Revised Mechanisms of the Catalytic Alcohol Dehydrogenation and Ester Reduction with the Milstein PNN Complex of Ruthenium

Article abstract of DOI:10.1021/acs.organomet.9b00542

The combined experimental/DFT computational study of RuH₂(CO)[Et₂NCH₂PyCH₂Pt-Bu₂] (2) suggests that this dihydride is the catalyst of the acceptorless alcohol dehydrogenation and ester hydrogenation reactions developed in the group of Milstein, whereas the corresponding alkoxide RuH(OR)(CO)[Et₂NCH₂PyCH₂Pt-Bu₂] (4) is an important reaction intermediate. A relatively fast equilibrium of dihydride 2 and ethanol with ethoxide 4 and H₂ was demonstrated by NMR experiments, as well as the proton exchanges occurring between the OH of ethanol, RuH, and the CH₂ groups of the PNN ligand backbone of 2 and 4. A detailed critical discussion of the previously proposed mechanisms with the Milstein catalyst is presented. This paper also reports the preparation of the osmium dihydride OsH₂(CO)[Et₂NCH₂PyCH₂Pt-Bu₂] (2-Os) and a comparative study of 2, 2-Os, and the Noyori-type osmium catalyst OsH₂(CO)[PyCH₂NHCH₂CH₂NHPt-Bu₂].

Full text of DOI:10.1021/acs.organomet.9b00542

Article
pubs.acs.org/Organometallics
Cite This: Organometallics XXXX, XXX, XXX−XXX
Revised Mechanisms of the Catalytic Alcohol Dehydrogenation and
Ester Reduction with the Milstein PNN Complex of Ruthenium
Dmitry G. Gusev*
Department of Chemistry and Biochemistry, Wilfrid Laurier University, Waterloo, Ontario N2L 3C5 Canada
S
* Supporting Information
ABSTRACT: The combined experimental/DFT computational study
of RuH2(CO)[Et2NCH2PyCH2Pt-Bu2] (2) suggests that this dihydride
is the catalyst of the acceptorless alcohol dehydrogenation and ester
hydrogenation reactions developed in the group of Milstein, whereas
the corresponding alkoxide RuH(OR)(CO)[Et2NCH2PyCH2Pt-Bu2]
(4) is an important reaction intermediate. A relatively fast equilibrium
of dihydride 2 and ethanol with ethoxide 4 and H2 was demonstrated by
NMR experiments, as well as the proton exchanges occurring between
the OH of ethanol, RuH, and the CH2 groups of the PNN ligand
backbone of 2 and 4. A detailed critical discussion of the previously
proposed mechanisms with the Milstein catalyst is presented. This paper also reports the preparation of the osmium dihydride
OsH2(CO)[Et2NCH2PyCH2Pt-Bu2] (2-Os) and a comparative study of 2, 2-Os, and the Noyori-type osmium catalyst
OsH2(CO)[PyCH2NHCH2CH2NHPt-Bu2].
tion” that has been well-documented and extensively reviewed
in the recent literature.10−20
INTRODUCTION
■
In 2005−2006, Milstein and co-workers developed several
catalytic reactions promoted by a single ruthenium compound.
Prominent among these were the acceptorless dehydrogenative
coupling of alcohols and the reduction of esters of Scheme 1.1,2
The work of Milstein attracted the attention of theoretical
chemists who extensively pursued mechanisms featuring 1 as
the catalyst.21−28 The computational studies were summarized
in 2015 by Li and Hall,29 who concluded that the
dehydrogenative coupling of alcohols proceeded on 1 via the
so-called bifunctional double hydrogen transfer (BDHT)
mechanism following the steps of Scheme 3. These involve
Scheme 1. Acceptorless Dehydrogenative Coupling of
Alcohols and the Reduction of Esters
Scheme 3. Dehydrogenative Ester Synthesis29
The catalyst of these reactions was the unusual 16-electron
dearomatized complex, 1 (Scheme 2), capable of adding H2 in
Scheme 2. Milstein Catalyst and Dihydride 21,2
alcohol dehydrogenation on 1, followed by formation of a
hemiacetal intermediate, further dehydrogenated by 1 to give
the product ester. Catalyst 1 is regenerated via intramolecular
extrusion of H2 from 2. The ester reduction of Scheme 1b can
be presumed to be the reverse of the process of Scheme 3.
This study is concerned with the reactivity and speciation of
1 and 2 with the organic compounds expected to be present
under the typical catalytic conditions of the reactions of
Scheme 1. This paper combines experiment with DFT
solution to give corresponding 18-electron dihydride, 2. The
pyridine-based pincer ligand of 2 will be further referred to as
the “PNN ligand”. Milstein and co-workers summarized their
work in several publications3−9 and formulated the paradigm
of “metal−ligand cooperation by aromatization−dearomatiza-
Received: August 8, 2019
© XXXX American Chemical Society
A
DOI: 10.1021/acs.organomet.9b00542
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I further prepared the previously unknown OsHCl(CO)[PNN]
(1.45 g, 80%) by PNN ligand exchange with OsHCl(CO)(AsPh3)3.
The dihydride OsH2(CO)[PNN] (2-Os) (0.84 g, 89%) was
subsequently produced by treating the hydridochloride with
Li[HBEt3] in THF. This dihydride is structurally related to the
osmium complex OsH2(CO)[PyCH2NHCH2CH2NHPt-Bu2] (3-Os)
from our group,34 shown in Scheme 6. 2-Os is stable in air for at least
modeling, and the product is a detailed mechanistic picture
that provides important insights into the reaction pathways of
the Milstein catalyst. Steps 1 and 3 of the mechanism of
Scheme 3 appear to be unlikely under the catalytic conditions.
EXPERIMENTAL OBSERVATIONS
It is appropriate to briefly review the known reactivity of complex 1.
The important observations are summarized below.
■
Scheme 6. Osmium Complexes 2-Os and 3-Os
(i) Reactivity toward hydrogen: Bubbling H2 through a dark
solution of 1 in toluene-d8 produced a color change to yellow due to
the quantitative formation of 2 according to Scheme 2. The product
dihydride was isolated and crystallographically characterized.1,30
(ii) Reactivity toward methanol and water: The addition of 5 equiv
of methanol to a dark-brown solution of 1 in toluene-d8 resulted in an
immediate color change to yellow due to the quantitative formation of
the methoxide, RuH(OMe)(CO)[PNN],30 illustrated in Scheme 4.
24 h as a solid, and it is stable with respect to H2 loss in solution.
Osmium hydrides typically demonstrate improved overall thermal
stability compared to the ruthenium analogues.
Scheme 4. Reaction of 1 with Methanol30
The catalytic activity of 2 and 2-Os in the reactions of Scheme 1
was tested, and the results are summarized in Tables 1 and 2.
a
Table 1. Dehydrogenation of Ethanol to Ethyl Acetate
b
c
d
e
line
cat
EtOH
solvent
t-BuOK
TON
1
2
3
4
5
6
7
2
0.2
0.2
0.2
0.04
0.04
none
none
none
toluene
toluene
none
none
0.5
2.0
none
1.0
none
315
145
0
71
60
The product is labile; it was reported to form “mostly complex 1 and
methanol, upon drying at room temperature.” Similarly, 1 equiv of
water reacted with 1 in THF immediately to give the hydroxide trans-
RuH(OH)(CO)[PNN].31
(iii) Reactivity toward carbonyls: Sanford et al. demonstrated that
complex 1 adds CO2, aldehydes, and formate esters “to generate room
temperature stable addition products”, e.g., benzaldehyde reacted
rapidly and irreversibly to give a mixture of isomers (Scheme 5).32
2
2
2
2
2-Os
3-Os
f
f
0.2
0.2
640
5140
none
none
a
After 20 h at 90 °C, S/C = 104 in neat EtOH and 2 × 103 in toluene.
b
c
d
e
Catalyst, 2 × 10−5 moles. Substrate, moles. Base, mol %. Ethanol
f
Scheme 5. Reaction of 1 with Benzaldehyde32
turnover number. With 9.3 mL of toluene, to maintain equal catalyst
concentration in all experiments of Table 1.
