Dioxygen activation by an organometallic Pd(II) precursor: Formation of a Pd(IV)-OH complex and its C-O bond formation reactivity

Article abstract of DOI:10.1039/c3cc49387c

The complex (Me₃tacn)Pd^II(CH₂CMe ₂C₆H₄) is readily oxidized by O₂ or H₂O₂ to yield the Pd^IV-OH complex [(Me ₃tacn)Pd^IV(OH)(CH₂CMe₂C ₆H₄)]⁺. Thermolysis of this product leads to the selective C(sp²)-O reductive elimination of 2-tert-butylphenol, no C(sp³)-O elimination product being detected. This system represents a rare example of selective C(sp²)-O bond formation that is relevant to Pd-catalyzed aerobic C-H hydroxylation reactions. The Royal Society of Chemistry.

Full text of DOI:10.1039/c3cc49387c

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Dioxygen Activation by an Organometallic Pd(II)
Precursor: Formation of a Pd(IV)-OH Complex and Its
C-O Bond Formation Reactivity
Cite this: DOI: 10.1039/x0xx00000x
Fengrui Qu,a Julia R. Khusnutdinova,a,b Nigam P. Rath,c and Liviu M. Miricaa,*
Received 00th January 2012,
Accepted 00th January 2012
DOI: 10.1039/x0xx00000x
www.rsc.org/
The complex (Me3tacn)PdII(CH2CMe2C6H4) is readily
oxidized by O2 or H2O2 to yield the PdIV-OH complex
[(Me3tacn)PdIV(OH)(CH2CMe2C6H4)]+. Thermolysis of this
product leads to the selective C(sp2)-O reductive elimination
Complex
(COD)Pd(CH2CMe2C6H4) in diethyl ether.7 The single crystal
X-ray characterization of reveals a square planar geometry
1 was prepared by reacting Me3tacn with
1
around the PdII center that is bound to two C and two N atoms,
while the third N atom of the Me3tacn ligand points away from
the Pd center (Fig. 1, left), similar to the previously reported
(Me3tacn)PdIIMe2 complex.6d The Pd-C distances are 2.010 Å
and 2.016 Å, respectively, similar to those found for other
palladacycles complexes supported by N-donor ligands.8 NMR
analysis reveals one singlet peak for the three N-methyl groups
of the Me3tacn ligand, indicating the three N-Me groups are
rapidly exchanging on the NMR timescale. In addition, the
dynamic behavior of Me3tacn leads to a plane of symmetry
incorporating the palladacycle fragment, as suggested by the
singlet NMR peaks observed for Pd-CH2CMe2 and Pd-
CH2CMe2 at 1.80 and 1.26 ppm, respectively.
of 2-t
-butyl-phenol, no C(sp3)-O elimination product being
detected. This system represents a rare example of selective
C(sp2)-O bond formation that is relevant to Pd-catalyzed
aerobic C-H hydroxylation reactions.
Palladium-catalyzed C-H functionalization reactions have been
developed over the past two decades as important and versatile
tools in organic synthesis.1,2,3 Despite the wide range of such
synthetic methods, there is a dearth of oxidative C-H
functionalization
reactions
using
inexpensive
and
environmentally friendly oxidants such as O2. While the
majority of aerobic Pd-catalyzed reactions involve a Pd0/PdII
catalytic cycle,4 several recent studies have proposed high-
valent PdIII or PdIV species as active intermediates in aerobic C-
H functionalization reactions.5 We have recently employed
multidentate flexible ligands to stabilize high-valent PdIII and
PdIV complexes and studied in detail their reactivity.6 In
addition, such high-valent Pd species can be generated via
aerobic oxidation of PdII precursors,6c,d,g which represents an
improvement over the expensive and hazardous oxidants
typically used to generate high-valent Pd intermediates in
catalytic or stoichiometric reactions.5 For example, we have
reported that (Me3tacn)PdIIMe2 can be oxidized by O2 to
generate the isolable [(Me3tacn)PdIVMe3]+ complex formed
upon methyl group transfer upon the aerobic oxidation to
PdIV.6d Herein we report the palladacycle complex
Scheme 1 Oxidative reactivity of the PdII complex
1.
(Me3tacn)PdII(CH2CMe2C6H4)
oxidation with O2 or H2O2 to directly form the isolable complex
[(Me3tacn)PdIV(OH)(CH2CMe2C6H4)]+ (
) without the need for
alkyl group transfer (Scheme 1). Thermolysis of leads to
(
1
)
that undergoes rapid
2
2
selective formation of 2-tert-butyl-phenol. Additional reactivity
studies suggest that the tridentate ligand employed herein leads
to selective C(sp2)-O bond formation, while no C-halide bond
formation was observed for the analogous PdIV-halide
complexes, suggesting that ligand denticity can be used to
control the selectivity of these high-valent Pd complexes in
various C-heteroatom bond formation reactions.
