Unexpected CNN-to-CC Ligand Rearrangement in Pincer-Ruthenium Precatalysts Leads to a Base-Free Catalyst for Ester Hydrogenation

Article abstract of DOI:10.1021/acs.organomet.9b00373

We report the conversion of a series of CNN-pincer-ruthenium complexes Ru(CNN)HCl(CO) to a CC-chelated form Ru(CC)(PR₃)₂H(CO) on reaction with sodium tert-butoxide and monodentate phosphines. When the phosphine is triphenylphosphine, cis-phosphine complexes form at room temperature, which convert to the trans isomer at elevated temperatures. When the phosphine is tricyclohexylphosphine, only the trans-phosphine isomer is observed. The CC-chelated complexes are active catalysts for the hydrogenation of esters, without the need for added base. The ligand structure-activity relationship in the series of CC-chelated complexes mirrors that in the precursor CNN-Ru complexes, potentially indicating a common catalytic mechanism. Density functional theory calculations establish a plausible mechanism for the CNN-to-CC rearrangement and demonstrate that this rearrangement is potentially reversible under the conditions of ester hydrogenation catalysis.

Full text of DOI:10.1021/acs.organomet.9b00373

Article
pubs.acs.org/Organometallics
Cite This: Organometallics XXXX, XXX, XXX−XXX
Unexpected CNN-to-CC Ligand Rearrangement in Pincer−
Ruthenium Precatalysts Leads to a Base-Free Catalyst for Ester
Hydrogenation
Linh Le, Jiachen Liu, Tianyi He, Jack C. Malek, Tia N. Cervarich, John C. Buttner, John Pham,
Jason M. Keith,* and Anthony R. Chianese*
Department of Chemistry, Colgate University, 13 Oak Drive, Hamilton, New York 13346, United States
*
S Supporting Information
ABSTRACT: We report the conversion of a series of CNN−pincer−
ruthenium complexes Ru(CNN)HCl(CO) to a CC-chelated form
Ru(CC)(PR ) H(CO) on reaction with sodium tert-butoxide and
3
2
monodentate phosphines. When the phosphine is triphenylphosphine,
cis-phosphine complexes form at room temperature, which convert to
the trans isomer at elevated temperatures. When the phosphine is
tricyclohexylphosphine, only the trans-phosphine isomer is observed.
The CC-chelated complexes are active catalysts for the hydrogenation
of esters, without the need for added base. The ligand structure−
activity relationship in the series of CC-chelated complexes mirrors
that in the precursor CNN-Ru complexes, potentially indicating a common catalytic mechanism. Density functional theory
calculations establish a plausible mechanism for the CNN-to-CC rearrangement and demonstrate that this rearrangement is
potentially reversible under the conditions of ester hydrogenation catalysis.
INTRODUCTION
with N-Me, N-Bn, or O is highly detrimental to cataly-
■
5d,f,h,6b,h,9
6g,7k
sis,
some systems are similarly active
or more
The catalytic hydrogenation and dehydrogenation of polar
substrates have advanced significantly in the past decade since
the reports of Milstein and co-workers describing a PNN−
pincer−ruthenium complex that is active under mild
conditions for the hydrogenation of esters and the reverse
reaction, dehydrogenation of primary alcohols to give esters.
10
active when N−H is substituted with N-Me. Ester hydro-
genation catalysts have also been reported that feature no
obvious acidic sites on the ligand.
6c,7h,11
To facilitate the
1
development of improved catalysts, it is clearly of continued
importance to probe the relationship between catalyst
structure and activity in ester hydrogenation and related
hydrogenations of polar bonds and to work to understand the
potentially complicated and varied catalytic mechanisms.
Several groups have reported catalysts for ester hydro-
genation or the reverse reaction based on pincer N-
heterocyclic carbene (NHC) ligands, as shown in Chart
2
In this work, it was demonstrated that a CH linker on the
2
pincer ligand can be reversibly deprotonated. This acid/base
reactivity of the ligand was proposed to be involved in metal−
ligand cooperative activation of dihydrogen and transfer to
polar substrates, analogous to the historically significant
catalytic systems of Shvo and Noyori for ketone and imine
hydrogenation.
3
4
5d,12
1
.
Each catalyst has the possibility of reversible ligand
deprotonation, either at an N−H group or CH linker. For
2
Since Milstein’s 2006 disclosure, many transition-metal
catalysts for ester hydrogenation have been reported, including
eight we are aware of that give at least 10,000 turnovers at full
their CNN-Ru catalysts, Song and co-workers observed
stoichiometric deprotonation at the CH linker arm connecting
2
12c
5
the NHC and pyridine rings. Computations indicated that
deprotonation at the alternate linker arm connecting the
substrate conversion. These highly active catalysts employ
ruthenium or osmium and feature ligands designed with the
metal−ligand cooperative mechanism in mind. Although the
availability of detailed experimental mechanistic information is
pyridine and NEt groups was less favorable by 9 kcal/mol.
2
We have reported a series of CNN−pincer ruthenium
catalysts for ester hydrogenation, which differs from those of
5
c,6
limited,
computation has offered additional insight into
5
a,c,6b,d,f,7
Song and San
directly linked, so that the only available site for ligand
deprotonation is the CH linker between the pyridine and NR
́
chez in that the pyridine and NHC rings are
questions that are not easily probed experimentally.
Recently, the long-accepted involvement of reversible ligand
deprotonation as an integral part of the catalytic cycle has been
called into question, both for the Noyori ketone hydrogenation
2
2
13
groups. A detailed study of the effect of ligand structure on
7
k,8
system and for ester hydrogenation catalysts featuring N−H
6
g,7k
functionality.
Although many examples exist where
Received: June 3, 2019
synthetic elimination of the N−H functionality by replacement
©
XXXX American Chemical Society
A
DOI: 10.1021/acs.organomet.9b00373
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Article
1
2c
Chart 1. Pincer−NHC Catalysts for Ester Hydrogenation
stituted variant gave a mixture of products. For this complex,
a clean deprotonation of the CH linker between the NHC and
2
pyridine rings was observed when PPh was also added to the
3
reaction mixture, allowing formation of a coordinatively
saturated species.
When we combined the yellow pincer−ruthenium complex
t
Ru-dipp-Et with an excess of NaO Bu and pyridine in
benzene-d at room temperature, we observed rapid formation
6
of a homogeneous, red solution, which contained the
anticipated dearomatized species Ru-dipp-Et-pyr, shown in
Scheme 1, as the major species. While we have characterized
t
Scheme 1. Reaction with NaO Bu and Pyridine
1
this complex in solution by H NMR, COSY, and NOESY, it
decomposed slowly at room temperature, and we were not able
to isolate it.
1
The H NMR spectrum of Ru-dipp-Et-pyr shows the lack of
symmetry expected for the chiral-at-metal complex shown: four
catalyst activity showed that activity increased with increasing
14
steric bulk on the NHC substituent. A striking effect of the
i
doublet signals are observed for the isopropyl CH groups, two
3
amine substituent was also observed, as NEt or N Pr groups
2
2
septets are observed representing the isopropyl methine
hydrogens, and the two N-ethyl groups are diastereotopic.
Signals for Ru-bound pyridine are not observed, which is
consistent with fast exchange between free and bound pyridine
at room temperature. The Ru-bound hydride is observed at
gave high activity while an NMe2 group led to greatly
diminished activity.
In an effort to understand the catalytic mechanism, we began
studying the stoichiometric reactivity of the precatalysts in the
t
presence of the strong base, NaO Bu, required for catalyst
−
13.56 ppm. A NOE signal is observed between the hydride
activation. In addition to the anticipated deprotonation of the
and one isopropyl CH group, consistent with the coordination
3
CH linker arm, we also observed an unexpected rearrange-
2
geometry shown in Scheme 1. The upfield shifts of the
ment of the complex, where the CNN−pincer ligand converts
to a CC-chelating form through C−H activation of the
pyridine ring. In this Article, we report the isolation of a series
of these rearranged ruthenium complexes and their application
as catalysts for ester hydrogenation. We find that the CC-
chelated catalysts are effective without the need for a basic
additive. Importantly, the structure−activity relationship
mirrors that of the precursor CNN−Ru precatalysts,
potentially indicating a common catalytic mechanism. Through
computation, we present an energetically plausible mechanism
for the rearrangement and establish that the CNN and CC
forms of the catalyst are thermodynamically similar, indicating
that either form is thermally accessible under our catalytic
conditions.
resonances on the pyridine ring are consistent with
dearomatization.
