Organometallic catalysis in aqueous solution. The hydrolytic activity of a water-soluble ansa-molybdocene catalyst

Article abstract of DOI:10.1021/om7004657

The synthesis, characterization, and reactivity of the new water-soluble ansa-molybdocene catalyst [{C₂Me₄(C₅H ₄)₂}Mo(OH)(OH₂)][OTs] (3) and the related hydroxo-bridged dimer [(C₂Me₄(C₅H ₄)₂)Mo(M-OH)]₂[OTs]₂ (5) are described. The effect of the ethylene bridge on the metallocene structure was evaluated by comparing the crystal structures of (C₂Me ₄(C₅H₄)₂)MoH₂ (2) and 5 to those of the nonansa analogues. The ethylene bridge changed the bite angles of the metallocene fragment by only a few degrees in both ansa structures. To probe the electronic consequences of the tetramethylethylene bridge, the (C ₂Me₄(C₅H₄)₂)Mo(CO)H (4) complex was prepared. On the basis of the V(C≡O) stretching frequencies, the ansa ligand C₂Me₄(C₅H₄) ₂ was found to be electron-withdrawing relative to two η⁵C₅H₅ ligands. The reactivity of 3 in nitrile hydration, phosphate ester hydrolysis, and carboxylic acid ester hydrolysis was explored, and the rate constants for these transformations were compared to rate constants obtained using the Cp₂Mo(OH)(OH ₂)⁺ and Cp′₂Mo(OH)(OH₂) ⁺ catalysts. In all cases, the Cp₂Mo(OH)(OH ₂)⁺ catalyst, having intermediate electron density, had the largest rate constants. The reactivity trends for the three catalysts are explained by the relative electrophilicities of the Mo centers. If electrondonating cyclopentadienyl ligands are employed, the reactivity of the bound substrate is decreased relative to Cp and the rate is decreased. Conversely, if electron-withdrawing Cp cyclopentadienyl ligands are employed, the reactivity of the bound hydroxo nucleophile is decreased and the rate is decreased. In the case of the Cp₂Mo(OH)(OH₂)⁺ complex, these two opposing trends converge, and optimal activity is observed.

Full text of DOI:10.1021/om7004657

Organometallics 2007, 26, 5179-5187
5179
Organometallic Catalysis in Aqueous Solution. The Hydrolytic
Activity of a Water-Soluble ansa-Molybdocene Catalyst
Takiya J. Ahmed, Lev N. Zakharov, and David R. Tyler*
Department of Chemistry, UniVersity of Oregon, Eugene, Oregon 97403
ReceiVed May 10, 2007
The synthesis, characterization, and reactivity of the new water-soluble ansa-molybdocene catalyst
[{C2Me4(C5H4)2}Mo(OH)(OH2)][OTs] (3) and the related hydroxo-bridged dimer [{C2Me4(C5H4)2}Mo-
(µ-OH)]2[OTs]2 (5) are described. The effect of the ethylene bridge on the metallocene structure was
evaluated by comparing the crystal structures of {C2Me4(C5H4)2}MoH2 (2) and 5 to those of the non-
ansa analogues. The ethylene bridge changed the bite angles of the metallocene fragment by only a few
degrees in both ansa structures. To probe the electronic consequences of the tetramethylethylene bridge,
the {C2Me4(C5H4)2}Mo(CO)H (4) complex was prepared. On the basis of the ν(CtO) stretching
frequencies, the ansa ligand C2Me4(C5H4)2 was found to be electron-withdrawing relative to two η5-
C5H5 ligands. The reactivity of 3 in nitrile hydration, phosphate ester hydrolysis, and carboxylic acid
ester hydrolysis was explored, and the rate constants for these transformations were compared to rate
constants obtained using the Cp2Mo(OH)(OH2)+ and Cp′2Mo(OH)(OH2)+ catalysts. In all cases, the Cp2-
Mo(OH)(OH2)+ catalyst, having intermediate electron density, had the largest rate constants. The reactivity
trends for the three catalysts are explained by the relative electrophilicities of the Mo centers. If electron-
donating cyclopentadienyl ligands are employed, the reactivity of the bound substrate is decreased relative
to Cp and the rate is decreased. Conversely, if electron-withdrawing Cp cyclopentadienyl ligands are
employed, the reactivity of the bound hydroxo nucleophile is decreased and the rate is decreased. In the
case of the Cp2Mo(OH)(OH2)+ complex, these two opposing trends converge, and optimal activity is
observed.
Introduction
Molybdocenes containing aqua and hydroxo ligands are
water-soluble, and several such complexes have been extensively
used as catalysts and mediators in aqueous-phase reactions.1-12
The Cp2Mo(OH)(OH2)+ complex was the first organometallic
Figure 1. Structures of (a) a water-soluble molybdocene catalyst
and (b) a water-soluble ansa-molybdocene.
complex reported to hydrolyze phosphate esters7,10,11 at rates
comparable to the excellent Co(III) amine hydrolysis catalysts
studied by Chin et al.13 Later investigations of the Cp′2Mo-
(OH)(OH2)+ (Cp′ ) η5-C5H4Me) complex (Figure 1a) in our
laboratory extended the utility of the molybdocenes to catalytic
hydration2,3 and H/D exchange reactions,4-6 the latter being one
of the few examples of C-H bond activation in water. Ongoing
efforts to exploit molybdocenes for environmentally benign
transformations of organic substrates have continued with an
exploration of the electronic and steric effects of substituted
cyclopentadienyl ligands on the reactivity of the molybdocenes.
ansa-Ligands (bridged cyclopentadienyl rings; Figure 1b) offer
a convenient method of altering the geometric structure and
electronics of the cyclopentadienyl ligands without the use of
substituents containing functional groups that may interfere with
the catalyst active site.
ansa-Bridges were shown to have a significant impact on
the geometric structure, electronic structure, and reaction
chemistry of molybdocenes.14-26 Molecules with one-atom
bridges (the type most commonly studied) significantly reduce
* Corresponding author. E-mail: dtyler@uoregon.edu.
(1) Breno, K. L.; Ahmed, T. J.; Pluth, M. D.; Balzarek, C.; Tyler, D. R.
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10.1021/om7004657 CCC: $37.00 © 2007 American Chemical Society
Publication on Web 09/07/2007

5180 Organometallics, Vol. 26, No. 21, 2007
Scheme 1. Proposed Mechanism of Intramolecular Hydroxide Attack
Ahmed et al.
the bite angle of the metallocene moiety and enhance the
bonding of the Cp rings to the metal center. The stronger Cp-M
bonds in these molecules were recently shown to be the result
of a more stable acceptor orbital on the Cp ligand with
consequent increased back-donation from the metal center.27 In
a Mo(IV) metallocene, this results in an even more electrophilic
metal center.17
The studies reported herein were conducted in order to
investigate the reactivity of the more electrophilic metal center
of ansa molybdocenes in aqueous-phase hydration and hydroly-
sis reactions. The general mechanism of Cp(′)2Mo(OH)(OH2)+-
mediated hydrolysis (Cp(′) ) η5-C5H5 or η5-C5H4Me) is Lewis
acid activation of the substrate followed by intramolecular attack
of the coordinated hydroxo ligand (Scheme 1).2 In prior studies,
improved catalytic performance was noted for transformations
of nitriles containing electron-withdrawing groups due to a
greater positive charge on the electrophilic carbon center.3 For
similar reasons, it was postulated that a more electrophilic metal
center might also lead to enhanced activation of the substrate
and enhanced reactivity. Alternatively, a more electrophilic
metal center will also influence the rate of attack by a
coordinated nucleophile.
