Ambient-Pressure and Base-Free Aldehyde Hydrogenation Catalyst Supported by a Bifunctional Abnormal NHC Ligand

Article abstract of DOI:10.1021/acs.organomet.8b00729

Catalytic aldehyde hydrogenation is an essential and routinely used chemical synthesis process in both academia and industry. However, there is a serious scarcity of efficient homogeneous catalysts for this process to work under highly demanding atmospheric-pressure, base-free, and aqueous conditions. Addressing this problem, herein, we report an iridium-based catalyst for facile atmospheric-pressure and base-free hydrogenation of various aromatic, heteroaromatic, and aliphatic aldehydes. The catalyst also displays excellent chemoselectivity toward aldehyde over other carbonyl functionalities and unsaturated motifs. Moreover, the catalyst is found to work in H₂O (and in H₂O-ethanol) medium at ambient temperature. All of the above attributes have been possible to incorporate into this unique catalyst via employing a hybrid bifunctional ligand, which plays a crucial role in facilitating the cleavage of H₂ as well as effectively delivering hydride to the substrate without any help of base or pressure.

Full text of DOI:10.1021/acs.organomet.8b00729

Article
pubs.acs.org/Organometallics
Cite This: Organometallics XXXX, XXX, XXX−XXX
Ambient-Pressure and Base-Free Aldehyde Hydrogenation Catalyst
Supported by a Bifunctional Abnormal NHC Ligand
Subhash Garhwal, Babulal Maji, Shrivats Semwal, and Joyanta Choudhury*
Organometallics & Smart Materials Laboratory, Department of Chemistry, Indian Institute of Science Education and Research
Bhopal, Bhopal 462 066, India
S
* Supporting Information
ABSTRACT: Catalytic aldehyde hydrogenation is an essential
and routinely used chemical synthesis process in both
academia and industry. However, there is a serious scarcity
of efficient homogeneous catalysts for this process to work
under highly demanding atmospheric-pressure, base-free, and
aqueous conditions. Addressing this problem, herein, we report
an iridium-based catalyst for facile atmospheric-pressure and
base-free hydrogenation of various aromatic, heteroaromatic,
and aliphatic aldehydes. The catalyst also displays excellent
chemoselectivity toward aldehyde over other carbonyl
functionalities and unsaturated motifs. Moreover, the catalyst
is found to work in H2O (and in H2O−ethanol) medium at
ambient temperature. All of the above attributes have been
possible to incorporate into this unique catalyst via employing
a hybrid bifunctional ligand, which plays a crucial role in facilitating the cleavage of H2 as well as effectively delivering hydride to
the substrate without any help of base or pressure.
independently by Hanson9a and Do,9b which hydrogenate
aldehydes under 1 atm H2 pressure and base-free conditions
with some limitations, such as using tetrahydrofuran (THF)
solvent, 4 atm pressure, and longer reaction time (64 h at 60
INTRODUCTION
■
Aldehyde-to-alcohol is a fundamental organic transformation
utilized on a regular basis not only in academic laboratories but
also in industry for the synthesis of various fine and bulk
chemicals.1 To realize such a transformation, environmentally
unfriendly traditional reduction with NaBH4, boranes, LiAlH-
(OR)3, or Bu3SnH is still employed, leading to a large amount
of undesirable waste.2 This problem necessitated development
of a catalytic aldehyde hydrogenation (CAH) protocol using
H2 gas as a clean and green reagent.3 Accordingly, there has
been a gradual evolution of many highly efficient homogeneous
hydrogenation catalysts, pioneered by Milstein, Kirchner,
Beller, Kempe, and others,4 to fulfill some of the practical
requirements such as using ambient temperature, earth-
abundant metals, etc. These individual successes were achieved
using high-pressure H2 gas and an inorganic/organic base.
