C-H bond activation by [{(Diimine)Pd(μ-OH)}2]2+ dimers: Mechanism-guided catalytic improvement

Article abstract of DOI:10.1002/anie.200804455

(Chemical Equation Presented) Clearly different: The mechanism of C-H activation by air- and water-tolerant complexes of the type [{(diimine)Pd(μ- OH)}₂]²⁺ (see scheme; Ar=tBu₂C ₆H₃, solv=MeOH or trifluoroethanol) and [(diimine)Pd(OH₂)₂]²⁺ has been investigated. Surprisingly, there are significant mechanistic differences in activation by the dimeric Pd complex and the analogous Pt species, with the Pd species found to be considerably more reactive.

Full text of DOI:10.1002/anie.200804455

Angewandte
Chemie
DOI: 10.1002/anie.200804455
À
C H Activation
2+
À
C H Bond Activation by [{(Diimine)Pd(m-OH)}2] Dimers:
Mechanism-Guided Catalytic Improvement**
John E. Bercaw,* Nilay Hazari, Jay A. Labinger,* and Paul F. Oblad
À
Practical methods for the selective functionalization of C H
bonds could have a significant environmental and economic
impact, in areas ranging from fuels and commodity chemicals
to pharmaceuticals.[1] Although there are now many tran-
À
sition-metal complexes that can activate C H bonds, most of
these compounds are unstable or inactive in the presence of
water or potential functionalized products, such as alcohols.
As water is usually a by-product of oxidative functionalization
(especially when using O2) and alcohols are often desirable
products, this incompatibility represents a large barrier to the
À
development of catalysts for the transformation of C H
bonds. To address this problem, several groups have reported
À
C H bond activation reactions using metal alkoxide and
hydroxy complexes which occur even in the presence of free
À
Scheme 1. Proposed mechanism for C H bond activation of cyclo-
hexene by 1a. Ar=3,5-tBu2C6H3.
alcohols and, in some cases, water.[2]
We recently reported that the air- and water-tolerant
dimeric hydroxy-bridged dimers [{(diimine)M(OH)}2]2+ (M =
Pt (1a), Pd (1b)), can effect not only stoichiometric activation
cant differences between the mechanisms of reactions involv-
ing 1b and 1a.
À
of a variety of C H bonds (subject to the requirement that a
multidentate ligand can be produced), but also the catalytic
conversion of cyclohexene into benzene, using dioxygen as
the terminal oxidant, when the metal is Pd.[3] The proposed
Whereas compound 2a, the proposed active species for
À
C H activation starting with dimeric 1a, has not been
1
isolated, and only characterized using H NMR spectrosco-
py,[3] we have previously isolated monomeric [(diimine)Pd-
(OH2)2]2+ (2b).[4] Although stoichiometric reactions of 2b
with cyclohexene do not yield clean products (presumably
because the h3-cyclohexenyl complex rapidly undergoes
further reaction[5]), stoichiometric reactions with indene
were shown to cleanly yield the h3-indenyl species 4b
[Eq. (1)].[3] This reaction was used for detailed mechanistic
studies.[6]
À
mechanism for C H bond activation of cyclohexene by Pt
involves initial acid-mediated conversion of dimeric [{(diim-
ine)Pt(OH)}2]2+ (1a) into monomeric [(diimine)Pt(OH2)2]2+
(2a), subsequent displacement of water by cyclohexene at a
comparable rate, and then fast conversion of the cyclohexene
adduct into an h3-cyclohexenyl species 3a, with concomitant
loss of H3O+ (Scheme 1). In dichloroethane (or a dichloro-
ethane/trifluoroethanol mixture) the dimeric complex 1a
reacts extremely slowly (or not at all) with C H bonds in the
Kinetics were monitored by 1H NMR spectroscopy under
the conditions shown in Equation (1), with varying indene
À
absence of acid, and kinetic data in the presence of acid are
consistent with consecutive (pseudo) first-order reactions,
with the first step being first order in HBF4 and the second
step being first order in cyclohexene. Surprisingly, the second
step is also first order in HBF4. We expected that the
À
palladium analogue would follow a similar pathway for C H
bond activation, but results presented herein indicate signifi-
concentration, and the results show that the reaction is first
order in Pd and indene.[7] The effect of adding acid to the