Complex 3-Os was also retested in this work, and the results allow us
to compare the Milstein- and the Noyori-type catalysts. The principal
Table 2. Catalytic Hydrogenation of Ethyl Acetate (EA) and
a
Methyl Hexanoate (MH)
b
c
d
e
f
g
Observations of This Paper. While a fair amount of information
is available for 1, only NMR data and the molecular structure have
been reported for 2.1,30 This dihydride was previously obtained on a
30 mg scale, and the report1 noted that 2 was “stable only under an
atmosphere of H2”; thus, isolated 2 was “dried with H2 flow.” I
similarly prepared 2 (0.37 g, 80%) by pressurizing a solution of 1 with
H2. In agreement with the previous work, the product is a yellow
crystalline solid (Figure S1) that however showed no color change at
room temperature under argon or vacuum. A sample of 2 left in air
overnight exhibited only a trace of decomposition in the NMR spectra
(Figures S3 and S4). Thus, crystalline 2 appears to be stable with
respect to H2 loss for all practical purposes, and it is relatively resistant
to degradation even in air. Complex 2 is considerably more stable
compared to 1, which requires low-temperature storage and should be
handled expediently at room temperature.33 Dihydride 2 is sparingly
soluble in organic solvents (e.g., ca. 0.007 M in benzene-d6), whereas
it rapidly reacts with, and readily dissolves in, methanol and
dichloromethane to give solutions of the known methoxide and
chloride compounds, RuHX(CO)[PNN], X = OMe30 and Cl,1
respectively.
cat
ester
solvent
none
PhMe
base
S/C
104
TON
conv
1
2
3
4
5
6
7
8
2
EA, 250
EA, 50
none
none
0.3
0
70
0
3.5
h
2
2
2
2
2
2
2
2
2
2 × 103
104
EA, 250
EA, 250
EA, 250
EA, 250
EA, 50
MH, 200 none
MH, 40
MH, 40
none
none
none
none
4745
5600
6200
6425
2000
3316
1956
2000
0
87
0
9773
9415
47.5
56.0
62.0
64.3
100
33.2
97.8
100
0
0.5
104
0.75
1.0
104
104
h
PhMe
2.0
1.5
2 × 103
104
2 × 103
2 × 103
104
i
j
j
9
PhMe
PhMe
none
none
2.0
none
1.0
none
none
none
10
11
12
13
14
15
2-Os EA, 200
2-Os EA, 250
2-Os MH, 40
3-Os EA, 250
none
PhMe
none
104
0.9
0
j
2 × 103
104
k
l
97.7
94.2
3-Os MH, 200 none
104
a
b
Conditions: 3 h at 100 °C, initial p(H2) = 50 bar. Catalyst.
Substrate, millimoles. t-BuOK, mol %. The substrate-to-catalyst
ratio. Ester to alcohol turnover number. Percent conversion of ester
to alcohol. In 21.3 mL of toluene. TON = 2920 to hexyl hexanoate.
In 23.5 mL of toluene. p(H2) = 8 bar after 3 h. TON = 205 to hexyl
hexanoate.
c
d
e
As previously noted,1 complex 2 slowly eliminates H2 in benzene-d6
at room temperature, resulting in a color change from the initial bright
yellow of 2 to a dull brownish-yellow, due to the formation of 1. The
two complexes are distinct in the NMR spectra, where the relative
amount of 1 is ca. 6% in 15−20 min after dissolution.
f
g
h
i
j
k
l
B
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objective of the experiments was to guide the DFT computational
work (vide infra). It is for this reason, that the focus here is on the
reactions of small molecules (the substrates employed in the
calculations): ethanol and ethyl acetate.
(for details, see Figures S8−12). No 1 was seen in the NMR spectra.
A trace amount of ethyl acetate formed, reaching 5 mol % versus 4
after 2 days.
Upon selective irradiation of the OH resonance at 4.4 ppm, a
1
difference H NOE spectrum (Figure 1) revealed saturation transfer
Milstein and co-workers tested 1 (0.1 mol %) in the dehydrogen-
ation of three primary alcohols: 1-butanol (neat), 1-hexanol, and
benzyl alcohol (in toluene).1 These produced the corresponding
symmetrical esters with TON = 900−990, in 4−6 h under reflux. The
observations of Table 1 show that the dehydrogenation of ethanol to
ethyl acetate by 2 works best in neat substrate (entry 1), whereas the
use of base (entries 2 and 3) or solvent toluene (entry 4) were
detrimental. The lower efficiency of 2 with ethanol (TON = 315) is
likely due to the low boiling point of this substrate; hence, the
operating temperature reduced by >30 °C compared to the conditions
of the original work of Milstein with the higher alcohols. Osmium
analogue 2-Os is about two times more efficient than 2 and afforded
TON = 640 to ethyl acetate. Under the same conditions, complex 3-
Os gave TON = 5140.
In the catalytic hydrogenation of ethyl acetate to ethanol (Table 2),
no reaction was observed for the neat substrate under neutral
conditions (3 h reaction time at 100 °C in all experiments). A low
activity was found for ethyl acetate reduction by 2 in toluene, TON =
70. Milstein and co-workers reported TON = 86 for ethyl acetate with
1 (1 mol %) in dioxane after 12 h at 115 °C under p(H2) = 5.3 atm;
other esters similarly tested by Milstein (benzoates, dimethyl
terephthalate, ethyl butyrate, and hexyl hexanoate) afforded TON =
82−100 within 4−7 h.2
Apparently, the Milstein catalyst has not been investigated in ester
reduction under basic conditions. The experiments of Table 2 (entries
3−6) have demonstrated that hydrogenation of ethyl acetate is
dramatically accelerated by even a trace of t-BuOK, and the reaction is
best performed with at least 1 mol % base, to give TON = 6425 to
ethanol. The reduction of methyl hexanoate with 0.01 mol % 2 and
1.5 mol % t-BuOK gave TON = 3316 to hexanol, accompanied by a
significant amount of the trans-esterification product, hexyl hexanoate
(TON = 2920, entry 8). Methyl hexanoate could be successfully
reduced with 0.05 mol % 2 in toluene (entries 9 and 10).
Figure 1. Difference NOE/saturation transfer 1H NMR spectrum of 2
(0.1 M in toluene-d8) with 9.2 equiv of EtOH. The OH resonance of
ethanol at 4.4 ppm was irradiated
to the hydrides of 2 and 4, to the PCH2 protons of 2, and to the CH2
protons of the PNN ligand backbone of 4. The latter further produced
the distinct NOEs for the proximal protons of the Py and t-Bu groups.
