the Ni-catalyzed
coupling reactions of alkyl fluorides with aryl Grignard reagents and cross-coupling reactions.
in the presence of 1,3-butadiene are proposed (Scheme 4).
Scheme 4 Proposed catalytic cycles of the Ni-catalyzed four-component coupling
These reactions are triggered by the oxidative dimerization of
1
,3-butadiene on Ni(0), generated in situ by the reduction of Ni 3.1. Stoichiometric reaction. To gain insight into the present
salt with Grignard reagents, to form the bis(
-allyl)nickel A (step reaction, we conducted stoichiometric reaction using
A). The reaction of A with aryl Grignard reagents yields the NiBr
(dme), 1a, and 2–4 equiv of 2j in the presence of excess

2
anionic Ni complex B, which has higher nucleophilicity towards 1,3-butadiene (Table 4).12 However, when 2 equiv of 2j was
alkyl fluorides. Although the four potent nucleophilic centers added to reduce Ni(II) to Ni(0), which then undergoes the
exist in complex B, namely the Ni center, the ipso carbon of Ar
group, and the - and -positions of the -allyl group, two
reaction pathways operate. When the -carbon of the -allyl
group attacks the alkyl fluoride (step C), four-component
coupling product 3 is yielded through the reductive elimination
oxidative dimerization of 1,3-butadiene to form A (step A in
Scheme 4), only 14% of 1a reacted, suggesting that bis(
allyl)nickel is inert toward alkyl fluorides (entry 1). When 3 equiv




-


of 2j was used, 80% of 1a was consumed to give 3aj in 75% yield
(entry 2). Almost a quantitative yield of 3aj was obtained with 4
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equiv of 2j (entry 3). These results indicate that the anionic showed sharp signals including two allyl groups (
) and one
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nickel complex B (Scheme 4), generated by the reaction of bis(

-
2,6-dimethylphenyl group (

) (Fig. 1c), which could be assigned
DOI: 10.1039/C7SC04675H
allyl)nickel A with Grignard reagents, is the actual intermediate to the corresponding nickelate complex 5,28 along with signals
of the reaction of alkyl fluorides.
of free 1,3-butadiene (). The formed nickelate complex 5 was
stable in THF for a day even at room temperature.
Table 4 Stoichiometric reactions of Ni(II) with 1a and 2j
In order to isolate the nickelate complex, we tested various
organometallic reagents and ligands for the counter cation.
Lithium bearing polyether ligands such as 1,2-dimethoxyethane
(
DME) and 12-crown-4 ether was found to be a suitable counter
cation. For instance, when Ni(cod) was treated with 2,6-
dimethylphenyllithium (6) and 1,3-butadiene in Et O and then
DME was added, nickelate complex 7 was obtained as an orange
semi-solid in 94% yield (Scheme 5). H NMR spectrum of thus
2
Conv. 1a (%)a
3aj (%)a
2
Entry
o-TolMgBr
2 equiv
3 equiv
1
2
3
14
80
99
10
75
95
1
4 equiv
formed nickelate 7 is in good agreement with the above-
mentioned NMR spectra when using the corresponding
Grignard reagent 2m (Fig. 1c).
a
Determined by GC.
3
.2. Synthesis and characterization of nickelate complexes. 1H NMR
were conducted (eqn (3)).12
-allyl)nickel complex A has been proposed as the
key intermediate in the oligomerization of 1,3-butadiene by Ni
catalyst,26,27 the reaction of Ni(cod)
with 1,3-butadiene in THF-
did not show clear evidence of its formation, and broadened
,3-butadiene peaks were observed along with that of free COD
studies on the reaction of Ni(cod)
Although bis(
2

2
d
1
8
(Fig. 1a to 1b). This is probably due to the rapid equilibria
between complex A and many possible -complexes of Ni(0) as

well as free 1,3-butadiene.24 Variable temperature (VT) NMR
results of the mixture indicated that the equilibria are fast even
at the low temperature of –55 °C.24 When the mixture of
Scheme 5 Isolation of anionic Ni complexes.
Ni(cod)
2
and 1,3-butadiene was treated with 2,6-
dimethylphenylmagnesium bromide (2m), the spectrum
8 9 8 12
Fig. 2 ORTEP drawing of one of the four asymmetric units of [Ni(C H )(C H )·Li(12-
2 4 5 12 2
crwon-4) ] (thf)(C H ) (8) with thermal ellipsoids at the 50% probability level. All
hydrogen atoms and solvent molecules are omitted for clarity.
Recrystallization of the nickelate complex 7 to obtain
crystals suitable for X-ray was not successful. However, fine
crystals of 8 were obtained by changing DME to 12-crown-4
(
Scheme 5). As shown in Fig. 2,24,29 the crystal structure of 8
contains anionic Ni and the Li cation, where the octadiene
moiety, generated by the oxidative dimerization of 1,3-
butadiene, binds to Ni center in 1
also revealed that the C–C double bond (C6=C7) of the
group has the Z-configuration. The Ni center carries
,
3-fashion as expected. It is
-allyl
-allyl,


-
allyl, and aryl groups in a square planar geometry.
1
Fig. 1 H NMR spectra for the reaction of Ni(0) with 1,3-butadiene and 2m in THF-
d
8 2 2 2
at 20 °C. (a) Ni(cod) , (b) Ni(cod) and 5 equiv of 1,3-butadiene, and (c) Ni(cod) ,
3.3. Reactivities of nickelate complexes. When isolated Ni
1
,3-butadiene (5 equiv), and 2m (2 equiv).
complex 7 was used as catalyst, the four-component coupling
6
| J. Name., 2012, 00, 1-3
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reaction of n-OctF (1a), 2,6-dimethylmagnesium bromide (2m),
and two molecules of 1,3-butadiene could proceed to give 3am
in 88% yield (eqn (4)).12
Table 5 Activation parameters of four-component coupling reaction View Article Online
DOI: 10.1039/C7SC04675H
ArMgBr
G‡273
H‡
S‡
(kJ/mol)
(kJ/mol)
(J/Kmol)
2
2
a
j
87.4 ± 7.6
85.0 ± 5.1
87.3 ± 10.6
62.9 ± 3.9
63.5 ± 2.7
78.8 ± 5.6
–89.9 ± 12.4
–78.6 ± 8.7
–31.1 ± 18.0
2
m
In contrast, when 7 was treated with 2 equiv of n-OctF (1a) in butadiene, indicating steps A and B are relatively fast. At higher
1
THF-d
spectrum. The addition of MgCl
the reaction to give 3am in 10% yield (Scheme 6).12 As shown in might be due to the aggregation of Grignard reagents.
Scheme 7, when PhZnI (9) and PhLi (10) were used instead of
Next, we conducted the reaction at different temperatures
Grignard reagents, neither four-component coupling product 3ab (30–50 °C) using o-tolyl- and 2,6-dimethylphenylmagnesium
8
at 40 °C for 4 h, no change was observed in its H NMR concentrations of the Grignard reagent (> ca. 0.5 M), the
2
to the reaction mixture promoted reaction became slower. The reason is not clear yet, but this
1
2
nor cross-coupling product 4ab was yielded. PhMgCl (2b’) also gave bromide (2j and 2m), and the results are plotted in Figs. 4a and
a mixture of 3ab and 4ab albeit in somewhat lower total yields 4b, respectively. Eyring plots of these data employing the rate
compared to PhMgBr (2b) (Scheme 7).30 These results imply that the law d[3a]/dt = kobs[1a] showed good linear relationships (Fig. 4c),
Mg cation contributes to the reaction of the nickelate intermediate the resulting parameters are summarized in Table 5. Similar
B with alkyl fluorides to activate the C–F bond by coordination to F.30 analysis was also conducted for the reaction of p-
fluorophenylmagnesium bromide (2a).
These data indicate that the present four-component
coupling reaction is mainly controlled by enthalpy factors in all
cases employing Grignard reagents (2a, 2j, and 2m). The
introduction of one methyl group into the ortho-position (o-
TolMgBr (2j) vs. p-FC
activation parameters, probably because the ortho-methyl
group locates far from the reacting -allylic carbon in the
transition state. In contrast, the activation parameters changed
significantly upon the introduction of methyl groups into both
ortho-positions (2m), which increased the activation enthalpy.32
Activation parameters of the Ni-catalyzed cross-coupling
6 4
H MgBr (2a)) showed a small effect on the

