Mechanism of alcohol oxidation by dipicolinate vanadium(V): Unexpected role of pyridine

Article abstract of DOI:10.1021/ja105739k

Dipicolinate vanadium(V) alkoxide complexes (dipic)V^V(O)(OR) (OR = isopropoxide (1), n-butanoxide (2), cyclobutanoxide (3), and α-tert-butylbenzylalkoxide (4)) react with pyridine to afford vanadium(IV) and 0.5 equiv of an aldehyde or ketone product. The role of pyridine in the reaction has been investigated. Both NMR and X-ray crystallography experiments indicate that pyridine coordinates to 1, which is in equilibrium with (dipic)V^V(O)(OⁱPr)(pyr) (1-Pyr). Kinetic studies of the alcohol oxidation suggest a pathway where the rate-limiting step is bimolecular and involves attack of pyridine on the C-H bond of the isopropoxide ligand of 1 or 1-Pyr. The oxidations of mechanistic probes cyclobutanol and α-tert-butylbenzylalcohol support a two-electron pathway proceeding through a vanadium(III) intermediate. The alcohol oxidation reaction is promoted by more basic pyridines and facilitated by electron-withdrawing substituents on the dipicolinate ligand. The involvement of base in the elementary alcohol oxidation step observed for the dipicolinate system is an unprecedented mechanism for vanadium-mediated alcohol oxidation and suggests new ways to tune reactivity and selectivity of vanadium catalysts.

Full text of DOI:10.1021/ja105739k

Published on Web 12/01/2010
Mechanism of Alcohol Oxidation by Dipicolinate Vanadium(V):
Unexpected Role of Pyridine
Susan K. Hanson,* R. Tom Baker,‡ John C. Gordon, Brian L. Scott,
L. A. “Pete” Silks, and David L. Thorn
Chemistry, Bioscience, and Materials Physics Applications DiVisions, Los Alamos National
Laboratory, Los Alamos, New Mexico 87544, United States
Received June 29, 2010; E-mail: skhanson@lanl.gov
Abstract: Dipicolinate vanadium(V) alkoxide complexes (dipic)VV(O)(OR) (OR ) isopropoxide (1), n-
butanoxide (2), cyclobutanoxide (3), and R-tert-butylbenzylalkoxide (4)) react with pyridine to afford
vanadium(IV) and 0.5 equiv of an aldehyde or ketone product. The role of pyridine in the reaction has
been investigated. Both NMR and X-ray crystallography experiments indicate that pyridine coordinates to
1, which is in equilibrium with (dipic)VV(O)(OiPr)(pyr) (1-Pyr). Kinetic studies of the alcohol oxidation suggest
a pathway where the rate-limiting step is bimolecular and involves attack of pyridine on the C-H bond of
the isopropoxide ligand of 1 or 1-Pyr. The oxidations of mechanistic probes cyclobutanol and R-tert-
butylbenzylalcohol support a two-electron pathway proceeding through a vanadium(III) intermediate. The
alcohol oxidation reaction is promoted by more basic pyridines and facilitated by electron-withdrawing
substituents on the dipicolinate ligand. The involvement of base in the elementary alcohol oxidation step
observed for the dipicolinate system is an unprecedented mechanism for vanadium-mediated alcohol
oxidation and suggests new ways to tune reactivity and selectivity of vanadium catalysts.
Introduction
center and deprotonation of the coordinated alcohol by base,
followed by ꢀ-hydride elimination to generate a palladium(II)
Catalytic aerobic oxidation of alcohols is an attractive method
for the synthesis of ketones, aldehydes, and carboxylic acids.
Using air as an oxidant offers significant environmental and
economic benefits over traditional stoichiometric oxidants like
potassium permanganate, chromium- and DMSO-based reagents,
and Dess-Martin periodinane.1-3 Since the initial discovery
of palladium-catalyzed aerobic alcohol oxidation reported by
Blackburn and Schwartz, more recent work by Uemura, Stahl,
Sigman, Stoltz, and others has described highly effective
palladium catalysts that operate under mild conditions.4-10
Extensive investigations of the palladium systems have given
rise to significant advances both in optimizing known catalysts
and more importantly, the discovery of new catalysts.6-8 In
general, mechanistic studies of the palladium systems support
a pathway involving coordination of alcohol to the palladium
hydride intermediate.2,8
Recently, a number of base metal catalysts for aerobic alcohol
oxidation have been uncovered, including copper and vanadium
complexes.3,11-14 The use of earth-abundant metals is advanta-
geous in terms of catalyst cost and availability, but these metals
typically react by different mechanisms than their precious-metal
counterparts. For example, a hydrogen atom abstraction pathway
is often invoked for the reactions of copper complexes.15-17
The mechanism of alcohol oxidation has important ramifications
for the reaction selectivity; a copper dimer of redox-active
phenolate ligands reported by Wieghardt and co-workers is
thought to react by hydrogen atom abstraction and catalyzes
the oxidation of secondary alcohols to ketones and diols.18
Vanadium complexes are also emerging as promising cata-
lysts for aerobic alcohol oxidation. Uemura and co-workers
reported the aerobic oxidation of phenyl- and alkyl-substituted
‡ Current address: Department of Chemistry and Centre for Catalysis
Research and Innovation, University of Ottawa, Ottawa, ON, Canada K1N
6N5.
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17804 J. AM. CHEM. SOC. 2010, 132, 17804–17816
10.1021/ja105739k  2010 American Chemical Society

Alcohol Oxidation by Dipicolinate Vanadium(V)
A R T I C L E S
Scheme 1. (a) Hydride-Transfer Step Proposed by Uemura and Co-workers for the Oxidation of Propargylic Alcohols20 and (b) Oxidation of
Cyclopropyl-Substituted R-Hydroxy Ester A, As Observed by Toste and Co-workers, Proceeds with No Ring Opening, Suggesting a
Hydride-Transfer Pathway24
propargylic alcohols catalyzed by VIV(O)(acac)2.19,20 The sub-
strate scope of this reaction was subsequently extended by
Ragauskas and co-workers, who found that the combination of
VIV(O)(acac)2 and DABCO (DABCO ) 1,4-diazabicyclo[2.2.2]-
octane) catalyzed the aerobic oxidation of benzylic and allylic
alcohols in ionic liquid solvent.21,22 More recently, Ohde and
Limberg have reported a metavanadate-cinnamic acid system
which is also effective for the aerobic oxidation of activated
alcohols.23 Toste and Chen have developed processes for the
aerobic oxidative kinetic resolution of R-hydroxyesters, R-hy-
droxyamides, and R-hydroxyphosphonates using chiral Schiff-
base vanadium complexes.24-26 At higher temperatures, Ve-
lusamy and Punniyamurthy have found that V2O5 catalyzes the
aerobic oxidation of primary and secondary aliphatic alcohols
in toluene solvent.27
Despite an increasing frequency of reports of metal-catalyzed
aerobic oxidation, little is known about the mechanism of
vanadium-mediated alcohol oxidation. Uemera and co-workers
found that the radical inhibitors 2,6-di-tert-butyl-4-methylphenol
(BHT) and galvinoxyl did not affect the catalytic oxidation of
propargylic alcohols, and thus proposed that the reaction
proceeds through a vanadium(III) intermediate formed via
hydride transfer from the alkoxide ligand to the vanadium-oxo
ligand (Scheme 1a).19,20 A similar pathway for the oxidative
kinetic resolution of R-hydroxyesters was proposed by Toste
and co-workers, based on the finding that the cyclopropyl-
substituted R-hydroxyester A was oxidized with no ring opening
(Scheme 1b).24 Chen and co-workers also favored a hydride-
transfer pathway for the oxidative kinetic resolution of R-hy-
droxyesters, amides, and phosphonates, but no in-depth mecha-
nistic study has been carried out on any of the catalytic
systems.25,26
electron pathways involving a vanadium(IV) intermediate have
also frequently been invoked for vanadium mediated alcohol
oxidation. The mechanism of the stoichiometric oxidation of
alcohols by vanadate (VVO2+) in aqueous acidic solution has
been extensively studied, and is thought to proceed through
radical intermediates.28-31 Ohde and Limberg have proposed a
hydrogen atom abstraction pathway for the oxidation of alcohols
by a vanadium(V) cinnamate complex, based on a primary
kinetic isotope effect and an observed correlation of the turnover
frequency with homolytic C-H bond strength.23 Given the
variety of pathways proposed, a greater understanding of the
mechanisms of vanadium-mediated alcohol oxidation could
facilitate the development of more effective and versatile aerobic
oxidation catalysts.
We report here the results of a detailed study of the
mechanism of alcohol oxidation by dipicolinate vanadium(V).
Our findings suggest that the alcohol oxidation reaction proceeds
by an entirely different pathway than that proposed for palladium
or copper complexes, and differs substantially from what has
been proposed for other vanadium catalysts. Kinetic studies have
elucidated the role of pyridine in the elementary oxidation step,
and oxidation of two substrate probes suggests a two-electron
pathway involving a vanadium(III) intermediate. Trends in
reactivity based on varying substitution of the dipicolinate ligand
and the pyridine base are established.
Results
Synthesis of Vanadium(V) Alkoxide Complexes. As previ-
ously reported,32 the isopropoxide ligand on the complex
(dipic)VV(O)(OiPr) (1) (dipic ) dipicolinate) exchanges readily
with free alcohol at room temperature, enabling the facile
synthesis of a number of alkoxide derivatives. The n-butanoxide
complex (dipic)VV(O)(OBu) (2) was prepared by reaction of 1
with an excess of 1-butanol in acetonitrile solvent, followed by
removal of the solvent under vacuum. The complexes (dipic)-
VV(O)(OCyBu) (3) (OCyBu ) cyclobutanoxide) and (dipic)-
VV(O)(TBA) (4) (TBA ) R-tert-butylbenzylalkoxide) were
prepared from cyclobutanol and R-tert-butylbenzylalcohol using
similar procedures (Figure 1, see experimental section for
Although hydride-transfer pathways were proposed for the
vanadium-catalyzed alcohol oxidations discussed above, one-
(19) Maeda, Y.; Kakiuchi, N.; Matsumura, S.; Nishimura, T.; Uemura, S.
Tetrahedron Lett. 2001, 42, 8877–8879.
(20) Maeda, Y.; Kakiuchi, N.; Matsumura, S.; Nishimura, T.; Kawamura,
T.; Uemura, S. J. Org. Chem. 2002, 67, 6718–6724.