Interestingly, cross-peaks indicative of chemical exchange
were observed by NOESY for resonances representing the
diastereotopic N-ethyl groups of Ru-dipp-Et-pyr. This
2
,12c
observation is consistent with dechelation of the NEt group,
2
inversion about nitrogen, and recoordination to exchange the
environments of the two ethyl groups.
t
CNN-to-CC Rearrangement with NaO Bu and PPh .
3
When we combined the pincer−ruthenium complexes Ru-
t
Mes-Et and Ru-dipp-Et with an excess of NaO Bu and PPh in
3
toluene at room temperature, we initially observed complex
mixtures, each of which converged to one product overnight.
We identified these products as the CC-chelated complexes
shown in Scheme 2, where the pyridine and amine nitrogen
RESULTS AND DISCUSSION
■
Formation of Dearomatized CNN-pincer Ligand with
t
t
Scheme 2. Reaction with NaO Bu and PPh
3
NaO Bu and Pyridine. Since our CNN−pincer−ruthenium
precatalysts for ester hydrogenation, shown in Chart 1, require
the addition of a strong base for activation, we began by
studying the reactivity of these hydridochloride complexes with
t
strong bases such as NaO Bu and KN(SiMe ) . These
3
2
reactions gave intractable mixtures of ruthenium-containing
products for several of our precatalyst variants. Song and co-
workers noted a similar issue in their work: their 2,6-
diisopropylphenyl-substituted variant (see Chart 1) cleanly
gave a five-coordinate species featuring a deprotonated,
dearomatized CNN−pincer ligand, while the mesityl-sub-
B
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Article
donors have dissociated, and a pyridine C−H bond has been
activated. C−H cyclometalation of pyridine rings is quite
common and has been observed before in closely related
systems. Liang and Song observed a similar CC-chelating
binding mode in pyridine−NHC complexes of ruthenium and
Et-PPh , indicating that one phosphine ligand is trans to the
NHC.
3
Cis−Trans Isomerization in PPh Complexes. When
3
cis-Ru-Mes-Et-PPh3 is heated at 80 °C overnight, an
isomerization reaction occurs (Scheme 3). The product was
1
5
iron. Milstein and co-workers observed a CC-chelating
binding mode when attempting complexation of their NHC−
Scheme 3. Cis−Trans Isomerization
12b
bipyridine ligand (see Chart 1) with Ru(PPh ) HCl(CO).
3
3
The same group also observed rearrangement of a phosphine−
bipyridine PNN−pincer ligand to a PNC-binding form on
1
6
ruthenium.
The solid-state structure of cis-Ru-dipp-Et-PPh3 was
determined by X-ray crystallography. Figure 1 shows the
isolated and identified as trans-Ru-Mes-Et-PPh , where the
3
hydride and a phosphine ligand have exchanged sites with no
other rearrangement at the metal center. The crystal structure
was determined; an ORTEP diagram is shown in Figure 2. The
Figure 1. ORTEP diagram of cis-Ru-dipp-Et-PPh , showing 50%
3
probability ellipsoids. Phenyl groups and hydrogen atoms other than
the ruthenium-hydride are omitted for clarity.
molecular structure. The geometry is nearly octahedral,
distorted by a small 77.5° bite angle for the bidentate ligand
and a large 103.7° angle between the PPh ligands. The
3
arrangement of ligands around the metal center is consistent
with a lack of isomerization other than the CNN-to-CC
rearrangement: the newly added phosphine ligands occupy the
Figure 2. ORTEP diagram of trans-Ru-dipp-Et-PPh , showing 50%
probability ellipsoids. Phenyl groups and hydrogen atoms other than
the ruthenium-hydride are omitted for clarity.
3
sites vacated by the displaced chloride ligand and NEt group
2
of the reactant.
NMR spectroscopy indicates that the solution structures of
cis-Ru-Mes-Et-PPh and cis-Ru-dipp-Et-PPh are consistent
coordination geometry is again that of a distorted octahedron.
3
3
3
1
with the crystal structure of cis-Ru-dipp-Et-PPh . Two
P
The P−Ru−P angle is 145.6°, as the PPh ligands are bent
3
3
resonances are observed for each complex, with small P−P
coupling constants of 21.6 and 21.8 Hz, respectively. Each
ruthenium hydride appears as a doublet of doublets. The
coupling constants between the ruthenium hydride and
phosphorus are consistent with one phosphorus trans to H
away from the NHC moiety and toward the hydride, likely to
minimize a steric clash between the phenyl groups and the
mesityl group.
The NMR spectrum of trans-Ru-Mes-Et-PPh in solution is
3
consistent with its solid-state structure. Two equivalent
phosphorus nuclei are observed. The ruthenium hydride signal
appears as a triplet, with a 28.2 Hz coupling constant to
phosphorus. The carbonyl and carbene carbons each appear in
and one cis to H: 34.4 and 77.4 Hz for cis-Ru-Mes-Et-PPh ,
3
C
1
3
and 32.3 and 76.1 Hz for cis-Ru-dipp-Et-PPh . In the
3
NMR spectrum, each of the CO and carbene resonances
appears as a doublet of doublets due to splitting by
phosphorus. The CO carbons show two small P−C coupling
1
3
the C NMR spectrum as triplets, with P−C coupling
constants of 10.1 and 5.7 Hz, respectively.
constants: 13.2 and 6.7 Hz for cis-Ru-Mes-Et-PPh , and 10.6
When cis-Ru-dipp-Et-PPh is heated at 80 °C overnight, an
3
3
and 7.1 Hz for cis-Ru-dipp-Et-PPh , indicating that both
analogous cis−trans isomerization occurs. In this instance, an
equilibrium is established, with an approximately 1:4 ratio of
the cis isomer to the trans isomer. The ratio of isomers did not
change upon further heating, but some decomposition began
3
phosphine ligands are cis to CO. The carbene carbons each
show one small and one large P−C constant: 80.4 and 6.0 Hz
for cis-Ru-Mes-Et-PPh , and 80.4 and 6.7 Hz for cis-Ru-dipp-
3
C
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to occur. Since the trans complex was not formed cleanly, we
did not attempt to isolate it.
CNN-to-CC Rearrangement with NaO Bu and PCy .
t
3
We observed the same ligand rearrangement reaction when our
CNN−pincer ruthenium complexes were combined with
t
NaO Bu in the presence of tricyclohexylphosphine. Because
these products were observed to be highly active catalysts for
ester hydrogenation (vide infra), we prepared a series of four
such CC-chelated complexes, as shown in Scheme 4. In each
case, we only observed products where the two PCy ligands
3
were mutually trans, presumably because of the larger size of
the cyclohexyl group as compared to phenyl.
t
Scheme 4. Reaction with NaO Bu and PCy3
X-ray crystal structures were determined for three PCy3
complexes: Ru-Mes-Et-PCy (Figure 3), Ru-dipp-Me-PCy
3
3
i
(
Figure 4), and Ru-dipp- Pr-PCy (Figure 5). These three
3
complexes share the same coordination geometry, which is
analogous to trans-Ru-Mes-Et-PPh , described above. A
3
noteworthy feature of all three crystal structures of PCy3
derivatives is a significant distortion away from C symmetry,
resulting from steric interactions between the bulky PCy3
ligands and NHC aryl substituents. The lower image in Figure
s
Figure 3. ORTEP diagram of Ru-Mes-Et-PCy , showing 30%
probability ellipsoids. Cyclohexyl groups and hydrogen atoms other
than the ruthenium-hydride are omitted for clarity. The lower view
3
3
, showing the Ccarbene−Ru−Cpyridine plane horizontally,
shows the distortion away from C symmetry.
s
demonstrates this distortion. From this perspective, the mesityl
group bends upward, while the upper PCy ligand bends away
3
from it. The upper CNHC−Ru−P bond angle is 109.0°, while
the analogous lower angle is 100.1°. The distortion results in a
2
nontrivial pyramidalization of an sp -hybridized nitrogen in the
benzimidazole ring: the N-bound carbon of the mesityl group,
C(55), is 0.52 Å away from the mean plane of the NHC ring.