Scheme 6 Stoichiometric reaction of nickelate complex 7 with 1a: Effect of Mg ion.
reaction of alkyl (pseudo)halides with n-BuMgCl in the presence
‡
of 1,3-butadiene were also determined:

G
273 = 55.3 ± 6.0
‡
‡
kJ/mol,

H = 51.2 ± 2.6 kJ/mol, and

S = –14.8 ± 12.3 J/Kmol
H = 57.3 ± 4.0 kJ/mol,
‡
‡
for iodide;

G
273 = 61.9 ± 8.6 kJ/mol,

‡
‡
and

S = –16.9 ± 16.7 J/Kmol for bromide; and
G
273 = 71.1 ±
‡
‡
9
.8 kJ/mol, H = 52.7 ± 4.9 kJ/mol, and S = –67.6 ± 18.0
Scheme 7 Reaction of arylzinc, aryllithium, and aryl Grignard reagents. Conversion J/Kmol for tosylate.25b These data correspond to step E in
and yields were determined by GC.
Scheme 4 and show similar tendency with step C, suggesting
similar transition states between the four-component coupling
and the cross-coupling reactions.
3
(
.4. Kinetic studies. We performed kinetic studies using n-OctF
1a) and o-TolMgBr (2j). Initial reaction rates were measured by
changing the concentration of one reagent from the optimized
conditions, which is 1a at 0.33 M, 2j at 0.50 M, NiBr (dme) at
.017 M, and 1,3-butadiene at 1.0 M at 40 °C.31 The rate of the
3.5. Reaction mechanisms of the nickelate complex with alkyl
fluorides. A unique feature of the present catalytic reaction is
2
3
22
the facile cleavage of C(sp )–F bond. To elucidate the reaction
mechanisms, we conducted the reaction of a radical clock 1n33
with Grignard reagent 2a, and obtained the four-component
coupling product 3na and the cross-coupling product 4na in
0
four-component coupling reaction was plotted against the
reagent concentration (Fig. 3), clearly showing first-order
kinetics with respect to the catalyst and 1a. The rate for the
four-component coupling reaction can be expressed as
37% and 38% yields, respectively, with no cyclized products
(eqn (5)). Similarly, the reaction using 2,6-dimethylphenyl
d[3aj]/dt
= k[NiBr
2
(dme)]0.98[1a]0.86, suggesting that the
Grignard reagent 2m instead of 2a selectively afforded 3nm in
reaction of nickelate complex B with 1a (step C) is the rate-
determining step. Interestingly, the reaction rates do not
depend on the concentrations of Grignard reagent 2j or 1,3-
9
3% yield (eqn (6)).12 These results clearly indicate that
3
nickelate intermediates cleave the C(sp )–F bond via an ionic
mechanism for both the four-component and cross-coupling
reactions.
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View Article Online
DOI: 10.1039/C7SC04675H
-1.6
-1.4
-1.2
-1.0
-0.8
-0.6
-1.2
-1.0
-0.8
-0.6
-0.4
-0.2
-
9.4
9.6
9.8
-10.0
10.2
10.4
-9.4
-
-9.6
-
-9.8
y = 0.857x - 8.75
R² = 0.994
-10.0
-10.2
-10.4
-
-
ln([n-OctF (1a)]0)
ln([o-TolMgBr (2j)]0)
-0.2 0.0 0.2
-4.8
-4.6
-4.4
-4.2
-4.0
-3.8
-3.6
-0.6
-0.4
0.4
0.6
-
9.4
9.6
9.8
10.0
10.2
10.4
-9.4
-
-9.6
-
-9.8
y = 0.978x - 5.79
R² = 0.989
-
-10.0
-10.2
-10.4
-
-
ln([NiBr2(dme)]0)
ln([1,3-butadiene]0)
= 0.21 to 0.45 M, (b) [2j
Fig. 3 Double logarithm plots of the initial reaction rates against initial concentrations of each substrate. (a) [1a
]
0
]
0
= 0.33 to 0.66 M, (c)
[NiBr
2
(dme)]
0
= 0.010 to 0.023 M, and (d) [1,3-butadiene]
0
= 0.67 to 1.34 M.
0
33.0
.0030
0.0031
0.0032
0.0033
0.0034
0.15
0.10
0.05
0.00
0.15
-
R² = 0.991
R² = 0.999
R² = 0.991
R² = 0.993
R² = 0.993
R² = 0.999
R² = 0.997
0.10
0.05
0.00
-33.5
R² = 0.997
R² = 0.998
y = -7638.8x - 9.4525
R² = 0.995
-
-
34.0
34.5
R² = 0.993
y = -9477.4x - 3.744
R² = 0.985
0
1000
2000
3000
4000
0
1000
2000
3000
4000 -35.0
Fig. 4 (a) Time-course of the reaction of 1a with 2j at 30 °C (

), 35 °C (

), 40 °C (

), 45 °C (

), and 50 °C (). (b) Time-course of the reaction of 1a with 2m at 30 °C
(
), 35 °C ( ), 40 °C ( ), 45 °C ( ), and 50 °C (). (c) Eyring plot of the reaction using 2j () and 2m ().



