What is the rate of the Csp2-Csp2 reductive elimination step? Revealing an unusually fast Ni-catalyzed negishi-type oxidative coupling reaction

Article abstract of DOI:10.1021/ja903833u

(Graph Presented) For a direct quantitative investigation of the Csp ²-Csp² reductive elimination rate within a catalytic cycle, a novel oxidative coupling system in the presence of a Ni catalyst and desyl chloride as the oxidant is devised. The reaction progress profiles of arylzinc reagents exhibit zero-order kinetic behavior, and a reductive elimination step is confirmed as the ratedetermining step. This allows direct measurement of the Csp²-Csp² reductive elimination rate constant within a catalytic cycle. The rate constants of p-MePhZnCl are obtained in the range 0.23 to 3.5 s^-1 from 0 to -35°C, which are unusually fast reaction rates. According to the Arrhenius equation, the values of ΔH^? and ΔS^? (ΔH ^? = 9.7 kcal mol^-1, ΔS^? = 35 J mol^-1 K^-1) are obtained. The small value of ΔH^? reveals that the reductive elimination step of Csp²-Ni-Csp² is an extremely facile process.

Full text of DOI:10.1021/ja903833u

Published on Web 07/06/2009
What is the Rate of the Csp2-Csp2 Reductive Elimination Step? Revealing an
Unusually Fast Ni-Catalyzed Negishi-Type Oxidative Coupling Reaction
Liqun Jin,† Hua Zhang,† Peng Li,† John R. Sowa, Jr,‡ and Aiwen Lei*,†,§
College of Chemistry and Molecular Sciences, Wuhan UniVersity, Wuhan, 430072, P. R. China, Seton Hall
UniVersity, Department of Chemistry and Biochemistry, South Orange, New Jersey 07079, and State Key
Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
354 Fenglin Lu, Shanghai, 200032, P. R. China
Received May 12, 2009; E-mail: aiwenlei@whu.edu.cn
Although reductive elimination has been known for over 40 years
and is an essential step in coupling reactions,1-6 within the catalytic
cycle, there are very few quantitative kinetic studies of the Csp2-Csp2
reductive elimination.7,8 Investigation of stoichiometric reactions of
biaryl Ni, Pd, and Pt complexes reveals valuable insight into the
reductive elimination step.9-11 The rate constants of the reductive
elimination of Csp2-Pd-Csp2 and Csp2-Pt-Csp2 systems have been
measured to be in the range of 10-3 to 10-5 s-1.9,10 In sharp contrast,
catalytic reactions for Csp2-Csp2 couplings appear to be much faster,
as catalytic processes can occur at temperatures as low as -30 °C
which indicates a much lower energy activation barrier.12
Recently, we have been focusing on oxidative coupling reactions
and were inspired to investigate the kinetics of Csp2-Csp2 coupling
reactions (Scheme 1).18-20 With the proper choice of oxidant A-B
and organometallic reagents that rapidly undergo oxidative addition
and transmetalation, reductive elimination might become a rate-
determining step and, therefore, can be measured quantitatively. Herein,
we report our efforts in the kinetic measurement of the Csp2-Csp2
reductive elimination step in a catalytic sequence occurring through a
Ni-catalyzed Negishi-type oxidative coupling reaction.
The model system we have devised shown in eq 1 consisted of
desyl chloride (2-chloro-1,2-diphenylethanone) 2 as the A-B type
oxidant and aryl zinc 1. Our initial studies began with reactions
catalyzed by Pd(OAc)2 at 20 and 0 °C. As shown in Figure 1, plots
of [Ar-Ar] formation vs time gave straight lines which indicates
that the reaction rate is independent of [1] and [2]. Since
Ni-catalyzed coupling reactions are also known, we then investi-
gated the kinetics with our newly devised model employing
Ni(acac)2 as the catalyst. To our surprise, these reactions were so
fast that they went to completion within seconds at 20, 10, and
even 0 °C (Figure 1). Thus, we further lowered the reaction
temperature to -35 °C, so that we could obtain a significant number
of data points. At this temperature, the reaction was completed
within 6 min, and the kinetic plot was also a straight line. Again,
this clearly shows that the reaction rate is independent of [1] and
[2].8,21
Collman et al. in 1987 discussed that the rates of many reductive
elimination reactions are very difficult to obtain because they are
so exothermic and the corresponding oxidative addition is un-
known.13 In fact, until today, there are still few bis-aryl Ni and Pd
complexes that have been employed to study the reductive
elimination step.9-11,14 To obtain a quantitative measurement of
reductive elimination, stoichiometric systems have to be carefully
designed to provide meaningful data. For example, recently, the
corresponding Pt complexes have been successfully investigated.9
However, it is possible that these systems do not accurately reflect
the reductive elimination rate in the catalytic cycle.15
To gain an accurate measurement of the rate of Csp2-Csp2
reductive elimination within a catalytic reaction, it should be the
rate-determining step.8,16,17 In cross-coupling reactions, when aryl
chlorides or aryl bromides are utilized as electrophiles, oxidative
addition is usually the rate-determining step.5,16 Although aryl
iodides are known to react more rapidly, to our knowledge,
reductive elimination has not been shown to be rate-limiting with
these electrophiles. Thus, it is important to devise a new system
that allows quantitative investigation of reductive elimination rates
within the catalytic cycle.
Scheme 1. Proposed Mechanism for the Oxidative Coupling
Reaction
Figure 1. Reaction progress profiles for oxidative coupling reactions in
the presence of different catalyst systems at varied temperatures with in
situ IR.
† Wuhan University.
‡ Seton Hall University.
§ Chinese Academy of Sciences.
9
9892 J. AM. CHEM. SOC. 2009, 131, 9892–9893
10.1021/ja903833u CCC: $40.75  2009 American Chemical Society

