Transmetalation is the rate-limiting step: Quantitative kinetic investigation of nickel-catalyzed oxidative coupling of arylzinc reagents

Article abstract of DOI:10.1021/ja1045296

Transmetalation is the rate-limiting step! The transmetalation between arylzinc reagents and ArNi^IIR was confirmed as the rate-limiting step in the nickel-catalyzed oxidative coupling reactions. It was proved to be an excellent model allowing the first quantitative measurement of the kinetic rate constants of transmetalation from a live catalytic system. Rate constants from 0.04 to 0.31 M^-1 s^-1 were obtained for different arylzinc reagents under the conditions, and the activation enthalpy ΔH ^? was 14.6 kcal/mol for PhZnCl. The substituent effect on the transmetalation was also gained for the first time from the catalytic reaction.

Full text of DOI:10.1021/ja1045296

Published on Web 06/29/2010
Transmetalation is the Rate-Limiting Step: Quantitative Kinetic Investigation
of Nickel-Catalyzed Oxidative Coupling of Arylzinc Reagents
†
†
†,§
†
,†,‡
Liqun Jin, Jie Xin, Zhiliang Huang, Jun He, and Aiwen Lei*
College of Chemistry and Molecular Sciences, Wuhan UniVersity, Wuhan 430072, P. R. China, Department of
Chemistry, College of Science, Huazhong Agricultural UniVersity, Wuhan 430070, P. R. China, and State Key
Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
3
54 Fenglin Lu, Shanghai 200032, P. R. China
Received May 25, 2010; E-mail: aiwenlei@whu.edu.cn
Abstract: Transmetalation is the rate-limiting step! The trans-
II
metalation between arylzinc reagents and ArNi R was confirmed
as the rate-limiting step in the nickel-catalyzed oxidative coupling
reactions. It was proved to be an excellent model allowing the
first quantitative measurement of the kinetic rate constants of
transmetalation from a live catalytic system. Rate constants from
-
1
-1
0.04 to 0.31 M
s
were obtained for different arylzinc reagents
q
under the conditions, and the activation enthalpy ∆H was 14.6
kcal/mol for PhZnCl. The substituent effect on the transmetalation
was also gained for the first time from the catalytic reaction.
Transmetalation is one of the elementary reactions in organo-
metallic chemistry and involves an organometallic reagent R M as
2
Figure 1. Linear relationship between initial rate and arylzinc concentration.
a nucleophile to react with another metal intermediate. For example,
2
1
as shown in eq 1, the transmetalation of R M with XMcatR , which
appears in most cross-coupling reactions, results in another
intermediate, R McatR , and MX:
reaction of 1 was first-order in [1] and zeroth-order in [2a] (see
the Supporting Information), suggesting that the rate-limiting step
should be the transmetalation; this provided us the opportunity to
quantitatively investigate this step from the catalytic system.
The speculated pathways for the oxidative coupling of 1a,
2
1
1
0
including the oxidative addition of Ni with 2a, the consequent
For clarification regarding different organometallic reagents, a
number of named reactions (e.g., Negishi coupling, which involves
double transmetalations TM-I and TM-II, and the final reductive
elimination to obtain biphenyl (3a), are illustrated in Scheme 1.
2
RZnX) are prosperous in the cross-coupling field. Cross-coupling
reactions have already been extensively studied and widely applied
on both academic laboratory and industrial scales during the past
Scheme 1. Speculated Mechanism of the Model Reaction
3
three decades. However, only scarce efforts have been devoted to
kinetic investigations of transmetalation, especially for Negishi
4
coupling. Undoubtedly, gaining insights into a reaction is of benefit
to its application. Herein, we report the first quantitative measure-
ment of kinetic rate constants of transmetalations involving orga-
nozinc reagents from a “live” catalytic system.
In general, the transmetalation of organozinc reagents with
1
5
R McatX is considered to be a facile process. To quantitatively
and accurately measure the rate constants from a “live” catalytic
process, the precondition is that transmetalation should be the rate-
5
,6
limiting step.
However, to the best of our knowledge, few
examples of “traditional Negishi coupling reactions” in which the
4
c
transmetalation is the rate-limiting step have been reported.
The first-order kinetic dependence on [1a] indicated that either
TM-I or TM-II was the rate-determining step. The two intermedi-
ates II-1 and II-2 resulting from TM-I would have a phenyl anion
as a δ donor, which should make them more electronegative than
the intermediate I. Thus, one could reasonably deduce that TM-I
should be faster than TM-II. Thus, TM-II should be the rate-
limiting step.
Recently, we uncovered dramatic differences between “arylzinc”
reagents originating from ArMgCl and ArLi. When desyl chloride
2a) was used as the oxidant, the oxidative coupling of arylzinc 1
formed from ArLi was much slower than that of the one formed
from ArMgCl. As shown in Figure 1, the oxidative coupling
7
(
†
Wuhan University.
§
As described in Scheme 1, if the reaction proceeds along path
1, then TM1-II, the transmetalation between 1a and Ni-Cl, would
Huazhong Agricultural University.
‡
Shanghai Institute of Organic Chemistry.
10.1021/ja1045296  2010 American Chemical Society
J. AM. CHEM. SOC. 2010, 132, 9607–9609 9 9607