The analogous distance (referred to as x below) is 0.37 Å for
i
Ru-dipp-Me-PCy and 0.57 Å for Ru-dipp- Pr-PCy .
3
3
A search of the Cambridge Structural Database reveals that
17
this distortion is quite unusual. In 9130 published crystal
structures where a transition metal is bound to an NHC (based
on imidazole or benzimidazole, excluding imidazoline-based
structures with a C−C single bond in the five-membered ring),
the mean distance x is 0.081 Å with a standard deviation of
0
.070. Only seven published structures lacking disorder
contain a distance x greater than 0.50 Å. These structures
feature multidentate ligands with an unusually strained chelate
1
8
ring, a monodentate ligand where the N-substituents are part
19
of a ring fused to the NHC ring, and a monodentate ligand
with neopentyl N-substituents, which are very bulky but
20
capable of shifting to one side of the imidazole plane.
Dynamic Behavior of trans-PCy Complexes. The four
Figure 4. ORTEP diagram of Ru-dipp-Me-PCy , showing 50%
probability ellipsoids. Cyclohexyl groups and hydrogen atoms other
than the ruthenium-hydride are omitted for clarity.
3
3
PCy complexes described in the above paragraph exhibited
3
dynamic behavior in solution, as observed by NMR spectros-
copy. At room temperature, broad resonances are observed for
D
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lower phosphine moves out, is consistent with the chemical
exchange behavior observed by NMR.
Ester Hydrogenation: Catalyst Comparison. The
CNN−Ru precursors to the rearranged, CC-chelated com-
plexes described above form catalysts for ester hydrogenation
t
13,14
upon activation with NaO Bu.
Our previous ester hydro-
genation experiments were conducted at 105 °C, while the
CNN-to-CC ligand rearrangements occur at room temper-
ature. Although phosphine ligands were not added to catalytic
reactions in our previous work, it is plausible that a similar
ligand rearrangement occurs during catalysis, potentially as a
pathway for activation or deactivation. To probe for this
possibility, we tested the new CC-chelated complexes as
catalysts for the hydrogenation of ethyl benzoate.
Table 1 shows the results of this catalyst comparison. Most
of the newly synthesized complexes are effective catalysts for
a
Table 1. Comparison of CC-Chelated Catalysts
i
Figure 5. ORTEP diagram of Ru-dipp- Pr-PCy , showing 50%
3
probability ellipsoids. Cyclohexyl groups and hydrogen atoms other
than the ruthenium-hydride are omitted for clarity.
entry
[Ru]
mol %
% yield
1
2
3
4
5
6
cis-Ru-Mes-Et-PPh3
cis-Ru-dipp-Et-PPh3
Ru-Mes-Et-PCy3
0.2
0.2
0.2
0.8
0.1
0.2
>99
98
>99
29
99
98
nuclei that would be chemically equivalent if the complex
possessed a time-averaged mirror plane coincident with the
Ru-dipp-Me-PCy3
Ru-dipp-Et-PCy3
1
31
CC ligand. To characterize this dynamic behavior, H and
P
i
Ru-dipp- Pr-PCy3
NMR spectra were collected at 220 K. At this temperature, the
a
Each reaction was carried out at a range of catalyst loadings; the
lowest loading giving at least 95% yield is reported.
NMR spectra are consistent with C -symmetry. Two
1
3
1
inequivalent P resonances are observed for each complex,
and each ruthenium hydride appears as a doublet of doublets
rather than a triplet. H resonances for the ortho and meta
1
the hydrogenation of ethyl benzoate under the conditions
employed. Although the addition of a strong base was required
for the CNN−Ru precursors, these CC-chelated complexes are
active without an additive. The highest turnover number of
substituents on the N-aryl rings, mesityl or 2,6-diisopropyl-
phenyl, decoalesce, as do those for the two hydrogens on the
CH -linker. From this data, it is not straightforward to
2
determine whether the three cyclohexyl groups on each
phosphine ligand are equivalent, so it is not clear whether
rotation about the Ru−P bonds is fast or slow at 220 K.
Although it is conceivable that the low-symmetry complexes
observed at low temperature are different from the solid-state
structures determined by X-ray crystallography, cis-PCy3
990 was observed for Ru-dipp-Et-PCy ; notably, this was the
3
most effective ligand in our previous work employing the
CNN−pincer form of these catalysts, with in situ activation by
t
14
NaO Bu.
It is especially noteworthy that Ru-dipp-Me-PCy
poor catalyst for this transformation, while a simple change of
the NMe
same effect was observed in our previous work: precatalysts
with an NMe group were nearly inactive, while those featuring
forms a
3
i
species, for example, the P−P and H−P coupling constants
group to NEt or N Pr results in high activity. The
2 2 2
2
offer strong evidence against this. For the four complexes, J
PP
ranges from 195 to 206 Hz, much larger than is typical for cis-
phosphine complexes. P−H coupling constants, measurable for
Ru-dipp-Me-PCy and Ru-dipp-Me-PCy , range from 26.9 to
2
i
an NEt or N Pr group were highly active once activated with
2 2
14
t
NaO Bu. The observation of the same subtle ligand effect on
catalytic activity for both sets of complexes suggests that they
may share a common catalytic intermediate (vide infra).
Ester Hydrogenation: Substrate Scope. With the
3
3
3
5.0 Hz, consistent with the hydrides being cis to both
phosphorus ligands in each complex. We propose that the
structure in solution closely mirrors that observed in the solid
state, where the PCy ligands are nearly trans. In this case, a
identification of Ru-dipp-Et-PCy as the catalyst of choice,
3
3
motion (Scheme 5) where the N-aryl group flips from up to
down, while the upper phosphine ligand moves in and the
we studied its activity for the hydrogenation of a range of ester
substrates (Table 2). Full conversion to the alcohol products
was obtained for aromatic and aliphatic esters. The lactone
phthalide (Entry 5) was not fully hydrogenated, even at the
highest catalyst loading tested.
Scheme 5. Dynamic Process in PCy Complexes
3
The ability to hydrogenate esters in the absence of an added
6c
strong base may be useful when base has the potential to
cause undesired side reactions. For example, alkoxide bases are
known to catalyze the racemization of α-chiral esters, which
has been exploited in the dynamic kinetic resolution of racemic
9
,21
esters via hydrogenation.
However, if the ester reactant is
E
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a
7h,11,24
Table 2. Substrate Scope
“triphos” family of ligands
and the Cp*-Ir-bipyridine
6c
system recently reported by Sanford and Goldberg.
The CC-chelated complex Ru-dipp-NEt -PCy3 and its
2
analogs have no potentially basic ligand site in close proximity
to the metal, as required for the MLC mechanism. If the
ligands retained this binding mode in the catalytic cycle, an
MLC mechanism would likely not be operative, a finding that
could have broad implications for catalyst design. To probe
this possibility, we began by assessing the mechanism of the
CNN-to-CC ligand rearrangement using density functional
theory.
First, we assessed the relative thermodynamic stability at
98.15 K of four ruthenium complexes that might plausibly
2
form by reaction of Ru-dipp-Et with a strong base in the
presence of PCy (Chart 2). The species with the lowest free
3
Chart 2. Thermodynamic Comparison of Possible Products
of HCl Elimination from Ru-dipp-Et (L = PCy3)
energy is B, an 18-electron, five-coordinate, square-planar
ruthenium(0) complex formed by formal reductive elimination
of HCl from Ru-dipp-Et and addition of one PCy ligand. The
3
four-coordinate, 16-electron square-planar complex A, formed
a
by removal of PCy , is higher in free energy by 8.5 kcal/mol.
3
Each reaction was carried out at a range of catalyst loadings; the
b
The isomeric ruthenium(II) hydride complexes A-dearom and
lowest loading giving at least 95% yield is reported. The reactant (S)-
ethyl ibuprofen had >99% ee, as determined by GC.
B-dearom, resulting from deprotonation of the CH linker
2
instead of the metal center, were calculated to be higher in free
energy by 10.5 and 6.1 kcal/mol, respectively. Note that B-
dearom is structurally analogous to the spectroscopically
observed complex Ru-dipp-Et-pyr (vide supra), except that the
enantiopure, a loss of optical purity would be detrimental.