Fig. 1 ORTEP representation of
1
1
(left) and the cation of [2]ClO4 (right). Selected
, Pd1-C1, 2.015(3); Pd1-C8, 2.010(6); Pd1- N1,
bond lengths (Å) and angels (o):
2.215(4); Pd1-N3, 2.240(3); C1-Pd1-C8, 78.99(14); 2, Pd1-C1, 2.024(2); Pd1-C8,
2.061(2); Pd1-O1, 2.0185(17); Pd1-N1, 2.263(2); Pd1-N2, 2.117(2); Pd1-N3,
2.227(2); O1-Pd1-C1, 87.29(9); O1-Pd1-C8, 90.02(8); C1-Pd1-C8, 81.36(9).
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The cyclic voltammogram (CV) of
1
in 0.1
M
=
used as an oxidant for oxidatively-induced C-heteroatom bond
formation reactions (see below).
We next sought to study the C-O bond formation reactivity of
Bu4NPF6/MeCN shows a reversible oxidation wave at E1/2
−0.53 V (∆Ep = 71 mV) vs. Fc+/Fc,7 which is significantly
lower than those for analogous PdIIMe2 complexes with
2, especially the selectivity of the C-O bond formation, as C-
bidentate N-donor ligands,6c and only slightly higher than our heteroatom bond formation studies from asymmetric
previously reported complex (Me3tacn)PdIIMe2.6d We attribute dihydrocarbyl-PdIV complexes are rare.11 When
the low redox potential of to the ability of the Me3tacn ligand 110 °C in DMSO, a new transient species (
2
was heated to
1
4) is observed
to provide an axial donor atom and thus stabilize the oxidized followed by formation of 2-tert-butylphenol in up to 74% yield,
high-valent Pd species that generally adopt a geometry with a as determined by NMR and GC-MS (Scheme 3).12 C-O bond
higher coordination number.6i
formation was also observed in other polar aprotic solvents:
The observed low redox potential for
1
prompted us to study thermolysis in DMF leads to the formation of 2-tert-
its oxidation by O2. Exposure of a colorless solution of
1
to O2 butylphenol in a comparable yield.7 Interestingly, the organic
in presence of H2O (10% H2O:MeCN v:v) generates rapidly a product that would result from C(sp3)-O reductive elimination,
1
yellow solution, and H NMR analysis reveals the formation of PhCMe2CH2OH, was not detected under any of the
a
new species identified as the PdIV complex experimental conditions examined. In addition, C-C bond
[(Me3tacn)PdIV(OH)(CH2CMe2C6H4)]+
(2). The yield of 2 can formation to form a benzocyclobutane derivative is unlikely
be increased to >98 % when the oxidation is performed in due to the strain of the four-membered ring product.
presence of either 10% 1.0 M phosphate buffer (pH 7.4) or a
slight excess of acid.7 These results suggest that aerobic
oxidation of
1 requires the presence of protons for O2 reduction,
and addition of acid or even use of a buffered solution ensures a
rapid reduction of O2 over the course of the reaction. In
addition, complex
quantitative yield upon addition of 5 equiv H2O2 (Scheme 1).
The PdIV product can isolated as the perchlorate salt, [
]ClO4,
2 can also be rapidly generated in almost
2
and characterized by X-ray crystallography, NMR, and ESI-
MS.7 X-ray analysis reveals an octahedral Pd center with the
two C atoms and two N atoms in the equatorial plane, while the
third N donor from Me2tacn and the hydroxide ligand occupy
the axial positions (Fig. 1, right). The Pd-C distances (2.024 Å
and 2.061 Å) are similar to the only other PdIV(CH2CMe2C6H4)
complex supports by a tridentate N-donor ligand,9 while the Pd-
Scheme 3 Aryl C-O bond reductive elimination upon thermolysis of 2.
The
complex
4
was
o
tentatively
assigned
as
[(Me3tacn)PdII(CH2CMe2-
-OH-C6H4)]+ based on ESI-MS and
NMR. ESI-MS of the reaction mixture shows the presence of a
peak at m/z 426.1717 (calcd. [(Me3tacn)PdII(CH2CMe2-
o
-OH-
1
C6H4)]+ 426.1731),13 while the H NMR spectrum reveals a
OH distance (2.018 Å) is similar to those of other palladacycle
singlet at 2.16 ppm for the Pd-CH2 group, similar to complex
(singlet at 1.80 ppm) and in the typical range of 1.96-2.37 ppm
for and
PdII(CH2CMe2Ph)14 PdII(CH2CMe2- -C6H4)15
complexes with N donor ligands.