A similar spectrum was obtained when irradiating H′P at δ 2.87 (see
Figure S13), while the irradiation of HN at δ 4.86 transferred the
saturation to NCH2 of 2 at 3.76 ppm (see Figure S14). Of the two
protons HP and H′P, only the latter could be positively identified,
whereas HP is apparently exchanging rapidly and is tentatively
assigned in Figure 1 at 3.3 ppm near the broad OCH2 resonance at
3.58 ppm. These observations are consistent with an equilibrium
depicted in Figure 1, also involving reversible dearomatization−
aromatization of the PNN ligand, OH/RuH scrambling and OH/CH2
proton exchange between ethanol and 2 and 4, all operating on the
NMR relaxation time scale. An equilibrium constant of 0.18 and ΔG =
1.0 kcal/mol were calculated for the forward reaction of Figure 1,
using the known concentration of ruthenium in the sample and
assuming [H2] = 0.003 mol/L in solution, which is the solubility of
hydrogen gas in toluene under normal conditions.37 This corresponds
to ΔG = −3.5 kcal/mol with p(H2) = 1 atm (the Gibbs energy of H2
changes by −4.48 kcal/mol upon the transfer from toluene into the
gas phase).37
For comparison, a similar experiment with 3-Os (0.1 M in toluene-
d8) and 9.5 equiv of ethanol gave ΔG = −2.5 kcal/mol for the
equilibrium between 3-Os, ethanol, and the ethoxide, OsH(OEt)-
(CO)[PyCH2NHCH2CH2NHPt-Bu2] under 1 atm H2 (1H −17.23,
2JHP = 19.2 Hz; 31P δ 79.0, see Scheme 7). Upon irradiation of the
OH resonance, only one hydride of 3-Os (δ −5.27) experienced
saturation transfer, whereas irradiation of OsH at δ −17.23 resulted in
saturation transfer to the other hydride of 3-Os, resonating at δ −5.01.
These observations are consistent with the equilibrium of Scheme 7,
where ethanol reacts with 3-Os selectively on one side of the complex,
presumably due to the directing effect of the N−H group. The
observations with 3-Os are reminiscent of the stereoselective
Osmium analogue 2-Os proved practically inactive in ester
hydrogenation, whereas as expected,34 3-Os afforded nearly
quantitative conversions for ethyl acetate and methyl hexanoate
with TON = 9773 and 9415, respectively (Table 2, entries 14 and
15). The results with 3-Os serve as an important reminder that with
the right catalyst the reduction of alkyl alkanoates is facile, and this
catalytic reaction does not intrinsically require base or solvent.
Several additional observations are reported next, and their
mechanistic significance will be fully appreciated in a later section.
The first observation is related to the attempted hydrogenation of
ethyl acetate in methanol (3.83 M, MeOH/EtOAc = 4.0) with 0.025
mol % 2, without base under p(H2) = 50 bar. After 3 h at 100 °C, 75%
of ethyl acetate was converted to methyl acetate and ethanol (TON =
3000), and an additional 11% was reduced straight to ethanol (TON
= 440). Thus, 2 is an efficient transesterification catalyst. Trans-
esterification of esters with 1 and sec-alcohols has been reported.35 For
example, refluxing hexyl hexanoate with an 8-fold excess of 2-propanol
in toluene gave TON = 67 to isopropyl hexanoate in 19 h.35
Formation of 2 from 1 in 2-propanol has been documented.36
I further enquired into what happens to 2 in the presence of
ethanol. The dihydride rapidly loses H2 and readily dissolves in neat
ethanol to give a single product (31P δ 105.2) displaying a hydride
2
resonance at δ −17.64 (d, JHP = 28.8 Hz), assigned to the ethoxide,
RuH(OEt)(CO)[PNN] (4). The analogous methoxide complex
2
resonates at δ 103.7 in 31P NMR and δ −18.99 (d, JHP = 28.0 Hz)
Scheme 7. Reaction of 3-Os with Ethanol
1
in H NMR in methanol-d4 (see Figure S16).
A sample of 2 proved particularly interesting (31 mg, 6.7 × 10−5
mol, in 0.63 mL of toluene-d8 with added ethanol). With 3.7 equiv of
EtOH, 2 and 4 were observed by NMR in a 1:7 ratio; however, the
dihydride was not fully dissolved. Increasing the amount of ethanol to
9.2 equiv gave a homogeneous solution (accompanied by the release
of ca. 1.5 mL of H2). The 1H NMR spectrum of this solution
displayed 2 and 4 in a 1:49 ratio, which was not changed after 2 days
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exchange processes of the related ruthenium PN(H)P complexes with
water and ethanol, reported by Schneider and Gauvin.38,39
Complex 2-Os proved poorly soluble in ethanol (and other
common organic solvents). For example, 10 mg of 2-Os dissolved in
0.7 mL of ethanol upon heating to 80 °C, only to crystallize back at
room temperature. An X-ray analysis of the crystalline material
returned the molecular structure of 2-Os presented in Figure 2.
Complexes 2 and 2-Os are isostructural.
existence of the conformation 2′ where the pyridine ring is
approximately in the PNN ligand plane, as illustrated in Figure 4.
Figure 4. View of the calculated structure of 2′ with the t-Bu and Et
groups removed for clarity.
The Gibbs energy of 2′ is 4.9 kcal/mol above that of 2, thus the
structure should be accessible at room temperature. Clockwise
rotation of the pyridine ring in 2′ will result in the inversion of the
molecular configuration for 2. For example, the axial hydrogens H′
and H″ of 2 in Figure 3 become equatorial after the inversion.
The rearrangement of the PNN ligand backbone has the effect of
“exchanging” H1 and H2 of 2 between sides I and II and averaging
Figure 2. Structure of 2-Os with the thermal ellipsoids at 50%.
Selected bond distances (Å) and angles (deg): Os−P1 2.2482(12),
Os−N1 2.238(4), Os−N2 2.106(4), Os−C1 1.840(5), Os−H1
1.63(6), Os−H2 1.72(7), N1−Os−P1 160.05(11), N2−Os−P1
82.44(11), N2−Os−N1 77.65(15), C1−Os−P1 94.69(15), C1−
Os−N1 105.26(18), H1−Os−H2 166(3).
1
their H chemical shifts. Similarly, the reorientation of the pyridine
fragment has the effect of “moving” the X-ligand of trans-
RuHX(CO)[PNN] from side I to side II, without physically
exchanging the H and X ligands. This process is illustrated in Figure
5 for ethoxide 4, for which the DFT calculations gave two distinct
DFT Computational Data. Important Structural Features of
the PNN Complexes. The known structurally characterized complexes
trans-RuHX(CO)[PNN] (X = Cl,1 OH,31 OC(O)H,40 OPh-2-
C3H6)36 all adopt a molecular geometry similar to that illustrated for
2-Os in Figure 2. Noteworthy, the pyridine fragment is rotated out of
the PNN ligand plane, rendering the two sides inequivalent. For
example, in the DFT-optimized structure of 2 in Figure 3, the three
Figure 5. View of the calculated structures of 4, looking down the
OC−Ru−N axis.
structures, expected to exist in equilibrium in solution. The X ligand
of RuHX(CO)[PNN] is repeatedly “visited” by H′ and H″, upon a
turn of the pyridine fragment.
Stoichiometric Reactions of 1. Scheme 8 shows calculated Gibbs
energies for the additions of 1 with H2, acetaldehyde, ethanol, 1-
ethoxy ethanol, and water. The calculated values are in a qualitative
agreement with the experimental observations of the quantitative
product formation in all cases. The computed reactions are
moderately exergonic, by −2 to −6 kcal/mol at room temperature.
Only the acetaldehyde addition is accompanied by a larger ΔG: −10.1
kcal/mol (M06-L) and −13.7 kcal/mol (MN15-L), in agreement with
the previously noted irreversible at room temperature formation of
the analogous complex with benzaldehyde of Scheme 5. The
calculations suggest that H2 elimination from 2 via metal−ligand
cooperation proceeds with the activation barrier of 25.0 kcal/mol
(M06-L) to 27.4 kcal/mol (MN15-L).