C O M M U N I C A T I O N S
The kinetic profiles in both Pd- and Ni-catalyzed oxidative
coupling reactions show that the rates are independent of [1] and
[2]. This indicates a zero-order kinetic behavior. With the catalytic
cycle shown in Scheme 1, if either the oxidative addition or
transmetalation step is the rate-determining step, the reaction rate
will decrease as 1 or 2 is consumed, resulting in a first-order kinetic
curve. If the reductive elimination is the slow step, the reaction
rate will only depend on [Ar-Ni-Ar]. The rate will be independent
of [1] and [2] and will show a zero-order kinetic curve. Thus, data
in Figure 1 imply that the reductive elimination step in this oxidative
coupling reaction might be the rate-determining step.
To confirm that the reductive elimination is indeed a rate-limiting
step, it is necessary to perform the kinetic studies with different
initial [1] and [2] (see Supporting Information Figure S1). All
reactions exhibit zero-order kinetic plots and show identical rates.
The results do indicate that the rate of this oxidative coupling is
independent of [1] and [2] and that reductive elimination is the
rate-limiting step. It is also noteworthy that the catalytic reaction
is first-order in Ni(acac)2 (see Supporting Information Figure S2)
and the overlay of the same excess experiments suggests that
catalyst deactivation does not occur (see Supporting Information
Figure S1).22
Thus far, all evidence connects the zero-order kinetic behavior
with reductive elimination as the rate-limiting step. However,
another possibility exists. If the Ni species generated from the
reductive elimination of Ar-Ni-Ar is different from the Ni species
required for oxidative addition of 2, and the rate-determining step
is the transformation between these two species, then zero-order
kinetics will also be observed. We define this transformation as
the “black-box process”.23 To distinguish between the reductive
elimination as the rate-limiting step or the “black-box process”,
reactions of arylzinc reagents bearing different functionalities were
carried out (see Supporting Information Figure S3). The oxidative
coupling reactions of p-MeOPhZnCl and p-ClPhZnCl were carried
out at -10 °C in the presence of 0.2 mol % Ni(acac)2, and different
rates were observed (Table 1, entries 8 and 9). This excludes the
possibility of the “black-box process” as the rate-limiting step.
Hence, reductive elimination as the rate-determined step in this Ni-
catalyzed oxidative coupling is unambiguously confirmed.
s-1 at -35 °C to 3.5 s-1 at 0 °C, which is ∼3-4 orders of
magnitude greater than the reported values.9
For the Arrhenius parameters, plots of ln(k/T) vs 1/T (see
Supporting Information Figure S4) for the reaction of p-MePhZnCl
give a smooth linear relationship, allowing calculation of the
activation energy in the oxidative coupling reaction. According to
the Arrhenius equation, we obtain the values of ∆H‡ and ∆S‡ (∆H‡
) 9.7 kcal mol-1, ∆S‡ ) 35 J mol-1 K-1). In addition, the positive
∆S‡ value is consistent with reductive elimination as the rate-
limiting step.
The remarkable feature of our results is that the system uniquely
allows direct quantitative investigation of a Csp2-Csp2 reductive
elimination within a catalytic cycle. Even at -35 °C, the rate
constant of the reductive elimination of Csp2-Csp2 is 0.23 s-1
,
which is an unusually fast reaction rate. The value itself reveals
the facile nature of Csp2-Csp2 reductive elimination process.
The novel and reliable oxidative coupling model allows us to gain
an insight into the activation energy barrier and entropy of the
