Disentangling ligand effects on metathesis catalyst activity: Experimental and computational studies of ruthenium-aminophosphine complexes

Article abstract of DOI:10.1021/jacs.8b02324

Second-generation ruthenium olefin metathesis catalysts bearing aminophosphine ligands were investigated with systematic variation of the ligand structure. The rates of phosphine dissociation (k₁; initiation rate) and relative phosphine reassociation (k_-1) were determined for two series of catalysts bearing cyclohexyl(morpholino)phosphine and cyclohexyl(piperidino)phosphine ligands. In both cases, incorporating P-N bonds into the architecture of the dissociating phosphine accelerates catalyst initiation relative to the parent [Ru]-PCy₃ complex; however, this effect is muted for the tris(amino)phosphine-ligated complexes, which exhibit higher ligand binding constants in comparison to those with phosphines containing one or two cyclohexyl substituents. These results, along with X-ray crystallographic data and DFT calculations, were used to understand the influence of ligand structure on catalyst activity. Especially noteworthy is the application of phosphines containing incongruent substituents (PR₁R′₂); detailed analyses of factors affecting ligand dissociation, including steric effects, inductive effects, and ligand conformation, are presented. Computational studies of the reaction coordinate for ligand dissociation reveal that ligand conformational changes contribute to the rapid dissociation for the fastest-initiating catalyst of these series, which bears a cyclohexyl-bis(morpholino)phosphine ligand. Furthermore, the effect of amine incorporation was examined in the context of ring-opening metathesis polymerization, and reaction rates were found to correlate well with catalyst initiation rates. The combined experimental and computational studies presented in this report reveal important considerations for designing efficient ruthenium olefin metathesis catalysts.

Full text of DOI:10.1021/jacs.8b02324

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Disentangling Ligand Effects on Metathesis Catalyst Activity: Experimental
and Computational Studies of Ruthenium–Aminophosphine Complexes
Crystal K. Chu, Tzu-Pin Lin, Huiling Shao, Allegra L. Liberman-Martin, Peng Liu, and Robert H. Grubbs
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.8b02324 • Publication Date (Web): 05 Apr 2018
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Page 1 of 27
Journal of the American Chemical Society
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Disentangling Ligand Effects on Metathesis Catalyst Activity:
Experimental and Computational Studies of Ruthenium–
Aminophosphine Complexes
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†
†
‡
†
‡
Crystal K. Chu, Tzu-Pin Lin, Huiling Shao, Allegra L. Liberman-Martin, Peng Liu,* and
†
Robert H. Grubbs*
†Arnold and Mabel Beckman Laboratories of Chemical Synthesis, California Institute of Technology, Pasadena,
California 91125, United States
‡Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, United States
ABSTRACT: Second-generation ruthenium olefin metathesis catalysts bearing aminophosphine ligands were investigated
with systematic variation of the ligand structure. The rates of phosphine dissociation (k ; initiation rate) and relative
1
phosphine reassociation (k-1) were determined for two series of catalysts bearing cyclohexyl(morpholino)phosphine and
cyclohexyl(piperidino)phosphine ligands. In both cases, incorporating P–N bonds into the architecture of the dissociating
phosphine accelerates catalyst initiation relative to the parent [Ru]–PCy complex; however, this effect is muted for the
3
tris(amino)phosphine-ligated complexes, which exhibit higher ligand binding constants in comparison to those with
phosphines containing one or two cyclohexyl substituents. These results, along with X-ray crystallographic data and DFT
calculations, were used to understand the influence of ligand structure on catalyst activity. Especially noteworthy is the
application of phosphines containing incongruent substituents (PR
1
2
R’ ); detailed analyses of factors affecting ligand
dissociation, including steric effects, inductive effects, and ligand conformation, are presented. Computational studies of
the reaction coordinate for ligand dissociation reveal that ligand conformational changes contribute to the rapid
dissociation for the fastest-initiating catalyst of these series, which bears a cyclohexyl-bis(morpholino)phosphine ligand.
Furthermore, the effect of amine incorporation was examined in the context of ring-opening metathesis polymerization,
and reaction rates were found to correlate well with catalyst initiation rates. The combined experimental and computational
studies presented in this report reveal important considerations for designing efficient ruthenium olefin metathesis
catalysts.
9
INTRODUCTION
complexes as viable olefin metathesis catalysts led to the
1
0
development of catalyst G1 (Figure 1). The lower activity
of G1 in comparison to molybdenum catalysts was later
addressed through the development of second-generation
Since its discovery in the 1950s, olefin metathesis has
evolved into a versatile and powerful reaction for organic
1
synthesis. Molybdenum, tungsten, and ruthenium
1
1
ruthenium olefin metathesis catalysts, notably G2, in
catalysts have been extensively investigated in the
synthesis of natural and unnatural products, including the
formation of substituted olefins and cyclic organic
which a phosphine is substituted for an N-heterocyclic
12,13
carbene (NHC) ligand.
The bis(pyridine) complex G3
2
and related complexes have proven to be fast-initiating,
enabling cross metathesis of challenging substrates and
compounds. Furthermore, significant efforts toward the
14
3
development of olefin metathesis polymerizations,
notably ring-opening metathesis polymerization (ROMP)
and acyclic diene metathesis (ADMET), have enabled the
synthesis of new functional materials and have led to
4
ROMP to produce polymers with controlled molecular
15
5
weight and low dispersity; additionally, complex G3 can
6
serve as a useful precursor for variants of catalyst G2 that
bear various organic substituents on the phosphine.
16
7
important industrial applications.
Complexes based on molybdenum and tungsten were
the earliest reported well-defined olefin metathesis
catalysts, and since their initial discovery, have been widely
8
used for their high reactivity. Extensive research of
ruthenium-based complexes has resulted in catalysts with
increased functional group tolerance and stability to air
and moisture. Demonstration of ruthenium alkylidene
1
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Page 2 of 27
Figure 1. Established ruthenium olefin metathesis catalysts.
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6
RESULTS AND DISCUSSION
Mechanistic studies of olefin metathesis promoted by
second-generation ruthenium catalysts have suggested
that these reactions occur by a dissociative pathway, in
which phosphine dissociation occurs to form a 14-electron
intermediate in an initiation step prior to olefin binding
In this study, nitrogen-containing heterocycles were
systematically introduced in place of the cyclohexyl groups
in complex G2 to probe the effect of P–N bonds on catalyst
activity. NMR spectroscopic and X-ray crystallographic
data were obtained to gather structural information, and
these data were analyzed in the context of kinetics studies.