It is worth noting that water, ethanol, and 1-ethoxy ethanol of
Scheme 8 were calculated in a toluene solvent continuum. The
energies would change under other conditions. It is instructive to
consider one example: the reaction of 1 in neat ethanol. The
corresponding M06-L calculation gave ΔG = −5.1 kcal/mol for the
formation of 4 in ethanol versus ΔG = −6.3 kcal/mol in toluene in
Figure 3. View of the calculated structure of 2, looking down the
OC−Ru-N axis.
closest H1···carbon distances are 3.03 and 3.19 Å (toward Pt-Bu) and
3.21 Å (toward NEt), whereas the nearest H2···carbon distances are
shorter: 2.87 Å (to Pt-Bu) and 2.89 and 3.06 Å (to NEt). In
agreement with this observation is the consistent finding of the X-
ligand of trans-RuHX(CO)[PNN] on the less hindered side I, in
proximity to the axial H′ atom of the nitrogen arm of the PNN ligand.
It is notable, however, that 1H NMR spectra of 2 and 2-Os display
single chemical shifts for the hydrides and also for the diastreotopic
CH2 protons of the PNN ligand (see Figures S2 and S7), indicating a
rapid fluxional process in solution. This behavior is explained by the
D
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a
Scheme 8. Reaction Energies of 1
Scheme 9. Mechanism of Ethanol Dehydrogenation and
Proton Exchange with 2 and 4
a
a
Calculated with M06-L and (energies in parentheses) MN15-L
functionals, in toluene continuum (all 1 M solutes, at 298.15 K). The
origin of the Gibbs energies (kcal/mol) is 1 with H2 (1 atm), water,
acetaldehyde, ethanol, or 1-ethoxy ethanol, respectively; mass balance
is ensured throughout
Scheme 8. Some uncertainty in ΔG is unavoidable when calculating
hydrogen-bonded species.
Equilibrium of Figure 1 and Ethanol Dehydrogenation with 2. A
minimal model of the reaction of 2 with ethanol seems to require two
molecules of ethanol: one to react with 2 and the other to simulate
hydrogen bonding in the system.
Protonation of 2 by ethanol gives the cationic dihydrogen complex
Int 1 of Scheme 9. The reverse of this step, together with rotation of
the H2 ligand in Int 1, should lead to RuH/OH scrambling. The
ethoxide of Int 1 can further reversibly deprotonate the PNN ligand
to give the dearomatized Int 2, leading to the observed OH/PCH2
proton exchange between ethanol and 2. The energies of TS2, TS3,
and Int 1 are consistent with fast exchange processes on the T1
relaxation rate scale of the protons in the complexes of this study (1/
T1 = ca. 0.5−2 s−1).
H2 eliminations from Int 1 and Int 2 appear barrierless, as no
transition structure could be located by the calculations, indicating the
highly labile nature of the coordinated dihydrogen in these
intermediates. H2 loss from Int 1 leads to Int 3, followed by
formation of ethoxide 4·EtOH. The computed formation of 4·EtOH
from 2·(EtOH)2 is exergonic by −4.5 to −5.2 kcal/mol, in a
reasonable agreement with the experimental estimate of −3.5 kcal/
mol.
H2 elimination from Int 2 gives 1·(EtOH)2 that should collapse to
ethanol complex Int 4·EtOH, further leading to 4·EtOH. Low-energy
TS6 explains the rapid OH/CHP proton exchange between ethanol
and 4 of Figure 1, assuming that Int 4·EtOH itself exchanges with the
ethanol in solution. It is worth stressing that this EtOH/CHP proton
exchange operates directly between ethanol and the PNN ligand of 4·
EtOH via Int 4·EtOH; this proton exchange does not require
formation of 1.
a
Calculated with M06-L and (energies in parentheses) MN15-L
functionals, in toluene continuum (all 1 M solutes, at 298.15 K). The
Gibbs energies (kcal/mol) are per mole of 2·(EtOH)2, under 1 atm
H2. Mass balance is ensured throughout
There are two additional reactions that can take place in the
catalytic solution. One is the reversible deprotonation of the PNN
ligand in Int 3 leading to 1·(EtOH)2 via TS5. The other process
connects 1·(EtOH)2 with Int 5 via TS9. This initially requires 1·
(EtOH)2 to rearrange into a higher-energy structure 1′·(EtOH)2,
illustrated in Figure 6. Scheme 9 and Figure 6 relate to the ideas of
others. Methanol-assisted elimination of the methoxide ligand from
trans-IrH(OCH3)(C6H5)(PMe3)3 was proposed by Blum and
Milstein as a mechanism leading to trans-IrH2(C6H5)(PMe3)3 and
formaldehyde.44 Zeng and Li previously modeled addition of 2-
methoxyethanol to 1 leading to 2 and 2-methoxyacetaldehyde
through the intermediates analogous to Int 4, complex 4, TS7, and
Int 5, without however taking into account hydrogen bonding in the
system.24 The reaction of 1′·(EtOH)2 via TS9 was calculated by
Wang and co-workers.23
The computational studies of Hopmann and Morello45 as well as
Yang46 on the mechanism of ketone hydrogenation catalyzed by
FeH2(CO)[2,6-(CH2PiPr2)2C5H3N] revealed pathways proceeding
with and without dearomatization of the PNP ligand. Such pathways
are also distinct in the dehydrogenation of ethanol of Scheme 9,
diagrammed in Figure 7. Pathway 1 does not involve dearomatized
intermediates, whereas pathway 2 involves dearomatization of the
PNN ligand. Pathways 1 and 2 diverge from Int 1 where the
competing events are the H2 loss on the one hand and deprotonation
of the PNN ligand via TS3 on the other. These pathways converge
again in 4·EtOH, to proceed further via common TS7, Int 5, and TS8.
With current computational methods, the barriers for the considered
pathways (dearomatization or nondearomatization) are similar and
appear equally likely to occur. Considering that 2 with EtOH and 4
with H2 in toluene exist in a relatively fast equilibrium at room
The rearrangement of ethoxide 4·EtOH via TS7 and the
subsequent hydride elimination in Int 5 via TS8 are kinetically
feasible under ambient conditions; however, the net process, EtOH(l)
→ MeCHO(l) + H2 (1 atm), is an endergonic reaction: ΔG° = 10.2
kcal/mol.41,42 The calculated energies for the reaction EtOH(1M,
toluene) → MeCHO(1M, toluene) + H2 (1 atm) are ΔG = 8.4 kcal/
mol (M06-L) and 4.1 kcal/mol (MN15-L), the M06-L calculation
being apparently more accurate. Obviously, the aldehyde is a short-
lived species that should not accumulate in the reaction solution
where it is in a slow equilibrium with 1-ethoxyethanol (K = 0.6 and
ΔG = −0.3 kcal/mol, at room temperature).43
E
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Figure 6. M06-L optimized geometries of 1·(EtOH)2, 1′·(EtOH)2, and TS9 (most hydrogens are not shown for clarity). Selected distances (Å): 1·
(EtOH)2, C1···H1 2.10, O1−H1 0.98, O1···H2 1.82; 1′·(EtOH)2, C1···H1 2.21, O1−H1 0.98, O1···H2 1.87, Ru−H3 2.52; TS9, C1···H1 1.35,
O1−H1 1.30, O1···H2 1.73, Ru−H3 2.17.
a
Scheme 10. Catalytic Formation of Ethyl Acetate
Figure 7. Reaction pathways of the catalytic dehydrogenation, EtOH
→ MeCHO + H2 (g, 1 atm).
temperature (see Figure 1), neither pathway of Figure 7 is rate-
determining in the overall slow catalytic ester synthesis.