Kuriyama and co-workers have reported the use of a
preactivated catalyst in the hydrogenation of α-chiral esters
monodentate ligand L is PCy rather than pyridine.
3
22
with minimal loss of optical purity. Clarke has successfully
We then identified an energetically plausible pathway for the
conversion of B into the observed product Ru-dipp-Et-PCy3,
as detailed in Figure 6. First B converts to C by dechelation of
employed the weaker base K CO3 in Mn-catalyzed ester
2
hydrogenation, which also allows retention of chirality for α-
2
3
chiral esters. We attempted the hydrogenation of (S)-ethyl
ibuprofen, catalyzed by Ru-dipp-Et-PCy3 with no basic
additive (entry 9). Although only 86% yield was obtained at
the highest catalyst loading attempted, a minimal loss of
enantiopurity was observed, from 99% in the reactant to 98%
in the product. Further investigations of the applications of
base-free ester hydrogenation are in progress.
the NEt arm. Decoordination of the pyridine nitrogen and
2
rotation around the Nbenzimidazole−C
bond via CD-TS
pyridine
gives D, a C−H σ-complex. C−H oxidative addition then
proceeds through DE-TS to give E, a 16-electron, five-
coordinate ruthenium(II) species where the vacant site is trans
to the newly formed hydride ligand. An associatively induced
isomerization through transition-state EP-TS gives Ru-dipp-
Mechanistic Analysis of CNN-to-CC Rearrangement
by DFT. As noted in the Introduction, all of the most active
catalysts for ester hydrogenation have been designed with the
metal−ligand cooperative (MLC) mechanism in mind. The
same is largely true for the broader class of catalysts for the
hydrogenation and dehydrogenation of polar C−O and C−N
bonds, notable exceptions being catalysts based on the tripodal
Et-PCy , where the hydride has moved trans to the NHC and
3
the incoming PCy ligand binds trans to the previously bound
3
PCy . At 298.15 K, the overall rearrangement of B to Ru-dipp-
3
Et-PCy is calculated to be thermodynamically favorable by 9.3
3
kcal/mol.
We have also calculated the relative free energies of the
species in Figure 6 at 378.15 K or 105 °C, the operating
F
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Figure 6. Free energy profile for the conversion of B into Ru-dipp-Et-PCy via dechelation of the pincer ligand followed by C−H activation.
3
Solvent-corrected free energies at 298.15 K are given in kcal/mol.
temperature of the catalytic reactions reported above. At this
Air-Free Gradient Flash Chromatography. Complexes trans-
Ru-Mes-Et-PPh , Ru-Mes-Et-PCy , Ru-dipp-Me-PCy , Ru-dipp-Et-
temperature, the conversion of Ru-dipp-Et-PCy back to B is
3
3
3
3
i
PCy , and Ru-dipp- Pr-PCy did not survive silica gel chromatog-
calculated to be thermodynamically uphill by only 5.9 kcal/
3
3
raphy in air but were air-stable in dichloromethane/ethyl acetate
solution for at least an hour. These complexes were purified by
gradient flash chromatography using a Teledyne Isco Combiflash RF
system, taking precautions to exclude air, while the compounds were
in contact with silica gel. Nitrogen was supplied to the gas intake of
the Combiflash system. The prepacked silica-gel cartridge to be used
was installed and purged with nitrogen for 30 min before loading the
samples. The chromatography solvents were sparged with nitrogen for
30 min before loading the samples and continually during
chromatography. Solvent pumps were primed three times with
degassed solvent before introducing solvent to the column. To load
the sample, the crude reaction mixture in toluene was filtered through
a PTFE disc in the glovebox, transferred to a capped plastic syringe,
and removed from the glovebox along with a separate syringe
containing 10 mL of degassed dichloromethane. At the start of the
chromatographic run, the filtered reaction solution was injected,
followed by the dichloromethane chaser. As purified product eluted,
the solution was immediately transferred to a round-bottom flask, and
the solvent was removed by rotary evaporation. Purified, dried
samples were stored in the glovebox.
mol, with a highest barrier of 23.5 kcal/mol through CD-TS
(
see Table S1 for the complete list of energies). Therefore, it is
plausible that the CC-chelated precatalysts we have synthe-
sized serve as a latent form of a catalytically active CNN−
pincer complex under our catalytic conditions. Because of the
dramatic effect of the amine alkyl substituents on catalytic
activity, we believe catalysis through a CNN−pincer binding
mode is probable.
CONCLUSION
■
In summary, we have demonstrated that a class of CNN−
pincer ruthenium precatalysts for ester hydrogenation under-
goes an unusual rearrangement to a CC-chelated form in the
t
presence of NaO Bu and phosphine ligands. The CC-chelated
complexes are highly active catalysts for ester hydrogenation,
without the requirement of exogenous base. Computational
analysis showed that reversion to a catalytically active CNN-
chelated form is possible under the conditions employed. A
detailed experimental and computational investigation of the
catalytic reaction mechanism is in progress.
Ru-dipp-Et-pyr. In the glovebox, Ru-dipp-Et (10 mg, 0.017
t
mmol), pyridine (8 mg, 0.1 mmol), and NaO Bu (9.5 mg, 0.099
mmol) were combined in 0.5 mL of C D and stirred at room
6
6
temperature for 30 min to give a red solution. This solution was
transferred to a J-Young NMR tube, and NMR spectra were recorded
at room temperature. This complex decomposed slowly at room
temperature in solution or upon removal of solvent and was not
EXPERIMENTAL SECTION
■
General Methods. Unless stated otherwise, all reactions were
carried out either on a Schlenk line under argon or in an argon-filled
MBraun Labmaster 130 glovebox. Solvents were purified by sparging
with argon and passing through columns of activated alumina, using
an MBraun Solvent Purification System. All reagents and materials
were commercially available and were used as received, unless
otherwise noted. NMR spectra were recorded at room temperature on
1
3
isolated. H NMR (C
D
): δ 7.59 (d, JHH = 8.1 Hz, 1H, CHbenzimid);
6
6
3
3
7.53 (t, JHH = 7.8 Hz, 1H, CHdipp); 7.42 (d, JHH = 7.8 Hz, 1H,
3
3
CHdipp); 7.34 (d, JHH = 7.8 Hz, 1H, CHdipp); 6.95 (t, JHH = 7.8 Hz,
1H, CHbenzimid); 6.85−6.80 (m overlapped with free pyridine,
3
CHbenzimid and CHpyridine); 6.46 (d, JHH = 7.8 Hz, 1H, CHbenzimid);
1
13
3
3
a Bruker spectrometer (400 MHz for H NMR and 100 MHz for
C
6.10 (d, JHH = 9.1 Hz, 1H, CHpyr); 5.82 (d, JHH = 6.8 Hz, 1H,
CHpyridine); 4.41 (s, 1H, CHlinker); 3.28 (m, NCH CH ); 3.12 (m,
); 2.76 (sept, JHH = 6.8 Hz, 1H, CHiPr); 2.47−2.36 (m,
NMR) and referenced to the residual solvent resonance (δ in parts
per million, J in Hz). Elemental analyses were performed by
Robertson Microlit, Madison, NJ. Detailed NMR assignments for
the newly reported ruthenium complexes are given in the Supporting
Information.
2
3
3
NCH
2H, NCH
7.0 Hz, 3H, CH ); 1.27 (t, J = 6.8 Hz, 3H, NCH CH ); 1.00 (t,
CH
2
3
3
CH and CHiPr); 2.14 (m, 1H, NCH CH ); 1.61 (d, JHH =
3 2 3
2
3
3‑iPr
HH
2
3
3
3
JHH = 6.8 Hz, 3H, NCH CH ); 0.95 (d, J = 7.0 Hz, 3H, CH3‑iPr);
2
3
HH
G
DOI: 10.1021/acs.organomet.9b00373
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
0
.93 (d, 3JHH = 7.0 Hz, 3H, CH3‑iPr); 0.77 (d, 3JHH = 7.0 Hz, 3H,
CPPh3); 124.68 (s, Cdipp); 123.70 (s, Cdipp); 122.38 (s, Cbenzimid);
CH3‑iPr); −13.46 (s, 1H, RuH).
