New molybdenum catalysts for alkyl olefin epoxidation. Their implications for the mechanism of oxygen atom transfer

Article abstract of DOI:10.1021/ja002697u

We report here the design, synthesis, and characterization of new (dioxo)Mo(VI) epoxidation catalysts based on monoanionic tridentate ligands. Two important features distinguish these catalysts from those previously reported. First, their coordination env

Full text of DOI:10.1021/ja002697u

862
J. Am. Chem. Soc. 2001, 123, 862-869
New Molybdenum Catalysts for Alkyl Olefin Epoxidation. Their
Implications for the Mechanism of Oxygen Atom Transfer
Judith M. Mitchell and Nathaniel S. Finney*
Contribution from the Department of Chemistry and Biochemistry, UniVersity of California,
San Diego, La Jolla, California 92093-0358
ReceiVed July 21, 2000
Abstract: We report here the design, synthesis, and characterization of new (dioxo)Mo(VI) epoxidation catalysts
based on monoanionic tridentate ligands. Two important features distinguish these catalysts from those previously
reported. First, their coordination environment remains well-defined during the epoxidation reaction. Second,
the ligand design does not permit simultaneous coordination of olefin and alkyl hydroperoxide. Based on the
study of these new catalysts, we conclude that direct oxygen atom transfer from coordinated alkyl peroxide to
olefin remains the simplest mechanism consistent with the available data. We discuss literature discrepancies
in this regard.
Introduction
and thus easily explains the observation that electron-rich olefins
react more quickly than electron-poor olefins. It is also consistent
with the observation that allylic alcohols are epoxidized more
rapidly than unfunctionalized olefins: rapid precoordination of
the Lewis-acidic metal center to the hydroxyl group accelerates
the epoxidation by making it an intramolecular process.5 The
enhanced reactivity of allylic alcohols relative to alkyl olefins
in Mo(VI) and V(V) systems has also been used to argue against
the intermediacy of peroxometallacycles such as C, as simul-
taneous hydroxyl coordination and metallacyle formation would
lead to a highly strained bicyclic intermediate. Finally, and
perhaps most importantly, direct oxygen atom transfer is the
simpler of the two mechanisms and must be preferred in the
absence of contrary evidence.
Contrary evidence does, however, exist: there are kinetic data
indicating that many Mo(VI)-mediated epoxidations exhibit a
non-first-order dependence on olefin concentration, which
cannot be accounted for by the direct oxygen atom transfer
mechanism. The intermediacy of Mo(VI)-olefin complexes was
first invoked to explain the kinetic profile of stoichiometric
epoxidations mediated by MoO(O2)2‚L complexes (L ) HMPA,
DMF, etc.).6 The observation of saturation kinetics as olefin
concentration was increased led to the proposal of reversible
formation of B. At low olefin concentration, formation of B
would be rate limiting, while at high olefin concentration this
preequilibrium would be saturated (reminiscent of Michaelis-
Menten kinetics), leading to a rate-determining step that is no
longer dependent on olefin concentration. Similar kinetic studies
of catalytic epoxidations based on both (dioxo)Mo(VI) and oxo-
(bisperoxo)Mo(VI) complexes are also consistent with the
formation of Mo(VI)-olefin intermediates.7 In the context of
Molybdenum-catalyzed epoxidation is an important process
for the production of both bulk and fine chemicals: it remains
the basis for the industrial production of propylene oxide, and
is a convenient laboratory method for the epoxidation of more
complicated alkyl olefins.1,2 Despite its long history and
industrial relevance, the mechanism of Mo(VI)-catalyzed ep-
oxidation of olefins with alkyl hydroperoxides remains a subject
of debate.2 Certain details of the mechanismsformation of a
Mo(VI) alkyl peroxide and transfer of the distal oxygen atom
of the alkyl peroxide rather than an oxo ligandsare generally
agreed upon. However, it remains a point of contention whether
the reaction proceeds by direct oxygen atom transfer or via the
formation of a Mo(VI)-olefin complex (Scheme 1). Our efforts
to resolve this mechanistic ambiguity are described herein.
Background
The conflicting mechanisms are summarized in Scheme 1.
The direct oxygen atom transfer mechanism (Path A) involves
a concerted single-step process in which an olefin nucleophile
attacks a Mo(VI)-coordinated alkyl hydroperoxide electrophile,
producing epoxide and metal alkoxide. The alternative mech-
anism (Path B) involves reversible binding of the olefin to a
Mo(VI) alkyl hydroperoxide complex (B). In the most com-
monly discussed variation, B undergoes rearrangement to
peroxymetallacycle C, which fragments into epoxide and metal
alkoxide.3
The arguments in favor of direct oxygen atom transfer may
be summarized as follows.4 Direct transfer depicts the olefin
as a nucleophile reacting with an electrophilic oxygen center,
(1) (a) Landau, R.; Sullivan, G. A.; Brown, D. D. Chemtech 1979, 602-
607. (b) Sheldon, R. A. In Aspects of Homogeneous Catalysis; Ugo, R.,
Ed.; D. Reidel: Boston, 1981; Vol. 4.
(4) (a) Sharpless, K. B.; Townsend, J. M.; Williams, D. R. J. Am. Chem.
Soc. 1972, 94, 295-296. (b) Chong, A. O.; Sharpless, K. B. J. Org. Chem.
1977, 42, 1587-1590.
(5) While most commonly associated with V(V) catalyst systems
(Hoveyda, A. H.; Evans, D. A.; Fu, G. C. Chem. ReV. 1993, 93, 1307-
1370, and references therein), it has also been observed with Mo(VI):
Sharpless, K. B.; Michaelson, R. C. J. Am. Chem. Soc. 1973, 95, 6136-
6137.
(2) (a) Mimoun, H. Angew. Chem., Int. Ed. Engl. 1982, 21, 734-750.
(b) Di Furia, F.; Modena, G. Pure Appl. Chem. 1982, 54, 1853-1866. (c)
Mimoun, H. Catal. Today 1987, 1, 281-295. (d) Jørgensen, K. A. Chem.
ReV. 1989, 89, 431-458. (e) Schurig, V.; Betschinger, F. Chem. ReV. 1992,
92, 873-888.