Initiation rates and the relative phosphine reassociation
rates were measured, together providing a metric to
compare aminophosphine binding strengths. Trends in
ligand binding strengths and initiation rates were
1
7,18
(
Scheme 1).
affected by the rate of phosphine dissociation (k
rate) and the relative rate of phosphine reassociation (k-1).
Thus, the activity of these catalysts is
1
; initiation
1
9
Following formation of the 14-electron intermediate, the
likelihood of phosphine reassociation versus productive
0
1
2
3
4
5
6
7
8
9
0
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2
3
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0
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0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
olefin binding (k-1/k ) can be experimentally determined;
2
27
higher binding affinity of the olefin in comparison to the
phosphine, rather than differences in initiation kinetics,
has been shown to be the underlying cause for the
investigated using DFT calculations, which account for
important parameters affecting ligand properties.
Furthermore, the use of phosphines bearing incongruent
20
increased metathesis activity of G2 compared to G1.
substituents allows for
a
more comprehensive
understanding of ligand structure, providing additional
information regarding the effects of sterics and ligand
conformation on phosphine dissociation. Detailed
analyses of the kinetics and computational studies, along
with the application of the new catalysts in ROMP studies,
revealed important factors affecting ligand dissociation
energy, initiation rates, and catalyst activity.
Scheme 1. Proposed Dissociative Mechanism for
Second-Generation Ruthenium Olefin Metathesis
Catalysts
Synthesis of Ruthenium Catalysts Featuring
Aminophosphine Ligands. Two new series of second-
generation ruthenium olefin metathesis catalysts bearing
Dissociation rate constants have been reported for a
variety of second-generation ruthenium catalysts bearing
21
aminophosphine
ligands
in
place
of
the
alkyl- or arylphosphine ligands. Although phosphine
tricyclohexylphosphine present in catalyst G2 were
synthesized. Morpholine and piperidine substituents were
targeted due to their similarity in steric profile to
cyclohexane.
electronics are not known to strongly correlate with ligand
reassociation, initiation rates have been shown to increase
with decreasing -donor strength of alkyl- and
arylphosphines. With this in mind, we decided to further
investigate phosphines with unique -donating properties
as ligands for metathesis catalysts. Phosphines containing
electron-withdrawing substituents, notably halogenated
arenes, have been studied; however, the incorporation of
P–X bonds, where X is an electronegative heteroatom, has
been much less explored in this context. Aminophosphine
ligands provide access to a broad range of -donating and
Treatment of the appropriate chlorophosphine with
excess morpholine or piperidine produced the
corresponding aminophosphines L1–L6 (Scheme 2).
Complexations to form catalysts 1–6 were achieved by
reacting the bis(pyridine) catalyst G3 with an excess of the
1
6
desired aminophosphine in THF.
22
-accepting properties of relevance to many catalytic
23,24
applications.
NMR studies of aminophosphine adducts
Scheme 2. Synthesis of Complexes 1–6
have demonstrated decreased -basicity of select ligands
25
in comparison to triphenylphosphine. On the other hand,
structural studies of N-pyrrolidinyl, pyrrolyl, and related
phosphines have attributed their electron-rich, basic
properties to donation from the nitrogen lone pairs to the
26
lone pair of phosphorus. Drawn to these unique
attributes, we became interested in evaluating the
influence of aminophosphine ligands in the context of
second-generation ruthenium metathesis catalysts. These
ligands are particularly well suited to systematically
investigate the effect of incorporating P–X bonds on
metathesis catalyst activity, quantified herein through
rates of initiation, relative phosphine reassociation, and
ROMP. The combined experimental and computational
results underline the importance of several key factors in
promoting phosphine dissociation, providing guidance for
the future design of efficient ruthenium olefin metathesis
catalysts.
Second-generation ruthenium olefin metathesis
catalysts with aromatic phosphine ligands are known to be
faster-initiating than their alkylphosphine counterparts,
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Journal of the American Chemical Society
and the effects of replacing the PCy
3
ligand with PPh
3
in G2
ligated complexes. Selected bond lengths and bond angles,
including those reported for the parent catalyst G2, are
displayed in Table 2 for comparison.
1
2
3
4
5
6
7
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9
1
1
1
1
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1
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1
2
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4
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5
5
5
5
5
5
5
6
21b
and related catalysts have been well studied for ring-
28
21a
closing metathesis (RCM) and ROMP reactions. Thus,
following the successful synthesis of catalysts 1–6, we
became interested in potentially faster-initiating species
Catalysts 4–6 all have similar Ru–C1 bond lengths
when compared to that of the parent catalyst G2 (Table 2).
Additionally, the Ru–P bond of catalyst 4, with one
piperidine substituent, is longer than that of catalyst 5,
which contains two piperidine rings; these Ru–P bond
lengths show no direct correlation with rates of phosphine
dissociation (vide infra). While these analyses reveal no
clear trend in the Ru–P and Ru–C1 distances, the Ru–C8
bond lengthens with increasing incorporation of P–N
bonds. This observation suggests that the trans influence
derived from aromatic amines. To this end,
pyrrolylphosphine ligand was synthesized, providing
access to complex 7 (Figure 2).
a
N
N
Cl
0
1
2
3
4
5
6
7
8
9
0
1
2
3
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5
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9
0
1
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0
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4
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9
0
1
2
3
4
5
6
7
8
9
0
Ru
P
Cl
Ph
N
increases in the order of PCy < L4 < L5 < L6. Furthermore,
3
these complexes crystallize in such a way that one
substituent on the phosphine ligand occupies a position
below a mesityl ring (NHC) that is oriented away from the
benzylidene. For complexes 5 and 6, a piperidine ring
occupies this position (Figures 4 and 5), whereas one of the
two cyclohexyl rings takes this position for G2 and 4
7
Figure 2. Ruthenium-based olefin metathesis catalyst bearing
a pyrrolylphosphine ligand. X-ray crystal structure of 7 with
50% probability ellipsoids (right) and hydrogen atoms
omitted for clarity.
