Detailed study of C-O and C-C bond-forming reductive elimination from stable C2N2O2-ligated palladium(IV) complexes

Article abstract of DOI:10.1021/ja9014474

This paper describes the synthesis of a series of Pd^IV complexes of general structure (N-C)₂Pd^IV(O₂CR) ₂ (N-C ) a rigid cyclometalated ligand; O₂CR) carboxylate) by reaction of (N-C)_2<

Full text of DOI:10.1021/ja9014474

Published on Web 05/21/2009
Detailed Study of C-O and C-C Bond-Forming Reductive
Elimination from Stable C2N2O2-Ligated Palladium(IV)
Complexes
Joy M. Racowski, Allison R. Dick, and Melanie S. Sanford*
Department of Chemistry, UniVersity of Michigan, 930 North UniVersity AVenue,
Ann Arbor, Michigan 48109
Received February 24, 2009; E-mail: mssanfor@umich.edu
Abstract: This paper describes the synthesis of a series of PdIV complexes of general structure
(N∼C)2PdIV(O2CR)2 (N∼C ) a rigid cyclometalated ligand; O2CR ) carboxylate) by reaction of (N∼C)2PdII
with PhI(O2CR)2. The majority of these complexes undergo clean C-O bond-forming reductive elimination,
and the mechanism of this process has been investigated. A variety of experiments, including Hammett
plots, Eyring analysis, crossover studies, and investigations of the influence of solvent and additives, suggest
that C-O bond-forming reductive elimination proceeds via initial carboxylate dissociation followed by C-O
coupling from a 5-coordinate cationic PdIV intermediate. The mechanism of competing C-C bond-forming
reductive elimination from these complexes has also been investigated and is proposed to involve direct
reductive elimination from the octahedral PdIV centers.
Studies of C-O bond formation at PdIV have proven
Introduction
challenging for two major reasons. First, there are relatively
few examples of isolable PdIV complexes containing oxygen
donor ligands.8,9 Second, the available complexes are typically
stabilized by the presence of multiple σ-alkyl and/or aryl ligands.
As a result, investigations of C-O bond-forming reductive
elimination have been hampered by competing C-C coupling
processes.8,9 Hence, we sought to design a new model system
that would allow for systematic mechanistic investigations of
C-O bond-forming reductive elimination from PdIV centers.
We reasoned that PdIV complexes of general structure
(N∼C)2PdIV(O2CR)2 (B) (N∼C ) a rigid cyclometalated ligand)
might serve as attractive models for A on the basis of several
key design features (Scheme 2). First, the N∼C ligands were
selected to stabilize the desired PdIV species, due to their rigid,
bidentate structures8–10 and the fact that they contribute two
electron-donating σ-aryl ligands to the high oxidation state Pd
Our group has recently reported a Pd-catalyzed reaction for
the ligand-directed acetoxylation of carbon-hydrogen bonds
using PhI(OAc)2 as the terminal oxidant (Scheme 1).1-3 The
key carbon-oxygen coupling step of this transformation was
proposed to involve C-O bond-forming reductive elimination
from a rare, high oxidation state PdIV species of general structure
A.1,4 While analogous C-O bond-forming reductive elimination
reactions from NiIII,5 PdII,6 and PtIV 7 centers have been studied
extensively, detailed investigation of such reactions at PdIV
complexes has thus far remained elusive.8,9
(1) For directed C–H bond acetoxylation with ArI(OAc)2, see: (a) Dick,
A. R.; Hull, K. L.; Sanford, M. S. J. Am. Chem. Soc. 2004, 126, 2300.
(b) Desai, L. V.; Hull, K. L.; Sanford, M. S. J. Am. Chem. Soc. 2004,
126, 9542. (c) Kalyani, D.; Sanford, M. S. Org. Lett. 2005, 7, 4149.
(d) Kalberer, E. W.; Whitfield, S. R.; Sanford, M. S. J. Mol. Catal.,
A 2006, 251, 108. (e) Desai, L. V.; Stowers, K. J.; Sanford, M. S.
J. Am. Chem. Soc. 2008, 130, 13285.
(2) For examples of directed C–H bond acetoxylation with other oxidants,
see: (a) Giri, R.; Liang, J.; Lei, J. G.; Li, J. J.; Wang, D. H.; Chen,
X.; Naggar, I. C.; Guo, C.; Foxman, B. M.; Yu, J. Q. Angew. Chem.,
Int. Ed. 2005, 44, 7420. (b) Desai, L. V.; Malik, H. A.; Sanford, M. S.
Org. Lett. 2006, 8, 1141. (c) Reddy, B. V. S.; Reddy, L. R.; Corey,
E. J. Org. Lett. 2006, 8, 3391. (d) Wang, G. W.; Yuan, T. T.; Wu,
X. L. J. Org. Chem. 2008, 73, 4717.
(6) (a) Komiya, S.; Akai, Y.; Yamamoto, T.; Yamamoto, A. Organome-
tallics 1985, 4, 1130. (b) Mann, G.; Hartwig, J. F. J. Am. Chem. Soc.
1996, 118, 13109. (c) Widenhoefer, R. A.; Zhong, H. A.; Buchwald,
S. L. J. Am. Chem. Soc. 1997, 119, 6787. (d) Widenhoefer, R. A.;
Buchwald, S. L. J. Am. Chem. Soc. 1998, 120, 6504. (e) Mann, G.;
Incarvito, A. L.; Rheingold, A. L.; Hartwig, J. F. J. Am. Chem. Soc.
1999, 121, 3224. (f) Shelby, Q.; Katoaka, N.; Mann, G.; Hartwig,
J. F. J. Am. Chem. Soc. 2000, 122, 10718. (g) Mann, G.; Shelby, Q.;
Roy, A. H.; Hartwig, J. F. Organometallics 2003, 22, 2775. (h)
Stambuli, J. P.; Weng, Z.; Incarvito, C. D.; Hartwig, J. F. Angew.
Chem., Int. Ed. 2007, 46, 7674.
(3) For examples of other PdII/IV-catalyzed acetoxylation reactions using
PhI(OAc)2, see: (a) Alexanian, E. J.; Lee, C.; Sorensen, E. J. J. Am.
Chem. Soc. 2005, 127, 7690. (b) Liu, G.; Stahl, S. S. J. Am. Chem.
Soc. 2006, 128, 7179. (c) Desai, L. V.; Sanford, M. S. Angew. Chem.,
Int. Ed. 2007, 46, 5737. (d) Li, Y.; Song, D.; Dong, V. M. J. Am.
Chem. Soc. 2008, 130, 2962.
(7) (a) Williams, B. S.; Holland, A. W.; Goldberg, K. I. J. Am. Chem.