(II)-catalyzed36-40 hydrolysis reactions that proceed by intra-
molecular nucleophilic attack demonstrated that the rate of
hydrolysis can be affected by (1) the acidity of the protonated
hydroxo nucleophile, (2) the tendency of the active catalyst to
dimerize, and (3) steric changes that lead to stabilization of the
cyclic intermediate. With regard to the first of these factors,
note that the protonated nucleophile in water-soluble molyb-
docene complexes is relatively acidic (pKa1 ≈ 5.5). Therefore,
the expected decrease in the pKa of the relatively electrophilic
ansa complex is not expected to influence the concentration of
the active catalyst or the reactivity of the molybdocene at neutral
pH. As for the second factor, the tendency of the molybdocenes
to dimerize may influence the rate of catalysis and must be taken
into account. Last, because ansa linkages are known to alter
the geometric structure of metallocenes, any structural changes
in the ansa complex must be carefully analyzed to determine
their significance.
In an initial study of how a more electrophilic molybdocene
complex reacts toward intramolecular nucleophilic attack, the
silyl-bridged ansa-molybdocene [SiMe2(C5H4)2Mo(OH)(OH2)]-
[OTs] was studied.1 Unfortunately, the Si-Cp bonds of
[SiMe2(Cp2Mo(OH)(OH2)]2+ were unstable to hydrolysis, and
an aqueous solution of the complex readily degraded to give
Other molecular parameters may influence the rate, as well.
2+
Investigations of Co(III)-,13,28,29 Ir(III)-,30 Cu(II)-,31-35 and Zn-
the [Cp2Mo(OH)(OH2)]+ and [Cp2Mo(µ-OH)]2 complexes.
To avoid problems associated with the hydrolysis of C-Si
bonds, the previously unexplored ethylene-bridged ansa-
molybdocene [{C2Me4(η5-C5H4)2}Mo(OH)(OH2)][OTs] and its
related binuclear analogue [{C2Me4(η5-C5H4)2}Mo(µ-OH)]2-
[OTs]2 were prepared (Figure 2). In addition to being less
susceptible to hydrolysis, the ethylene bridges were also chosen
because they generally induce minimal structural changes in
the bite angles and ring tilts of bent metallocenes,27 thereby
avoiding the large structural changes caused by one-atom ansa
bridges. The changes in reactivity for an ethylene-bridged ansa
catalyst, therefore, can be solely attributed to electronic changes
at the metal center and not to steric changes. The results reported
below expand our understanding of the reactivity of substituted
molybdocenes as well as the general ansa effect in molybdocene
systems. (In this paper, “substituted molybdocenes” refers to
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B. J.; Heinekey, D. M. Inorg. Chem. 2004, 43, 3475-3483.
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2002, 1861-1866.
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tallics 1997, 16, 5763-5769.
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M. L. H.; Stephens, A. H. H. J. Chem. Soc., Dalton Trans. 1998, 2689-
2696.
(24) Jourdain, I. V.; Fourmigue, M.; Guyon, F.; Amaudrut, J. Organo-
metallics 1999, 18, 1834-1839.
(25) Churchill, D. G.; Bridgewater, B. M.; Parkin, G. J. Am. Chem. Soc.
2000, 122, 178-179.
(26) Churchill, D. G.; Janak, K. E.; Wittenberg, J. S.; Parkin, G. J. Am.
Chem. Soc. 2003, 125, 1403-1420.
(27) Zachmanoglou, C. E.; Docrat, A.; Bridgewater, B. M.; Parkin, G.;
Brandow, C. G.; Bercaw, J. E.; Jardine, C. N.; Lyall, M.; Green, J. C.;
Keister, J. B. J. Am. Chem. Soc. 2002, 124, 9525-9546.
(28) Chin, J.; Banaszczyk, M.; Jubian, V.; Zou, X. J. Am. Chem. Soc.
1989, 111, 186-90.
(35) Itoh, T.; Hisada, H.; Usui, Y.; Fujii, Y. Inorg. Chim. Acta 1998,
283, 51-60.
(36) Fujii, Y.; Itoh, T.; Onodera, K.; Tada, T. Chem. Lett. 1995, 305-6.
(37) Bazzicalupi, C.; Bencini, A.; Berni, E.; Bianchi, A.; Fedi, V.; Fusi,
V.; Giorgi, C.; Paoletti, P.; Valtancoli, B. Inorg. Chem. 1999, 38, 4115-
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(29) Chin, J.; Zou, X. J. Am. Chem. Soc. 1988, 110, 223-5.
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7.
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Chem. 2004, 210, 23-29.
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D. R.; Burstyn, J. N. Inorg. Chem. 1999, 38, 2961-2968.
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Organometallic Catalysis in Aqueous Solution
Organometallics, Vol. 26, No. 21, 2007 5181
this decreases the yield considerably. The 1H and 13C NMR spectra
for 2 are provided in the Supporting Information and show the
material obtained by sublimation is spectroscopically pure. 1H NMR
(C6D6): δ 4.92 (m, 4, C5H4), 4.69 (m, 4, C5H4), 0.75 (s, 12, C2-
Me4), -6.88 (2, s, MoH2). 13C{1H} NMR (THF-d8): δ 106.82 (s,
C5H4, Cipso), 82.99 (s, C5H4), 72.94 (s, C5H4), 46.32 (s, C2Me4),
27.23 (C2Me4). IR (Nujol mull): 1774 cm-1 (ν(Mo-H)).
Figure 2. (a) Water-soluble ethylene-bridged molybdocene catalyst
[{C2Me4(η5-C5H4)2}Mo(OH)(OH2)][OTs] and (b) its binuclear
analogue [{C2Me4(η5-C5H4)2}Mo(µ-OH)]2[OTs]2.
Synthesis of [{C2Me4(η5-C5H4)2}Mo(µ-OH)]2[OTs]2 (5). This
synthesis was adapted from the preparation of [Cp′2Mo(µ-OH)]2-
[OTs]2.44 A solution of p-toluenesulfonic acid monohydrate (0.48
g, 2.5 mmol) in acetone/water (70 mL/0.70 mL) was added to the
orange solid (0.850 g, 2.7 mmol) obtained by the preceding
description. The orange-red solution was refluxed for 8 h, during
which time a gray-green suspension formed. The solvent was
removed under reduced pressure to leave a light brown-gray solid
that was rinsed with benzene and hexanes. As discussed in the
Results and Discussion section, this procedure, which with non-
ansa Cp ligands gives dimer complexes of the type [Cp2Mo(µ-
OH)]2[OTs]2, instead gives 3 as the major product when using the
ansa-C2Me4(η5-C5H4)2 ligand (0.73 g, 57% based on all monomer
product). In this instance, the dimeric complex [{C2Me4(η5-C5H4)2}-
Mo(µ-OH)]2[OTs]2 (5) formed only as a minor product. Attempts
to purify 3 by crystallization yielded pure [{C2Me4(η5-C5H4)2}-
Mo(µ-OH)]2[OTs]2 (5). Specifically, upon standing for 2-3 days,
a saturated solution of 3 yielded green crystals of 5 as the dihydrate.