the reaction of nickelate intermediates with alkyl fluorides.
When a series of substituents (Cl, F, OMe, or Me) were
introduced into the 4-position of 2-methylphenyl Grignard
reagent, a moderately large difference in the reaction rates was
observed, with the electron-donating groups accelerating the
reaction. With the observed initial reaction rates, the rate
X
constant k for each Grignard reagents were calculated (Table
6).
Among Hammett plots of various substituent constants,
Yukawa-Tsuno’s 0, which is determined by the electronic
effects of the aromatic substituents on the reaction center
connected by methylene tether(s), showed a satisfactory linear
relationship (R = 0.962) with a negative

value of –1.178 (Fig.
2 mechanism of
5
). This negative value is in accord with the S

N
the rate-determining step, in which electron-donating
substituents accelerate the nucleophilic attack by increasing the
electron density of the allylnickel intermediates.
This result is also in good agreement with the observed
electronic effects on the selectivity of the four-component
3
.6. Hammett plots regarding rate-determining step (step C). We
next investigated the effects of the electron
donating/withdrawing groups in the aryl Grignard reagents on
8
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Table 6 Reaction rates of different Grignard reagents
View Article Online
DOI: 10.1039/C7SC04675H
R
H
2j)
12.7
Cl
(2p)
4.80
F
(2o)
7.47
OMe
(2q)
12.8
Me
(2r)
17.8
(
k
X
(10–3 s–1)
Fig. 7 Molecular structures of nickelate complexes 11 (left) and 8 (right). Bottom:
the dihedral angle between square planar Ni plane and the aryl ring.
0
0
0
.4
.2
.0
-
0.2
0.4
0.6
-
-
-0.2
0.0
0.2
0.4
Fig. 8 Space-filling models of the nickelate complexes (top view) in Fig. 7. The
reacting carbon of the -allyl group and Ni atom are shown in orange and green,
Fig. 5 Hammett plot of the relative reaction rates against Yukawa-Tsuno’s 0
.
respectively.
coupling and the cross-coupling reactions. As mentioned in
Section 1 regarding the results in Scheme 2, electron-deficient
Grignard reagents showed higher selectivities for four-
component coupling over cross-coupling compared to electron- constants (Yukawa-Tsuno’s
rich ones. For instance, the ratio between the four-component (R = 0.945) with the slope of +0.862 (Fig. 6). With
coupling product 3 and cross-coupling product 4 is 1.7:1 for p- for step C, for the cross-coupling reaction (step E) is
fluorophenyl Grignard reagent (2a), 1:1.9 for p-tolyl Grignard calculated to be –1.366. The relatively large negative value of
(
k
C
/k
/4
C
E
). Therefore, the ratio of selectivity between X and H,
)/(3 /4
E. A plot of log[(3 /4 )/(3 /4 )] against the substituent
(3
X
X
H
H
), is equal to (kCX/kEX)/(kCH/kEH) = (kCX/kCH)/(kEX/kEH)
=
/
X
X
H
H
0
 ) shows a good linear relationship
3
4
C
 = –1.178

E

E
in comparison to
of the Ni reaction site with the Ar group.
C
 is also ascribable to the direct connection
reagent (2c), and 1:3.3 for p-dimethylaminophenyl Grignard
reagent (2f). This selectivity is related to the relative reaction
rates of the nucleophilic attack by the -position of the -allyl
3
.7. Steric effects on selectivity: four-component coupling vs. cross-
group of nickelate intermediate B (step C) and that by the nickel
center (step E). This can be explained by that electron-donating
groups on aryl group increase the electron density on the
directly connected Ni more effectively, compared to that on the
coupling reactions. The effect of the ortho-substituent(s) on aryl
Grignard reagents to suppress the cross-coupling reaction could be
explained by the molecular structure of nickelate intermediates. Fig.
7
shows the crystal structure of the nickelate complexes having
remote -carbon of the -allyl group.
phenyl (11)35 and 2,6-diemthylphenyl (8) groups. Although the
octadienediyl moiety binds to the Ni center in the same fashion in
both cases, the orientation of the aryl ring shows a large difference:
the dihedral angle () of -C of -allyl, Ni, ipso-C, and ortho-C are 43°
for 11, and 98 to 107° for 8.
Since the selectivity is determined by the relative rates of
step C vs. step E in Scheme 4, the product ratio 3/4 can be
expressed by the relative rate constants between step C and step E
0
0
0
.4
.2
.0
Fig. 8 shows the space-filling model of complexes 11 and 8. The
Ni center (green) of phenyl complex 11 is open to the approach of
alkyl fluorides (Fig. 7, left) while such an approach to the Ni of
complex
8 is blocked by the orthogonally oriented 2,6-
diemethylphenyl group (right). Therefore, alkyl fluorides react with
the less hindered -carbon of the -allyl group (orange), giving rise to
the four-component coupling product 3.
-0.2
-0.4
-0.6
3
.8. Competitive reactions. Next, we conducted the competitive
reactions of o-tolyl Grignard reagents with/without a para-
substituent (2j vs. 2o–2r), and the relative rates k /k and the total
of substituted Grignard reagents yields at the early stage of 40 min reaction time are shown in Table
-0.6
-0.4
-0.2
0.0
0.2
0.4
X
H
Fig. 6 Relationship between the product ratio 3/4
0
against
 .
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Gaussian 0937 program, followed by single-p
calculations at the M06/6-311+G(d,p) level with the SMD
o
i
ntArtic
energy
le Online
Table 7 Competitive reaction of Grignard reagents
V
ie
w
DOI: 10.1039/C7SC04675H
38
model (THF). The energy reported here includes the electronic
energy, zero-point energy, thermal correction at 298 K and 1
atm, and solvent effect correction. The molecular structures
3
9
were drawn with CYLView. The experimental finding discussed
in Section 3 revealed that nickelate complexes are readily
formed under the reaction conditions, and the reaction of
nickelate complex with alkyl fluorides is the rate- and
selectivity-determining step of the whole catalytic cycle. In
order to reveal two competing reaction pathways, we thus
focused on the reaction of the nickelate complex with alkyl
fluorides to give the four-component coupling and cross-
coupling products.
Entry
R
k
X
/k
–
H
Total yield (%)a
1
2
3
4
5
H (2j)
Cl (2p)
F (2o)b
Me (2q)
OMe (2r)
36
25
34
46
43
1.12
0.68
0.61
0.18
a
Total yield of the products at 40 min. b Due to the difficulty in analysis,
competitive reaction with 2,4-dimethylphenylmagnesium bromide (2q) instead of
j was performed to give kF/kMe = 1.12 and calculated with kMe/kH = 0.61.
4
0
4
.1. Reaction pathways. Previously, we and another research
4
1
2
group reported theoretical calculations of the cross-coupling
reaction of alkyl halides with alkyl Grignard reagents involving
nickelate complexes as catalytic active species. In both studies,
it was revealed that S 2 attack of the nickelate complex toward
1
5
0
0
0
.4
.2
.0
N
alkyl halides, which corresponds to step E in Scheme 4, is the
rate-determining step. However, due to the difficulties of
building the initial models of anionic intermediates, the Mg
-
0.2
0.4
0.6
0.8
1.0
-
40
cation was omitted in our calculations. Chass, Kantchev, and
-
41
Fang employed a simple model without methylene tethers. In
-
addition, the reaction of alkyl fluorides was not considered in
-
41
‡
these reports. In the latter study, a very large G value of 138
-
1.0 -0.8 -0.6 -0.4 -0.2 0.0
0.2
0.4
kJ/mol was evaluated for the reaction of an anionic Ni complex
with EtBr, which is obviously inconsistent with our experimental
Fig. 9 Hammett plot of the relative reaction rates obtained in the competitive
+

p
observations that activation energy of the corresponding
reaction against
‡
process employing n-NonBr is as low as
kJ/mol.25b