Whereas the use of pressurized H2 gas needs specialized
experimental setup to take care of safety issues, the presence of
base may mediate aldol-type side reactions from aldehyde or
may limit the functional group tolerance.5 Thus, developing
suitable catalysts that work both at atmospheric pressure of H2
as well as under base-free conditions is highly desirable (Figure
1a). The use of base could be avoided for some of the recently
developed catalysts by Kirchner,6a Grainger,6b van Leeuwen,6c
Zhang,6d and others7 via exploring new ligands and various
metals. Similarly, high pressure was avoided with Crabtree’s
catalyst using 50 mol % of base as an essential additive.8 To the
best of our knowledge, only two catalysts were reported
°C) for aliphatic aldehydes, and no demonstration of
chemoselectivity (Figure 1b). In contrast to atmospheric-
pressure and base-free aldehyde hydrogenation with H2, the
transfer hydrogenation of aldehyde with a non-H2 hydrogen
source is well-developed, and many elegant mild catalysts were
reported.10 At this juncture, considering the existing status of
the relatively economic10f CAH protocol, we paid attention to
develop a unique ligand which would serve two crucial
functions to facilitate the key steps of the catalytic cycle for the
hydrogenation reaction. For facile H−H bond cleavage at mild
pressure and temperature without any external base, we relied
on an Ir−anionic benzimidazolato motif having a free basic
imino nitrogen in the ring (exo nitrogen site) to capture the
proton (H+) generated from H2. In our previous work, we
found that this exo basic imino nitrogen is susceptible toward
protonation.11 In parallel, for efficient hydride transfer, we also
configured the ligand with the powerful σ-donor capacity of an
abnormal NHC (aNHC) moiety based on the imidazol-5-
ylidene motif.12 Based on these considerations, the hybrid
bifunctional ligand, as depicted in Figure 1c, was designed to
utilize the corresponding Cp*Ir-based complex [Ir]-Cl for
Received: October 8, 2018
© XXXX American Chemical Society
A
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(Figure 2b and Supporting Information, SI). Initially, catalytic
hydrogenation reaction of benzaldehyde was screened with 0.5
mol % loading of [Ir]-Cl under base-free and hydrogen balloon
conditions (H2 pressure of about 1 bar) in ethanol as solvent at
35 °C (Figure 2c). Delightedly, just after 3 h of reaction time,
98% yield of benzyl alcohol was recorded by gas chromato-
graphic (GC) analysis. Interestingly, the yield was found to be
85% when the reaction was analyzed after 2 h. Other organic
solvents such as acetonitrile (CH3CN) or dichloromethane
(CH2Cl2) resulted in <5% yield of product. On the other hand,
in water (H2O), nearly quantitative yield (99%) of benzyl
alcohol was obtained after 2 h under identical conditions. An
ambient temperature of 27
1 °C was also found to be
perfectly suitable for furnishing 99% product yield in H2O in
just 2 h. Decreasing the reaction time to 1 h led to a decrease
in yield to 85%. It is noteworthy that many aromatic aldehydes
are not soluble in water. To address this issue, the efficacy of
[Ir]-Cl was tested in H2O−EtOH (2:1, v/v) mixed solvent
under identical conditions. The screening results with
benzaldehyde were found to be almost the same in this
mixed aqueous ethanol solvent, as well, furnishing 99% yield of
benzyl alcohol after 2 h at 27 1 °C. Notably, conversion of
benzaldehyde to benzyl alcohol did not take place in the
absence of hydrogen gas, thus ruling out the possibility of
hydride transfer from EtOH (or H2O) in this catalysis.
Figure 1. Current status of aldehyde hydrogenation catalysts toward
developing an atmospheric-pressure and base-free version (a,b) and
the present approach (c).
With the above-developed highly practical, simple, and mild
reaction conditions in hand, the activity of this promising
catalyst, [Ir]-Cl, was explored toward hydrogenation of several
aromatic, heteroaromatic, and aliphatic aldehydes in H2O or
H2O−EtOH (2:1, v/v) mixed solvent, as shown in Table 1. A
similarly high activity was observed with a variety of aromatic
aldehydes containing electron-donating (−Me, −OMe) as well
as electron-withdrawing (−F, −Cl, −Br) substituents, affording
the corresponding benzyl alcohols in 85−99% yield without
any side products. Moreover, substituents such as −OH,
−NO2, and −CN on the arene backbone could also lead to
high yield (93−97%) of the benzyl alcohol products without
any adverse interference to or inhibition of the catalytic
activity. Intramolecular chemoselectivity was examined with
aromatic substrates containing both aldehyde and other
carbonyl functionalities like ketone, ester, amide, etc. For
these substrates, only the aldehyde group was selectively
hydrogenated to alcohol without compromising the yield of
the desired alcohols (85−98%). For many catalysts, selectivity
between aldehyde and ketone becomes an issue because of
facile, atmospheric-pressure and base-free hydrogenation of
various routinely used aromatic, heteroaromatic, and aliphatic
aldehydes. Furthermore, the catalyst was found to work in a
much desirable chemoselective fashion, in H2O as well as in
aqueous ethanol solvent and also at ambient temperature.