(The water molecules could be readily removed by heating under
reduced pressure.) Anal. Found for 5: C, 55.78; H, 5.79; S, 6.22.
Calcd for C23H28SO4Mo: C, 55.64; H 5,68; S, 6.46. Data for 3:
1H NMR (DMSO): δ 7.71 (d, 2, p-OTs), 7.32 (d, 2, p-OTs), 6.95-
(m, 4, C5H4), 6.00 (m, 4, C5H4), 2.29 (s, 3, p-OTs-Me), 0.726 (s,
12, C2Me4). 13C{1H} NMR (D2O): δ 142.70 (s, p-OTs), 139.60
(s, p-OTs), 132.99 (s, C5H4, Cipso), 129.65 (s, p-OTs), 125.57 (p-
OTs), 119.89 (s, C5H4), 84.73 (s, C5H4), 43.73 (s, C2Me4) , 26.17
(s, C2Me4), 20.67 (s, p-OTs-Me). Data for 5: 1H NMR (DMSO):
δ 7.71 (d, 2, p-OTs), 7.32 (d, 2, p-OTs), 7.45(m, 4, C5H4), 7.07
(m, 4, C5H4), 6.13 (m, 4, C5H4), 5.99 (m, 4, C5H4), 2.29 (s, 3,
p-OTs-Me), 0.689 (s, 24, C2Me4).
substitution on the cyclopentadienyl rings. Likewise, “unsub-
stituted” refers to a molecule with η5-C5H5 rings.)
Experimental Section
General Procedures. All experiments were performed under a
nitrogen atmosphere using a glovebox or a Schlenk line. All solvents
were dried and distilled from appropriate drying agents. Solvents
and substrates were then purged with nitrogen or degassed using
three freeze-pump-thaw cycles. Solutions buffered to pD 6.8 were
prepared by dissolving N-morpholinopropylsulfonic acid (MOPS)
hemisodium salt in D2O. The compounds C2Me4(C5H4MgCl)2,41
MoCl4‚dme,42 [Cp2Mo(µ-OH)]2[OTs]2,43 and [Cp′2Mo(µ-OH)]2-
44
[OTs]2 were prepared as described in the literature.
All hydrolysis and hydration reaction samples were prepared in
a glovebox under an atmosphere of N2 in Wilmad 9 in. precision
NMR tubes or Wilmad J-Young screw cap NMR tubes. Reactions
carried out in the Wilmad 9 in. NMR tubes were flame sealed while
frozen. Reaction tubes were heated in an oil bath. 1H NMR spectra
were obtained using a Varian Inova 500 MHz (500.104 MHz for
1H and 125.764 MHz for 13C) or 600 MHz NMR spectrometer
(599.982 MHz for 1H and 150.879 MHz for 13C). 1H NMR
resonances were integrated relative to the 7.657 ppm tosylate peak
from the catalyst counterion or to the 2.10 ppm MOPS buffer
resonance. Phosphate ester hydrolysis was monitored using a
Hewlett-Packard 8453 UV/vis spectrophotometer. IR spectra were
obtained using a Nicolet Magna IR 530 spectrometer.
Synthesis of [{C2Me4(η5-C5H4)2}MoCl2] (1). The following
preparation was adapted from that reported by Green et al.23 for
the analogous tungsten complex. Approximately 300 mL of Et2O
was added to a previously stirred mixture of MoCl4·dme (7.8 g, 24
mmol) and C2Me4(C5H4MgCl)2 (15 g, 24 mmol) to obtain a grayish-
brown suspension. After 3 days, the solvent was removed from
the red-brown suspension in vacuo, leaving a pale, pink-brown solid
that was extracted with toluene in a Soxhlet apparatus for 24 h.
The toluene was removed under reduced pressure, and the red-
brown solid was washed with hexanes to yield 2.3 g (26%) of {C2-
Me4(η5-C5H4)2}MoCl2 as a fine brown powder. 1H NMR (CDCl3):
δ 6.14 (m, 4, C5H4), 5.84 (m, 4, C5H4), 1.00 (s, 12, C2Me4). 13C-
{1H} NMR (CDCl3): δ 127.59 (s, C5H4, Cipso), 122.41 (s, C5H4),
82.95 (s, C5H4), 45.89 (s, C2Me4), 27.45(C2Me4). Anal. Found: C,
52.53; H, 5.87; Cl, 17.61. Calcd for C16H20Cl2Mo·0.20 C7H8: C,
52.56; H, 5.48; Cl, 17.83.
Generation of [{C2Me4(C5H4)2}Mo(CO)H][OTs] (4). A J-
Young tube containing 0.5 mL of 0.5 mM 3 in D2O was charged
with 20 psi CO. After heating at 90 °C for 12 h, the D2O was
removed under reduced pressure, CDCl3 was immediately added,
and the 1H NMR and IR spectra were obtained. 1H NMR (CDCl3):
δ 7.87 (d, 2, p-OTs), 7.17 (d, 2, p-OTs), 6.35(m, 2, C5H4), 6.23
(m, 2, C5H4), 5.75 (m, 2, C5H4), 5.12 (m, 2, C5H4), 2.35 (s, 3,
p-OTs-Me), 1.29 (d, 12, C2Me4), -7.29 (s, 1, Mo-H). IR
(CDCl3): 2028 cm-1 (ν(CtO)).
X-ray Structure Determinations of [{C2Me4(η5-C5H4)2}MoH2]
(2) and [{C2Me4(η5-C5H4)2}Mo(µ-OH)]2[OTs]2·2H2O (5). Crystals
suitable for X-ray diffraction analysis were grown by slow
evaporation of benzene solutions of 2 and saturated aqueous
solutions of 3. X-ray diffraction experiments were carried out on a
Bruker Smart Apex diffractometer at 173 K (2) or 150 K (5) using
Mo KR radiation (λ ) 0.71070 Å). Absorption corrections were
done by SADABS. Crystallographic data for 2 and 5 and the details
of data collection and refinement of the crystal structures are given
in the Supporting Information. The structures were solved using
direct methods and refined with full-matrix least-squares methods
based on F2. All non-H atoms were refined with anisotropic thermal
parameters. The H atoms coordinated to the Mo atom in 2 and all
H atoms in 5 were found on the F-map and refined with isotropic
thermal parameters. Other H atoms in 2 were treated in calculated
positions and refined in a rigid group model. It should be mentioned
that on the residual density of 2 there are two relatively high peaks,
6.04 and 4.53 e·Å-3. The distances from the Mo(1) atoms and these
peaks are about 1.6 Å, and they form with the Mo atom a linear
fragment with an angle 177°. Attempts to remove these two peaks
by changing absorption corrections failed. Data collection with two
Synthesis of [{C2Me4(η5-C5H4)2}MoH2] (2). A suspension of
NaBH4 (0.80 g, 21 mmol) in THF was added to a solution of 1
(2.0 g, 5.3 mmol) in THF dropwise at -78 °C. The brown
suspension was allowed to warm to room temperature and stirred
overnight. After removing the THF under reduced pressure, the
orange solid was extracted into benzene and pumped to dryness,
leaving an oily, orange solid. The [{C2Me4(η5-C5H4)2}MoH2] thus
obtained (0.850 g, 52%) was not purified further but immediately
used to generate complexes 3 and 5, as described in the next section.
