Mechanistic studies of olefin metathesis by ruthenium carbene complexes using electrospray ionization tandem mass spectrometry

Article abstract of DOI:10.1021/ja9938231

The olefin metathesis reaction of the Grubbs ruthenium carbene complexes has been investigated in the gas phase by electrospray ionization tandem mass spectrometry. Relative rates of reaction for substituted ruthenium benzylidenes and alkylidenes after removal of one phosphine ligand were interpreted with the aid of linear free energy analysis and kinetic isotope effects. The experimental observations are consistent with a reaction profile in which the metallacyclobutane structure is a transition state rather than an intermediate, although alternative explanations cannot be wholly ruled out. Electron withdrawal on the carbene moiety is found to accelerate the metathesis reaction when only the metathesis step itself is examined. Quantum chemical calculations at a variety of levels were performed to check for the consistency of the interpretation.

Full text of DOI:10.1021/ja9938231

8204
J. Am. Chem. Soc. 2000, 122, 8204-8214
Mechanistic Studies of Olefin Metathesis by Ruthenium Carbene
Complexes Using Electrospray Ionization Tandem Mass Spectrometry
Christian Adlhart, Christian Hinderling, Harold Baumann, and Peter Chen*
Contribution from the Laboratorium f u¨ r Organische Chemie der Eidgen o¨ ssischen
Technischen Hochschule, Z u¨ rich, Switzerland
ReceiVed October 27, 1999
Abstract: The olefin metathesis reaction of the Grubbs ruthenium carbene complexes has been investigated in
the gas phase by electrospray ionization tandem mass spectrometry. Relative rates of reaction for substituted
ruthenium benzylidenes and alkylidenes after removal of one phosphine ligand were interpreted with the aid
of linear free energy analysis and kinetic isotope effects. The experimental observations are consistent with a
reaction profile in which the metallacyclobutane structure is a transition state rather than an intermediate,
although alternative explanations cannot be wholly ruled out. Electron withdrawal on the carbene moiety is
found to accelerate the metathesis reaction when only the metathesis step itself is examined. Quantum chemical
calculations at a variety of levels were performed to check for the consistency of the interpretation.
Introduction
has elucidated many aspects of the catalytic cycle for this class
of metathesis catalyst. With cationized phosphine ligands,12
ruthenium benzylidene complex was even rendered soluble and
a
Olefin metathesis is one of the very few, or arguably even
the only, fundamentally novel organic transformations discov-
ered in the past four decades. Following the initial report of
homogeneously catalyzed metathesis of propylene in 1967, the
basic mechanistic picture of the reaction was worked out with
1
3
1
active in water, methanol, or aqueous emulsions. Despite the
wide application of the metathesis reaction, particularly for the
new ruthenium carbene complexes, several mechanistic ques-
tions remain outstanding. What determines the selectivity in the
reaction? What is the rate-determining step? Is the metalla-
cyclobutane an intermediate or transition state? In an earlier
contributions from the groups of Calderon, Katz, Casey, Grubbs,
Schrock, and others.2 The Chauvin mechanism3 via metal
carbene complexes has been amply supported by experiment
and is now accepted as an accurate depiction of the general
course of the reaction. The unique transformation has found
1
4
report, we used electrospray ionization tandem mass spec-
trometry (ESI-MS/MS) to investigate the cationized ruthenium
carbene complexes in the gas phase.
considerable application in the Shell higher olefin process
4
We report here further mechanistic studies on the (Cy2RP)-
Cl2RudCHAr complex, including isotopic labeling, kinetic
isotope effects, and the influence of electron-donating or
-withdrawing substituents on the rates of 2 f 3 and 2 f 4
(SHOP) for the large-scale production of long-chain R-olefins
and ring-opening metathesis polymerization (ROMP), com-
mercialized by B. F. Goodrich (Telene) and Hercules (Metton)
5
for reaction-injection molding (RIM), and CDF-Chimie (Nor-
(Scheme 1), which suggest that the metallacyclobutane structure
sorex) and Degussa-H u¨ ls (Vestenemer) for specialty resins. The
metathesis reaction has furthermore been applied in organic
is a transition state rather than an intermediate in the metathesis
reaction, at least for the ruthenium carbene complexes. Further
6
synthesis; for example, several recent syntheses of a variety
of natural and nonnatural products use a ring-closing metathesis
to accomplish difficult macrocyclizations. The recent introduc-
(
7) Miller, S. J.; Kim, S. H.; Chen, Z. R.; Grubbs, R. H. J. Am. Chem.
7
Soc. 1995, 117, 2108. Miller, S. J.; Blackwell, H. E.; Grubbs, R. H. J. Am.
Chem. Soc. 1996, 118, 9606. F u¨ rstner, A.; Langemann, K. J. Org. Chem.
1996, 61, 3942. F u¨ rstner, A.; Langemann, K. Synthesis 1997, 792. Nicolaou,
K. C.; He, Y.; Vourloumis, D.; Vallberg, H.; Yang, Z. Angew. Chem., Int.
Ed. Engl. 1996, 35, 2399. Yang, Z.; He, Y.; Vourloumis, D.; Vallberg, H.;
Nicolaou, K. C. Angew. Chem., Int. Ed. Engl. 1997, 36, 166. Xu, Z.;
Johannes, C. W.; Houri, A. F.; La, D. S.; Cogan, D. A.; Hofilena, G. E.;
Hoveyda, A. H. J. Am. Chem. Soc. 1997, 119, 10302. Kamat, V. P.;
Hagiwara, H.; Suzuki, T.; Ando, M. J. Chem. Soc., Perkin Trans. 1 1998,
2253.
(8) Nguyen, S. T.; Johnson, L. K.; Grubbs, R. H.; Ziller, J. W. J. Am.
Chem. Soc. 1992, 114, 3974.
(9) Demonceau A.; Noels, A. F.; Saive, E.; Hubert, A. J. J. Mol. Catal.
1992, 76, 123.
tion of well-defined late transition metal metathesis catalysts,
particularly ruthenium complexes,8,9 has significantly broadened
the scope of the reaction due to their substantial tolerance of
heteroatom-containing functional groups which had poisoned
1
0,11
earlier catalysts. Mechanistic work from the Grubbs group
(
1) Calderon, N.; Chen, H. Y.; Scott, K. W. Tetrahedron Lett. 1967,
327.