Coupling of Acetaldehyde To Give Ethyl Acetate. Aldehyde is a
a
Calculated with M06-L and (energies in parentheses) MN15-L
transient species in the catalytic reactions of Scheme 1, being
functionals, in toluene continuum (all 1 M solutes, at 298.15 K). The
Gibbs energies (kcal/mol) are per mole of 2 with EtOH. Mass
balance is ensured throughout
consumed in two ways: by reinserting into a Ru−H bond of 2 to
regenerate 4, or by adding with the alkoxide. The latter process leads
to ester. The details were elaborated by Hasanayn and Baroudi in
2013 for the Milstein catalyst,47 whereas the first mechanistic ideas of
this catalytic process were formulated by Gru
̈
tzmacher’s group in
The C−O coupling of Scheme 10 leading to ester was
experimentally demonstrated with 3-Os and the Shvo catalyst,
RuH(CO)2[η5-C5Ph4OH]. These hydrides are highly efficient for
the Tishchenko-like disproportionation of aldehydes: 2RCHO →
RC(O)OCH2R, affording TON up to 20 000.49−51 In this process,
the metal alkoxide is produced by insertion of the substrate aldehyde
with the hydride catalyst; the rest of the catalytic cycle is the same as
in Scheme 10.49,50
2008 for a Noyori-type system.48 The mechanism of Hasanayn and
Baroudi for acetaldehyde is illustrated in Scheme 10, by following the
reaction from the ground-state structure of 4. This simplified reaction
model does not consider the intermolecular hydrogen bonding in the
catalytic solution, that renders the calculated formation of 4 from 2
less exergonic when compared with the experimental estimate, ΔG =
−3.5 kcal/mol.
The reaction steps of Scheme 10 include the outer-sphere addition
of acetaldehyde to 4, affording Int 6 (expected to exist in equilibrium
with the off-cycle 1-ethoxy ethoxide of Scheme 8). Int 6 can rearrange
via “slip” TS11, followed by hydride abstraction in TS12 to give the
ester and 2. Ethoxide 4, and subsequently acetaldehyde, are
regenerated from 2 and ethanol as in Scheme 9, where the H2
transfer into the gas phase may, in practice, be the rate-limiting
process. Stationary points TS10 and Int 6 exist only on the MN15-L
pathway. According to the M06-L intrinsic reaction coordinate (IRC)
calculation, TS11 connects 4 and acetaldehyde directly with Int 7.
When attempted with 2, the catalytic disproportionation of
acetaldehyde to ethyl acetate in toluene was unsuccessful.
Acetaldehyde with 2 should give ethoxide 4, which is a labile species
due to the equilibrium between 4 and ethanol complex Int 4, via low-
lying TS13, as in Scheme 10. It is possible that at high aldehyde
concentration displacement of the alcohol from Int 4 can produce
dearomatized 1 that would add to the aldehyde as in the reactions of
Schemes 5 and 8.
Catalytic Transesterification and Ester Hydrogenolysis. Scheme
10 can be rearranged to interpret another catalytic process with 2: the
F
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transesterification of ethyl acetate in methanol. The reaction is started
by insertion of the ester into a Ru−H bond of 2, affording Int 7,
further rearranging to Int 6. Acetaldehyde elimination from Int 6 is
practically barrierless to give ethoxide 4. The EtO−/MeO− metathesis
in methanol is expected to transform 4 into the corresponding
ruthenium methoxide. Acetaldehyde readdition with the methoxide,
followed by the final steps of the cycle of Scheme 11, regenerate 2
accompanied by methyl acetate.
hydrogenolysis of ethyl acetate can be due to relatively high-energy
TS11 and thus slow C−O bond cleavage of the ester.
DISCUSSION
■
The experimental and computational observations allow us to
address several questions. It is appropriate to start by asking
perhaps the most obvious: What is the catalyst of the reactions of
Scheme 1? Among the species of Schemes 8−11, dihydride 2 is
an isolable compound. This complex is involved in a key step
of alcohol dehydrogenation−the formation of H2; it is also
complex 2 that acts as a reducing agent toward the carbonyls. If
one must name a single species as “the catalyst” of the
reactions of Scheme 1, then this should be dihydride complex
2.
Scheme 11. Catalytic Transesterification and Ester
a
Hydrogenolysis
Since the existing ideas about the role of 1 in catalysis are
principally supported by DFT calculations, it is worth noting
that the latter deal with model species in isolation, often in the
gas phase. The stationary points optimized in silico may be
irrelevant under the experimental conditions; thus, computa-
tional studies are at risk of pursuing ideas disconnected from
reality. A reaction mechanism is not “proven” by calculation, it
is only judged reasonable or not, and even a rejected
mechanism can be rejected for wrong reasons. This situation
becomes particularly precarious when the experimental
information is scarce.
An illustration of the above points is the catalytic
dehydrogenation of primary alcohols. According to the
BDHT mechanism of Wang and co-workers,23 also preferred
by Li and Hall,29 the dehydrogenation takes place on 1 via TS9
through the two-step process of Scheme 12, that gives the
a
Scheme 12. Reactions of 1 with Ethanol
a
Calculated with M06-L and (energies in parentheses) MN15-L
functionals, in toluene continuum (all 1 M solutes, at 298.15 K). The
Gibbs energies (kcal/mol) are per mole of 2 with EtOAc. Mass
balance is ensured throughout
Under H2, an alternative reaction from 2 and EtOAc via 4 is the
ester hydrogenolysis: EtOAc + H2 → EtOH + MeCHO. This is an
unfavorable process accompanied by ΔG° = 7.1 kcal/mol (obtained
from the standard molar Gibbs energies of formation of the liquid
species under 1 atm H2).41 The calculated M06-L reaction energy in
toluene is reasonably close: ΔG = 6.0 kcal/mol, whereas the
corresponding MN15-L energy is less accurate, ΔG = 11.7 kcal/mol.
In an anhydrous aprotic solvent media (i.e., when pathway 1 of
Figure 7 is not operative), ethoxide of 4 can directly deprotonate the
PNN ligand in TS13, to give dearomatized ethanol complex Int 4.
Displacement of ethanol by H2 would give dihydrogen complex Int 8;
this can rearrange into 2 via the intramolecular reprotonation of the
PNN ligand in TS1. The hydrogenolysis reaction encounters two
high-energy barriers, TS11 and TS1 (at 28.3 and 31.0 kcal/mol,
respectively, from the M06-L calculations). This is consistent with the
observation of a slow reduction of ethyl acetate in toluene that gave
3.5% conversion after 3 h at 100 °C. Accumulation of the alcohol
product in the catalytic solution should make the reaction steps
connecting 4 and 2 fast. We know this from the experiment of Figure
1, interpreted in Scheme 9. Therefore, the slow rate of the
a
The M06-L Gibbs energies (kcal/mol) are per mole of 1·(EtOH)2.
Mass balance is ensured throughout
aldehyde and 2. In experiment, 1 reacts with methanol to form
RuH(OCH3)(CO)[PNN], and 1 with ethanol is expected to
give the analogous ethoxide. This is because 1 can coordinate
ethanol in Int 4. Subsequent protonation of the dearomatized
PNN ligand is facile and gives ethoxide 4. Then, anagostic Int
5 of Scheme 12 originates from the ethoxide via TS 7, as
proposed by Zeng and Li24 and in this paper (Scheme 9).