The selective formation of 2-tert-butylphenol from
1
1
PdIV-OH complexes.8a The H NMR of
2 in CD3CN exhibits
two doublets at 4.05 ppm and 3.97 ppm for the Pd-CH2 group,
o
supporting a geometry lacking a plane of symmetry.7
2
represents a rare example of C-OH elimination from an
organometallic PdIV complex. While Caryl-O bond formation
reactions from PdIV have been reported (e.g., Caryl-OH bond
formation from PdIV monoaryl complexes16 or Caryl-carboxylate
elimination from PdIV bis-aryl complexes17), the selective Caryl
-
O vs. Calkyl-O bond formation reactivity has not been observed
before. The mechanism of this reaction likely involves a
concerted Caryl-O elimination from a PdIV center, as proposed
Scheme 2 Proposed mechanism for aerobic oxidation of 1.
recently.16 Moreover, the effect of concentration of
2
on the
On the basis of previous mechanistic studies of the aerobic
oxidation of (Me3tacn)PdIIMe2,6d we propose an analogous
yield of 2-tert-butylphenol suggests that
mechanism for Calkyl-O bond formation is unlikely.
In order to provide insight into the observed selective C(sp2)-
vs. C(sp3)-O bond formation reactivity for
DFT
a bimolecular
mechanism for the O2 activation by
1 that involves the
formation of an PdIV-OOH intermediate followed by the
formation the PdIV-OH product (Scheme 2). Indeed, the ESI-
MS of the oxidation reaction solution shows two peaks with
m/z values of 426.1732 and 442.1685, corresponding to
O
2,
calculations were employed to determine the activation
parameters for the two possible C-O bond formation steps.
[(Me3tacn)PdIV(OH)(CH2CMe2C6H4)]+ (
2
, calcd. m/z 426.1739)
and [(Me3tacn)PdIV(OOH)(CH2CMe2C6H4)]+
, calcd. m/z
442.1688), respectively.7 The decrease of the peak intensity of
over time is accompanied by an increase of the relative peak
First, the geometry optimized structure of
2 was determined
using the M06/CEP-31G level of theory and with solvent
(
3
correction,7 and then the transition states for both C(sp2)-O vs.
C(sp3)-O bond formation reactions were calculated to yield H‡
∆
3
values of 21.9 and 25.2 kcal/mol, respectively (Scheme 4 and
Figure S27). The lower enthalpy of activation by 3.3 kcal/mol
for the former transition state supports the observed selectivity
and suggests that C(sp2)-O bond-forming reductive elimination
is preferred from a PdIV center supported by a tridentate ligand.
Interestingly, the opposite selectivity was recently observed by
Sanford et al. for C(sp3)-F vs. C(sp2)-F coupling from a PdIV
center supported by a bidentate ligand (see below).11
intensity of
formation of
2, supporting the intermediacy of 3 during the
2
. A similar mechanism was also proposed for the
aerobic oxidation of related PdII and PtII organometallic
complexes.6c,e,g,10 Compared to the aerobic oxidation of
(Me3tacn)PdIIMe2, the oxidation of
1
by O2 to yield an isolable
PdIV product does not require and alkyl group transfer step that
cannot occur for 2 6d
Thus, it can expected that O2 could be
.
2 | J. Name., 2012, 00, 1-3
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1. E. Negishi, Handbook of Organopalladium Chemistry for Organic
Synthesis, John Wiley & Sons, Hoboken, NJ, 2002.
2. P. M. Henry, Palladium Catalyzed Oxidation of Hydrocarbons, D.
Reidel, Boston, 1980.
3. a) O. Daugulis, H.-Q. Do, D. Shabashov, Acc. Chem. Res., 2009, 42,
1074; b) K. M. Engle, T.-S. Mei, M. Wasa, J.-Q. Yu, Acc. Chem. Res.,
2012, 45, 788.
Scheme 4 Calculated activation parameters for C(sp2)-O vs. C(sp3)-O bond
formation reactivity of
4. a) S. S. Stahl, Science, 2005, 309, 1824; b) S. S. Stahl, Angew. Chem. Int.
Ed., 2004, 43, 3400; c) B. M. Stoltz, Chem. Lett., 2004, 33, 362; d) E. M.