Soc. 1999, 121, 252. (b) Williams, B. S.; Goldberg, K. I. J. Am. Chem.
Soc. 2001, 123, 2576. (c) Vedernikov, A. N.; Binfield, S. A.; Zavalij,
P. Y.; Khusnutdinova, J. R. J. Am. Chem. Soc. 2006, 128, 82. (d)
Khusnutdinova, J. R.; Zavalij, P. Y.; Vedernikov, A. N. Organome-
tallics 2007, 26, 3466. (e) Khusnutdinova, J. R.; Newman, L. L.;
Zavalij, P. Y.; Lam, Y.-F.; Vedernikov, A. N. J. Am. Chem. Soc. 2008,
130, 2174. (f) Smythe, N. A.; Grice, K. A.; Williams, B. S.; Goldberg,
K. I. Organometallics 2009, 28, 277.
(4) A related mechanism was also proposed for the Pd(OAc)2-catalyzed
acetoxylation of benzene with PhI(OAc)2. See: Yoneyama, T.;
Crabtree, R. H. J. Mol. Catal. A 1996, 108, 35.
(5) (a) Matsunaga, P. T.; Hillhouse, G. K. J. Am. Chem. Soc. 1993, 115,
2075. (b) Matsunaga, P. T.; Mavropoulos, J. C.; Hillhouse, G. K.
Polyhedron 1995, 14, 175. (c) Han, R.; Hillhouse, G. L. J. Am. Chem.
Soc. 1997, 119, 8135. (d) Koo, K.; Hillhouse, G. L. Organometallics
1998, 17, 2924.
9
10974 J. AM. CHEM. SOC. 2009, 131, 10974–10983
10.1021/ja9014474 CCC: $40.75  2009 American Chemical Society

Reaction of (N∼C)2PdII with PhI(O2CR)2
A R T I C L E S
Scheme 1. Proposed Mechanism for Pd-Catalyzed Acetoxylation of 2-Phenylpyridine
Scheme 2. Design of Complex B for Study of C-O Bond-Forming Reductive Elimination from PdIV
Scheme 3. Oxidation of (Phpy)2PdII (1) with PhI(OAc)2
complex.8–11 Additionally, we hypothesized that the rigid and
chelating nature of the two N∼C ligands would limit competing
C-C bond-forming processes relative to the desired C-O
coupling. Finally, we reasoned that the two carboxylates could
be incorporated by oxidation of (N∼C)2PdII with PhI(O2CR)2,
which is the same terminal oxidant used for the catalytic
reactions in Scheme 1.
We report herein detailed studies on the synthesis and
reactivity of PdIV complexes of general structure B. These
complexes are readily prepared by the oxidation of (N∼C)2PdII
with PhI(O2CR)2 and are remarkably stable at room temper-
ature.12,13 However, at elevated temperatures, most undergo
clean C-O bond-forming reductive elimination to afford ester
products. This paper describes full mechanistic investigations
of this C-O bond-forming process and also provides mecha-
nistic insights into competing C-C coupling reactions.
min produced a single inorganic product (2) (Scheme 3).
Complex 2 was isolated in 93% yield as a pale yellow solid by
precipitation with diethyl ether. This species was remarkably
stable in the solid state and could be stored for 12 months at
-35 °C without significant decomposition.
The 1H NMR spectrum of 2 in acetone-d6 shows 16 distinct
aromatic signals between 6.29 and 9.46 ppm and two different
acetate resonances at 1.63 and 1.74 ppm. This spectroscopic
data is indicative of an unsymmetrical octahedral PdIV species
with two different Phpy and acetate ligand environments. Further
characterization of 2 by X-ray crystallography confirmed that
this complex has an octahedral geometry with cis-phenylpyridine
and acetate ligands (Figure 1). This is a highly unusual example
of a room temperature stable PdIV complex containing a C2N2O2
coordination environment.
Results and Discussion
Initial Investigations. 2-Phenylpyridine (Phpy) was selected
as the N∼C chelating ligand due to its high reactivity in Pd-
catalyzed C-H activation/acetoxylation reactions1 and the
availability of the starting material (Phpy)2PdII (1).14 Gratify-
ingly, treatment of 1 with PhI(OAc)2 in CH2Cl2 at 25 °C for 30
We next examined the reactivity of PdIV complex 2 toward
thermally induced reductive elimination. Two possible reductive
elimination reactions are possible from 2 - carbon-oxygen
bond-forming reductive elimination to generate 2-(2-acetoxy-
phenyl)pyridine (3) and/or C-C bond-forming reductive elimi-
nation to afford 2,2′-di(pyridin-2-yl)biphenyl (4) (Scheme 4).
Literature reports have shown that related PdIV species [for
example, (bipy)PdIV(Me)3(O2CPh) (bipy ) 2,2′-bipyridine)]
undergo C-C bond formation at comparable or faster rates than
the desired C-O coupling reaction.8,9
(8) (a) Canty, A. J.; Traill, P. R.; Skelton, B. W.; White, A. H. J.
Organomet. Chem. 1992, 433, 213. (b) Canty, A. J.; Jin, H.; Roberts,
A. S.; Skelton, B. W.; White, A. H. Organometallics 1996, 15, 5713.
(c) Yamamoto, Y.; Ohno, T.; Itoh, K. Angew. Chem., Int. Ed. 2002,
41, 3662. (d) Yamamoto, Y.; Kuwabara, S.; Matsuo, S.; Ohno, T.;
Nishiyama, H.; Itoh, K. Organometallics 2004, 23, 389.
(9) For examples where PdIV complexes containing O-donor ligands were
detected at low temperature, see: (a) Canty, A. J.; Jin, H. J. Organomet.
Chem. 1998, 565, 135. (b) Canty, A. J.; Jin, H.; Skelton, B. W.; White,
A. H. Inorg. Chem. 1998, 37, 3975. (c) Canty, A. J.; Done, M. C.;
Skelton, B. W.; White, A. H. Inorg. Chem. Commun. 2001, 4, 648.
(d) Canty, A. J.; Denney, M. C.; Skelton, B. W.; White, A. H.
Organometallics 2004, 23, 1122.
We were pleased to find that heating a solution of 2 in CH3CN
for 30 min at 80 °C resulted in the formation of 3 as the sole
(10) For examples of rigid bidentate ligands stabilizing PdIV complexes,
see: (a) Canty, A. J. Acc. Chem. Res. 1992, 25, 83. (b) van Asselt, R.;
Rijnberg, E.; Elsevier, C. J. Organometallics 1994, 13, 706. (c) Canty,
A J.; van Koten, G. Acc. Chem. Res. 1995, 28, 406. (d) Suginome,
M.; Kato, Y.; Takeda, N.; Oike, H.; Ito, Y. Organometallics 1998,
17, 495. (e) Campora, J.; Palma, P.; del Rio, D.; Lopez, J. A.; Alvarez,
E.; Connelly, N. G. Organometallics 2005, 24, 3624.
