Dynamic ?-Bonding of Imidazolyl Substituent in a Formally 16-Electron Cp Ru(2-P, N)+ Catalyst Allows Dramatic Rate Increases in (E)-Selective Monoisomerization of Alkenes

Article abstract of DOI:10.1021/acscatal.8b04345

Alkene isomerization can be an atom-economical approach to generating a wide range of alkene intermediates for synthesis, but fully equilibrated mixtures of disubstituted internal alkenes typically contain significant amounts of the positional as well as geometric (E and Z) isomers. Most classical catalyst systems for alkene isomerization struggle to kinetically control either positional or E/Z isomerism. We report coordinatively unsaturated, formally 16-electron Cp Ru catalyst 5, which facilitates simultaneous regio- A nd stereoselective isomerization of linear 1-alkenes to their internal analogues, providing consistent yields of (E)-2-alkenes greater than 95%. Because nitrile-free catalyst 5 is more than 400 times faster than previously published nitrile-containing analogues 2 + 2a, very reasonable 0.1-0.5 mol % loadings of 5 complete ambient-temperature reactions within 15 min to 4 h. UV-vis, NMR, and computational studies depict the imidazolyl fragment on the phosphine as a hemilabile, four-electron donor in ²-P,N coordination. For the first time, we show direct experimental evidence that the PN ligand has accepted a proton from the substrate by characterizing the intermediate Cp Ru[??³-allyl][¹-P)P-N⁺H], which highlights the essential role of the bifunctional ligand in promoting rapid and selective alkene isomerizations. Moreover, kinetic studies and computations reveal the role of alkene binding in selectivity of unsaturated catalyst 5.

Full text of DOI:10.1021/acscatal.8b04345

Research Article
pubs.acs.org/acscatalysis
Cite This: ACS Catal. 2019, 9, 7217−7231
Dynamic π‑Bonding of Imidazolyl Substituent in a Formally 16-
Electron Cp*Ru(κ2‑P,N)+ Catalyst Allows Dramatic Rate Increases in
(E)‑Selective Monoisomerization of Alkenes
Erik R. Paulson,† Curtis E. Moore,‡ Arnold L. Rheingold,‡ David P. Pullman,† Ryan W. Sindewald,†
Andrew L. Cooksy,† and Douglas B. Grotjahn*,†
†Department of Chemistry and Biochemistry, San Diego State University, 5500 Campanile Drive, San Diego, California 92182-1030,
United States
‡Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093,
United States
S
* Supporting Information
ABSTRACT: Alkene isomerization can be an atom-economical
approach to generating a wide range of alkene intermediates for
synthesis, but fully equilibrated mixtures of disubstituted internal
alkenes typically contain significant amounts of the positional as
well as geometric (E and Z) isomers. Most classical catalyst
systems for alkene isomerization struggle to kinetically control
either positional or E/Z isomerism. We report coordinatively
unsaturated, formally 16-electron Cp*Ru catalyst 5, which
facilitates simultaneous regio- and stereoselective isomerization
of linear 1-alkenes to their internal analogues, providing
consistent yields of (E)-2-alkenes greater than 95%. Because
nitrile-free catalyst 5 is more than 400 times faster than
previously published nitrile-containing analogues 2 + 2a, very reasonable 0.1−0.5 mol % loadings of 5 complete ambient-
temperature reactions within 15 min to 4 h. UV−vis, NMR, and computational studies depict the imidazolyl fragment on the
phosphine as a hemilabile, four-electron donor in κ2-P,N coordination. For the first time, we show direct experimental evidence
that the PN ligand has accepted a proton from the substrate by characterizing the intermediate Cp*Ru[η3-allyl][κ1-P)P−N+H],
which highlights the essential role of the bifunctional ligand in promoting rapid and selective alkene isomerizations. Moreover,
kinetic studies and computations reveal the role of alkene binding in selectivity of unsaturated catalyst 5.
KEYWORDS: alkenes, isomerization, selectivity, catalyst, bifunctional, π-bonding
alkene substrates but showed signs of deactivation with certain
substrates (silyl, dienes) and would not tolerate protic or C
O functionality.7 Hilt et al. had significant success with four-
component catalyst systems.8 For Hilt’s Ni system, optimum
selectivity required cryogenic temperatures, whereas the Co
system operated at room temperature. Dobereiner’s system
tolerates protic and CO, silyl, and diene functional groups,
although their presence or longer-chain alkenes needed longer
reaction times and/or higher catalyst loadings.9
At present, two recent catalysts achieve high positional and
(E)-selectivities with geometric selectivities higher than those
for (Z)-selective systems. In 2014, we disclosed the Cp*
analogue of the zipper catalyst 110 (2 + 2a, Chart 1) as a
mixture of two complexes in equilibrium which can selectively
achieve >95% yields of (E)-2-alkenes with no detectable (Z)-
isomers by 1H NMR and GC and little (<3%) over-
INTRODUCTION
■
While there are a number of catalysts that can achieve selective
isomerization for compounds containing specific functional
groups such as allylic alcohols,1,2 ethers,3 and amines,4 few
isomerization catalysts exist that can exhibit regio- and/or
stereoselectivity in a general fashion for substrates that do not
contain branching or other steric factors that could inhibit
repeated isomerizations down a chain. There has been a
significant improvement in the controlled positional isomer-
ization of 1-alkenes to 2-alkenes in the last 20 years, but most
of these catalysts give (E)-2 and (Z)-2 product in close to
thermodynamic ratio of about 4:1 for linear unbranched
alkenes.5,6
The challenge is more acute when attempting to control
both positional and E/Z selectivity. Four recent catalysts that
are positional- and (Z)-selective are shown in Chart 1 with
performances summarized in Table 1. High (Z)-selectivity
combined with positional selectivity remains an unmet
challenge; (E)/(Z)-ratios for 2-alkenes were in the range
1:5.6 to 1:2.6. The catalyst of Holland et al. acted on linear
Received: November 5, 2018
Revised: June 21, 2019
© XXXX American Chemical Society
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considered nitrile-free complex 5 (Scheme 1). Nitrile
inhibition had been demonstrated by us on two occasions:
Chart 1. Geometric and Positionally Selective Alkene
Isomerization Catalysts
Scheme 1. Synthesis of Complexes 3−10
(1) addition of an equivalent of CH3CN to 2 + 2a slowed the
catalyst by a factor of 2, and (2) addition of 1.5−2 equiv of
CH3CN slows Cp catalyst 1 but not in a way that prevents
isomerization of 2-alkene to 3-alkene.13 Hence, our hypothesis
was that 5 would be faster than 2 + 2a because of a lack of
competition of nitrile and alkene. As described herein, the
synthesis of 5 avoids production of the mixture of 2 + 2a from
which it had proved impossible to remove enough nitrile to
make pure mononitrile species 2. More significantly, here, we
show that 5 is more than 400 times faster than 2 + 2a and
about 1/10 as fast as Cp analogue 1. However, like the 2 + 2a
mixture, 5 has the ability to form (E)-2 alkenes in ca. 95%
yields and excellent selectivity. Here, we also describe the
unusual ability of the ruthenium-bound imidazole ring to
engage in π-bonding, thus stabilizing the formally 16-electron
Ru center of 5. Moreover, we show that it is the steric bulk of
the Cp* ligand and not its greater electron donation that is
responsible for slowing the further positional isomerization.
