Quantitative kinetic investigation on transmetalation of ArZnX in a Pd-catalysed oxidative coupling

Article abstract of DOI:10.1039/c3cc44894k

Transmetalation is the rate-limiting step. [R-Pd-Ar] was suggested to be the resting species from the kinetic studies. Quantitative measurement of the transmetalation of ArZnCl with [R-Pd-Ar] from a live Pd-catalysed oxidative coupling reaction was conducted and the corresponding activation enthalpy was determined as 12.3 kcal mol^-1. The Royal Society of Chemistry 2013.

Full text of DOI:10.1039/c3cc44894k

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DOI: 10.1039/C3CC44894K
ARTICLE TYPE
Quantitative Kinetic Investigation on Transmetalation of ArZnX in a
Pd-Catalysed Oxidative Coupling
a
a
a
a,b
JingLi, LiqunJin, Chao Liu, and Aiwen Lei*
Received (in XXX, XXX) XthXXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
5
DOI: 10.1039/b000000x
Transmetalation is the rate-limiting step. The [R-Pd-Ar] was
suggested to be the resting species from the kinetic studies.
Quantitative measurement of the transmetalation of ArZnCl
with [R-Pd-Ar] from a live Pd-catalysed oxidative coupling
reaction was conducted and the corresponding activation
1
0
enthalpy was determined as 12.3 kcal/mol.
16
Transmetalation is one of the most important elementary
reactions in transition-metal-catalysed coupling reactions. It
involves the transfer of an organo group from one metal to the
1
2
8
4
0
1
2
2
3
3
4
4
5
0
5
0
5
0
5
other and introduces a σ-bonded carbon atom into the
1
coordination sphere of the transition metal centre. Up to now,
transmetalation step has been investigated in many reports.
2
-
However, most of the explorations focused on the Stille reaction
and Suzuki–Miyaura reaction
1
1
12-18
, in which transmetalation has
been assigned to be the rate-limiting step. Compared with the
organoboron reagents and organotin reagents, the organozinc
reagents exhibit higher reactivity in Pd-catalysed coupling
reactions and the transmetalation of organozinc reagents with
1
.5
3.0
4.5
6.0
7.5
-5
[Pd] (x10 M)
1
19
50
R M X is generally considered to be a facile process.
cat
Therefore, it is more difficult to quantitatively obtain the kinetic
data of transmetalation from Pd-catalysed Negishi couplings.
Espinet and co-workers have sequentially reported the
experimental and computational results on the transmetalation of
Fig.1 Dependence of the initial rates on catalyst concentrations for the
homo-coupling of 1a. Reaction conditions: 1a (0.35 M in THF, 4.0 mL),
-5
-5
Pd(OAc)
2
(1.1×10
M–6.6×10
M
in THF), 2-chloro-1,2-
-2
o
diphenylethanone (3a) (7.5×10 M in THF, 0.3 mmol), -20 C.
[
RalkylPdCl] with the ZnMe or ZnMeCl through stoichiometric
2
20-22
experiments.
However, it is usually not the rate determining
5
6
6
7
5
0
5
0
The dependence of the initial rates on catalyst concentrations
was first tested by using 1a as the substrate with different
palladium concentrations. Monitored by in-situIR, the reaction
rates were measured (Fig.1). A linear relationship was obtained
by plotting the initial rates vs [Pd(OAc) ], suggesting that the
reaction is first-order dependent on [Pd(OAc) ]. This indicated
that the rate-limiting step of the Pd-catalysed oxidative homo-
coupling of 1a might be involved in the catalytic cycle.
Then, the kinetic studies with different concentrations of 1a
and 3a were performed to confirm the rate-limiting step. A linear
line was obtained by plotting initial rates vs [1a], demonstrating
that this reaction exhibited a first-order kinetic behaviour on [1a]
step within a catalytic cycle which makes the rate constants for
transmetalation from a “live” catalytic process difficult to be
measured quantitatively and accurately. Hence, detailed
quantitative kinetic data of transmetalation in Pd-catalysed
Negishi-type reaction were still rare.