(11) For the first example of the use of multiple strongly σ-donating alkyl
ligands to stabilize a PdIV center, see: Byers, P. K.; Canty, A. J.;
Skelton, B. W.; White, A. H. J. Chem. Soc., Chem. Commun. 1986,
1722. For numerous more recent examples, see refs 8, 9.
(12) Dick, A. R.; Kampf, J.; Sanford, M. S. J. Am. Chem. Soc. 2005, 127,
12790.
(13) For more recent reports of related PdIV complexes stabilized by
cyclometalated ligands, see: (a) Whitfield, S. R.; Sanford, M. S. J. Am.
Chem. Soc. 2007, 129, 15142. (b) Furuya, T.; Ritter, T. J. Am. Chem.
Soc. 2008, 130, 10060.
Figure 1. ORTEP structure of (Phpy)2PdIV(OAc)2 (2).
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A R T I C L E S
Racowski et al.
Scheme 4. Possible Organic Products of Reductive Elimination
from 2
There is literature precedent for each of these mechanisms
in reductive elimination reactions at group 10 metal centers.
For example, mechanism A has been implicated for sp3 C-O,7
sp3 C-halogen,15 sp3 C-N,16 and sp2 C-halogen17 bond-forming
reductive elimination from PtIV. A concerted-type mechanism
has been proposed for sp2 C-O,6 sp2 C-N,18 and sp2 C-S19
bond-forming reductive elimination from PdII centers. Finally,
mechanism C has been reported for some C-C bond-forming
reactions from PtIV.20
We aimed to distinguish between these mechanistic possibili-
ties by systematically studying C-O bond-forming reductive
elimination from (Arpy)2PdIV(O2CR)2 (Arpy ) substituted
arylpyridine, O2CR ) substituted carboxylate). These complexes
were synthesized by the reaction of 1 with PhI(O2CR)2 (Scheme
7).21 Our initial investigations in this area provided preliminary
evidence in support of mechanism C.12 More recently, a
computational study by Liu and co-workers has suggested that
mechanism B is operating in these systems.22 To gain further
insights into this transformation, we have carried out numerous
additional experiments to probe both C-O and related C-C
bond-forming reductive elimination processes from (Arpy)2-
PdIV(O2CR)2. As detailed below, these new investigations, as
well as reevaluation/reinterpretation of our previous data, lead
us to conclude that mechanism A is, in fact, most likely
operating in this system.
Scheme 5. Reductive Elimination from (Phpy)2PdIV(OAc)2 (2)
Scheme 6. Possible Mechanisms for C-O Bond-Forming
Reductive Elimination from I
Mechanism of C-O Bond-Forming Reductive Elimination:
Carboxylate Exchange. Our mechanistic studies first probed the
viability of mechanism A by investigating whether complex 2
undergoes exchange between free and bound carboxylates at
temperatures below those required for reductive elimination
(Scheme 8). Because 2 is coordinatively saturated, carboxylate
exchange would require dissociation of an acetate ligand via a
process analogous to the first step of mechanism A. Notably,
Goldberg and co-workers have shown that such exchange
reactions occur rapidly at the PtIV complex fac-(dppbz)PtMe3-
(OAr) (dppbz ) bis(diphenylphosphino)benzene), which un-
dergoes C-O bond-forming reductive elimination via mecha-
nism A.7b
organic product in nearly quantitative yield (95%) as determined
by H NMR spectroscopy (Scheme 5). The inorganic product
1
of this reaction was the cyclometalated PdII dimer 5, which was
obtained in 98% yield. To our knowledge, this is the first direct
observation of sp2 C-O bond-forming reductive elimination
from an isolated PdIV center. As a result, this system presented
a unique opportunity for mechanistic studies relevant to the
proposed product-forming step in Pd-catalyzed C-H bond
acetoxylation reactions.1–4
Carboxylate exchange was first studied by treating complex
2 with 1 equiv of NBu4(O2CC9H19) at 25 °C in acetone-d6.
Importantly, these conditions are far milder than those required
to induce C-O bond-forming reductive elimination from 2.
1
Analysis of the reaction by H NMR spectroscopy after 5 min
showed formation of one major new PdIV species with charac-
Mechanistic Considerations. We considered three mechanisms
for C-O bond-forming reductive elimination from complexes
of general structure I (Scheme 6). The first possibility was an
ionic mechanism (A), which would proceed via carboxylate
dissociation from I to form five-coordinate intermediate II,
followed by reductive elimination from this cationic species.
Mechanism B, concerted bond formation, would involve direct
C-O reductive elimination from the coordinatively saturated
octahedral PdIV complex I. Finally, Mechanism C, chelate
dissociation, would involve dissociation of an N-donor ligand
to generate the neutral 5-coordinate species III, followed by
reductive elimination. Notably, within all three mechanisms,
there are two distinct carboxylates that could participate in C-O
bond-forming reductive elimination. In mechanism A, C-O
coupling from intermediate II could occur via nucleophilic
attack by the dissociated carboxylate or by direct reaction of
the coordinated carboxylate. In mechanisms B and C, reductive
elimination could involve C-O coupling with the carboxylate
trans to the pyridine nitrogen or with the carboxylate trans to
the σ-Ar ligand.
1
teristic upfield and downfield H NMR resonances at 6.31 and
(14) Jolliet, P.; Gianini, M.; von Zelewsky, A.; Bernardinelli, G.; Stoeckli-
Evans, H. Inorg. Chem. 1996, 35, 4883.
(15) (a) Goldberg, K. I.; Yan, J.; Winter, E. L. J. Am. Chem. Soc. 1994,
116, 1573. (b) Goldberg, K. I.; Yan, J.; Breitung, E. M. J. Am. Chem.
Soc. 1995, 117, 6889.
(16) Pawlikowski, A. V.; Getty, A. D.; Goldberg, K. I. J. Am. Chem. Soc.
2007, 129, 10382.
(17) Yahav-Levi, A.; Goldberg, I.; Vigalok, A.; Vedernikov, A. N. J. Am.
Chem. Soc. 2008, 130, 724.
(18) Driver, M. S.; Hartwig, J. F. J. Am. Chem. Soc. 1997, 119, 8232.
(19) (a) Baranano, D.; Hartwig, J. F. J. Am. Chem. Soc. 1995, 117, 2937.
(b) Mann, G.; Baranano, D.; Hartwig, J. F.; Rheingold, A. L.; Guzei,
I. A. J. Am. Chem. Soc. 1998, 120, 9205.
(20) (a) Crumpton, D. M.; Goldberg, K. I. J. Am. Chem. Soc. 2000, 122,
962. (b) Crumpton-Bregel, D. M.; Goldberg, K. I. J. Am. Chem. Soc.