reaction described in Equation (1) was also tested by varying
the BF3 concentration (which reacts with cosolvent trifluoro-
ethanol (TFE) to generate H+). The data are consistent with a
two-term rate law, in which one component is zero order in
BF3 and the other component is first order in BF3.[7] Chemi-
cally, these data could be explained by parallel steps for the
displacement of coordinated water by indene, one acid-
assisted and the other not. The acid dependence is analogous
to that for the reaction of 2a with cyclohexene,[3] and suggests
that general acid catalysis assists in the displacement of
[*] J. E. Bercaw, N. Hazari, J. A. Labinger, P. F. Oblad
Arnold and Mabel Beckman Laboratories of Chemical Synthesis,
California Institute of Technology
Pasadena, CA 91125 (USA)
E-mail: bercaw@caltech.edu
jal@caltech.edu
[**] This work was supported by BP through the MC2 program, and
Caltech through a Switzer fellowship to P.F.O. We thank Larry
Henling and Michael Day for assistance with crystallography.
Supporting information for this article (Experimental details,
kinetics analyses, and X-ray information for 1b and 2b) is available
on the WWW under http://dx.doi.org/10.1002/anie.200804455.
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Communications
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coordinated water by indene, as a result of weakening the Pd
À
OH2 or Pt OH2 bond; a similar effect has been reported in
related systems.[8] Thus, under acidic conditions, both 2a and
À
2b effect C H activation by the same pathway: rate-limiting
À
coordination of substrate followed by rapid C H activation.
The reaction of 2b with indene is not inhibited by water,
indicating that substitution of coordinated water by indene is
associative. On the other hand, addition of greater than
50 equivalents of water causes an increase in the rate.[7]
Analysis of the 1H NMR spectrum (in the absence of
indene) reveals that, as the quantity of free water is increased,
resonances corresponding to the hydroxy-bridged dimer 1b
are detected along with those of 2b. Thus, at high concen-
trations, it appears that water is a sufficiently strong base to
deprotonate 2b and establish an equilibrium between 1b and
2b. When such a solution is treated with indene, the
resonances for 1b disappear significantly faster than those
for 2b, as resonance peaks corresponding to the indenyl
species 4b emerge. These results imply that there is a direct
Figure 1. Graph of ([4b]endÀ[4b])0.5 against time during the reaction of
1b with 40 equivalents of indene in CH2Cl2/TFE (5.5:1 mixture,
675 equivalents of TFE). [4b]end =final concentration of product 4b.[7]
À
pathway for C H activation with 1b that does not involve 2b
as an intermediate, in contrast to the platinum analogue 1a.
Addition of stronger bases, such as 2,6-lutidine, triethyl-
amine, or 1,8-bis(dimethylamino)naphthalene, to solutions of
2b results in rapid and complete deprotonation to 1b.[7] When
these deprotonation reactions were attempted on a prepara-
tive scale, the protonated amine could not be cleanly
separated from the product. However, the use of a solid-
supported base, polystyrene-bound diethylamine, allowed the
isolation of pure 1b in 85% yield [Eq. (2)],[7] representing a
significant improvement on the previous method.[3,4]
À
Scheme 2. Proposed mechanism for palladium-catalyzed C H bond
activation of indene by 1b. Ar=3,5-tBu2C6H3, solv=MeOH or TFE.
À
coordinated solvent by indene, and finally by fast C H
activation. The rate-determining step, indicated by the
detected first-order indene-concentration dependence and
also the absence of a detectable p-bound indene intermediate,
also explains why the reaction is faster for 1b than for
dications 2a and 2b, as water is probably more tightly bound
to the dicationic center in the latter, thus slowing displace-
ment, whereas TFE or methanol bound to the monocationic
monomer generated from 1b would be more readily dis-
placed.[10]
A solution of 1b in CH2Cl2 reacted with indene to form 4b
even at room temperature, albeit very slowly (t1/2 ꢀ 3 days).