(3) Other pathways for the conversion of B to epoxide can be envisioned.
As this work focuses on the formation of B rather than subsequent steps,
this point will not be addressed further.
(6) (a) Mimoun, H.; de Roch, I. S.; Sajus, L. Tetrahedron 1970, 26, 37-
50. (b) Arakawa, H.; Moro-oka, Y.; Ozaki, A. Bull. Chem. Soc. J. 1974,
47, 2958-2961.
10.1021/ja002697u CCC: $20.00 © 2001 American Chemical Society
Published on Web 01/16/2001

New Mo Catalysts for Alkyl Olefin Epoxidation
J. Am. Chem. Soc., Vol. 123, No. 5, 2001 863
Scheme 1. Possible Epoxidation Mechanisms
Path B, the greater reactivity of more electron-rich olefins is
explained by enhanced precoordination to the electron-deficient
Mo(VI) center. The increased reactivity of allylic alcohols has
been addressed by arguing that formation of epoxide via a
bicyclic intermediate is either less unfavorable than intuition
might suggest or reflects kinetic rather than thermodynamic
control.8
Figure 1.
While it is clear that, in its simplest form, direct oxygen atom
transfer cannot account for the observed non-first-order kinetics,
two important caveats must be made regarding these kinetic
data. First, while the data may demonstrate that Mo(VI)-olefin
complexes do form, this does not prove they are essential for
oxygen atom transfer. Second, unlike the stoichiometric MoO-
(O2)2‚L oxidations, virtually all of the catalytic epoxidations
for which kinetic characterization has been reported involve
multiple catalytically active Mo(VI) species, as a result of either
uncontrolled ligand exchange or the use of a Mo(0) catalyst
precursor.9,10,11 While some of these systems, as noted above,
display non-first-order olefin kinetics, others are reported to be
linearly dependent on olefin concentration.12 Whether the
formation of Mo(VI)-olefin complexes is integral or incidental
to the catalytic cycle thus remains an open question.
simultaneous coordination of olefin and bidentate alkyl peroxide.
We began by analyzing common features of the coordination
environments of transition state A and intermediate B (Scheme
1). Taking into account the presence of two cis spectator oxo
ligands, the required formation of a triangularly coordinated
monoanionic bidentate alkyl peroxide,13 and the propensity for
Mo(VI) to become seven-coordinate,14 three coordination sites
and one valence remain available for association of ligand and/
or olefin. Transition structure A should be able to accommodate
a tridentate monoanionic ligand. In contrast, intermediate B,
which requires a vacant coordination site for the olefin, should
not be able to accommodate such a ligand. Thus, if Mo(VI)
complexes of monoanionic tridentate ligands proved catalytically
active, it would provide prima facie evidence that the reaction
does not require olefin precoordination.15,16
Synthesis and Characterization of Molybdenum Com-
plexes. Among the many possible topologies for monoanionic
tridentate ligandssa ligand class largely unexplored in transition
metal catalysisswe selected the readily available compound 1
and the corresponding Mo(VI) complexes 2-4 for study (Figure
1). The syntheses of ligand 1 and Mo(VI) complex 2 are
illustrated in Scheme 2. Formation of the imine derived from
3,5-di-tert-butyl salicylaldehyde and 2-methylaminopyridine
Experimental Design
Our approach to addressing this mechanistic issue relies on
(dioxo)Mo(VI) epoxidation catalysts designed to preclude
(7) Su, C.-C.; Reed, J. W.; Gould, E. S. Inorg. Chem. 1973, 12, 337-
342.
(8) Mimoun, H. J. Mol. Catal. 1980, 7, 1-29.
(9) For demonstration of the presence of multiple catalytically active
Mo(VI) species, see: (a) Sheldon, R. A. Recl. TraV. Chim. 1973, 92, 253-
266. (b) Sheldon, R. A. Recl. TraV. Chim. 1973, 92, 367-373. (c) Talsi, E.
P.; Shalyaev, K. V.; Zamaraev, K. I. J. Mol. Catal. 1993, 83, 329-346. (d)
Talsi, E. P.; Klimov, O. V.; Zamaraev, K. I. J. Mol. Catal. 1993, 83, 347-
366.
(10) For a discussion of the kinetic implications of the presence of
multiple catalytically active species (including Mo(VI)-olefin complexes),
see: (a) Di Furia, F.; Modena, G. Pure Appl. Chem. 1982, 54, 1853-1866.
(b) Bortolini, O.; Conte, V.; Di Furia, F.; Modena, G.. J. Mol. Catal. 1983,
19, 331-343. (c) Sapunov, V. N. J. Mol. Catal. 1980, 7, 149-158.
(11) For representative studies on an exceptionally well-characterized
catalytic epoxidation system based on 7-coordinate MoO(O2)2‚L complexes
bearing neutral bidentate ligands, see: (a) Thiel, W. R.; Priermeier, T.
Angew. Chem., Int. Ed. Engl. 1995, 34, 1737-1738. (b) Thiel, W. R. J.
Mol. Catal. A 1996, 117, 449-454. (c) Thiel, W. R.; Eppinger, J. Chem.
Eur. J. 1997, 3, 696-705. (d) Hroch, A.; Gemmeker, G.; Thiel, W. R.
Eur. J. Org. Chem. 2000, 1107-1114 and references therein.
(12) (a) Sheng, M. N.; Zajacek, J. G. J. Org. Chem. 1970, 35, 1839-
1843. (b) Howe, G. R.; Hiatt, R. R. J. Org. Chem. 1971, 36, 2493-2497.
(c) Baker, T. N., III; Mains, G. J.; Sheng, M. N.; Zajacek, J. G. J. Org.
Chem. 1973, 38, 1145-1148.
(13) “Triangular” coordination is an accepted prerequisite for oxygen-
atom transfer, and is consistent with both the solution and crystal structures
of oxovanadium alkyl hydroperoxide complexes, as well as theoretical
models of oxygen atom transfer: (a) Mimoun, H.; Chaumette, P.; Mignard,
M.; Saussine, L. NouV. J. Chim. 1983, 467-475. (b) Mimoun, H.; Mignard,
M.; Brechot, P.; Saussine, L.; Rueil-Malmaison, F. J. Am. Chem. Soc. 1986,
108, 3711-18. (c) Bach, R. D.; Wolber, G. J.; Coddens, B. A. J. Am. Chem.