(21) Jiang, N.; Ragauskas, A. J. Tetrahedron Lett. 2006, 48, 273–276.
(22) Jiang, N.; Ragauskas, A. J. J. Org. Chem. 2007, 72, 7030–7033.
(23) Ohde, C.; Limberg, C. Chem.sEur. J. 2010, 16, 6892–6899.
(24) Radosevich, A.; Musich, C.; Toste, F. D. J. Am. Chem. Soc. 2005,
127, 1090–1091.
(28) West, D. M.; Skoog, D. A. J. Am. Chem. Soc. 1960, 82, 280–283.
(29) Littler, J. S.; Waters, W. A. J. Chem. Soc. 1959, 1299–1305.
(30) Littler, J. S.; Waters, W. A. J. Chem. Soc. 1959, 4046–4052.
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Chem. Soc. 2006, 128, 6308–6309.
(26) Weng, S. S.; Shen, M. W.; Kao, J. Q.; Munot, Y. S.; Chen, C. T.
Proc. Natl. Acad. Sci. U.S.A. 2006, 103, 3522–3527.
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9
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A R T I C L E S
Hanson et al.
Figure 1. Vanadium(V) alkoxide complexes.
details). The dipicolinate alkoxide complexes generally co-
1
crystallize with one equivalent of the alcohol. The H NMR
spectra of the dipicolinate complexes in CD3CN show charac-
teristic resonances for the V-OCH protons on the alkoxide ligand
that are shifted significantly upfield from the corresponding
resonance of the free alcohol, at 6.35 ppm for 1, 5.99 ppm for
2, 6.41 ppm for 3, and 7.15 ppm for 4. The IR spectra of 1-4
show sharp νVdO stretching frequencies in the range of 988-991
cm-1
.
Several additional vanadium(V) isopropoxide complexes were
prepared using derivatives of dipicolinic acid. Reaction of
4-nitrodipicolinic acid (H2dipicNO2) or 4-chlorodipicolinic acid
(H2dipicCl) with VV(O)(OiPr)3 in isopropanol afforded the
complexes (dipicNO2)VV(O)(OiPr) (5) and (dipicCl)VV(O)(OiPr)
(6), respectively. 4-Methoxydipicolinic acid (H2dipicOMe) was
prepared using a published procedure,33,34 and reaction with
VV(O)(OiPr)3 in isopropanol yielded (dipicOMe)VV(O)(OiPr)
(7). Finally, reaction of 8-hydroxyquinoline-2-carboxylic acid
(H2HQC) with VV(O)(OiPr)3 in acetonitrile solvent yielded
(HQC)VV(O)(OiPr) (8). The 1H NMR spectra of complexes 5-8
(CD3CN) show resonances for the methine protons on the
isopropoxide ligand that shift downfield as the electron-donating
ability of the ligand increases, at 6.51 ppm for 5, 6.39 ppm for
6, 6.22 ppm for 7, and 6.07 ppm for 8. A single resonance is
evident in the 51V NMR spectra of complexes 5-8, appearing
at -588.2, -588.9, -590.3, and -549.8 ppm, respectively.
Coordination of Pyridine to 1. Addition of pyridine to a
CD3CN solution of 1 resulted in an immediate change in the
1H NMR chemical shifts of 1, suggestive of coordination of
pyridine to 1. The change in chemical shift was particularly
pronounced for the methine resonance on the isopropoxide
ligand of 1, which shifted from 6.35 ppm to 6.50 ppm upon
addition of 1 equiv pyridine. Titrating the sample with increasing
amounts of pyridine revealed that the chemical shifts of both 1
and pyridine varied as a function of pyridine concentration.
Sharp signals were observed for both pyridine and the isoprop-
oxide complex at room temperature, consistent with a fast
exchange process. A similar change in chemical shift as a
function of pyridine was also noted for the 51V NMR signal of
1 (Figure 2). In both the 1H and 51V NMR titration experiments,
the change in chemical shift leveled off at concentrations of
pyridine greater than ca. 0.6 M, indicating an equilibrium
coordination of pyridine according to eq 1. Titrations were also
Figure 2. Plot of 51V NMR chemical shift (CD3CN) vs concentration of
pyridine, 298 K (red squares, 2,6-di-tert-butylpyridine; purple diamonds,
2,6-lutidine; green triangles, 4-cyanopyridine; and blue circles, pyridine).
carried out with 4-cyanopyridine, 2,6-lutidine, and 2,6-di-tert-
butylpyridine (Figure 2). 2,6-Di-tert-butypyridine and 2,6-
lutidine are expected to be too sterically hindered to coordinate
to the vanadium center and the chemical shifts of 1 were
unaffected by the addition of either of these bulky bases,
confirming that the change in chemical shift observed for the
parent pyridine is due to pyridine coordination and not due to
a medium effect or a change in solvent polarity. From the NMR
data, values of Keq of 15((2) M-1 for pyridine and 2((1) M-1
for 4-cyanopyridine at 298 K could be calculated (using the
average of two independent titrations) according to eqs 2-3.
For pyridine, a value of Keq of 2((1) M-1 was also determined
at 340 K (the temperature at which kinetic studies of the pyridine
dependence of the reaction were carried out, Vide infra).
[1-Pyr]
[1][Pyr]
Keq
)
(2)
(3)
(33) Pellegatti, L.; Zhang, J.; Drahos, B.; Villette, S.; Suzenet, F.;
Guillaumet, G.; Petoud, S.; Toth, E. Chem. Commun. 2008, 6591–
6593.
δ - δ1
(δ1Pyr - δ)[Pyr]
(34) Gassner, A. L.; Duhot, C.; Bunzli, J. C. G.; Chauvin, A. S. Inorg.
Chem. 2008, 47, 7802–7812.
Keq
)
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Alcohol Oxidation by Dipicolinate Vanadium(V)
A R T I C L E S
Figure 3. X-ray structure of 1-Pyr (thermal ellipsoids shown at 50%
probability, H atoms omitted for clarity). Selected bond lengths (Å) for
1-Pyr: V1-O6 ) 1.585(1), V1-O5 ) 1.755(1), V1-O3 ) 1.958(1),
V1-O2 ) 1.951(1), V1-N1 ) 2.088(2), V1-N2 ) 2.369(2).
3 reacted in pyr-d5 solution over 30 min at 100 °C to afford
cyclobutanone (93% yield) and 9 (Scheme 2). No ring-opened
products were detected by 1H NMR spectroscopy. Thermoly-
sis of complex 4 in pyr-d5 solution (20 min at 100 °C)
afforded the ketone 2,2-dimethylpropiophenone (98% yield)
and 9 (Scheme 2). No C-C bond fission products (such as
benzaldehyde) were formed in this reaction. In contrast, in
the absence of pyridine in CD3CN solution, complex 4 reacted
more slowly (2 weeks at room temperature), affording
benzaldehyde (92% yield) as the major organic product.36
The fate of the tert-butyl moiety in this reaction is still under
investigation;37 however, the formation of benzaldehyde is
suggestive of radical intermediates. To test for the possible
involvement of radicals, the reactivity of 4 was studied in
the presence of 9,10-dihydroanthracene. In the reaction of 4
in pyr-d5 solvent, no change in reaction products or yield
The coordination of pyridine was confirmed by X-ray
crystallography; yellow crystals of (dipic)VV(O)(OiPr)(pyr) (1-
Pyr) were obtained by diffusing diethyl ether into a pyridine
solution of 1 at -20 °C. The pyridine ligand in 1-Pyr is
coordinated trans to the oxo ligand, and the distance between
the vanadium center and the pyridine nitrogen is relatively long
(2.369(2) Å) compared to that between the vanadium and the
nitrogen of the dipic ligand (2.088(2) Å). The vanadium-oxo
(1.585(1) Å) and vanadium-isopropoxide oxygen (1.755(1) Å)
bond distances in 1-Pyr are nearly identical to those of 1
(1.588(3), 1.756(3) Å).32 Consistent with a fast exchange of
free and bound pyridine, the equilibrium described in eqs 1 and
2 was established immediately upon dissolving isolated 1-Pyr
in CD3CN.
1
and no formation of anthracene was detected by H NMR
Thermolysis of Vanadium(V) Alkoxide Complexes. Com-
plexes 1 and 2 are stable for days in acetonitrile solution at
room temperature. In the absence of base, 1 and 2 reacted very
slowly at elevated temperatures. For instance, when a solution
of 1 in CD3CN was heated at 100 °C for 3 weeks, less than
25% of the starting material reacted, as judged by integration
against an internal standard. However, complex 1 reacted cleanly
with pyridine in CD3CN solution over several days at room
temperature (or 30 min at 100 °C) to afford acetone (0.5 equiv,
100% yield), isopropanol (0.5 equiv, 100% yield), and the
vanadium(IV) complex (dipic)VIV(O)(pyr)2 (9), according to eq
4 (yields expressed as a percentage of the theoretical maximum
based on the oxidizing equivalents of vanadium consumed). The
butanoxide complex 2 reacted in pyr-d5 solution over 30 min
at 100 °C to afford butyraldehyde (80%) and 9. Complex 9 has
spectroscopy. However, when 9,10-dihydroanthracene (4
equiv) was added to the reaction of 4 in CD3CN, the
formation of anthracene (12% yield, based on the oxidizing
equivalents of vanadium consumed) was observed by 1H
NMR spectroscopy.
The 8-quinolinate-2-carboxylate (HQC) complex 8 reacted
in pyr-d5 solvent over 2.5 h at 100 °C to afford acetone (0.5
equiv, 90% yield) and the new vanadium(IV) complex (HQC)-
VIV(O)(pyr)2 (10). Complex 10 was characterized by elemental
analysis, as well as UV-vis and IR spectroscopy (νVdO ) 957
cm-1). The orientation of the oxo ligand in 10 with respect to
the HQC ligand is unclear, as several crystals of 10 grown from
pyridine solution were found to be disordered. Complex 10 was
recrystallized from DMSO, yielding the complex (HQC)-
VIV(O)(DMSO)2 (11). Complex 11 showed a vanadium-oxo
stretch in the IR spectrum at νVdO ) 950 cm-1, and X-ray
diffraction (Figure 4) revealed that the oxo ligand is trans to a
DMSO ligand, in contrast to the related complex (dipic)-
VIV(O)(DMSO)2.38
1
been previously described and was characterized by IR, H
NMR, and UV-vis spectroscopy and X-ray crystallography.35
To gain insight into the mechanism of alcohol oxidation,
the oxidation of mechanistic probes cyclobutanol and R-tert-
butylbenzylalcohol was studied. Cyclobutanoxide complex
Scheme 2. Oxidation of Cyclobutanol and R-tert-Butylbenzyl Alcohol
9
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A R T I C L E S
Hanson et al.