2003, 125, 9442. (c) Arthur, K. L.; Wang, Q. L.; Bregel, D. M.;
Smythe, N. A.; O’Neill, B. A.; Goldberg, K. I.; Moloy, K. G.
Organometallics 2005, 24, 4624.
(21) Stang, P. J.; Boehshar, M.; Wingert, H.; Kitamura, T. J. Am. Chem.
Soc. 1988, 110, 3272.
(22) Fu, J.; Li, Z.; Liang, S.; Guo, Q.; Liu, L. Organometallics 2008, 27,
3736.
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Reaction of (N∼C)2PdII with PhI(O2CR)2
A R T I C L E S
Scheme 7. General Synthetic Route to (Phpy)2PdIV(O2CR)2
Scheme 8. Potential Products of Carboxylate Exchange Reaction
Scheme 9. Independent Synthesis of Complex 19 and ORTEP Picture of 19
9.49 ppm. These are slightly shifted relative to the starting
material, which has signals at 6.29 and 9.44 ppm. We
hypothesized that this new complex was the monoacetate adduct
19 where the acetate ligand trans to C was replaced with
O2CC9H19. The selective replacement of this OAc can be
rationalized on the basis of the larger trans influence of the σ-aryl
ligand versus the pyridine nitrogen.23
10)]. Electrospray MS of all of the possible products (which
were each synthesized independently)25 showed major peaks
consistent with loss of the acetate ligand trans to the σ-aryl
group. For example, the peak for (Phpy)2PdIV-
(OAc-d3)(OAc) (2a-d3) was [(Phpy)2PdIV(OAc)]+ (MW )
473.0) while that for (Phpy)2PdIV(OAc)(OAc-d3) (2b-d3) was
[(Phpy)2PdIV(O2CCD3)]+ (MW ) 476.0). Furthermore, coin-
jection of a 1: 1 mixture of 2: 2-d6 showed peaks of equal
intensity, demonstrating that peak intensities can be used to
determine the relative concentrations of these species.
The isolation of 19 from the reaction mixture proved
challenging, as this species was not readily separable from
tetrabutylammonium-containing byproducts. Thus, an authentic
sample of 19 was synthesized independently by reaction of
(Phpy)2PdIV(Cl)(OAc)24 (21) with 1 equiv of AgO2CC9H19
(Scheme 9). This product showed identical 1H NMR resonances
to those observed in the exchange reaction. In addition, its
structure was unambiguously established by X-ray crystal-
lography (Scheme 9).
When a 1: 1 mixture of (Phpy)2PdIV(OAc)2 and NBu4(OAc-
d3) was combined in CH2Cl2, stirred for 20 min, and then
analyzed by electrospray MS, a single peak for [(Phpy)2PdIV-
(OAc)]+ (MW ) 473.0) was observed (Scheme 10). This result
indicates that neither 2b-d3 nor 2-d6 is formed, thereby providing
further evidence that carboxylate exchange occurs solely at the
site trans to the σ-aryl ligand.
1
While H NMR spectroscopic analysis was consistent with
19 as the major product of the exchange process, we were unable
to definitively establish whether small quantities of 20 and 7
were also formed, since these have closely overlapping 1H NMR
resonances. As such, electrospray mass spectrometry was used
to analyze the products of a related reaction [the thermoneutral
exchange between (Phpy)2PdIV(OAc)2 and NBu4(OAc-d3) (Scheme
As discussed above, carboxylate exchange cannot occur by
an associative mechanism, since the starting complex is coor-
dinatively saturated. Thus, the observation of rapid exchange
suggests strongly that carboxylate dissociation (the first step of
mechanism A) can occur at temperatures below those required
for reductive elimination. However, more experiments were
(23) Crabtree, R. H.; The Organometallic Chemistry of Transition Metals,
4th ed.; John Wiley & Sons, Inc: Hoboken, NJ, 2005.
(24) Whitfield, S. R. Ph.D. Thesis, University of Michigan, 2008.
(25) These complexes were synthesized by reaction of (Phpy)2PdIV(Cl)-
(OAc) or (Phpy)2PdIV(Cl)(OAc-d3) with the corresponding silver
carboxylate. See the Supporting Information for full details.
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A R T I C L E S
Racowski et al.
Scheme 10. Electrospray MS Data for Reaction between 2 and NBu4(OAc-d3)
Scheme 11. Original Crossover Experiment from Ref 12
Scheme 13. Selectivity of C-O Bond-Forming Reductive
Elimination from 2b-d3
Scheme 12. AcO/AcO-d3 Crossover Experiment
(O2CC9H19)2 (7) was used for these studies due to its high
solubility in many different solvents.
The rate of C-O bond-forming reductive elimination from
7 was examined as a function of solvent under standard
conditions (55 °C, 15.2 mM in solvent with 5% v/v pyridine).28
The disappearance of starting material 7 and concomitant
1
formation of 23 and 24 were monitored by H NMR spectros-
copy. Interestingly, changing the solvent had very little influence
on the reaction rate, and kobs varied by only ∼3-fold over a
wide array of solvents (Table 1). In addition, there was no clear
correlation between kobs and the solvent polarity. For example,
nearly identical rates were observed in benzene and acetone
(krel ) 1), despite a large difference in dielectric constant (ε )
2.3 and 21, respectively). Furthermore, comparable and rela-
tively fast rates were observed in nonpolar CDCl3 (ε ) 4.8, krel
) 2.3) and polar CH3CN (ε ) 38, krel ) 2.4).
required to determine whether this exchange was mechanistically
relevant to C-O bond-forming reductive elimination.
Mechanism of C-O Bond-Forming Reductive Elimination:
Crossover Studies. We next investigated whether crossover
between free and bound carboxylate occurred during the course
of the reductive elimination reaction. A first crossover study
involved thermolysis of the bis-benzoate complex 8 in the
presence of 5 equiv of NBu4OAc in either CDCl3 or DMSO
(Scheme 11).12 Analysis of the reaction mixture by GC and
GCMS showed that the predominant organic product was 22,
and that <5% of the crossover product 3 was formed.
We reasoned that the absence of crossover might be due to
an electronic bias for reductive elimination of the benzoate in
preference to the acetate ligand. As such, we designed a system
to eliminate this electronic bias and differentiate the bound and
free carboxylates solely based on isotopic labeling. However,
thermolysis of (Phpy)2PdIV(OAc-d3)2 (2-d6) in the presence of
5 equiv of NBu4OAc under otherwise identical conditions to
Scheme 11 still afforded <6% of crossover product 3 (Scheme
12).
