Kinetic studies of the ni-catalyzed cross-coupling of alkyl halides and a tosylate with butyl grignard reagent in the presence of 1,3-butadiene

Article abstract of DOI:10.1246/cl.2011.1024

Kinetic studies of the nickel-catalyzed cross-coupling reaction of alkyl bromides, iodides, and tosylates with butyl Grignard reagents in the presence of butadiene were performed. The reaction rate was first order with respect to the halides and the nickel catalyst. The butyl Grignard reagent, at concentrations of ca. 0.4M or higher, had little effect on the reaction rate. The relative reactivities and activation parameters were determined for these alkyl halides and a tosylate.

Full text of DOI:10.1246/cl.2011.1024

doi:10.1246/cl.2011.1024
1024
Published on the web September 5, 2011
Kinetic Studies of the Ni-catalyzed Cross-coupling of Alkyl Halides and a Tosylate
with Butyl Grignard Reagent in the Presence of 1,3-Butadiene
Takanori Iwasaki,1 Asako Tsumura,1 Takehiro Omori,1 Hitoshi Kuniyasu,1 Jun Terao,2 and Nobuaki Kambe*1
1Department of Applied Chemistry, Graduate School of Engineering, Osaka University,
2-1 Yamadaoka, Suita, Osaka 565-0871
2Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University,
Katsura, Nishikyo-ku, Kyoto 615-8510
(Received July 1, 2011; CL-110556; E-mail: kambe@chem.eng.osaka-u.ac.jp)
Kinetic studies of the nickel-catalyzed cross-coupling reac-
tion of alkyl bromides, iodides, and tosylates with butyl Grignard
reagents in the presence of butadiene were performed. The
reaction rate was first order with respect to the halides and the
nickel catalyst. The butyl Grignard reagent, at concentrations of
ca. 0.4 M or higher, had little effect on the reaction rate. The
relative reactivities and activation parameters were determined for
these alkyl halides and a tosylate.
Cross-coupling reactions are useful and powerful tools for
connecting two different organic moieties via a single bond and
have been widely employed in organic synthesis.1 During the past
decade, the scope of this cross-coupling has been expanded to the
use of alkyl halides as a coupling partner.2 In a previous study, we
reported that nickel as well as palladium and copper showed
unique catalytic activities for cross-coupling reactions in which
alkyl halides were used in the presence of a ³-carbon ligand such
as 1,3-butadiene or an alkyne.3 The Ni/butadiene system (eq 1)
showed particularly high performance, allowing the selective
alkyl-alkyl cross-coupling of alkyl halides with a Grignard
reagent4 in the presence of various functional groups.5 Further-
more, the turn-over number can reach the order of 107.6 In order to
probe this reaction in more detail, we performed kinetic studies
and report on the results obtained.
Figure 1. Time course of the reaction of n-C9H19Br (1a, 0.2 M) with
n-BuMgCl (0.6 M) using 2.5 mol % of a Ni salt (0.005 M) and 1,3-
butadiene (0.2 M) in THF at 0 °C.
NiX
2
+
RMgCl
Alkyl
X
Alkyl
R
ð1Þ
1
2
3
We first examined the time course for the reaction of nonyl
bromide (1a) with excess butyl Grignard reagent using various
Ni salts and 1,3-butadiene in THF at 0 °C. As shown in Figure 1,
all of the Ni salts afforded tridecane (3a) exclusively in
quantitative yield based on the bromide within 15 min, but an
induction period was observed for several salts probably due to
their low solubilities in THF. NiBr2/dme (dme: dimethoxyethane)
and [Ni(acac)2] did not show any apparent induction period.
Therefore, we used NiBr2/dme as the source of the Ni catalyst
throughout this kinetic study.
We then examined order of the rate for each reagent. A
reaction using NiBr2/dme, similar to that of Figure 1 was
performed using different concentrations of nonyl bromide (1a)
at ¹35 °C and the reaction was quenched with 1 M HCl(aq) after
stirring for 90 s. These results were plotted in Figure 2 and a
good straight line was obtained, indicating that this reaction obeys
Figure 2. n-C9H19Br (1a, 0.082-0.38M), n-BuMgCl (0.6 M), NiBr2/
dme (2.5 mol %, 0.005 M), 1,3-butadiene (0.2 M), at ¹35 °C for 90 s.
similar manner, the yield of undecane (3b) was plotted against the
concentration of the Ni catalyst employed, and the results are
shown in Figure 3. These data clearly indicate that the reaction
rate is first order with respect to the catalyst concentration.