Figure 4. X-ray structure of 11 (thermal ellipsoids shown at 50%
probability, H atoms omitted for clarity). Selected bond lengths (Å) for 11:
V1-O1 ) 1.603(2), V1-N1 ) 2.011(2), V1-O2 ) 2.033(2), V1-O6 )
2.048(2), V1-O3 ) 2.070(2), V1-O5 ) 2.198(2).
The dipicOMe complex 7 reacted in pyr-d5 solution (30 min
at 100 °C) to afford acetone (0.5 equiv, 98% yield) and
(dipicOMe)VIV(O)(pyr)2 (12). Complex 12 was characterized
by X-ray crystallography, UV-vis and IR spectroscopy, and
elemental analysis. The VdO stretching frequency of 960 cm-1
is slightly lower than that of the parent dipic complex 9 (965
cm-1), and the X-ray structure of 12 (Figure S1, Supporting
Information) indicates that the oxo ligand is trans to the nitrogen
of the dipic ligand. The dipicCl complex 6 also reacted in pyr-
d5 solvent (30 min at 100 °C), yielding acetone (0.5 equiv, 100%
yield) and a green-brown precipitate. The precipitate showed a
VdO stretch in the IR at 962 cm-1, consistent with (dipic-
Cl)VIV(O)(pyr)2 (13).39
Figure 5. Kinetic plots of the thermolysis of 1 in pyr-d5 solvent (319 K):
top, fit to integrated first-order rate law; bottom, fit to integrated second-
order rate law.
(16).35 Within seconds of mixing the two complexes in pyridine
solution, the intense purple color of the VIII dimer faded and
the solution turned a green color. UV-vis and IR spectra of
the reaction mixture were consistent with quantitative formation
of (dipic)VIV(O)(pyr)2 (9) (eq 5).
Unlike the other complexes, dipicNO2 complex 5 did not react
cleanly in pyridine solution to form vanadium(IV) and acetone.
Complex 5 co-crystallized with water and reacted in pyridine
solution to generate the cis-dioxo complex [(dipicNO2)-
VV(O)2]HPyr (14). Repeated attempts to obtain complex 5 free
of water by recrystallization of 5 from isopropanol or by pre-
drying the dipicNO2 ligand under high vacuum (48 h) or over
molecular sieves were unsuccessful. Complex 14 was isolated
1
in 52% yield, and H and 51V NMR spectra were consistent
with those reported by Crans and co-workers for the cis-dioxo
complex [(dipicNO2)VV(O)2]K.40
Conproportionation of VIII/VV. The reactions of the dipic
vanadium(V) complexes described above produce vanadium(IV)
and 0.5 equiv of a two-electron-oxidized organic product. One
possible pathway for this reaction would be an initial two-
electron oxidation of the alkoxide ligand of the vanadium(V)
complex, forming a vanadium(III) intermediate. A subsequent
fast conproportionation reaction between vanadium(V) and
vanadium(III) would result in the formation of the vanadium(IV)
product. This type of VV/VIII conproportionation reaction was
tested. A pyridine solution of [(dipic)VV(O)2]HPyr (15) was
treated with 0.5 equiv of the dimer [(dipic)VIII(pyr)2]2(µ-O)
Kinetic Studies of Isopropanol Oxidation: Determination
of Reaction Order. The reaction of 1 in pyridine-d5 solvent to
form acetone and 9 was monitored by H NMR spectroscopy.
1
(35) Hanson, S. K.; Baker, R. T.; Gordon, J. C.; Scott, B. L.; Sutton, A. D.;
Thorn, D. L. J. Am. Chem. Soc. 2009, 131, 428–429.
Fitting the disappearance of 1 to the integrated first- and second-
order rate laws indicated that the reaction is first-order in
vanadium through at least three half-lives (Figure 5). In pyridine-
d5 solvent at 319 K, the observed first-order rate constant was
kobs ) 7.0(5) × 10-5 s-1 for the rate law d[Vt]/dt ) -kobs[Vt],
where [Vt] is the total concentration of compounds 1 and 1-Pyr.
When the reaction was carried out in the presence of the
potential radical trap 9,10-dihydroanthracene (0.06 M), the
reaction products and rate were unaffected (kobs ) 6.8(5) × 10-5
s-1). The thermolysis of 1 in pyridine-d5 solvent was also
monitored by 51V NMR spectroscopy. The first-order disap-
(36) The vanadium product of this reaction was a pale green precipitate,
formulated as (dipic)VIV(O)(CD3CN)x. Dissolution of this material in
pyridine formed the known compound (dipic)VIV(O)(pyr)2.
1
(37) tert-Butanol was detected by H NMR in approximately 70% yield,
along with several other minor unidentified products.
(38) Hanson, S. K.; Baker, R. T.; Gordon, J. C.; Scott, B. L.; Thorn, D. L.
Inorg. Chem. 2010, 49, 5611–5618.
(39) The related complex (dipicCl)VIV(O)(H2O)2 has been reported: Smee,
J. J.; Epps, J. A.; Ooms, K.; Bolte, S. E.; Polenova, T.; Baruah, B.;
Yang, L.; Ding, W.; Li, M.; Willsky, G. R.; la Cour, A.; Anderson,
O. P.; Crans, D. C. J. Inorg. Biochem. 2009, 103, 575–584.
(40) Smee, J. J.; Epps, J. A.; Teissedre, G.; Maes, M.; Harding, N.; Yang,
L.; Baruah, B.; Miller, S. M.; Anderson, O. P.; Willsky, G. R.; Crans,
D. C. Inorg. Chem. 2007, 46, 9827–9840.
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17808 J. AM. CHEM. SOC. VOL. 132, NO. 50, 2010

Alcohol Oxidation by Dipicolinate Vanadium(V)
A R T I C L E S
Figure 6. Observed rate constants for the reaction of 1 at 319 K in pyr-d5
with varying concentrations of isopropanol.
Figure 8. Eyring plot for the reaction of 1 in pyridine-d5 solvent, 319-
360 K.
Table 1. Values of kobs for the Reaction of 1 in Pyr-d5 Solvent,
319-360 K
temp (K)
kobs (s-1
)
319
331
340
351
360
7.0(5) × 10-5
2.1(1) × 10-4
5.0(3) × 10-4
1.7(1) × 10-3
2.5(2) × 10-3
Table 2. Values of pKa, σ, and kbimol for the Reactions of
4-Substituted Pyridines with 1 (CD3CN, 340 K)
R
pKa ([H(R-Pyr)]+)44,45
σ42,43
kbimol (M-1 s-1
)
-OCH3
-CH3
-H
-CF3
-CN
6.47
6.03
5.25
2.63
1.90
-0.27
-0.17
0
0.55
0.63
7.6(6) × 10-4
3.0(4) × 10-4
1.1(3) × 10-4
5.3(6) × 10-6
4.1(4) × 10-6
Figure 7. Observed rate constants for the reaction of 1 in mixtures of
CD3CN and pyr-d5, 340 K.
Reaction of (dipic)V(O)OiPr with Substituted Pyridines. In
CD3CN solution, the reaction of complex 1 was studied with a
number of different para-substituted pyridines at 340 K. A
greater than 10-fold excess concentration of the pyridine was
used to ensure pseudo-first-order kinetic behavior. For 4-cyano-
pyridine and 4-trifluoromethylpyridine, the reactions were
carried out at pyridine concentrations of greater than 0.8 M.
For pyridine, 4-methylpyridine (4-picoline), and 4-methoxy-
pyridine, reactions were carried out at pyridine concentrations
of greater than 0.5 M. Approximate second-order rate constants
kbimol were calculated by dividing kobs by the concentration of
pyridine (Table 2). The reaction rate showed a significant
dependence on the pyridine substituent, with 4-methoxypyridine
reacting with 1 more than 200 times faster (kbimol ) 7.6(6) ×
10-4 M-1s-1) than 4-cyanopyridine (kbimol ) 4.1(4) × 10-6
M-1s-1). The data fit well to a Hammett plot, giving slope F )
-2.5 (r2 ) 0.995) (Figure 9).42,43 The log of the bimolecular
rate constant also correlates well with the pKa of the pyridine,44,45
giving a linear plot (r2 ) 0.985) (Figure 10).
pearance of 1 was observed, with no intermediates or other
species detected during the reaction.41
The concentration of added isopropanol was varied from 0
to 0.6 M (319 K), and no change in the reaction rate was
observed, indicating a zero-order dependence on isopropanol
(Figure 6). In contrast, the dependence of the reaction rate on
the concentration of pyridine was more complex (Figure 7). At
340 K, the reaction of 1 was carried out in mixtures of CD3CN
and pyr-d5 solvents, over a pyridine concentration range of
0-12.5 M. At higher concentrations of pyr-d5 (3-12.5 M), kobs
exhibited a linear dependence on pyridine concentration. A line
fit to the data for kobs vs [pyridine] for pyridine concentrations
of 3-12.5 M gave a slope of 3.2 × 10-5 and a positive
y-intercept of 1.1 × 10-4 (r2 ) 0.995). Deviation from this linear
dependence was observed at low concentrations of pyridine,
with the reaction rate approaching zero as the concentration of
pyridine approaches zero.
Measuring the reaction rate in pyr-d5 solvent at five temper-
atures between 319 and 360 K yielded activation parameters of
∆Hq ) 20(2) kcal/mol (85(4) kJ/mol) and ∆Sq ) -14(1) eu
(-57(6) J/mol·K) (Figure 8, Table 1). Finally, the deuterated
isopropoxide complex 1-d7 was prepared from the reaction of
1 with isopropanol-d8. Comparison of the reaction rates of 1
and 1-d7 in pyr-d5 solvent allowed for determination of a primary
kinetic isotope effect of kH/kD ) 5.7(5) at 340 K.
The reaction of 1 was also studied with 2,6-lutidine (0.5 M)
in CD3CN at 340 K. Acetone was produced in 67% yield, but
a side reaction occurred that was not observed for any of the
(42) Jaffe, H. H. Chem. ReV. 1953, 53, 191–261.
(43) Exner, O. In AdVances in Linear Free Energy Relationships; Chapman,
N. B., Shorter, J., Eds.; Plenum Press: London, 1972; pp 2-52.
(44) Mason, S. F. J. Chem. Soc. 1959, 1247–1253.
