C-H bond activation at palladium(IV) centers

Article abstract of DOI:10.1021/ja2051099

This communication describes the first observation and study of C-H activation at a Pd^IV center. This transformation was achieved by designing model complexes in which the rate of reductive elimination is slowed relative to that of the desired C-H activation process. Remarkably, the C-H activation reaction can proceed under mild conditions and with complementary site selectivity to analogous transformations at Pd^II. These results provide a platform for incorporating this new reaction as a step in catalytic processes.

Full text of DOI:10.1021/ja2051099

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CꢀH Bond Activation at Palladium(IV) Centers
Joy M. Racowski, Nicholas D. Ball, and Melanie S. Sanford*
University of Michigan, Department of Chemistry, 930 North University Avenue, Ann Arbor, Michigan 48109, United States
S Supporting Information
b
provide a platform for incorporating this reaction as a step in new
catalytic processes.
ABSTRACT: This communication describes the first ob-
servation and study of CꢀH activation at a PdIV center. This
transformation was achieved by designing model complexes
in which the rate of reductive elimination is slowed relative
to that of the desired CꢀH activation process. Remarkably,
the CꢀH activation reaction can proceed under mild
conditions and with complementary site selectivity to
analogous transformations at PdII. These results provide a
platform for incorporating this new reaction as a step in
catalytic processes.
In order to observe and study CꢀH activation at PdIV, it is
critical to slow competing CꢀX bond-forming reductive elim-
ination (kRE) while increasing the relative rate of the desired
CꢀH activation process (kCꢀH) (Scheme 1). On the basis of
these considerations, we initiated investigations of oxidatively
induced CꢀH activation at complex 1 (Scheme 2). This PdII
starting material contains a rigid bidentate sp2 N-donor
ligand [2,20-bis(4-tert-butylbipyridine (dtbpy)] and a chloride.
Both of these ligands are known to slow reductive elimination
(kRE) from high valent Pd intermediates,11ꢀ13 often enabling
detection/isolation of PdIII or PdIV species.1,2,11ꢀ13 In addition,
the tethered aryl CꢀH bond could undergo sp2 CꢀH activa-
tion to afford a five-membered palladacycle. The intramolecular
ver the past decade, high oxidation state palladium catalysis
nature of this CꢀH cleavage event is expected to increase
10
O
has found increasingly diverse applications in organic
synthesis.1 The development of new transformations in this area
has been guided by fundamental studies of PdIII and PdIV model
complexes, which have provided key insights into the unique
reactivity and mechanisms accessible at high valent palladium
centers.1,2 To date, these model studies have focused primarily
on reductive elimination from PdIII and/or PdIV species.1,2 In
contrast, the possibility of other organometallic transformations
at high oxidation state Pd has not been explored in detail. This is
likely due to the assumption that reductive elimination occurs
much faster than competing reactions.
kCꢀH
.
We first examined the oxidation of 1 with PhICl2, since this
reagent is known to react with PdII starting materials to yield
Scheme 1. Competing Reductive Elimination versus CꢀH
Activation at PdIV
Very recently, several groups have proposed a new reaction,
CꢀH activation at a transient PdIV intermediate, as a key step in
catalysis.3ꢀ7 This novel mode of reactivity has been implicated in
four different catalytic contexts: (i) CꢀH oxidative coupling
reactions,3 (ii) the carboamination of olefins,4 (iii) the acetoxyla-
tion of allylic CꢀH bonds,5 and (iv) the CꢀH arylation of
naphthalene.6,7 Remarkably, many of these catalytic reactions
proceed under unusually mild conditions3ꢀ5 and/or exhibit
unprecedented site selectivities.3,4,6 These results suggest that
harnessing CꢀH activation at PdIV could provide opportunities
for achieving distinct and complementary reactivity relative to
analogous (and much more common) transformations at PdII
centers.