We also show direct evidence for reversible and highly
positionally specific binding of alkenes as well as the first direct
spectroscopic evidence of the pendent imidazole involved in
proton transfer through an allyl intermediate.
isomerization, all with reasonably low loadings and mild
conditions (1 mol %, 40 °C, 48 h). After we started the work
reported here, in 2017, Huang et al. reported an iridium pincer
complex that generally furnishes 90−95% (E)-2 alkenes with
20−50:1 E/Z selectivity, also with low loadings and temper-
atures, though we note the authors purified alkene substrates
by distillation from LiAlH4.11 The suggested mechanism
includes oxidative addition of one of the C−H bonds of the
pyridine arm of the pincer ligand to generate the hydride for
insertion in an alkyl mechanism.12
We conclusively showed that the imidazolyl nitrogen in 2a
creates a catalyst that is >3000 times faster than an analogue of
2a with a P(iPr)3 ligand.13 However, comparing 1 and 2 + 2a,
the price of high positional control by the latter is about 1000-
fold reduced in rate. In the search for a more active catalyst, we
RESULTS AND DISCUSSION
■
Synthesis and Characterization of Complexes. Com-
plex 3 appeared to be an ideal intermediate to make 5 (Scheme
Table 1. Summary of Isomerization of Terminal Linear Alkenes with Selected Catalysts in Chart 1
a
b
catalyst
Holland 20147
mol %
0.5
time (min)
720
temp (°C)
conv (%)
not listed
% 2-alkene
E/Z ratio
TOF (min−1
>0.24
)
c
80
88
1:5.3
limited functional group tolerance
d
Hilt 2015 (Co)8a
Hilt 2015 (Ni)8b
10
10
90
360
rt
-60
95
90
92
1:5.6
1:2.6
0.11
0.025
e
72
catalysts made from Ph2PH, Zn, ZnI2, and MX2(dppb); Ni catalyst selectivity erodes at higher temperatures
Dobereiner 20189
0.5 30 66 94
fast, good functional group tolerance, but slower in their presence and with longer alkenes
c
c
c
c
c
92
86
96
95
97
1:4.0
>99:1
>99:1
25:1
6.3
65
Grotjahn 2007 (1)
0.1
15
rt
40
rt
98
98
96
98
fast, excellent (E)-selectivity; lower positional selectivity
Grotjahn 2014 (2+2a)
excellent (E)- and monoselectivity, but slow
Huang 201711
0.1
1
2880
0.034
2.0
480
fast, very (E)- and monoselective; alkenes distilled from LiAlH4 in many cases
this work (5) 0.1 180 rt
>400:1
5.4
fast, very (E)- and monoselective, good functional group tolerance
a
b
c
All reactions were run between 0.5−1.0 M in substrate. Calculated with conversions at indicated time point without factoring temperature. 2-
d
e
Hexene. 2-Hexadecene. 2-Decene.
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1
Table 2. JC−P (Hz) and 13C and 15N Chemical Shifts
(ppm)
1). In 1988, Tilley and Chaudret independently discovered the
pioneer complexes Cp*Ru(PR3)Cl, where R = iPr or Cy.
Cp*Ru(L)X complexes have been synthesized by complex-
ation of PR3 with either Cp*RuCl414 or a mixture of Cp*RuCl2
dimer and Zn.15 A striking feature of both reported complexes
is their blue color both in solution and in the solid state,
contrasting with yellow to orange color of 18-electron
CpRu(II) species mentioned here in this article. It has been
suggested that the blue color in these and subsequent
Cp*Ru(P)X complexes is the result of π-donation of a lone
pair from the halide to the metal center, which stabilizes a
formally 16-electron state.16
After Tilley’s and Chaudret’s initial discoveries, several 16-
electron complexes of the general formula Cp*Ru(L)X could
be accessed if L was a bulky phosphine ligand with the general
formula P(R1)2(R2), where R1 was isopropyl or cyclohexyl and
where X was either a halide16−19 or a weakly basic oxygen-
containing X-type ligand such as triflate, Ph3SiO−, or
CF3CH2O−.16,20,21 We reasoned that the Cp*RuCl fragment
could therefore accommodate the (diisopropyl)(imidazolyl)-
phosphine ligand employed in catalysts 1 and 2, although it
was not clear whether the ligand would bind in a monodentate
fashion to produce a 16-electron complex akin to Tilley and
Chaudret’s examples or would chelate through the imidazole as
well to produce an 18-electron complex. Because the switch of
the Cp ligand in catalyst 1 to the bulkier and more electron-
rich Cp* ligand in catalyst 2 + 2a engendered an increase in
monoselectivity, we wondered whether steric or electronic
factors lead to the change. We therefore made 4 (and
ultimately 6) with the more electron-poor tetramethyl-
(trifluoromethyl)cyclopentadienyl (Cp⧧) ligand, which has
been shown to mimic the sterics of Cp* and the electronics of
Cp.22,23
a
Im−C1
N(2)
N(1)−CH3
13C chemical
15N chemical
shift
15N chemical
complex
shift
J
shift
2
2a
142.5
148.3
141.9
146.0
152.0
151.9
146.5
152.5
152.6
152.3
58.0
28.5
51.9
43.7
19.3
21.7
34.7
24.1
22.1
25.2
n.d.
n.d.
n.d.
n.d.
bc
,
3
4
5
6
7
8
9
−100.6
−136.2
−147.0
−155.7
n.d.
−164.3
−158.3
−168.8
−213.1
−213.7
−203.1
−204.5
n.d.
−210.2
−203.7
bd
,
bd
,
d
d
10
−205.1
Data for 2 and 2a are from literature.13 n.d. = not determined. 16-
a
b
c
Electron crystal structure. N(2) unbound to Ru in the crystal
d
structure. N(2) bound to Ru in the crystal structure.
Figure 1. X-ray crystal structure of complex 3. Key bond lengths (Å)
with values for each independent molecule in the unit cell: Ru−P,
2.3582(13) and 2.3699(13); Ru−Cl, 2.703(12) and 2.3591(12); Ru−
Cp(centroid), 1.772 and 1.780, respectively.
Complexation of the requisite phosphine with [Cp*RuCl]4
or [Cp⧧RuCl]4 occurs efficiently in solvents such as acetone
and THF with a rapid change in color of the solution from
deep red to deep blue. The blue color is reminiscent of many
Cp*Ru 16-electron complexes, and NMR data for the major
species (>90% by 31P NMR) are also consistent with the
formally 16-electron species CpRRu(L)Cl (3, Cp* and 4, Cp⧧).
There is some evidence of equilibrium between these
monomeric species and related tetrameric species (see Figures
S9−S18 and the discussion in the Supporting Information).
The isopropyl group signals in the 1H NMR spectra of 3 and 4
appear as a pair of dd, suggesting a symmetrical static structure
such as that drawn in Scheme 1; alternatively, if solvent is
bound, forming an 18-electron species, the association of
solvent is weak. The 15N HMBC chemical shift of the basic
nitrogen of the imidazole in 3 (δ15N −100.6 ppm, Table 2) is
consistent with an unchelated imidazolylphosphine,24 as is the
coupling constant for the phosphorus to the C-2 of the
imidazole (1JCP = 51.9 Hz). Complexes 2 + 2a can be used as
with the HMBC data, the basic N(2) shows no interaction
with ruthenium, in contrast to 2 and to other systems
containing Cp*RuCl metal fragments with a P−N ligand. The
P−N ligands iPr2P-2-dimethylaminoindenide studied by
Stradiotto,25 Ph2P(CH2)2NMe2 by Kirchner,26 and Ph2P-
(CH2)2NH2 by Ikariya27−29 were shown to chelate through
both the phosphorus and nitrogen to Cp*RuCl, leading to 18-
electron complexes. All three published systems feature a P−
C−C−N−Ru five-membered chelate. From our lab, cationic
species 2 features a 4-membered chelate. We have shown
previously in an alkyne hydration catalytic system with a
pyridyl-phosphine ligand that the introduction of a tert-butyl
group adjacent to the nitrogen can greatly enhance the
hemilability of the chelate.24 We presume that the steric and
angle strain combined with the strong π-donation of the halide
prevents chelation from occurring in 3 and 4.