(41) See Supporting Information for representative 51V NMR spectra from
the reaction.
(45) Taagepera, M.; Henderson, W. G.; Brownlee, R. T. C.; Beauchamp,
J. L.; Holtz, D.; Taft, R. W. J. Am. Chem. Soc. 1972, 94, 1369–1370.
9
J. AM. CHEM. SOC. VOL. 132, NO. 50, 2010 17809

A R T I C L E S
Hanson et al.
Table 3. Values of kobs for Complexes 1 and 6-8 in pyr-d5
Solvent, 340 K
complex
kobs (s-1
)
6
1
7
8
∼1.4 × 10-3
5.0(3) × 10-4
3.3(6) × 10-4
2.1(2) × 10-5
donating phenolate group in the 8-quinolinate-2-carboxylate
complex 8 resulted in a significant reduction in reaction rate
(kobs ) 2.1(2) × 10-5 s-1). Determination of the rate constant
for the reaction of the dipicCl complex 6 was complicated by
precipitation of the vanadium(IV) product, which interfered with
1
integration of the H NMR spectrum at late reaction times.
However, it was possible to obtain an estimate of kobs ≈ 1.4 ×
10-3 s-1 using initial rate values, indicating that complex 6 reacts
faster than 1 in pyr-d5 solvent. The reaction rate of dipicNO2
complex 5 was not measured due to the reaction with water
noted above, forming the cis-dioxo complex 14.
Figure 9. Hammett plot for the reaction of 1 with para-substituted pyridines
in CD3CN solvent, 340 K.
Discussion
Vanadium complexes are effective catalysts for a variety of
oxidations, including the aerobic oxidation of activated
alcohols,21-23 the oxidative kinetic resolution of R-hydroxy-
esters, R-hydroxyamides, and R-hydroxyphosphonates,24-26 the
oxidative C-C bond cleavage of diols and R-hydroxy-
ketones,28,47-49 the stereoselective oxidative coupling of
naphthols,50,51 and the oxidative decarboxylation of 2- and
3-hydroxycarboxylic acids.52-54 Vanadium alkoxide complexes
are putative intermediates in nearly all of these transformations,
and thus there is considerable interest in their reactivity.55
A one-electron pathway involving a vanadium(IV) intermedi-
ate has often been proposed for vanadium-mediated oxidations.
For example, Littler and Waters have carried out detailed studies
+
of the stoichiometric oxidation of alcohols by vanadate (VVO2 )
Figure 10. Plot of pKa [H(R-Pyr)]+ versus log(kbimol/ko) for the reactions
in acidic aqueous solution and proposed a mechanism wherein
a vanadium(V) alkoxide complex reacts to generate vana-
dium(IV) and an organic radical, followed by a fast reaction of
the radical with a second equivalent of vanadium(V).28-31
Radical intermediates have also been invoked in the oxidative
decarboxylation of 2- and 3-hydroxycarboxylic acids,52-54 the
oxidative cleavage of R-hydroxyketones and glycols,28,47-49 and
a recently reported C-O bond cleavage reaction in lignin model
compounds.56
In contrast, a two-electron pathway involving a vanadium(III)
intermediate is thought to be operative in several catalytic
alcohol oxidation reactions. Hydride transfer from an alkoxide
ligand to a vanadium-oxo ligand was postulated as a key step
in the oxidative kinetic resolution of R-hydroxyesters, R-hy-
of 4-substituted pyridines.
unhindered pyridines. As the reaction progressed, the vanadi-
um(V) complex VV(O)(OiPr)3 was formed, reaching a maximum
of ∼28% yield at 80% conversion. The formation of VV(O)(O-
iPr)3 likely results from the removal of the dipicolinate ligand
from 1 in the presence of 2,6-lutidine and isopropanol, which
is formed as the reaction progresses.46 The lack of formation
of VV(O)(OiPr)3 in the reaction of 1 with the unhindered
pyridines may reflect the stabilization of complex 1 via pyridine
coordination, which does not occur for the bulky 2,6-lutidine.
In a separate experiment, thermolysis of VV(O)(OiPr)3 with
pyridine (3 equiv) in CD3CN solution yielded less than 5%
acetone after 3 weeks of heating at 100 °C, suggesting that
formation of VV(O)(OiPr)3 is not involved in the isopropanol
oxidation pathway.
Effect of the Ligand on the Rate of Stoichiometric
Isopropanol Oxidation. The reactions of vanadium(V) isoprop-
oxide complexes 6-8 in pyr-d5 solvent were monitored by H
NMR spectroscopy. At 340 K, the dipicOMe complex 7 reacted
more slowly (kobs ) 3.3(6) × 10-4 s-1) than the parent dipic
complex 1 (kobs ) 5.0(3) × 10-4 s-1). Replacing one of the
carboxylate groups on the dipic ligand with a more electron-
(47) Littler, J. S.; Mallet, A. I.; Waters, W. A. J. Chem. Soc. 1960, 2761–
2766.
(48) Mehrotra, R. N. J. Chem. Soc. B 1968, 1123–1127.
(49) Kirihara, M.; Takizawa, S.; Momose, T. J. Chem. Soc., Perkin Trans.
1 1998, 7–8.
1
(50) Barhate, N. B.; Chen, C. T. Org. Lett. 2002, 4, 2529–2532.
(51) Takizawa, S.; Katayama, T.; Kameyama, C.; Onitsuka, K.; Suzuki,
T.; Yanagida, T.; Kawai, T.; Sasai, H. Chem. Commun. 2008, 1810–
1812.
(52) Jones, J. R.; Waters, W. A.; Littler, J. A. J. Chem. Soc. 1961, 630–
633.
(53) Meier, I. K.; Schwartz, J. J. Am. Chem. Soc. 1989, 111, 3069–3070.
(54) West, D. M.; Skoog, D. A. Anal. Chem. 1959, 31, 583–586.
(55) Crans, D. C.; Chen, H.; Felty, R. A. J. Am. Chem. Soc. 1992, 114,
4543–4550.
(46) Removal of the dipicolinate ligand from vanadium under basic
conditions has been reported previously. Crans and co-workers found
that in aqueous solution [(dipic)VV(O)2]- undergoes hydrolysis at pH
>6.5 to form vanadate and dipic2-. See ref 57.
(56) Son, S.; Toste, F. D. Angew. Chem., Int. Ed. 2010, 49, 3791–3794.
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17810 J. AM. CHEM. SOC. VOL. 132, NO. 50, 2010

Alcohol Oxidation by Dipicolinate Vanadium(V)
A R T I C L E S
droxyamides, and R-hydroxyphosphonates, as well as the
catalytic oxidation of propargylic alcohols.20,24-26 A greater
understanding of when one- and two-electron oxidations take
place may provide opportunities for the development of more
effective vanadium oxidation catalysts.
Dipicolinate vanadium complexes have been studied exten-
sively in aqueous solution as insulin-mimetic compounds.39,40,57-60
Under non-aqueous conditions, dipicolinate vanadium(V) com-
plexes oxidize alcohols and have also been found to catalyze
the aerobic oxidation of lignin model compounds.38 The kinetic
studies presented above, together with the results of the oxidation
of substrate probes, strongly suggest the involvement of pyridine
in alcohol oxidation by dipicolinate vanadium(V) complexes.
Several possible mechanisms for this reaction are considered,
as discussed below.
R-tert-Butylbenzyl alcohol (tert-butylphenylcarbinol) and its
4-methoxy-substituted derivative have been used by Westheimer,
Waters, Baciocchi, Mayer, and others in mechanistic studies of
metal-mediated oxidations.70-75 Baciocchi and co-workers
determined that one-electron oxidation of R-tert-butyl-4-meth-
oxybenzyl alcohol generates a radical that undergoes rapid C-C
bond fission, providing a way to distinguish pathways that
proceed by hydride transfer or hydrogen atom transfer from
those proceeding by initial electron transfer.73 Thus, formation
of the ketone product indicates a hydride-transfer or hydrogen-
atom-transfer pathway, while formation of C-C bond fission
products (benzaldehyde) indicates a pathway that proceeds by
initial electron transfer.73 In the reaction of dipicolinate complex
4 in pyr-d5 solvent, the formation of 2,2-dimethylpropiophenone
(98%) is consistent with a hydride-transfer or hydrogen-atom-
abstraction pathway. Unlike complexes 1 and 2, which show
no reaction in the absence of pyridine, complex 4 reacts in
CD3CN solution (albeit slowly), affording benzaldehyde (92%)
as the major product. Both the benzaldehyde product and the
formation of anthracene observed when 9,10-dihydroanthracene
is added to this reaction are consistent with radical intermediates.
The fact that different products are formed in the oxidation of
R-tert-butylbenzyl alcohol in the absence and in the presence
of pyridine suggests that the pyridine is involved in the
formation of the ketone product, enabling the two-electron
pathway to dominate over a much slower one-electron pathway.
Oxidation of Mechanistic Probes. Rocˇek, Lee, Bakac,
Whitesides, and others have studied the oxidation of cyclobu-
tanol to distinguish between one- and two-electron oxidations
for a wide range of metals, including chromium, vanadium,
copper, iron, and cerium.61-69 The formation of cyclobutanone
indicates a two-electron oxidation, whereas formation of ring-
opened products such as 4-hydroxybutyraldehyde, butyraldehyde
and crotonaldehyde (3-butene-1-al, from radical disproportion-
ation), or suberaldehyde (1,8-octanedial, from radical dimer-
ization) indicates a one-electron oxidation pathway.61 The high
yield of cyclobutanone (93%) observed in the reaction of
dipicolinate vanadium complex 3 in pyr-d5 solvent is consistent
with a two-electron pathway involving a vanadium(III) inter-
mediate. The lack of ring-opened products in this reaction
resembles Toste’s finding that the cyclopropyl-substituted
R-hydroxyester A was oxidized by a vanadium(V) complex of
a Schiff-base ligand with no ring opening (Scheme 1b).24 In
Mechanistic analysis based on interpretation of the reactivity
of substrate probes can be complicated, due to the fact that the
probe can, in some cases, react by a different pathway than other
substrates. For example, Scott and Espenson found that cy-
clobutanol reacts with CrO2+ by a one-electron pathway, while
other aliphatic alcohols react by a two-electron pathway.76 This
mechanistic change was attributed to the greater energetic
expense of generating alkyl radicals from simple primary and
secondary alcohols, as well as the greater stability of the simple
aldehyde and ketone products as compared to the strained
cyclobutanone.76 Nevertheless, there are no known examples
where a one-electron oxidant reacts with cyclobutanol to afford
cyclobutanone as the product.65 Furthermore, for the dipicolinate
vanadium complexes, the results of the pyridine-promoted
oxidation of cyclobutanol and R-tert-butylbenzyl alcohol are
consistent. Taken together, the reactions of the mechanistic
probes are strong evidence in support of a base-promoted two-
electron pathway for the dipicolinate vanadium(V) oxidation
that proceeds through a vanadium(III) intermediate.
contrast, Rocˇek found that vanadate (VVO2 ) oxidized cyclobu-
+
tanol by a one-electron pathway, forming 4-hydroxybutyralde-
hyde in 94% yield.63
Kim, Nam, and co-workers have studied the oxidation of
cyclobutanol by non-heme oxo iron(IV) complexes and proposed
that formation of cyclobutanone results from an initial hydrogen
atom transfer, followed by a fast electron transfer, giving a net
hydride transfer and an iron(II) intermediate.64 A similar
pathway is possible for the dipicolinate vanadium system; the
observation of no ring-opened products strongly suggests that
a radical derived from cyclobutanol does not diffuse away from
the vanadium center during the reaction.64
(57) Crans, D. C.; Yang, L.; Jakusch, T.; Kiss, T. Inorg. Chem. 2000, 39,
4409–4416.