G
273 = 61.9 ± 8.6
+
7
. The Hammett plot of log(k
X
/k
H
) against 
p
showed a linear
One of the most critical reasons to give such inaccurate
results is due to the structure and position of the counter cation,
which coordinates to not only the leaving group (Br) but also a
relationship with a relatively small positive  value of +0.878 (Fig. 9),
indicating that electron-withdrawing substituents militate for the
formation of four-component coupling products in competitive
reactions. This is in large contrast to the separate reactions in which
electron-rich Ar group facilitated the reaction as in Table 6 and Fig. 5.
Another important finding from Table 7 is that electron-
withdrawing substituents retard the reaction and produce in lower
total yields. For instance, when o-tolyl Grignard reagent (2j) was used
alone, 36% of 3aj was yielded after 40 min (entry 1). The competitive
reaction of 2j and the electron-deficient 2p produced a mixture of

-ligand in the anionic part, resulting in the strained structure
4
1,42
of transition states.
Such cation- interactions are often
encountered in theoretical calculation of ate complex-mediated
4
3,44
transformations.
As mentioned above, Mg cation contributes to both the
four-component coupling and the cross-coupling reactions
+
(
Scheme 7), and the cationic part (Mg Br) of the nickelate
45
complex would exist as solvent separated ion pair in THF.
Therefore, we chose models that have four THF molecules on
the MgBr cation to fulfill the six-coordination sites of Mg in TSs.
The chosen solvent separated ion pair mode led many local
3aj and 3ap with a combined yield of 25% (entry 2). Use of electron-
rich Grignard reagent 2r along with 2j afforded products in 43% total
yield(entry 5). These results may indicate that the nickelate complex-
forming step (step B) prefers electron-deficient Grignard reagents. minima throughout theoretical calculations because of not only
However, the formed nickelate with electron-deficient Ar group many possibilities of relative position of anionic Ni moiety and
4
6
reacts with alkyl fluorides at relatively slow rates compared to those Mg cation but also the flexibility of the octadienediyl moiety
formed with electron-rich ones.
and alkyl fluorides. However, this model provides more
reasonable results compared to a model containing MgBr as
necked counter cation. The following discussions are carried out
4. Computational studies.
+
by typical optimized structures employing Mg Br·4THF as the
The mechanisms of the four-component coupling and cross-
coupling reactions were theoretically investigated using density
functional theory calculations. Molecular structures were
counter cation.
The energy profiles and the corresponding key transition
states are shown in Figs. 10 and 11, respectively. All the other
3
6
optimized at the M06 /6-31G(d,p) level of theory by using
1
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View Article Online
DOI: 10.1039/C7SC04675H
Fig. 10 Reaction pathways of nickel-catalyzed four-component coupling (blue) and cross-coupling (red) reactions of methyl fluoride, phenyl Grignard reagent, and 1,3-
butadiene.
geometric structures are presented in ESI. From INT1, there are occurs between the phenyl and methyl groups, giving rise to the
two different pathways that lead to four-component coupling product P14.
and cross-coupling products. On one hand, the methyl fluoride
The above results revealed that the rate-determining step is
is inserted with the methyl group pointing to the γ-carbon, the methyl group transfer, which corresponds to TS3 and TS10
forming an intermediate INT2 with a relative energy of 42.6 for the two competing pathways, respectively. The overall
kJ/mol. Through the transition state TS3 (78.5 kJ/mol), the energy barriers of the four-component coupling and the cross-
methyl group is transferred to the γ-carbon of the
giving rise to INT4. The energy of INT4 is as low as –210.8 kJ/mol, to TS10), respectively. This appreciably large difference may
revealing that the bond formation between methyl group and due, in part, to over estimation of the C–H- interaction
-allyl group coupling reactions are 78.5 (INT1 to TS3) and 65.8 kJ/mol (INT1