2) For several representative reviews spanning the three decades of
3
(
work, see: Katz, T. J. AdV. Organomet. Chem. 1978, 16, 283. Calderon,
N.; Lawrence, J. P.; Ofstead, E. A. AdV. Organomet. Chem. 1979, 17, 449.
Grubbs, R. H.; Tumas, W. Science 1989, 243, 907.
(
3) Herrison, J. L.; Chauvin, Y. Makromol. Chem. 1970, 141, 161.
(10) Schwab, P.; Grubbs, R. H.; Ziller, J. W. J. Am. Chem. Soc. 1996,
118, 100. Ulman, M.; Grubbs, R. H. Organometallics 1998, 17, 2484.
(11) Dias, E. L.; Nguyen, S. T.; Grubbs, R. H. J. Am. Chem. Soc. 1997,
119, 3887.
(12) Mohr, B.; Lynn, D. M.; Grubbs, R. H. Organometallics 1996, 15,
4317.
(4) Commercial aspects of olefin metathesis are reviewed in the
following: Ivin, K. J.; Mol, J. C. Olefin Metathesis and Metathesis
Polymerization; Academic Press: New York, 1997; pp 397-410.
(5) Goodall, B. L.; Kroenke, W. J.; Minchak, R. J.; Rhodes, L. F. J.
Appl. Polym. Sci. 1993, 47, 607. McCann, M.; McDonnell, D.; Goodall, B.
L. J. Mol. Catal. A 1995, 96, 31. Rhodes, L. F. European Patent 0 435 146
A2, 1990. Mazany, A. M. European Patent 0 755 938 A1, 1995.
(13) Lynn, D. M.; Mohr, B.; Grubbs, R. H. J. Am. Chem. Soc. 1998,
120, 1627.
(
46.
6) Grubbs, R. H.; Miller, S. J.; Fu, G. C. Acc. Chem. Res. 1995, 28,
(14) Hinderling, C.; Adlhart, C.; Chen, P. Angew. Chem. 1998, 110,
2831.
4
1
0.1021/ja9938231 CCC: $19.00 © 2000 American Chemical Society
Published on Web 08/10/2000

Olefin Metathesis of Ruthenium Carbene Complexes
J. Am. Chem. Soc., Vol. 122, No. 34, 2000 8205
Scheme 1
proceeds with an efficiency of between 10- and 10-5, making it an
unusually inefficient ion-molecule reaction even though it is likely to
be slightly exothermic. Although normal scans of the second quadrupole
are used to check for “cleanliness” of reactions, quantitative data were
measured in the segmented-scan mode to achieve a higher signal-to-
noise ratio. A single relative rate determination is the average of 15
individual measurements of conversion efficiency, each of which, in
turn, is a measurement of 2 reacting with a given substrate followed
immediately by a measurement of 1 with the same substrate for
normalization. Error bounds on the relative rates were determined from
a t-distribution by standard statistical methods and represent 95%
confidence limits. Because of the broad isotopic pattern in each peaks
ruthenium has seven naturally occurring isotopes and each of the two
chlorines has two isotopessa large mass change is needed to get clean
differentiation of product ion intensities in the presence of unreacted
starting ions. For example, the kinetic isotope effect determinations
using 1-d , prepared by reacting 1 with styrene-d , were performed by
4
experiments also directly probe reversibility in the ring-opening
metathesis reaction, which had been previously suggested as
an important factor in the selectivity of the reaction.
Experimental Section
The monocationic ruthenium benzylidene complex 1 was prepared
-
5
as previously reported by electrospray of a 10 M CH
the dichloride salt of the dicationic bis-phosphine [(Cy
CHPh], Cy ) cyclohexyl, R ) 2-(trimethylammonium)ethyl, prepared
2
Cl
2
solution of
2
RP)
2
Cl Rud
2
1
2,13
according to the literature procedure.
Mass spectrometric experi-
ments were performed in modified Finnigan MAT TSQ-7000 and TSQ-
4,15
7
00 spectrometers as described in earlier papers in this series.1 The
tube lens potentialsan indication of the severity of desolvation
conditions at the exit of the transfer capillaryswas typically kept at
1
10 V, which was found to be sufficient to both desolvate the
electrosprayed ions and furthermore induce loss of one phosphine ligand
from the initially produced bis-phosphine, generating 1. The mono-
phosphine complex 1 was then passed through the first octopole, into
which a partial pressure of 10-100 mTorr of a styrene derivative or
other olefin had been introduced by a needle valve. Collisions with
the olefins served to both thermalize the ions to the 70 °C manifold
6
8
selecting the isotopomer of 1-d at m/z ) 554 for subsequent daughter-
6
ion experiments. While the selected peak does not represent the
statistically most abundant isotopomer, it is a peak which should contain
no contribution from undeuterated 1. The particular selection introduces,
of course, primary ruthenium and secondary chlorine kinetic isotope
effects, but these should be much smaller than the desired secondary
deuterium kinetic isotope effects. For the secondary deuterium kinetic
isotope effect for the reaction in the reverse direction, 3 was reacted
16
temperature and induce metathesis to 2, which was then mass-selected.
The subsequent experiments using 2 were performed in daughter-ion
mode. The ions 2, mass-selected in the first quadrupole, were then
introduced into the second octopole with a nominal initial kinetic energy
of 3 eV (laboratory frame), where they reacted with either acyclic or
cyclic olefins, e.g., 1-butene, norbornene, or other substrates (3-5
mTorr). Product ions were then mass-analyzed in the second quadru-
pole.
with styrene or styrene-d (0.3 mTorr) to form 2 with the corresponding
8
level of deuteration. The reaction in this direction was done with a
nominal initial kinetic energy for 3 of 2 eV (laboratory frame). A
competing loss of trimethylamine from the phosphine ligand of 3 was
used as the reference in a competition to determine the rate of
metathesis. Assuming that there is no kinetic isotope effect on the
The details of the ion-molecule reaction in the second octopole
require discussion. In this experiment, the octopole functions more like
an ion drift cell, as opposed to a normal collision cell. Monte Carlo
modeling (see Appendix), combined with experimental determinations
of ion transit times through the octopole, finds that, under the conditions
employed in this experiment, the ions undergo up to ∼5000 collisions
trimethylamine loss, the ratio of 2 to [phosphine-NMe ] in the daughter-
ion mass spectrum for collision with styrene versus styrene-d is a
3
8
measure of the secondary deuterium kinetic isotope effect for the
metathesis reaction in the formally reverse direction. The result given
below is again the average of 20 measurements to obtain good statistics.