Mechanism of Isopropanol Oxidation by 1. The dipicolinate
vanadium(V) isopropoxide complex 1 reacts cleanly with
pyridine to form the vanadium(IV) complex 9 and 0.5 equiv of
acetone. No reaction of 1 is observed in the absence of pyridine,
suggesting a key role for the base in the stoichiometric
isopropanol oxidation.
(58) Li, M.; Smee, J. J.; Ding, W.; Crans, D. C. J. Inorg. Biochem. 2009,
103, 585–589.
(59) Buglyo, P.; Crans, D. C.; Nagy, E. M.; Lindo, R. L.; Yang, L.; Smee,
J. J.; Jin, W.; Chi, L. H.; Godzala, M. E., III; Willsky, G. R. Inorg.
Chem. 2005, 44, 5416–5427.
(60) Crans, D. C.; Yang, L.; Alfano, J. A.; Chi, L. H.; Jin, W.; Mahroof-
Tahir, M.; Robbins, K.; Toloue, M. M.; Chan, L. K.; Plante, A. J.;
Grayson, R. Z.; Willsky, G. R. Coord. Chem. ReV. 2003, 237, 13–22.
(61) Meyer, K.; Rocek, J. J. Am. Chem. Soc. 1972, 94, 1209–1214.
(62) Rocek, J.; Radkowsky, A. E. J. Am. Chem. Soc. 1973, 95, 7123–7132.
(63) Rocek, J.; Aylward, D. E. J. Am. Chem. Soc. 1975, 97, 5452–5456.
(64) Oh, N. Y.; Suh, Y.; Park, M. J.; Seo, M. S.; Kim, J.; Nam, W. Angew.
Chem., Int. Ed. 2005, 44, 4235–4239.
(70) Hampton, J.; Leo, A.; Westheimer, F. H. J. Am. Chem. Soc. 1956,
78, 306–312.
(71) Jones, J. R.; Waters, W. A. J. Chem. Soc. 1960, 2772–2773.
(72) Baciocchi, E.; Bietti, M.; Lanzalunga, O. Acc. Chem. Res. 2000, 33,
243–251.
(65) Pestovsky, O.; Bakac, A. J. Am. Chem. Soc. 2004, 126, 13757–13764.
(66) Chandler, W. D.; Wang, Z.; Lee, D. G. Can. J. Chem. 2005, 83, 1212–
1221.
(73) Baciocchi, E.; Bietti, M.; Putignani, L.; Steenken, S. J. Am. Chem.
Soc. 1996, 118, 5952–5960.
(74) Bryant, J. M.; Taves, J. E.; Mayer, J. M. Inorg. Chem. 2002, 41, 2769–
2776.
(67) Lee, D. G.; Chen, T. J. Org. Chem. 1991, 56, 5341–5345.
(68) Coleman, K. S.; Lorber, C. Y.; Osborn, J. A. Eur. J. Inorg. Chem.
1998, 1673–1675.
(75) Shearer, J.; Zhang, C. X.; Zakharov, L. N.; Rheingold, A. L.; Karlin,
K. D. J. Am. Chem. Soc. 2005, 127, 5469–5483.
(76) Scott, S. L.; Bakac, A.; Espenson, J. H. J. Am. Chem. Soc. 1992, 114,
4205–4213.
(69) Whitesides, G. M.; Sadowski, J. S.; Lilburn, J. J. Am. Chem. Soc.
1974, 96, 2829–2835.
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A R T I C L E S
Hanson et al.
Scheme 3. Possible Mechanisms for the Reaction of 1
Three possible pathways for the reaction of 1 are shown in
Scheme 3. All three pathways involve the coordination of
pyridine to 1, which is evident from the NMR titration
experiments and the X-ray structure of 1-Pyr. In each case, the
slow step of the reaction is unimolecular in vanadium and
involves breaking the C-H bond to generate a vanadium(III)
intermediate, which is implicated by the primary kinetic isotope
effect (kH/kD ) 5.7(5)). A subsequent fast conproportionation
of VIII and VV would form the observed products. Conpropor-
tionation of the vanadium(V) complex [(dipic)VV(O)2]HPyr (15)
and the vanadium(III) complex [(dipic)VIII(pyr)2]2(µ-O) (16)
occurred rapidly (in time of mixing) at room temperature,
suggesting that this type of VV/VIII conproportionation reaction
is kinetically viable.
One possibility is that coordination of pyridine to the
vanadium center facilitates hydride transfer to the vanadium-oxo
ligand. This is shown in path A, where initial coordination of
pyridine to 1 is followed by a unimolecular reaction of 1-Pyr
to afford a vanadium(III) intermediate. Due to the observed rapid
coordination and exchange of pyridine at room temperature and
the primary kinetic isotope effect (kH/kD ) 5.7(5)), the slow
step of this pathway must be hydride transfer from the
isopropoxide ligand of 1-Pyr to the vanadium-oxo. Were the
reaction proceeding by this pathway, electron-rich pyridines that
coordinate more strongly to the vanadium center would promote
faster hydride transfer than pyridines with electron-withdrawing
substituents. The overall rate law for path A is shown in eq 6.
At high pyridine concentrations, the rate law simplifies to
eliminate the overall dependence on pyridine, as shown in eq
7. This is in conflict with the observed linear dependence of
the reaction rate on pyridine at high pyridine concentrations,
thus ruling out path A.
k1Keq[Vt][pyr]
1 + Keq[pyr]
path A:
rate )
(6)
(7)
rate ) k1[Vt]
A second possible reaction pathway (path B) entails rapid
equilibrium coordination of pyridine to 1, followed by a
bimolecular reaction of 1-Pyr with pyridine, where the C-H
bond is broken in the rate-determining step. A bimolecular
reaction with pyridine would be consistent with the experimen-
tally determined negative entropy of activation (∆Sq ) -14(1)
eu). The overall rate law for this pathway is depicted in eq 8.
At high pyridine concentrations, the rate law simplifies to give
a linear dependence on pyridine, as shown in eq 9. Path B would
thus account for the linear dependence of the reaction rate on
pyridine observed at high pyridine concentrations. However,
the line fit to the experimental values of kobs vs [pyridine] at
high pyridine concentrations yields a positive y-intercept (+1.1
× 10-4) that would not be anticipated for path B. The observed
positive y-intercept suggests that another pathway may be
operating.
k1Keq[pyr]2[Vt]
path B:
rate )
(8)
(9)
1 + Keq[pyr]
rate ) k1[pyr][Vt]
Path C is similar to path B, but in this mechanism both
complexes 1 and 1-Pyr undergo bimolecular reactions with
pyridine to form the observed products. Path C would be
consistent with the observed negative entropy of activation and
9
17812 J. AM. CHEM. SOC. VOL. 132, NO. 50, 2010

Alcohol Oxidation by Dipicolinate Vanadium(V)
A R T I C L E S
kinetic isotope effect. The rate law for path C is shown in eq
10. At high pyridine concentrations, the rate law simplifies as
shown in eq 11, accounting for both the linear dependence on
pyridine concentration and the positive y-intercept observed in
the plot of kobs vs [pyridine].
requiring balancing the electronic demands of the alcohol
oxidation step with those required for regeneration of vanadi-
um(V).
Conclusions
Detailed investigations of the mechanism of alcohol oxidation
by dipicolinate vanadium(V) have been carried out. The
dipicolinate vanadium(V) isopropoxide complex 1 reacts cleanly
with pyridine in acetonitrile or pyridine solution to generate
the vanadium(IV) complex 9 and 0.5 equiv of acetone. Initial
coordination of pyridine to 1 is rapid on the NMR time scale at
room temperature, with Keq ) 15((2) M-1 for the formation
of 1-Pyr at 298 K. Preparation of 1-d7 allowed for determination
of a primary kinetic isotope effect of 5.7(5) at 340 K, revealing
that the C-H bond is broken in or before the rate-limiting step
of the oxidation. Oxidations of the mechanistic probes cyclo-
butanol and R-tert-butylbenzyl alcohol have been studied and
suggest a two-electron pathway proceeding through a vana-
dium(III) intermediate. Overall, the evidence points to a
mechanism where both 1 and 1-Pyr undergo a bimolecular
reaction with pyridine to generate a vanadium(III) intermediate.
Trends in the alcohol oxidation reaction have been established,
with more basic pyridines reacting more rapidly. Increasing
electron-donating ability of the ligand slows the alcohol
oxidation reaction, with the relative order of reactivity dipicCl
> dipic > dipicOMe > HQC.
k1[pyr][Vt]
k2Keq[pyr]2[Vt]
1 + Keq[pyr]
path C:
rate )
+
(10)
1 + Keq[Pyr]
rate ) (k1/Keq)[Vt] + k2[pyr][Vt]
(11)
For path C, values of Keq ) 2.2 M-1, k1 ) 3.1 × 10-4 M-1
s-1, and k2 ) 3.1 × 10-5 M-1 s-1 can be obtained from a least-
squares fit of the data to the overall rate law (eq 10). The value
of Keq ) 2.2 M-1 (340 K) determined from the least-squares
analysis of the kinetic data is in good agreement with Keq
)
2((1) M-1 (340 K) determined from the H NMR chemical
shifts of 1 in the presence of varying pyridine concentration.