The rate of carboxylate exchange was also investigated as a
function of solvent. In these experiments, 1 equiv of 7 and 1
equiv of Bu4N(OAc) were dissolved in the appropriate solvent
in an NMR tube at -38 °C, and the rate of formation of an
1
equilibrium mixture of 7 and 20 was monitored by H NMR
spectroscopy. Intriguingly, kobs for carboxylate exchange also
did not show a clear correlation with the polarity of the reaction
medium (Table 2). For example, the fastest rate (kkel ) 19) was
observed in CDCl3 (ε ) 4.8), while the slowest (krel ) ∼0.1)29
was in toluene-d8 (ε ) 2.4).
The solvent data for C-O bond-forming reductive elimination
(particularly the low correlation between ε and kobs) was initially
interpreted as a strong piece of evidence against mechanism
These results indicate that the nonexchangeable carboxylate
ligand participates selectively in the C-O bond-forming reac-
tion. This was confirmed by subjecting complex 2b-d3,25 which
contains two different carboxylate ligands, to the standard
reductive elimination conditions. The major product (>95%
yield) was 3-d3 and <5% of 3 was observed as determined by
(26) Byers, P. K.; Canty, A. J.; Crespo, M.; Puddephatt, R. J.; Scott, J. D.
Organometallics 1988, 7, 1363.
(27) Isaacs, N. S. Physical Organic Chemistry, 2nd ed.; Pearson Education:
New York, 1995.
(28) Initial investigations revealed that clean first order kinetics were not
observed in some solvents, and we hypothesized that this might be
due to formation of a highly reactive 3-coordinate PdII intermediate.
Closely related challenges have been observed in reductive elimination
reactions from PdII centers (for example, see ref 19a) and have been
resolved by the addition of external ancillary ligands, which serve to
trap unsaturated intermediates. Similarly, we found that the addition
of 5% of pyridine-d5 to the reductive elimination reactions of 7 in
each solvent resulted in clean first order kinetics over greater than
three half-lives. Qualitative time studies showed that added pyridine
had little effect on the relative rate in each of the solvents studied.
2
1H and H NMR spectroscopy (Scheme 13).
Mechanism of C-O Bond-Forming Reductive Elimination:
Solvent Effects. Polar solvents often accelerate reductive elimina-
tion and ligand exchange reactions that proceed via ionic
mechanisms.7,26,27 Thus, we next investigated the effect of
solvent on the rates of both C-O bond-forming reductive
elimination and carboxylate exchange in a series of solvents
with diverse polarities. The bis-decanoate complex (Phpy)2PdIV-
9
10978 J. AM. CHEM. SOC. VOL. 131, NO. 31, 2009

Reaction of (N∼C)2PdII with PhI(O2CR)2
A R T I C L E S
Table 1. Effect of Solvent on the Rate of Reductive Elimination
from 7
Table 3. Effect of AcOH on C-O Bond-Forming Reductive
Elimination and Carboxylate Exchange at 7
entry
solvent
ε
krel
entry
acid
krel C-O coupling
krel exchange
1
2
3
4
5
6
7
acetone-d6
C6D6
chlorobenzene-d5
DMSO-d6
CDCl3
21
1.0 ( 0.1
1.0 ( 0.1
1.0 ( 0.1
2.0 ( 0.3
2.3 ( 0.2
2.4 ( 0.1
3.1 ( 0.3
1
2
none
HOAc
1.0 ( 0.0a
1.0 ( 0.0b
4.5 ( 0.5b
2.3
5.6
47
4.8
38
3.6 ( 0.2a
a 40 °C in acetone-d6. b -35 °C in acetone-d6.
CD3CN
nitrobenzene-d5
Table 4. Effect of AgOTf on C-O Bond-Forming Reductive
Elimination and Carboxylate Exchange at 7
36
Table 2. Effect of Solvent on the Rate of Carboxylate Exchange
from 7
entry
acid
krel C-O coupling
krel exchange
1
2
none
AgOTf
1.0 ( 0.2a
1.0 ( 0.1b
8.7 ( 0.0b
16 ( 0.8a
a 23 °C in CDCl3. b -53 °C in CDCl3.
entry
solvent
ε
krel
Canty9b but is quite similar to that obtained for C-O bond-
forming reductive elimination from 7.30
1
2
3
4
toluene-d8
acetone-d6
CD3CN
2.4
21
38
<0.1
1.0 ( 0.1
2.0 ( 0.2
19 ( 1
Mechanism of C-O Bond-Forming Reductive Elimination:
Acidic Additives. Goldberg has shown that both Brønsted and
Lewis acids accelerate C-O and C-C bond-forming reductive
elimination from (dppe)PtIV(OAc)(Me)3 (dppe ) diphenylphos-
phinoethane), which both proceed via mechanism A.7b For
example, the addition of 0.1 equiv of AcOH increased the rate
of C-O coupling by a factor of 2, while the use of 0.1 equiv
of AgOTf lowered the temperature required for C-C bond-
forming reductive elimination from 99 to 25 °C. Both additives
were proposed to act by promoting AcO- dissociation. On the
basis of this report, we reasoned that if mechanism A were
operative in our system, both C-O bond-forming reduc-
tive elimination and carboxylate exchange at complex 7 should
be accelerated to similar extents by these additives.
We first studied the rate of C-O bond-forming reductive
elimination from (Phpy)2PdIV(O2CC9H19)2 (7) in the presence
of AcOH or AgOTf. The addition of AcOH (2.0 equiv) resulted
in a 3.6-fold acceleration of C-O bond-forming reductive
elimination (Table 3, entries 1 and 2), while AgOTf (0.3 equiv)
led to a 16-fold increase in kobs for this reaction (Table 4, entries
1 and 2).
CDCl3
4.8
A.7,9 However, the results from the corresponding solvent study
for carboxylate exchange indicate that this interpretation should
be reconsidered.
Mechanism of C-O Bond-Forming Reductive Elimination:
Entropy of Activation. Previous work has shown that reductive
elimination reactions proceeding via mechanism A are often
characterized by large negative values of ∆S‡. For example,
Canty has reported that C-Se bond-forming reductive elimina-
tion from PdIV has ∆S‡ ranging from -40 to -49 eu, depending
on the reaction solvent.9b This has been rationalized on the basis
of significant orientation of solvent molecules around the
charged transition state.