The two pathways of Scheme 12, via TS7 and TS9, were
previously considered by Li and Hall, who calculated the
corresponding transition structures, TS81 and TS57, respec-
tively, in Table 5 of their paper,29 with 2-metoxyethanol
instead of ethanol. Unlike the small energy difference in favor
of TS7 versus TS9 in Scheme 12, corresponding TS81 was
found to be 9−14 kcal/mol higher than TS57, depending on
G
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the functional used. Also, the calculated energies for TS81
were surprisingly large, ranging from 27.3 to 38.5 kcal/mol,
unlike the low energy of TS7. Zeng and Li reported a value of
23.7 kcal/mol for the same barrier as TS81. Neither calculation
in the literature included an explicit molecule of hydrogen-
bonded alcohol, which might explain the noted differences.
The alkoxide is most likely greatly stabilized through
hydrogen-bonding to EtOH in Int 5 and in TS7 and TS9.
When considering 1 in neat ethanol, as in the actual
dehydrogenative coupling of Table 1, the principal ruthenium
species in solution must be ethoxide 4, confirmed by the
experiment of Figure 1. An unobserved dearomatized species
that exists in equilibrium with the ethoxide is the ethanol
complex Int 4, however, only in trace amounts, since it is
considerably less stable than 4. Naturally, the 16-electron 1
should be practically nonexistent in neat ethanol, considering
the excess of EtOH vs the catalyst (10 000:1). Reducing this
ratio 5-fold while maintaining the catalyst concentration by
dilution with toluene reduced the TON from 315 to 71 (Table
1); that is, the reaction did not accelerate under the conditions
when 1 could be more abundant.
The three interpretations of alcohol dehydrogenation are
summarized in Scheme 14. According to Wang and co-workers
Scheme 14. Three Interpretations of the Catalytic Alcohol
Dehydrogenation23,24,29
It is worth pointing out a certain problem of invoking 1 in
the BDHT mechanism in step 3 of Scheme 3, which is a
bimolecular reaction between 1 and the hemiacetal. The latter
originates from the transient aldehyde; hence, the reaction rate
of step 3 is proportional to the product of two small numbers:
[1] × [hemiacetal]. This reaction between two transient
species, with 1 being practically nonexistent in neat alcohol, is
improbable, and the BDHT step 3 cannot be a productive
catalytic pathway in solution, even if it can be credibly modeled
in silico.
Another process that has been modeled in the DFT studies
on alcohol dehydrogenation is the elimination of H2 from 2 to
regenerate 1. This is an essential step when 1 is viewed as the
catalyst. H2 can be formed by protonation of a hydride in 2. It
was suggested that the proton comes from the PNN ligand,
according to Scheme 13a.23,24,29 This process encounters
as well as Li and Hall (the BDHT mechanism), the catalytic
turnover involves the bifunctional dehydrogenation of
RCH2OH on 1, and the catalyst is regenerated via the
intramolecular H2 elimination from 2. Zeng and Li, more
reasonably, allow 1 to form the alkoxide RuH(OCH2R)(CO)-
[PNN]; the rest of the process is the same as above.
Alternatively, the author proposes here that the catalyst is 2
and that the reaction proceeds via the alkoxide RuH(OCH2R)-
(CO)[PNN]. Catalyst 2 and the alkoxide are in a relatively fast
equilibrium in solution. In this solution, several dearomatized
intermediates can form (in pathway 2 of Figure 7), yet neither
is singularly important as facilitating the catalytic dehydrogen-
ation. The views expressed here agree with the results of the
calculations by Dub and Gordon who also proposed that
dehydrogenation reactions with the Milstein catalyst can
proceed via a chemically innocent ligand.19
Scheme 13. Protonation of 2
In ester hydrogenation, an interesting question is how 2 is
regenerated from the alkoxide RuH(OCH2R)(CO)[PNN] and
H2. It is worth noting that this process is relatively fast already
at room temperature; thus, this is not an operational concern.
Let us consider a reaction solution where some alcohol is
present, i.e., after a few (or more) catalytic turnovers. Then, 4·
EtOH of Scheme 9 is an appropriate minimal model of the
alkoxide intermediate. There are two pathways from 4·EtOH
to 2·(EtOH)2 in Scheme 9, for the sake of the present
discussion summarized in Scheme 15 with the focus on the key
intermediates and the principal reaction barriers. Path 1 does
not require metal−ligand cooperation. Path 2 involves
dearomatization. Along these pathways, the highest energy
barriers, TS3 and TS4, are within 1.1 kcal/mol. Considering
the computational errors, this difference is insignificant;
however, the two pathways should respond differently to the
increasing alcohol concentration upon ester reduction. The
concentration of dearomatized 1·(EtOH)2 should decrease,
whereas Int 3 is expected to be stabilized through the hydrogen
bonding with the alcohol product of the catalytic reaction.
In conclusion of this discussion, it is appropriate to reiterate
the special role of the metal alkoxides in the catalytic reactions
of Scheme 1. Alkoxides are abundant in solutions of 1 or 2
where a primary alcohol is a substrate or a product (and
optionally the solvent). In general, alkoxides LnM−OCH2R are
barrier TS1 at 25.0 kcal/mol (M06-L energy, see Scheme 8).
Alternatively, it is reasonable to propose that in an alcohol
media, hydridic 2 is protonated by the substrate alcohol. The
barrier for this process is 17.9 kcal/mol (M06-L energy, with R
= Me), i.e., 7.1 kcal/mol below TS1. The subsequent H2
elimination gives the hydrogen-bonded alkoxide RuH-
(OCH2R)(CO)[PNN].52 The related H2 formation and
elimination in the Noyori catalysts have been thoroughly
discussed.53
H
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disproportionation leading to esters.39,49,50 A study of the
coupling of aldehydes with primary amines to give amides also
implicated an alkoxide intermediate.56
a
Scheme 15. Two Pathways from 4 and H2 to 2
In conclusion, it seems fair to state that there is no
computational or experimental reason to support the BDHT
mechanism of Scheme 3 as the principal reaction pathway of
the dehydrogenative coupling of alcohols leading to esters.
Steps 1 and 3 of the mechanism of Scheme 3 are unlikely
under the catalytic conditions. Dearomatization of the PNN
ligand on ruthenium is facile in solution; however, this process
does not open a privileged catalytic pathway in the
(de)hydrogenation reactions. The Noyori-type systems pos-
sessing a protic N−H group remain superior in the
(de)hydrogenation reactions, most likely due to their ability
to stabilize intramolecularly the important ion-pair alkoxide
intermediates, e.g., Int 3 and Int 7, via hydrogen bonding to
the N−H functionality.
A certain concern can be expressed about the practice of gas-
phase modeling (geometry optimizations) of the hydrogen ion
(H+ and/or H−) transfers in some DFT studies of metal−
ligand cooperation, resulting in the artificially concerted
transition states, as has been recently highlighted by Dub.19
The concerted “proton transfer shuttle/relay”8,9,28,52,54,55,67
model is a particular suspect,19,57,64 that when encountered in a
gas-phase calculation must be verified by an optimization in a
solvent continuum.
a
The M06-L Gibbs energies (kcal/mol) are per mole of 4·(EtOH)2.
Mass balance is ensured throughout
important intermediates and/or off-loop species in the catalytic
hydrogenation and dehydrogenative coupling reac-
tions.49,50,56−63 DFT calculations demonstrated that the
Noyori-type catalysts act via discrete H−/H+ transfer steps,
via alkoxides as intermediates and/or off-loop species.19,53,64,65
Thus, the efficiency of a (de)hydrogenation catalyst much
depends on the properties of the corresponding alkoxide.