Ab initio and density functional theory (DFT) calculations were done
using the Gaussian 94 program package17 running on a DEC Alpha
AXP 8400 5/300 or HP/Convex Exemplar SPP2000/X-32 computer.
All structures were fully optimized without symmetry constraints;
vibrational frequencies were found to be positive for all intermediates.
Structures optimized as transition-state structures were confirmed to
have only one negative frequency. Details from the computional studies
are given in the Supporting Information.
1
4
in the second octopole. Moreover, the initial kinetic energy of the
ions is lost in the first several collisions. Although there is no applied
longitudinal electric field, the continuous ion current into the octopole
creates by way of space-charge effects a slight potential that drives the
ions through. Based on a comparison of chemical conversion with
collision number, the prototype reaction (1 + butene) f (3 + styrene)
(
15) Hinderling, C.; Plattner, D. A.; Chen, P. Angew. Chem. 1997, 109,
72. Hinderling, C.; Feichtinger, D.; Plattner, D. A.; Chen, P. J. Am. Chem.
Soc. 1997, 119, 10793. Feichtinger, D.; Plattner, D. A. Angew. Chem. 1997,
2
(17) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Gill, P. M. W.;
Johnson, B. G.; Robb, M. A.; Cheeseman, J. R.; Keith, T.; Petersson, G.
A.; Montgomery, J. A.; Raghavachari, K.; Al-Laham, M. A.; Zakrzewski,
V. G.; Ortiz, J. V.; Foresman, J. B.; Cioslowski, J.; Stefanov, B. B.;
Nanayakhara, A.; Challacombe, M.; Peng, C. Y.; Ayala, P. Y.; Chen, W.;
Wong, M. W.; Andres, J. L.; Replogle, E. S.; Gomperts, R.; Martin, R. L.;
Fox, D. J.; Binkley, J. S.; Defrees, D. J.; Baker, J.; Stewart, J. P.; Head-
Gordon, M.; Gonzalez, C.; Pople, J. A. Gaussian 94, Revision C.3; Gaussian,
Inc.: Pittsburgh, PA, 1995.
1
1
7
09, 1796. Feichtinger, D.; Plattner, D. A.; Chen, P. J. Am. Chem. Soc.
998, 120, 7175. Kim, Y. M.; Chen, P. Int. J. Mass Spectrom. 1999, 185-
, 871.
(16) In other work, we have shown that 10 mTorr collision gas in the
first octopole is sufficient to completely thermalize the kinetic energy
distribution of the electrosprayed ions, as evidenced by the disappearance
of any dependence of collision-induced dissociation thresholds on the
capillary temperature.

8206 J. Am. Chem. Soc., Vol. 122, No. 34, 2000
Adlhart et al.
Figure 1. Hammett plots for the relative rate data in Table 1. The
solid diamonds represent the reactions with 1-butene; the open diamonds
are the reactions with norbornene. A least-squares fit constrained to
go through the origin is shown for each series.
Syntheses and characterization of 4-[(Z)-2-pentenyl-3,4,4,5,5,5-d
6
]-
cyclopentene, 4-[(Z)-2-pentenyl-3,4,4,5,5,5-d ]cyclopentane, and 5-vin-
6
1
8
ylnorborn-2-ene are straightforward and are also given in the
Supporting Information.
Results
Figure 2. Daughter-ion mass spectra taken by reaction of the mass-
selected ruthenium propylidene complex 3, m/z ) 498, with 10 mTorr
As mentioned in the Introduction, there are several outstand-
ing mechanistic questions in the metathesis reaction catalyzed
by ruthenium carbene complexes. Addressing these questions
are two kinds of experiments reported in the present work.
Relative rate measurements for substituted ruthenium ben-
zylidenes provide the data for kinetic isotope effect and linear
free energy relationship analyses. Bifunctional substrates permit
an experimental probe of reversibility in ring-opening metath-
esis. Last, the quantum chemical calculations on the models
for species along the reaction coordinate assist in the interpreta-
tion of the experimental data, although, as will be seen in the
Discussion, it is not altogether clear whether the computed
complexes, with PH3 as a ligand for reasons of computational
of either 4-[(Z)-2-pentenyl-3,4,4,5,5,5-d
6
]-cyclopentene (left-hand spec-
]-cyclopentane (right-hand
trum) or 4-[(Z)-2-pentenyl-3,4,4,5,5,5-d
6
spectrum) in the collision cell.
H
D
d gives secondary deuterium kinetic isotope effects of k /k
8
) 0.80 ( 0.03 and 0.96 ( 0.04 for the acyclic metathesis of
1-butene and ring-opening metathesis of norbornene, respec-
tively. The reaction of a ruthenium propylidene complex with
styrene, entries 17 and 18 in Table 1, shows a secondary
H
D
deuterium kinetic isotope effect of k /k ) 0.86 ( 0.07 when
the styrene is perdeuterated.
Reversibility in Ring-Opening Metathesis. In our previous
communication, we had reported kinetic evidence for the
importance of intramolecular π-complexation and reverse reac-
tion in ring-opening metathesis. A more direct test can be made
with bifunctional substrates which offer the product of a ring-
opening metathesis reaction the chance to undergo a nonde-
generate ring-closing metathesis to a isotopically or otherwise
substituted complex distinguishable from the original complex
by mass.
efficiency, are good models for the actual complexes that have
+
[(Me3NCH2CH2)PCy2] as a ligand.
Relative Rates and Substituent Effects. Substituted ruthe-
nium benzylidene monophosphine complexes, prepared by
reaction of the electrosprayed parent ruthenium benzylidene with
a variety of substituted styrenes, react with 1-butene or
norbornene with the relative rates shown in Table 1.