When we ran the same reaction using different concentrations
of n-BuMgCl, an interesting result was obtained (Figure 4). The
reaction was accelerated with increasing concentrations of
n-BuMgCl up to ca. 0.4 M, while the rate became constant in
the region of higher concentrations.
This result can be explained by assuming an equilibrium
process I between the bis(³-allyl) complex (A)7 and ate complex
(B)8 and the subsequent rate-determining process II (Scheme 1).
When the concentration of RMgX is sufficiently high, the
equilibrium is shifted toward the ate complex (B), and its
concentration is not substantially increased at higher concentra-
tion of RMgX. However, at lower concentrations of RMgX, the
equilibrium is biased toward the bis(³-allyl) complex (A) and the
first-order kinetics with respect to nonyl bromide with a pseudo-
¹1
first-order rate constant kobs = 1.76 © 10¹3 s
for r = kobs[n-
C9H19Br].
The effect of the catalyst and Grignard reagent on the reaction
rate was examined using heptyl tosylate (1b) at 1 °C for 150 s. In a
Chem. Lett. 2011, 40, 1024-1026
© 2011 The Chemical Society of Japan
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1025
(a)
Figure 3. n-C7H15OTs (1b, 0.2 M), n-BuMgCl (0.6 M), NiBr2/dme
(0-0.014M), 1,3-butadiene (0.2 M), at 1 °C for 2.5 min.
(b)
Figure 5. (a) Time course of the cross-coupling of n-C9H19Br (0.2 M)
with n-BuMgCl (0.6 M) using NiBr2/dme (0.005 M) and 1,3-butadiene
(0.2 M) at ¹18 °C (blue iozenge), ¹24 °C (red square), ¹29 °C (green
triangle), ¹40 °C (purple circle), and ¹45 °C (orange box) in THF. (b)
Fitting the data in Figure 5a to the pseudo-first-order line.
Figure 4. n-C7H15OTs (1b, 0.2 M), n-BuMgCl (0.2-0.8 M), NiBr2/dme
(0.005 M), 1,3-butadiene (0.2 M), at 1 °C for 2.5 min.
are shown in Figures 5a and 5b. All reactions reached completion
on stirring to give 3a quantitatively (Figure 5a). From the slopes
of the lines in a plot of ln([1a]/[1a]0) against reaction time
(Figure 5b), rate constants kobs(Br) of eq 2 at each temperature
were obtained using several sets of data for the early stage of
reactions, and these results are listed in Table 1. These values are
in accord with that obtained from Figure 2 (vide supra). Similar
treatment of heptyl tosylate (1b) and hexyl iodide (1c) afforded
corresponding rate constants kobs(OTs) and kobs(I), and these data are
also summarized in Table 1.
With the slope and intercept of the Eyring plot using the data
from Table 1 (Figure 6), the activation parameters for the cross-
coupling were calculated and these findings are shown in Table 2.
The data indicate that the activation entropies are relatively small
and that the reaction rates are mainly controlled by enthalpy
factors (vide infra).
Ni
Ni
R
MgX
(A)
Alkyl
R
2
3
Alkyl
X
1
Ni
MgX
R
(B)
Scheme 1. Ni-Catalyzed cross-coupling reaction.
From these data, the relative reactivities of primary alkyl
iodides, bromides, and tosylates were estimated to be,
concentration of the ate complex (B) increases with increasing
concentration of RMgX, thus resulting in an acceleration of the
reaction rate. However, another possibility that process I could
become the rate-determining step when the concentration of
RMgX is low and/or the effect of the aggregation of RMgX
cannot be ruled out.
With these results, under conditions using excess amounts of
Grignard reagents and a constant amount of the Ni salt, the
reaction rate obeys pseudo-first-order kinetics for RX with
ꢁ
n-C7H15OTs:n-C9H19Br:n-C6H13I ¼ 0:015:1:15 ðat 25 CÞ
ꢁ
¼ 0:018:1:19 ðat 0 CÞ
¼ 0:022:1:25 ðat ꢂ25 ꢁCÞ
ð3Þ
suggesting that primary alkyl bromides react ca. 50 times faster
than the corresponding tosylates and iodides react ca. 20 times
faster than bromides.
r ¼ kX½RXꢀ½Niꢀ ¼ kobsðXÞ½RXꢀ
ð2Þ
A detailed mechanism that explains the rate-determining step
(process II) is not clear at this time, but a stepwise pathway
involving the oxidative addition of alkyl halides to solvent
separated ate complexes (B) leading to the formation of Ni(IV)
We then ran the reaction at different temperatures and the rate
constants were determined by fitting the data to the pseudo-first-
order rate equation. The results obtained using nonyl bromide (1a)
Chem. Lett. 2011, 40, 1024-1026
© 2011 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