1
comparisons for the JCP coupling constant, as both chelated
To examine this further, complexes 7 and 8, lacking the tert-
butyl group, were generated from the appropriate tetramer and
phosphine. Although some evidence for 16-electron species, or
at least rapid hemilability of the chelate, is presented in
solution (blue color for 7, symmetry in 1H NMR for 7 and 8),
X-ray crystal structures for 7 and 8 feature a chelated nitrogen
(Figure 2). The chelate lengthens the Ru−Cl bond of 7 as
compared to 3 (2.47 Å vs 2.36 Å), which could be ascribed to
lack of Ru−Cl multiple-bond character for 7.
1
(2) and unchelated (2a) forms of the complex exist. The JCP
in 3 much more closely resembles that in 2a (58.0 Hz) rather
than that in 2 (28.6 Hz).10 The large C-2 coupling constant for
complex 4 (J = 43.7 Hz) also suggests a lack of chelation and
hence 16-electron character.
Prolonged storage in cyclohexane at −40 °C gave crystals of
3 suitable for X-ray diffraction. The crystal structure of 3
(Figure 1, Table 3) shows a two-legged piano-stool structure
characteristic of 16-electron Cp*Ru complexes with P(1),
Cl(1), and Ru(1) coplanar with the Cp* centroid. Consistent
The mixture containing complex 3 was tested for isomer-
ization under similar conditions as those for 2 + 2a but was
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Figure 2. X-ray crystal structure of complexes 7 and 8. Key bond
lengths (Å) and angles (deg): 7: Ru−P, 2.3906(10); Ru−N,
2.203(4); Ru−Cl, 2.4713(10); Ru−Cp(centroid), 1.779; P−Ru−N,
66.94(10). 8: Ru−P, 2.3925(9); Ru−N, 2.185(2); Ru−Cl, 2.4595(8);
Ru−Cp(centroid), 1.780; P−Ru−N, 66.92(7).
found to be a very poor catalyst (<1 turnover in 1 week).
There could be several reasons for the sluggish catalysis: (1)
the halide is too strong of a π-donor, thereby inhibiting binding
of the alkene to the metal center; (2) the neutral charge of the
complex disfavors binding of the alkene or formation of a
formally anionic allyl ligand that we have previously proposed
as an intermediate during catalysis; or (3) the monodentate
phosphine provides more steric demand due to free rotation of
the Ru−P and P−C(imidazolyl) bonds. To address all three
reasons, the mixture containing 3 was treated with TlPF6 to
make a cationic complex (5) in acetone, which was obtained in
98.2% yield.30 4 was converted to 6 in the same fashion.31
We expected that upon ionization and halide ligand loss
from 3, the cationic complex would bind the imidazole
nitrogen as well as another solvent molecule to produce an 18-
electron complex due to the removal of the π-stabilizing
chloride ligand. A significant upfield shift of the 15N HMBC
resonance for the basic imidazole nitrogen (δN = −147.0 ppm,
Table 2) occurs, which brings it within the range for P,N-
chelated imidazolyl phosphine ligands.24 However, the 1H
NMR spectrum shows sharp peaks for all resonances with one
septet of doublets (2H) for the isopropyl C−H protons and
two dd (each 6H) for the isopropyl-CH3 protons, suggesting
planar symmetry16 or fast reversible binding of solvent
molecules to the metal center.32 However, no broadening of
1
the H signals occurred, nor did we observe new signals (for
either bound acetone or desymmetrization of the phosphine
ligand) consistent with binding of acetone upon cooling the
solution to −30 °C.
Surprisingly, the color of the solution upon ionization
remains deep blue; UV−vis spectroscopy shows a large broad
absorption centered around 572 nm (ε = 748 L/mol·cm). The
combination of spectroscopic data point to the persistence of a
16-electron complex despite the removal of the halide ligand.
The blue color remains upon removal of solvent, and the
intensely blue powder is stable for months under air-free
conditions. Solutions of 5 can be made with undried acetone,
which can maintain their color and activity for a few days.
Crystals suitable for X-ray diffraction of 5 and 6 were grown
by vapor diffusion of diethyl ether into acetone. In the solid
state, complexes 5 and 6, like 3, exhibit planar symmetry with
P(1), N(2), and Ru (1) coplanar with the Cp centroid (Figure
3). No solvent molecules are coordinated, and there are no C−
H bonds close enough to the metal center to participate in
agostic interactions with the closest M−H interaction being
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closest comparison structurally to 5 is a pair of complexes from
Stradiotto, Cp*Ru(tBu2P−N-amidinate) complexes45 that
contain chelating anionic phosphine-amido ligands (Chart
2). To the best of our knowledge, 5 is the first reported
example of a fully characterized, cationic Cp*Ru(P−N) 16-
electron complex, and 6 is the first reported 16-electron Cp⧧Ru
phosphine complex of any kind.
Catalysis Scope and Limitations. As hypothesized, 5
proved to be an exceedingly efficient catalyst relative to its
nitrile-containing counterpart (Table 4). Isomerization reac-
tions of linear 1-alkenes to (E)-2-alkenes using catalyst 5 can
be performed at room temperature in acetone-d6 using as little
as 0.1 mol % catalyst and reach full conversion within 3 to 4 h
at this low loading (Table 5). In several cases, alkene samples
could be used as received once deoxygenation was performed
by bubbling nitrogen gas through the alkene substrates prior to
use. However, we suspect that trace impurities of allylic
peroxides in some of the alkene substrates lead to significant
deactivation of the catalyst at 0.1 mol % loadings. One solution
is pretreatment of the substrate by passing it through a small
plug of basic alumina. At catalyst loadings of ≥0.5 mol %, this
pretreatment was not necessary, and most substrates under-
went complete isomerization within 15 min to 1 h. In addition
to the alkenol and alkenol silyl ether substrates reported for 2 +
2a,10 we show that protected amide and ester substrates are
tolerated and isomerize efficiently at 1.0 mol %. In all cases
with conversions of starting 1-alkene at 95% or greater, yields
of (Z)-alkenes were less than 0.5%, and yields of 3-alkenes
were less than 3%, showing remarkable general selectivity for
formation of (E)-2-alkene products (Table 5).
To investigate the relative efficiency of 5 to the mixture of 2
+ 2a, we compared the half-life of conversion of 1-hexene to
(E)-2-hexene at room temperature using 0.25 mol % of each
catalyst. We found that while catalyst 2 + 2a reached ∼50%
conversion after 40 h, catalyst 5 reached 50% conversion in
only 5.6 min, making it >400 times faster at synthetically
reasonable loadings. The increase in efficiency can be directly
attributed to the lack of acetonitrile; in an attempt to mimic
the 2 + 2a system, 1.7 equiv of acetonitrile was added to a
solution of 5 and run with the same 0.25 mol % at room
temperature and achieved only 38% conversion after 48 h.
A major advantage that catalyst 5 has over 2 + 2a is its
ability to isomerize substrates that contain potentially strongly
binding or chelating functional groups, which can slow
catalysis. 2 + 2a (1 mol %, 40 °C, 48 h) was able to isomerize
the tert-butyldiphenylsilylether of pent-4-en-1-ol to provide
>90% yield of the (E)-2-isomer but required 6 mol % extra
phosphine ligand to prevent catalyst deactivation by way of an
arene complex.10 With the same substrate, catalyst 5 still
suffered from arene complex formation, but due to its greater
efficiency, 1 mol % 5 can achieve >95% yield of the (E)-2-
isomer within 10 min with no added ligand. This result opened
the door to testing other substrates containing phenyl groups;
9-phenyl-1-decene was isomerized smoothly with 1 mol % 5, as
was the phenylbutene discussed below.
Figure 3. X-ray derived molecular structures of the cations in
complexes 5 and 6 (PF6− anions omitted). Key bond lengths (Å) and
angles (deg) with values for each independent molecule in the unit
cell: 5 (one molecule in unit cell): Ru−P, 2.386(2); Ru−N,
2.242(10); Ru−Cp(centroid), 1.773; N−Ru−P, 68.3(2). 6 (two
molecules in unit cell): Ru−P, 2.3905(6) and 2.3930(6); Ru−N,
2.1501(18) and 2.1599(18); Ru−Cp(centroid), 1.775 and 1.773; N−
Ru−P, 69.00(5) and 68.92(5), respectively.
between one of the methyl groups of an isopropyl with M−H
distances 3.0 Å for 5 and 3.1 Å for 6.