Addition of a small amount of TFE or MeOH (typically a 6:1
ratio of CH2Cl2 to the alcohol) results in a dramatic increase
in rate (t1/2 ꢀ 5 min). A smaller increase in rate is obtained by
adding THF, pentafluoropyridine, or even water (t1/2 ꢀ 1 day),
but those reactions give lower yields and more impurities. In
contrast, 1a, 2a, and 2b all require elevated temperatures to
react with indene at an appreciable rate.
The kinetic isotope effect (KIE) for the conversion of
1,1,3-trideuteroindene[11] into the deuterated indenyl complex
[D2]-4b was determined by comparing rate constants for
parallel reactions, which reveals a value of kH/kD = 1.6(1).
This value is slightly larger than expected for rate-determin-
ing p coordination of indene (kH/kD ꢀ 1) but significantly
The kinetics for the reaction of 1b with varying concen-
trations of indene and TFE (or MeOH, when it was used as
1
additive) were determined using both H NMR and UV/Vis
À
spectroscopy. The results reveal half-order dependence on Pd
concentration (Figure 1) and first-order dependence on both
indene and TFE (or MeOH) concentrations.[7] These findings
are consistent with the mechanism shown in Scheme 2,
consisting of an equilibrium involving the fast, solvent-
assisted separation of 1b into two monocationic monomers[9]
(which explains both the half-order Pd-concentration depend-
ence and the substantial increase in rate when TFE or MeOH
is added), followed by the rate-determining displacement of
lower than would be expected for rate-determining C H
activation (kH/kD ꢀ 3.5–6). Previously, we have tentatively
postulated that KIE values of around 2 (detected for similar
À
C H activation reactions with other {Pt(diimine)} systems)
À
indicate that neither coordination of the substrate nor C H
activation is completely rate-determining, and the measured
KIE reflects both steps.[12] That possibility cannot be dis-
À
counted in this case, although it is clear that C H activation is
not entirely rate determining.
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At this stage, the exact reasons for the differences in
reactivity between 1a and 1b are unclear. The proposed
mechanism implies that the hydroxy bridges are more readily
broken by solvent for 1b than for 1a, although 1b seems to be
less basic than 1a (Keq ꢀ 1000mÀ1 for the reaction of 1b with
HBF4 (3.62 equiv) at room temperature to form 2b, whereas
the corresponding reaction with 1a results in complete
conversion into 2a).[7] Conversely, the reaction between acid
and 1a takes almost 3 days to go to completion, whereas the
corresponding reaction with 1b equilibrates in 10 minutes,
suggesting that the kinetic barrier to breaking apart 1a is
considerably greater than that for 1b. After 1a and 1b have
been protonated, the reactivities of the resulting Pt and Pd
complexes 2a and 2b are more similar: the two complexes
[1] a) R. H. Crabtree, J. Chem. Soc. Dalton Trans. 2001, 2437;
b) J. A. Labinger, J. E. Bercaw, Nature 2002, 417, 507; c) U. Fekl,
K. I. Goldberg, Adv. Inorg. Chem. 2003, 54, 259.
[2] a) W. J. I. Tenn, K. J. H. Young, G. Bhalla, J. Oxgaard, W. A.
Goddard, R. A. Periana, J. Am. Chem. Soc. 2005, 127, 14172;
b) Y. Feng, M. Lail, K. A. Barakat, T. R. Cundari, T. B. Gunnoe,
J. L. Petersen, J. Am. Chem. Soc. 2005, 127, 14174; c) S. K.
Hanson, D. M. Heinekey, K. I. Goldberg, Organometallics 2008,
27, 1454.
[3] T. J. Williams, A. J. M. Caffyn, N. Hazari, P. F. Oblad, J. A.
Labinger, J. E. Bercaw, J. Am. Chem. Soc. 2008, 130, 2418.
[4] L. J. Ackerman, J. P. Sadighi, D. M. Kurtz, J. A. Labinger, J. E.