Soc. 1984, 106, 6098-6099.
(14) For representative overviews of the extensive coordination chemistry
of Mo(VI), see: (a) Stiefel, E. I. Prog. Inorg. Chem. 1977, 22, 1-223. (b)
Holm, R. H. Chem. ReV. 1987, 87, 1401-1449. (c) Syamal, A.; Maurya,
M. R. Coord. Chem. ReV. 1989, 95, 183-238.
(15) To the our knowledge, no 20-electron Mo(VI) complexes have been
reported. For transient electrochemical generation of an unstable, low-valent
20-electron Mo complex, see: Ballivet-Tkatchenko, D.; Boughriet, A.;
Bre´mard, C. Inorg. Chem. 1986, 25, 826-831.
(16) For work with coordinatively saturated oxo(porphyrin)Mo(V) and
oxo(porphyrin)Ti(IV) catalysts, see: (a) Ledon, H. J.; Durbut, P.; Varescon,
F. J. Am. Chem. Soc. 1981, 103, 3601-3603. (b) Ledon, H. J.; Varescon,
F. Inorg. Chem. 1984, 23, 2735-2737.

864 J. Am. Chem. Soc., Vol. 123, No. 5, 2001
Mitchell and Finney
Scheme 2
Table 1. Epoxidation of Olefins 9-12
Scheme 3
substrate product
R
R′
n
temp (°C) time (h) yield (%)a
5
6
7
8
9
10
11
12
H
CH3
H
H
H
CH3
1
2
1
1
55
40
40
30
28
8
24
25
75
75
75
90
CH3 CH3
a Reaction yields were determined by HPLC; see Experimental
Section for details.
Scheme 4
Figure 2. X-ray structure of 2.
1
could also be monitored by TLC or H NMR. Catalysts 2, 3,
and 4 exhibit virtually identical activity, indicating that the µ-oxo
dimer, the azide, and the chloride are readily converted to a
common active monomer under the reaction conditions.21 As a
matter of convenience, the majority of our studies have been
carried out on 2.
proceeded in essentially quantitative yield under standard
conditions; acidic reduction then provided 1 in 85% yield.
Refluxing a slight excess of this ligand with 1 equiv of MoO2-
(acac)2 in methanol led, after cooling and filtration, to the
isolation of 2 (65%) as an orange crystalline solid. Complex 2
was identified as a µ-oxo dimer by X-ray crystallographic
analysis (Figure 2);17,18 while the formation of a dimer was not
anticipated, it is reminiscent of the low solubility of (porphyrin)-
Mo(V) µ-oxo dimers.19 The location of the neutral donor atoms
opposite the two oxo substituents and the anionic ligands
opposite one another is typical of (dioxo)Mo(VI) species. The
lability of this complex is demonstrated by the formation of
the corresponding monomeric azide (3) upon treatment with
TMSN3, or the chloride (4) upon treatment with TMSCl
(Scheme 3).
The yields for epoxidation of 5-8 mediated by 2 are shown
in Table 1. As anticipated, the trisubstituted olefin 8 is more
reactive than the disubstituted olefins 6 and 7, and all three are
more reactive than 5. The reaction is stereospecific: 6 gives
rise exclusively to epoxide 10, and 7 produces 11 as the sole
product. That the trans olefin 6 reacts more quickly than the
cis olefin 7 is somewhat surprising, in light of the kinetic
preference for cis olefins exhibited by most epoxidation
catalysts,22 and presumably reflects geometric details of the
active Mo(VI)-alkyl peroxide complex. The use of excess tert-
butyl hydroperoxide is necessary to minimize product inhibition
by tert-butyl alcohol; even with 2.5 equiv of peroxide, the
epoxidation begins to slow noticeably after 60-70% conver-
sion.23
Epoxidation of Alkyl Olefins. Complexes 2-4 are active
catalysts for the epoxidation of alkyl olefins 5-8, chosen as
representative epoxidation substrates (Scheme 4, Table 1).
Epoxidations were carried out in benzene with anhydrous tert-
butyl hydroperoxide as the terminal oxidant.20 Reactions were
typically followed by HPLC (see Experimental Details), but
In the absence of 4 Å molecular sieves, epoxides 9-12
underwent partial conversion to the corresponding diols, evi-
dence of Mo(VI)-catalyzed hydrolysis.24 Under comparable
conditions employing MoO2(acac)2 as the Mo(VI) source, we
(17) Single crystals of 2 were grown from CH3OH/CH2Cl2. Crystal-
lographic analysis was carried out by Dr. Joseph Ziller at the University of
California, Irvine. Crystallographic data (excluding structure factors) for
the structure reported in this paper have been deposited with the Cambridge
Crystallographic Data Centre as supplementary publication no. CCDC
133407. Copies of the data can be obtained free of charge on application
to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (fax: (+44)1223-
336-033; e-mail: deposit@ccdc.cam.ac.uk).
(18) In some cases, we have isolated a mixture of 2 and a compound
tentatively identified as the terminal methoxide complex. Formation of the
latter can be avoided by the addition of a small amount of water to the
reaction mixture.
(21) Efforts to isolate the intermediate Mo(VI)-tert-butyl hydroperoxide
complex have not yet been successful.
(22) The ordering of Z vs E reactivity is the reverse of that observed
with (porphyrin)M- and (salen)M-catalyzed epoxidation reactions (M )
Cr, Fe, Mn). See: (a) Jacobsen, E. N. In ComprehensiVe Organometallic
Chemistry II; Wilkinson, G., Stone, F. G. A., Abel, E. W., Hegedus, L. S.,
Eds.; Pergamon: New York, 1995; Vol. 12, Chapter 11.1. (b) Katsuki, T.
Coord. Chem. ReV. 1995, 140, 189-214.
(23) The addition of excess (>10 equiv) of tert-butyl alcohol completely
suppresses catalytic activity, consistent with extensive literature precedent.