121.77 (s, Cbenzimid); 117.63 (s, C ); 113.77 (s, Cbenzimid); 110.91 (s,
pyr
cis-Ru-Mes-Et-PPh . In the glovebox, Ru-Mes-Et (75 mg, 0.13
Cbenzimid); 58.73 (s, CH NEt ); 46.94 (s, NCH CH ); 28.26 (s,
3
2
2
2
3
t
mmol), a stir bar, triphenylphosphine (209 mg, 0.80 mmol), NaO Bu
CH ); 28.22 (s, CH ); 24.96 (s, CH ); 24.90 (s, CH ); 23.10
iPr iPr 3‑iPr 3‑iPr
3
1
1
(
77 mg, 0.80 mmol), and benzene (4 mL) were added to a vial and
(s, CH3‑iPr); 22.65 (s, CH3‑iPr); 12.02 (s, NCH CH ). P{ H} NMR
2 3
2
2
stirred overnight at room temperature. The mixture was filtered
through a PTFE disk and layered with 30 mL of pentane, which
resulted in the slow precipitation of a white solid. The solid was
washed with pentane and dried under vacuum. Yield: 96 mg, 72%. H
NMR (CD Cl ): δ 8.81 (d, J = 8.0 Hz, 1H, CHbenzimid); 7.40 (m,
(CD
Anal. Calcd for C66
C, 72.50; H, 6.27; N, 4.90.
trans-Ru-Mes-Et-PPh . In the glovebox, Ru-Mes-Et (96 mg,
2
Cl
2
): δ 44.87 (d, JPP = 21.8 Hz); 27.98 (d, JPP = 21.8 Hz).
H
66
N
OP Ru: C, 72.44; H, 6.08; N, 5.12. Found:
4
2
1
3
3
0.170 mmol), a stir bar, triphenylphosphine (267 mg, 1.02 mmol),
2
2
HH
3
3
t
6
7
H, CHPPh3); 7.19 (t, J = 7.8 Hz, 1H, CH
.8 Hz, 3H, CHPPh3); 7.06 (t, J = 7.8 Hz, 3H, CHPPh3); 7.03 (t,
); 7.13 (t, J =
NaO Bu (98 mg, 1.02 mmol), and toluene (10 mL) were added to a
HH
benzimid
HH
3
vial and stirred overnight at 80 °C. The crude reaction mixture was
then purified by air-free gradient flash chromatography, using a
gradient of 0 to 100% ethyl acetate in dichloromethane. Yield: 106
HH
3
3
JHH = 7.8 Hz, 1H, CHbenzimid); 7.01 (t, J = 7.8 Hz, 6H, CHPPh3);
HH
3
6
.97 (s, 1H, CHMes); 6.92 (s, 1H, CHMes); 6.88 (t, J = 7.4 Hz, 6H,
HH
1
3
3
mg, 59%. H NMR (CD Cl ): δ 8.72 (d, JHH = 8.0 Hz, 1H,
CHPPh3); 6.69 (m, 6H, CH ); 6.55 (d, JHH = 8.1 Hz, 1H,
2 2
PPh3
3
3
4
CHbenzimid); 7.17 (t, J
HH
6H, CHPPh3); 7.04−6.95 (m, 25H, CH
H, CH ); 6.53 (d, J = 8.0 Hz, 1H, CH
= 7.7 Hz, 1H, CHbenzimid); 7.12−7.07 (m,
CH
); 6.40 (dd, J = 7.6 Hz, J = 1.4 Hz, 1H, CH ); 6.15
benzimid
HH
HP
pyr
3
3
and CHbenzimid); 6.89 (s,
(
d, J = 7.4 Hz, 1H, CH ); 3.55 (s, 2H, CH NEt ); 2.46 (q, J
PPh3
HH
pyr
2
2
HH
3
3
2
); 6.33 (dt, J
=
=
7.2 Hz, 4H, NCH CH ); 2.29 (s, 3H, CH3‑Mes); 2.04 (s, 3H,
Mes
HH
benzimid
HH
2
3
4
3
3
7.4 Hz, J = 1.2 Hz, 1H, CH ); 6.08 (d, J = 7.4 Hz, 1H,
CH3‑Mes); 1.22 (s, 3H, CH
); 0.98 (t, JHH = 7.2 Hz, 6H,
HP pyr HH
3‑Mes
3
2
2
CH ); 3.52 (s, 2H, CH NEt ); 2.43 (q, JHH = 7.1 Hz, 4H,
NCH CH ), −8.41 (dd, J = 34.4 Hz, J = 77.4 Hz, 1H, RuH).
pyr
2
2
2
3
HP
HP
13
1
2
2
NCH CH ); 2.34 (s, 3H, CH
); 1.18 (s, 6H, CH3‑Mes) 0.96 (t,
C{ H}n2o NMR (CD Cl ): δ 207.60 (dd, J = 80.4 Hz, J = 6.0
2
3
3‑Mes
2
2
CP
CP
3
1
2
2
2
J
= 7.1 Hz, 6H, NCH CH ); −7.07 (t, J = 28.2 Hz, RuH).
HH
2
3
HP
Hz, C ); 204.50 (dd, J = 13.2 Hz, J = 6.7 Hz, CCO); 162.40
NHC
CP
CP
3
1
2
3
2
2
C{ H} NMR (CD Cl ): δ 212.88 (t, J = 5.7 Hz, CNHC); 206.36
2 2 CP
(
t, J = 2.6 Hz, C ); 151.91 (dd, J = 9.9 Hz, J = 15.2 Hz,
CP
pyr
CP
CP
2
3
3
(t, J = 10.1 Hz, C ); 163.18 (t, J = 2.2 Hz, C ); 152.36 (s,
Cpyr); 151.09 ( J = 17.3 Hz, Cpyr); 150.72 (s, C ); 138.81 (s,
CP pyr
Cdipp); 137.26 (t, J = 21.5 Hz, CPPh3); 137.26 (s, Cdipp); 137.09 (s,
C ); 151.64 (t, J = 3.8 Hz, C ); 150.70 (s, C ); 139.30 (s,
CMes); 138.47 (dd, J = 35.0 Hz, J = 1.6 Hz, CPPh3); 138.26 (s,
CMes); 137.06 (dd, J = 29.1 Hz, J = 1.3 Hz, C ); 136.74 (s,
CMes); 136.68 (d, J = 3.2, C
CP CO CP pyr
pyr
CP
pyr
pyr
2
2
3
CP
CP
1
2
3
CP
CP
CP
PPh3
2
4
2
Cbenzimid); 134.33 (s, Cdipp); 133.52 (t, J = 5.9 Hz, CPPh3); 132.78
(s, Cbenzimid); 128.98 (s, Cdipp); 128.64 (s, CPPh3); 127.19 (t, J = 4.5
); 134.33 (d, J = 10.9 Hz,
CP
CP
benzimid
CP
3
2
C
PPh3); 133.78 (s, CMes); 133.30 (d, J = 11.0 Hz, CPPh3); 132.08 (d,
CP
CP
4
Hz, CPPh3); 122.11 (s, Cbenzimid); 121.86 (s, Cbenzimid); 118.14 (s, Cpyr);
JCP = 1.7, Cbenzimid); 129.54 (s, CMes); 128.72 (s, CMes); 128.64 (s,
3
114.39 (s, Cbenzimid); 108.67 (s, Cbenzimid); 58.27 (s, CH NEt ); 46.88
2
2
CPPh3); 128.52 (s, CPPh3); 127.32 (d, J = 8.6 Hz, two meta CPPh3
peaks overlapped); 122.32 (s, Cbenzimid); 122.24 (s, Cbenzimid); 117.34
CP
(
s, NCH CH ); 20.89 (s, CH3‑Mes); 17.43 (s, CH3‑Mes); 12.03 (s,
2 3
31
1
NCH CH ). P{ H} NMR (CD Cl ): δ 51.24 (s). Anal. Calcd for
2
3
2
2
(
s, C ); 113.90 (s, Cbenzimid); 108.90 (s, Cbenzimid); 58.61 (s,
pyr
C H N OP Ru: C, 71.91; H, 5.75; N, 5.32. Found: C, 71.88; H,
6
3
60
4
2
CH NEt ); 46.91 (s, NCH CH ); 20.92 (s, CH ); 18.33 (s,
CH3‑Mes); 16.91 (s, CH
2
2
2
3
3‑Mes
3
1
1
5.87; N, 5.04.