However, compound 2 may be sublimed at 110 °C at 1 Torr, but
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Organometallics 2000, 19, 2927-2931.

5182 Organometallics, Vol. 26, No. 21, 2007
Ahmed et al.
different crystals of 2 were done, and in both cases such peaks
were found. Crystals of 2 are extremely unstable in air, and the
existence of these peaks seems to be related to a small amount of
decomposition during crystal mounting on the diffractometer. All
calculations were performed using the SHELXTL package.
Crystals of 5 have two polymorphic phases, and the structures
of both of them were determined (see Supporting Information). Both
structures have the same dimeric Mo units and tosylate as
counterions, but the structural function of a solvent water molecule
is different. In 5, the µ-OH groups of the dimeric Mo hydrogen
bond to the O atoms of the OTs counterions (Figure 5). In the
second polymorph, the µ-OH groups form hydrogen bonds with
the solvent water molecules, which form a further hydrogen-bonding
network with the tosylate anions.
Preparation of Catalyst Stock Solutions. Stock solutions of 3,
[Cp2Mo(OH)(OH2)][OTs], and [Cp′2Mo(OH)(OH2)][OTs] were
prepared by dissolving crystals of the respective dimeric complex
5, [Cp2Mo(µ-OH)2]2[OTs]2, or [Cp′2Mo(µ-OH)2]2[OTs]2 in 0.13 M
MOPS-buffered D2O to give solutions ranging from 2 to 15 mM
total molybdenum concentration ([Mo]total). The total molybdenum
concentration in each solution was determined using a known
amount of tetrabutylammonium tetrafluoroborate as an internal
standard. The catalyst concentration for the non-ansa catalysts was
calculated from the total molybdenum concentration using the
relationships [Mo]total ) [OTs-] ) 2[dimer] + [monomer] and Keq
) [monomer]2/[dimer]. (As will be discussed below, the active
monomeric catalyst is in equilibrium with an inactive dimeric
species.) In the case of the ansa catalyst, [Mo]total ) [OTs-] )
[monomer].
Nitrile Hydration. 3-Hydroxypropionitrile (3-10 µL) was added
to 0.50 mL of catalyst solution. The tube was then heated to 80 °C
for 14 days. Addition of 3-HPN caused the stock solution of [Cp′2-
Mo(OH)(OH2)][OTs] to turn pink, while the other two solutions
remained yellow. 1H NMR spectroscopy (D2O) was used to monitor
the disappearance of 3-hydroxypropionitrile at 3.78 ppm (t, J )
6.0 Hz, 2H, HOCH2CH2CN) and 2.67 ppm (t, J ) 6.0 Hz, 2H,
HOCH2CH2CN) and the appearance of 3-hydroxypropionamide at
3.76 ppm (t, J ) 6.0 Hz, 2H, HOCH2CH2CONH2) and 2.45 ppm
(t, J ) 6.0 Hz, 2H, HOCH2CH2CONH2).
In all cases, the proton chemical shifts were referenced to residual
HOD, and the chemical shifts at 80 °C are shifted slightly
downfield. At 80 °C, the Cp resonance for [Cp2Mo(µ-OH)]2[OTs]2
appears at 6.384 ppm, and [Cp2Mo(OH)(OH2)][OTs] shifts to 6.187
ppm. Likewise, at 80 °C, the [Cp′2Mo(µ-OH)]2[OTs]2 resonances
appear at 6.345 and 6.038 ppm, and [Cp′2Mo(µ-OH)(OH)2][OTs]
resonances appear at 5.926 and 5.775 ppm.
Results and Discussion
Aqueous Solubility and Behavior of Molybdocenes. The
aqueous solubility of Cp2MoX2-type molecules is attributed to
spontaneous and rapid hydrolysis of the Mo-X bonds to afford
ionic complexes containing inner-sphere aqua and hydroxo
ligands that are capable of hydrogen bonding. The aquated
molybdocene Cp2Mo(OH2)2+ was found to have pKa values of
5.5 and 8.5.45 Of the aquated species generated by hydrolysis
of Cp2MoX2, the Cp2Mo(OH)(OH2)+ cation present at neutral
pH was shown to be catalytically most active.6,10 However, in
a previous study, the monomer species were shown to be in
equilibrium with the inactive µ-hydroxo dimer [Cp2Mo(µ-
OH)]2 (eq 1).44 The equilibrium constants for the reactions
2+
in eq 1 were determined to be (3.5 ( 0.1) × 10-2 × 10-2
M
and (7.9 ( 0.1) × 10-2 M for R ) H at pH 3.5 and R ) Me
at pH 7, respectively. Comparison of these values indicates that
the addition of a methyl substituent to each Cp ring shifts the
monomer-dimer equilibrium in favor of the monomer. How-
ever, the equilibria were measured at different pH values.
Because the equilibrium processes are sensitive to pH, for the
accurate interpretation of the kinetic data it was necessary to
measure Keq for both systems under the conditions used for the
catalysis reactions discussed below.
The equilibria in 0.13 M MOPS D2O solutions (pD 6.8) at
25 and 80 °C were investigated by determining the change in
the monomer and dimer concentrations in solutions containing
various concentrations of total molybdocene. The respective
monomer and dimer concentrations were plotted as [monomer]2
versus [dimer] and are shown in Figure 3. From these data, the
equilibrium constants, the changes in standard enthalpy, and
the changes in standard entropy were calculated (Table 1).
Consideration of the standard enthalpy and entropy changes
gives some insight into the effect of adding a methyl substituent
to each Cp ring. With both equilibria, formation of the monomer
is enthalpically disfavored, roughly indicating that the Mo-
OH bonds in the dimer are stronger than the Mo-OH2 bonds
in the monomer. Stronger solvation of the dicationic dimer
species compared to the monocationic monomer will also
contribute to the positive ∆H°. However, the ∆H° is 4.7 kcal/
mol smaller for the equilibrium with the Cp′ ligand versus the
unsubstituted Cp ligand. This result indicates that the stability
gained through dimerization of [Cp′2Mo(OH)(OH2)][OTs] is
much less than that gained through dimerization of [Cp2Mo-
(OH)(OH2)][OTs], consistent with a decrease in the Lewis
acidity of the metal center in Cp′2Mo2+. The decreased stability
p-Nitrophenyl Phosphate Hydrolysis. The appropriate catalyst
solution (2 mL) was added to a nitrogen-filled cuvette and placed
in a water bath heated to 30 °C. After 30 min, a 20 µL aliquot of
0.45 mM NPP was added to the catalyst solution. The production
of p-nitrophenolate anion was monitored at 400 nm until no further
change in absorbance was observed.