Importantly, as reported in our previous communication,
norbornene reacts with the parent ruthenium benzylidene
monophosphine complex much faster than does 1-butene. A plot
The cyclopentane derivative does not react with 3 under the
relatively mild conditions in this experiment; the cyclopentene
derivative, on the other hand, leads to approximately 10%
conversion of 3 to 3-d6 (Scheme 2), as seen in Figure 2,
indicating clearly that the ring-opening metathesis of cyclopen-
tene had occurred and is furthermore reversible. While the ring-
opening metathesis product of 1 and norbornene can be forced
to undergo the reverse reaction regenerating norbornene, harsh
conditionsshigh collision energies, i.e., .3 eV in the laboratory
framesare clearly needed to surmount the thermochemical
barrier posed by reconstruction of the strained ring. Confirming
this is the reaction of 1 with the bifunctional substrate
of the logarithm of the relative rates for 2 reacting with 1-butene
or norbornene against Hammett σ-parameters19 is linear for both
reactions, shown in Figure 1. For the reaction of 2 and 1-butene,
F ) 0.69 ( 0.10, indicating a modest acceleration of the acyclic
metathesis reaction by electron-withdrawing groups on the aryl
group of the substituted ruthenium benzylidene. For the reaction
of 2 and norbornene, on the other hand, F ) -0.08 ( 0.09,
indicating essentially no electronic influence on the rate of the
particular ring-opening metathesis reaction.
Moreover, examination of the entries in Table 1 for the
reactions of the carbene complex formed from 1 and styrene-
5
-vinylnorborn-2-ene. Acyclic metathesis at the pendant vinyl
group produces 5, while ring-opening metathesis yields either
or 7 (Scheme 3). Significantly, no trace of 8 can be seen for
conditions used in the relative rate measurements reported in
(
18) Ploss, H.; Ziegler, A.; Zimmermann, G. J. Prakt. Chem. 1972, 314,
4
1
67.
6
(
19) March, J. AdVanced Organic Chemistry, 4th ed.; Wiley: New York,
992; p 280.

Olefin Metathesis of Ruthenium Carbene Complexes
J. Am. Chem. Soc., Vol. 122, No. 34, 2000 8207
Table 1. Relative Rates for the Reactions of Ruthenium Carbenes, Determined by Reaction of 1 in the First Octopole with an Olefin, Mass
Selection of the Intermediate Carbene in the First Quadrupole, Reaction with an Olefin in the Second Octopole, and Finally Mass Analysis in
a
the Second Octopole
a
Rates are listed relative to that in entry 3 (marked “a”), entry 11 (marked “b”), or entry 17 (marked “c”). Each rate is the average of 15-20
measurements; error bounds are given as 95% confidence bounds based on a t-distribution. [Ru] indicates a ruthenium center complete with ligands.
For entries 17 and 18, the propylidene complex was prepared in solution rather than in situ.

8208 J. Am. Chem. Soc., Vol. 122, No. 34, 2000
Adlhart et al.
Scheme 2
Scheme 3
this work, even in segmented-scan mode, placing an upper limit
on the amount of 8 at ,0.1%.
sets for the geometry optimization of ruthenium complexes for
which experimental geometries are known. He found that all-
electron basis sets were superior to basis sets with effective core
potentials (ECPs) and that, furthermore, polarization functions
on the ruthenium were needed to reproduced experimental bond
lengths. We compared geometries for 10, computed using the
best basis set from Broo (MIDI + 3f on Ru, D95 on PH3, and
D95** on CH2 and Cl), with that using LANL2DZ and found
significant differences. Moreover, we optimized 10 using density
functional calculations and compared the geometry to those
computed using ab initio methods up to MP4, and we found
that B3LYP performed well in comparison to the MP4 calcula-
tion. With regard to computational speed, the increase in the
number of electrons in the all-electron basis sets (compared to
basis sets with an ECP) is more than outweighed by the
availability of analytical gradients and second derivatives.
Structures, relative energies, and zero-point energies for the
complexes 9-12 are shown in Figure 3. To place all of the
species on a common energy scale, either PH3 or ethylene is
Quantum Chemical Calculations. Full geometry optimiza-
tion and calculation of vibrational frequencies were done for
all complexes. Several of the species showed multiple non-
equivalent minima, so the geometries were intentionally per-
turbed and then reoptimized to ensure that the global minimum
could be identified. (PH3)2Cl2RudCH2 (9) is a model for the
Grubbs catalyst itself. (PH3)Cl2RudCH2 (10) represents the
species formed after dissociation of one phosphine from 9. The
2
π-complex of 10 and ethylene, (PH3)Cl2RudCH2(η -H2Cd
CH2), is 11. (PH3)Cl2Ru(-CH2CH2CH2-) (12a and 12b) are
two isomeric metallacyclobutanes. 12a is formed directly from
1
1 through TS1, while 12b is formed from 12a by a pseudoro-
tation through TS2. Different levels of theory were checked to
establish the level needed to obtain reliable results; the best
previous calculations used the B3LYP/LANL2DZ method.
Broo20 has reported a study of the reliability of various basis
(20) Broo, A. Int. J. Quantum Chem. Symp. 1996, 30, 119.

Olefin Metathesis of Ruthenium Carbene Complexes
J. Am. Chem. Soc., Vol. 122, No. 34, 2000 8209
Figure 3. Structures, relative energies, and zero-point energies of complexes 9-12 and transition states, TS
with the Broos basis set. Zero-point energies for the deuterated species are given for a single deuteration on the CH
in kilocalories per mole.
1
and TS
2
, according to B3LYP calculations
unit. All energies are given
2
included in the calculation of energy relative to 9 when
necessary. Although the calculation places the metallacyclo-
butane structure 12a above the π-complex 11, consistent with
the absence of an observable (by NMR) or isolable metallacy-
clobutane in this reaction, another metallacyclobutane 12b was
found at lower energy.
catalyst which has been characterized in solution, there has been
1
4
only the previous report from this group, although the
prototype reaction has been studied mass spectrometrically for
2
2
+
+
several simple metal carbenes, e.g., [MndCH2] , [FedCH2] ,
+
and [CodCH2] , mostly by reaction with deuterated ethylene.
The questions concerning the role of the various ligands and
substitution on those ligands require that the elaborated complex,
The isomeric structure could be accessed from 11 only via
1
2a and transition state TS2. The latter lies above the transition
as close to the solution-phase catalyst as possible, be studied.