2
2
With Ni-catalysed oxidative coupling as a proper kinetic model,
our group has successfully revealed the transmetalation of
1
9
arylzinc with nickel catalyst, which offered an opportunity to
quantitatively acquire the kinetic data of transmetalation of
arylzinc from a live catalytic reaction. With this idea in mind, this
work reported
a
quantitative kinetic investigation of
transmetalation between arylzinc and [R-Pd-Ar] from Pd-
catalysed oxidative homo-coupling reactions.
The Pd-catalysed homo-coupling of ArZnCl was investigated
as the kinetic model reaction to reveal the quantitative
measurement of transmetalation, in which desyl chloride was
applied as the oxidant (Eq.1).
(
Fig.2). Meanwhile, initial rates were identical when the reactions
were carried out with different concentrations of 3a, which
indicated that the reaction was zero-order on [3a] (Fig.3). These
kinetic results revealed that the transmetalation step should be the
rate-limiting step and only [ArZnCl] was involved in the rate law
when the concentration of Pd catalyst was identical (Eq.2).
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[journal], [year], [vol], 00–00 |1

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rate = kobs×[ArZnCl] (Eq.2)
paths. If the reaction follows Path1, the transmetalation between
a and Pd-R would be the rate-limiting step, and the initial rate
1
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would vary by employing different oxidants (R-Cl). If Path 2 was
DOI: 10.1039/C3CC44894K
followed, the transmetalation between 1a and Pd-Cl would be the
35 rate-limiting step, and the reaction rate would not be affected by
different oxidants (R-Cl).
Consequently, the kinetic investigations of the homo-coupling
of 1a under different substituted oxidants (R-Cl) were then
1
2
8
4
0
carried out. When CF substituted oxidant (3b) was utilized, the
3
4
4
5
0
5
0
reaction displayed first order on arylzinc and zero order on
oxidant, suggesting that transmetalation is the rate limiting step
when 3b was the oxidant in Pd-catalyzed homocoupling of
arylzinc reagent (Figure S7-1). Same kinetic behavior was also
determined when Me substituted oxidant (3c) was employed. On
the basis of the above kinetic results, we then investigated the
reaction rate by using different oxidants under identical
conditions. As shown in Fig.4, when employing different
oxidants (3a, 3b, 3c), varied initial rates could be observed,
demonstrating that II-1 was involved in the rate-limiting step,
0.08
0.16
1a] (M)
Fig.2 Dependence of the initial rates on concentrations of 1a. Reaction
0.24
0.32
[
-2
condition: 2-chloro-1,2-diphenylethanone (3a) (5.0×10 M in THF, 0.3
mmol), p-MeC ZnCl (1a) (0.053 M–0.32 M in THF, 6.0 mL) ,
Pd(OAc) (3.3×10 M in THF), 30 C.
5
6 4
H
-5
o
2
1
which should be assigned to TM II in path 1.
1
4
2
0
8
6
1
1
Scheme 1 Pd-catalysed oxidative homo-coupling reaction
0.06
0.09
3a] (M)
0.12
0.15
[
0
.03
.02
Fig.3 Kinetic profiles of the homo-coupling of 1a under different
concentrations of 3a. Conditions: p-MeC ZnCl (1a) (0.31 M in THF,
4.0 mL), 2-chloro-1,2-diphenylethanone (3a) (0.050M–0.15 M in THF),
6
H
4
1
0
0
-
5
o
2
Pd(OAc) (3.3×10 M in THF), 10 C.
As shown in Scheme 1, there are two theoretical paths for this
reaction. For path 1, oxidative addition of RCl to Pd(0) affords
0.01
R: CF (3b)
3
[
R-Pd-Cl], the subsequent transmetalation between 1a and TM-I
H (3a)
Me (3c)
0
.00
1
2
2
3
5
0
5
0
furnishes the intermediate [Ar-Pd-R]. Then, the second
transmetalation between 1a and II-1 forms [Ar-Pd-Ar], and the
reductive elimination of [Ar-Pd-Ar] produces Ar-Ar. For path 2,
oxidative addition of RCl to Pd(0) affords [R-Pd-Cl], the
subsequent transmetalation between 1a and TM-I furnishes the
intermediate [Ar-Pd-Cl]. Then, the second transmetalation
between 1a and II-2 forms [Ar-Pd-Ar], and the reductive
elimination of [Ar-Pd-Ar] produces Ar-Ar.