the γ-carbon is largely exothermic. Then, MgBrF·4THF between THF on Mg cation and Ph group in TS10 that would not
dissociates from the reaction system, and INT5 is formed with be probable, or would exert only a small effect if possible, in the
an energy of –227.7 kJ/mol. The subsequent reductive practical conditions surrounded by THF molecules as the solvent
elimination takes place between the phenyl group and the (vide infra).
terminal carbon via TS6 with a low energy barrier of 60.8 kJ/mol
As shown in Fig. 11, in both TS3 and TS10, the Mg cation
to produce INT7. Finally, INT7 exchanges with two 1,3- moiety (Mg Br·4THF) binds to the fluorine atom to associate
+
butadiene molecules to form the product P8.
On the other hand, MeF can be inserted into INT1 to form Mg Br·4THF moiety and the anionic part is found, and therefore
INT9 (25.8 kJ/mol), with the methyl group pointing to Ni. Next, the angle of the participating atoms, C-C-F for TS3 and Ni-C-F for
elimination process, where no other short contact between
+
the methyl group is transferred to Ni via transition state TS10
65.8 kJ/mol) to form INT11 with an energy of 1.5 kJ/mol. After
elimination of MgBrF·4THF with an energy release of 31.5
kJ/mol, INT12 is generated, in which both phenyl and methyl
groups are bound to Ni. Through the transition state TS13,
which has an energy barrier of 5.3 kJ/mol, reductive elimination
TS10, is 171° and 177°, respectively. These linear structures of
TSs clearly agree with the S 2 mechanism of the C–C bond
forming step of both reaction pathways.
(
N
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ortho-methyl group significantly increases the energy barriers
View Article Online
DOI: 10.1039/C7SC04675H
of both TS3 and TS10. In particular, irrespective to the alkyl
fluorides, TS10 has an energy barrier above 106 kJ/mol, and
therefore is clearly disfavored compared with TS3. In the case
of 2,6-dimethylphenyl Grignard reagent, the energy barrier of
TS10 increases to 134.2 kJ/mol. However, in this case, the
energy barrier of TS3 is much lower (97.3 kJ/mol). From these
results, it is clear that the ortho-methyl group significantly
influences the selectivity between the four-component
coupling and the cross-coupling reactions by favoring the
former.
We next calculated TS3 and TS10 using n-OctF instead of
MeF (Table 8). The structure of the alkyl fluoride affects the
energy barriers at transition states (especially for TS10), but it
has no effect on the selectivity once the ortho-methyl group is
bF iog n. d1 1d iMs t oa lne cc eu sl .a r structures of important transition states in Fig. 10 with selected present. Those computational results agree well with the
experimental observations (Table 5). In the case of TS10, the
energy barrier of MeF rises by far more than that of n-OctF by
increasing steric hindrance of the aryl group. These results are
4.2. Steric effects on the rate-determining step. To analyze the
effect of ortho-substitution on the selectivity, we initially
conducted exploratory calculations using a set of models
including both isomers arising from the orientation of
unsymmetric o-Tol group at M06/6-31G(d,p) level of theory,
where 2-methyl-up means that the methyl group on o-Tol group
Table 8 Calculated energy barriers (in kJ/mol) of TS3 and TS10 with various aryl Grignard
reagents (R -MgBr) and alkyl fluorides (R -F)
1
2
R1
R2
TS3
TS10
G‡
TS3–TS10)
12.7
6.5
–19.3
–8.6
(
Ph
Ph
Me
n-Oct
Me
n-Oct
Me
78.5
86.7
97.0
98.3
97.3
94.5
65.8
80.2
116.3
106.9
134.2
117.5
is in the same direction with the -allyl group, and 2-methyl-
4
7
down means the opposite isomer, and revealed that TS10-2-
methyl-down is the most energetically favorable in four
2
2
-methylphenyl
-methylphenyl
,6-dimethylphenyl
,6-dimethylphenyl
possible TSs (Fig. S19). This is due to the short C–H- interaction
2
2
–36.9
–23.0
between THF on Mg cation and o-Tol group. When one THF
molecule was introduced between Mg cation and o-Tol group
to suppress the interaction, TS3 became much more favorable
than TS10 in both isomers (+33.1 kJ/mol for up and +14.4 kJ/mol
n-Oct
2
4
for down) (Fig. S20). Because the nickelate is surrounded by
solvent molecules (THF) under the practical conditions, the
latter models involving five THF molecules seem to be more
probable and consist with the experimental results. However,
due to the flexibility of the structures, there are many local
minima of the model with five THF molecules, thereby, we
decided to conduct further theoretical calculations using the
models containing four THF molecules on Mg cation.
Other important findings in the introductory investigation
are as follows: (i) a configuration orienting ortho-methyl group
toward reacting face is energetically favor in TS3 (TS3-2-methyl-
up) compared to the opposite orientation (TS3-2-methyl-down)
‡
(
G = 2.5 kJ/mol), (ii) in TS10, a configuration, oriented ortho-
methyl group to the opposite side (TS10-2-methyl-down), is
‡
more favorable than TS10-2-methyl-up (G = 18.7 kJ/mol),
and (iii) -hydrogens of alkyl fluorides are close to aryl group in
both cases of TS-10-2-methyl-up (H-H distances with ortho-
methyl group are 2.13 and 2.32 Å) and TS-10-2-methyl-down
(H-H distances with ortho-C–H bond are 2.24 and 2.24 Å). These
short H-H distances may contribute to increase energy barrier
2
4
of TS10, resulting in high four component coupling selectivity.
Fig. 12 Optimized structures and the corresponding energy barriers for the
transition states of γ-carbon attack (TS3) and Ni-attack (TS10) toward MeF for 2-
methylphenyl and 2,6-dimethylphenyl Grignard reagents. Bond distances
between key atoms are given.
Next, TS3 and TS10 with various aryl Grignard reagents and
alkyl fluorides were calculated at the higher level of theory
(M06/6-311+G(d,p)), and the results are summarized in Table 8,
Fig. 12 (for MeF), and Fig. 13 (for n-OctF). Introducing the first
1
2 | J. Name., 2012, 00, 1-3
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Journal Name
due to their tight structure, where sum of C–F and C–Ni bonds found between
ARTICLE
-H of the -allyl

-H of the n-Oct group and


View Article Online
DOI: 10.1039/C7SC04675H
1
2
of TS10 with MeF is 4.22 Å (R = Ph, R = Me: Fig. 11) in sharp group in both cases of TS3-Ph-n-Oct (2.19 Å) and TS3-2,6-
contrast to the long bond length of TS10 with n-OctF (4.47 Å for dimethylphenyl-n-Oct (2.14 Å) though a similar short distance
1
2
24
R = Ph, R = n-Oct: Fig. 13). These differences in TS10 by alkyl is also found in TS10s, where
fluorides reflect the reaction mechanism, where TS10 with MeF methylene proton (2.18 and 2.19 Å). These short H-H distances
is pure S 2 mechanism due to the less stability of Me cation, but are not principal factor on the observed selectivity. On the other
TS10 with n-OctF has a somewhat S 1 character. The natural hand, compared with the H-H distance of 2.01 Å in TS10-Ph-n-
bond orbital (NBO) analysis of these TSs at the M06/6- Oct, the H-H distance in TS10-2,6-dimethyl-n-Oct is as short as
11+G(d,p)-SMD(THF) level of theory supports the difference in 1.97 Å, indicating that there is an obvious repulsive interaction
mechanism, where the atomic charge of the reacting carbon in between the transferred n-Oct group and ortho-methyl group,
-H of the n-Oct is close to a
N
N
4
8
3
2
4
TS10 with n-OctF is more positive than that of TS10 with MeF.
which is responsible for the large increment in the energy
Therefore, in the case of TS10 with n-OctF, bond distances of C– barrier of TS10.
F and C–Ni could be elongated to minimize steric repulsions.
The TS10 with n-OctF seems to be more likely and well- 4.3. Electronic effects on the rate-determining step. Besides
describes the effect of the counter cation in the C–F bond the steric effects, the electronic effects also affect the rate-
cleavage step.
determining step and reaction rates. As shown in Section 3.6,
As discussed in Section 3.7, the ortho-substitution effect the electron-donating group at the 4-position of 2-
mainly stems from the steric effects in the nickelate complexes. methylphenyl Grignard reagent accelerates the reaction,
Due to the ortho-substitution(s), the Ni center that acts as the whereas the reaction slows down when an electron-
reacting site at transition state TS10 is partly covered, resulting withdrawing group such as F and Cl is present at this position.
in an increased energy barrier of TS10. To reveal the origin of To investigate the electronic effects, the energy barrier of TS3
the steric effect, the structures of TS3 and TS10 based on phenyl based on 2-methylphenyl Grignard reagent with various
and 2,6-dimethylphenyl Grignard reagents are shown in Fig. 13 substituents at the 4-position were calculated (Table 9). Only
with representative short contacts. A short H-H distance is
TS3 was considered here, because TS10 has been revealed to be
highly disfavored as shown in Fig. 12. Compared with the case
of 2-methylphenyl (R = H), substitution by F and Cl at the 4-
position increases the energy barrier of TS3, while the energy
barrier is significantly reduced when an electron-donating
2
group such as OMe and NMe is introduced. These theoretical
results are consistent with the experimental observations
mentioned above.
The NBO analysis was performed to further study the charge
on the -carbon of the -allyl group in TS3. As shown in Table 9,
the 4-position substitution moderately affects the charge state
of γ-carbon: electron-donating groups here increase the charge
4
9
while electron-withdrawing groups reduce it. This is in good
agreement with the reaction mechanism and observed
electronic effects on the reaction rate (Section 3.6).
To further study the electronic effects on the selectivity
between four-component coupling and cross-coupling
reactions, the energy barriers of TS3 and TS10 based on para-
Table 9 Calculated energy barriers (in kJ/mol) of TS3 based on 2-methyl-4-R-phenyl
Grignard reagents and methyl fluoride and charge (|e|) of γ-carbon
R
ΔG‡
H
97.0
F
98.3
Cl
97.6
Me
94.9
OMe
92.2
NMe
91.2
2
Fig. 13 Optimized structures and the corresponding energy barriers for the
γ-C
–0.388
–0.387
–0.376
–0.390
–0.388
–0.390
transition states of γ-carbon attack (TS3) and Ni-attack (TS10) toward n-OctF for
phenyl and 2,6-dimethylphenyl Grignard reagents. Bond distances between key
atoms and representative short H-H distances are given.
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so
Table 10 Difference in calculated energy barriers (in kJ/mol) of TS3 and TS10 based on p-
Mechanistic studies including observation andVie
i lation of
w Article Online
RC
6
H
4
MgBr and n-OctF
the anionic nickel complexes as well as kin
DO
e
I:ti1
c
0.
s
10
t
ud
3
9/
i
C
es7S
c
C
l
0
arif d
4
6
7
ie5H
the detail of reaction mechanism as follows: (i) anionic nickel
complexes are the key intermediate at the C–C bond forming
step with alkyl fluorides, and the corresponding neutral Ni
complex is inert toward alkyl fluorides, (ii) the C–C and C–Ni
bond forming steps are the rate-determining step in the four-
component coupling and cross-coupling reactions, respectively,
(
iii) therefore, the selectivity of these two products is
determined by the relative reactivity between the -carbon of
the -allyl group and the Ni atom of the anionic nickel