See, for instance: Sheng, M. N.; Zajacek, J. G. AdV. Chem. Ser. 1968, 76,
418.
(19) Ledon, H. J.; Bonnet, M. C.; Brigandat, Y.; Vaescon, F. Inorg. Chem.
1980, 19, 3488-3491.
(20) Hill, J. G.; Rossiter, B. E.; Sharpless, K. B. J. Org. Chem. 1983,
48, 3607-3608.
(24) Conversion of epoxide to diol is a common side reaction in Mo-
(VI)-catalyzed epoxidation systems. For an archetypal case, in which a glycol
chelate of Mo(VI) was isolated and characterized, see ref 9b.

New Mo Catalysts for Alkyl Olefin Epoxidation
J. Am. Chem. Soc., Vol. 123, No. 5, 2001 865
Scheme 5. Putative Ligand Displacement
observe slightly higher catalytic activity but significantly less
hydrolysis, which leads us to conclude that Lewis acidity and
catalytic activity are not necessarily correlated. Another obser-
vation highlighting the Lewis acidity of these new molybdenum
catalysts is that the addition of 10 equiv of triethylamine or
HMPA is sufficient to suppress epoxidation completely, sug-
gesting that these donor ligands occupy the seventh coordination
site and prevent η2-coordination of the alkyl hydroperoxide.25
On the basis of the observation that complexes 2-4 are
effective catalysts for the epoxidation of alkyl olefins, we
conclude that Mo(VI)-olefin complexes are not essential
participants in the catalytic cycle. To reinforce this conclusion,
we carried out the additional experiments described in the
following section.
Ligand Dissociation and Epoxidation Kinetics. Our ligand
design and the interpretation of our results are based on the
assumption that the tridentate monoanionic ligand does not
dissociate from the Mo(VI) center during the epoxidation, and
therefore no vacant coordination site for the olefin is available.
However, we have considered a scenario in which olefin
manages to avail itself of a coordination site otherwise occupied
by ligand. This hypothesis is illustrated in Scheme 5: if a
coordination site is opened by or for the olefin as a result of
partial ligand dissociation (formation of F),26 it should be
possible to induce similar ligand dissociation in 3 by addition
of a stronger donor ligand such as HMPA (formation of F′).
HMPA is a known inhibitor of stoichiometric MoO(O2)2‚L
epoxidations as well as various Mo(VI)-catalyzed epoxidationss
including the present one. Further, in the context of mechanistic
proposals involving Mo(VI)-olefin complexes, such inhibition
has been taken as evidence that HMPA binds much more
strongly to Mo(VI) than does olefin.2
Coordination of ligand 1 to Mo(VI) results in pronounced
changes in the chemical shifts of the pyridine ring protons
(Figure 3), and pronounced diasterotopicity of the two sets of
methylene protons. These H NMR signals should thus serve
as a good indicator of whether the pyridine remains ligated to
1
the Mo(VI) center of 3 in the presence of HMPA. The results
1
of a H NMR titration of 3 in CDCl3 with up to ∼15% v/v
HMPA are shown in Figure 3A. Only modest changes in the
chemical shifts of the pyridine ring protons occur upon addition
of HMPA; the diastereotopic methylene protons (not shown)
exhibit a similar change in chemical shift, but no appreciable
change in line width. Similar changes occur in the spectrum of
the ligand by itself (Figure 3B), indicating that these variations
derive from the change in solvent composition rather than the
formation of F′. This in turn reasonably excludes the possibility
that much weaker donor ligands such as olefin would be able
to induce such ligand dissociation, and argues against the
formation of an intermediate such as F. As an alternative probe
for pyridine dissociation, we have tried to trap the free pyridine
nitrogen by treatment of 2 in CDCl3 with an excess of
methanesulfonic acid. Again, no changes in the signals of the
pyridine ring protons are observed. Finally, we note that NMR
spectra of 3 at higher temperature (70 °C) provide no evidence
of fluctional behavior in the ligand: the signals for the pyridine
ring and diastereotopic methylene protons do not exhibit any
appreciable change in line width or chemical shift.
Ultimately, the invocation of Mo(VI)-olefin intermediates
derives from the kinetic profile of certain epoxidation systems.
Assuming that, as concluded above, Mo(VI)-olefin complexes
are not involved in the catalytic cycle, the epoxidation of 8
should be rigorously first order in olefin. Kinetic analysis of
the epoxidation was carried out under the conditions indicated
in Scheme 4 and Table 1, employing olefin concentrations (0.4-
1.6 M)27 in the range where nonlinear dependence on olefin
concentration has previously been observed. As the data in
Figure 4 indicate, the individual concentration runs all follow
first-order kinetics, and lead to the extraction of a common
(25) The widely accepted assumption of η2 alkyl peroxide coordination
(ref 13) is central to our interpretation, and we are unaware of any Mo-
(VI)/tert-butyl hydroperoxide epoxidations in which only η1 alkyl peroxide
coordination has been proposed. In support of this assumption, preliminary
1H NMR experiments en route to isolating a Mo(VI) alkyl peroxide complex
lead us to assign the chemical shift (CDCl3, 300 MHz) of the η2-coordinated
tert-butyl peroxide as 1.40 ppm, 0.17 ppm downfield from the signal for
free tert-butyl hydroperoxide. This is very similar to the chemical shifts
reported for η2 V(V) tert-butyl peroxide complexes (ref 13b).
absolute rate constant, k ) (2.9 ( 0.5) × 10-3 M-1 s-1 28
. While
lack of evidence is not proof, kinetic analysis of our system, in
(26) The 1H NMR spectra of 3 do not exhibit any change in the presence
of an excess of styrene or olefin 8. The 1H NMR spectra of crude
epoxidation reaction mixtures show no free ligand, arguing against
displacement of the ligand by tert-butyl peroxide and/or tert-butyl alcohol.
(27) At 1.6 M, the reaction is approximately 5% v/v olefin.
(28) This rate constant is at the lower end of those previously reported
for Mo(VI)-mediated alkene epoxidations, both stoichiometric and catalytic,
reflecting the relatively low reactivity of the present system. See ref 12.