In a series of papers, Grubbs and co-workers8
,10-13
have
state TS1, which in a degenerate metathesis reaction is the
transition state leading to product. Accordingly, 12b should be
kinetically inaccessible in the reaction.
mapped out much of the important features of the metathesis
reaction catalyzed by well-characterized ruthenium carbene
2
3-25
complexes. Recent work from other groups
has added
Discussion
further to the understanding of the reaction. Although some of
the experimental papers have included computational compo-
nents, there has been only a single full computational paper on
the metathesis reaction catalyzed by ruthenium carbene com-
plexes. Despite the body of work that has appeared in these
reports, there remain outstanding questions, three of which were
listed in the Introduction: What determines the selectivity in
the reaction? What is the rate-determining step? Is the metal-
lacyclobutane an intermediate or transition state?
Electrospray ionization tandem mass spectrometry has re-
cently emerged as a powerful tool for mechanistic and analytical
studies of organometallic reactions and other catalyzed reac-
2
6
1
4,15,21
tions.
Nevertheless, for the metathesis reaction by a
(21) Colton, R.; Traeger, J. C. Inorg. Chim. Acta 1992, 201, 153. Canty,
A. J.; Traill, P. R.; Colton, R.; Thomas, I. M. Inorg. Chim. Acta 1993, 210,
9
1. Colton, R.; D’Agostino, A.; Traeger, J. C. Mass Spectrom. ReV. 1995,
1
4, 79 and references therein. Kane-Maguire, LA. P.; Kanitz, R.; Sheil, M.
M. J. Organomet. Chem. 1995, 486, 243. Lipshutz, B. H.; Stevens, K. L.;
James, B.; Pavlovich, J. G.; Snyder, J. P. J. Am. Chem. Soc. 1996, 118,
(22) Stevens, A. E.; Beauchamp, J. L. J. Am. Chem. Soc. 1979, 101,
6449. Jacobson, D. B.; Freiser, B. S. J. Am. Chem. Soc. 1985, 107, 67.
Jacobson, D. B.; Freiser, B. S. J. Am. Chem. Soc. 1985, 107, 2605.
(23) Hansen, S. M.; Rominger, F.; Metz, M.; Hofmann, P. Chem. Eur.
J. 1999, 5, 557.
6
796. Jiao, C. Q.; Freiser, B. S.; Carr, S. R.; Cassidy, C. J. J. Am. Soc.
Mass Spectrom. 1995, 6, 521. Gatlin, C. L.; Turecek, F. In Electrospray
Ionization Mass Spectrometry; Cole, R. D., Ed.; John Wiley: New York,
1
997; Chapter 15. Dzhabieva, Z. M.; Kozlovskii, V. P.; Shul’ga, Yu. M.;
(24) Hansen, S. M.; Volland, M. A. O.; Rominger, F.; Eisentr a¨ ger, F.;
Hofmann, P. Angew. Chem. 1999, 111, 1360.
(25) Tallarico, J. A.; Bonitatebus, P. J., Jr.; Snapper, M. L. J. Am. Chem.
Soc. 1997, 119, 7157.
Dodonov, A. F.; Belov, G. P. Russ. Chem. Bull. 1996, 45, 474. Saf, R.;
Schitter, R.; Mirtl, C.; Stelzer, F.; Hummel, K. Macromolecules 1996, 29,
7
651. Aliprantis, A. O.; Canary, J. W. J. Am. Chem. Soc. 1994, 116, 6985.
Wilson, S. R.; Wu, Y. Organometallics 1993, 12, 1478. Alpin, R. T.;
Baldwin, J. E.; Schofield, C. J.; Waley, S. G. FEBS Lett. 1990, 277, 212.
(26) Aagaard, O. M.; Meier, R. J.; Buda, F. J. Am. Chem. Soc. 1998,
120, 7174.

8210 J. Am. Chem. Soc., Vol. 122, No. 34, 2000
Adlhart et al.
Scheme 4
In the previous communication,14 we had argued on kinetic
grounds that ring-opening metathesis polymerization (ROMP)
of cyclopentene and cyclohexene was inefficient (in comparison
to ROMP of cyclobutene or norbornene), not because the ring-
opening metathesis itself was inherently slow, but rather because
the facile formation of an intramolecular π-complex, favored
for the longer, more flexible spacers derived from cyclopentene
and cyclohexene, both introduced an unfavorable preequilibrium
and promoted an unproductive ring-closing metathesis. This
conjecture finds confirmation in the direct probes for reversible
ROM by the substituted cyclopentenes and norbornenes in the
present study. The ROM of cyclopentene is readily reversible,
while that of norbornene is not. As had been argued by Patton
and McCarthy, strain release in the substrate is not the principal
determinant in all but perhaps one of the several orders-of-
magnitude difference in apparent ROMP reactivity of cyclo-
hexene versus norbornene in solution. The easy intramolecular
π-complexationsprimarily a steric effectsand concomitant ring-
closing metathesis are the controlling factors.
Electronic effects on relative rates, on the other hand, are
seen in Figure 1. As is evident from the Hammett plot of relative
rates versus substituents for the reaction of ruthenium ben-
zylidenes with 1-butene, the reaction is accelerated by electron-
withdrawing substituents on the carbene moiety. Qualitative
reaction coordinates are depicted in Schemes 4 and 5. The
overall topology conforms to the general picture for a bi-
molecular ion-molecule reaction proceeding via initial com-
plexation.28 While there is no attempt here to quantify the well
depths or barrier heights, the reaction coordinates were con-
structed with the following considerations:
(1) The reactions 2 f 3 and 2 f 4 are both exothermic,
with the latter being much more exothermic than the former.
(2) The ion-dipole complex for the gas-phase reaction is
assumed to correspond functionally to the π-complex of the
solution-phase reaction.
(3) While a solution-phase reaction which proceeded at less
than the diffusion-controlled rate would necessarily have a rate-
limiting transition state above the entering asymptote, gas-phase
ion-molecule reactions with a central barrier (in the conven-
tional double-well potential) below the reactant asymptote can
both proceed with less than unit reaction efficiency and display
27
29
substituent and isotope effects. Nevertheless, because the
reaction 2 f 3 displays an extraordinarily low reaction
-
4
-5
efficiency of 10 -10 for an exothermic ion-molecule
(28) Farneth, W. E.; Brauman, J. I. J. Am. Chem. Soc. 1976, 98, 7891.
Olmstead, W. N.; Brauman, J. I. J. Am. Chem. Soc. 1977, 99, 4219.