Ethyl Acetate Hydrolysis. Ethyl acetate (5-20 µL) was added
to 0.50 mL of the catalyst stock solutions and heated to 80 °C for
7-9 days. The reaction was monitored by the disappearance of
1
ester H NMR resonances (500 MHz, D2O) at 4.05 ppm (q, J )
7.0 Hz, 2H, CH3CO2CH2CH3), 1.96 ppm (s, 3H, CH3CO2CH2CH3),
and 1.15 ppm (t, J ) 7.0 Hz, 2H, CH3CO2CH2CH3) and the
appearance of ethanol and acetic acid at 3.55 ppm (q, J ) 7.0 Hz,
2H, HOCH2CH3), 1.08 ppm (t, J ) 7.0 Hz, 3H, HOCH2CH3), and
1.95 (s, 3H, CH3CO2H).
Equilibrium Constant Determinations. Solutions containing
various concentrations of [Cp2Mo(µ-OH)]2[OTs]2 and [Cp′2Mo(µ-
OH)]2[OTs]2 were prepared using a 0.13 M MOPS D2O solution.
The concentrations of monomer and dimer were determined by
1
integrating the respective Cp H NMR resonances relative to the
OTs resonance at 7.657 ppm. For Cp2Mo2+, the dimer resonance
at 5.929 ppm decreased relative to the monomer resonance at 5.724
ppm with decreasing total molybdocene concentration. For Cp′2-
Mo2+, the dimer resonances at 5.904 and 5.623 ppm decreased
relative to the monomer resonances at 5.389 and 5.352 ppm with
decreasing total molybdocene concentration. Samples used for the
determinations at 80 °C were preheated in an oil bath for 1 h before
insertion into a 600 MHz NMR spectrometer preheated to 80 °C.
(45) Kuo, L. Y.; Kanatzidis, M. G.; Sabat, M.; Tipton, A. L.; Marks, T.
J. J. Am. Chem. Soc. 1991, 113, 9027-45.
(46) Schultz, A. J.; Stearley, K. L.; Williams, J. M.; Mink, R.; Stucky,
G. D. Inorg. Chem. 1977, 16, 3303-6.
(47) Ren, J.-G.; Tomita, H.; Minato, M.; Ito, T.; Osakada, K.; Yamasaki,
M. Organometallics 1996, 15, 852-9.

Organometallic Catalysis in Aqueous Solution
Organometallics, Vol. 26, No. 21, 2007 5183
Figure 3. Plots of ([CpR2Mo(OH)(OH2)][OTs])2 versus [CpR2-
Mo(µ-OH)]2[OTs]2 in 0.13 M MOPS D2O solution (pD 6.8). For
Figure 4. 1H NMR spectra showing hydrolysis of [{C2Me4-
(C5H4)2}Mo(µ-OH)]2 (D) to give [C2Me4Co2Mo(OH)(OH2)]+ (M).
OTs- denotes the tosylate counterion resonances.
R ) H, (0) Keq ) (2.7 ( 0.1) × 10-4 M at 25 °C and (O) Keq
)
(1.4 ( 0.2) × 10-3 M at 80 °C. For R ) Me, (9) Keq ) (2.5 (
0.1) × 10-2 M at 25 °C and (b) Keq ) (3.7 ( 0.3) × 10-2 M at 80
°C.
Table 1. Equilibrium Constants and Standard
Thermodynamic Parameters for the Equilibrium in Eq 1 in
0.13 M MOPS Buffer (pH 6.8)
of the Mo-OH bonds in [Cp′2Mo(µ-OH)]22+ may also be due
to unfavorable steric interactions between the Cp′ methyl
substituents on dimerization.
R ) H
R ) Me
K
K
eq at 25 °C (M)
eq at 80 °C (M)
(2.7 ( 0.1)× 10-4
(1.4 ( 0.2) × 10-3
6.2 ( 0.5
(2.5 ( 0.1) × 10-2
(3.7 ( 0.3) × 10-2
1.5 ( 0.1
The hydrolysis of [Cp2Mo(µ-OH)]2[OTs]2 is entropically
favored, but the hydrolysis of [Cp′2Mo(µ-OH)]2[OTs]2 is
entropically disfavored (Table 1). Because hydrolysis of the
dimer can superficially be described as three molecules reacting
to give two, ∆S° was expected to be negative. On the other
hand, conversion of the dication into two monocations should
lead to a positive ∆S° because less solvent ordering is involved
in solvating the less charged monomeric molecule. Accordingly,
one may conclude that the latter factor is most important in
determining the entropy in the hydrolysis of [Cp2Mo(µ-OH)]2-
[OTs]2, where ∆S° is positive. The addition of the methyl
substituent decreases the solvation energy of the dimer, with a
concomitant decrease in importance of the molecular charge
and solvent order. In this case, the former factor apparently
dominates, and the entropy of the system decreases because the
dimer reacts with two water molecules to give two monomeric
species.
In summary, the addition of a methyl substituent to the Cp
rings shifts the monomer-dimer equilibrium in favor of the
monomer because the Mo-OH bonds of [Cp′2Mo(µ-OH)]2-
[OTs]2 are weaker due to the decreased electrophilicity of the
metal center and because of unfavorable steric interactions
between the methyl groups. Because of the negative ∆S°,
formation of the Cp′Mo(OH)(OH2)+ monomer becomes less
favorable at elevated temperature.
∆H° (kcal/mol)
∆S° (eu)
4.3 ( 0.3
-2.3 ( 0.2
the monomeric [C2Me4Cp2Mo(OH)(OH2)]+ as the major product
and the dimeric [C2Me4Cp2Mo(µ-OH)]2[OTs]2 only as a minor
product. The dimeric [C2Me4Cp2Mo(µ-OH)]2[OTs]2 species was
also generated in solution by dissolving [C2Me4Cp2Mo(OH)-
(OH2)]+ in aqueous methanol. This yielded a mixture of
monomer and dimer. To obtain pure, solid [C2Me4Cp2Mo(µ-
OH)]2[OTs]2, the dimer was crystallized from a supersaturated
solution of [C2Me4Cp2Mo(OH)(OH2)]+ in water or water was
removed at reduced pressure from a solution of [C2Me4Cp2-
Mo(OH)(OH2)]+. Once obtained by either of these methods,
the dimer will readily undergo hydrolysis in water to afford
1
the monomer, as shown by the H NMR spectra in Figure 4.