reductive elimination, which derived from a living catalytic cycle.
Moreover, it is also remarkable that this is a system without
phosphine or nitrogen based ligands, and the small value of ∆H‡
reveals that, for this particular reaction, fundamentally the reductive
elimination step is an extremely facile process.
Acknowledgment. This work was supported by the National
Natural Science Foundation of China (20702040, 20832003) and
the startup fund from Wuhan University.
Supporting Information Available: Experimental procedures and
compound characterization data. This material is available free of charge
via the Internet as http://pubs.acs.org.
References
(1) Singleton, D. M.; Kochi, J. K. J. Am. Chem. Soc. 1967, 89, 6547–6555.
(2) Tatsumi, K.; Hoffmann, R.; Yamamoto, A.; Stille, J. K. Bull. Chem. Soc.
Jpn. 1981, 54, 1857–1867.
(3) Brown, J. M.; Cooley, N. A. Chem. ReV. 1988, 88, 1031–1046.
(4) Ozawa, F. In Fundamentals of Molecular Catalysis; Kurosawa, H.,
Yamamoto, A., Eds.; Elsevier: New York, 2003; Vol. 3, pp 479-512.
(5) Espinet, P.; Echavarren, A. M. Angew. Chem., Int. Ed. 2004, 43, 4704–
4734.
(6) Hartwig, J. F. Inorg. Chem. 2007, 46, 1936–1947.
(7) Amatore, C.; Jutand, A. Organometallics 1988, 7, 2203–2214, and
references therein.
(8) Mathew, J. S.; Klussmann, M.; Iwamura, H.; Valera, F.; Futran, A.;
Emanuelsson, E. A. C.; Blackmond, D. G. J. Org. Chem. 2006, 71, 4711–
4722.
(9) Shekhar, S.; Hartwig, J. F. J. Am. Chem. Soc. 2004, 126, 13016–13027.
(10) Osakada, K.; Onodera, H.; Nishihara, Y. Organometallics 2005, 24, 190–
192.
(11) Koizumi, T.-A.; Yamazaki, A.; Yamamoto, T. Dalton Trans. 2008, 3949–
3952.
Table 1. Reductive Elimination Reaction Rate Constants of
a
Csp2-Ni-Csp2
(12) Martin, R.; Buchwald, S. L. J. Am. Chem. Soc. 2007, 129, 3844–3845.
(13) Collman, J. P.; Hegedus, L. S.; Norton, J. R.; Finke, R. G. Principles and
applications of organotransition metal chemistry; University Science Books:
Mill Valley, CA, 1987; p 323.
(14) Tsou, T. T.; Kochi, J. K. J. Am. Chem. Soc. 1979, 101, 7547–7560.
(15) Albeniz, A. C.; Espinet, P.; Martin-Ruiz, B. Chem.sEur. J. 2001, 7, 2481–
2489.
(16) Jordan, R. B. Organometallics 2007, 26, 4763–4770.
(17) Johnson, J. B.; Bercot, E. A.; Rowley, J. M.; Coates, G. W.; Rovis, T.
J. Am. Chem. Soc. 2007, 129, 2718–2725.
(18) Jin, L.; Zhao, Y.; Zhu, L.; Zhang, H.; Lei, A. AdV. Synth. Catal. 2009,
351, 630–634.
(19) Zhao, Y.; Jin, L.; Li, P.; Lei, A. J. Am. Chem. Soc. 2008, 130, 9429–9433.
(20) Zhao, Y.; Wang, H.; Hou, X.; Hu, Y.; Lei, A.; Zhang, H.; Zhu, L. J. Am.
Chem. Soc. 2006, 128, 15048–15049.
a For details of kinetic profiles, see Supporting Information.
(21) Zhang, H.; Luo, X.; Wongkhan, K.; Duan, H.; Li, Q.; Zhu, L.; Wang, J.;
Batsanov, A. S.; Howard, J. A. K.; Marder, T. B.; Lei, A. Chem.sEur. J.
2009, 15, 3823–3829.
Our model reaction provides an opportunity to quantitatively
determine the rate and the Arrhenius parameters for the Csp2-Csp2
reductive elimination step. In Table 1, we have explored the kinetics
of the reactions with different aryl zinc reagents and different
temperatures. All of the reactions exhibit zero-order kinetics, and
the rate constants for the reductive elimination range from 0.23
(22) Refer to the explanation of Donna Blackmond in J. Org. Chem. 2006, 71,
4711-4722.
(23) Because the black-box process does not involve substrates, if it is a rate-
limiting step, zero-order kinetics will be observed. In addition, the reaction
with different substrates will also occur at the same rate.
JA903833U
9
J. AM. CHEM. SOC. VOL. 131, NO. 29, 2009 9893