Asubiojo, O.I.; Brauman, J. I. J. Am. Chem. Soc. 1979, 101, 3715. Pellerite,
M. J.; Brauman, J. I. J. Am. Chem. Soc. 1980, 102, 5993. Sharma, S.;
Kebarle, P. J. Am. Chem. Soc. 1982, 104, 19. Caldwell, G.; Magnera, T.
F.; Kebarle, P. J. Am. Chem. Soc. 1984, 106, 959. McMahon, T. B.; Heinis,
T.; Nicol, G.; Hovey, J. K.; Kebarle, P. J. Am. Chem. Soc. 1988, 110, 7951.
(29) A particularly well-documented study finds for gas-phase proton-
transfer reactions between pyridine bases that even for the case where the
central barrier is below the entering asymptote of an exothermic reaction,
the reaction efficiency can be on the order of 0.1 with a primary deuterium
isotope effect kH/kD around 1.4. See: Jasinski, J. M.; Braumann, J. I. J.
Am. Chem. Soc. 1980, 102, 2906. The general theory of kinetic isotope
effectssand solution-phase experiments in generalsfinds primary deuterium
isotope effects that are much larger, a typical value being k /k ) 6-8 for
H
D
proton transfer through a linear transition state. The argument used in the
present studysattenuation of substituent and isotope effects when the rate-
limiting transition state is pulled well below the entering asymptotesis, in
fact, supported by the proton-transfer study.
(
27) Patton, P. A.; McCarthy, T. J. Macromolecules 1984, 17, 2939.
Patton, P. A.; McCarthy, T. J. Polym. Prepr. 1985, 26, 66. Patton, P. A.;
McCarthy, T. J. Macromolecules 1987, 20, 778.

Olefin Metathesis of Ruthenium Carbene Complexes
J. Am. Chem. Soc., Vol. 122, No. 34, 2000 8211
Scheme 5
reaction, the rate-determining transition states in the upper panels
of Schemes 4 and 5 have been depicted (for convenience) to
lie at roughly the level of the entering asymptote.30 This is not
meant, however, to imply a quantitative assessment.
determining transition state, which is also consistent with the
assignment of the rate-determining step for the gas-phase
reaction 2 f 3.
Either the two-step metathesis reaction 2 f 3 depicted in
Scheme 4 (upper trace) or the one-step reaction depicted in
Scheme 5 (upper trace) would be consistent with the substituent
and (forward direction) isotope effect. If the two-step reaction
were to be correct, as is usually assumed, one can also argue
that, for the reaction 2 f 3, metallacyclobutane formation in
the upper trace in Scheme 4 must be rate-determining because
the acyclic metathesis reaction is merely a slightly perturbed
degenerate reaction, which when slightly exothermic as postu-
lated above places the first transition state higher than the
second. The distinction comes from the comparison with 2 f
(4) The Hammond Postulate is assumed to be valid.
Within this framework, the particular direction of the sub-
stituent effect is easily rationalized if one proceeds from the
assumption that the ruthenium center in 1 is electron-deficient
and is accordingly destabilized by electron-withdrawing sub-
stituents on the benzylidene fragment. The aryl group on the
corresponding metallacyclobutane is, however, no longer in
direct conjugation to the ruthenium. By this logic, the metal-
lacyclobutane, and any putative transition state leading to it from
a carbene complex, is destabilized less by electron withdrawal
than either the carbene or the carbene/olefin π-complex would
be, leading to a moderately large, positive Hammett F value.
This would necessarily make rate-determining that transition
state in which a metallacyclobutane structure is formed.
Furthermore, the secondary deuterium kinetic isotope effect in
4
, which, in contrast, shows neither an electronic substituent
effect nor a secondary deuterium kinetic isotope effect and
provides the first clue to the rate-determining step in the reaction.
The difference in F cannot be due to reversibility in the ring-
opening metathesis, because, although ROM of cyclopentene
goes both ways under the present conditions, the probe with
H
D
the forward direction, k /k ) 0.80 ( 0.03, considered in the
2
3
usual way, indicates an sp f sp transition going to the rate-
5-vinylnorborn-2-ene clearly rules out reversibility except under
(
30) The observed secondary deuterium isotope effect for the acyclic
forcing conditions for the ROM reaction of norbornene.
metathesis reaction 2 f 3 is not attenuated at all relative to expectations
from theory or solution-phase studies, while that for the ROM reaction 2
f 4 has been completely washed out. The qualitative surfaces in Schemes
The principal difference relevant to the two different F values
is the different exothermicities of the acyclic metathesis of
1-butene versus the ring-opening metathesis of norbornene. We
expect the gas-phase reaction of 2 f 3 to be mildly exothermic
4
and 5 correspond to potential energy surfaces. Inclusion of entropysor,
equivalently, transformation to free energy surfacesswould raise the
transition states more than the entering asymptote because of the loss of
translational and rotational entropy in the formation of a complex from
two components. A quantitative treatment with RRKM theory is not possible
because the real complexes are too large for a reasonable level of quantum
chemical theory to calculate reliable frequencies. Nevertheless, the important
comparisonsthe reaction of 2 f 3 versus 2 f 4scan be made without
recourse to quantitative rates.
1
0
because, as Grubbs noted, an alkyl group is both smaller and
more electron-donating than a phenyl and, accordingly, should
stabilize the ruthenium center. The ring-opening metathesis of
norbornene, 2 f 4, should be much more exothermic because,
in addition to the electronic and steric factors, the strain release

8212 J. Am. Chem. Soc., Vol. 122, No. 34, 2000
Adlhart et al.
upon cleavage of the olefinic linkage in norbornene should add
and 170°, respectively.34 The phosphine in complexes 2-4 is
accordingly much more sterically demanding than PH3 (in the
calculations), which would destabilize any complex in which
any of the other ligands are in van der Waals contact with the
phosphine. One could suggest that the very large phosphine
changes the reaction coordinate sufficiently that the computed
path, shown in Figure 3, does not describe the experimentally
studied reaction. An alternative explanation would be that
substituent effects and isotope effects for what is effectively a
chemically activated gas-phase reaction function differently from
those in thermal reactions in solution, where each intermediate
is thermalized before proceeding to the next step. A similar
situation had been suggested for the multistep formation of
3
1
approximately 15 kcal/mol to the reaction exothermicity. If
the increased reaction exothermicity, by the Hammond postulate,
were to pull whichever transition state was rate-limiting to an
energy well below the starting point of the reaction, then both
electronic substituent effects and the secondary deuterium kinetic
isotope effect should be greatly attenuated. In either Scheme 4
or 5, the thermochemistry going from the carbene and nor-
bornene to the first π-complex should not be too different from
that in the corresponding step in acyclic metathesis because little
3
2
of the strain in norbornene is released by π-complexation.
