Bimetallic palladium catalysis: Direct observation of Pd(III)-Pd(III) intermediates

Article abstract of DOI:10.1021/ja906935c

(Chemical Equation Presented) PhI(OAc)₂ is a common oxidant for Pd-catalyzed C-H bond functionalizations. Mechanistic hypotheses since the 1960s have suggested a Pd(II)/Pd(IV) mechanism. Here we present evidence for the relevance of bimetallic Pd(III) complexes to catalysis. A bimetallic Pd(III) acetate was isolated and can afford product by bimetallic reductive elimination.

Full text of DOI:10.1021/ja906935c

Published on Web 11/09/2009
Bimetallic Palladium Catalysis: Direct Observation of Pd(III)-Pd(III)
Intermediates
David C. Powers, Matthias A. L. Geibel, Johannes E. M. N. Klein, and Tobias Ritter*
Department of Chemistry and Chemical Biology, HarVard UniVersity, 12 Oxford Street,
Cambridge, Massachusetts 02138
Received August 18, 2009; E-mail: ritter@chemistry.harvard.edu
Scheme 1. Discrete Bimetallic Pd(III) Intermediate in Acetoxylation
Pd(II)/Pd(IV) redox cycles have been proposed for a variety of
palladium-catalyzed transformations since 1971.1,2 In 2009, bime-
tallic Pd(III) intermediates were put forth as a mechanistic alterna-
tive to the frequently invoked Pd(II)/Pd(IV) redox cycles.3 Our
account disclosed previously unrecognized reactions from organo-
metallic Pd(III) complexes but did not provide evidence for the
generality of bimetallic Pd(III) intermediates in catalysis. Here we
report the first direct observation of bimetallic Pd(III) complexes
in C-H acetoxylation reactions. The Pd(III) intermediates were
obtained by oxidation of Pd(II) catalysts with PhI(OAc)2, one of
the most common oxidants for oxidative palladium catalysis. Our
results demonstrate that bimetallic Pd(III) complexes should be
considered as relevant reaction intermediates in a class of Pd-
catalyzed reactions previously suggested to proceed via Pd(II)/
Pd(IV) redox cycles.2
Pd-catalyzed aromatic C-H acetoxylation was first reported in
1966.4 In acetic acid, oxidants such as K2Cr2O7, Pb(OAc)4, and
N2O2 oxidize benzene to phenyl acetate under Pd catalysis.5 Stock
proposed a Pd(II)/Pd(IV) mechanism for this class of reactions in
1981.6 Crabtree reported the first Pd(OAc)2-catalyzed acetoxylation
of arenes with the terminal oxidant PhI(OAc)2 (eq 1):7
sensitive bimetallic Pd(III) complex 3 was observed and could be
isolated in 88% yield. Complex 3 is stable in solution and in the
solid state below -10 °C and was characterized crystallographically
(Figure 1).
Bimetallic 3 is not the catalyst resting state and cannot be
observed during catalysis. However, we observed the formation
and reaction of 3 under pseudocatalytic conditions by sequential
addition of reagents at controlled temperatures. We treated
Pd(OAc)2 with excess substrate 1 and observed the dimer 2 in
the presence of 5 equiv of 1.15 Subsequent addition of 5 equiv
of PhI(OAc)2 at -10 °C afforded the Pd(III) dimer 3 in 66%
yield.16 When the purified intermediate 3 in the presence of 20
equiv of substrate 1 was warmed to 40 °C, bimetallic reductive
elimination occurred, affording product 4 in 91% yield. Reduc-
tive elimination from 3 in the absence of 1 afforded product 4
in only 6% yield. Likewise, the Pd(OAc)2-catalyzed reaction 1
f 4 with 100 mol % Pd did not afford 4 upon heating at 80 °C
for 12 h. Both results suggest the consumption of product 4 by
Pd after reductive elimination.17
Since 2004, Sanford8 and Yu9 have pioneered practical, directed
C-H acetoxylation reactions that also employ Pd(OAc)2 as the
catalyst. Reductive elimination from well-defined Pd(IV) com-
plexes, shown for C-C bond formation by Canty10 and for C-O
bond formation by Sanford,11 has been observed. However, the
relevance of Pd(IV) complexes to Pd-catalyzed acetoxylation
has not been established.
While several bimetallic complexes of Pt(III) have been re-
ported,12 only a few organometallic Pd(III) complexes have been
described: five paddlewheel complexes by Cotton and Lahuerta13
and five carboxylate-bridged bimetallic complexes by us.3 We have
shown that reductive elimination from bimetallic Pd(III) complexes
can form carbon-heteroatom bonds and implicated bimetallic
palladium complexes in catalysis through kinetic analysis. However,
when oxidants such as NCS were employed, the proposed bimetallic
Pd(III) complexes were not observed during catalysis. To evaluate
the potential generality of bimetallic Pd(III) complexes as inter-
mediates in catalysis, we studied the oxidation of Pd(II) catalysts
with PhI(OAc)2, one of the most common oxidants for Pd-catalyzed
C-H bond functionalizations.2
After reductive elimination from 3 in the presence of 1, the
bimetallic Pd(II) complex 2 was observed by 1H NMR spectroscopy.
Cyclopalladation (first reported by Cope in 196514) of 2-phe-
nylpyridine (1) with Pd(OAc)2 afforded the bimetallic Pd(II)
complex 2, in which the two palladium nuclei are held in proximity
by bridging acetate ligands (Scheme 1). When bimetallic Pd(II)
complex 2 was treated with PhI(OAc)2 at -35 °C, the thermally
Figure 1. ORTEP diagram of Pd(III) 3 with ellipsoids drawn at the 50%
probability level; kinetic competence of 3 and incompetence of 5.
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17050 J. AM. CHEM. SOC. 2009, 131, 17050–17051
10.1021/ja906935c  2009 American Chemical Society