To name the most important, and perhaps an obvious,
criteria: the alkoxides must be kinetically labile. This is critical
in alcohol dehydrogenation, where LnM−OCH2R should
rearrange into the corresponding zwitterion LnM+(κ-H−
C(R)O−) to produce the aldehyde, as in Scheme 12. In the
hydrogenation reactions, alkoxide elimination opens a pathway
to the heterolytic splitting of H2: LnM−OCH2R + H2 ⇌
LnMH + RCH2OH.
Note that LnMH is the hydrogenation catalyst, and we may
want this to be reasonably abundant for efficient ester
reduction. Since typically [H2] ≪ [RCH2OH], the equilibrium
naturally shifts toward the alkoxide, as we have seen with 2 and
3-Os. It is for this reason that, ideally, the alkoxides LnM−
OCH2R should not only be kinetically labile but also
thermodynamically relatively unstable. It is unsurprising that 4
and OsH(OEt)(CO)[PyCH2NHCH2CH2NHPt-Bu2] are not
isolable species. One may reasonably expect efficient catalysts
for the reactions of Scheme 1 to form alkoxides unstable with
respect to elimination of RCH2OH or RCHO. Formation of
esters RC(O)OCH2R has also been observed,39,66 e.g.,
RuH(OEt)(PPh3)[SNS]·EtOH (SNS = HN(CH2CH2SEt)2)
gave RuH2(PPh3)[SNS] and ethyl acetate on mild heating.66
Understandably, the requirements of catalytic hydrogenation
and dehydrogenation are somewhat in conflict. While we want
a low concentration and rapid recycling of the alkoxide to
increase the concentration of the hydrogenation catalyst LnMH
in the former process (hydrogenation), the latter (dehydrogen-
ation) greatly depends on efficient H2 transfer into the gas
phase. Thus, the dehydrogenation should benefit from
increased concentration [H2], and thus [LnM−OCH2R], in
solution. The estimated reaction Gibbs energy for the highly
successful osmium catalyst: 3-Os + EtOH ⇌ OsH(OEt)-
(CO)[PyCH2NHCH2CH2NHPt-Bu2] + H2 is ΔG = −2.5
kcal/mol, in toluene under 1 atm H2. This value may serve as a
useful reference of the desirable thermodynamic stability of
LnMH with RCH2OH versus LnM−OCH2R with H2.
MATERIALS AND METHODS
■
Experimental Details. Complex RuHCl(CO)[PNN] and the
PNN ligand were obtained from Strem Chemicals. All other chemicals
and solvents were purchased from Sigma-Aldrich. Ethyl acetate,
methyl hexanoate, and toluene were filtered through activated basic
alumina in an argon glovebox, where they were further stored and
used together with the anhydrous ethanol and toluene-d8 which were
stored with 3 Å molecular sieves. The NMR spectra were collected on
a Agilent DD2 400 MHz spectrometer. For quantitative integration,
the 1H{13C} NMR spectra were obtained using 15° pulses and a
relaxation delay of 30 s.
Preparation of 2. In an argon glovebox, anhydrous THF (10 mL)
was pipetted into a 100 mL round-bottomed flask containing
RuHCl(CO)[PNN] (0.5 g, 1.02 mmol) and t-BuOK (0.138 g, 1.23
mmol), and the mixture was magnetically stirred for 50 min. After
solvent removal, the dark residue was dried for 2 h under vacuum of
an oil pump. This material was extracted with 38 mL of an anhydrous
benzene/hexane solvent mixture (3:7 v/v) while magnetically stirring
for 1 h. The solution was filtered and transferred into the glass liner of
a 300 mL Parr autoclave (note that 1 is thermally unstable; therefore,
the above manipulations must be all performed without delays). The
reactor was removed from the glovebox, pressurized to 50 bar H2, and
left overnight without heating or stirring. Next, the autoclave was
depressurized, taken back into the glovebox and opened under Ar to
reveal the crystalline yellow product in a light-orange mother liquor.
The solid was filtered, washed with hexane (4 × 6 mL), and dried
under vacuum of an oil pump for 1 h. Yield: 370 mg (80%) of a
yellow crystalline solid. The 1H, 13C, and 31P NMR data for this
material (in C6D6) were consistent with the previously reported data
(see the Supporting Information for details).
Preparation of OsHCl(CO)[PNN]. First, OsHCl(CO)(AsPh3)3
was prepared (3.99 g, 90% yield) following the previously reported
procedure,68 modified by replacing 2-methoxyethanol with 2-
ethoxyethanol and refluxing (the bath at 140 °C) the mixture for
20 h. This modification is recommended for future use.
In an argon glovebox, a 48 mL pressure tube equipped with a 9.5
mm × 13 mm SCIENCEWARE rare-earth spinbar was charged with
3.68 g (3.10 mmol) of OsHCl(CO)(AsPh3)3; then, the PNN ligand
(1.11 g, 3.40 mmol) was added as a solution in 20 mL of diglyme.
The tube was tightly closed, removed from the box, and placed into
It remains to be added that alkoxides LnM−OCH2R are
prominently involved in the C−O bond formation in the
dehydrogenative coupling of Scheme 1a, and they are the key
intermediates in the related Tishchenko-like aldehyde
I
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an oil bath preheated to 160 °C. Upon stirring, the solids dissolved
within 15 min, affording a dark-tea colored solution that was stirred at
160 °C for 1 h. After cooling, the product crystallized at room
temperature. For product isolation, the tube was taken back into the
glovebox. The solid was filtered, washed with diglyme (4 × 6 mL),
then dried under vacuum for 3 h. Yield: 1.45 g (80%) of a bright
to 0.1 mg. Next, 9.59 g of ethanol was added. After taking the tube out
of the box, it was connected to a vacuum/Ar manifold. Under argon,
the stopper was replaced by a finger condenser connected to a
circulating refrigerated bath. When the temperature in the refrigerated
bath reached −5 °C, the flask was placed in a ethylene glycol bath on
top of a hot plate stirrer. The argon tank was closed, and the gas
released as the bath temperature increased to 90 °C was allowed to
pass freely through a mineral oil bubbler. Throughout the reaction,
the temperature in the coldfinger was maintained between −10 and
−15 °C and in the bath at 90 °C, while stirring at 1100 rpm.
Computational Details. All calculated ruthenium species of this
paper are diamagnetic and possess a zero net charge. The DFT
calculations were carried out with Gaussian 1669 using the MN15-L70
and M06-L71,72 functionals. The basis sets used for the geometry
optimizations included Def2QZVP (with def2 ECP) for Ru, and
Def2SVPD for all other atoms (together with the W06 density fitting
basis set).73,74 The polarizable continuum model (IEFPCM) was used
in all without exception calculations (solvent = toluene), with the radii
and nonelectrostatic terms of Truhlar and co-workers’ SMD solvation
model (scrf = smd).75 All geometry optimizations were accompanied
by frequency calculations. The nature of the transition states TS2,
TS4, TS6, TS7, TS9, and TS11 was confirmed by IRC calculations.
The reaction Gibbs energies were obtained by combining the
calculated energies for the nongaseous species with the standard
state 1.89 kcal/mol correction following the approach recommended
in the recent literature.76,77 Dynamics has not been taken into account
when modeling the structures of Scheme 9 with the explicit,
hydrogen-bonded ethanol.