Likewise, formation of the metallacyclobutane releases little
strain if the metallacyclobutane is a bound intermediate, as
assumed in Scheme 4. Strain release should, however, greatly
lower the transition state for metallacyclobutane cleavage in
Scheme 4, which nevertheless does not affect the preceding rate-
determining transition state. This argues against Scheme 4 as a
description of the reaction coordinate for the gas-phase metath-
esis reactions of 2. On the other hand, Scheme 5 shows the
reaction coordinate for a one-step reaction, i.e., metallacyclobu-
tane as transition state. By Hammond’s postulate, the rate-
determining transition state will be pulled down by the strain
release on going from reactant to product. Supporting the
argument is the isotope effect on the acyclic metathesis reaction,
going in the opposite direction. Entries 17 and 18 in Table 1
3
5
benzene in flames. Further computational studies are needed
to clarify the issues.
Interestingly, if the structures 9-12, TS1, and TS2 are simply
taken as such, without regard to computed relative energies,
one can compute secondary deuterium kinetic isotope effects
for the reactions according to Scheme 4 or 5 using the calculated
zero-point energies. Using an admittedly crude model, eq 1,
one needs only frequencies for each structure to get the isotope
3
6
effects on an elementary reaction step. Using T ) 343 K and
ts
iH
ts
iD
transition-state modes
hν
hν
1
H
D
k /k ≈
exp -
-
×
∏i
[
(
)
]
H
D
clearly indicate that k /k ) 0.86 ( 0.07 for the reaction ([Ru]d
CHEt + styrene) f ([Ru]dCHPh + 1-butene). Typically, the
only way that an acyclic metathesis reaction of a ruthenium
2 kT
kT
r
jH
r
jD
reactant modes
hν
hν
1
exp
-
(1)
∏
[
(
)
]
33
benzylidene complex and an R-olefin could show a substantial
2
kT
kT
j
inverse secondary deuterium kinetic isotope effect in both the
forward and reVerse directions would be if Scheme 5 described
the reaction coordinate. We note also that no ion corresponding
in mass to the metallacyclobutane could be observed in any of
the acyclic metathesis experiments. A single, published com-
putational study of the entire metathesis reaction for a ruthenium
carbene complex in solution finds no intermediate at the
metallacyclobutane structure,26 in agreement with the current
experimental results.
the zero-point energies in Figure 3, we find for three hypothetical
H
D
q
reactions, kinetic isotope effects of k /k ) 1.09 for 11 f [TS ]
1
H
D
q
H
D
f 12a, k /k ) 1.42 for 12a f [TS ] f 11, and k /k )
1
q
0.77 for 11 f [12a] f 11. For the last of the three reactions,
the calculation was made assuming that 12a was a transition
state as in Scheme 5. Accordingly, the two-step mechanism in
Scheme 4 should show a small normal isotope effect if the first
step is rate-determining. Even if the two transition states in the
top panel of Scheme 4 were close enough in energy so that
neither is clearly rate-determining, the symmetry of the reaction
coordinate would reduce the overall kinetic isotope effect to
The present computational results find, in contrast to the
arguments above, a minimum at the metallacyclobutane struc-
ture. Single-point energy calculations at the optimized critical
points with the CCSD(T) method find only small changes in
the relative energies. Nevertheless, the computationsthe best
that can be done in the present circumstancessdoes have
problems. The prediction that 9 lies far above all of the other
species and, moreover, far above all of the transition states
would suggest that the experimentally determined rate of
metathesis by 2 should be close to the collision rate. Quantitative
measurement of the rate for the acyclic metathesis of 1-butene
by 2 finds that the acyclic metathesis rate is lower than the
collision rate by between 4 and 5 orders-of-magnitude (vide
infra). The most important difference between the computed
structures 9-12 and the measured complexes 2-4 is the
phosphine. The Tolman cone angles of PH3 and PCy3 are 87°
q
something like that for 11 f [TS1] f 12a. The experimental
result does not agree with this prediction. On the other hand,
the calculation of the expected isotope effect for the reaction
q
according to the reaction, 11 f [12a] f 11, yields an inverse
isotope effect of the same magnitude as seen in the experiment,
again suggesting that the metallacyclobutane is a transition state.
One should be careful not to make too much of this last results
if, in fact, the reaction coordinate is substantially altered by a
sterically demanding phosphine, then the agreement with
experiment derives from only the general trends accompanying
hybridization changes.
Can these gas-phase results be reconciled with the solution-
phase reactivity studies by Grubbs? While the solution-phase
studies of the ruthenium carbenes with Cl, Br, I, acetate, or
trifluoroacetate on the metal center indicated increased meta-
(31) The strain release upon cleavage of one ring of norbornene in a
ROM reaction can be estimated from exothermicity of the homodesmotic
equation: (2 × ethane) + norbornene f cis-1,3-dimethylcyclopentane +
Z-2-butene.
1
1
thesis activity with electron withdrawal, consistent with the
present Hammett analysis, the effect was explained as a trans-
(32) It has been argued that while there is a difference in the
π-complexation of norbornene versus cyclopentene with an unsaturated
tungsten carbene, the difference is not large. Ivin, K. J.; Lapienis, G.;
Rooney, J. J. Makromol. Chem. 1982, 183, 9. Also, the heats of hydrogena-
tion of ethylene and norbornene are surprisingly similar.
(34) Collman, J. P.; Hegedus, L. S. Principles and Applications of
Organotransition Metal Chemistry; University Science Books: Mill Valley,
CA, 1980; p 58.
(35) Stein, S. E.; Walker, J. A.; Suryan, M. M.; Fahr, A. 23rd Symposium
(International) on Combustion; The Combustion Institute: Pittsburgh, PA,
1990; pp 85-90.
(36) Lowry T. S.; Richardson, K. S. Theory and Mechanism in Organic
Chemistry, 2nd ed.; Harper & Row: New York, 1981; Chapter 2.