(
Figure 3). These structural differences translate to steric
and conformational effects important to catalyst reactivity
vide infra).
Initiation Kinetics by H NMR Spectroscopy. The
Characterization of New Catalysts by NMR
Spectroscopy and X-Ray Crystallography. Table 1 lists
(
31
the P NMR chemical shifts for catalysts G2 and 1–6 along
1
with the corresponding free phosphine ligands. In both the
morpholine- and piperidine-based series, the P resonance
31
effect of P–N bonds on catalyst activity was first analyzed
by comparing catalyst initiation rates for 1–6. The rate
of the free phosphine shifts downfield as amine
31
constants of phosphine dissociation (k
1
) for complexes G2
substitution increases. The same P trend is observed in
and 1–6 were measured at 30 C in toluene-d
8
. These
the ruthenium complexes, with the exception of the
tris(amino)phosphine complexes 3 (116.9 ppm) and 6 (118.7
experiments allow for the comparison of two complete
series of new morpholinophosphine- (Figure 6) and
piperidinophosphine-ligated (Figure 7) catalysts along
with the known parent catalyst G2. Initiation rate
constants of the complexes were determined using a
previously described method involving quenching with
excess ethyl vinyl ether under pseudo-first-order
conditions and monitoring the disappearance of the
ppm),
which
are
more
shielded
than
the
bis(amino)phosphine congeners 2 (131.9 ppm) and 5 (133.0
ppm), respectively. Notably, a similar nonlinear trend has
been observed in series of aminophosphine complexes of
3
1
PdCl
2
in which the
P
resonance of the
tris(amino)phosphine complex is upfield from that of the
29
disubstituted analogue. Collectively, these observations
denote intricate steric and electronic effects exerted by
these ligands, as evidenced in the crystallographic, kinetic,
and computational analyses (vide infra).
1
21a,30
benzylidene resonance by H NMR spectroscopy.
3
1
a
N2
N1
Table 1. Signature P NMR Chemical Shifts
C8
free ligand
31
catalyst
cat. ( P)
ligand
 ppm
31
(
P)
Cl1
Ru
Cl2
G2
1
29.4
92.2
131.9
116.9
92.1
PCy
3
8.8
75.6
98
20.6
16.6
33.9
2.2
C1
L1
P
2
L2
L3
N3
3
114.7
75.9
98.8
116.8
4
L4
L5
L6
16.2
34.0
1.9
5
133.0
118.7
6
Figure 3. X-ray crystal structure of catalyst 4 with 50%
probability ellipsoids. Hydrogen atoms have been omitted for
clarity.
aMeasured in benzene-d
.
6
To gain structural information, catalysts 4–6,
containing piperidine-substituted phosphine ligands, were
selected for further characterization by X-ray
crystallography (Figures 3–5). The crystal structures
confirm the connectivity expected for these phosphine-
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included for the systematic study of amine incorporation,
1
2
3
4
5
6
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9
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1
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1
1
2
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2
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3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
7
was later tested in ROMP studies (Figure 13).
N2
N1
4
C8
Ru
G2
1
2
3
Cl1
3.5
3
Cl2
y = 7.91E-03x
C1
y = 1.55E-03x
N4
P
2
.5
2
y = 4.38E-03x
N3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
.5
1
y = 1.98E-04x
Figure 4. X-ray crystal structure of catalyst 5 with 50%
probability ellipsoids. Hydrogen atoms have been omitted for
clarity.
0.5
0
0
500
1000
1500
2000
2500
3000
N2
N1
time (s)
C8
Figure 6. Initiation rates of catalyst series 1–3 bearing
morpholinophosphine ligands and catalyst G2 determined by
Cl1
Cl2
Ru
1
H NMR spectroscopy at 30 C with [Ru]
= 0.017 M and [ethyl
. The rate
0
C1
N3
vinyl ether] = 0.5 M (30 equiv.) in toluene-d
constants (s ) of phosphine dissociation are reported as the
slopes of the lines fit to pseudo-first-order kinetics.
8
P
N4
-
1
N5
3.5
G2
4
5
6
3
y = 4.10E-03x
y = 3.13E-03x
Figure 5. X-ray crystal structure of catalyst 6 with 50%
probability ellipsoids. Hydrogen atoms have been omitted for
clarity.
2.5
2
y = 5.67E-04x
y = 1.98E-04x
1
.5
Table 2. Selected Bond Lengths (Å) and Bond Angles
º) for Complexes G2 and 4–6.
(
1
bond length
Ru–C1
G2
complex 4
1.836(2)
complex 5
1.839(3)
complex 6
1.825(5)
2.121(4)
0.5
0
1.835(2)
2.085(2)
2.4245(5)
2.3988(5)
2.3912(5)
G2
Ru–C8
2.0877(19)
2.4340(5)
2.4032(5)
2.3860(5)
complex 4
99.70(8)
94.79(6)
165.40(6)
2.097(3)
0
500
1000
1500
time (s)
2000
2500
3000
Ru–P
2.3820(10)
2.3944(9)
2.4005(10)
complex 5
102.32(14)
100.29(11)
157.29(9)
2.394(3)
2.374(5)
2.421(3)
complex 6
102.1(2)
Ru–Cl1
Figure 7. Initiation rates of catalyst series 4–6 bearing
piperidinophosphine ligands and catalyst G2 determined by
Ru–Cl2
bond angle
C1–Ru–C8
C1–Ru–P
C8–Ru–P
1
H NMR spectroscopy at 30 C with [Ru]
0
= 0.017 M and [ethyl
. The rate
100.24(8)
95.89(6)
163.73(6)
vinyl ether] = 0.5 M (30 equiv.) in toluene-d
100.64(17) constants (s ) of phosphine dissociation are reported as the
8
-
1
slopes of the lines fit to pseudo-first-order kinetics.
157.17(14)
Table 3. Summary of Initiation Rates for 1–6 and G2.
Under the same conditions, an experiment to determine
the initiation rate of catalyst 7, bearing a pyrrolylphosphine
ligand, resulted in full consumption of the benzylidene
faster than the time scale to obtain a precise rate
measurement. As expected, catalyst 7 initiates faster than
all other complexes reported in this study containing
morpholine and piperidine substituents; the lower limit of
-
1
catalyst
k
1
(s ) at 30 C
krel (rel to G2)
1.98  10-4
4.38  10-3
7.91  10-3
1.55  10-3
G2
1
1
22
40
8
2
3
-
2
-1
the initiation rate constant for this catalyst is > 2 × 10 s .