The rate of C-O bond-forming reductive elimination from
7 was examined over a range of temperatures from 30 to 70 °C
in both CDCl3 and DMSO-d6. Eyring plots showed that ∆S‡ is
close to zero in both solvents (∆S‡ ) -1.4 ( 1.9 eu in CDCl3
and +4.2 ( 1.4 eu in DMSO-d6). While values of ∆S‡ between
10 and -10 eu are considered difficult to interpret, these values
are substantially less negative than those reported by Canty.27
As such, we initially viewed this data as inconsistent with
mechanism A.12
The influence of AcOH on the rate of carboxylate exchange
was next determined, and, remarkably, a very similar effect was
observed. For example, the addition of AcOH (2.0 equiv)
resulted in a 4.5-fold increase in the rate (Table 3, entry 2),
while AgOTf (0.3 equiv) afforded an 8.7-fold increase in kobs
for exchange (Table 4, entry 2). These results are consistent
Similar studies were conducted to obtain an Eyring plot for
carboxylate exchange. In these experiments, the reaction of 7
with 1.0 equiv of Bu4N(OAc) in CDCl3 was monitored by H
NMR spectroscopy over temperatures ranging from -58 to -38
°C, and an Eyring plot provided ∆S‡ ) -7.2 ( 3 eu. Again,
this value is considerably less negative than those reported by
(29) Carboxylate exchange in toluene progressed too slowly to measure
quantitatively at -38 °C (i.e., no observable exchange occurred after
6 h).
(30) More investigation is needed to understand why the entropy of
activation is so small in this system. See ref 34 for a possible
explanation.
1
9
J. AM. CHEM. SOC. VOL. 131, NO. 31, 2009 10979

A R T I C L E S
Racowski et al.
Scheme 14. C-O Bond-Forming Reductive Elimination from 8-18
Table 5. kobs for Reductive Elimination from
(Arpy)2PdIV[O2C(p-AcC6H4)]2
Compound
kobs (s-1 ×105)
∼3a
with the hypothesis that carboxylate exchange and C-O bond-
forming reductive elimination are mechanistically linked.
Mechanism of C-O Bond-Forming Reductive Elimination:
Carboxylate Electronic Effects. A series of PdIV complexes
(8-18) were designed to place both σ- and π-electron donating
and electron withdrawing substituents on the benzoate ligand.
The kinetics of C-O bond-forming reductive elimination from
PdIV complexes 8-18 was then studied at 60 °C in a solution
of 5% v/v C5D5N in CDCl3 (Scheme 14).28 A Hammett plot of
this data showed very good correlation with σpara (R2 ) 0.95)
and yielded a F value of -1.36 ( 0.04 (Figure 2).
A previous report showed that F ) +1.44 for C-O bond-
forming reductive elimination from (dppbz)PtMe3(OAr), which
proceeds by mechanism A.7b As such, we initially reasoned that
the observed F value of -1.36 provided evidence against an
ionic mechanism.12 However, the overall value of F (Fobs) for a
reaction proceeding by mechanism A is the sum of Feq and F2
(Figure 3).31 The Fobs of +1.44 in the Pt system was rationalized
based on the assumption that |Feq| > |F2|;7b however, since the
overall F (Fobs) is a composite, a positive F value is not an
inherent feature of such mechanisms.32 Thus, since all of the
possible mechanisms (A, B, and C) involve the carboxylate
acting as a nucleophilic partner in a rate-determining C-O bond-
forming step (Scheme 6), the observed negative F value is
potentially consistent with any of these pathways.
*OMe (46)
Me (47)
H (15)
F (48)
Cl (49)
4.81
20.0
3.64
36.9
∼320a
*CF3 (50)
a These values of kobs are approximate, as samples of 46 and 50 were
contaminated with ∼10% of inseparable impurities.
in CDCl3. Reductive elimination generally proceeded fastest
with electron-withdrawing substituents (Table 5), although
Hammett plots showed only modest correlation with σpara (R2
) 0.80), σ+ (R2 ) 0.79), and σ- (R2 ) 0.84). This is consistent
with the Ar ring acting as the electrophilic partner in C-O
coupling.
Mechanism of C-O Bond-Forming Reductive Elimination:
Ligand Rigidity. We originally hypothesized that a decrease in
reaction rate with increasing N∼C ligand rigidity would provide
support for mechanism C.12 Complexes 62-64 were designed
to systematically vary the flexibility of the tether between the
two pyridine rings (Figure 4). The kinetics of C-O bond-
1
forming reductive elimination from 62-64 was studied by H
NMR spectroscopy at 50 °C in a solution of 5% v/v C5D5N in
CDCl3. As summarized in Table 6, the rates of reductive
elimination did show a correlation with the rigidity of the N∼C
ligand. For example, complex 62 reacted twice as fast as 63
and more than 10 times faster than the most rigid 64.
Mechanism of C-O Bond-Forming Reductive Elimination:
Arylpyridine Electronic Effects. A series of complexes containing
electronically varied arylpyridine ligands (15 and 46-50) were
designed to place different electron withdrawing and electron
donating substituents trans to the Pd-bound carbon atom. The
kinetics of C-O bond-forming reductive elimination from 15
and 46-50 were studied at 60 °C in a solution of 5% v/v C5D5N
As discussed above, we originally interpreted these results
as being most consistent with the chelate dissociation mechanism
(C).12,20 However, a number of literature reports have shown
that rigid ancillary ligands stabilize PdIV complexes toward
reductive elimination, even when the ligand plays no direct role
in the bond-forming process.10 Therefore, these results do not
definitively establish or rule out any of the three mechanistic
manifolds.
Summary of Mechanistic Data for C-O Bond-Forming Reduc-
tive Elimination. Mechanisms A, B, or C for C-O bond-forming
reductive elimination from (N∼C)2PdIV(O2CR)2 are kinetically
indistinguishable; therefore, we have conducted a series of
alternative mechanistic experiments to interrogate this trans-
formation. Our original communication suggested that mecha-
nism C, chelate dissociation, was most consistent with initial
studies of this process.12 This conclusion was based on 5 key
pieces of data: (i) the absence of a clear correlation between
kobs and solvent polarity, (ii) the lack of crossover between free
and bound carboxylate, (iii) the small entropy of activation, (iv)
Figure 2. Hammett plot for C-O bond-forming reductive elimination from
8-18.
(31) Exner, O. Correlation Analysis of Chemical Data; Plenum Press: New
York, 1988.
(32) Reductive elimination reactions from (Phpy)2PdIV(O2CAr)2 have the
added complication that these complexes contain two different
carboxylate ligands. If mechanism A were operating, these two ligands
would serve two very different roles in the first step of the reaction -
one would dissociate to form an anion (stabilized by electron
withdrawing groups), while the other would remain bound to cationic
intermediate II (stabilized by electron donating groups).
Figure 3. Values of F for each step of mechanism A.
9
10980 J. AM. CHEM. SOC. VOL. 131, NO. 31, 2009

Reaction of (N∼C)2PdII with PhI(O2CR)2
A R T I C L E S
Figure 4. Effect of ligand rigidity on C-O bond-forming reductive elimination.