33−35
Cp*Ru(P−P)+ and Cp*Ru(N−N)+/0
16-electron
complexes have been well-studied. In the absence of
coordinating solvent molecules, agostic C−H bonds or even
trace amounts of dinitrogen are known to lead to 18-electron
complexes,36 so to make mono- and bidentate cationic
Cp*Ru(PP) complexes, ionizations were performed with
fluorobenzene under argon.19,25 Related 16-electron N−N
chelates appear to be more stable due to strong σ-donation.
Although Cp- and Cp*Ru(P−N) systems have been shown
by Stradiotto, Ikariya, and our group to be effective catalysts
for alkyne hydration, alkene hydrosilylation,37 alkene isomer-
ization,10,24,38−41 and hydrogenation of ketones, epoxides,27
imides,42 esters, and carboxamides,43 well-defined, formally
unsaturated Cp*Ru(P−N) complexes are quite rare; several
reported in the literature exhibit characteristics of 16-electron
species but cannot be isolated because of chemical instability.
Stradiotto observed that upon abstraction of the halide from
the Cp*Ru(iPr2P-2-dimethylaminoindenide)Cl complex,
either oxidative addition of one of the methyl C−H bonds
or arene complexation occurred (Chart 2), although a 16-
electron intermediate was suggested.25,37,44 Similarly, Kirchner
observed oxidative addition of a methyl C−H bond.26 These
transformations could be facilitated by the removal of the
stabilizing π-donation afforded by the chloride ligand. The
Chart 2. Known Cp*Ru(PN) Complexes
Terminal alkene substrates containing unsaturated moieties
in the 5-position present an interesting thermodynamic
challenge for catalyst 5. In these substrates, if a double bond
is isomerized once, the resulting product is not conjugated, but
if a second isomerization occurs, the result is a conjugated π-
system that provides significant extra stability over the
unconjugated isomer. For example, an equilibrium mixture of
1-phenylbutenes, established between 25 and 55 °C, gave
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a
Table 4. Isomerization of 1-Hexene with 1, 2, 5, and 6
d
catalyst
mol %
0.1
time
1-hexene
(E)-2-hexene
(E)-3-hexene
TOF (min−1
)
1
15 min
20 min
48 h
3 h
32 h
2
2
2
2
86
79
96
97
97
11
20
2
1.5
0.7
65
49
0.034
bc
,
e
2 + 2a
1
0.1
0.1
5
6
5.4
0.51
2
a
b
c
d
Reactions were run at 0.50 M in acetone-d6 with internal standard. Reaction was run at 40 °C. From ref 10. Calculated with conversions at the
e
indicated time point. TOF at 40 °C.
ratios of conjugated 1-phenyl-(E)-2-butene to unconjugated 1-
phenyl-(E)-3-butene that ranged from 92:6 to 94:3.46−48
Similarly, an equilibrium mixture of hexenones was reported to
contain ∼16% unconjugated hex-(E)-4-en-2-one, ∼7% con-
jugated hex-(Z)-3-en-2-one, and ∼77% conjugated hex-(E)-3-
en-2-one.49 If the ratios are recalculated excluding the (Z)-
isomer, the ratio becomes 83:17 in favor of the conjugated (E)-
isomer.
Table 5. Alkene Yields (%) and E/Z Selectivity Using
Catalyst 5
a
Given the strong thermodynamic preference for the
conjugated internal isomer, a true challenge for catalyst 5 is
the isomerization of the terminal alkene substrates for these
two systems: 5-hexen-2-one (Table 5, entry 18) and 1-phenyl-
4-butene (Table 5, entry 19). 1,2-Epoxy-5-hexene (Table 5,
entry 20) and 1,7-octadiene (Table 5, entry 21), are also prone
to overisomerization: in the former case, an internal
conjugated diene can result, and in the latter case, using 1,
we have observed ring opening and conjugated enal
formation.50
Higher catalyst loadings are ultimately required for the
diene, enone, and phenyl substrates, likely due to chelation or
deactivation of the catalyst via arene complex formation. The
results for 1-phenyl-4-butene are striking (Table 5, entry 19):
catalyst 5 can achieve a 91.9:4.3 ratio of unconjugated and
conjugated products, the complete opposite of the thermody-
namic ratio mentioned above. Overisomerization at later times
was slow likely due to catalyst deactivation by arene
complexation. Selective monoisomerization was also seen
with 1,2-epoxy-5-hexene (Table 5, entry 20) with very little
enal formation due to the deactivation of catalyst by
decarbonylation of the aldehyde.50 In entry 18, 5-hexen-2-
one suffers from more rapid overisomerization51 with a
maximum yield of monoisomerized product at 66% at 4 h,
but monoisomerization is still favored over conjugation by
around 3:1 at this point. The conversion of 1,7-octadiene to
(2E,6E)-2,6-octadiene requires the migration of two separate
double bonds; nevertheless, with higher 2 mol % loading, the
doubly monoisomerized product yield reaches >94% within 10
min, but the conjugated diene does not appreciably increase
within 24 h.
Sterics or Electronics? The pentamethylcyclopentadienyl
(Cp*) ligand is both more electron-rich and sterically bulky
than the cyclopentadienyl (Cp) ligand.52,53 Given the distinct
differences in reactivity between Cp-containing catalyst 1
(which is fast but not positionally selective) and Cp*-
containing 2 + 2a and 5 (which are selective for
monoisomerization), we wanted to investigate whether the
change in selectivity during catalysis is the result of steric or
electronic influences between the Ru center and the alkene.
Catalytic and structural comparisons between Cp- and Cp*Ru
complexes54−60 have been undertaken, employing the 1-
(trifluoromethyl)-2,3,4,5-tetramethylcyclopentadienyl (Cp⧧)
ligand developed by Gassman,22 reported to mimic the
a
Reactions were run at room temperature with 0.50 M substrate in
b
acetone-d6. Conservative estimates; for in-depth analysis, see Figures
S46−S66 and Tables S6 and S7. n.d. = not determined because of
either signal overlap or broadness. Reactions were run in triplicate.
c
d
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electronics of the Cp ligand and sterics of the Cp*
ligand.22,23,61
reveals four MOs with π-bonding character (HOMO−9,
HOMO−8, HOMO−7, and HOMO−5) and three MOs that
are antibonding (HOMO−2, HOMO−1, and HOMO) with
respect to the two atoms, resulting in one “net” π-bond. The
LUMO is also antibonding with π-symmetry with respect to
ruthenium and chloride. A similar bonding scenario can be
seen when we subjected Tilley and Chaudret’s Cp*Ru(iPr3P)-
Cl complex to the same computational analysis (see Table
S86) and is consistent with other analyses of Cp*Ru(PR3)X
systems.
Upon abstraction of the halide from 3 and 4 to form
complexes 5 and 6, respectively, crystal structure and NMR
data are consistent with a two-legged piano stool complex with
planar symmetry, similar to 3 and other formally 16-electron
complexes. The computed molecular orbitals for complexes 5
and 6 indicate a similar π-stabilizing interaction. For complex
5, the HOMO−7 (Figure 4) represents a π-bonding
To obtain the Cp⧧ analogue (6) of catalyst 5, the
[Cp⧧RuCl]4 tetramer was first prepared following a protocol
by Evju and Mann62 in which they speculated the tetramer had
formed during the synthesis. The [Cp⧧RuCl2]2 dimer was
reduced with Zn metal in refluxing methanol; the tetramer was
isolated in 91% yield, characterized, and a crystal structure was
obtained (see Figure S3). The requisite phosphine was added
to [Cp⧧RuCl]4, leading to complex 4, which was cleanly
ionized with TlPF6 to obtain complex 6 in 94% yield. The
crystal structure of 6, like that of 5, shows a cationic, formally
16-electron species. A comparison of the structures reveals
similarities: Ru−P bond distance is essentially identical
(2.386(2) Å for 5, 2.3905(6) Å for 6) as is the distance
from the metal center to the Cp centroid (1.773 Å for 5, 1.775
Å for 6), both well within the margin of error. However, the
Ru−N distance in 6 (2.1501(18) Å) is almost 0.1 Å shorter
than that in 5 (2.242(10) Å). This is perhaps a consequence of
the nitrogen being directly trans to the carbon containing the
−CF3 group in the crystal structure.