Values of k1 ) 3.1 × 10-4 M-1 s-1 and k2 ) 3.1 × 10-5 M-1
s-1 determined from the least-squares fit of the rate law are also
in good agreement with the slope (3.2 × 10-5) and y-intercept
(+1.1 × 10-4) of the line fit to kobs vs [pyridine] at pyridine
concentrations of 3-12.5 M (where the y-intercept ) k1/Keq
and the slope ) k2).
1
Hydride transfer from a vanadium-alkoxide ligand to a
vanadium-oxo ligand has been postulated as a key step in
vanadium-mediated alcohol oxidation by Toste, Chen, and
Uemura.20,24-26 The involvement of pyridine in the elementary
alcohol oxidation step determined for dipicolinate vanadium(V)
is a substantial departure from what has been previously
proposed and is a newly recognized type of mechanism for
vanadium-mediated alcohol oxidation. Notably, the oxidation
of benzylic and allylic alcohols reported by Ragauskas employs
a nitrogen base (DABCO) co-catalyst, providing an indication
that the involvement of base in the reaction of vanadium-alkoxide
complexes is not limited to the dipicolinate system described
here.21,22 Using a base to promote alcohol oxidation could
provide a new handle with which to tune reactivity of vanadium
catalysts and could potentially even provide a means to control
stereochemistry in alcohol oxidation reactions. Future studies
will explore the generality of base-promoted alcohol oxidation
and focus on the development of more effective vanadium
alcohol oxidation catalysts.
While the experimental evidence supports pathway C, the
precise nature of the C-H bond-breaking step remains some-
what ambiguous. The reaction is much faster with more basic
pyridines, suggesting an attack of pyridine on the C-H bond.
The reaction rate correlates well with the pKa of the conjugate
acid of the substituted pyridine, but also with σ, fitting a
Hammett plot with F ) -2.5. Jaffe and Fischer have shown
that for 3- and 4-substituted pyridines, the acid dissociation
reaction fits well to a Hammett plot, with pKa for the pyridinium
ion vs σ giving F ) 5.7.77,78 The magnitude of F for the reaction
of 1 is less than 5.7, suggesting that the buildup of positive
charge on the pyridine occurs to a lesser extent than in
protonation.79 The negative value of F demonstrates that
electron-donating substituents on the pyridine accelerate the
reaction. Electronic structure calculations to further clarify the
nature of the transition state are currently underway; however,
initial calculations are consistent with the observation of pyridine
coordination to 1 and suggest that a pyridine-assisted pathway
may be favored over an intramolecular H-atom abstraction.80
Experimental Section
Varying the electronics of the dipic ligand has a significant
impact on the rate of isopropanol oxidation, with HQC complex
8 reacting more slowly than 1 and dipicCl complex 6 reacting
faster. However, in considering a complete catalytic cycle for
the aerobic oxidation of alcohols, while electron-withdrawing
ligands enhance the Lewis acidity of the vanadium center and
facilitate the alcohol oxidation step, they also render the resulting
vanadium(IV) complex more electron-deficient, and thus slow
down the reaction of vanadium(IV) with oxygen to form
vanadium(V). The development of more active catalysts will
General Considerations. Unless specified otherwise, all reac-
tions were carried out under a dry argon atmosphere using standard
glovebox and Schlenk techniques. Pyridine-d5, DMSO-d6, D2O, and
CD3CN were purchased from Cambridge Isotope Laboratories.
Pyridine-d5 and CD3CN were dried over CaH2. Anhydrous grade
acetonitrile, pyridine, and diethyl ether were obtained from Fisher
Scientific and used as received. 4-Nitrodipicolinic acid was
purchased from ACES Pharma (Branford, CT), and 4-chloro-
dipicolinic acid was purchased from Small Molecules, Inc. (Hobo-
ken, NJ). 1H and 51V NMR spectra were obtained at room
temperature on a Bruker AV400 MHz spectrometer, with chemical
shifts (δ) referenced to the residual solvent signal or referenced
externally to VV(O)(Cl)3 (0 ppm). UV-vis spectra were obtained
on an HP 8452A diode array spectrometer, and IR spectra were
obtained on a Varian 1000 FT-IR Scimitar series or a Perkin-Elmer
Spectrum One instrument. Elemental analyses were performed by
Atlantic Microlab (Norcross, GA). (dipic)VV(O)(OiPr) (1),32 (dipic)-
(77) Jaffe, H. H.; Doak, G. O. J. Am. Chem. Soc. 1955, 77, 4441–4444.
(78) Fischer, A.; Galloway, W. J.; Vaughan, J. J. Chem. Soc. 1964, 3591–
3596.
(79) Fischer, A.; Galloway, W. J.; Vaughan, J. J. Chem. Soc. 1964, 3596–
3599.
(80) Dong, H.; Hrovat, D.; Borden, W. T. Unpublished results.
9
J. AM. CHEM. SOC. VOL. 132, NO. 50, 2010 17813

A R T I C L E S
Hanson et al.
VV(O)(OEt),32 [(dipic)VV(O)2]HPy (15),35 and [(dipic)V(pyri-
dine)2]2(µ-O) (16)35 were prepared according to published proce-
dures. 4-Methoxydipicolinic acid was prepared by base-catalyzed
hydrolysis of 4-methoxypyridine-2,6-dicarboxylic acid dimethyl
ester33 according to a published procedure.34
) 7.6 Hz, Py), 7.44-7.37 (m, 5H, V-OCH-Ph), 7.31-7.23 (m,
5H, R-tert-butylbenzyl alcohol), 7.15 (s, 1H, V-OCH), 4.32 (s, 1H,
R-tert-butylbenzyl alcohol), 1.07 (s, 9H, V-OC(C(CH3)3), 0.87 (s,
9H, R-tert-butylbenzyl alcohol). 51V NMR (CD3CN, 105 MHz):
-579.0 (s). IR (thin film): νCdO ) 1690 cm-1, νVdO ) 988 cm-1
.
(dipic)VV(O)(OiPr)-d7 (1-d7). Complex 1 (0.208 g, 0.593 mmol)
and isopropanol-d8 (0.350 g, 5.15 mmol) were dissolved in CH3CN
(4 mL). The mixture was stirred at room temperature for 5-10
min, and then the solvent was removed under vacuum. The yellow
residue was dissolved in CH3CN (2 mL), and more isopropanol-d8
(0.590 g, 8.68 mmol) was added. The solvent was removed again
under vacuum, leaving a pale yellow solid. Yield: 0.214 g (99%).
Integration of the 1H NMR spectrum of the yellow solid indicated
that the extent of deuteration in the isopropoxide ligand was
approximately 93%.
(dipicNO2)VV(O)(OiPr) (5). 4-Nitrodipicolinic acid (0.223 g,
1.05 mmol) was suspended in isopropanol (8 mL), and VV(O)(OiPr)3
(248 µL, 1.05 mmol) was added. The reaction mixture was stirred
at room temperature for 4 h, during which time a yellow precipitate
formed. The yellow solid was collected on a frit, washed with
diethyl ether (3 × 1 mL), and dried under vacuum. Yield: 0.320 g
1
(90%). Integration of the H NMR spectrum of the yellow solid
product indicated that the complex co-crystallized with 0.5 equiv
of isopropanol. Anal. Calcd for [(dipicNO2)VV(O)OiPr]2 ·iPrOH
C23H26N4O17V2: C, 47.50; H, 5.85; N, 3.69. Found: C, 47.49; H,
(dipic)VV(O)(OBu) (2). In a vial, (dipic)V(O)OiPr (0.166 g,
0.472 mmol) and 1-butanol (0.360 g, 4.86 mmol) were suspended
in CH3CN (2 mL). The solution was stirred for approximately 5
min, during which time all of the solid dissolved. The solvent was
removed under vacuum, leaving a yellow residue. The yellow
residue was then stirred with diethyl ether (8 mL), yielding a yellow
suspension. The yellow solid was allowed to settle, and the
supernatant was removed by pipet. The resulting yellow solid was
washed with diethyl ether (5 mL) and then dried under vacuum.
5.75; N, 3.77. H NMR (CD3CN, 400 MHz): δ 8.80 (s, 2H, Py),
1
6.51 (h, 1H, J ) 6.0 Hz, V-OCH), 3.86 (h, 1H, J ) 6.0 Hz,
isopropanol), 2.55 (s, 1H, isopropanol OH), 1.68 (d, 6H, J ) 6.0
Hz, V-isopropoxide), 1.08 (d, 6H, J ) 6.0 Hz, isopropanol). 51V
NMR (CD3CN, 105 MHz): -588.2 (s). IR (thin film): νNdO ) 1553
cm-1, 1366 cm-1, νCdO ) 1695 cm-1, νVdO ) 992 cm-1
.
(dipicCl)VV(O)(OiPr) (6). 4-Chlorodipicolinic acid (0.263 g,
1.31 mmol) was dissolved in methanol (10 mL). The solution was
filtered through a Teflon syringe filter to remove a fine brown solid,
and the solvent was removed under vacuum. The remaining solid
was then suspended in isopropanol (8 mL), and VV(O)(OiPr)3 (294
µL, 1.25 mmol) was added. The reaction mixture was stirred for
4 h at room temperature, forming a light tan suspension. The tan
solid was collected on a frit, washed with diethyl ether (2 × 2
mL), and dried under vacuum. The crude product was then
recrystallized by dissolving in CH3CN (2 mL), filtering through a
glass wool pipet, and cooling to -20 °C overnight. The yellow
crystals were washed with diethyl ether (2 × 2 mL) and dried under
1
Integration of the H NMR spectrum of the yellow solid product
indicated that the complex co-crystallized with 1 equiv of 1-butanol.
1
Yield: 0.124 g (70%). H NMR (CD3CN, 400 MHz): δ 8.56 (t,
1H, J ) 7.6 Hz, Py), 8.23 (d, 2H, J ) 7.6 Hz, Py), 5.99 (t, 2H, J
) 6.4 Hz, V-OCH2), 3.47 (t, 2H, J ) 6.4 Hz, 1-butanol), 1.99 (m,
2H, V-butanoxide), 1.58 (sextet, 2H, J ) 7.6 Hz, V-butanoxide),
1.43 (m, 2H, 1-butanol), 1.32 (sextet, 2H, J ) 7.6 Hz, 1-butanol),
1.03 (t, 3H, J ) 7.2 Hz, V-butanoxide), 0.895 (t, 3H, J ) 7.6 Hz,
1-butanol). 51V NMR (CD3CN, 105 MHz): -569.5 (s). IR (thin
film): νCdO ) 1682 cm-1, νVdO ) 990 cm-1. Anal. Calcd for
C15H22NO7V: C, 47.50; H, 5.85; N, 3.69. Found: C, 47.49; H, 5.75;
N, 3.77.