Scheme 2. Oxidation of 1 with PhICl2: Formation of 2 and 3
(N∼N = dtbpy)
While the reports described above have proposed CꢀH
activation at PdIV during catalysis, there is currently no literature
precedent for such a transformation. As such, we sought to design
model systems to demonstrate the viability of this reaction and to
probe reactivity and site selectivity in this context.8,9 This
communication demonstrates that, with the appropriate choice
of supporting ligands, CꢀH activation at a PdIV center can
proceed rapidly at room temperature. Furthermore, we show that
the site selectivity of this transformation can be dramatically
different from that at analogous PdII complexes. These results
Received: June 2, 2011
Published: October 21, 2011
r
2011 American Chemical Society
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Scheme 3. Low Temperature NMR Study of Reaction of 4
with d5-PhICl2
Table 1. Variation of Oxidant (N∼N = dtbpy)
Entry
Oxidant
X (Product)
Yield (%)
1
2
3
4
PhICl2
Cl (5-Cl)
77
73
nra
86
isolable PdIV products.13 As shown in Scheme 2, the reaction
produced two major inorganic compounds: PdIICl2(dtbpy)
(2, 83% yield) and complex 3 (16% yield). Both 2 and 3 are
PdII species rather than the desired PdIV products; however, 3 is
remarkable in that it contains a σ-aryl rather than a σ-alkyl ligand
bound to Pd. We hypothesized that 2 and 3 might be formed
from transient PdIV intermediate I, which could undergo com-
peting sp3-CꢀCl bond-forming reductive elimination (to liber-
ate 2) and CꢀH activation/sp3-CꢀCl bond formation to
generate 3. While these were promising initial results, complex
3 remained a minor side product under all conditions examined.
Additionally, efforts to observe putative PdIV intermediates I
and/or II were unsuccessful in this system.
PhI(TFA)2
PhI(OAc)2
NFTPT
TFA (5-TFA)
OAc (5-OAc)
OTf (5-OTf)
a No reaction observed after 12 h at 25 °C.
The results in Scheme 2 suggest that kRE is significantly faster
than kCꢀH for intermediate I. We reasoned that this problem
could be addressed by (1) replacing the chloride with an X-type
ligand that is less prone to reductive elimination and (2)
limiting the conformational flexibility of the tethered CꢀH
substrate. As such, we next targeted PdII(CF3)(2-PhC6H4)-
(dtbpy) (4) as our PdII starting material. The incorporation of
the CF3 ligand was a particularly important design feature, since
several recent reports have shown that PdIV(CF3)(Aryl) com-
plexes can be stable to reductive elimination at or above room
temperature.14 Complex 4 was prepared in 58% yield by the
reaction of PdII(I)(2-PhC6H4)(dtbpy) with CsF/TMSCF3
in THF.
Figure 1. ORTEP plot of 5-TFA.
1
1
15 aromatic protons, and a Hꢀ H COSY allowed assignment
of five distinct protons on the pendant phenyl ring.16 This indicates
that the ring is not yet cyclometalated (and also shows that rotation
aboutthe arylꢀaryl bond is slow on the NMR time scale). 19Fꢀ C
13
HBMC further confirmed that 8 contains a single σ-aryl ligand,
as the CF3 fluorines showed only one correlation with an aromatic
carbon. In contrast, two 19Fꢀ C HMBC correlations were
13
observed for the cyclometalated product 5-Cl. Finally, a DOSY
experiment showed that 5-Cl and 8 have nearly identical diffusion
coefficients at ꢀ15 °C, indicating that these complexes have similar
hydrodynamic radii. This is consistent with the formulation of 8asa
monomeric octahedral complex.
The treatment of 4 with 1 equiv of PhICl2 in MeCN at 25 °C
for 35 min resulted in a color change from pale yellow to dark
yellow along with the formation of products 5-Cl, 6, and 7 in 81%,
1
12%, and 11% yield as determined by H NMR spectroscopic
analysis of the crude reaction mixture (eq 1). Complex 5-Cl was
isolated in 77% yield by recrystallization from CH2Cl2/Et2O.