RESULTS AND DISCUSSION
■
The hybrid benzimidazolato aNHC-bound Cp*Ir complex,
[Ir]-Cl, was synthesized as shown in Figure 2a. The
coordination modes of the ligand in [Ir]-Cl were characterized
by H NMR and 13C{1H} NMR spectroscopy and electron-
1
spray ionization mass spectrometry (ESIMS) and confirmed
unambiguously by single-crystal X-ray diffraction studies
similar energies of hydrogenation of aldehydes (−ΔH°298
=
16−20 kcal/mol) and ketones (−ΔH°298 = 14 kcal/mol),13
although steric factors favor the aldehyde kinetically. More-
over, complete intermolecular chemoselectivity toward hydro-
genation of aldehyde over other unsaturated organic substrates,
such as alkene, alkyne, ketone, and enone, was also achieved
with this catalyst in competitive reactions using an equimolar
mixture of benzaldehyde and the respective cosubstrates. While
heteroaromatic aldehydes were tested, interestingly, no
decomposition and/or unselective reaction was observed for
the hydrogenation of 2-furaldehyde and 2-thiophenecarbox-
aldehyde, and high yields of the respective alcohols (94 and
93%, respectively) were obtained. The efficacy of [Ir]-Cl was
checked for aliphatic aldehydes also. Gratifyingly, hexanal and
heptanal were hydrogenated easily under similar balloon
pressure conditions to their alcohol products in 95 and 92%
yields, respectively, after 3 h reaction time. Finally, a reaction
Figure 2. Synthesis (a), structure (b), and activity (c) of the catalyst
[Ir]-Cl.
B
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Table 1. Scope (A), Chemoselectivity (B), Scalability (C)
1
Figure 3. VT (263−313 K) H NMR spectroscopic monitoring of a
stoichiometric reaction of [Ir]-Cl (0.002 mmol) and PhCHO (0.002
mmol) in the presence of H2 in CD3OD: monitoring of PhCHO peak
(a); PhCH2OH, PhCH2OD, and H2 peaks (b); Ir−H peak (c); and
ligand N-Me and C-Me peaks (d).
at 4.57 ppm was also observed along with the Ir−H peak at
−14.6 ppm at the lower temperatures, whereas both peaks
disappeared at higher temperatures, suggesting a plausible
reversibility of the H2 cleavage step. To probe this, a similar
a
b
Solvent = H2O−EtOH. Time = 3 h. See SI for details.
1
was conducted with 5 mmol of benzaldehyde, which furnished
an isolated yield of 95% after 4 h.
VT H NMR experiment, but without introducing benzalde-
hyde into the NMR tube, was monitored from 233 to 313 K in
CD3OD (Figure 4). Indeed, the appearance of the sharp Ir−H
peak along with a broad H2 peak at lower temperature regime
and slow, gradual disappearance of the same with increasing
temperature (Figure 4a,b) supported such a hypothesis of
reversible cleavage of H2 by the catalyst, generating a fast
equilibrium of the type (Ir-solvento + H2) ↔ Ir−H species.
The broadening effect of the ligand backbone protons (along
with Cp* protons) with increasing temperature was also
observed as expected for a fast equilibrium between two Ir
species (Figure 4c−e). The plausible N−H peak could not be
traced probably due to hydrogen bonding and/or H/D
exchange with the solvent (CD3OD). In this regard, previously,
Xiao also demonstrated that the N−H peak present within the
ligand backbone of similar Ir complexes could not be observed
in 1H NMR spectra because of hydrogen bonding.14 Attempts
to isolate and crystallize the Ir−H species from a reaction of
[Ir]-Cl and H2(g) under an atmosphere of H2 were
unsuccessful, even at low temperature.