Table 6. Rate of C-O Bond-Forming Reductive Elimination as a
Function of Ligand Rigidity
Scheme 15. Competing C-O and C-C Bond-Forming Reductive
Elimination from 64
entry
complex
krel
Table 7. Effect of Solvent on the Product Ratio of Reductive
Elimination from 67
1
2
3
62
63
64
1.9
1.0
∼0.1a
a The slow reaction rate along with competing C-C bond-formation
prevented quantitative rate measurement in this system.
the negative F value obtained upon substitution of the carboxyl-
ate ligand, and (v) the decreased reaction rate with more rigid
N∼C ligands.33
However, we have conducted a variety of new experiments,
and these, along with a re-evaluation of the previous data, have
led us to conclude that mechanism A is, in fact, most likely
operating in this system. These new experiments were particu-
larly focused on the exchange of free and bound carboxylate at
(Phpy)2PdIV(O2CR)2, which is expected to proceed by an
identical mechanism to the first step of mechanism A. This
exchange occurs at temperatures far below reductive elimination,
and shows similar solvent effects and activation parameters to
C-O bond-formation.34 In addition, the rates of carboxylate
exchange and of C-O coupling are increased to very similar
extents upon addition of AcOH and AgOTf, additives that have
both been reported to promote carboxylate dissociation. The
C-C bond-forming reactions discussed below offer further
evidence in support of mechanism A. In addition, they provide
a more complete picture of the reactivity of these PdIV
complexes.
entry
solvent
ratio 66:68
krel for C-O coupling from 7
1
2
3
4
5
6
CH3CN
CHCl3
nitrobenzene
DMSO
acetone
0.2:1
0.77:1
2.2:1
3.3:1
13:1
2.4
2.3
3.1
2.0
1.0
1.0
benzene
>20:1
Mechanism of C-C Bond-Forming Reductive Elimination:
Solvent Effects. A first study probed the effect of solvent on the
relative rates (krel) of C-C and C-O bond-forming reductive
elimination from (Bzq)2PdIV(O2CC9H19)2 (67). The values of krel
were determined under a standard set of conditions (80 °C, 4 h,
15.2 mM) on the basis of the ratio of C-C coupled product 66
to C-O coupled product 68 in the crude reaction mixtures. As
summarized in Table 7, solvent had a significant influence on
the product distribution, with the ratio of 66:68 ranging from
>20:1 to 0.2:1. While there was no clear relationship between
the dielectric constant of the solvent and the product ratio, the
largest amounts of 66 were observed in solvents where C-O
coupling from the analogous 2-phenylpyridine complex
(Phpy)2PdIV(O2CC9H19)2 (7) was relatively slow. For example,
in benzene and acetone (with krel ) 1 for C-O bond-forming
reductive elimination from 7), >10:1 selectivity was observed
for 66 (Table 7, entries 5 and 6). Conversely, in CH3CN and
CHCl3, (solvents where C-O bond-forming reductive elimina-
tion from 7 was relatively fast), 68 was the major organic
reductive elimination product (entries 1 and 2).
C-C Bond-Forming Reductive Elimination from (Bzq)2PdIV-
(O2CR)2. In the context of the ligand rigidity studies, we noted
that benzo[h]quinoline complex 64 reacted to form significant
quantities of C-C bond-forming reductive elimination product
66 along with the expected C-O coupled product 65 (Scheme
15). This result was intriguing, since analogous C-C coupling
was not observed in any of the phenylpyridine systems. As such,
a series of experiments was designed to further interrogate the
mechanism of this process.
(33) Calculations on C-O bond-forming reductive elimination reactions
from 10 (ref 22) suggested that mechanisms A and B are relatively
close in energy (∆G‡ ) 31.4 and 26.4 kcal/mol, respectively). In
contrast, mechanism C was calculated to have a much larger activation
energy of 44.3 kcal/mol.
(34) While the observed solvent effects and activation parameters are
somewhat unexpected for a system involving ionic intermediates, they
may result from an unusually early or late transition state that has
relatively little charge buildup.
Mechanism of C-C Bond-Forming Reductive Elimination:
Acidic Additives. Complex 67 was subjected to standard reduc-
tive elimination conditions (80 °C, 3 h, 15.2 mM in acetone) in
the presence of 5.0 equiv of AcOH or 0.10 equiv AgOTf
(additives that accelerate C-O bond-forming reductive elimina-
9
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A R T I C L E S
Racowski et al.
Table 8. Effect of Acidic Additives on the Product Ratio of
Reductive Elimination from 67
Table 10. Effect of NBu4(O2CC9H19) on the Product Distribution of
Reductive Elimination from 67
entry
additive
ratio 66:68
entry
additive
ratio 66:68
1
2
3
none
NBu4(O2CC9H19)
NBu4PF6
0.2:1
2:1
0.2:1
1
2
3
none
AcOH (5.0 equiv)
AgOTf (0.1 equiv)
13:1
3.6:1
0.10:1
Scheme 16. Proposed Mechanisms for C-C and C-O
Table 9. Solvent Effects on Product Distribution of Reductive
Elimination from Complex 69
Bond-Forming Reductive Elimination from (N∼C)2PdIV(O2CR)2
entry
solvent
organic product
1
2
3
4
pyridine-d5
acetone-d6
DMSO-d6
CD3CN
66
66
66
66
was added, the selectivity completely reversed, and 66 pre-
dominated (66:68 ratio ) 2:1). To confirm that this effect was
not just due to the increased ionic strength of the solution, a
control experiment was conducted using 1 equiv of NBu4PF6.
This experiment provided an identical product ratio to the initial
reaction (66:68 ) 0.2:1). Therefore, the reversal in product
selectivity is clearly specific to the carboxylate ion.
tion from (Phpy)2PdIV(O2CC9H19)2 (7)), and the ratio of organic
products was determined using 1H NMR spectroscopy. As
summarized in Table 8, both additives led to a large increase
in the relative amount of the oxygenated product 68. For
example, with AcOH, the ratio of 66 to 68 changed from 13:1
to 3.6: 1. The effect was even more dramatic with AgOTf, where
the major organic product was 68 (ratio of 66:68 ) 0.10:1).
Mechanism of C-C Bond-Forming Reductive Elimination:
Carboxylate Electronics. Our earlier studies showed that C-O
bond-forming reductive elimination from (Phpy)2PdIV(O2CAr)2
is slowed significantly with electron withdrawing benzoate
ligands (cf., Figure 2), and, as such, we first examined
complexes of general structure (Bzq)2PdIV(O2CAr)2, where the
substituents on the benzoate ligands were systematically varied.