1026
Table 1. Rate constans kobs(X) (s¹1) of cross-coupling of RX with n-
BuMgCla
¹1
¦G‡ = 87.1 kJ mol at 20 °C, ¦H‡ = 10 kJ mol¹1, and ¦S‡ =
¹2.6 © 102 J K¹1 mol
.
It is interesting that reaction of a Pd
¹1 12
X = OTs
complex with alkyl halides has a small activation enthalpy and is
controlled by an entropy factor, while the reaction of the Ni
complex (B) with alkyl halides is enthalpy-controlled.
In conclusion, it was revealed that Ni-catalyzed alkyl-alkyl
cross-coupling using 1,3-butadiene obeys first-order kinetics for
the alkyl halide and the Ni catalyst but the concentration of the
Grignard reagents exerts little effect on the rate at concentrations
higher than ca. 0.4 M. The reaction rates of an alkyl tosylate,
bromide, and iodide at different temperatures were measured and
activation parameters for these compounds were obtained.
Temp/°C 22
21
9
4
¹3
¹1
¹3
¹4
¹3
¹4
¹3
¹6
¹3
¹5
¹4
k
obs(X)/s 4.58 © 10 3.77 © 10 1.81 © 10 1.20 © 10 5.00 © 10
Temp/°C ¹8
¹15
¹20
¹25
¹1
k
obs(X)/s 2.26 © 10 1.82 © 10 5.76 © 10 1.19 © 10
X = Br
Temp/°C ¹18
¹24
¹29
¹40
¹45
¹1
¹3
¹3
¹3
¹4
¹4
k
obs(X)/s 5.16 © 10 3.94 © 10 1.89 © 10 4.86 © 10 2.05 © 10
X = I
This work was supported by a Grant-in-Aid for Scientific
Research (S) No. 20225004 from the Ministry of Education,
Culture, Sports, Science and Technology, Japan.
Temp/°C ¹52
¹56
¹60
¹65
¹1
¹3
¹3
¹3
¹4
k
obs(X)/s 3.21 © 10 1.66 © 10 1.04 © 10 5.12 © 10
aReaction conditions: RX (0.2 M), n-BuMgCl (0.6 M), NiBr2/dme
(0.005 M), 1,3-butadiene (0.2 M).
This paper is in celebration of the 2010 Nobel Prize awarded
to Professors Richard F. Heck, Akira Suzuki, and Ei-ichi Negishi.
References and Notes
1
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Figure 6. Eyring plot of data of Table 1.
Table 2. Activation free energies (0 °C) and activation parameters of
Ni-catalyzed cross-coupling
¦H‡/
kJ mol
¦S‡/
J K¹1 mol
R-X
ꢀGz273/kJ mol
¹1
¹1
¹1
n-Heptyl-OTs (1b)
n-Nonyl-Br (1a)
n-Hexyl-l (1c)
71.1 « 9.8
61.9 « 8.6
55.3 « 6.0
52.7 « 4.9 ¹67.6 « 18.0
57.3 « 4.0 ¹16.9 « 16.7
51.2 « 2.6 ¹14.8 « 12.3
3
4
a) J. Terao, H. Watanabe, A. Ikumi, H. Kuniyasu, N. Kambe, J. Am.
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Alkyl
R
Alkyl
X
2
1
Alkyl
R
Ni
Ni
MgX
(A)
MgX
R
(B)
(C)
5
6
Scheme 2. Reaction of Alkyl-X with an ate complex intermediate.
7
8
B. Büssemeier, P. W. Jolly, G. Wilke, J. Am. Chem. Soc. 1974, 96, 4726.
D. Alberti, R. Goddard, A. Rufińska, K.-R. Pörschke, Organometallics
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Single step mechanism via direct attack of R of the complex (B) to
Alkyl-X 1 with or without interaction between Ni and alkyl carbon
cannot be ruled out. According to ref. 3a, radical mechanism via
electron transfer from the ate complex (B) to alkyl halides would not be
likely.
intermediates (C) and a subsequent reductive elimination seems
likely (Scheme 2).9 Theoretical calculations regarding this path-
way suggest the possibility of Ni(IV) intermediates (C).10,11 If the
reaction proceeds via C, although counter Mg cations may play
important roles in the real system, the activation parameters
shown in Table 2 correspond to this oxidative addition step,
because the calculations suggest that the successive reductive
elimination step is highly exergonic with a low energy barrier and
so should be rapid, even at low temperatures.10 Fu performed a
kinetic study of the oxidative addition of alkyl halides to Pd(0) as
a key step in Pd-catalyzed cross-coupling and revealed that
activation parameters of the oxidative addition of nonyl bromide
with Pd[P(t-Bu)2Me]2 leading to n-C9H19PdBr[P(t-Bu)2Me]2 were
9
10 L. M. Pratt, S. Voit, F. Okeke, N. Kambe, J. Phys. Chem. A 2011, 115,
2281.
11 As a similar mechanism, lithium cuprates (R2CuLi) react with R¤X to
give R-R¤ via Cu(III) intermediates. a) S. H. Bertz, S. Cope, D. Dorton,
M. Murphy, C. A. Ogle, Angew. Chem., Int. Ed. 2007, 46, 7082. b) T.
Gärtner, N. Yoshikai, M. Neumeier, E. Nakamura, R. M. Gschwind,
Chem. Commun. 2010, 46, 4625.
12 I. D. Hills, M. R. Netherton, G. C. Fu, Angew. Chem., Int. Ed. 2003, 42,
5749.
Chem. Lett. 2011, 40, 1024-1026
© 2011 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/