0
1000
2000
3000
t (s)
Fig.4 Kinetic profiles of homo-coupling reaction of 1a under different
oxidants. Conditions: p-MeC ZnCl (1a) (0.27 M in THF, 4.0 mL),
oxidants (3a, 3b, 3c) (5.0×10 M in THF, 0.2 mmol), Pd(OAc)
5
5
6 4
H
-2
-5
2
(2.8×10
o
M in THF), 10 C.
1
We have confirmed that the transmetalation TM II is the rate-
limiting step, which provided an opportunity to quantitatively
measure the activation energy of this transmetalation step from
the Pd-catalysed oxidative homo-coupling. Then, the kinetic
investigations were carried out at different temperatures. Plotting
the ln(kobs/T) vs 1/T (Fig.5) gives a smooth linear relationship,
allowing the calculation of the activation energy for this
transformation. According to the Eyring Equation, the activation
From the data described above, this reaction exhibited a first-
order kinetic behaviour on [1a], suggesting that either TM-I or
TM-II was the rate-limiting step. According to the Scheme 1, the
two intermediates II-1 and II-2 resulting from TM-I would have
a phenyl anion as a δ donor, which would make them more
electronegative and slow down the second transmetalation step.
Thus, TM-II should be the rate-limiting step. Moreover, the
intermediates II-1 and II-2 are crucial in distinguishing the two
6
0
19
6
5
2
|Journal Name, [year], [vol], 00–00
This journal is © The Royal Society of Chemistry [year]

Page 3 of 3
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enthalpy was determined to be 12.3 kcal/mol.
Research Team in University (IRT1030) was also acknowledged.
In order to gain further insights into the substituent effects, we
investigated the reaction in the presence of different para–
substituted arylzinc reagents including p-MeOC H ZnCl, p-
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DOI: 10.1039/C3CC44894K
Notes and references
a
6
4
3
4
5
0
College of Chemistry and Molecular Sciences, Wuhan University, Wuhan,
5
MeC
6
H
4
ZnCl, PhZnCl, p-BrC
6
H
4
ZnCl and p-ClC
6
H
4
ZnCl. Initial
gave a linear
4
30072, P. R. China. E-mail: aiwenlei@whu.edu.cn.
b
rates have been obtained. Plotting the log(k/k
H
) vs σ
p
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of
Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu,
Shanghai, 200032, P. R. China.
† Electronic Supplementary Information (ESI) available: detailed
experimental procedures and kinetic parameters detected by a Mettler
Toledo ReactIR™ 15 spectrometer. See DOI:10.1039/b000000x/
free energy relationship with a ρ value of -2.37, suggesting that
electron-rich arylzinc reagents displayed higher reaction rates
than electron-deficient arylzinc reagents (Fig.6). The result
further supported that the transmetalation is the rate-limiting step.
1
0
1
.
L. Jin and A. Lei, Org. Biomol. Chem., 2012, 10, 6817-6825.
45 2. P. Espinet and A. M. Echavarren, Angew. Chem., Int. Ed., 2004, 43,
704-4734.
-
-
-
-
-
12
13
14
15
16
4
3. R. Alvarez, M. Perez, O. Nieto Faza and A. R. de Lera,
Organometallics, 2008, 27, 3378-3389.
4. A. L. Casado and P. Espinet, J. Am. Chem. Soc., 1998, 120, 8978-
8985.
k
50
5. A. Ricci, F. Angelucci, M. Bassetti and C. Lo Sterzo, J. Am. Chem.
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6. B. Crociani, S. Antonaroli, L. Canovese, P. Uguagliati and F.
Visentin, Eur. J. Inorg. Chem., 2004, 732-742.
0
.0032
0.0034
0.0036
0.0038
5
6
6
5
0
5
7. A. Ariafard, Z. Lin and I. J. S. Fairlamb, Organometallics, 2006, 25,
1
/T
Fig.5 Eyring plots for the homocoupling of p-MeC
conditions: 2-chloro-1,2-diphenylethanone (3a) (7.5×10 M in THF, 0.3
mmol), p-MeC H ZnCl (0.31 M in THF, 4.0 mL), Pd(OAc) (3.3×10 M
6 4 2
in THF).