866 J. Am. Chem. Soc., Vol. 123, No. 5, 2001
Mitchell and Finney
Figure 3. Titration of 3 with HMPA.
which even incidental olefin coordination should be precluded,
is entirely consistent with the conclusion that metal-olefin
complexes are not involved in the epoxidation reaction.
Olefins as Epoxidation Inhibitors. We have not yet been
successful in isolating a Mo(VI) alkyl peroxide (e.g., 13, Figure
5).29 This precludes the most definitive experiment: kinetic
analysis of a stoichiometric epoxidation with such a complex.
Such experiments have previously been carried out with oxo-
(bisperoxo)Mo(VI) and (oxo)V(V) alkylperoxo complexes (14
and 15, Figure 5), and appear to contradict our conclusion that
metal-olefin complexes are not essential intermediates in the
epoxidation process. For both 14 and 15, nonlinear rate
dependence on olefin concentration is reported, and particular
attention is paid to the presence of an open coordination site
for olefin coordination. In the case of 14, these reports are the
origin of the argument in favor of olefin coordination and
oxametallacycle formation.
These observations do not, however, necessarily contradict
our conclusion. Although seldom discussed, a simple alternative
interpretation of the behavior of 14 is that oxygen atom transfer
is mediated by the uncomplexed oxo(bisperoxo)Mo(VI) species
(14, L ) vacant). If the HMPA and olefin complexes, which
should have a less electrophilic metal center, are significantly
less reactive than the uncoordinated peroxometal complex, the
observed kinetic data are satisfactorily explained without
(29) To our knowledge, no Mo(VI) alkyl peroxide has ever been isolated
and characterized. Efforts to prepare peroxo metal complexes, either by
treatment of 2 with H2O2 or incubation of 1 with MoO(O2)2‚DMF (ref 6a),
have likewise been unsuccessful.

New Mo Catalysts for Alkyl Olefin Epoxidation
J. Am. Chem. Soc., Vol. 123, No. 5, 2001 867
and the Sharpless asymmetric dihydroxylation.33 Future work
will focus on the isolation of Mo(VI)-alkyl peroxide intermedi-
ates and the application of 2-4 and related catalysts to other
reactions.
Experimental Details
General Notes and Procedures. Melting points were obtained in
open capillary tubes with a Thomas Scientific Uni-Melt melting point
apparatus, and are uncorrected. 1H NMR spectra were obtained on
Varian HG-300 (300 MHz) or HG-400 (400 MHz) spectrometers.
Chemical shifts (δ) are reported in parts per million (ppm) relative to
residual solvent (CHCl3, s, δ 7.26). Multiplicities are given as
follows: s (singlet), d (doublet), t (triplet), q (quartet), dd (doublet of
doublets), dt (doublet of triplets), m (multiplet). Proton-decoupled 13
C
NMR spectra were obtained on Varian HG-300 (75 MHz) or HG-400
(100 MHz) spectrometers. 13C chemical shifts are reported relative to
CDCl3 (t, δ 77.0). IR stretches are given in cm-1; spectra were obtained
on a Nicolet 550 Series II Spectrophotometer. Mass spectroscopic
analyses were provided by the facility at The Scripps Research Institute,
with the exception of 2, for which analysis was carried out by JEOL,
Inc. (Peabody, MA).
High-pressure liquid chromatographic (HPLC) analyses were carried
out on a Hewlett-Packard Series 1100 HPLC system equipped with a
diode array UV detector. UV detection was performed at 210 nm. Silica
gel chromatographic purifications were performed by flash chroma-
tography with silica gel (Selecto, 32-63 µm) packed in glass columns;
eluting solvent for each purification was determined by thin-layer
chromatography (TLC). Analytical TLC was performed on aluminum
plates coated with 0.25 mm silica gel using UV light, ethanolic
p-anisaldehyde, or aqueous potassium permanganate for visualization.
Manipulations under an inert atmosphere were carried out with
standard Schlenk line techniques. Tetrahydrofuran (THF), CH2Cl2, Et2O,
and benzene were dried by passage through a column of activated
alumina.34 Toluene solutions of anhydrous tert-butyl hydroperoxide
were prepared by the method of Sharpless et al.20 All other reagents
and solvents were reagent grade and were used without further
purification unless otherwise specified.
Epoxidation: Representative Procedure. In a typical epoxidation
reaction, 2 (0.015 g, 0.032 mmol) and tert-butyl hydroperoxide (0.470
mL of a 4.26 M solution in toluene, 2.000 mmol) were combined in
benzene (0.500 mL) containing 4 Å molecular sieves (ca. 0.100 g) and
benzophenone (0.020 g, 0.110 mmol) as an internal standard. The
resulting mixture was warmed to 30 °C under nitrogen and allowed to
stir 30 min, at which time 8 (0.120 mL, 0.800 mmol) was added.
Reactions were monitored qualitatively by TLC and quantitatively
by 1H NMR or HPLC. For NMR analysis, samples were concentrated
and epoxide quantified by integration vs benzophenone. For HPLC
analysis, samples were obtained by removing a reaction aliquot and
filtering through silica gel (15% i-PrOH-hexanes eluent) to remove
Mo(VI) complexes. The sample was then diluted with 15% i-PrOH-
hexanes, and epoxide quantified by integration vs benzophenone (210
nm, 1 mL/min, 2% i-PrOH-hexanes, 4.6 mm × 200 mm Waters
Spherisorb S5CN). For preparative reactions, the reaction mixture was
concentrated and chromatographed directly on silica gel (20% EtOAc-
hexanes).
Figure 4. Kinetic analysis of the epoxidation of 8 at several
concentrations.
requiring that Mo(VI)-olefin complexes appear directly in the
catalytic cycle.30 The apparent requirement for a vacant
coordination site on the Mo(VI) center thus does not derive from
a need to coordinate olefin, but rather the enhanced reactivity
of coordinatively unsaturated Mo(VI) species.31 In the case of
15, if one assumes that both olefin and HMPA are capable of
displacing the weakly bound second oxygen of η2-coordinated
alkyl peroxide (formation of 16), it is not surprising that both
serve as inhibitors of oxygen atom transfer. In this context, it
appears that Mo(VI) complexes such as 13 are sufficiently
sterically hindered to prevent olefin coordination, although
coordination to smaller donors such as the oxygen center of
HMPA is still possible.