After establishing the merits of the present catalyst in CAH
process, we next sought to gain insights into the mechanistic
issues related to the catalytic cycle. At first, a stoichiometric
reaction containing [Ir]-Cl (0.002 mmol) and benzaldehyde
(0.002 mmol) in a Wilmad low-pressure/vacuum (LPV) NMR
tube with occasional charging of H2 gas from an external
1
balloon source was followed by H NMR spectroscopy in
CD3OD at ambient temperature (see SI). A hydride signal at
−14.6 ppm was observed just after 10 min, along with the
signals due to benzyl alcohol (a broad singlet at 4.60 ppm for
PhCH2OH and a broad triplet at 4.58 ppm for PhCH2OD),
which was generated in a small amount. After another 10 min,
upon the disappearance of the hydride signal, the mixture was
again charged with H2 gas, and the reaction was followed at 10
min intervals. A gradual decrease of the benzaldehyde signals at
10.0 ppm (a singlet) with concomitant increase of the benzyl
alcohol signals was observed. No other intermediate was
observed in this experiment. To investigate this stoichiometric
reaction further, a similar experiment was monitored by
variable-temperature H NMR (VT H NMR) spectroscopy
from 263 to 313 K in CD3OD (Figure 3). Upon increasing the
temperature, a gradual decrease of hydride and benzaldehyde
peaks along with increase of benzyl alcohol peak was recorded
(Figure 3a−c). Interestingly, the intensity of the methyl peaks
of the catalyst backbone remained unchanged throughout the
experiment (Figure 3d), suggesting the integrity of the catalyst.
In the above VT 1H NMR experiment, the signal due to H2 gas
Next, for the present CAH reaction by [Ir]-Cl, initial rate
kinetics was carried out to determine the order of each
component, and the results suggested a rate law of rate =
1
1
k
obs[cat][H2][aldehyde]. A plausible catalytic cycle was
depicted in Figure 5. The initial dissociation of the chloride
ligand from [Ir]-Cl followed by reversible cleavage of H2 was
already supported by the VT 1H NMR experiments. Inhibition
of rate by added chloride was also observed (see SI, Figure S8).
The actual mechanism of H2 cleavage needs further extensive
C
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investigation and is the subject of a future study. The first-
order rate dependence on an aldehyde suggested involvement
of a bimolecular reaction between the Ir−H species and the
aldehyde, which was not coordinated directly to the metal
center in its primary coordination sphere (required zero-order
dependency and inner-sphere hydride transfer15), indicating
the possibility of an outer-sphere hydride transfer pathway. To
check the nature of hydride and proton transfer to aldehyde to
form alcohol, rates of the catalytic hydrogenation of
benzaldehyde with 0.5 mol % of [Ir]-Cl were evaluated in
water at 27
1 °C under the following four reaction
conditions: (i) H2 balloon, H2O solvent; (ii) H2 balloon, D2O
solvent; (iii) D2 balloon, H2O solvent; and (iv) D2 balloon,
D2O solvent (Figure 6a). The plausible H/D exchange
between the acidic NH proton on the catalyst and the solvent
(as suggested earlier from 1H NMR experiments) allowed us to
compare the relative reactivity of NH and ND. On the other
1
hand, as discussed previously, H NMR studies suggested no
H/D exchange between Ir−H and solvent D under the present
reaction conditions (neutral medium) (see SI), although acid-
catalyzed Ir−H/D2O exchange was reported previously.16
With this information in hand, the above four experiments
afforded the following deuterium kinetic isotope effect (DKIE)
values: (i) k(Ir−H)(N−H)/k(Ir−D)(N−H) = 2.05
0.03; (ii)
k
k
(Ir−H)(N−H)/k(Ir−H)(N−D) = 1.04
(Ir−H)(N−H)/k(Ir−D)(N−D) = 2.07
0.05; and (iii)
0.05. These values of
DKIEs suggested the involvement of only Ir−H hydride
transfer to the aldehyde CO group in the rate-determining
step. A Hammett plot of relative reactivities of para-substituted
benzaldehydes to unsubstituted benzaldehyde resulted in a
small reaction constant (ρ) value of +1.47 (Figure 6b),
indicating development of only small negative charge on the
carbonyl carbon of benzaldehyde in the transition state, in line
with the outer-sphere hydride delivery mechanism.17 This is in
contrast to the relatively large ρ value of +4.7 observed for
NaBH4 reduction of benzaldehyde, implying a more anionic
nature of the transition state.18 Of course, more experiments
will be required to scrutinize our proposal and to consider
other alternatives, especially for the hydride and proton
transfer steps. For example, a solvent (H2O/EtOH)-assisted
NH proton transfer step via hydrogen bonding could not be
ruled out at this stage. Nevertheless, we believe that the
abnormal Ir-bound imidazol-5-ylidene-based strong σ-donor
NHC ligand must have favored the hydride transfer
significantly by making the Ir−H species more hydridic.