Characterization of 5-Cl by NMR spectroscopy, mass spectro-
metry, and X-ray crystallography (of a close analogue, vide infra)
revealed that this is an octahedral PdIV complex containing a
cyclometalated biphenyl ligand. This indicates that the desired
CꢀH activation event has occurred.
Mass spectrometry experiments provided further insights into
the molecular structure of 8. ESI-MS showed a peak at 631.1312,
which corresponds to the mass of [Pd(CF3)(2-PhC6H4)(Cl)-
(dtbpy)]+. Notably, electrospray ionization commonly results in
loss of one X-type ligand from PdIV complexes.2g For example,
ESI-MS of 5-Cl affords a peak at 595.1560, corresponding to the
mass of [5-ClꢀCl]+. MALDI, a softer ionization technique,
resulted in a peak at 667.1, which corresponds to [Pd(CF3)
(2-PhC6H4)(Cl)2(dtbpy)+H]+.
All of the NMR and MS data presented above are consistent
with formulation of intermediate 8 as a PdIV complex of general
structure PdIV(CF3)(2-PhC6H4)(Cl)2(dtbpy). The diamagnetic
nature of this complex clearly indicates that it is not a monomeric
PdIII species. The NMR diffusion experiment along with MALDI
MS data provide evidence against alternative formulations as a
PdIII dimer or a square planar PdII complex.17 Overall, the char-
acterization data are fully consistent with the CꢀH activation event
occurring at PdIV intermediate 8, thereby representing the first
demonstration that high oxidation state Pd can mediate this trans-
formation.
In order to gain insights into the mechanism of the CꢀH
activation process, we monitored the reaction of 4 with C6D5ICl2
1
at ꢀ30 °C in CD3CN (Scheme 3). H and 19F NMR analysis
showed fast consumption of starting material and the formation
of transient intermediate 8.15 Upon warming to RT, this inter-
mediate decayed over 35 min with first-order kinetics to form
mixture of 5-Cl and 6 (final ratio of 5-Cl:6 = 1.0:0.27 under these
conditions). Intermediate 8 shows resonances associated with
We next explored the reaction of 4 with other 2eꢀ oxidants.
While no reaction was observed with iodobenzene diacetate
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COMMUNICATION
Scheme 4. Site Selectivity of CꢀH Activation at PdIV
Figure 2, the X-ray structure confirms that 12-Cl (and by analogy
12-OTf) is the product of CꢀH activation at HA.
For comparison, we examined an analogous cyclopalladation
reaction at the PdII σ-DMB complex 14-F (eq 3), which was
generated in situ by the treatment of 14-I with AgF. Cyclopalla-
dation at 14-F was sluggish at room temperature and required
heating to 60 °C in benzene for 4 h to proceed to completion.
Furthermore, this reaction afforded >10:1 selectivity for activa-
tion of the less sterically hindered CꢀH bond (HA).21 This
selectivity is similar to that observed in numerous other cyclo-
palladation reactions at PdII centers but very different from that
observed in Scheme 4 (1.7:1).22 The significant difference in
both rate and selectivity for this CꢀH activation at PdII versus PdIV
highlights the dissimilarity of these processes and demonstrates the
potential value of PdIV-mediated CꢀH activation in catalysis.
Figure 2. ORTEP plot of 12-Cl.
In summary, this communication describes the first observa-
tion and study of CꢀH activation at PdIV. This transformation
was achieved by designing model complexes in which the rate of
reductive elimination is slowed relative to that of the desired
competing CꢀH activation process. Remarkably, the CꢀH
activation reaction can proceed under mild conditions and with
different site selectivity than analogous transformations at PdII.
Investigations are underway to elucidate the mechanism of CꢀH
activation at PdIV and to identify further intra- and intermole-
cular examples of this new reaction. We anticipate that such
studies will ultimately enable the rational incorporation of PdIV-
mediated CꢀH activation into Pd-catalyzed processes.