); 12.00 (s, NCH CH ). P{ H} NMR
3‑Mes
2 3
2
2
Ru-Mes-Et-PCy . In the glovebox, Ru-Mes-Et (50 mg, 0.89
3
(
CD Cl ): δ 46.83 (d, J = 21.6 Hz); 31.08 (d, J = 21.6 Hz).
2 2 PP PP
mmol), a stir bar, tricyclohexylphosphine (149 mg, 0.532 mmol),
Anal. calcd. for C H N OP Ru: C, 71.91; H, 5.75; N, 5.32. Found:
C, 71.50; H, 5.68; N, 5.26.
63
60
4
2
t
NaO Bu (51 mg, 0.53 mmol), and toluene (7 mL) were added to a
vial and stirred overnight at room temperature. The crude reaction
mixture was purified by air-free gradient flash chromatography, using a
gradient of 0 to 100% ethyl acetate in dichloromethane. The residue
was then recrystallized by layering acetonitrile over a concentrated
dichloromethane solution in the glovebox. The colorless solid formed
was washed with a 6:1 mixture of acetonitrile to dichloromethane,
cis-Ru-dipp-Et-PPh . In the glovebox, Ru-dipp-Et (50 mg, 0.082
3
t
mmol), a stir bar, triphenylphosphine (130 mg, 0.50 mmol), NaO Bu
(
48 mg, 0.50 mmol), and toluene (5 mL) were added to a vial and
stirred overnight at room temperature. A short silica gel column was
performed in the glovebox using a 6 mL plastic syringe and a PTFE
filter disk. The crude product was loaded with toluene, and impurities
were washed away with dichloromethane (ca. 15 mL). The product
was then eluted with THF (ca. 10 mL). The resulting green film after
evaporation of THF was dissolved in benzene and frozen. A green
powder was obtained after sublimation of benzene. Yield: 65 mg, 79%.
1
then dried under vacuum. Yield: 41 mg, 43%. H NMR (CD Cl ): δ
2
2
3
3
8
.94 (d, J = 7.9 Hz, 1H, CH
); 7.81 (d, J = 7.2 Hz, 1H,
HH
benzimid HH
3
3
CH ); 7.13 (t, J = 7.9 Hz, 1H, CHbenzimid); 7.00 (t, J = 7.9 Hz,
pyr
HH
HH
3
1
H, CHbenzimid); 6.94 (s, 2H, CH ); 6.76 (d, J = 7.2 Hz, 1H,
Mes HH
3
CH ); 6.51 (d,
J
= 7.9 Hz, 1H, CHbenzimid); 3.67 (s, 2H,
CH NEt ); 2.55 (q, J = 7.2 Hz, 4H, NCH CH ); 2.28 (s, 3H,
1
3
pyr
HH
H NMR (CD Cl ): δ 8.82 (d, J = 8.0 Hz, 1H, CHbenzimid); 7.27 (t,
3
2
2
HH
3J
2
2
HH
2
3
= 7.7 Hz, 1H, CH ); 7.26−7.20 (m, 7H, CH and CHPPh3);
HH
dipp
dipp
CH3‑Mes); 1.99 (br s, 6H, CH
); 1.87−0.72 (br m, 66H, CHPCy3);
3‑Mes
3
3
7
.13 (t, 2H, J = 7.2 Hz, CHbenzimid); 7.06 (d, J = 8.0 Hz, 1H,
3
2
HH
HH
1.02 (t, J = 7.2 Hz, 6H, NCH CH ); −8.25 (t, J = 31.7 Hz,
HH
2
3
HP
CHdipp); 7.05−6.92 (m, 7H, CH
and CHbenzimid); 6.88 (m, 6H,
1
3
2
PPh3
RuH). C NMR (CD Cl ): δ 217.78 (t, J = 4.4 Hz, CNHC); 207.88
2 2 CP
(t, J = 11.2 Hz, CCO); 163.00 (s, C ); 157.52 (t, J = 14.4 Hz,
CP pyr CP
CHPPh3); 6.79 (m, 6H, CH ); 6.63−6.58 (m, 7H, CH
and
2
2
PPh3
PPh3
3
3
CH ); 6.45 (d, J = 8.0 Hz, 1H, CH
); 6.12 (d, J = 7.4
pyr
HH
benzimid
HH
Cpyr); 152.82 (s, C ); 150.21 (s, C ); 138.63 (s, Cbenzimid); 137.78
pyr pyr
2
Hz, 1H, CH ); 3.52 (AB pattern, J = 13.7 Hz, 2H, CH NEt );
pyr
HH
2
2
(s, CMes); 137.10 (s, Cdipp); 134.78 (s, CMes); 132.95 (Cbenzimid);
129.43 (s, CMes); 121.70 (s, CMes); 121.58 (s, CMes); 118.05 (s, Cpyr);
113.77 (s, Cbenzimid); 108.84 (s, Cbenzimid); 58.92 (s, CH NEt ); 46.68
3
3
2
.40 (q, J = 7.0 Hz, 4H, NCH CH ); 2.15 (sept, J = 6.8 Hz,
HH 2 3 HH
3
3
1
H, CH ); 2.09 (sept, J = 6.8 Hz, 1H, CH ); 0.93 (t, J = 7.0
iPr
HH
iPr
HH
2
2
3
Hz, 6H, NCH CH ); 0.83 (d, J = 6.8 Hz, 3H, CH3‑iPr); 0.58 (d,
2
3
HH
(s, NCH CH ); 37.32 (br s, CPCy3); 29.87 (br s, CPCy3); 29.67 (br s,
2 3
3
3
JHH = 6.8 Hz, 3H, CH3‑iPr); 0.50 (d, J = 6.8 Hz, 3H, CH ); 0.48
HH
3‑iPr
CPCy3); 28.00−27.75 (br m, CPCy3); 26.75 (s, C ); 20.72 (s,
PCy3
31 1
d, 3JHH = 6.8 Hz, 3H, CH ); −8.79 (dd, J = 32.3 Hz, J
2
2
=
(
7
CH3‑Mes); 19.69 (br s, CH
); 11.94 (s, NCH CH ). P{ H} NMR
3‑iPr
HP
HP
3‑Mes 2 3
1
3
2
1
6.1 Hz, 1H, RuH). C NMR (CD Cl ): δ 209.98 (dd, J = 80.4
(CD Cl ): δ 48.13 (br s). H NMR (CD Cl , 220 K, hydride region):
2
2
CP
2 2 2 2
2
2
2
31
1
2
Hz, J = 5.7 Hz, C ); 204.65 (dd, J = 10.6 Hz, J = 7.1 Hz,
CCO); 162.02 (t, J = 3.0 Hz, C ); 153.62 (dd, J = 10.4 Hz, J
δ −8.09 (br). P{ H} NMR (CD Cl , 220 K): δ 51.4 (d, J = 195
CP
NHC
CP
CP
2
2
PP
3
2
2
2
CP
pyr
CP
CP
Hz); 44.4 (d, J = 195 Hz). Anal. Calcd for C H N OP Ru: C,
PP 63 96 4 2
3
3
=
15.3 Hz, Cpyr); 153.22 (dd, J = 6.1 Hz, J = 2.6 Hz, C );
69.52; H, 8.89; N, 5.15. Found: C, 68.63; H, 8.72; N, 5.10. Although
this complex appeared pure by NMR, a more satisfactory analysis
could not be obtained.
CP
CP
pyr
4
1
3
1
1
1
50.72 (s, C ); 148.57 (s, C ); 147.30 (s, C ); 139.26 (d, J
=
pyr
dipp
dipp
CP
1
3
.4 Hz, C
); 138.66 (dd, J = 34.5 Hz, J = 1.8 Hz, CPPh3);
benzimid
1
CP
CP CP
2
37.56 (d, J = 28.4 Hz, CPPh3); 134.51 (s, Cdipp); 134.26 (d, J
=
=
Ru-dipp-Me-PCy . In the glovebox, Ru-dipp-Me (50 mg, 0.87
CP
3
2
4
1.0 Hz, CPPh3); 133.25 (d, J = 11.2 Hz, CPPh3); 132.06 (d, J
mmol), a stir bar, tricyclohexylphosphine (146 mg, 0.519 mmol),
CP
CP
t
.9 Hz, Cbenzimid); 129.74 (s, Cdipp); 128.50 (s, C ); 128.45 (s,
NaO Bu (50 mg, 0.52 mmol), and toluene (7 mL) were added to a
PPh3
3
3
CPPh3); 127.40 (d, J = 8.5 Hz, CPPh3); 127.26 (d, J = 8.8 Hz,
vial and stirred overnight at room temperature. As NMR showed the
CP
CP
H
DOI: 10.1021/acs.organomet.9b00373
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
3
reaction was not complete, the solution was heated at 80 °C for 3 h.