Third, no monomer-dimer equilibrium in D2O was detectable
1
by H NMR spectroscopy. Last, the water solubility of the
molybdocene is greatly reduced upon addition of the tetra-
methylethylene linkage. The impact of this decreased solubility
is shown by the fact that the hydrolysis and hydration reactions
discussed below were performed using solutions of C2Me4Cp2-
Mo(OH)(OH2)+ that were less than 3 mM, whereas solutions
of Cp2Mo(OH)(OH2)+ and Cp′2Mo(OH)(OH2)+ were up to 15
mM in total molybdenum concentration. Further investigations
of the aqueous behavior of the C2Me4Cp2Mo(OH)(OH2)+
catalyst are ongoing and will be discussed in more detail in a
subsequent paper.
Effect of the Ethylene Bridge on the Geometric Structure
of Molybdocenes. Crystal structures of C2Me4Cp2MoH2 (2) and
[C2Me4Cp2Mo(µ-OH)]2[OTs]2 (5) are shown in Figures 5 and
6, respectively. In both structures, the cyclopentadienyl rings
adopt an eclipsed conformation enforced by the bridging atoms.
In the structure of C2Me4Cp2MoH2, the bite angle and Mo-Cp
bond distances are only slightly reduced from the unsubstituted
dihydride molecule (Table 2). In contrast, the methylene-bridged
molybdocene prepared by Labella et al. has a bite angle reduced
by ∼20°.18 The Mo-H bond distances are essentially equal in
all three molecules. More importantly, the ansa-molybdocene
dimer 5, shown in Figure 6, is essentially isostructural to that
of the nonbridged analogues, [(C5H5)2Mo(µ-OH)]2[OTs]2 and
[(C5H4Me)2Mo(µ-OH)]2[OTs]2. Each molybdocene center ex-
hibits a distorted pseudo-tetrahedral environment (counting the
Mo-Cpcentroid as a single “coordination” site) with bridging
Synthesis of [{C2Me4(C5H4)2}Mo(OH)(OH2)][OTs]: Effect
of the Ethylene Bridge on Aqueous Solubility and Behavior.
The ansa ligand had at least four effects on the behavior of
molybdocenes in water. First, the [{C2Me4(C5H4)}MoCl2]
complex exhibited different behavior in water from other Cp2-
MoX2-type complexes in that it did not undergo hydrolysis. The
water-soluble ansa complexes were, therefore, accessed from
the dihydrido compounds {C2Me4(C5H4)2}MoH2 via hydrogena-
tion of acetone in the presence of trace water in acetone solvent
(eq 2).
Second, although the route in eq 2 has been used previously
( )
for direct access to the dimeric structure [Cp2 ′ Mo(µ-OH)]22+ 43,44
,
the reaction using the {C2Me4(C5H4)2}MoH2 complex produces

5184 Organometallics, Vol. 26, No. 21, 2007
Ahmed et al.
Table 4. Comparison of Selected Spectral Data for
Cp2Mo(IV) Carbonyl Compounds
compound
CtO (cm-1
)
δ Mo-H
-8.09b
ref
(C5H4Me)2Mo(CO)H
(C5H5)2Mo(CO)H
{C2Me4(C5H4)2}Mo(CO)H
2008a
2020c
2028d
2
48
-7.29d
this work
b
c
d
a KBr pellet. (CD3)2CO. CHCl3. CDCl3.
geometric parameters for the Mo-O-Mo-O core, the bite
angles, and Cpcentroid-Mo distances.
Effect of the Ethylene Bridge on the Electronic Structure.
In order to determine the effect of the ethylene bridge on the
electron density of the Mo center, the CO-containing [{C2Me4-
(C5H4)2}Mo(CO)H][OTs] complex was prepared with the idea
of using the ν(CtO) frequency as a probe. The complex was
prepared using the method previously reported for the Cp′
analogue (eq 3). Note that other synthetic routes to the Cp2-
Mo(CO)H+ complex are reported in the literature. In those
routes, the carbonyl complex was generated by the oxidation
of Cp2MoCO using CpMoH(CO)3 (eq 4) or by reduction of Cp2-
MoH2 with [CpMo(CO)3]2 in the presence of CO (eq 5).48
Selected spectroscopic data for the various CO-containing
molybdocenes are shown in Table 4. Comparison of the carbonyl
stretching frequencies reveals that the ethylene-bridged molyb-
docene is relatively electron-withdrawing, as indicated by the
CtO stretch at highest frequency, followed by Cp2Mo(CO)-
(H)+ and Cp′2Mo(CO)H+. Note that this trend indicates that
the electronic effect of the ethylene bridge is not inductive (as
is the case in the Cp′2Mo(CO)H+ complex containing non-
bridging methyl substituents). Instead, it is logical to propose
that the electron-withdrawing nature of the ansa bridge is caused
by enhanced back-donation into a relatively low-energy bis-
(cyclopentadienyl) ligand acceptor orbital, as explained by
Parkin, Green, and co-workers in their comprehensive study of
ansa-zirconocene complexes.27
Figure 5. X-ray crystal structure of (C2Me4Cp2)MoH2. The Cp
and bridge protons were omitted for clarity. Thermal ellipsoids are
drawn at the 50% probability level.
Figure 6. X-ray crystal structure of [{C2Me4(C5H4)2}Mo(µ-OH)]2-
[OTs]2 (5). The H atoms were omitted for clarity. Thermal ellipsoids
are drawn at the 50% probability level.
hydroxo ligands hydrogen-bonded to the tosylate counterions.
A comparison of selected angles and bond lengths is shown in
Table 3. Note that there are only marginal variations in the
Effect of the Ethylene Bridge on Catalysis. To explore the
effect of the more electrophilic molybdocene center in C2Me4-
Cp2Mo(OH)(OH2)+ in reactions proceeding via intramolecular
Table 2. Comparison of Selected Bond Distances and Angles for the Molybdocene Dihydrides
Cp-Mo-Cp (deg) H-Mo-H (deg) Cp-Mo (Å) H-Mo (Å)
145.8 75.5(3) 1.942, 1.946 1.685(3)
ligand
(C5H5)2
ref
46
{C2Me4Cp2}
{CMe2Cp2}
141.9
121
85(3)
80.3
1.936, 1.933
1.913, 1.912
1.68(7), 1.70(6)
1.66(5), 1.72(7)
this work
18
Table 3. Comparison of Selected Bond Distances and Angles for the Molybdocene Dimers
[{(C5H4R)2}Mo(µ-OH)]2[OTs]2
[{C2Me4(C5H4)2}Mo(µ-OH)]2[OTs]2
R ) Ha
R ) Meb
Mo-O
2.101(1)
2.112(1)
1.983
2.092(2)
2.100(2)
2.001(5)
1.996(5)
66.21(10)
113.79(10)
128.3
2.106(3)
2.095(3)
2.001(3)
1.997(3)
67.0(1)
113.0(1)
130.0
Mo-O(1A)
Mo-Cp(1)c
Mo-Cp(2)c
1.984
O(1)-Mo-(O1A)
Mo1-O(1)-Mo1A
Cp(1)-Mo-Cp(2)c
66.90(5)
113.10(5)
129.6
b
c
a Ref 47. Ref 44. Distances and angles are to the centroid of the Cp rings.