(PhI(OAc)2, Table 1, entry 3),2g both iodobenzene bistrifluor-
oacetate PhI(TFA)2 and N-fluoro-2,4,6-trimethylpyridinium tri-
flate (NFTPT)14 reacted with 4 within 10 min at RT to afford
cyclometalated PdIV complexes where X = trifluoroacetate and
triflate (5-TFA and 5-OTf, respectively). The structure of the
trifluoroacetate complex was confirmed by X-ray crystallography,
and an ORTEP picture of 5-TFA is shown in Figure 1. Con-
sistent with the solution NMR data, the crystal structure shows
an unsymmetrical ligand environment around the octahedral
PdIV center, with the trifluoroacetate group trans to one σ-aryl
ligand and the trifluoromethyl group trans to one N of the dtbpy
(Figure 1).
Substrate 9 was also examined in order to probe the accessi-
bility of a six-membered palladacycle (eq 2). In this case, reaction
with PhICl2 for 10 min at 25 °C returned the ortho-chlorinated
PdII product 10 in 95% yield. This result suggests that a six-
membered palladacycle was generated but that the resulting PdIV
intermediate underwent rapid CꢀCl bond-forming reductive
elimination under the reaction conditions.18
’ ASSOCIATED CONTENT
S
Supporting Information. Experimental details and spec-
b
troscopic and analytical data for new compounds. This material is
available free of charge via the Internet at http://pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
mssanfor@umich.edu
’ ACKNOWLEDGMENT
We thank the National Science Foundation (CHE-0545909) for
support of this work, and N.D.B. thanks the NIH (F31GM089141)
for a predoctoral fellowship. Dr. Antek Wong-Foy and Dr. Jeff
Kampf are gratefully acknowledged for X-ray crystallography, and
we acknowledge funding from NSF Grant CHE-0840456 for X-ray
instrumentation. We are also grateful to Dr. Eugenio Alavarado and
Ansis Maleckis, for assistance with NMR spectroscopic analysis,
and Dr. Dipa Kalyani and Ansis Maleckis, for ligand synthesis.
Finally, we conducted a series of experiments to compare this
CꢀH activation at PdIV to analogous transformations at PdII
centers. A σ-aryl ligand derived from 2-iodo-3,50-dimethyl-1,
10-biphenyl (ligand abbreviated σ-DMB) was used, since it
contains two sterically and electronically differentiated sites for
CꢀH activation (HA and HB). As shown in Scheme 4, the
treatment of σ-DMB complex 11 with NFTPT at RT in MeCN
produced a 1.7:1 mixture of two isomeric products 12-OTf and
13-OTf in 64% yield.19,20 While 12-OTf/13-OTf could not be
completely separated, the mixture was characterized using a
variety of two-dimensional NMR experiments (see Supporting
Information for details). In addition, treatment of 12-OTf/13-
OTf with NaCl afforded the corresponding chloride complexes
(12-Cl/13-Cl), and the structure of the major isomer was
definitively established by X-ray crystallography. As shown in
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COMMUNICATION
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Scheme 4.
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(15) When the reaction was conducted at ꢀ30 °C, the initial NMR
spectrum showed the presence of intermediate 8 along with some of the
CꢀH activation product 5-Cl (ratio 8:5-Cl = 3:1). The [8] did not
change over several hours at ꢀ30 °C, and this ratio remained constant
over that time. Conversion of 8 to a mixture of 5-Cl and 6 only occurred
when the mixture was warmed. These data suggest that the 5-Cl formed
initially in the ꢀ30 °C experiment is generated by a different, heretofore
undetected intermediate. See Supporting Information for a detailed
discussion.
(16) 1H NMR spectroscopic studies of the oxidation of 4-d5
(in which the pendant phenyl ring is deuterated) further confirmed
the assignment of the five aromatic protons of this ring in intermediate 8.
(17) A key remaining question is the stereochemistry about the
octahedral PdIV center in 8. We have conducted several experiments
to probe this, and they provide tentative support for the structure
shown in Scheme 3. See Supporting Information (p S21) for a detailed
discussion.
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