Conclusion
In conclusion, we have reported the first members of a new
class of Mo(VI) epoxidation catalysts based on nonlabile
monoanionic tridentate ligands. Designed to preclude simulta-
neous coordination of olefin and bidentate alkyl peroxide, the
activity of these catalysts supports an epoxidation mechanism
involving direct oxygen atom transfer to olefin. This in turn
leads us to conclude that previous reports of nonlinear olefin
concentration dependence may be ascribed to complex kinetics
resulting from the presence of multiple catalytically active
species, or the formation of tangential Mo(VI)-olefin complexes
which complicate kinetic analysis. While this conclusion leads
to discontinuity with the mechanism of other catalytic processes
in which d0-olefin complexes or metallacycles are established
intermediates (olefin metathesis and polymerization, e.g.),32 it
is in keeping with recent mechanistic studies of two other
important catalytic oxidation systems: the Jacobsen epoxidation
Kinetic Analyses. Kinetic data were obtained for the epoxidation
of 8 according to the above procedure, at varying initial concentrations
of olefin. Reaction progress was monitored by HPLC, as described
(32) For leading references, see: (a) Ziegler Catalysis; Fink., G.,
Mu¨lhaupt, R., Brintzinger, H. H., Eds.; Springer: Berlin, 1995. (b) Ivin,
K. J.; Mol, J. C. Olefin Metathesis and Metathesis Polymerization; Academic
Press: San Diego, 1997.
(30) Kinetic analysis of the stoichiometric epoxidation of 1-methylcy-
clohexene with MoO(O2)2‚HMPA suggests that the uncomplexed oxo-
(peroxo)Mo(VI) species is 10-60 times as reactive as the HMPA complex
(ref 10b). A similar (albeit attenuated) effect for olefin complexation follows
as a logical inference.
(31) Recent work on catalytic epoxidations with oxo(bisperoxo)Mo(VI)
(14, L ) neutral bidentate ligand; ref 11) indicate that the apparent need
for a vacant coordination site on the metal center derives from a requirement
for η2-coordination of the alkylperoxide terminal oxidant.
(33) For leading references, see: (a) Finney, N. S.; Pospisil, P. J.; Chang,
S. B.; Palucki, M.; Konsler, R. G.; Hansen, K. B.; Jacobsen, E. N. Angew.
Chem., Int. Ed. Engl. 1997, 36, 1720-1722. (b) Linde, C.; Arnold, M.;
Norrby, P. O.; Akermark, B. Angew. Chem., Int. Ed. Engl. 1997, 36, 1723-
1725. (c) DelMonte, A. J.; Haller, J.; Houk, K. N.; Sharpless, K. B.;
Singleton, D. A.; Strassner, T.; Thomas, A. A. J. Am. Chem. Soc. 1997,
11, 99907-99908.
(34) Pangborn, A. B.; Giardello, M. A.; Grubbs, R. H.; Rosen, R. K.;
Timmers, F. J. Organometallics 1996, 15, 1518-1520.

868 J. Am. Chem. Soc., Vol. 123, No. 5, 2001
Mitchell and Finney
Figure 5.
above. All data presented in Figure 4 are the average of three
experimental runs.
J ) 12 Hz, 1H), 1.23 (s, 9H), 1.19 (s, 9H). 13C NMR (100 MHz, CDCl3,
25 °C) δ 157.1, 156.4, 151.1, 143.5, 139.6, 137.7, 124.1, 124.0, 123.1,
122.0, 121.5, 54.0, 43.1, 34.8, 34.3, 31.6, 30.1. IR (thin film) ν 3209,
2956, 2089 (N3), 924 (ModO), 896 (ModO). MS (70 eV): m/z (%)
455 (100) [(ligand)MoO2+]. HRMS (C21H29N2O3Mo): calcd 455.1232,
obsd 455.1226 [[(ligand)MoO2]+].
E-1-Phenyl-3-pentene (6): To a solution of 6-phenyl-2-hexyne (3.3
g, 20.8 mmol) in liquid ammonia (10 mL) was added small pieces of
sodium metal (0.97 g, 42.0 mmol, 2.02 equiv). The blue solution was
stirred vigorously at -33 °C for 2 h, after which dry THF (5 mL) was
added and the ammonia was allowed to evaporate. Solid NH4Cl was
then added cautiously to quench the reaction. The resulting solution
was diluted with hexanes (75 mL) and washed with saturated NH4Cl
(3 × 75 mL). The organic phase was dried over Na2SO4 and
concentrated under reduced pressure to afford a yellow oil, which was
purified by flash column chromatography (100% hexanes) to yield
olefin 6 (2.23 g, 66%) as a colorless liquid. 6: 1H NMR (400 MHz,
CDCl3, 25 °C) δ 7.17-7.30 (m, 5H), 5.43-5.46 (m, 2H), 2.60 (t, 2H,
J ) 8 Hz), 1.99-2.04 (m, 2H), 1.65-1.70 (m, 5H). IR (neat) ν 3040,
2922, 2848, 1604, 1500, 1451, 964, 710.
Z-1-Phenyl-3-pentene (7): n-Butyllithium (32 mL, 51 mmol) was
added dropwise via syringe over 10 min to a suspension of ethyltri-
phenylphosphonium iodide (22.5 g, 54 mmol, 1.05 equiv)35 in dry THF
(150 mL) at -78 °C. After the reaction mixture was stirred under a
nitrogen atmosphere for 2 h, a solution of 3-phenylpropionaldehyde
(7.6 mL, 58 mmol, 1.13 equiv) in THF (15 mL) was added dropwise
via syringe over 5 min. The reaction mixture was warmed to room
temperature and stirred for 12 h, then filtered through a pad of silica
with hexanes. The filtrate was concentrated under reduced pressure,
and the residue was purified by flash column chromatography (100%
hexanes) to yield olefin 7 (4.97 g, 63%) as a colorless liquid. 7: 1H
NMR (300 MHz, CDCl3, 25 °C) δ 7.17-7.31 (m, 5H), 5.40-5.51 (m,
2H), 2.67 (t, 2H, J ) 8 Hz), 2.37 (q, 2H, J ) 8 Hz), 1.61 (s, 3H). IR
(neat) ν 3016, 2925, 2855, 1604, 1496, 1454, 698.