Organometallic Catalysis in Aqueous Solution
Organometallics, Vol. 26, No. 21, 2007 5185
hydroxide attack, three reactions were investigated: (1) the
hydration of 3-hydroxypropionitrile (HPN); (2) the hydrolysis
of p-nitrophenyl phosphate (NPP); and (3) the hydrolysis of
ethyl acetate (EtOAc). As explained in the Introduction, the
electron-withdrawing ansa-Cp ligand could lead to enhanced
activation of a bound substrate; however, it could also reduce
the reactivity of the coordinated hydroxo nucleophile. To
investigate the relative importance of these two competing
factors, the rate constants for the reactions above catalyzed by
the relatively electron poor ansa-molybdocene complex 3 were
compared to those of the nonsubstituted molybdocene complex
Cp2Mo(OH)(OH2)+ and to the relatively electron-rich Cp′2Mo-
(OH)(OH2)+ catalyst. All reactions were performed in 0.13 M
MOPS-buffered D2O with less than 3% catalyst. The rate
constants (kapp) reported below are second-order rate constants
for the hydrolysis and hydration reactions, obtained by dividing
the observed rate constant obtained from first-order fits of
substrate concentration versus time by the active catalyst
concentration or, in the case of HPN hydration, directly from
the GIT iterative kinetics fitting program. The details of the
GIT models and an example fit are shown below. The active
catalyst concentration, [cat.], was determined from the total
molybdocene concentration using the appropriate equilibrium
constants reported above. Because no monomer-dimer equi-
librium was observed for the ansa catalyst, the total molyb-
docene concentration equals the active catalyst concentration.
Nitrile Hydration. Prior studies established the pathway in
Scheme 1 for the hydration of nitriles catalyzed by molyb-
docenes.3 It was also previously shown that the reactions are
retarded by reversible coordination of the nitrile substrate (eq
6) and irreversible coordination of the amide product (eq 7),
which leads to degradation of the catalyst.3 Electron-withdraw-
ing nitriles, however, exhibited increased catalytic activity with
no product inhibition. Of the molybdocene-catalyzed hydrations
reported earlier, the hydration of 3-hydroxypropionitrile (HPN)
was the most efficient and was, therefore, chosen for this study.
Although no product inhibition was noted with HPN, H/D
exchange of the R-hydrogen atoms was observed (eq 8).
Figure 7. GIT fit of kinetics data for C2Me4Cp2Mo(OH)(OH2)+-
catalyzed hydration of 3-hydroxypropionitrile.
Table 5. Comparison of Kinetic Data for
3-Hydroxypropionitrile Hydration at 81 °C
[monomer] [substrate] kapp (M-1 s-1 k2 (M-1 s-1
ligand
(mM)
(M)
× 103)
× 104)
C2Me4(C5H4)2
(C5H5)2
(C5H4Me)2
1.2
1.3
1.8
0.10
0.26
0.092
1.2 ( 0.1
5.3 ( 0.7
4.3 ( 0.5
3.9 ( 0.3
5.1 ( 0.7
1.6 ( 0.2
for HPN hydration decrease in the order Cp2Mo(OH)(OH2)+
∼ Cp′2Mo(OH)(OH2)+ > C2Me4Cp2Mo(OH)(OH2)+. The rate
constants for H/D exchange give a slightly different trend than
those for nitrile hydration, decreasing in the order Cp2Mo(OH)-
(OH2)+ ∼ C2Me4Cp2Mo(OH)(OH2)+ > Cp′2Mo(OH)(OH2)+.
Although the trends for nitrile hydration and H/D exchange are
intriguing, it should be noted that the variations in the rate
constants for the three catalysts are only marginal. Such small
changes in the rate constants for these catalysts show that the
rate of nitrile hydration and H/D exchange is effectively
unchanged for molybdocenes within the range of electron
densities studied herein.
The sensitivity of HPN hydration to changes in electron
density of the molybdocene catalyst may be reduced due to
preferential coordination of the alcohol functionality of HPN
as opposed to the nitrile group. Several observations indicate
that HPN does in fact bind to the active site of the ansa catalyst
through the alcohol functionality. Alcohol coordination was
1
observed in the H NMR spectrum of the reaction mixture by
comparison of the aromatic Cp protons for the active catalyst
to those of the catalyst in methanol/water mixtures (Figure 8).
Note in the figure that the Cp resonances give two sets of
pseudotriplets at essentially the same shift value (about 6.2 and
6.5 ppm in both cases). This result implies a similar ligand
environment for each Mo atom. The complex in aqueous
methanol must bind through the oxygen, and the implication
therefore is that the HPN is bonded through the oxygen atom.
In addition, H/D exchange of the R-hydrogens is observed over
the course of the reaction, resulting in a decrease in intensity
1
of the corresponding nitrile and amide resonances in the H
The reaction kinetics for nitrile hydration and product
inhibition were modeled using an iterative kinetics fitting
program (GIT) applied to eqs 9 and 10.
NMR spectrum. Molybdocene-catalyzed H/D exchange reac-
tions in alcohols are known to proceed by initial coordination
of the alcohol functionality.6
kapp
Phosphate Hydrolysis. The rate laws for phosphate hydroly-
sis using the molybdocene catalysts are pseudo-first-order, and
a first-order fit of the kinetic data obtained using Cp′2Mo(OH)-
(OH2)+ is shown in Figure 9. The rate constants are shown in
Table 6. Comparison of these data to those in Table 5 shows
catalyst + nitrile 8 catalyst + amide
(9)
k2
catalyst + amide
98 catalyst + amide-d2
(10)
An example of a fit is shown in Figure 7, and lists of the
rate constants for 3-hydroxypropionitrile hydration (kapp) and
H/D exchange (k2) are shown in Table 5. The rate constants
(48) Adams, M. A.; Folting, K.; Huffman, J. C.; Caulton, K. G. Inorg.
Chem. 1979, 18, 3020-3.

5186 Organometallics, Vol. 26, No. 21, 2007
Ahmed et al.
1
Figure 8. Aromatic regions of the H NMR spectra of (a) a HPN hydration reaction mixture at 8 h and (b) the catalyst in a 1:1 water/
methanol mixture. The proposed structures of (c) HPN coordination via the alcohol and (d) the ansa-molybdocene methanol adduct. OTs
) C6H4Me, D ) [C2Me4Cp2Mo(µ-OH)]2[OTs]2, M ) [C2Me4Cp2Mo(OH)(OH2)][OTs], and A ) [C2Me4Cp2Mo(OCH3)(OH2)][OTs].
Table 7. Comparison of Ethyl Acetate Hydrolysis Kinetics
for Listed Molybdocenes at 80 °C
[monomer]
(mM)
[EtOAc]
(M)
kapp (M-1 s-1
10-3
×
ligand
)
{C2Me4(C5H4)2}
(C5H5)2
(C5H4Me)2
2.2
2.3
9.0
0.12
0.43
0.50
4.0 ( 0.2
17 ( 1
1.4 ( 0.3
environment are counteractive. In other words, the increase in
activation of the substrate by the more electrophilic Mo center
is offset by deactivation of the hydroxo leaving group. With
the electron-donating Cp′ ligand, the increase in nucleophilicity
of the hydroxo ligand is offset by the reduced reactivity of the
substrate. It is interesting to note that phosphate ester hydrolysis
is much more sensitive to alterations in the electronic environ-
ment of the metal center; the rate constant kapp is decreased by
an order of magnitude as a result of an increase or decrease in
the electron density of the Mo center as opposed to a factor of
4 or less in HPN hydration. In this case, changes in the
electronics of the Mo center seem to affect the reactivity of the
nucleophile and substrate to the same extent, leading to similar
kapp values for Cp′2Mo(OH)(OH2)+ and C2Me4Cp2Mo(OH)-
(OH2)+.