complexes, (iv) electron-donating groups on the aryl group
accelerates the C–C and C–Ni bond formations with alkyl
fluorides due to the S
reactions, where Ni is more effectively activated than the
remote -carbon, (v) the Mg cation plays crucial roles in
N
2 type reaction mechanism in both

R
ΔΔG‡
exp. ratio
4/3)
H
6.5
1.4
F
–2.7
0.60
Cl
–1.9
1.0
Me
5.0
1.9
OMe NMe
2
activation of C–F bond by its coordination, whereas other
typical metal cations such as Li and Zn are not effective, and (vi)
the bis(-allyl)nickel complex prefers electron-deficient aryl
5.0
2.3
8.9
3.3
(
Grignard reagents to form anionic Ni complexes. On the basis of
above experimental observations and DFT calculations, the
catalytic cycles of the both four-component coupling and cross-
coupling reactions are accomplished, in which the cation
substituted phenyl Grignard reagents and n-OctF were
calculated, and G of the two reaction pathways (TS3–TS10)
‡
and selectivities based on experimental results are summarized
in Table 10. The calculated results generally agree well with the
experimental observations. The electron-withdrawing group
such as F and Cl at the 4-position obviously destabilizes TS10 in
.7 and 1.9 kJ/mol than TS3, respectively, and therefore, favors
the four-component coupling products 3. The electron-
donating group (Me or NMe ), on the other side, disfavors TS3
+
+
Mg Br∙4THF rather than Mg Br plays a crucial role to activate
+
the C–F bond. The theoretical calculations with Mg Br∙4THF
model not only explain very well the experimental results such
as activation energy barriers but also unravel the origins of
substituent effect (ortho-substituent and para-substituent) on
the selectivity and reaction rates in terms of steric and
electronic effects.
2
2
and gives rise to the reversal ratio of 3:4. Those results suggests
that the electronic effects plays important role in the reactions
with phenyl Grignard reagents (no ortho-substitution) though
the impact on selectivity is relatively smaller than steric effects
Although such anionic species of transition metals have
sometime been proposed as the key intermediates in catalytic
bond formation, their structure as well as chemical
characteristics are unclear in many cases. Our results
demonstrate their synthetic utility as promising intermediates
for C–C bond forming reactions. The present study provides
useful information in organometallic and synthetic organic
chemistry, for developing efficient and straightforward
(Section 4.2).
Conclusions
We examined the reaction mechanism, substituent effects, and multicomponent reactions as well as anionic transition metal
origins of the selectivity of the Ni-catalyzed four-component complexes as a unique and powerful catalytic intermediates.
coupling of alkyl fluorides, aryl Grignard reagents, and two
molecules of 1,3-butadiene and the competing cross-coupling
reaction. The introduction of ortho-substituent(s) into the aryl
Conflicts of interest
Grignard reagents efficiently suppresses the cross-coupling There are no conflicts to declare.
reaction, giving four-component coupling products in good
yields with perfect regio- and stereoselectivity. The present
catalysis selectively provides four-component coupling Acknowledgements
products and does not form three-component coupling
This work was partly supported by JSPS KAKENHI Grant
products without the dimerization of 1,3-butadiene, in sharp
contrast to previous reports of a similar Ni-catalyzed
multicomponent coupling reaction employing 1,3-dienes and
Numbers JP25248025, JP16H06039, JP16H06511, JP16H04104,
and JP25105734 in “Molecular Activation Directed toward
Straightforward Synthesis”; JP16H01150 in “Middle Molecular
Strategy”; JSPS Japanese-German Graduate Externship from
JSPS; and Nanotechnology Platform Japan program from MEXT.
Computations were performed at the Research Center for
Computational Science, Okazaki, Japan. T.I. thanks The UBE
Foundation, The Sumitomo Foundation, The Uehara Memorial
7
carbonyl electrophiles. This difference arises from the different
mechanism in the present reaction: the anionic Ni
intermediates generated by the reaction of Ni(0) with two 1,3-
butadiene molecules and aryl Grignard reagents is the key
intermediate, and it enables the use of alkyl fluorides as the
prospective alkylating reagent through C–F bond cleavage.
1
4 | J. Name., 2012, 00, 1-3
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(
c) J. Terao, H. Todo, S. A. Begum, H. Kuniyasu aVniedwNAr.tiKcleamOnblinee,
Foundation, and The Iketani Science and Technology
Foundation. T.Y. thanks the Alexander von Humboldt
Foundation for a postdoctoral fellowship. We are grateful to
Prof. Satoshi Minakata and Prof. Masato Ohashi (Osaka
University) for numerous fruitful discussions.
Angew. Chem. Int. Ed., 2007, 46, 2086; (d) T. Iwasaki, R.
DOI: 10.1039/C7SC04675H
Imanishi, R. Shimizu, H. Kuniyasu, J. Terao and N. Kambe, J.
Org. Chem., 2014, 79, 8522; (e) T. Iwasaki, K. Yamashita, H.
Kuniyasu and N. Kambe, Org. Lett., 2017, 19, 3691.
15 (a) J. Terao, H. Watanabe, A. Ikumi, H. Kuniyasu and N. Kambe,
J. Am. Chem. Soc., 2002, 124, 4222. For synthetic applications:
(b) T. Iwasaki, K. Higashikawa, V. P. Reddy, W. W. S. Ho, Y.
Fujimoto, K. Fukase, J. Terao, H. Kuniyasu and N. Kambe, Chem.
Eur. J., 2013, 19, 2956; (c) A. Ghaderi, T. Iwasaki, A. Fukuoka,
J. Terao and N. Kambe, Chem. Eur. J., 2013, 19, 2951; (d) T.
Aiba, M. Sato, D. Umegaki, T. Iwasaki, N. Kambe, K. Fukase, Y.
Fujimoto, Org. Biomol. Chem., 2016, 14, 6672.
Notes and references
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c) R. Baker, M. S. Nobbs and P. M. Winton, J. Organomet. 19 Selected examples in which anionic intermediates were
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20 Our reports on the catalytic cross-coupling reaction involving
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6
7
2
007, 9, 1871.
8
9
For reactions involving alkyne insertion, see: (a) M. Kimura, K.
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Kimura, Heterocycles, 2012, 84, 339.
For reviews on the reaction of carbonyl compounds, 1,3-
butadiene, and organometallic reagents in 1:1:1 ratio, see: (a) 21 For recent reports on nickelate complexes in organic
Y. Tamaru, J. Organomet. Chem., 1999, 576, 215; (b) S.-i. Ikeda,
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1
1
1 For multicomponent reactions using chlorosilanes as
heteroatom electrophiles, see: (a) J. Terao, A. Oda, A. Ikumi,
A. Nakamura, H. Kuniyasu and N. Kambe, Angew. Chem. Int.
Ed., 2003, 42, 3412; (b) J. Terao, A. Oda and N. Kambe, Org.
Lett., 2004, 6, 3341.
1
1
1
2 T. Iwasaki, X. Min, A. Fukuoka, H. Kuniyasu and N. Kambe,
Angew. Chem. Int. Ed., 2016, 55, 5550.
22 For representative reviews on C–F bond cleavage in organic
syntheses, see: (a) J. L. Kiplinger, T. G. Richmond and C. E.
Osterberg, Chem. Rev., 1994, 94, 373; (b) T. Braun and R. N.
Perutz, Chem. Commun., 2002, 2749; (c) H. Torrens, Coord.
Chem. Rev., 2005, 249, 1957; (d)J. Terao, H. Todo, H. Watabe,
A. Ikumi, Y. Shinohara and N. Kambe, Pure Appl. Chem., 2008,