Compound Characterization. N-(2-Pyridyl)methyl-2-hydroxy-
3,5-di-tert-butylbenzaldimine: To a solution of 2-hydroxy-3,5-di-tert-
butylbenzaldehyde (1.13 g, 4.82 mmol) in CH3OH (10 mL) was added
neat 2-aminomethylpyridine (0.50 mL, 4.85 mmol, 1.01 equiv). The
solution was allowed to stir for 2 h, whereupon concentration and drying
in vacuo afforded the corresponding imine as a yellow solid in
quantitative yield. 1: 1H NMR (300 MHz, CDCl3, 25 °C) δ 8.57-
8.59 (m, 2H), 7.69 (dt, J ) 8, 8, 2 Hz, 1H), 7.43 (d, J ) 2 Hz, 1H),
7.38 (d, J ) 8 Hz, 1H), 7.18-7.20 (m, 1H), 7.17 (d, J ) 2 Hz, 1H),
4.94 (s, 2H), 1.47 (s, 9H), 1.33 (s, 9H). IR (KBr) ν 2957, 1632. HRMS
(C21H28N2O): calcd 325.2280, obsd 325.2268 [M+].
N-(2-Pyridyl)methyl-2-hydroxy-3,5-di-tert-butylbenzylamine (1):
A solution of the imine (1.56 g, 4.82 mmol) in CH3CN (20 mL) was
treated with NaBH3CN (0.76 g, 12.10 mmol, 2.51 equiv) and allowed
to stir for 15 min, at which time acetic acid (1 mL) was added. After
2 h, the reaction mixture was diluted with Et2O (20 mL) and washed
with 1 M NaOH (2 × 40 mL) and brine (1 × 40 mL). The organic
phase was dried over Na2SO4 and concentrated to afford an orange
oil, which was purified by chromatography on silica gel (1% CH3-
OH-CH2Cl2) to afford the ligand as a pale yellow oil (1.33 g, 4.10
mmol, 85%). 1: 1H NMR (300 MHz, CDCl3, 25 °C) δ 8.58 (d, J ) 5
Hz, 1H), 7.67 (dt, J ) 8, 8, 2 Hz, 1H), 7.19-7.24 (m, 3H), 6.84 (d, J
) 2 Hz, 1H), 3.99 (s, 2H), 3.94 (s, 2H), 1.43 (s, 9H), 1.29 (s, 9H). IR
(KBr) ν 3250-3400, 2955. HRMS (C21H30N2O): calcd 327.2436, obsd
327.2435 [M+].
Complex 2: MoO2 (acac)2 (1.33 g, 4.10 mmol) was added in one
portion to a hot (50 °C) solution of 1 (1.33 g, 4.10 mmol) in CH3OH
(5 mL). The reaction was maintained at 50 °C for 2 h, during which
time a bright orange crystalline solid precipitated. Complex 2 (0.81 g,
2.65 mmol, 65%) was isolated by filtration of the hot reaction mixture,
followed by washing with CH3OH (2 × 5 mL) and drying in vacuo. 2:
1
mp 232-235 °C dec. H NMR (300 MHz, CDCl3, 25 °C) δ 8.69 (d,
J ) 5 Hz, 1H), 7.49 (dt, J ) 8, 8, 2 Hz, 1H), 6.98-7.01 (m, 1H), 6.94
(d, J ) 2 Hz, 1H), 6.90 (d, J ) 8 Hz), 6.83 (d, J ) 2 Hz, 1H), 5.47-
5.49 (m, 1H), 5.16 (dd, J ) 16, 8 Hz, 1H), 4.72 (dd, J ) 13, 3 Hz,
1H), 3.92 (d, J ) 16 Hz, 1H), 3.82 (dd, J ) 13, 3 Hz, 1H), 1.23 (s,
9H), 1.18 (s, 9H). 13C NMR (75 MHz, CDCl3, 25 °C) δ 157.9, 156.9,
150.5, 141.8, 138.5, 137.5, 123.8,123.5, 122.2, 121.6, 121.0, 54.5, 53.3,
34.9, 34.2, 31.7, 30.2. IR (KBr): ν 3431, 2955, 920 (ModO), 880
(ModO). Elemental Analysis: calcd (C42H58N4O7Mo2) C 54.67%, H
6.33%, N 6.07%, obsd C 54.33%, H 6.06%, N 6.00%. MS (70 eV):
m/z (%) 455 (50) [(ligand)MoO2+]. HRMS (C21H29N2O3Mo): calcd
455.1232, obsd 455.1236 [[(ligand)MoO2]+].
1-Phenyl-3,4-dimethyl-3-pentene (8): n-Butyllithium (40 mL, 64
mmol, 1.01 equiv) was added dropwise via syringe over 10 min to a
suspension of 2-propyltriphenylphosphonium bromide (24.3 g, 63.1
mmol)26 in dry Et2O (150 mL). After the reaction mixture was stirred
under a nitrogen atmosphere for 2 h, a solution of 3-phenylpropional-
dehyde (10 mL, 76 mmol, 1.2 equiv) in Et2O (25 mL) was added
dropwise via syringe over 5 min. The reaction mixture was refluxed
for 12 h, then filtered through a pad of silica with hexanes. The filtrate
was concentrated under reduced pressure, and the residue was purified
by flash column chromatography (100% hexanes) to yield olefin 8 (5.17
g, 51%) as a colorless liquid. 8: 1H NMR (300 MHz, CDCl3, 25 °C)
δ 7.27-7.32 (m, 2H), 7.19-7.22 (m, 3H), 5.18 (t, 1H, J ) 8 Hz),
2.63 (t, 2H, J ) 8 Hz), 2.30 (q, 2H, J ) 8 Hz), 1.69 (s, 3H), 1.57 (s,
3H). IR (neat) ν 3025, 2969, 2925, 2856, 1725, 1606, 1500, 1463, 1375,
760, 700.
Complexes 3 and 4: The preparation of complex 3 is representative.