While the reaction kinetics of this complex are not
4.10  10-3
4
21
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3.13  10-3
5.67  10-4
5
16
3
estimate for the value of k-1/k
y-intercept provides a predicted value of the initiation rate
1
k
2
, and the reciprocal of the
1
2
3
4
6
k
1
(Equation 1).
The estimated values of k-1/k for catalysts G2 and 1–6
2
In all cases, the aminophosphine ligands dissociate at
a faster rate than the PCy ligand of catalyst G2 (Table 3).
are presented in Table 4. For the morpholinophosphine
series (1–3), the rate of phosphine reassociation directly
correlates with amine substitution. As an increasing
number of morpholine substituents is systematically
introduced into the ligand structure of catalyst G2, a
gradual increase in k-1 is observed. However, this trend is
not observed for the piperidinophophine series (4–6).
Instead, the kinetics of phosphine reassociation are much
less varied across this series, and all estimated values of k-1
are similar to that of the parent catalyst G2.
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
3
In fact, complex 2, containing a ligand with two
morpholine substituents, initiates ~40 times faster than
the parent catalyst and has the highest initiation rate of
these two series. Interestingly, the tris(amino)phosphine-
ligated complexes in both series appear to have anomalous
reactivity. While amine substitution seems to dramatically
accelerate phosphine dissociation for both mono- and
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
bis(amino)phosphines relative to the PCy
3
ligand of
catalyst G2, this effect is somewhat muted for the
tris(amino)phosphine-ligated complexes 3 and 6, which
are the slowest initiating complexes of each respective
series. The initiation rates of catalysts 4–6, although faster
than that of catalyst G2, decrease with increasing
piperidine substitution (Figure 7). These data suggest that
factors other than inductive effects associated with
heteroatom incorporation significantly contribute to
phosphine donor strength and dissociation rates. Further
investigations of catalyst activity, including comparison of
phosphine reassociation rates and DFT studies, were
required to understand the observed trends in initiation
rates.
12000
10000
8
000
6000
4000
2000
0
y = 3028.58x + 5075.71
R² = 0.99
1
Determination of k-1/k
2
by H NMR Spectroscopy.
In order to gain a more complete understanding of the
effect of amine substitution on the strength of phosphine
binding in second-generation ruthenium catalysts, we next
performed experiments to compare the phosphine
0
0.5
1
1.5
2
[P]/[olefin]
Figure 8. Example plot of 1/kobs vs. [P]/[olefin] to measure k
-
reassociation rate constants (k-1) at 30 C in toluene-d
8
by
1
1
1
/k
2
for catalyst G2 determined by H NMR spectroscopy at 30
H NMR spectroscopy. Following phosphine dissociation,
the 14-electron intermediate, which is equivalent for all
catalysts discussed in this study, can remain in the catalytic
cycle and undergo olefin binding (k
rebind to the metal (k-1). Thus, the measurable ratio k-1/k
determined from the slope of the line of best fit according
to Equation 1, represents the relative likelihood of these
two events. Because phosphine dissociation leads to the
same 14-electron intermediate in each case, the
propagation rate k
catalysts G2 and 1–6. For this reason, studies to determine
also allow for the comparison of phosphine
reassociation rates (k-1) across catalysts 1–6.
C with [Ru]
0
8
= 0.017 M in toluene-d .
Furthermore, the measured initiation rates in Table 3
are consistent with predicted values (within 10%) from
kinetics experiments performed to compare the relative k-1
constants. Along with the linear fitting of 1/kobs vs.
[P]/[olefin], this observation is consistent with the
dissociative mechanism presented in Scheme 1, rather than
the associative and interchange mechanisms proposed for
2
) or the phosphine can
2
,
3
1
3
2
2
is expected to be equivalent for
other classes of metathesis catalysts.
Observed Trends for Phosphine Binding. The
combined results from kinetics studies of complexes 1–6
were analyzed in detail to determine the effect of amine
substituents on phosphine binding and to identify key
factors that correlate to the observed trends. The relative
k
-1/k
2
1
푘−ꢀ[푎푚ꢁ푛ꢂ푝ℎꢂꢃ푝ℎꢁ푛푒]
푘 푘 [ꢂ푙푒푓ꢁ푛]
1
=
+
(1)
ratios of k-1 to k were calculated for each complex, and
1
푘표푏푠
푘ꢀ
ꢀ
2
We applied a previously described procedure21a for
determining relative phosphine reassociation rates to
aminophosphine-ligated catalysts, in order to evaluate the
effect of P–N bonds on the propensity of these ligands to
rebind to the ruthenium center. An example of the results
of such an experiment, which incorporates a large excess
of ethyl vinyl ether and free phosphine, for catalyst G2 is
shown in Figure 8. The slope of the line of best fit is an
Table 4. Estimated k-1/k
Values for Catalysts G2, 1–6.a
2
catalyst
k-1/k
2
G2
1
0.60
1.44
1.82
3.00
2
3
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4
5
0.70
0.57
0.71
Increasing the number of morpholine substituents
causes a steady increase in initiation rates when comparing
catalysts G2, 1, and 2. However the
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
6
tris(morpholino)phosphine ligand breaks this trend, and
dissociates at a significantly slower rate. In comparison, the
incorporation of piperidine rings into the ligand
composition of catalyst G2 leads to faster-initiating
catalysts, but initiation rates decrease as more piperidine
substituents are introduced. Despite these differences, the
tris(amino)phosphine-ligated complexes 3 and 6 are
clearly the slowest-initiating catalysts for both series.
Investigations of aminophosphine nucleophilicity have
a
1
Measured using H NMR spectroscopy at 30 C with [Ru]
0.017 M in toluene-d
0
=
8
.
this equilibrium constant k-1/k , which we will term Kassoc,
is used as a metric for ligand binding strength. Thus, a
more strongly donating ligand is expected to have a higher
assoc, and these values provide an approximation of the
relative phosphine binding constants. Normalized values
for k , k-1, and Kassoc are compared across each series 1–3 and
4–6 in Figure 9.