C O M M U N I C A T I O N S
6-d5 (eq 2; see the Supporting Information):
Reductive elimination by first-order kinetics in bimetallic Pd(III)
complex was established by following product formation from a
methylated analogue of 3 for accurate 1H NMR integration. All of
the reactions shown in Scheme 1 can be carried out in CH2Cl2,
AcOH, or a mixture thereof. The isolation of 3, however, required
addition of CH2Cl2 because 3 was not stable at the freezing point
of AcOH (17 °C) or above. Observation of both oxidation of 2
with PhI(OAc)2 and reductive elimination from 3 to 4 is consistent
with the participation of bimetallic Pd(III) intermediates in the Pd-
catalyzed C-H functionalization of arenes with the oxidant
PhI(OAc)2.
Rate-determining cyclometalation precludes the kinetic implication of
bimetallic Pd complexes during oxidation and reductive elimination;
however, bimetallic palladium complexes were implicated in the rate-
determining step of related C-H oxidations with weaker oxidants than
PhI(OAc)2, in which case cyclopalladation is not rate-determining.3,19
In conclusion, our report discloses the first evidence of bimetallic
Pd(III) intermediates in Pd-catalyzed acetoxylation. On the basis of
this evidence and our previous kinetic implication of a bimetallic Pd
complex in the rate-determining step of C-H functionalization with
NCS, we propose that bimetallic Pd(III) complexes are responsible
for a large class of C-H oxidations previously proposed to proceed
via Pd(II)/Pd(IV) redox cycles.
Discrete monometallic Pd(IV) complexes such as 5 (Figure
1) have been considered as models for the high-valent palladium
complexes from which C-O reductive elimination could occur
during catalysis.11b We measured the initial rate of the reaction
from 1 to 4 (shown on the left of Scheme 1) catalyzed by 8 mol
% Pd(OAc)2, 8 mol % monometallic Pd(IV) complex 5, or 4
mol % bimetallic Pd(III) complex 3. The initial rate of product
formation with catalyst 5 was half as fast as the initial rate with
Pd(OAc)2 as the catalyst. Therefore, the Pd(IV) complex 5 is
not kinetically competent for catalysis. The initial rate of product
formation with bimetallic Pd(III) complex 3 is higher than the
rate observed with Pd(OAc)2, which demonstrates that 3 is
kinetically competent for catalysis. The observation and kinetic
competence of 3, as well as the kinetic incompetence of 5, cannot
exclude the potential transient intermediacy of Pd(IV) complexes
other than 5. For example, our data cannot rule out the formation
and relevance to catalysis of monoaryl Pd(IV) complexes.
Kinetic analysis under conditions of catalysis, the isolation
of both 2 and 3, and the independent observation of all three
fundamental reactionssbimetallic oxidative addition, bimetallic
reductive elimination, and cyclometalationsare consistent with
the proposed catalytic cycle shown in Figure 2. Measurement
of the initial rate of acetoxylation as a function of PhI(OAc)2
concentration showed a zeroth-order kinetic dependence with
respect to oxidant, which precludes rate-determining oxidation.
Observation of an intramolecular primary kinetic isotope effect
of kH/kD ) 5.1 and an intermolecular primary isotope effect of
kH/kD ) 5.0 is consistent with rate-determining cyclopallada-
tion.18 The isotope effects were determined by acetoxylation of
substrate 6-d and by competing acetoxylation between 6 and
Acknowledgment. We thank Peter Mu¨ller for X-ray crystal-
lographic analysis and Sanofi-Aventis for a graduate fellowship for
D.C.P.
Supporting Information Available: Detailed experimental proce-
dures, spectroscopic data for all new compounds, and crystallographic data
for 3 (CIF). This material is available free of charge via the Internet at
http://pubs.acs.org.
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Figure 2. Proposed bimetallic Pd(II)/Pd(III) catalytic cycle.
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