To a solution of 2 (0.020 g, 0.02 mmol) in dry CH2Cl2 (1.5 mL) was
added TMSN3 (100 µL, 0.76 mmol, 37.7 equiv). The reaction was
allowed to stir and sealed with a septum and Parafilm, at room
temperature for 90 h, at which time volatiles were removed under
vacuum, affording 3 as an unstable hygroscopic orange powder. As an
alternative, the reaction may be carried out in CDCl3, allowing
spectroscopic characterization without concentration. 3: mp >200 °C
Epoxides 9-12: The preparation of 4-Phenyl-1-butene oxide (9) is
representative. m-Chloroperbenzoic acid (70% w/w, 0.21 g, 0.73 mmol,
1.09 equiv) was added to a solution of 4-phenyl-1-butene (5, 0.1 mL,
1
dec. H NMR (300 MHz, CDCl3, 25 °C) δ 9.10 (d, J ) 6 Hz, 1H),
(35) Ethyl- and 2-propyltriphenylphosphonium bromide were prepared
by heating the corresponding alkyl bromide with 1 molar equiv of
triphenylphosphine in a sealed tube. The salts were used without further
purification.
7.66 (dt, J ) 8, 8, 2 Hz, 1H), 7.20-7.40 (m, 1H), 6.95-7.05 (m, 2H),
6.91 (d, J ) 2 Hz. 1H), 5.15-5.25 (m, 1H), 4.76 (d, J ) 12 Hz, 1H),
4.58 (dd, J ) 16, 8 Hz, 1H, CH2), 4.00 (d, J ) 16 Hz, 1H), 3.89 (d,

New Mo Catalysts for Alkyl Olefin Epoxidation
J. Am. Chem. Soc., Vol. 123, No. 5, 2001 869
Table 2. Summary of Crystallographic Data for 2
and concentrated under reduced pressure to afford 9 (0.093 g, 95%) as
a colorless liquid. 9: 1H NMR (300 MHz, CDCl3, 25 °C) δ 7.21-7.36
(m, 5H), 2.96-3.02 (m, 1H), 2.74-2.92 (m, 3H), 2.51 Hz (dd, 1H, J
) 5, 3.0 Hz), 1.83-1.99 (m, 2H). IR (neat) ν 3033, 2986, 2919, 2858,
1602, 1501, 1461, 1266.
E-1-Phenyl-3-pentene oxide (10): 1H NMR (300 MHz, CDCl3, 25
°C) δ 7.16-7.31 (m, 5H), 2.74 (dq, 1H, J ) 5, 2 Hz), 2.63-2.69 (m,
3H), 1.67-1.89, 1.48-1.66, 1.29 (d, 3H, J ) 5 Hz). IR (neat) ν 3027,
2981, 2929, 1606, 1496, 1454, 1380, 1029, 859, 747, 700.13C NMR
(75 MHz, CDCl3, 25 °C) δ 141.9, 128.3, 128.2, 125.7, 59.6, 54.5, 35.7,
31.6, 27.8, 17.8. MS (70 eV): m/z (%) 176 (50) [M+].
Z-1-Phenyl-3-pentene oxide (11): 1H NMR (300 MHz, CDCl3, 25
°C) δ 7.21-7.36 (m, 5H), 2.70-3.10 (m, 4H), 1.77-1.98 (m, 2H),
1.18 (d, 3H, J ) 5 Hz). IR (neat) ν 3060, 2963, 2919, 2850, 1600,
1500, 1463, 1394, 756, 700.
1-Phenyl-3,4-dimethyl-3-pentene oxide (12): 1H NMR (300 MHz,
CDCl3, 25 °C) δ 7.21-7.31 (m, 5H), 2.71-2.94 (m, 3H), 1.78-2.01
(m, 2H), 1.31 (s, 3H), 1.17 (s, 3H). IR (neat) ν 2963, 2925, 1731, 1600,
1500, 1456, 1375, 1119, 700.
empirical formula
formula weight
temperature
C42H58Mo2N4O7
922.80
158(2) K
wavelength
0.71073 Å
crystal system
space group
unit cell dimensions
monoclinic
P21/n
a ) 13.4504(11) Å, R ) 90°
b ) 8.5521(7) Å, â ) 95.630(2)°
c ) 38.577(3) Å, γ ) 90°
4416.1(6) Å3
volume
Z
4
density (calcd)
absorption coeff
F(000)
crystal size
θ range for data collection
index ranges
1.388 Mg/m3
0.618 mm-1
1912
0.21 × 0.16 × 0.06 mm3
1.06 to 28.32°
-17 e h e 14, -10 e k e 11,
-50 e l e 49
28422
10587 [R(int) ) 0.0570]
96.2%
semiempirical (Bruker SADABS)
0.9639 and 0.8811
full-matrix least-squares on F2
no. of reflcns collected
no. of independent reflcns
completeness to θ ) 28.32°
absorption correction
max and min transmission
refinement method
Acknowledgment. The authors thank the UCSD Academic
Senate, an ARCS Foundation Fellowship (J.M.M.), and the
Petroleum Research Fund administered by the American
Chemical Society (33779-G1) for support of this research. We
are indebted to the National Science Foundation (CHE-9709183)
for support of the Departmental NMR facilities.
no. of data/restraints/parameters 10587/0/497
goodness-of-fit on F2
final R indices [I > 2σ(I)]
R indices (all data)
extinction coefficient
largest diff peak and hole
1.196
R1 ) 0.0529, wR2 ) 0.0979
R1 ) 0.0829, wR2 ) 0.1064
0.00024(4)
0.964 and -1.019 e‚Å-3
Supporting Information Available: Tables of crystal data,
structure solution and refinement, atomic coordinates, bond
lengths and angles, and anisotropic thermal parameters for 2
(PDF) and an X-ray crystallographic file (CIF). This material
is available free of charge via the Internet at http://pubs.acs.org.
0.67 mmol) in chloroform (4 mL) at 0 °C, and the solution was warmed
to room temperature. After the solution was stirred for 12 h, CH2Cl2
(20 mL) was added, and the reaction mixture was washed with 2.5 M
NaOH (4 × 25 mL). The organic phase was dried over sodium sulfate
JA002697U