Albeit slower than 5, complex 6 is also able to cleanly
isomerize 1-hexene to >95% (E)-2-hexene using 0.1 mol %
catalyst after 32 h. Because the alkene isomerization positional
selectivity more closely aligns with that of catalyst 2 + 2a and 5
than that of 1 (Chart 3 and Table 4), it can be inferred that the
Chart 3. Steric and Electronic Influences on Selectivity
selectivity for monoisomerization for catalysts 2 + 2a and 5 is a
result of increased steric bulk of the Cp* ligand rather than its
increased electron-donating ability. Despite the comparable
selectivity of 6 and 5, the lower rate of the former makes 6 a
rather inferior choice for practical use. A hypothesis for why 6
is slower than 5 is discussed below.
Figure 4. Computed molecular orbitals for complex 5. Top left:
HOMO−7 (face view). Middle left: ChemDraw of HOMO−7 (face
view). Bottom left: HOMO−7 (edge view). Top right: LUMO (face
view). Middle right: ChemDraw of LUMO (face view). Bottom right:
LUMO (edge view).
Bonding and Stability in 16e− Complexes 5 and 6.
The major increase in activity of catalyst 5 over 2 + 2a clearly
results from an open coordination site and the lack of the
competitive nitrile ligand for the alkene. An intriguing question
arises as to why the catalyst is stable enough to be isolable in
the solid state and in weakly binding solvents such as acetone
and THF yet reactive enough to efficiently isomerize terminal
alkenes. To probe this question, a computational study was
undertaken to analyze the orbitals involved in stabilization of
the 16-electron species. The WB97XD functional with an SDD
basis set with effective core potential was used for ruthenium,
and the cc-pVDZ basis set was used for all other atoms after
benchmarking with experimental data for Ru−N and Ru−P
bond distances, NMR, and UV−vis (see Tables S71−S79 on
pages S234−S238 in the Supporting Information for details).
An analysis of the relevant molecular orbitals with π-
symmetry between the ruthenium and chloride in complex 3
interaction between the coordinated basic nitrogen and the
two neighboring carbons of the imidazole and the metal center.
This bonding MO resembles a filled molecular orbital on the
free ligand and a large majority of its contribution and can
therefore be assigned as a ligand-to-metal π-donation. For
complex 6, the HOMO−8 is a similar π-type bonding orbital,
albeit with the electron density shifted from the C4 carbon
toward the phosphorus atom, which contributes 19% toward
the bonding orbital as opposed to only 3% for 5.63 The π-
donation shown from the imidazole provides the metal with
the missing two electrons from the formal 16-electron
assignment to generate an electronically saturated complex in
a similar fashion to the Cp*Ru(PR3)X (where X = Cl, Br, I,
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OR, NR)16,21,45,64 but differs in that the donation originates
from a π-system on the imidazole rather than a lone pair on an
anionic X atom. While π-donation is not needed to generate a
16-electron cationic Cp*Ru species, as seen with Cp*Ru(P−
P)+ and Cp*Ru(N−N)+ complexes, the competent π-donating
ability of imidazole65,66 likely leads to a higher level of stability
for complexes 5 and 6.
Scheme 2. Reactions of 5 with Ethylene and Propylene
It should be noted that the bulk of the tert-butyl group on
the N-methyl-4-tert-butylimidazole moiety also contributes to
the persistent 16-electron nature of 5 and 6 in solution.
Complexes 9 and 10, formed by ionization of 7 and 8,
resolved, consistent with four unique methyls in 11 and
strongly implicating one ethylene and chelated PN ligand.
Binding of Propylene Forming Two Diastereomers. When
propylene is introduced to a solution of 5, the blue color
lightens considerably, and NMR data at low temperatures
(≤−30 °C) are consistent with a mixture of two diastereomers,
12 and 13 (Scheme 2), as the major species in a roughly 4:1
ratio. Signals corresponding to the minor diastereomer are
broader but become sharper around −60 °C. For the two
major species, at all temperatures, the imidazole C−H signal in
the 1H NMR spectra as well as the singlet in 31P NMR spectra
shift upfield relative to those of complex 5; moreover, the
isopropyl C−H protons appear as two distinct signals,
signifying a desymmetrization of the complex consistent with
binding of the propylene. In addition, between −40 and −60
1
respectively, lack the tert-butyl group. Although the H NMR
spectra of 9 and 10 also appear symmetrical at room
temperature, they lack the characteristic blue color that is
prevalent in the 16-electron Cp*Ru complexes and likely
undergo rapid reversible binding of solvent. Whether the
difference in behavior is due to steric or electronic properties
of the tert-butyl group is not clear.
The LUMO of complexes 5 and 6, on the other hand, is
antibonding with respect to the ruthenium and the π-system of
the imidazole, much like in complex 3. The LUMO resides
mostly on the ruthenium (56% for both 5 and 6), suggesting
that if an incoming ligand binds to the metal and its electrons
populate the LUMO, the π-bonding interaction could be
severed to establish a coordinatively saturated complex that
retains its 18-electron count. The flat and diffuse shape of the
LUMO appears to be ideal to accommodate the π-orbital of an
alkene as opposed to a lone pair on a solvent molecule.
Evidence of the alkene−metal LUMO interaction for catalyst 5
can be seen in the spectrometric changes that occur upon
addition of alkenes to solutions of the catalyst, which can
provide direct indications of the behavior for isomerization
with 5.
1
°C, 3 additional signals in H NMR spectra begin to resolve
(one broad and two doublets) between 2.5 and 3.8 ppm that
integrate to one proton each for the major species. These new
signals could represent the alkene C−H peaks for bound
propylene, although no crosspeaks are observed between these
signals in 2D COSY NMR spectra. To obtain definitive
evidence for alkene binding in both diastereomers, a mixture of
triply labeled (13C)3-propylene and 5 was prepared. Figure 5
Studies of Alkene Binding. Using NMR and UV−vis
spectroscopies, clear evidence of alkene binding can be seen
with small alkenes such as ethylene and propylene, providing
insights into the structure of alkene complexes formed using
complex 5. Furthermore, the interaction of hexene isomers
with 5 provides compelling insight into the selectivity of
isomerization.
Binding of Ethylene. The most prominent feature of a UV−
visible spectrum of catalyst 5 is a broad, intense absorbance
with a maximum of 582 nm, which is responsible for its deep
blue color. Time-dependent density functional theory calcu-
lations of the complex ascribe this absorbance to two major
transitions: HOMO→LUMO and HOMO−1→LUMO, which
are both metal-to-π* (Ru-imidazole) transitions. If the LUMO
is populated by an incoming ligand such as an alkene, the
transitions should be quenched, and the blue color should
diminish as the complex attains 18 electrons. These changes
are clearly observed when ethylene is bubbled through a
solution of 5: the solution changes color from deep blue to a
light yellow, and there is almost complete bleaching (96%
reduction) of the absorbance at 582 nm.
Figure 5. Signals assigned to the methyl of bound propene in 12 and
13. Shown is the aliphatic region (21 to 25 ppm) of the 13C NMR
spectrum (150.7 MHz, acetone-d6) of a solution of (13C3)-propylene
and 5.
shows the 13C NMR signals for the carbon of the −CH3 group
(R1 or R2 in Scheme 2) for bound propylene. The larger,
upfield signal at 22.9 ppm is roughly four times larger than the
broader downfield signal at 23.8 ppm (and the methyl group
for free propylene appears at 19.7 ppm).