1
K
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
kk 1
1
kk -
-
1
1
k K- 1as
/
s
k
o
1
c
kk 1
1
kk -
-
1
1
soc
k K- 1as/k1
1
.0
.8
1.0
0.8
0.6
0.4
0.2
0.0
0
0.6
0.4
0
.2
.0
0
G2
1
2
3
G2
4
5
6
Catalyst
Catalyst
1
Figure 9. Comparisons of k , k-1, and Kassoc for catalyst series bearing morpholinophosphine ligands (1–3) and piperidinophosphine
ligands (4–6) as well as catalyst G2. All values are normalized with respect to the highest value in each data set (denoted by
shading).
shown a related trend in which nucleophilicity increases
DFT-Optimized Geometries and Computed
Phosphine Dissociation Energies for
3
3
with the number of amine substituents. As stated
previously, the observed trend in k-1 for the morpholine
series does not hold for the piperidine series. These data
suggest that k-1 rate constants do not correlate well with
inductive effects related to phosphine composition.
Morpholinophosphine Catalysts. The morpholine-
containing catalysts 1–3 were selected for further
computational studies to understand factors affecting
3
4
phosphine dissociation energies. Catalyst 2, ligated with
cyclohexyl-bis(morpholino)phosphine L2, was of special
interest since it is the fastest-initiating complex of both
series. The structure and conformational flexibility of L2
were studied by computational methods. Two
The values of Kassoc were compared and normalized
with respect to that of catalyst G2, which has a higher
association constant than catalysts 1–6. Although the
trends in phosphine dissociation and reassociation rates in
the morpholine series differ from those in the piperidine
series, the overall trend in Kassoc are the same for both series
of aminophosphine-ligated catalysts. For both charts
shown in Figure 9, a U-shaped trend is observed for the
phosphine association constants as the number of P–N
bonds increases from 0 (for catalyst G2) to 3 (for catalysts
conformations
were
identified
for
the
morpholinophosphine ligand, with varied orientation of
substituents in relation to the phosphorus lone pair,
3
5
positioned along the z-axis.
These low-energy
conformations are consistent with the conformation of the
3
6
PCy ligand in crystal structures. Conformation A, which
3
is less stable in the case of the free ligand, contains a
morpholine substituent that is coplanar with the
phosphorus xy-plane (Figure 10). The ring in this position
will be referred to as the “coplanar” substituent. In
conformation A, the nitrogen lone pair of the coplanar ring
is anti-periplanar to the phosphorus lone pair. Previous
spectroscopic studies of aminophosphines have suggested
that one nitrogen lone pair must take an unprivileged
orientation, resulting in a repulsive, pseudo- interaction
3
and 6). While the incorporation of 1 or 2 amine
substituents dramatically decreases the binding strength
of the phosphine in comparison to G2, catalysts 3 and 6
with
3 amine substituents show increased ligand
association constants Kassoc. Gaining an understanding of
the origin of the observed trends in Kassoc, and the factors
contributing to phosphine dissociation energy, warranted
further computational investigations.
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Journal of the American Chemical Society
phosphine donor strength. In contrast, the optimized
with the phosphorus lone pair.37 The lone pair–lone pair
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
repulsive interaction results in conformation A being the
less stable conformer. Furthermore, the orthogonal
cyclohexyl ring present in this ligand conformation
exhibits significant steric clash with both morpholine
rings. In comparison, conformation B contains two
orthogonal morpholine rings and a coplanar cyclohexyl
ring with respect to the phosphorus xy-plane, and is the
favored conformation for the free phosphine.
structures of complexes 2 and 3 both contain a coplanar
morpholine ring oriented toward the N-mesityl; similar
structural characteristics are confirmed in the crystal
structures of the analogous complexes in the piperidine
series 5 and 6 (Figures 4 and 5). The decreased
pyramidalization of the morpholine nitrogen atom
compared to the cyclohexyl carbon leads to smaller
phosphine-NHC repulsions in 2 and 3 compared to the
repulsions observed in G2 and 1 (Figure 11).
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Distortion of the aminophosphine ligand is another
factor that promotes phosphine dissociation. The
computed ligand distortion energies (Edistort
)
in
complexes G2 and 1–3 clearly indicate more significant
distortion of ligand L2 in complex 2 compared to those of
the other phosphine ligands (Table 5). The enhanced
distortion of L2 is due to a conformational change upon
binding to the ruthenium center. In comparison to the free
ligand, the metal-bound ligand L2 adopts a higher energy
conformation with
a
coplanar morpholine ring
(
Conformation A, Figure 10) to minimize steric clashes
with the NHC mesityl group. Thus, while it does not
exhibit the phosphine-NHC steric interactions that
promote phosphine dissociation in complexes G2 and 1,
complex 2 has a low G due to a significant contribution
d
Figure 10. Two perspectives of conformations A and B of ligand
L2 and the computed relative energies. All energies were
from ligand distortion energy.
calculated
using
the
Mo6/def2TZVP/SMD(toluene)//M06/def2SVP level of theory.
In order to provide insight into the origin of the
relative aminophosphine association constants, Kassoc
shown in Figure 9, the DFT-optimized geometries (Figure
1) as well as the Gibbs free energies (G ) and enthalpies
H ) of phosphine dissociation (Table 5), were computed
for parent catalyst G2 and complexes 1–3. The calculated
and H values agree with the U-shaped trend from
experimentally determined lower phosphine
dissociation energies were calculated for complexes 1 and
in comparison to G2 and 3. The optimized catalyst
,
1
d
(
d
G
d
d
K
assoc
;
2
structures depict variations in ligand conformation and
steric repulsions between the coplanar phosphine
substituent and the NHC mesityl group. We surmised that
the U-shaped trend in phosphine dissociation energy is the
combined result of these factors as well as inductive effects
derived from increased heteroatom incorporation.
Therefore, we conducted a detailed computational analysis
of the contributions of these individual factors.
Figure 11. DFT-optimized structures for complexes G2 and 1–3
depicting steric repulsions between the N-mesityl and P-
cyclohexyl groups in G2 and 1 and the preferred ligand
conformations in 1 and 2.
The parent complex G2, bearing a PCy
3
ligand,
displays an unfavorable steric interaction between the
NHC mesityl and the coplanar cyclohexyl ring (Figure 11).
Similarly, in complex 1, a coplanar cyclohexyl ring is
oriented toward the N-mesityl, a conformation that is
corroborated by the crystal structure of the analogous
monopiperidinophosphine-ligated complex 4 (Figure 3).