Beck, N. P. Grimster, R. Hatley, M. J. Gaunt, J. Am. Chem. Soc., 2006,
128, 2528; e) M. S. Sigman, D. R. Jensen, Acc. Chem. Res., 2006, 39,
221; f) A. N. Campbell, S. S. Stahl, Acc. Chem. Res., 2012, 45, 851; g)
A. N. Vedernikov, Acc. Chem. Res., 2012, 45, 803; h) K. M. Gligorich,
M. S. Sigman, Chem. Commun., 2009, 3854; i) Z. Shi, C. Zhang, C.
Tang, N. Jiao, Chem. Soc. Rev., 2012, 41, 3381.
5. a) T. W. Lyons, M. S. Sanford, Chem. Rev., 2010, 110, 1147; b) L.-M.
Xu, B.-J. Li, Z. Yang, Z.-J. Shi, Chem. Soc. Rev., 2010, 39, 712; c) P.
Sehnal, R. J. K. Taylor, I. J. S. Fairlamb, Chem. Rev., 2010, 110, 824; d)
D. C. Powers, T. Ritter, Top. Organomet. Chem., 2011, 35, 129; e) J. R.
Khusnutdinova, L. M. Mirica, in C-H Activation and Functionalization,
Transition Metal Mediation, Royal Society of Chemistry, 2012; f) K.
Muniz, Angew. Chem. Int. Ed., 2009, 48, 9412.
6. a) J. R. Khusnutdinova, N. P. Rath, L. M. Mirica, J. Am. Chem. Soc.,
2010, 132, 7303; b) J. R. Khusnutdinova, N. P. Rath, L. M. Mirica,
Angew. Chem. Int. Ed., 2011, 50, 5532; c) J. R. Khusnutdinova, N. P.
Rath, L. M. Mirica, J. Am. Chem. Soc., 2012, 134, 2414; d) J. R.
Khusnutdinova, F. Qu, Y. Zhang, N. P. Rath, L. M. Mirica,
Organometallics, 2012, 31, 4627; e) F. Tang, F. Qu, J. R.
Khusnutdinova, N. P. Rath, L. M. Mirica, Dalton Trans., 2012, 41,
14046; f) J. Luo, J. R. Khusnutdinova, N. P. Rath, L. M. Mirica, Chem.
Commun., 2012, 48, 1532; g) F. Tang, Y. Zhang, N. P. Rath, L. M.
Mirica, Organometallics, 2012, 31, 6690; h) J. Luo, N. P. Rath, L. M.
Mirica, Organometallics, 2012, 31, 3343; i) L. M. Mirica, J. R.
Khusnutdinova, Coord. Chem. Rev., 2013, 299.
2
.
The oxidation reactivity of
oxidants such as N-fluoro-2,4,6-trimethylpyridinium triflate,
PhICl2 and I2. The corresponding products,
[(Me3tacn)PdIV(F)(CH2CMe2C6H4)]+ ), [(Me3tacn)PdIV(Cl)
(CH2CMe2C6H4)]+ ( ) and [(Me3tacn)PdIV(I)(CH2CMe2C6H4)]+
) were isolated, and [6]ClO4 and [7]I were structurally
characterized to reveal a coordination geometry similar to that
of
(Fig. S28).7 Interestingly, no C-halide reductive
elimination was observed upon prolonged heating of either
or
. By comparison, examples of C(sp3)-F and C(sp2)-F bond
1 was also tested using other
(
5
6
(
7
2
5, 6,
7
formation upon reductive elimination from PdIV complexes
supported by bidentate ligands were recently reported,17a,18 and
the formation of a five-coordinate intermediate via ligand
dissociation11 or the presence of a hemi-labile sulfonamide
ligand18 was proposed during C-F reductive elimination. This
suggests that formation of a five-coordinate PdIV intermediate is
likely a prerequisite for facile C(sp2)-F bond formation
reactivity and such intermediate is not easily accessible for 2,
most likely due to the presence of the three strong amine donors
of Me3tacn. The calculated transition states for the C(sp2)-F and
C(sp3)-F bond formation reactions from
∆
5 yield comparable
H‡ values of 29.4 and 30.5 kcal/mol, respectively (Figure
7. See ESI for more details.
S27),7 strongly suggesting that both types of C-halide bond
formation from the (Me3tacn)PdIV center are disfavored.
Overall, this observed ligand-controlled bond formation
reactivity can be exploited for developing selective aerobically-
induced C-O bond formation catalytic transformations, which
are currently being investigated by us.
8. a) A. J. Canty, H. Jin, A. S. Roberts, B. W. Skelton, A. H. White,
Organometallics, 1996, 15, 5713; b) J. Campora, P. Palma, D. del Rio, J.