1
lemon-yellow solid containing a trace (ca. 3 mol %) of diglyme. H
NMR (400 MHz; CD2Cl2): δ 7.65 (t, J = 7.8 Hz, 1H), 7.32 (d, J = 7.9
Hz, 1H), 7.19 (d, J = 7.7 Hz, 1H), 5.20 (d, J = 14.7 Hz, 1H), 4.01
(dd, J = 14.7, 2.8 Hz, 1H), 3.89 (m, 1H), 3.64 (m, 2H), 3.05 (dd, J =
17.2, 8.9, 1H), 2.97 (pd, J = 6.4, 2.8, 1H), 2.87 (m, 1H), 1.31 (d, J =
7.0, 9H), 1.28 (d, J = 7.2, 9H), 1.21 (t, J = 7.0 Hz, 3H), 1.12 (t, J =
7.2 Hz, 3H), −17.06 (d, J = 19.0 Hz, 1H). 13C{1H} NMR (100 MHz;
CD2Cl2): δ 192.59 (d, J = 9.1 Hz, 1C), 162.91 (d, J = 2.8 Hz, 1C),
161.50 (d, J = 2.6 Hz, 1C), 137.12 (s, 1C), 120.87 (d, J = 8.7 Hz, 1C),
120.01 (s, 1C), 66.27 (s, 1C), 58.31 (s, 1C), 50.98 (d, J = 1.2 Hz,
1C), 39.10 (d, J = 24.2, 1C), 38.76 (d, J = 18.5 Hz, 1C), 36.27 (d, J =
29.8 Hz, 1C), 30.75 (d, J = 2.5 Hz, 3C), 29.32 (d, J = 4.1 Hz, 3C),
12.08 (s, 1C), 9.60 (s, 1C). 31P{1H} NMR (162 MHz; CD2Cl2): δ
60.7 (s, JPOs = 266.0 Hz).
Preparation of OsH2(CO)[PNN] (2-Os). First, 4.64 g (5.2 mL) of
a 1 M solution of Li[HBEt3] (5.2 mmol) was added to 1 g (1.73
mmol) of OsHCl(CO)[PNN] in a 20 mL vial. The resulting yellow
suspension was magnetically stirred for 2 h. The product was filtered
using a 15 mL fritted funnel, washed with THF (4 × 1.5 mL), and
dried under vacuum of an oil pump for 2 h. Yield: 0.84 g (89%) of a
bright yellow solid containing ca. 4% of the unreacted OsHCl(CO)-
[PNN]. 1H NMR (400 MHz; C6H6): δ 6.77 (t, J = 7.8 Hz, 1H), 6.47
(d, J = 7.8 Hz, 1H), 6.26 (d, J = 7.6 Hz, 1H), 3.77 (s, 2H), 3.14 (m,
4H), 2.99 (d, J = 8.7 Hz, 2H), 1.41 (d, J = 12.7 Hz, 18H), 0.92 (t, J =
7.1 Hz, 6H), −4.47 (d, J = 11.0 Hz, 2H). 13C{1H} NMR (100 MHz;
C6H6): δ 197.33 (d, J = 9.7 Hz, 1C), 161.96 (d, J = 3.5 Hz 1C),
159.43 (d, J = 2.8 Hz, 1C), 133.11 (s, 1C), 119.65 (d, J = 8.4 Hz, 1C),
117.95 (s, 1C), 70.95 (s, 1C), 58.24 (d, J = 1.5 Hz, 2C), 39.62 (d, J =
21.0 Hz, 1C), 36.04 (d, J = 23.3 Hz, 2C), 29.94 (d, J = 3.9 Hz, 6C),
12.14 (s, 2C). 31P{1H} NMR (162 MHz; C6D6): δ 76.4 (s).
NMR Data for 4 (Extracted from the Spectra in Figures S8−
S15). 1H NMR (400 MHz; toluene-d8, in the presence of ca. 8 equiv
ASSOCIATED CONTENT
■
S
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.organomet.9b00542.
Representative NMR spectra, computed energies, a
summary of the crystal data collection and refinement
parameters for 2-Os (PDF)
3
3
of EtOH): δ 7.08 (t, J = 7.6 Hz, 1H, Py), 6.87 (d, J = 7.6 Hz, 1H,
Cartesian coordinates of the metal complexes (XYZ)
Py), 6.71 (d, 3J = 7.6 Hz, 1H, Py), 4.85 (d, 2J = 14.8 Hz, 1H, NCH),
3.42 (dd, J = 14.8, 2.7 Hz, 1H, NCH), 3.39 (q, J = 7.2 Hz, 3H,
NCH2), 2.87 (d, J = 8.9 Hz, 1H, PCH), 2.58 (m, 1H, NCH2), 2.47
(m, 1H, NCH2), 1.34 (d, J = 13.2 Hz, 9H, CH3), 1.13 (d, J = 12.8
3
Accession Codes
1
CCDC 1946190 contains the supplementary crystallographic
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 Cam-
bridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
3
3
3
3
Hz, 9H, CH3), 1.09 (t, J = 7.1 Hz, 3H), 0.97 (t, J = 7.2 Hz, 3H),
−16.11 (d, 2J = 29.2 Hz, 1H), resonances of the Ru(OEt) group and
one PCH proton cannot be directly identified due to the exchanges of
Figure 1 (see the accompanying discussion). 13C{1H} NMR (100
MHz; toluene-d8): δ 208.5 (CO), 161.8 (d, J = 2.3 Hz, C, Py), 161.3
(d, J = 4.5 Hz, C, Py), 136.4 (s, CH, Py), 119.9 (d, J = 9.5 Hz, CH,
Py), 119.5 (s, CH, Py), 64.8 (d, J = 1.4 Hz, NCH2Py), 54.5 (s,
NCH2), 49.7 (d, J = 1.4 Hz, NCH2), 37.3 (d, J = 11.4 Hz, PCH2),
37.2 (d, J = 19.1 Hz, C, t-Bu), 36.1 (d, J = 26.3 Hz, C, t-Bu), 30.0 (d, J
= 3.2 Hz, CH3, t-Bu), 29.6 (d, J = 5.2 Hz, CH3, t-Bu), 11.2 (s, CH3),
8.3 (s, CH3); the spectrum also displays broad resonances at 57.5
(OCH2) and 18.8 (CH3) due to the exchanging Ru(OEt) and EtOH.
31P{1H} NMR (162 MHz; toluene-d8): δ 107.3 (s).
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: dgoussev@wlu.ca.
ORCID
Dmitry G. Gusev: 0000-0003-3302-356X
Funding
Hydrogenation. The hydrogenations of ethyl acetate and methyl
hexanoate were performed under initial p(H2) = 50 bar, in a 300 mL
stainless-steel Parr reactor. Inside an argon glovebox, the required
quantities of the catalyst (and t-BuOK, when used) were weighed out
on a calibrated analytical balance accurate to 0.1 mg. A balance
accurate to 1 mg was used for taking the calculated masses of the
esters. The reactor was loaded and assembled inside the glovebox,
then taken outside and pressurized under H2. The pressurized reactor
was disconnected from the H2 tank and placed into an oil bath
preheated to 100 °C on a hot plate stirrer. This temperature was
maintained for 3 h while magnetically stirring at 400 rpm.
Natural Sciences and Engineering Research Council (NSERC)
of Canada, Discovery grant program.
Notes
The author declares no competing financial interest.
ACKNOWLEDGMENTS
■
D.G. is thankful to the NSERC of Canada-Discovery grant
program, CFI LOF program, Compute Canada, and Wilfrid
Laurier University for support. D.G. is also indebted to Prof. L.
Dawe, Wilfrid Laurier University, for the help with the
structure determination of 3-Os.
Acceptorless Dehydrogenative Coupling. In an argon glove-
box, 11.5 mg of 2 was added into a 50 mL Schlenk tube (also
containing a microstirbar) on a calibrated analytical balance accurate
J
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