These steric clashes between the P-cyclohexyl and N-
mesityl promote phosphine dissociation from catalysts G2
While dissociation of ligands with more cyclohexyl
substituents (e.g. G2 and 1) is promoted by steric
interactions, the dissociation of ligands with more
morpholine substituents (e.g. 2 and 3) is promoted by
Table 5. Calculated Phosphine Ligand Dissociation
(G
d
, H ) and Distortion (Edistort) Energies.
d
and 1; the lower G
d
of 1 can be attributed to the inductive
effect of the morpholine substituent leading to lower
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Promoters of
Ligand
distortion of the phosphine ligand. The dissociation from
complex 3 is promoted by increased inductive effects;
however, significant contributions from phosphine-NHC
steric interactions and ligand distortion are not observed
to promote the dissociation of L3.

G
d
H
(kcal/mol)
d
Edistort
(kcal/mol)
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
catalyst
a
a
b
(
kcal/mol)
Dissociationc
G2
1
12.6
30.3
2.9
2.7
Steric
Steric,
Inductive
9.9
27.8
Table 6. Calculated Tolman Electronic Parameter
Inductive,
Distortion
a
(
TEP) Values of Phosphine Ligands.
2
9.5
27.6
5.7
Conformation Ab
Conformation Bb
3
11.9
29.2
1.9
Inductive
TEP (cm-1)
TEP (cm-1)
ligand
All
energies
were
calculated
using
the
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
PCy
3
---
2060.0
2064.3
2068.3
---
Mo6/def2TZVP/SMD(toluene)//M06/def2SVP level of theory.
are defined as the
Gibbs free energy and enthalpy differences, respectively,
between the optimized catalyst and the 14-electron complex
plus the free phosphine. Ligand distortion energy (Edistort) is
defined as the energy difference between the metal-bound
phosphine ligand geometry and the optimized free ligand
geometry. ”Steric” refers to steric repulsions between the
a
Ligand dissociation energies G
d
and H
d
L1
2058.5
2063.5
2068.3
L2
L3
b
a
Vibrational frequencies computed with B3LYP/6-31G(d)-
LANL2DZ in the gas phase in Ni(CO) L; computed
3
c
b
frequencies are scaled with a scaling factor of 0.962. In each
coplanar cyclohexyl ring on the phosphine ligand and the
NHC mesityl group. “Inductive” describes the inductive effect
arising from electron-withdrawing morpholine substituents.
case, conformation A contains a morpholine ring coplanar to
the phosphorus xy-plane, whereas conformation B features a
coplanar cyclohexyl ring, analogous to the structures in Figure
10. TEP values that correspond to the preferred phosphine
conformations in complexes G2 and 1–3 are highlighted in
bold.
“
Distortion” refers to distortion of the phosphine ligand in the
catalyst.
inductive effects of the nitrogen atoms, which decrease the
donor ability of the phosphorus lone pair. This electronic
effect is corroborated by the computed Tolman Electronic
Modeling of the Reaction Coordinate of Ligand
Dissociation
for
Fast-Initiating
Catalyst
2.
3
8
Parameter (TEP) values for PCy
3
and L1–L3 (Table 6). As
Computational studies of the reaction coordinate for
phosphine ligand dissociation according to the mechanism
in Scheme 1 were performed to determine the origin of the
high initiation rate for catalyst 2, and the reason for faster
phosphine dissociation for 2 in comparison to 1. The
reaction coordinate diagrams for the dissociation of
catalysts 1 and 2 are shown in Figure 12. While ligand L1 in
catalyst 1 maintains the same conformation (B) throughout
the dissociation process, L2 undergoes a conformational
change after the Ru–P distance is elongated to greater than
3.0 Å. As discussed above, in the ground state of catalyst 2,
L2 adopts the more distorted conformation A (Edistort = 5.7
kcal/mol) to minimize phosphine-NHC steric repulsions.
As the Ru–P bond lengthens during phosphine
dissociation, the phosphine-NHC repulsion diminishes,
and thus the less distorted conformation B becomes more
favorable. Although location of the phosphine dissociation
transition states was not successful, the computed reaction
coordinate diagrams suggest that the dissociation of L2 is
kinetically more favorable than that of L1 due to the
adoption of a lower energy conformation of L2 in the
transition state region. Therefore, the stabilizing effect
resulting from this conformational change from A to B is
proposed to be the reason that catalyst 2 has a higher rate
expected, morpholine substitution increases TEP values
within a single ligand conformation, indicating decreased
phosphine donor strength. For ligands L1 and L2, two
different conformations, which contain either a coplanar
morpholine (A) or a coplanar cyclohexyl group (B) were
individually considered. In these cases, conformation A,
which features anti-periplanar geometry of the nitrogen
and phosphorus lone pairs, exhibits higher phosphine
3
7
donor strength than conformation B. Thus, the donor
ability of the phosphine ligand is dependent on both
inductive effects and the preferred ligand conformation in
the catalyst. The lowest energy phosphine ligand
conformations in complexes 1 and 2, L1(B) and L2(A), have
-
1
-1
similar TEP values (2064.3 cm and 2063.5 cm ,
respectively), suggesting that these two ligands have
similar donor strength. Nonetheless, the phosphine donor
strength alone cannot explain the dissociation energy
trend. While complex 3 exhibits the strongest inductive
effects expected to promote phosphine dissociation, a
relatively high G is observed, indicating the significant
contributions of other factors, notably steric interactions
and ligand distortion, in promoting ligand dissociation.
d
The computational analysis revealed that the
combined contributions from steric interactions, inductive
effects, and ligand distortion result in the U-shaped trends
of phosphine dissociation (k
1
) than 1 and is the fastest-
initiating catalyst in the series.
in Kassoc and G . Accounting for the key promoters of
d
ligand dissociation for each complex, listed in Table 5,
provides an explanation for this trend. Ligand dissociation
is promoted in G2 and 1 by phosphine-NHC steric
repulsions, and G is further reduced in 1 due to inductive
effects of the morpholine substituent. Dissociation from
d
complex 2 is promoted by inductive effects and greater
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Journal of the American Chemical Society
3
0
1
2
3
4
5
6
7
8
9
25
20
15
10
5
2
(A) at 4.8 Å
ΔEdistort= 3.6 kcal/mol
2
(B) at 4.8 Å
ΔEdistort= 0.2 kcal/mol
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
2(B)
ΔEdistort= 2.4 kcal/mol
1
(B)
2(A)
2(B)
2(A)
ΔEdistort= 5.7 kcal/mol
0
2
.4 2.6 2.8 3.0 3.2 3.4 3.6 3.8 4.0 4.2 4.4 4.6 4.8 5.0
Ru-P distance (Å)
Figure 12. Reaction coordinate diagrams of phosphine ligand
dissociation for catalysts 1 and 2. The corresponding ligand
conformation is designated in parentheses (see Figure 10).