The crude reaction mixture was then purified by air-free gradient flash
chromatography, using a gradient of 0 to 100% ethyl acetate in
dichloromethane. The residue was then recrystallized by layering
acetonitrile over a concentrated dichloromethane solution in the
glovebox. The colorless solid formed was washed with a 6:1 mixture
(CD Cl ): δ 8.96 (d, J = 8.0 Hz, 1H, CHbenzimid); 7.79 (d, 3J
=
HH
2
2
HH
HH
3
3
7.2 Hz, 1H, CH ); 7.34 (t, J = 7.8 Hz, 2H, CHdipp); 7.25 (t, J
= 7.8 Hz, 2H, CH ); 7.13 (t, J = 8.0 Hz, 1H, CHbenzimid); 7.00 (t,
JHH = 8.0 Hz, 1H, CH
CH ); 6.69 (d, JHH = 8.0 Hz, 1H, CHbenzimid); 3.70 (s, 2H,
pyr
HH
3
dipp
HH
3
3
); 6.96 7.79 (d, J = 7.2 Hz, 1H,
benzimid
HH
3
pyr
i
3
NCH Pr); 3.04 (sept, J = 6.6 Hz, 2H, CH ); 2.0−0.0 (br m,
2
HH
iPr
3
of acetonitrile to dichloromethane, then dried under vacuum. Yield:
78H, CH
and CH3‑dipp); 0.99 (d, J = 6.6 Hz, 12H, CH );
PCy3 HH 3‑iPr
2
1 mg, 25%. 1H NMR (C D ): δ 9.51 (d, JHH = 8.0 Hz, 1H,
3
−8.58 (t, J = 31.6 Hz, RuH). C NMR (CD Cl ): δ 220.37 (t,
2
13
6
6
HP
2
2
3
2
2
3
CHbenzimid); 8.24 (d, J = 7.2 Hz, 1H, CH ); 7.37−7.30 (br, 3H,
CHdipp); 7.22 (d, J = 7.2 Hz, 1H, CH ); 7.14 (t, J = 8.0 Hz,
H, CHbenzimid); 6.86 (t, J = 8.0 Hz, 1H, CHbenzimid); 6.73 (d, J
J
= 4.7 Hz, CNHC); 207.63 (t, J = 11.3 Hz, CCO); 162.77 (t, J
HH
pyr
CP CP CP
3
3
2
HH
pyr
HH
= 2.0 Hz, C ); 156.00 (t, J = 14.6 Hz, C ); 154.54 (s, Cpyr);
pyr CP pyr
3
3
1
152.84 (s, C ); 147.69 (s, Cdipp); 140.57 (s, Cbenzimid); 136.09 (s,
HH
HH
pyr
=
8.0 Hz, 1H, CHbenzimid); 3.82 (s, 2H, CH NMe ); 2.37 (s, 6H,
Cdipp); 132.93 (s, Cbenzimid); 129.26 (s, Cdipp); 124.29 (br s, Cdipp);
2
2
N(CH ) ), 2.11−0.25 (br m, 78H, CH
and CH
); −8.21 (t,
CP
121.68 (s, Cbenzimid); 120.76 (s, Cbenzimid); 117.13 (s, C ); 113.70 (s,
3
2
PCy3
3‑dipp
pyr
2
13
2
i
J
= 31.6 Hz, RuH). C NMR (C D ): δ 220.71 (t, J = 4.7 Hz,
Cbenzimid); 112.01 (s, Cbenzimid); 51.22 (s, CH N Pr ); 48.35 (s,
HP
6
6
2
2
2
3
CNHC); 268.01 (t, J = 11.2 Hz, CCO); 164.06 (t, J = 2.0 Hz,
C ); 158.10 (t, J = 14.1 Hz, C ); 153.17 (s, Cpyr); 150.95 (s,
C ); 148.07 (s, Cdipp); 141.14 (s, Cbenzimid); 136.72 (s, Cdipp); 133.47
N(CH (CH ) ) ); 36.21 (br s, CPCy3); 29.70 (br s, CPCy3); 28.56 (br
2 3 2 2
CP
CP
2
s, Cdipp); 27.82 (br s, CPCy3); 26.71 (br s, CPCy3); 26.25 (br s, Cdipp);
pyr
CP
pyr
3
1
1
23.19 (br s, Cdipp); 20.56 (s, N(CH
(CH ). P{ H} NMR
): δ 47.44 (br m). H NMR (CD Cl , 220 K, hydride
2 2
)
)
pyr
2
3
2
2
1
(
s, Cbenzimid); 129.84 (s, Cdipp); 124.89 (br s, Cdipp); 122.56 (s,
(CD
2
Cl
2
2
31
1
region): δ −8.48 (dd, J = 27.0, 34.8 Hz). P{ H} NMR (CD Cl ,
20 K): 51.0 (d, J = 204 Hz); 42.2 (d, J = 204 Hz). Anal. Calcd
Cbenzimid); 121.59 (s, Cbenzimid); 118.35 (s, C ); 114.81 (s, Cbenzimid);
HP
2
2
pyr
2
2
2
1
12.44 (s, Cbenzimid); 66.57 (s, CH NMe ); 46.57 (s, N(CH ) ); 37.00
PP PP
2
2
3 2
for C H N OP Ru: C, 70.49; H, 9.22; N, 4.84. Found: C, 70.15; H,
(
br s, CPCy3); 30.36 (br s, CPCy3); 29.07 (br s, Cdipp); 28.27 (br s,
); 27.21 (br s, CPCy3); 26.85 (br s, Cdipp); 23.83 (br s, Cdipp).
68 106
4
2
8
.83; N, 4.85.
C
PCy3
31
1
1
General Procedure for Ester Hydrogenation. In an argon-
P{ H} NMR (CD Cl ): δ 46.71 (br s).). H NMR (CD Cl , 220 K,
2
2
2
2
2
31
1
filled glovebox, the ruthenium complex, ester, and tetradecane as
internal standard were dissolved in toluene and transferred to a test
tube containing a stir bar. The tube was placed in a stainless-steel
pressure reactor inside the glovebox, which was subsequently sealed
and brought out. Then, the reactor was pressurized with 30 bar of H2
and vented three times to remove the argon atmosphere, and finally it
hydride region): δ −8.45 (dd, J = 26.9, 35.0 Hz). P{ H} NMR
HP
2
2
(
CD Cl , 220 K): 50.9 (d, J = 203 Hz); 42.1 (d, J = 203 Hz).
2 2 PP PP
Anal. Calcd for C H N OP Ru: C, 69.72; H, 8.96; N, 5.08. Found:
64
98
4
2
7
0.31; H, 8.82; N, 4.53.