However, the low solubility of these compounds precluded
quantitative mechanistic studies. Thus, subsequent efforts
aimed to compare (Bzq)2PdIV(O2CC9H19)2 (67) to (Bzq)2PdIV-
(O2CC9F19)2 (69), which contains sterically similar but highly
electron withdrawing perfluorinated carboxylates. In all of the
solvents examined (pyridine-d5, acetone-d6, DMSO-d6, and
CD3CN), electron deficient complex 69 was much less reactive
than 67, and it could be recovered quantitatively from the
reaction mixtures following our standard reductive elimination
Proposed Mechanism for C-C and C-O Bond-Forming
Reductive Elimination from (N∼C)2PdIV(O2CR)2. The solvent,
additive, and ligand effect studies, as well as the influence of
added carboxylate, all suggest that reductive elimination pro-
cesses from 67 occur via the pathway outlined in Scheme 16.
This proposal is consistent with all of the mechanistic data and
also provides a unifying mechanism for C-O and C-C bond-
forming reductive elimination for complexes of general structure
(N∼C)2PdIV(O2CR)2. In this scenario, C-O bond-forming
reductive elimination from 67 proceeds by an analogous
mechanism to that proposed for (Phpy)2PdIV(O2CR)2 (via pre-
equilibrium carboxylate dissociation followed by C-O coupling,
mechanism A). In contrast, C-C bond-forming reductive
elimination takes place by direct reductive elimination from the
6-coordinate starting material 67.
The data presented above are all consistent with Scheme 16.
In the presence of added carboxylate, the equilibrium for
carboxylate dissociation (step i of mechanism A) should be
shifted to the left, thereby leading to increased formation of
the C-C coupled product by direct reductive elimination from
I. Under conditions that accelerate C-O bond-forming reductive
elimination by mechanism A (i.e., solvents like CH3CN or
CHCl3, additives like HOAc or AgOTf, electron donating
carboxylate ligands), the C-O coupled product predominates.
In contrast, under conditions shown to slow C-O coupling (e.g.,
solvents like acetone or benzene, electron withdrawing car-
boxylate ligands), the C-C coupled product is formed in high
yield.
conditions (80 °C,
3 h). Complete consumption of
(Bzq)2PdIV(O2CC9F19)2 required heating at 80 °C for 3-16 d
depending on the solvent. In addition, C-C coupled 66 was
the sole organic product in every solvent examined (Table 9).
Mechanism of C-C Bond-Forming Reductive Elimination:
Added Carboxylate. Under standard reaction conditions (80 °C,
3 h, 15.2 mM in CH3CN), 68 was the major product, and the
1
66:68 ratio was 0.2:1 as determined by H NMR spectroscopy
(Table 10, entry 1). However, when 1 equiv of NBu4(O2CC9H19)
9
10982 J. AM. CHEM. SOC. VOL. 131, NO. 31, 2009

Reaction of (N∼C)2PdII with PhI(O2CR)2
A R T I C L E S
Scheme 17. Effect of AgBF4 on the Product Distribution of Reductive Elimination from 71
To provide final evidence in support of this mechanistic
Scheme 18. Rational Design of Conditions To Achieve C-C
manifold, we generated [(Bzq)2PdIV(O2R)]+ in situ and examined
the distribution of organic products from this species. As shown
in Scheme 17, treatment of (Bzq)2PdIV(Cl)(OAc) (71) with
AgBF4 at 80 °C [conditions that are expected to afford
[(Bzq)2PdIV(OAc)]BF4 (72)] resulted in rapid C-O bond-
forming reductive elimination to afford 73, with none of the
C-C coupled product 66 observed by 1H NMR spectroscopy.35
This result is in striking contrast to the reaction of 71 in the
absence of AgBF4, which yielded a 1:0.21 ratio of 73:66, as
well as to the reaction of (Bzq)2PdIV(OAc)2 (74) (which gave a
0.5:1 ratio of 73:66). Therefore, it provides a final piece of
compelling evidence in support of the proposed mechanism.
Unified Mechanism: C-C Coupling from Phenylpyridine
Complexes. If Scheme 16 does, in fact, represent a unified
mechanism for reductive elimination from (N∼C)2PdIV(O2CR)2,
we reasoned that it should be possible to rationally design
conditions to achieve C-C coupling from complexes where
N∼C ) 2-phenylpyridine. Guided by the studies above, we
examined conditions under which krel for C-O bond-forming
reductive elimination is predicted to be slow - with a highly
electron withdrawing carboxylate ligand and in the presence of
an excess of added carboxylate. We were delighted to find that
the reaction of (Phpy)2PdIV(O2CAr)2 [Ar ) p-CF3C6H4] in the
presence of 5 equiv of Bu4N(O2CAr) at 80 °C in DMSO for
5 h resulted in a 1.6:1 mixture of oxygenated product 32 to
biaryl product 4 (Scheme 18). This result demonstrates that
perturbations of the ancillary ligand set and additives have
similar effects in the 2-phenylpyridine and benzoquinoline
complexes, providing support for similar mechanisms in both
systems.
Bond-Forming Reductive Elimination from (Phpy)2PdIV(O2CAr)2
Complexes
These complexes have allowed us to conduct the first detailed
mechanistic studies of C-O bond-forming reductive elimination
from PdIV centers. In addition, we have studied competing C-C
coupling processes. Based on these investigations, we propose
that C-O bond-forming reductive elimination proceeds via an
ionic mechanism involving initial carboxylate dissociation,
followed by C-O coupling from a 5-coordinate cationic
intermediate. In contrast, the C-C bond-forming reaction is
believed to involve direct reductive elimination from the
octahedral PdIV starting material. Our mechanistic understanding
of these processes has facilitated the rational tuning of ancillary
ligands and reaction conditions in order to control the ratio of
organic products. Current efforts are focused on applying the
mechanistic insights obtained from these studies toward the
design and optimization of new PdII/IV-catalyzed reactions that
form both carbon-oxygen and carbon-carbon bonds.
Acknowledgment. We thank the National Science Foundation
(CHE-0545909), the Alfred P. Sloan Foundation and the Camille
and Henry Dreyfus Foundation for support of this work. A.R.D.
thanks Eli Lilly for a graduate fellowship. In addition, we are
grateful to Eugenio Alvarado and Chris Kojiro for assistance with
NMR spectroscopy and Jeff Kampf for X-ray crystallography.
Conclusions
This paper described the synthesis of a series of unusually
stable PdIV complexes of general structure (N∼C)2PdIV(O2CR)2.
Supporting Information Available: Experimental details and
spectroscopic data for new compounds. This material is available
free of charge via the Internet at http://pubs.acs.org.
(35) Only C-O coupled products were formed in this reaction; however,
both acetoxylated product 73 and the corresponding phenol (presum-
ably formed by ester hydrolysis under the reaction conditions) were
observed.
JA9014474
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J. AM. CHEM. SOC. VOL. 131, NO. 31, 2009 10983