Previously, it was shown that strong electron-donating ligands
enhance hydricity of metal hydrides.19 Additionally, Peris’s
work on CO2 hydrogenation also suggested that an Ir-
abnormal NHC catalyst performed better than its Ir-normal
NHC counterpart, presumably due to the higher electron
donor character of the former.12c
Figure 4. VT (233 K−313 K) 1H NMR spectroscopic monitoring of a
stoichiometric reaction of [Ir]-Cl (0.002 mmol) and H2 in CD3OD:
monitoring of Ir−H peak (a); H2 peak (b); Cp*-Me peak (c); ligand
N-Me and C-Me peaks (d); and ligand aromatic backbone peaks (e).
Figure 5. Plausible mechanistic steps.
CONCLUSION
■
In summary, a highly efficient, chemoselective, aldehyde
hydrogenation catalyst was developed for general applicability
under atmospheric-pressure, base-free, ambient temperature
and aqueous conditions. A variety of substituted aromatic
aldehydes as well as heteroaromatic and aliphatic aldehydes
were tested successfully with this practical catalyst. This may
compliment the existing mild transfer hydrogenation protocol
of aldehyde. Applicability toward complex organic molecules
and in-depth mechanistic study are ongoing.
Figure 6. KDIE rate plots (a) and Hammett plot (b).
D
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ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.organo-
met.8b00729.
■
S
̈
2018, 47, 1459−1483. (b) Gorgas, N.; Stoger, B.; Veiros, L. F.;
Kirchner, K. Highly Efficient and Selective Hydrogenation of
Aldehydes: A Well-Defined Fe(II) Catalyst Exhibits Noble-Metal
Activity. ACS Catal. 2016, 6, 2664−2672. (c) Zell, T.; Ben-David, Y.;
Milstein, D. Highly efficient, general hydrogenation of aldehydes
catalyzed by PNP iron pincer complexes. Catal. Sci. Technol. 2015, 5,
822−826. (d) Elangovan, S.; Topf, C.; Fischer, S.; Jiao, H.;
Spannenberg, A.; Baumann, W.; Ludwig, R.; Junge, K.; Beller, M.
Selective Catalytic Hydrogenations of Nitriles, Ketones, and
Aldehydes by Well-Defined Manganese Pincer Complexes. J. Am.
Chem. Soc. 2016, 138, 8809−8814. (e) Fleischer, S.; Zhou, S.; Junge,
K.; Beller, M. General and Highly Efficient Iron-Catalyzed Hydro-
genation of Aldehydes, Ketones, and α,β-Unsaturated Aldehydes.
Experimental details and spectra (PDF)
Accession Codes
CCDC 1854352 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.
̈
Angew. Chem., Int. Ed. 2013, 52, 5120−5124. (f) Rosler, S.; Obenauf,
AUTHOR INFORMATION
Corresponding Author
*E-mail: joyanta@iiserb.ac.in.
ORCID
Subhash Garhwal: 0000-0002-0093-9224
Joyanta Choudhury: 0000-0003-4776-8757
Notes
■
J.; Kempe, R. A Highly Active and Easily Accessible Cobalt Catalyst
for Selective Hydrogenation of CO Bonds. J. Am. Chem. Soc. 2015,
137, 7998−8001. (g) Kallmeier, F.; Irrgang, T.; Dietel, T.; Kempe, R.
Highly Active and Selective Manganese C = O Bond Hydrogenation
Catalysts: The Importance of the Multidentate Ligand, the Ancillary
Ligands, and the Oxidation State. Angew. Chem., Int. Ed. 2016, 55,
11806−11809. (h) Spasyuk, D.; Vicent, C.; Gusev, D. G. Chemo-
selective Hydrogenation of Carbonyl Compounds and Acceptorless
Dehydrogenative Coupling of Alcohols. J. Am. Chem. Soc. 2015, 137,
3743−3746. (i) Baldino, S.; Facchetti, S.; Zanotti-Gerosa, A.;
Nedden, H. G.; Baratta, W. Transfer Hydrogenation and Hydro-
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The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Financial support from DST-SERB (Grant No. EMR/2016/
003002) and IISER Bhopal and fellowships from IISER Bhopal
(to S.G.) and UGC (to B.M. and S.S.) are gratefully
acknowledged.
(5) Smith, M. B.; March, J. Advanced Organic Chemistry, 5th ed.;
Wiley Interscience: New York, 2001.
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F
DOI: 10.1021/acs.organomet.8b00729
Organometallics XXXX, XXX, XXX−XXX