C O M M U N I C A T I O N S
be the rate-limiting step. This reaction rate would not be affected
if the oxidant RCl were varied. If the reaction proceeds along path
2
, then TM2-II, the transmetalation between 1a and R-Ni, would
be the rate-limiting step, and the reaction rate would vary if different
oxidants RCl were employed.
Therefore, we investigated the kinetic behaviors of the oxidative
coupling of 1a using the different oxidants 2a, 2b, 2c, and 2d
(
2
Figure 2). The completely different reaction rates shown in Figure
clearly revealed that the reaction proceeds along path 2 and TM2-
II is the rate-limiting step. In addition, we also obtained the
-1
quantitative rate constants. The rate constant for 2b was 0.13 M
-1
s , which was larger than that for 2a. The rate constant for 2c
was 0.064 M- s , which was smaller than that for 2a. In addition,
1 -1
the reaction employing the other oxidant 2d was the slowest, with
a rate constant of 0.021 M-
1
s
-1
8
.
Figure 4. (top) Kinetic profiles of different compounds 1 and (bottom)
the Hammett correlation plot.
difference at least discloses that the transmetalation between PhZnCl
1
a and [Ni-R] is much slower than the subsequent reductive
elimination.
We further investigated the transmetalation reactions using
different ArZnCl, all of which were prepared from the corre-
sponding ArLi using ZnCl
2
; the results are exhibited in Figure
4
. The rate constant of the transmetalations of p-MePhZnCl,
-
1
p-MeOPhZnCl, and p-ClPhZnCl were 0.18, 0.31, and 0.04 M
-
1
s , respectively. Plotting log(k/k
0
p
) versus σ for these substrates
Figure 2. Kinetic profiles of the transmetalation with different oxidants.
2
indeed gave a rather linear relation (correlation coefficient r )
0.99248), and the negative slope (-1.75) can be associated with a
developing positive charge in the transition state.
After it was confirmed that the transmetalation TM2-II is the
rate-limiting step, our model reaction provided an opportunity to
quantitatively measure the rate constant and the activation param-
eters. The kinetic investigation of the oxidative coupling of 1a was
carried out at different temperatures. As shown in Figure 3, the
perfect linear kinetic profiles at different reaction temperatures
further confirmed the first-order kinetic behavior of the reaction.
Plotting ln(k/T) versus 1/T also allowed us to calculate the activation
II
In conclusion, the transmetalation of ArZnCl with RNi Ar was
confirmed as the rate-limiting step in the oxidative coupling
reactions. It was proved to be an excellent model allowing the first
quantitative measurement of the kinetic rate constants of trans-
metalation from a live catalytic system. The activation enthalpy
q
∆H for transmetalation was obtained for the first time, and the
q
parameters, and the activation enthalpy ∆H was found to be 14.6
substituent effect on the transmetalation was also measured for the
first time from the catalytic reaction. These quantitative measure-
ments for the transmetalation of arylzinc reagents will provide
guiding significance in improving the selectivity of the cross-
coupling reactions in synthetic applications.
kcal/mol. Because TM2-II is the rate-limiting step, we could
q
assume that this ∆H value was for the transmetalation. According
q
to the kinetic investigation in our previous report, ∆H for the
5
reductive elimination of PhNiPh is 9.7 kcal/mol. The energy
Acknowledgment. This work was supported by the National
Natural Science Foundation of China (20702040, 20832003,
2
0972118).
Supporting Information Available: Experimental details and
kinetic data. This material is available free of charge via the Internet
at http://pubs.acs.org.
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