Binding of Hexene Isomers and Their Transformation. For
5 to accomplish (E)-selective monoisomerization of most
alkene substrates, the rate of isomerization of 1- to (E)-2-
alkene must be much higher than that of the (E)-2- to (E)-3-
alkene transformation. The kinetic preference of the first
isomerization over the second could be linked to either
binding/release of the alkene from the catalyst or an
1H NMR data for the species formed from 5 and ethylene
are fully consistent with structure 11 (Scheme 2), which is an
18-electron complex containing a single bound ethylene. In the
1H NMR spectrum, the ethylene signal is visible as a broad
signal centered at 2.45 ppm. When the sample is cooled to −30
°C, 4 separate ethylene C−H signals are visible, ranging from
2.1 to 3.5 ppm, which become sharper upon further cooling.
Two isopropyl C−H and four isopropyl-CH3 peaks are also
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intermediate step in the mechanism, or both. Both NMR and
UV−visible spectroscopy allow characterizing the binding of
catalyst and hexene isomers, elucidating binding contributions
to selectivity, and potentially identifying steps in the catalytic
cycle.
The visible behavior of the catalyst in the presence of larger
isomerizable alkenes such as 1-hexene is more complex than
when ethylene is present. When the isomerization of 1-hexene
is performed with catalyst 5, the solution is initially lighter in
color but still retains a blue coloration. As the reaction
proceeds, the blue color deepens, typically reaching its
maximum when the 1-hexene amount is minimized. When
the reaction was observed using UV−vis spectroscopy (Figure
6, top), a significant drop in the absorbance at 582 nm occurs
While UV−vis spectroscopy illustrates differences between
the interactions of 1- and (E)-2-hexene with 5, NMR
spectroscopy should allow for simultaneous determination of
both catalyst and alkene concentrations. As detailed below, we
are unable to identify signals for bound hexene in the NMR
spectra, but fortunately, we can use readily identifiable catalyst-
derived signals assigned to alkene complexes and large signals
for free alkene. Changes in the intensity and position of catalyst-
derived signals provide useful information on relationships between
catalyst, alkenes, and alkene complexes. Careful 1H NMR
spectroscopic analysis of the isomerization of 1-hexene at
room temperature and at −40 °C reveal both markedly
different binding behavior and product distribution, which
provides support for the hypothesis that relative binding
affinities of various alkene isomers have a strong influence on
product selectivity.
1
In the H NMR spectrum of the isomerization of 1-hexene
with 5 at room temperature (Figure 7), the chemical shifts of
Figure 6. UV−visble spectra of 5 before and after addition of hexenes.
Top: 5 with 200 equiv of added 1-hexene monitored every 2−10 min.
Bottom: 5 with 200 equiv of added (E)-2-hexene monitored every 2−
10 min, starting 4 min after addition.
when 1-hexene is introduced, and then throughout the course
of the next 30 min, the intensity of the absorbance partially
recovers.
We attribute the initial decrease in absorption to binding of
1-hexene to the complex, which populates the LUMO and
quenches the metal-to-LUMO transition and therefore the
absorbance at 582 nm, as was the case with ethylene. As the 1-
hexene is consumed, the absorbance intensity partially returns,
suggesting an increase in amount of free complex (Figure 6
top); we hypothesize that the (E)-2-hexene product does not
bind as favorably as 1-hexene to the catalyst. Further evidence
for the hypothesis is that in a separate experiment, addition of
(E)-2-hexene to a solution of 5 produces essentially no drop in
absorbance (Figure 6 bottom). A scenario in which 1-hexene
binds to catalyst to a greater extent than (E)-2-hexene may
explain why 5 isomerizes 1- to (E)-2-hexene faster than (E)-2-
to (E)-3-hexene. Significantly, the fact that ethylene completely
bleaches the 582 nm absorbance whereas 1-hexene reduces the
absorbance by only ∼20% after 4 min suggests strongly that
significant amounts of catalyst remain uncomplexed even in
the presence of 200 equiv of 1-hexene.67
Figure 7. Stacked 1H NMR spectra (500 MHz, acetone-d6) of the first
90 min of isomerization of 1-hexene (0.5 M) with 0.3 mol % 5. Top:
Vinyl region indicating relative amounts of 1- and (E)-2-hexene.
Bottom: Signal for C−H of imidazole.
protons associated with the catalyst monotonically change as
the isomerization occurs. The changes suggest that the
observed signal may arise from more than one species in fast
equilibrium and that the concentrations of alkenes and their
complexes are changing.
To slow alkene exchange and observe discrete alkene signals,
data were acquired at −40 °C. The isomerization progress and
catalyst monitoring are seen in Figure 8. Several significant
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Figure 9. First 90 min of isomerization of 1-hexene (0.5 M) with 0.3
mol % 5 at room temperature. Graph of conversion of 1-hexene into
(E)-2-hexene and the Δδ of C5−H signal of the imidazole ring on the
PN ligand, where Δδ is the difference in chemical shift from that of
free catalyst 5 (see text).
analogy to reaction at −40 °C, there are two alkene complexes
early in the reaction as well as free catalyst 5. The two alkene
complexes are bound 5(1-hexene) complex (14 and 15, Chart
4) because the data suggest that formation of 5((E)-2-hexene)
Chart 4. Putative Observed Alkene Complexes in Low-
Temperature (−40 °C) Isomerization of 1-Hexene
Figure 8. Isomerization of 1-hexene (0.5 M) at −40 °C (500 MHz,
acetone-d6) using 1.2 mol % 5. Starting with the 0 min time point, the
labels at right are for every other time point. Top: Vinyl region
indicating relative amounts of 1- and (E)-2-hexene. Bottom: Signal for
C5−H of imidazole of catalyst-derived species.
complex (16, Chart 4) is not nearly as favorable: the value of
Δδ is largest when a large excess of 1-hexene is present early in
the reaction and small and even zero when a large excess of
(E)-2-hexene present.
differences are apparent, most notably the decoalescence of the
single signal for the imidazole C5−H. Initially, two major
signals are present at 7.04 and 7.18 ppm in roughly a 2:1 ratio
(Figure 8). While free catalyst 5 could be responsible for one
of the two signals, the intensity of the signals does not vary
much before 500 min, at which time both begin to decrease as
a signal at 7.19 ppm emerges. Because alkene binding in the
equilibrium 5 + alkene ⇆ 5(alkene) should be more favorable
entropically at lower temperatures, we instead assigned the
7.04 and 7.18 ppm signals to two different diastereomers of
5(1-hexene) (14 and 15, Chart 3), and the emerging 7.19 ppm
signal to 5((E)-2-hexene) (16, Chart 3).68a,b
Then, we analyzed the room temperature data using what is
observable at −40 °C. In the lower part of Figure 7, the
uppermost trace shows the C5−H signal for pure 5.
Observable 3 min after addition of 1-hexene, at which time
55% of the 1-hexene remains, is a broad signal with an upfield
shift of 0.089 ppm relative to the signal for free 5 (Figure 9).
The C5−H signal continues to migrate downfield as the
reaction progresses with the Δδ (the difference in chemical
shift from that of free catalyst 5) becoming smaller until the
reaction time approaches 40 min, after which Δδ does not
change. Notably, the measured value for the chemical shift for
the imidazole signal at the 40 min point (7.277 ppm) is only
0.002 ppm less than the signal for 5 in the absence of alkene
and hence experimentally identical. We hypothesize that in
At room temperature, the rate of decrease in Δδ mirrors the
rate of conversion of 1-hexene (Figure 9), which suggests that
the concentration of the complexes are linked to the
concentration of 1-hexene. If the observed imidazole CH
chemical shift is a weighted average of the individual chemical
shifts of protons in 5, 14, and 15,69 the relative concentrations
of 5 and the alkene components can be determined by
comparing the chemical shifts of intact catalyst 5 and of 5(1-
alkene) (Δδ/Δδ100%). To establish the chemical shift value for
100% bound complex, we used the weighted average (7.09
ppm) of the chemical shifts for the two imidazole C−H signals
of complexes 14 and 15, as measured at −40 °C.