Bercaw, Organometallics 2003, 22, 3884.
[5] Previous studies have shown that 2b is able to catalytically
convert cyclohexene into benzene under an atmosphere of O2.[3]
We believe that, in stoichiometric reactions, an h3-cyclohexenyl
species is initially formed, but is unstable and decomposes to
give palladium(0) and organic by-products, such as 1,3-cyclo-
hexadiene.
[6] To exclude the possibility that the difference in behavior is due
to changing the organic substrate rather than the metal, some
kinetic studies were carried out for the reaction of [{(diimine)Pt-
(m-OH)}2]2+ (1a) and indene in the presence of acid.[7] The
À
activate C H bonds by the same pathway and at comparable
rates.
These conclusions—that the hydroxy-bridged dimer 1b is
the most reactive species in the Pd system, considerably more
À
reactive than either 2a or 2b towards C H bond activation,
and that there is an important solvent-assisted component in
the rate law—suggest a way to substantially improve the
catalytic conversion of cyclohexene into benzene [Eq. (3)].
Our previous studies involved 2b (or mixtures of 1b and 2b)
in the noncoordinating solvent dichloroethane. In a typical
experiment, after 24 h under 1 atm of O2 with 5 mol% of 2b
as the catalyst, 8% of the cyclohexene had been converted
into benzene; furthermore, there was an initiation period
before any reaction occurred, and competing disproportiona-
tion of cyclohexene to benzene and cyclohexane was a major
side reaction.[3] In contrast, under the same conditions but
using only 1 mol% of pure 1b as the catalyst and TFE as
solvent, conversion was 25% after 24 h, with no induction
period or competing isomerization.[7]
À
mechanism of C H activation appears to be completely the
same as that for reactions between 1a and cyclohexene.[3]
[7] Experimental details and more extensive discussion are pro-
vided in the Supporting Information.
[8] a) G. Annibale, P. Bergamini, V. Bertolasi, M. Bortoluzzi, M.
Cattabriga, B. Pitteri, Eur. J. Inorg. Chem. 2007, 5743; b) M.
Bortoluzzi, G. Annibale, G. Paolucci, B. Pitteri, Polyhedron
2008, 27, 1497.
[9] Consistent with this proposal it has been demonstrated that
reaction of 1a with PEt3 results in the formation of
[(diimine)Pt(OH)(PEt3)]+. Similarly, reaction of 1b with
MeCN or DMSO results in the formation of new complexes
1
which contain resonances in the H NMR spectrum consistent
with species of the type [(diimine)Pd(OH)(MeCN)]+ or
[(diimine)Pd(OH)(dmso)]+, respectively; both of these Pd
species activate indene to form 4b (see the Supporting
Information for more details). Furthermore, half-order depend-
ence on Pd concentration has been detected in the
[(neocuproine)Pd(OAc)2]-catalyzed aerobic oxidation of alco-
hols, for which a hydroxy-bridged dimeric palladium complex
was proposed to be the active species. See I. W. C. E. Arends, G.
ten Brink, R. A. Sheldon, J. Mol. Catal. A: Chem. 2006, 251, 246.
Such optimization of catalytic reactions by means of
mechanistic understanding is a major goal of fundamental
research in homogeneous catalysis, which we hope to
continue to exploit in our further studies aimed at utilizing
À
[10] For a discussion on the effect of charge in C H activation by
dicationic platinum(II) complexes see: T. G. Driver, T. J. Wil-
liams, J. A. Labinger, J. E. Bercaw, Organometallics 2007, 26,
294.
À
1b and related species for catalytic C H activation.
[11] For the synthesis of 1,1,3-trideuteroindene, see M. Yasuda, C.
Pak, H. Sakurai, Bull. Chem. Soc. Jpn. 1980, 53, 502.
[12] H. A. Zhong, J. A. Labinger, J. E. Bercaw, J. Am. Chem. Soc.
2002, 124, 1378.
Received: September 10, 2008
Published online: November 12, 2008
À
Keywords: C H activation · homogeneous catalysis · kinetics ·
oxidation · palladium
.
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