A. Lopez, E. Alvarez, N. G. Connelly, Organometallics, 2005, 24, 3624.
9. J. Campora, P. Palma, D. del Rio, E. Carmona, C. Graiff, A. Tiripicchio,
Organometallics, 2003, 22, 3345.
10. a) V. V. Rostovtsev, J. A. Labinger, J. E. Bercaw, T. L. Lasseter, K. I.
Goldberg, Organometallics, 1998, 17, 4530; b) V. V. Rostovtsev, L. M.
Henling, J. A. Labinger, J. E. Bercaw, Inorg. Chem., 2002, 41, 3608; c)
E. M. Prokopchuk, H. A. Jenkins, R. J. Puddephatt, Organometallics,
1999, 18, 2861; d) E. M. Prokopchuk, R. J. Puddephatt, Can. J. Chem.,
2003, 81, 476; e) J. R. Khusnutdinova, P. Y. Zavalij, A. N. Vedernikov,
Organometallics, 2007, 26, 2402; f) A. N. Vedernikov, Chem. Commun.,
2009, 4781.
In summary, we report herein an organometallic PdII complex
1
that undergoes facile aerobic oxidation to form a stable PdIV-
OH complex
2 that was isolated and fully characterized. The O2
activation reactivity is due to the low oxidation potential of
1
supported by the tridentate amine ligand Me3tacn that can
effectively stabilize the octahedral geometry of the generated
PdIV center. Interestingly, thermolysis of the organometallic
11. J. M. Racowski, J. B. Gary, M. S. Sanford, Angew. Chem. Int. Ed., 2012,
51, 3414.
PdIV-OH complex
2
leads to selective C(sp2)-O vs. C(sp3)-O
12. Trace water is likely the source of protons for the formation of 2-tert-
butylphenol. When the reaction was performed in D2O, the product 2-
(CMe2(CH2D))-phenol was obtained (see ESI for more details).
13. The starting material 2 also has an m/z of 426.1739. However, the peak
observed by ESI-MS persists even after 2 has reacted completely based
on 1H NMR, indicating that a new product with a similar mass is formed
(m/z calcd for 4: 426.1731).
14. a) E. Gutierrez, M. C. Nicasio, M. Paneque, C. Ruiz, V. Salazar, J.
Organomet. Chem., 1997, 549, 167; b) L. Ortiz de la Tabla, I. Matas, E.
Alvarez, P. Palma, J. Campora, J. Chem. Soc., Dalton Trans., 2012, 41,
14524.
bond formation and formation of 2-tert-butylphenol. This
represents a rare example of a selective Caryl-O reductive
elimination from a PdIV-OH complex that is formed via aerobic
oxidation of a PdII precursor and thus is relevant to Pd-
catalyzed aerobic hydroxylation reactions.19 Moreover, the
observed preference for C-O vs. C-halide bond formation
reactivity is currently explored for the development of selective
aerobic C-O bond formation transformations.
Notes and references
Department of Chemistry, Washington University, One Brookings
15. J. Campora, J. A. Lopez, P. Palma, D. del Rio, E. Carmona, P. Valerga,
a
C. Graiff, A. Tiripicchio, Inorg. Chem., 2001, 40, 4116.
Drive, St. Louis, Missouri 63130-4899, mirica@wustl.edu
b Current address: Department of Organic Chemistry, Weizmann Institute
of Science, Rehovot 76100, Israel.
16. W. Oloo, P. Y. Zavalij, J. Zhang, E. Khaskin, A. N. Vedernikov, J. Am.
Chem. Soc., 2010, 132, 14400.
17. a) J. M. Racowski, A. R. Dick, M. S. Sanford, J. Am. Chem. Soc., 2009,
131, 10974; b) A. R. Dick, J. W. Kampf, M. S. Sanford, J. Am. Chem.
Soc., 2005, 127, 12790.
c Department of Chemistry and Biochemistry, One University Boulevard,
University of Missouri – St. Louis, Missouri 63121-4400.
†
Electronic Supplementary Information (ESI) available: Experimental
18. T. Furuya, D. Benitez, E. Tkatchouk, A. E. Strom, P. P. Tang, W. A.
details, spectroscopic characterization, computational details, and X-ray
crystallographic data. See DOI: 10.1039/c000000x/
Goddard, T. Ritter, J. Am. Chem. Soc., 2010, 132, 3793.
19. Y.-H. Zhang, J.-Q. Yu, J. Am. Chem. Soc., 2009, 131, 14654.
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