Both conformations A (more distorted with a coplanar
morpholine ring) and B (less distorted with a coplanar
cyclohexyl ring) are considered for catalyst 2. The lowest-
energy dissociation pathway of catalyst 2 follows the solid line,
starting from conformation
conformation B at longer Ru–P distances. All energies were
calculated using the Mo6/SDD-6-
11+G(d,p)/SMD(toluene)//B3LYP/SDD-6-31G(d) level of
theory.
Figure 13. ROMP reaction profiles of aminophosphine-ligated
complexes 4–7 compared to known catalysts G2 and G3.
The ROMP of 8 was performed in DCM at 25 ºC and
monomer conversion was monitored by size-exclusion
1
chromatography (SEC) and H NMR spectroscopy. All
tested aminophosphine-ligated complexes had higher
rates of polymerization than the parent catalyst G2, which
showed the lowest rate of conversion and broadest
molecular weight distribution. For the piperidine catalyst
series 4–6, rates of polymerization directly correlate with
initiation rates; while amine substitution causes an
increase in reactivity relative to G2, the rate of
polymerization decreases as the number of P–N bonds (n)
increases, provided n > 0. The dispersities of the resulting
polymers follow a similar trend, with catalyst 4 providing a
narrower molecular weight distribution in comparison to
6. Furthermore, although none of the catalysts in this
series prove to be as efficient as G3 in the ROMP of 8,
polymerization with the fast-initiating pyrrolylphosphine-
ligated catalyst 7 proceeded with a rate of conversion
slightly higher than that of G3, with similarly low dispersity
(1.03). Through the utilization of aminophosphine ligands,
a simple change to a substituent in the phosphine ligand
of G2 results in the formation of much more efficient
ROMP catalysts with reaction kinetics comparable to G3.
A and continuing on to
3
Ring-Opening Metathesis Polymerizations. In
order to investigate the catalytic activity of the new
complexes, they were next evaluated in ROMP, and the
reaction kinetics as well as dispersities of the resulting
polymers were compared. The substituted norbornene 8
was selected as a model monomer to distinguish the
catalytic activities of piperidinophosphine-ligated
complexes 4–6 from those of catalysts G2 and G3, and to
identify potential correlations with the previously
determined rate constants (Figure 13). Catalyst G3 is
known to be an efficient and effective ROMP catalyst,
while use of the parent catalyst G2 can lead to uncontrolled
molecular weights and broad molecular weight
3
9
15
distributions. Furthermore, the activity of the fast-
initiating catalyst 7 containing a pyrrole substituent was
evaluated.
CONCLUSIONS
A new class of olefin metathesis catalysts, based on the
incorporation of P–N bonds in the phosphine ligand
architecture of second-generation ruthenium catalyst G2,
was synthesized. Following facile synthesis of the
aminophosphine ligands from morpholine and piperidine,
the catalysts were formed in one step from complex G3.
The initiation rate and relative phosphine reassociation
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Journal of the American Chemical Society
Page 10 of 27
rate constants were determined, allowing for the
comparison of aminophosphine ligand binding strengths.
The results of kinetics and computational studies reveal
that a combination of steric, inductive, and ligand
conformational effects contribute to the observed trends
in phosphine dissociation. Furthermore, DFT calculations
suggest that a ligand conformational change during
phosphine dissociation is responsible for the accelerated
initiation rate of catalyst 2. Finally, the application of
aminophosphine-ligated catalysts to ROMP demonstrates
that simple changes to the substituents on the phosphine
ligand can lead to a dramatic enhancement in catalyst
reactivity. This study unambiguously disentangles the
steric, electronic, and conformational effects of
aminophosphine ligands on ruthenium metathesis catalyst
activity. Investigations of novel phosphine classes, notably
those containing incongruent substituents and P–X bonds,
will facilitate catalyst design and accelerate the
development of efficient, fast-initiating metathesis
catalysts.
Ed. 2003, 42, 1900–1923. (c) Schrock, R. R.; Hoveyda, A. H. Angew.
Chem., Int. Ed. 2003, 42, 4592–4633. (d) Grubbs, R. H. Tetrahedron
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
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4
4
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4
4
4
4
4
4
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5
5
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2
004, 60, 7117–7140. (e) Hoveyda, A. H.; Zhugralin, A. R. Nature
2007, 450, 243–251. (f) Hoveyda, A. H. J. Org. Chem. 2014, 79,
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9, 3012–3043. (b) Monfette, S.; Fogg, D. E. Chem. Rev. 2009, 109,
3783–3816.
3. For reviews, see: (a) Buchmeiser, M. R. Chem. Rev. 2000, 100,
1565–1604. (b) Knall, A.-C.; Slugovc, C. In Olefin Metathesis:
Theory and Practice; Grela, K., Ed.; John Wiley & Sons, Inc.:
Hoboken, NJ, 2014; pp 269–284.
0
1
2
3
4
5
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3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
4
. For reviews of ROMP, see: (a) Bielawski, C. W.; Grubbs, R. H.
Prog. Polym. Sci. 2007, 32, 1–29. (b) Leitgeb, A.; Wappel, J.;
Slugovc, C. Polymer 2010, 51, 2927–2946. (c) Schrock, R. R. Acc.
Chem. Res. 2014, 47, 2457–2466.
5. For a review of ADMET, see: Atallah, P.; Wagener, K. B.; Schulz,
M. D. Macromolecules 2013, 46, 4735–4741.
6. Sutthasupa, S.; Shiotsuki, M.; Sanda, F. Polym. J. 2010, 42, 905–
915.