At room temperature, at the first time point (3 min) when
55% of 1-hexene remains, Δδ is ∼47% of its maximum, which
suggests 47% complexation and 53% free 5 despite a ∼150-fold
excess of 1-hexene at this time point. The ratio of [1-hexene]/
[14 + 15] remains consistent at ∼350:1 until <10% of 1-
hexene is left. Considering the constancy of the ratio, we
project that ∼90% of the catalyst contains bound alkene
initially (when 100% of original 1-hexene is present, S/C ratio
would be 333) and ∼87% when 96% 1-hexene remains for a
calculated value of 14 for Kb(1‑hexene) = ([14 + 15]/[5][1-
hexene])
When the maximum amount of (E)-2-hexene is reached
(96%), Δδ is around 1% of the maximum value, which suggests
that 99% of catalyst is free of alkene. If the assumption is that
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all of the alkene complexes are of (E)-2-hexene (even though
this is not likely due to much more favorable binding of 1-
hexene), we can establish an upper limit to the equilibrium
binding constant for (E)-2-hexene (Kb((E)‑2‑hexene) = ([16]/
[5][(E)-2-hexene]), which is calculated to be ∼0.02. Thus, the
ratio of Kb(1‑hexene)/Kb((E)‑2‑hexene) is evaluated to be at least
700:1 by this chemical shift perturbation method.
coordination, but further work will be needed to evaluate our
hypothesis., Finally, the signal at 7.19 ppm representing
complex 16 (5((E)-2-hexene)) grows in when the amount of
1-hexene has dipped below 20% of its initial value.
A comparison of the relative stabilities of 14 + 15 and 16
(and therefore the relative binding affinities of 1-hexene and
(E)-2-hexene) can be made by comparing the composition of
the mixture of hexene isomers when the concentrations of
bound 1-hexene and (E)-2-hexene are equal. At 715 min, the
sum of the intensities of the signals at 7.04 and 7.18 ppm
roughly equals the intensity of the signal at 7.19 ppm. At that
point, the percentages of 1-hexene and (E)-2-hexene are 1.5
and 92.1%, respectively. We conclude that there is a 61-fold
higher binding affinity for 1-hexene with 5 at −40 °C. This
ratio is lower than that calculated at room temperature
(∼700:1) with the caveat that the two methods used to
determine the ratios are not the same.
Then, we turned to further analysis of the data acquired at
−40 °C. Figure 10 shows graphs of the conversion of 1-hexene
Systematic experimental comparisons of the binding of
alkene isomers are rare, and such a study of binding to
+
CpRuL2 appears to be nonexistent; however, there are a fair
number of studies with other metal fragments that compare a
greater alkene steric and electronic diversity.70 One approach is
to determine binding equilibria L−M + alkene ⇆ (alkene)M +
L. Two-coordinate L−M = (nitrile)Au(NHC)+ species do not
seem to discriminate much in displacements.71 Keq values
follow: 1-hexene 25, propene 6.8, and trans- and cis-butene
12.5 and 38, respectively. Perhaps the closest study sterically to
our case are five-coordinate species (nitrile)Pd(PPh3)(Cp)+.72
Keq values follow: ethylene 13.5, propylene 1.14, and trans- and
cis-2-butenes 0.04 and 0.22, respectively. Of particular note is
the ratio of Keq values for propylene and trans-2-butene: 28.
Our hypothesis is that our six-coordinate complexes 5(alkene)
bearing rather bulky ligands are likely even more sensitive to
alkene sterics. In support of this idea, we note Tolman’s study
of NiL3 + alkene ⇆ (alkene)NiL2 + L, where L = P(O-ortho-
tolyl)3.73 Keq values follow: 1-hexene, 0.5 and trans- and cis-2-
hexenes, 0.0027 and 0.0022, respectively. Here, the selectivity
for 1-hexene over (E)-2-hexene is 185:1.
To add insight as to why the binding affinity of (E)-2-hexene
relative to that of 1-hexene should increase as temperature
decreases, we computed the free energies and enthalpies of
alkene and nitrile binding (Table 6). The difference in binding
Figure 10. Isomerization of 1-hexene (0.5 M) at −40 °C using 1.2
mol % 5 in acetone-d6. Top: Relative percentages of 1-hexene, (E)-2-
hexene, and (E)-3-hexene over time. Bottom: Intensities of signals at
7.19, 7.18, and 7.04 ppm corresponding to imidazole C−H signal for
1- and (E)-2-hexene complexes.
Table 6. Computed Free Energies and Enthalpies of Binding
with Catalyst/Alkene Complexes
at −40 °C along with the relative intensities of the C−H
imidazole signals for the three alkene complexes. The rate of
conversion of 1-hexene at −40 °C is unchanged over the first
500 min with a fit to linearity of R2 = 0.997, which means that
the rate is independent of the concentration of 1-alkene. The
likely reason is that the catalyst is saturated with bound alkene
throughout the first 500 min. Interestingly, the changes in the
concentrations of the two 1-hexene complexes differ: the
integration of the C−H signal at 7.18 ppm remains unchanged
throughout the first 500 min, which would have to be constant
if d(1-hexene)/dt = k[5]. In contrast, the integration of the
signal at 7.04 ppm decreases throughout the reaction. Because
in only one of the diastereomers (15) does the allylic position
appear to be in the right location to be deprotonated by the
pendent imidazole, the other diastereomer 14 may not convert
directly to product; we tentatively assign the 7.18 ppm signal
to 15 and the 7.04 ppm signal to 14 where the latter may have
to convert to the former through alkene decoordination−
a
a
free energy (kcal/mol)
enthalpy (kcal/mol)
catalyst
1-hexene
(E)-2-hexene
1-hexene
(E)-2-hexene
b
1-CH3CN
11.4
6.1
10.4
4.1
17.0
14.1
10.7
16.0
13.5
8.7
5
6
2.7
0.3
a
Gas phase calculation at 298 K. All values are relative to those for
encounter complexes of alkene and catalyst. Without acetonitrile; Cp
analogue of 5 that has yet to be detected or identified experimentally.
b
free energies of 1-hexene and (E)-2-hexene with 5 at room
temperature (2.0 kcal/mol) is larger than the enthalpy
difference (0.6 kcal/mol); therefore, as the entropic term
decreases (i.e., at lower temperatures), the difference in
binding affinity should decrease, as suggested from experiment.
If positional selectivity is largely dictated by differences in
binding affinities of terminal and internal alkenes, then
isomerization should be less positionally selective at lower
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temperatures provided the binding affinities are more similar,
as suggested by computational and spectroscopic analysis.
Evidence for this hypothesis is reflected in the lower selectivity
for the formation of (E)-2-hexene at −40 °C with a maximum
yield of (E)-2-hexene of 92% as opposed to 96% at room
temperature. While other steps during the catalytic cycle can
also play a factor in determining the relative rates of
isomerization for the 1- to (E)-2-alkene and the (E)-2- to
(E)-3-alkene, binding affinities clearly provide a strong
contribution to the positional selectivity during catalysis with
5, perhaps because 5 does not need to lose a ligand.
Alkene complex 5(1-hexene) is computed to be 2 kcal/mol
more stable than isomeric 5((E)-2-hexene) for a ratio of 29:1
at 298 K. The 2 kcal/mol free energy difference is greater than
the analogous difference for isomeric alkene complexes of
catalyst 1 (1 kcal/mol) but less than for complexes of 6 (2.4
kcal/mol). The selectivity of the catalysts (6 ≈ 5 > 1) mirrors
the calculated preferences for 1-alkene binding (6 ≈ 5 > 1).