Figure 9. Kinetic data for hydrolysis of p-nitrophenyl phosphate
promoted by Cp′2Mo(OH)(OH2)+ fit to the exponential equation y
-4
) 1.06e-1.87×10 , R2 ) 0.992.
Figure 10. Cp2Mo(OH)(OH2)+-catalyzed hydrolysis of ethyl
acetate fit to the exponential equation y ) 0.382e-0.136, R2 ) 0.994.
Table 6. Comparison of NPP Hydrolysis Kinetics at 30 °C
ligand
[monomer] (mM)
kapp (M-1 s-1 × 102)
{C2Me4(C5H4)}
(C5H5)2
(C5H4Me)2
0.50
0.80
3.8
1.6 ( 0.3
64 ( 9
5.3 ( 0.7
that the molybdocenes are more reactive toward phosphate
substrates than nitriles; however, phosphate hydrolysis (eq 11)
is not catalytic.10 The enhanced rate may be due to the greater
stability of the product PdO bonds relative to the CdO product
bonds that form in the nitrile hydration reactions. The lack of
turnover may be due to the greater stability of the four-
membered Mo-phosphate structure in the product (eqs 12 and
13). Nevertheless, the hydrolysis of p-nitrophenylphosphate
(NPP) was examined in order to further investigate the reactivity
of the molybdocene molecules toward intramolecular nucleo-
philic attack.
As shown in Table 6, NPP hydrolysis was most efficient using
the unsubstituted molybdocene catalyst Cp2Mo(OH)(OH2)+, as
the rate constants decrease in the order Cp2Mo(OH)(OH2)+
>
Carboxylic Ester Hydrolysis. The kinetic data for the
hydrolysis of ethyl acetate are summarized in Table 7. Again,
when comparing kapp values, the Cp2Mo(OH)(OH2)+ catalyst
Cp′2Mo(OH)(OH2)+ > C2Me4Cp2Mo(OH)(OH2)+. These results
support the hypothesis that the changes in the electronic

Organometallic Catalysis in Aqueous Solution
Organometallics, Vol. 26, No. 21, 2007 5187
is an order of magnitude more reactive than the C2Me4Cp2Mo-
(OH)(OH2)+ and Cp′2Mo(OH)(OH2)+ catalysts. As with the
other catalytic reactions, this trend suggests that Cp2Mo(OH)-
(OH2)+ has optimal electron density on the metal center for
reactions proceeding by intramolecular nucleophilic attack.
Effect of Monomer-Dimer Equilibrium on the Reaction
Rate. The formation of an inactive dimeric species was found
to be of critical importance in determining the reaction rates
for the Cu(II) macrocyclic amine phosphate ester hydrolysis
catalysts reported by Burstyn and co-workers.32 The Cu(II)-
promoted hydrolysis reactions were shown to exhibit a half-
order dependence on the total Cu(II) concentration, and the
active catalyst was proposed to be a monomer that exists in
equilibrium with a dimer (eq 14), analogous to the monomer-
dimer equilibrium observed with the molybdocene catalyst (eq
1). In an investigation of the effect of ligand structure on
reactions rates in the Cu(II) system, Burstyn and co-workers
found that the rate of hydrolysis increased with increasing ligand
size due to a resulting destabilization of the inactive dimeric
species. Other factors such as the Lewis acidity of the Cu(II)
center and steric constraints on the phosphate binding were also
proposed to have an affect on the reaction rates but were
concluded to be of secondary importance.
Summary and Key Insights
A major goal in homogeneous catalysis is identifying specific
ligand sets that afford selective catalytic transformations of
organic substrates with maximum turnover rates. Molybdocenes
have outstanding selectivity and moderate reactivity in the
hydration of nitriles in aqueous solution, and they display
promise in phosphate ester degradation. In an effort to explore
the reactivity of a more electrophilic molybdenum center toward
hydrolysis and hydration reactions, the tetramethylethylene-
bridged bis(cyclopentadienyl) ligand was employed. The eth-
ylene bridge was shown to alter the molybdocene catalyst in
three significant ways. First, the ethylene bridge greatly reduced
the water solubility of the catalyst. Second, the bridging ring
substituents suppressed formation of the inactive µ-hydroxo
dimer. Third, the ethylene bridge increased the electrophilicity
of the molybdenum center, as shown by the relatively high
energy ν(CtO) stretching frequency in C2Me4Cp2Mo(CO)H
compared with the analogous non-ansa-molybdocenes studied
herein.
Although the ansa linkage reduced the electron density at
the Mo center, the increase in the Lewis acidity did not increase
the reactivity of a bound substrate toward intramolecular
nucleophilic attack by the hydroxo ligand. In fact, the observed
trends in the rate constants did not correlate with the electron
density on the metal center. Instead, the Cp2Mo(OH)(OH2)+
catalyst, which has intermediate electron density, was the most
reactive toward every substrate examined. These results were
interpreted by evaluating the competing effects of changes in
the electrophilicity of the Mo center, namely, that an increase
in the electrophilicity will increase the reactivity of a bound
substrate toward nucleophilic attack but will also decrease the
reactivity of the bound hydroxo nucleophile.
Because of the monomer-dimer equilibrium in eq 1, the rates
of hydrolysis and hydration can be similarly affected by
dimerization in the non-ansa catalysts, especially in the case
of nitrile hydration, where changes in the electronics of the metal
center resulted in the smallest variations in rate constants.
Accordingly, although the unsubstituted Cp2Mo(OH)(OH2)+
catalyst is the most reactive toward intramolecular nucleophilic
attack, the rate of Cp2Mo(OH)(OH2)+-catalyzed hydration and
hydrolysis reactions per total molybdenum concentration may
not be fastest due to the extensive dimer formation. Note that
because the C2Me4Cp2Mo(OH)(OH2)+ catalyst is not in apparent
equilibrium with a dimeric species, the actual rate of hydration
or hydrolysis per mole of total Mo(IV) may be increased for
the ansa catalyst. Further studies on the effect of catalyst
dimerization in these molybdocene systems are underway in
our laboratory.
Acknowledgment is made to the NSF for the support of this
research. T.J.A. would also like to acknowledge the Haugland
Fellowship for partial support.
Supporting Information Available: Crystallographic data for
2, 5, and [{C2Me4(η5-C5H4)2}Mo(µ-OH)]2[OTs]2·2H2O and details
of the data collections and refinements of the crystal structures.
The H and 13C NMR spectra for synthetic intermediate 2. This
material is available free of charge via the Internet at http://
pubs.acs.org.
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