1
vacuum. Yield: 0.0926 g (23%). H NMR (CD3CN, 400 MHz): δ
8.28 (s, 2H, Py), 6.39 (h, 1H, J ) 6.0 Hz, V-OCH), 1.66 (d, 6H,
J ) 6.0 Hz, V-isopropoxide). 51V NMR (CD3CN, 105 MHz):
(dipic)V(O)(OCyBu) (3). (dipic)VV(O)(OEt) (0.1655 g, 0.512
mmol) and cyclobutanol (0.1534 g, 2.131 mmol) were dissolved
in CH3CN (3 mL), forming a yellow-orange solution. The solution
was allowed to stand at room temperature for 5-10 min, and then
the solvent was removed under vacuum. The resulting yellow-
orange solid was redissolved in CH3CN (1.25 mL) containing
cyclobutanol (0.160 g, 2.22 mmol). Orange-yellow crystals of 3
were obtained by slow diffusion of diethyl ether at -15 °C; complex
3 co-crystallized with 1 equiv of cyclobutanol. Yield: 0.136 g (71%).
1H NMR (CD3CN, 400 MHz): δ 8.57 (t, 1H, J ) 7.6 Hz, Pyr),
8.23 (d, 2H, J ) 7.6 Hz, Pyr), 6.41 (m, 1H, V-OCH), 4.06 (m, 1H,
cyclobutanol), 2.79-2.72 (m, 2H, V-cyclobutanoxide), 2.63-2.53
(m, 2H, V-cyclobutanoxide), 2.19-2.13 (m, 2H, cyclobutanol),
1.90-1.66 (m, 4H, V-cyclobutanoxide, cyclobutanol), 1.61-1.54
(m, 1H, cyclobutanol), 1.45-1.36 (m, 1H, cyclobutanol). 51V NMR
-588.9 (s). IR (thin film): νCdO ) 1694 cm-1, νVdO ) 990 cm-1
.
Anal. Calcd for C10H9ClNO6V: C, 37.72; H, 3.58; N, 7.65. Found:
C, 37.78; H, 3.54; N, 7.81.
(dipicOMe)VV(O)(OiPr) (7). 4-Methoxydipicolinic acid (0.028
g, 0.14 mmol) was suspended in isopropanol (2 mL). VV(O)(OiPr)3
(34 µL, 0.14 mmol) was added, and the reaction mixture was stirred
for 20 min at room temperature, forming a yellow suspension.
Diethyl ether (6 mL) was added, and the mixture was cooled to
-20 °C overnight. The supernatant was removed by pipet, and the
yellow powder washed with diethyl ether (3 mL) and dried under
1
vacuum. Integration of the H NMR spectrum of the yellow solid
product indicated that the complex co-crystallized with 0.5 equiv
of isopropanol. Yield: 0.038 g (84%). 1H NMR (CD3CN, 400 MHz):
δ 7.65 (s, 2H, Py), 6.22 (h, 1H, J ) 6.0 Hz, V-OCH), 3.86 (h, 1H,
J ) 6.0 Hz, isopropanol), 1.66 (d, 6H, J ) 6.4 Hz, V-isopropoxide),
1.08 (d, 6H, J ) 6.0 Hz, isopropanol). 51V NMR (CD3CN, 105
MHz): -590.3 (s). IR (thin film): νCdO ) 1683 cm-1, νVdO ) 991
(CD3CN, 105 MHz): -571.4 (s). IR (thin film): νCdO ) 1685 cm-1
νVdO ) 991 cm-1
,
.
(dipic)VV(O)(TBA) (4). In a vial, R-tert-butylbenzyl alcohol
(0.218 g, 1.35 mmol) was dissolved in CH3CN (3 mL). Calcium
hydride (0.030 g, 0.71 mmol) was added, and the suspension was
stirred at room temperature for 3 h. The solution was filtered through
a Teflon syringe filter into a second vial containing (dipic)V(O)(O-
iPr) (0.134 g, 0.382 mmol). The mixture was stirred at room
temperature for 20 min, forming a yellow solution. The solvent
was subsequently removed under vacuum, leaving a yellow residue.
CH3CN (3 mL) was added, and the resulting yellow suspension
was stirred at room temperature for 20 min. The solvent was again
removed under vacuum, leaving a yellow oily residue. Diethyl ether
(15 mL) was added, forming a yellow slurry, which was stirred
for 2 h at room temperature. The yellow solid was collected on a
frit, washed with diethyl ether (3 × 1 mL), and dried under vacuum.
cm-1
.
(HQC)VV(O)(OiPr) (8). In a vial, VV(O)(OiPr)3 (250 µL, 1.07
mmol) was added to a suspension of 8-hydroxyquinoline-2-
carboxylic acid (0.2016 g, 1.07 mmol) in CH3CN (6 mL). The
mixture was stirred at room temperature for 20 min, forming a dark
red solution. Cooling the solution overnight (-20 °C) yielded a
dark red solid. The supernatant was removed by pipet, and the red
solid was washed with diethyl ether (2 × 5 mL) and dried under
1
vacuum. Yield: 0.188 g (56%). H NMR (CD3CN, 400 MHz): δ
8.82 (d, 1H, J ) 8.4 Hz, HQC), 8.02 (d, 1H, J ) 8.8 Hz, HQC),
7.76 (t, 1H, J ) 8.0 Hz, HQC), 7.54 (d, 1H, J ) 8.4 Hz, HQC),
7.05 (d, 1H, J ) 7.6 Hz, HQC), 6.07 (h, 1H, J ) 6.0 Hz, V-OCH),
1.69 (overlapping doublets, 6H, J ) 8.0 Hz, V-isopropoxide). 51
V
NMR (CD3CN, 105 MHz): -549.8 (s). IR (thin film): νCdO ) 1702
cm-1, νVdO ) 990 cm-1. Anal. Calcd for C13H12NO5V: C, 49.86;
H, 3.86; N, 4.47. Found: C, 50.29; H, 3.74; N, 4.68.
1
Yield: 0.183 g (86%). H NMR (CD3CN, 400 MHz): δ 8.55 (t,
1H, J ) 7.6 Hz, Py), 8.23 (d, 1H, J ) 7.6 Hz, Py), 8.20 (d, 1H, J
9
17814 J. AM. CHEM. SOC. VOL. 132, NO. 50, 2010

Alcohol Oxidation by Dipicolinate Vanadium(V)
A R T I C L E S
Table 4. Crystallographic Data Collection Parameters for 1-Pyr and 11
(dipic)VV(O)(OiPr)(pyr) (1-Pyr)
(HQC)VIV(O)(DMSO)2 (11)
empirical formula
FW
C16H15N2O3V
334.24
C14H17NO6S2V
410.35
T (K)
140(1)
140(1)
wavelength (Å)
crystal description
space group
unit cell dimensions
(Å, deg)
0.71073
yellow block
P21/c
a ) 8.9203(10)
b ) 15.9259(19)
c ) 11.4477(13)
R ) 90
0.71073
brown needle
P21/c
a ) 14.241(5)
b ) 8.419(3)
c ) 15.213(5)
R ) 90
ꢀ ) 92.305(13)
γ ) 90
ꢀ ) 112.926(3)
γ ) 90
1679.8(10)
4, 1.623
0.869
844
V (Å3)
1625.0(3)
Z, F (Mg/m3)
4, 1.366
0.623
688
µ (mm-1
F(000)
)
crystal size
θ range (deg)
index ranges
0.14 × 0.10 × 0.08 mm
2.19-25.35
-10 e h e 10
0 e k e 19
0 e l e 13
15962, 6026 [R(int) ) 0.0652]
100.0
0.24 × 0.20 × 0.08 mm
2.71-25.34
-17 e h e 17
-10 e k e 10
-18 e l e 18
reflections collected, unique
completeness to θ (%)
refinement method
goodness of fit on F2
R1 (I > 2σ)
15195, 3064 [R(int) ) 0.0490]
99.9%
full-matrix least-squares on F2
S ) 0.793
full-matrix least-squares on F2
S ) 1.307
0.0373
0.1039
0.0348
0.0761
wR (I > 2σ)
(HQC)VIV(O)(pyr)2 (10). In a small glass vessel equipped with
a Teflon stopcock, (HQC)VV(O)(OiPr) (0.101 g, 0.322 mmol) was
dissolved in pyridine (2 mL). The solution was heated at 80 °C for
1 h. The volume of the pyridine was reduced to ∼0.5 mL under
vacuum, and the solution was allowed to stand at room temperature
for 4 days. The solution was then cooled to -20 °C, yielding green/
brown crystals. The supernatant was decanted, and the crystals were
washed with diethyl ether (1 × 6 mL) and dried under vacuum.
νVdO ) 957 cm-1. UV-vis (pyridine): λ ) 380 nm, ε ) 3600
M-1 cm-1; λ ) 350 nm, ε ) 3900 M-1 cm-1. Anal. Calcd for
C20H15N3O4V: C, 58.26; H, 3.67; N, 10.19. Found: C, 57.12; H,
3.70; N, 10.26.
Thermolysis of (dipic)VV(O)(OiPr) (1) in CD3CN. In a reseal-
able Teflon-capped NMR tube, complex 1 (4.2 mg, 0.012 mmol)
was dissolved in CD3CN (0.6 mL) containing 1,3,5-tri-tert-
butylbenzene (2.0 mM) as an internal standard. An initial 1H NMR
spectrum was recorded, and then the solution was heated at 100
°C. After heating of the solution for 3 weeks, integration of the 1H
NMR spectrum revealed that only ∼20% of 1 had reacted, forming
acetone in ca. 12% yield.