3 T. Iwasaki, A. Fukuoka, X. Min, W. Yokoyama, H. Kuniyasu and
N. Kambe, Org. Lett., 2016, 18, 4868.
4 (a) J. Terao, A. Ikumi, H. Kuniyasu and N. Kambe, J. Am. Chem.
Soc., 2003, 125, 5646; (b) J. Terao, H. Todo, H. Watanabe, A.
Ikumi and N. Kambe, Angew. Chem. Int. Ed., 2004, 43, 6180;
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Journal Name
8
0, 941; (e) H. Amii and K. Uneyama, Chem. Rev., 2009, 109, 36 Y. Zhao and D. G. Truhlar, Theor. Chem. Acc., 20V0i8ew, 1Ar2ti0cl,e2O1nl5in.e
2119.
37 M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A.
DOI: 10.1039/C7SC04675H
2
3 For C–C bond formation of alkyl fluorides, see: (a) T. Ooi, D.
Uraguchi, N. Kagoshima and K. Maruoka, Tetrahedron Lett.,
Robb, J. R. Cheeseman, G. Scalmani, V. Barone, B. Mennucci,
G. A. Petersson, H. Nakatsuji, M. Caricato, X. Li, H. P. Hratchian,
A. F. Izmaylov, J. Bloino, G. Zheng, J. L. Sonnenberg, M. Hada,
M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T.
Nakajima, Y. Honda, O. Kitao, H. Nakai, T. Vreven, J. A. Jr.
Montgomery, J. E. Peralta, F. Ogliaro, M. Bearpark, J. J. Heyd,
E. Brothers, K. N. Kudin, V. N. Staroverov, T. Keith, R.
Kobayashi, J. Normand, K. Raghavachari, A. Rendell, J. C.
Burant, S. S. Iyengar, J. Tomasi, M. Cossi, N. Rega, J. M. Millam,
M. Klene, J. E. Knox, J. B. Cross, V. Bakken, C. Adamo, J.
Jaramillo, R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin,
R. Cammi, C. Pomelli, J. W. Ochterski, R. L. Martin, K.
Morokuma, V. G. Zakrzewski, G. A. Voth, P. Salvador, J. J.
Dannenberg, S. Dapprich, A. D. Daniels, O. Farkas, J. B.
Foresman, J. V. Ortiz, J. Cioslowski and D. J. Fox, Gaussian 09,
Revision E.01; Gaussian, Inc.; Wallingford, CT, 2013.
1
997, 38, 5679; (b) K. Hirano, K. Fujita, H. Yorimitsu, H.
Shinokubo and K. Oshima, Tetrahedron Lett., 2004, 45, 2555;
c) T. Hatakeyama, S. Ito, M. Nakamura and E. Nakamura, J.
(
Am. Chem. Soc., 2005, 127, 14192; (d) J.Terao, S. A. Begum, Y.
Shinohara, M. Tomita, Y. Naitoh and N. Kambe, Chem.
Commun., 2007, 855; (e) M. Sai, H. Someya, H. Yorimitsu and
K. Oshima, Org. Lett., 2008, 10, 2545; (f) L. W. Erickson, E. L.
Lucas, E. J. Tollefson and , E. R. Jarvo, J. Am. Chem. Soc., 2016,
138, 14006. Also see, ref 19h.
2
2
4 See Electronic Supplementary Information for details.
5 For mechanistic studies on the cross-coupling reaction using
Ni/1,3-butadiene catalytic system, see: (a) J. Terao, Y. Naitoh,
H. Kuniyasu and N. Kambe, Chem. Commun., 2007, 825; (b) T.
Iwasaki, A. Tsumura, T. Omori, H. Kuniyasu, J. Terao and N.
Kambe, Chem. Lett., 2011, 40, 1024. See also ESI.
38 A. V. Marenich, C. J. Cramer and D. G. Truhlar, J. Phys. Chem.
B, 2009, 113, 6378.
2
6 (a) G. Wilke, Angew. Chem. Int. Ed., 1963, 2, 105; (b) B. Barnett,
B. Büssemeier, P. Heimbach, P. W. Jolly, C. Krüger, I. 39 C. Y. Legault, CYLView, 1.0b; Universitéde Sherbrooke: Canada,
Tkatchenko and G. Wilke, Tetrahedron Lett., 1972, 1457; (c) R.
Benn, B. Büssemeier, S. Holle, P. W. Jolly, R. Mynott, I. 40 L. M. Pratt, S. Voit, F. N. Okeke and N. Kambe, J. Phys. Chem.
Tkatchenko and G. Wilke, J. Organomet. Chem., 1985, 279, 63. A., 2011, 115, 2281
7 For computational study, see: S. Tobisch, Chem. Eur. J., 2003, 41 G. A. Chass, E. A. B. Kantchev and D.-C. Fang, Chem. Commun.,
, 1217. 2010, 46, 2727.
8 (a) S. Holle, P. W. Jolly, R. Mynott and R. Salz, Z. Naturforsch, 42 Although the reported TS is Mg assisted S
982, 37b, 675; (b) W. Kaschube, K.-R. Pörschke, K. angle of participating atoms, Ni, C, and Br, is bended ca. 140°.
2009; http://www.cylview.org.
2
2
9
N
2-like model, the
1
Angermund, C. Krüger and G. Wilke, Chem. Ber., 1988, 121, 43 For a recent example, see: H. Ogawa, H. Minami, T. Ozaki, S.
1
921. The formation of ate complexes by oxidative
Komagawa, C. Wang and M. Uchiyama, Chem. Eur. J., 2015, 21,
13904.
dimerization of 1,3-butadiene on arylnickel(0) is also
reported: (c) K. Jonas and C. Krüger, Angew. Chem. Int. Ed., 44 Our initial attempts to estimate TSs of the both four-
1980, 19, 520.
component coupling and cross-coupling reactions employing
+
2
9 CCDC-1572238 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
from the CCDC via www.ccdc.cam.ac.uk/data_request/cif.
Mg Br as a model of the counter cation resulted in
unsatisfactory results. As shown in below, in the TS of the
cross-coupling reaction (left), the MgBr cation shortly
contacts to the ipso-carbon of the Ph group (2.24 Å), and the
Ni atom attacks from the same side of the F atom (angle of Ni-
C-F = 86°). Similarly, the MgBr cation bonds to the Ni atom and
the ipso-carbon of the Ph group (Mg-Ni = 2.65 Å and Mg-C =
2.24 Å) with a narrow angle of Ni-C-F (152°) in TS of the four-
component coupling reaction (right). Due to their strained
structure, the activation energy of these TSs was calculated to
be 166 and 123 kJ/mol, respectively. These preliminary results
clearly indicate the necessity of more feasible models.
3
2
0 (a) When n-OctF (1a) was treated with 1 equiv of MgBr in THF
at 40 °C, only 7% of the corresponding n-OctBr was observed
after 10 h. This result indicates that the halogen exchange
reaction with Mg salt is not the major pathway in this reaction.
(
b) When an alkyl bromide instead of alkyl fluorides was
employed to the reaction of isolated nickelate complexes
bearing Li as the cation, the cross-coupling reaction took place
in the absence of an additional Mg salt in sharp contrast with
the case of alkyl fluorides. This result suggests that the
reaction of nickelates with alkyl bromides proceeds without
the assistance of Mg cation in TS due to the higher reactivity
of alkyl bromides. See ESI for details.
3
1 Under the standard conditions, there is a short (within 5 min)
induction period, probably arising from the reduction of the
Ni salt to Ni(0). Therefore, the fitting lines do not cross the
origin. The starting point of the plots is in the range of 3–5 min,
and the initial reaction rates were evaluated from the slope of
plots.
4
5 It is known that cuprates form solvent separated ion pair in
32 The enthalpy-entropy compensation plot showed an excellent
2
THF although they exist as contact ion pair in Et O. See: (a) M.
2
linear relationship with R = 0.999, suggesting the same
John, C. Suel, C. Behrens, M. Marsch, K. Harms, F. Bosold, R.
M. Gschwind, P. R. Rajamohanan and G. Boche, Chem. Eur. J.,
reaction mechanisms of these Grignard reagents. See: M. S.
Searle, M. S. Westwell and D. H. Williams, J. Chem. Soc., Perkin
Trans. 2, 1995, 141.
2
000, 6, 3060; (b) R. M. Gschwind, P. R. Rajamohanan, M. John
and G. Boche, Organometallics, 2000, 19, 2868. Also see ref
7.
3
3 The rate constant for the cyclization is known to be k = 4.0 ×
1
7
–1
1
0 s at 25 °C, see: M. Newcomb, S.-Y. Choi and J. H. Horner,
4
6 Theoretical studies on Ni-catalyzed cross-coupling reaction
using Grignard reagents have been reported, in which Mg
cation coordinates to a ligand on Ni. For instances: N. Yoshikai,
H. Matsuda and E. Nakamura, J. Am. Chem. Soc., 2009, 131,
J. Org. Chem., 1999, 64, 1225.
3
4 According to the Yukawa-Tsuno’s equation, log(k
X
/k
H
) =