Moreover, catalyst 1 had the largest computed binding
affinities for both alkenes, while 6 exhibited the smallest.
Substantiating the assumption that a favorable binding
equilibrium leads to a higher rate of catalysis, the trend for
binding affinities (1 > 5 > 6) also reflects the conversion rate,
at least for the 1-alkene. The computational results show
strong support for both the relative selectivities and relative
rates of catalysts 1, 5, and 6. Future work will explore
individual mechanistic steps other than alkene binding using
computations and kinetics.
Characterization of Allyl Intermediate. As shown in
binding studies with ethylene, propylene, and 1-hexene, the
coordinatively unsaturated nature of 5 provides for direct
spectroscopic observation of alkene complexes. We aimed to
find direct evidence for another key intermediate in the
catalytic cycle that is consistent with the bifunctional
mechanism proposed by ourselves38,41 and Fang74 in which
the phosphino-imidazole ligand acts as a pendant base,
shuttling an allylic proton between carbons.
In addition to the major NMR signals that are assigned to 12
and 13 when introducing propylene to 5, a number of small 1H
NMR signals corresponding to other minor species are present
and are more noticeable at the reduced temperatures. Table
S69 summarizes 1D and 2D 1H, 13C, and 15N NMR data, from
which we conclude that 12, 13, and 17 (R = H) can be formed
in a ratio of approximately 4:1:1 (where the assignment of
which signals belong to 12 and which to 13 is uncertain at this
time). In the proposed intermediate (see structure 17, R = H
in Scheme 3), the imidazole is protonated by the propylene,
generating an allylic anion stabilized by the metal. One
indication of 17 would be the presence of a downfield signal in
the 1H NMR spectrum corresponding to the N−H peak of the
protonated imidazole as well as downfield shift of the
imidazole CH proton. At low temperatures (−30 to −60 °C,
Figures S75−S86), both a downfield shifted CH singlet at 7.75
ppm and a very downfield singlet assigned to the N−H proton
are present at 12.4 ppm, which splits into a doublet (J = 100
Hz) when an 15N-labeled ligand is used. The 12.4 ppm doublet
is ascribed to the 15N-H of an unchelated and protonated
imidazole.75 Further analysis of the mixture by 2D NMR leads
to identification of most of the signals ascribable to 17 (Table
S69 and Figure S96). However, because of the presence of
multiple species (including the allyl, as one of the minor
species) with overlapping peaks, assignment of the allyl
protons and carbons remained tentative. Stronger direct
evidence for allyl ligand signals was made possible by using
(13C)3-propylene in 17:1 molar ratio with 5. At −40 °C, 3 sets
of multiplets are visible in the 13C NMR spectrum that can be
ascribed to propylene-derived species: the first largest set at
134, 116, and 19 ppm from excess free propylene, the second
set at 68, 60, 59, and 23 ppm ascribed to bound propylene
complexes 12 and 13 (Scheme 2, and Figure 7), and a third,
1
1
smaller set at 88 (t, JCC = 44.7 Hz), 45 (d, JCC = 44.7 Hz),
and 41 (d, JCC = 44.7 Hz) ppm76 associated with the allyl
1
species 17 (Figures S88−S94 and discussion in captions). The
allyl complex and free propylene sets of signals are quite sharp,
whereas the bound propylene signals are somewhat broad.
CONCLUSIONS
■
In summary, the coordinatively unsaturated Cp*Ru catalyst 5
provides the same exceptionally high selectivity for (E)-2-
alkenes as catalyst 2 + 2a with yields usually exceeding 95% but
with a dramatic increase in reaction efficiency (>400 times
faster). Expeditious isomerization occurs at room temperature
with practical loadings of 0.1 to 0.5 mol % for most substrates,
and commercial-grade substrates can be used after a simple
deoxygenation. The binding and reactivity studies of 5 with
alkenes, combined with computational modeling, depict the
imidazole moiety on the diisopropyl(2-methyl-4-tert-
butylimidazolyl)phosphine ligand as a hemilabile 4-electron
donor. For the first time, we appreciate the full versatility of the
pendent imidazole, which can change from 4-electron donation
in 5, where both the basic nitrogen lone pair and the imidazole
π-system donate to the ruthenium, to 2-electron donation in
18-electron species such as alkene complexes derived from 5
and zero donation in allyl complex 17, in which the imidazole
is protonated, a range that is unique in Cp*Ru(L)X chemistry
where L = P or N and X = P, N, or halide. In 5, breaking the
Ru−N bond of the κ2-P,N ligand provides two coordination
sites for the allyl intermediate that is formed during catalysis,
characterized here for the first time. UV−vis spectral data in
conjunction with low- and room-temperature NMR data and
kinetic analysis and computations have provided some initial
insights into the role of alkene binding in achieving selectivity
for monoisomerization. For the first time, we present direct
experimental evidence in the form of 17 (R = H) for formation
of an allyl complex from an alkene with protonation of the PN
ligand. A more comprehensive mechanistic study of the
isomerization mechanism, including not just alkene binding
and allyl formation but alkene and allyl transformation steps on
catalysts, is ongoing and will be reported in due course.
Scheme 3. Binding Modes of Imidazolyl Moiety and
Alkene/Allyl Ligand
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Research Article
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ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acscatal.8b04345.
■
S
Synthetic and testing procedures, NMR and UV−vis
spectral data, isomerization data, and computational data
(PDF)
Crystallographic information for [Cp⧧RuCl]4 (CIF)
Crystallographic information for 3 (CIF)
Crystallographic information for 5 (CIF)
Crystallographic information for 6 (CIF)
Crystallographic information for 7 (CIF)
Crystallographic information for 8 (CIF)
AUTHOR INFORMATION
Corresponding Author
*E-mail: dbgrotjahn@sdsu.edu.
ORCID
Curtis E. Moore: 0000-0002-3311-7155
David P. Pullman: 0000-0002-0437-5876
Douglas B. Grotjahn: 0000-0002-2481-7889
■
Notes
The authors declare the following competing financial
interest(s): Catalyst 5 is covered by US Patent 9708236
(July 18, 2017) on which D.B.G. and E.R.P. are two of the
inventors, but it is not currently sold commercially.
ACKNOWLEDGMENTS
■
We would like to thank Braden Silva for his advice and training
for the computational chemistry and Drs. LeRoy Lafferty and
Bennett Addison for their assistance as directors of the San
Diego State University NMR facility. We also thank Thomas
Chi Cao for first identifying alkene complexes in reaction
mixtures using complex 1 (manuscript in preparation).
Experimental work was supported by NSF Awards CHE-
1059107, CHE-1464781, and CHE-1800598. Computational
work is made possible by support from CHE-0947087.
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consistent with an equilibrium 5 + L ⇄ 5(L) (L = solvent or water)
being entropically favored at lower temperatures. Further work would
be needed to clarify. Nonetheless, here we can use the assignment of
the 7.19 ppm signal exclusively to 5((E)-2-hexene) to give an upper
bound for the amount of this internal alkene complex. (b) Just as
there can be two diastereomers of 5(1-hexene), for which we have
some experimental evidence, there can be two diastereomers of
5((E)-2-hexene). The single diastereomer 16 is shown because it
could reasonably arise from 15 through an allyl intermediate, but the
second diastereomer (neither pictured nor numbered) may be
present. At this time, we have not detected two diastereomers of
5((E)-2-hexene), but further work may do so.
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(76) (a) Inspection of structures suggests that in 17 (R = H), the
PN ligand is rotated so that the two ends of an η3-CH2CHCH2 ligand
would be magnetically inequivalent, and at low temperatures needed
to resolve NMR signals, we hypothesize that rotation of the bulky
7231
DOI: 10.1021/acscatal.8b04345
ACS Catal. 2019, 9, 7217−7231