(33) A two-step endothermic reaction (the reverse reaction) would show
an overall kinetic isotope effect that is the product of a normal equilibrium
isotope effect on the reversible first step and an inverse kinetic isotope
effect on the rate-determining second step. The two would largely cancel.

Olefin Metathesis of Ruthenium Carbene Complexes
J. Am. Chem. Soc., Vol. 122, No. 34, 2000 8213
effect on the initial ligand exchange equilibrium. On the other
hand, investigation of the metathesis reaction of ruthenium
benzylidenes, in this case with substitution on the aryl group
of either the carbene or the styrene substrate, found no clearly
10
interpretable electronic substituent effects in solution. As seen
above, the metathesis reaction of the ruthenium benzylidene
monophosphine complex is accelerated by electron withdrawal
on the benzylidene moiety. In solution, there is a ligand
exchange preceding this step in which one phosphine ligand
must first dissociate, and a further ligand exchange at the end
of the reaction after metathesis has occurred.1 The first ligand
exchange enters into the overall solution-phase rate as a
multiplicative factor, in the case that it is a preequilibrium, and
is adversely affected by electron withdrawal on the benzylidene.
Accordingly, the two effects run in opposite directions, making
the overall solution-phase electronic substituent effect ambigu-
ous. Both electron withdrawal and electron donation on the
ruthenium benzylidene were reported10 to decrease the rate of
metathesis by (Cy3P)2Cl2RudCHAr, which is understandable
if the effect on the ligand exchange dominates for electron-
withdrawing groups while the effect on the metathesis step itself
dominates for electron donors. The secondary deuterium kinetic
0,11
Figure 4. Simulation of the mean ion retention time in the gas-filled
octopole collision cell as a function of incident ion energy and gas
pressure for the reaction of ruthenium benzylidene complex 1 with
1-butene. The results at nominally negative incident ion energies come
from the high-energy tail of the ion kinetic energy distribution.
H
D
isotope effect, k /k ) 1.7, observed by Grubbs and co-
1
0
workers for the reaction (Cy3P)2Cl2RudCHPh + styrene-d8,
could likewise be attributed to a composite of three effects: the
kinetic isotope effect for the metathesis reaction itself and two
partition isotope effects37 for the ligand exchanges prior to and
following the metathesis.
Conclusion
Gas-phase mechanistic studies of the olefin metathesis by
ruthenium benzylidene complexes by way of electronic sub-
stituent effects, kinetic isotope effects, suggest that the putative
metallacyclobutane structure is a transition state rather than an
intermediate. Quantum chemical calculations indicate that there
are multiple, delicately balanced effects that need to be
considered. The gas-phase study, which avoids the solution-
phase problem of prior and subsequent ligand exchange reac-
tions, can nevertheless be reconciled with the solution-phase
results in a way that deconvolutes the various contributions to
the solution-phase chemistry.
Figure 5. Absolute product yields for the reaction 1 and 1-butene as
a function of the incident kinetic energy of 1 (laboratory frame) and
the pressure of 1-butene in the octopole collision cell.
Acknowledgment. Support of this project by the Forschung-
skommission der Eidgen o¨ ssischen Technischen Hochschule
Z u¨ rich, the Schweizerischer Nationalfonds zur F o¨ rderung der
wissenschaftlichen Forschung, and a graduate fellowship for
C.H. from the Stipendienfonds der Basler Chemischen Industrie
is aknowledged.
V is the relative velocity; σ is the Langevin collision cross
section; p is the gas pressure; e is the elementary charge; µ is
the reduced mass; ꢀ0 is the electrical permittivity of vacuum;
Re is the polarizability; k is Boltzmann’s constant; and T is the
absolute temperature.
Appendix 1
The application of Langevin theory for the collision cross
section greatly simplifies the calculation because, at this level
of approximation, the collision probability during a time step
is independent of the relative velocities of the collision partners
in the center-of-mass frame.
The velocity of the collision partner is taken from a
Boltzmann distribution with a random direction in the laboratory
frame of reference. For a collision the new direction of the ion
is chosen at random in the center-of-mass frame of reference
and then transformed back to the laboratory frame. This is
equivalent to having chosen a random impact parameter for the
collision. In Figure 4, the results of the simulation for three
pressures and a range of incident kinetic energies (laboratory
frame) are depicted. A test as to whether the simulation gave
realistic results was done by sending an ion of a given mass
through the first quadrupole, the octopole collision cell, and
The Monte Carlo modeling of ion motion in a gas-filled radio
frequency multipole ion guide was done as follows. The
differential equations for the ion motion in an ideal multipole
field were solved numerically without recourse to the effective
potential approximation using a fourth-order Runge-Kutta
numerical integration. Collisions were handled in a simplified
manner. The probability of a collision between the ion and a
buffer gas molecule during a single integration time step was
treated using Langevin theory:
e
Re
p
P ) nVσ )
2ꢀ0
x
µ kT
where P is the collision probability; n is the gas number density;
(
37) Shiner, V. J. J. Am. Chem. Soc. 1969, 91, 7748.

8214 J. Am. Chem. Soc., Vol. 122, No. 34, 2000
Adlhart et al.
the second quadrupole. The two quadrupoles were scanned with
a variable time delay between them. By measuring the transmit-
ted ion intensity as a function of the delay between the two
quadrupoles, the mean retention time in the octopole could be
determined. It was found to agree within a factor of 2 with the
simulation. Absolute reaction yields for the metathesis reaction
at the same incident ion energies and 1-butene pressures could
also be measured.
The plots of measured yield against the same pressure and
incident energy parameters are shown in Figure 5. Because the
Monte Carlo simulation realistically reproduces the experimen-
tally determined retention time of the ions in the gas-filled
octopole, the absolute collision number from the simulation,
up to ∼5000 collisions per ion, can be taken as reliable.
Furthermore, because the curves in Figures 4 and 5 are
approximately parallel, one can reduce the measured product
-
4
yield to a probability of reaction per collision of between 10
-
5
and 10 .
Supporting Information Available: Geometries, energies,
and frequencies for 9-12, as well as TS1 and TS2 from the ab
initio calculations, and the synthetic details and physical
characterization of the several compounds prepared in this study
(PDF). This material is available free of charge via the Internet
at http://pubs.acs.org.
JA9938231