Ru-dipp-Et-PCy . In the glovebox, Ru-dipp-Et (63 mg, 0.104
3
mmol), a stir bar, tricyclohexylphosphine (175 mg, 0.624 mmol),
NaO Bu (60 mg, 0.62 mmol), and toluene (5 mL) were added to a
t
was filled with 30 bar of H . The reactor was heated at 105 °C while
2
stirring for 20 h, after which it was allowed to cool for 1 h before
being vented carefully and opened. An aliquot of the reaction mixture
was taken and analyzed by GC-FID. Yields were calculated based on
the calibrated response factors of the product(s) relative to the
tetradecane standard.
vial and stirred overnight at room temperature. The crude reaction
mixture was then purified by air-free gradient flash chromatography,
using a gradient of 0 to 100% ethyl acetate in dichloromethane. The
residue was then recrystallized by layering acetonitrile over a
concentrated dichloromethane solution in the glovebox. The colorless
solid formed was washed with a 6:1 mixture of acetonitrile to
Computational Details. All density functional theory calculations
1
were performed using the Gaussian16 computational chemistry
dichloromethane, then dried under vacuum. Yield: 41 mg, 35%. H
25
3
package, revision B.01. The geometries and energies of all species
NMR (CD Cl ): δ 8.92 (d, J = 8.0 Hz, 1H, CHbenzimid); 7.81 (d,
26
2
2
HH
were calculated using the hybrid functional B3LYP, augmented with
3
3
J
= 7.2 Hz, 1H, CHpyr); 7.25 (t, J = 7.8 Hz, 2H, CHdipp); 7.25
HH
HH
the addition of empirical dispersion with Grimme’s D3 dispersion
(
d, 3JHH = 7.8 Hz, 1H, CHdipp); 7.14 (t, JHH = 8.0 Hz, 1H,
3
27
corrections (referred to as B3LYP-d3). Ru was modeled with the
3
3
CHbenzimid); 6.99 (t, J = 8.0 Hz, 1H, CH
); 6.78 (d, J =
28
HH
benzimid
HH
effective core potential of Hay and Wadt and the accompanying
3
7
2
.2 Hz, 1H, CH ); 6.69 (d, J = 8.0 Hz, 1H, CHbenzimid); 3.66 (s,
H, CH NMe ); 2.53 (q, J = 7.2 Hz, 4H, NCH CH ); 2.0−0.0 (br
29
pyr
HH
uncontracted basis set (including f polarization functions)
3
30
2
2
HH
2
3
collectively known as LANL08(f). All other elements were modeled
with the 6-311G(d,p) basis set. Complete structures with no
3
m, 78H, CHPCy3 and CH
); 1.02 (t,
J
= 7.2 Hz, 6H,
31
3‑dipp
HH
2
13
NCH CH ); −8.55 (t, J = 31.6 Hz, RuH). C NMR (CD Cl ): δ
2
3
HP
2
2
truncations were used in all cases and were optimized in the gas
phase. Frequency calculations ensured the absence of imaginary
vibrational modes for intermediates and exactly one for transition
states. Transition states were confirmed to lead to the intermediates
shown using intrinsic reaction coordinate calculations. Solvent
corrections were added with a polarizable continuum model with
radii and nonelectrostatic terms from Truhlar and co-workers’ SMD
2
2
2
1
1
20.91 (t, J = 4.7 Hz, C ); 208.08 (t, J = 11.3 Hz, CCO);
63.61 (s, C ); 157.90 (t, J = 14.3 Hz, Cpyr); 153.17 (s, C );
50.79 (s, Cpyr); 148.11 (s, Cdipp); 141.01 (s, Cbenzimid); 136.48 (s,
CP NHC CP
2
pyr
CP
pyr
Cdipp); 133.31 (s, Cbenzimid); 129.74 (s, Cdipp); 124.73 (br s, Cdipp);
22.17 (s, Cbenzimid); 121.28 (s, Cbenzimid); 118.57 (s, Cpyr); 114.06 (s,
Cbenzimid); 112.50 (s, Cbenzimid); 59.49 (s, CH NEt ); 47.17 (s,
1
2
2
32
N(CH CH ) ); 36.95 (br s, CPCy3); 30.12 (br s, CPCy3); 29.01 (br s,
Cdipp); 28.24 (br s, CPCy3); 27.13 (br s, CPCy3); 26.68 (br s, Cdipp);
2
3
2
solvation model, and with dielectric constants chosen for toluene.
Standard state corrections were added in order to adjust from 1 atm
3
1
1
3334
2
3.64 (br s, Cdipp); 12.42 (s, N(CH CH ) ). P{ H} NMR
2 3 2
to 1 M for solution-phase free energies.
1
(
CD Cl ): δ 45.37 (br s). H NMR (CD Cl , 220 K, hydride
2
2
2
2
3
1
1
region): δ −8.46 (br dd). P{ H} NMR (CD Cl , 220 K): 51.2 (d,
2
2
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.organo-
met.9b00373.
2
2
■
J
= 206 Hz); 42.2 (d, JPP = 206 Hz). Anal. Calcd for
PP
*
S
C H N OP Ru: C, 70.12; H, 9.09; N, 4.96. Found: C, 70.03; H,
6
6
102
4
2
8
.94; N, 4.88.
i
i
Ru-dipp- Pr-PCy . In the glovebox, Ru-dipp- Pr (50 mg, 0.079
3
mmol), a stir bar, tricyclohexylphosphine (133 mg, 0.473 mmol),
NaO Bu (46 mg, 0.47 mmol), and toluene (7 mL) were added to a
t
Experimental procedures for X-ray crystallography,
images of NMR spectra and detailed NMR assignments
for new compounds, and additional details of computa-
tional studies (PDF)
vial and stirred overnight at room temperature. The crude reaction
mixture was then purified by air-free gradient flash chromatography,
using a gradient of 0 to 100% ethyl acetate in dichloromethane. The
residue was recrystallized in the glovebox by layering acetonitrile over
a concentrated solution in dichloromethane. The colorless solid
formed was washed with a 6:1 mixture of acetonitrile to dichloro-
Atomic coordinates and energies for all computed
molecular structures, compiled as one file readable by
1
34
methane, then dried under vacuum. Yield: 33 mg, 37%. H NMR
the free program Mercury (XYZ)
I
DOI: 10.1021/acs.organomet.9b00373
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
Accession Codes
(6) (a) Takebayashi, S.; Bergens, S. H. Facile Bifunctional Addition
of Lactones and Esters at Low Temperatures. The First Intermediates
in Lactone/Ester Hydrogenations. Organometallics 2009, 28, 2349−
CCDC 1920334−1920338 contain the supplementary crys-
tallographic data for this paper. These data can be obtained
free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by
emailing data_request@ccdc.cam.ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
2351. (b) Werkmeister, S.; Junge, K.; Wendt, B.; Alberico, E.; Jiao, H.;
Baumann, W.; Junge, H.; Gallou, F.; Beller, M. Hydrogenation of
Esters to Alcohols with a Well-Defined Iron Complex. Angew. Chem.,
Int. Ed. 2014, 53, 8722−8726. (c) Brewster, T. P.; Rezayee, N. M.;
Culakova, Z.; Sanford, M. S.; Goldberg, K. I. Base-Free Iridium-
Catalyzed Hydrogenation of Esters and Lactones. ACS Catal. 2016, 6,
3113−3117. (d) Gusev, D. G. Dehydrogenative Coupling of Ethanol
and Ester Hydrogenation Catalyzed by Pincer-Type Ynp Complexes.
ACS Catal. 2016, 6, 6967−6981. (e) Espinosa-Jalapa, N. A.; Nerush,
A.; Shimon, L. J. W.; Leitus, G.; Avram, L.; Ben-David, Y.; Milstein, D.
Manganese-Catalyzed Hydrogenation of Esters to Alcohols. Chem. -
Eur. J. 2017, 23, 5934−5938. (f) van Putten, R.; Uslamin, E. A.;
Garbe, M.; Liu, C.; Gonzalez-de-Castro, A.; Lutz, M.; Junge, K.;
Hensen, E. J. M.; Beller, M.; Lefort, L.; Pidko, E. A. Non-Pincer-Type
Manganese Complexes as Efficient Catalysts for the Hydrogenation of
Esters. Angew. Chem., Int. Ed. 2017, 56, 7531−7534. (g) Yuwen, J.;
Chakraborty, S.; Brennessel, W. W.; Jones, W. D. Additive-Free
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AUTHOR INFORMATION
■
Corresponding Authors
(J.M.K.) E-mail: jkeith@colgate.edu.
(A.R.C.) E-mail: achianese@colgate.edu.
*
*
ORCID
Anthony R. Chianese: 0000-0002-9140-6115
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
2
017, 7, 3735−3740. (h) Junge, K.; Wendt, B.; Cingolani, A.;
We thank the National Science Foundation (CHE-1665144)
for support of the research project, and (CHE-1726308) for
the acquisition of an upgraded NMR spectrometer.
Spannenberg, A.; Wei, Z.; Jiao, H.; Beller, M. Cobalt Pincer
Complexes for Catalytic Reduction of Carboxylic Acid Esters.
Chem. - Eur. J. 2018, 24, 1046−1052.
(
7) (a) Hasanayn, F.; Baroudi, A. Direct H/OR and OR/OR′
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DOI: 10.1021/acs.organomet.9b00373
Organometallics XXXX, XXX, XXX−XXX