(
0
+
+
r
̅
R
), the value of r was estimated to be 0. This result may
indicate that in both reactions the contribution of resonance
effect is very small.
9590. Also see, ref 21h
4
7 The rotation barrier was estimated to be 55 kJ/mol by
calculation, suggesting possibility of both isomers. Indeed, VT
NMR of the nickelate complex having o-Tol group showed two
3
5 The X-ray crystallography data of 11 has been reported earlier,
see ref 13. CCDC-1478800.
1
6 | J. Name., 2012, 00, 1-3
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PleaseC dh oe mn oi ct a al dS cj ui es nt cme argins
Journal Name
ARTICLE
isomers, and the rotation barrier was determined to be 52.7
6.0 kJ/mol at 273 K. See ESI for details.
View Article Online
DOI: 10.1039/C7SC04675H
±
4
8 E. D. Glendening, A. E. Reed, J. E. Carpenter and F. Weinhold,
NBO, version 3.1; University of Wisconsin: Madison, WI, 1996.
9 The NBO charge of Ni did not change by the para-substituents
4
in all cases. This is due to the
Indeed, the total NBO charges of the Ni atom and the
ligand are –0.818 (H), –0.815 (F), –0.815 (Cl), –0.820 (Me), –
.819 (OMe), and –0.820 (NMe ). See ESI for details.

-allyl ligand in trans-position.

-allyl
0
2
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