5
788-5794.
6
4
H ZnCl (1a). Reaction
-2
8
.
A. Nova, G. Ujaque, F. Maseras, A. Lledos and P. Espinet, J. Am.
Chem. Soc., 2006, 128, 14571-14578.
-5
1
5
9. P. Nilsson, G. Puxty and O. F. Wendt, Organometallics, 2006, 25,
1285-1292.
1
1
0. M. H. Perez-Temprano, A. M. Gallego, J. A. Casares and P. Espinet,
Organometallics, 2011, 30, 611-617.
0
0
0
.6
.3
.0
1. A. L. Casado, P. Espinet and A. M. Gallego, J. Am. Chem. Soc., 2000,
122, 11771-11782.
MeO
Me
12. A. A. C. Braga, N. H. Morgon, G. Ujaque and F. Maseras, J. Am.
k
Chem. Soc., 2005, 127, 9298-9307.
H
k
13. B. P. Carrow and J. F. Hartwig, J. Am. Chem. Soc., 2011, 133, 2116-
-
0.3
0.6
2119.
Br
14. C. Amatore, A. Jutand and G. Le Duc, Chem.--Eur. J., 2011, 17,
-
Cl
70
2492-2503.
1
5. C. Amatore, A. Jutand and G. Le Duc, Angew. Chem., Int. Ed., 2012,
1, 1379-1382, S1379/1371-S1379/1374.
-0.30
-0.15
0.00
p
0.15
0.30
5
1
1
6. K. Matos and J. A. Soderquist, J. Org. Chem., 1998, 63, 461-470.
7. C. Sicre, A. A. C. Braga, F. Maseras and M. M. Cid, Tetrahedron,
2008, 64, 7437-7443.
Fig.6 Hammett plot for the homo-coupling reaction with different para-
substituted arylzinc reagents. Reaction conditions: 2-chloro-1,2-
-2
75
diphenylethanone (3a) (7.5×10 M in THF, 0.3 mmol), p-substituted
ArZnCl (MeO, Me, H, Br, Cl) (0.30 M in THF, 4.0 mL), Pd(OAc)
2
0
2
18. A. A. C. Braga, N. H. Morgon, G. Ujaque, A. Lledos and F. Maseras,
-5
o
(
2.8×10 M in THF), 10 C.
J. Organomet. Chem., 2006, 691, 4459-4466.
1
9. L. Jin, J. Xin, Z. Huang, J. He and A. Lei, J. Am. Chem. Soc., 2010,
32, 9607-9609.
In summary, the kinetic studies of palladium-catalysed
1
Negishi-type oxidative homo-coupling reaction of ArZnCl have
been quantitatively investigated. The in-situIR experiments
confirmed that the transmetalation between 1a and Pd-R is the
8
0
20. B. Fuentes, M. Garcia-Melchor, A. Lledos, F. Maseras, J. A. Casares,
G. Ujaque and P. Espinet, Chem.--Eur. J., 2010, 16, 8596-8599,
S8596/8591-S8596/8526.
2
5
≠
rate-limiting step. The corresponding activation enthalpy ∆H
(
12.3 kcal/mol) for this transmetalation is obtained quantitatively.
This work was supported by the 973 Program
21. J. A. Casares, P. Espinet, B. Fuentes and G. Salas, J. Am. Chem. Soc.,
2007, 129, 3508-3509.
(2012CB725302), the National Natural Science Foundation of 85 22. M. Garcia-Melchor, B. Fuentes, A. Lledos, J. A. Casares, G. Ujaque
3
0
China (21025206 and 21272180), and the China Postdoctoral
Science Foundation funded project (2012M521458). The support
from the Program for Changjiang Scholars and Innovative
and P. Espinet, J. Am. Chem. Soc., 2011, 133, 13519-13526.
This journal is © The Royal Society of Chemistry [year]
Journal Name, [year], [vol], 00–00 |
3