7. For reviews of olefin metathesis in industry, see: (a) Mol, J. C. J.
Mol. Catal. A: Chem. 2004, 213, 39–45. (b) Slugovc, C. In Olefin
Metathesis: Theory and Practice; Grela, K., Ed.; John Wiley & Sons,
Inc.: Hoboken, NJ, 2014; pp 329–333.
ASSOCIATED CONTENT
Supporting Information
Experimental procedures, spectroscopic data, crystallographic
data, CIFs of catalysts 4–7, computational methods, and
optimized Cartesian coordinates and energies. This material
is available free of charge via the Internet at
http://pubs.acs.org.
8. (a) Schrock, R. R.; Feldman, J.; Cannizzo, L. F.; Grubbs, R. H.
Macromolecules 1987, 20, 1169–1172. (b) Murdzek, J. S.; Schrock, R.
R. Organometallics 1987, 6, 1373–1374. (c) Schrock, R. R.; DePue,
R. T.; Feldman, J.; Schaverien, C. J.; Dewan, J. C.; Liu, A. H. J. Am.
Chem. Soc. 1988, 110, 1423–1435. (d) Bazan, G. C.; Khosravi, E.;
Schrock, R. R.; Feast, W. J.; Gibson, V. C.; O’Regan, M. B.; Thomas,
J. K.; Davis, W. M. J. Am. Chem. Soc. 1990, 112, 8378–8387. (e)
Schrock, R. R.; Murdzek, J. S.; Bazan, G. C.; Robbins, J.; DiMare,
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AUTHOR INFORMATION
Corresponding Authors
9. (a) Nguyen, S. T.; Johnson, L. K.; Grubbs, R. H.; Ziller, J. W. J.
Am. Chem. Soc. 1992, 114, 3974–3975. (b) Nguyen, S. T.; Grubbs, R.
H.; Ziller, J. W. J. Am. Chem. Soc. 1993, 115, 9858–9859.
10. Schwab, P.; Grubbs, R. H.; Ziller, J. W. J. Am. Chem. Soc. 1996,
*
*
pengliu@pitt.edu
rhg@caltech.edu
118, 100–110.
11. Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett. 1999, 1,
9
1
53–956.
2. For reviews of ruthenium catalysts containing NHC ligands,
see: (a) Samojłowicz, C.; Bieniek, M.; Grela, K. Chem. Rev. 2009,
09, 3708–3742. (b) Vougioukalakis, G. C.; Grubbs, R. H. Chem.
Rev. 2010, 110, 1746–1787.
3. Getty, K.; Delgado-Jaime, M. U.; Kennepohl, P. J. Am. Chem.
Notes
The authors declare no competing financial interest.
1
ACKNOWLEDGMENT
1
We thank Dr. David VanderVelde for assistance with NMR
spectroscopic experiments and Lawrence Henling for
assistance with X-ray crystallography. Dr. Mona Shahgholi
and Naseem Torian are acknowledged for assistance with
mass spectrometry. Dr. Adam Johns is thanked for helpful
discussions regarding aminophosphine and catalyst synthesis.
Dr. Choon Woo Lee, Dr. Keary Engle, Dr. William Wolf,
Lennon Luo, and Tonia Ahmed are acknowledged for helpful
discussions of kinetics of olefin metathesis. Materia, Inc. is
thanked for donation of catalyst G2. We acknowledge ONR
Soc. 2007, 129, 15774–15776.
14. Love, J. A.; Morgan, J. P.; Trnka, T. M.; Grubbs, R. H. Angew.
Chem., Int. Ed. 2002, 41, 4035–4037.
1
1
1
5. Choi, T.-L.; Grubbs, R. H. Angew. Chem., Int. Ed. 2003, 42, 1743–
746.
6. Sanford, M. S.; Love, J. A.; Grubbs, R. H. Organometallics 2001,
2
0, 5314–5318.
17. (a) van der EideEdwin, F.; Piers, W. E. Nat. Chem. 2010, 2, 571–
576. (b) Nelson, D. J.; Manzini, S.; Urbina-Blanco, C. A.; Nolan, S.
P. Chem. Commun. 2014, 50, 10355–10375.
(
N00014-13-1-0895 and N00014-14-1-0650) and ARPA-E (DE-
18. For computational studies of the dissociative pathway for
second-generation ruthenium catalysts, see: (a) Vyboishchikov, S.
F.; Bühl, M.; Thiel, W. Chem. Eur. J. 2002, 8, 3962–3975. (b)
Cavallo, L. J. Am. Chem. Soc. 2002, 124, 8965–8973. (c) Adlhart, C.;
Chen, P. J. Am. Chem. Soc. 2004, 126, 3496–3510. (d) Minenkov, Y.;
Occhipinti, G.; Heyndrickx, W.; Jensen, V. R. Eur. J. Inorg. Chem.
AR0000683) for financial support, and the Resnick
Sustainability Institute for a fellowship to A.L.L.-M. DFT
calculations were performed at the Center for Research
Computing at the University of Pittsburgh and the Extreme
Science and Engineering Discovery Environment (XSEDE)
supported by the National Science Foundation.
2012, 2012, 1507–1516.
1
9. Griffiths, J. R.; Diver, S. T. In Handbook of Metathesis; Grubbs,
R. H., Wenzel, A. G., O’Leary, D. J., Khosravi, E., Eds.; Wiley-VCH:
Weinheim, Germay, 2015; pp 273–303.
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1. (a) Sanford, M. S.; Love, J. A.; Grubbs, R. H. J. Am. Chem. Soc.
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7
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9
1
1
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1
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1
1
1
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2. Moloy, K. G.; Petersen, J. L. J. Am. Chem. Soc. 1995, 117, 7696–
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review of aminophosphine chemistry, see:
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H. J. Chem. Soc., Dalton Trans. 1999, 881–889.
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Ragone, F.; Cavallo, L. Catal. Sci. Technol. 2011, 1, 1287–1297. (b)
Liu, P.; Taylor, B. L. H.; Garcia-Lopez, J.; Houk, K. N., In Handbook
of Metathesis; Grubbs, R. H., Wenzel, A. G., O’Leary, D. J.,
Khosravi, E., Eds.; Wiley-VCH: Weinheim, Germay, 2015; pp 199–
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Chem. Soc. 2017, 139, 3896–3903.
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000, 33, 6239–6248.
For Table of Contents Only
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