Yield: 0.092 g (70%). IR (pyridine solution): νCdO ) 1672 cm-1
,
Thermolysis of (dipic)VV(O)(OBu) (2) in Pyridine-d5. In a
resealable Teflon-capped NMR tube, complex 2 (5.0 mg, 0.013
mmol) was dissolved in pyr-d5 (0.6 mL) containing ethyl acetate
1
(3.7 mM) as an internal standard. An initial H NMR spectrum
was recorded, and then the reaction was heated at 100 °C for 30
(HQC)VIV(O)(DMSO)2 (11). Complex 10 (0.040 g, 0.097 mmol)
was dissolved in DMSO (0.6 mL). Slow diffusion of diethyl ether
at room temperature yielded crystals of 11 suitable for X-ray
diffraction. IR (DMSO solution): νCdO ) 1657 cm-1, νVdO ) 950
cm-1. UV-vis (DMSO): λ ) 406 nm, ε ) 2200 M-1 cm-1; λ )
348 nm, ε ) 2300 M-1 cm-1. X-ray data are given in Table 4.
(dipicOMe)VIV(O)(pyr)2 (12). In a small, thick-walled glass
vessel equipped with a Teflon stopcock, complex 7 (0.022 g, 0.069
mmol) was dissolved in pyridine (1 mL). The mixture was heated
at 100 °C for 1 h and then cooled to room temperature, and the
volume of the solvent was reduced to ∼0.25 mL under vacuum.
Green crystals formed upon cooling to -20 °C overnight. The
supernatant was removed by pipet, and the crystals were washed
with diethyl ether (2 × 1 mL) and dried under vacuum. Yield:
0.0176 g (76%). IR (pyridine solution): νCdO ) 1673 cm-1, νVdO
min. The solution was cooled to room temperature, and integration
1
of the H NMR spectrum revealed formation of butyraldehyde in
80% yield. The NMR and IR spectra of the solution were consistent
with the formation of 9.
Thermolysis of (dipic)VV(O)(OCyBu) (3) in Pyridine-d5. In
an NMR tube, cyclobutanoxide complex 3 (4.0 mg, 0.013 mmol)
was dissolved in pyridine-d5 (0.6 mL) containing diethyl ether (12
mM) as an internal standard. The reaction was heated at 100 °C
for 30 min, resulting in a color change from yellow-orange to green.
1
Examination of the H NMR spectrum of the reaction mixture
revealed formation of cyclobutanone; a 93% yield was determined
by the average of four runs of this type. Performing the reaction
on a larger scale (26 mg) allowed for the isolation of 25.4 mg of
green crystals. Elemental analysis (found: C, 52.66; H, 3.49; N,
10.41) and the UV-vis spectrum of this material agreed with
formulation as (dipic)VIV(O)(pyr)2 (9) (94% yield).
) 960 cm-1. UV-vis (pyridine): λ ) 346 nm, ε ) 700 M-1 cm-1
.
Anal. Calcd for C18H15N3O6V: C, 51.44; H, 3.60; N, 10.00. Found:
C, 50.14; H, 3.30; N, 9.73.
Thermolysis of (dipic)VV(O)(TBA) (4) in Pyridine-d5. In a
resealable Teflon-capped NMR tube, complex 4 (6.8 mg, 0.012
mmol) was dissolved in pyr-d5 (0.6 mL) containing diethyl ether
(12 mM) as an internal standard. An initial 1H NMR spectrum was
recorded, and the solution was heated at 100 °C for 20 min, resulting
in a color change from yellow to green. Integration against the
internal standard revealed that 2,2-dimethylpropiophenone was
formed in 98% yield. Spiking the reaction mixture with a com-
mercial sample of 2,2-dimethylpropiophenone confirmed the identity
of this product. When a similar reaction was carried out in the
presence of 9,10-dihydroanthracene (0.051 M), no formation of
[(dipicNO2)VV(O)2]HPy (14). Complex 5 (38.9 mg, 0.116
mmol) was dissolved in pyridine (1 mL), forming a yellow solution.
Within minutes, the solution turned cloudy, and a tan solid
precipitate formed. After 20 min, the tan precipitate was collected
on a frit, washed with diethyl ether (2 × 1 mL), and dried under
vacuum. Yield: 0.0224 g (52%). 1H NMR (DMSO-d6, 400 MHz):
δ 9.52 (d, 2H, J ) 5.6 Hz, HPyr), 8.91 (t, 1H, J ) 7.2 Hz, HPyr),
8.85 (s, 2H, dipicNO2), 8.41 (t, 1H, J ) 6.8 Hz, HPyr). 51V NMR
(DMSO-d6, 105 MHz): -518.0 (s). NMR data in D2O were
consistent with those reported for [(dipicNO2)VV(O)2]K.40
1
anthracene was detected by H NMR.
9
J. AM. CHEM. SOC. VOL. 132, NO. 50, 2010 17815

A R T I C L E S
Hanson et al.
Reaction of 4 in CD3CN. In a resealable Teflon-capped NMR
tube, complex 4 (4.5 mg, 8.1 µmol) was dissolved in CD3CN (0.6
mL) containing THF (3.6 mM) as an internal standard. An initial
1H NMR spectrum was recorded, and then the solution was allowed
to stand in ambient light at room temperature. After 9 days, a green
16 faded, forming a green solution. Both the IR (νCdO ) 1677 cm-1
,
νVdO ) 964 cm-1) and UV-vis spectra of the solution were
consistent with quantitative formation of (dipic)VIV(O)(pyr)2 (9).
General Procedure for the Determination of the Equilibrium
Constant for Coordination of Pyridine to 1. In a resealable Teflon-
capped NMR tube, complex 1 (ca. 6 mg, 0.017 mmol) was dissolved
in CD3CN (0.6 mL). Pyridine was added in increments of 5-60
µL, over a concentration range of 0-3.5 M, and 1H and 51V NMR
spectra were recorded after each addition. The changes in 51V NMR
chemical shift or 1H NMR chemical shift (isopropyl methine proton)
were used to calculate Keq according to eqs 2 and 3, using Excel to
perform a least-squares fit to the data. Values of Keq for the
coordination of pyridine were determined from the average of two
independent titration experiments of this type. Analogous titrations
were conducted with 4-cyanopyridine, 2,6-lutidine, and 2,6-di-tert-
butylpyridine.
1
precipitate had formed, and integration of the H NMR spectrum
revealed the formation of benzaldehyde (92%) and tert-butanol
(74%), as well as several minor unidentified products resulting from
the tert-butyl moiety. When the reaction was conducted in CH3CN
(1 mL) on a slightly larger scale (16.5 mg of 4), 6.6 mg of the
green solid product was isolated after washing with diethyl ether
(1 mL) and drying under vacuum. Dissolution of this material in
pyr-d5 showed a peak corresponding to CH3CN, and the 1H NMR
and IR spectra were consistent with (dipic)VIV(O)(pyr)2.
The reaction of complex 4 (3.9 mg, 7.0 µmol) was also followed
in CD3CN (0.6 mL) in the presence of 9,10-dihydroanthracene (5.4
mg, 30 µmol) and a THF (9.0 mM) internal standard. After 9 days,
integration of the 1H NMR spectrum revealed that anthracene had
formed in 12% yield (based on the oxidizing equivalents of
vanadium consumed).
General Procedure for Kinetic Studies. Complex 1 (ca. 6 mg,
0.017 mmol) was weighed into a resealable Teflon-capped NMR
tube. The complex was dissolved in pyr-d5 (0.6 mL) or CD3CN/
pyr-d5 (0.6 mL total volume), and an internal standard was added
(THF, dioxane, or diethyl ether). The reaction was heated in the
probe of a Bruker AV400 MHz spectrometer, where the temperature
was calibrated using an ethylene glycol standard. 1H NMR spectra
were recorded at intervals, and the disappearance of complex 1
was followed by integration against the internal standard. Rate
constants were determined by monitoring the reaction through at
least three half-lives. For the reactions of 1 with 4-trifluorometh-
ylpyridine and 4-cyanopyridine, the reactions at 340 K were too
slow to monitor in the NMR probe. The NMR tubes were instead
heated in a temperature-controlled IKA oil bath and monitored
Thermolysis of (dipicCl)VV(O)(OiPr) (6) in Pyridine-d5. In a
resealable Teflon-capped NMR tube, complex 6 (13.4 mg, 0.0412
mmol) was dissolved in pyr-d5 (0.6 mL) containing diethyl ether
(0.037 M) as an internal standard. The reaction mixture was heated
at 100 °C for 30 min, during which time a green-brown precipitate
formed. The precipitate was allowed to settle, at which time
integration of the 1H NMR spectrum revealed the complete
consumption of 6 and formation of acetone (0.5 equiv, 100% yield).
The green solid was transferred to a vial, washed with diethyl ether
(2 × 0.5 mL), and dried under vacuum. Yield: 0.0156 g (89%).
The IR spectrum of this material (Nujol mull, νCdO ) 1660 cm-1
,
νVdO ) 962 cm-1) and elemental analysis (found: C, 47.14; H,
3.01; N, 9.32) were consistent with formulation as (dipicCl)-
VIV(O)(pyr)2.
1
periodically by H NMR spectroscopy.
Acknowledgment. This work was supported by Los Alamos
National Laboratory LDRD (ER 20100160 and Director’s PD
Fellowship to S.K.H.) and NSF via the Center for Enabling New
Technologies through Catalysis (CENTC). We thank Professors
W. T. Borden (UNT), D. Hrovat (UNT), S. L. Scott (UCSB), and
P. C. Ford (UCSB) for helpful discussions and collaborations, and
Dr. P. C. Stark (LANL) for help with instrumentation.
Thermolysis of (HQC)VV(O)(OiPr) (8) in Pyridine-d5. In a
resealable Teflon-capped NMR tube, complex 8 (5.0 mg, 0.016
mmol) was dissolved in pyr-d5 (0.6 mL) containing diethyl ether
1
(0.034 M) as an internal standard. An initial H NMR spectrum
was recorded, and then the solution was heated at 100 °C for 2.5 h,
during which time the color changed from dark red to yellow. After
the solution was cooled to room temperature, examination of the
1H NMR spectrum revealed formation of acetone (0.5 equiv, 90%
yield).
Supporting Information Available: Additional kinetic plots,
rate law derivations, X-ray structure of 12, and CIF files for
1-Pyr and 11. This material is available free of charge via the
Internet at http://pubs.acs.org.
Conproportionation of [(dipic)VV(O)2]HPyr (15) and [(dipic)-
VIII(pyridine)2]2(µ-O) (16). Complex 15 (4.2 mg, 0.0128 mmol) and
complex 16 (5.1 mg, 0.0067 mmol) were combined in a small vial.
Pyridine (1.5 mL) was added, and the solution was mixed at room
temperature. Within the time of mixing, the dark purple color of
JA105739K
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17816 J. AM. CHEM. SOC. VOL. 132, NO. 50, 2010