Chemoselective transfer hydrogenation of aldehydes in aqueous media catalyzed by a well-defined iron(II) hydride complex

Article abstract of DOI:10.1007/s00706-018-2279-7

Abstract: An iron(II) hydride PNP pincer complex is applied as catalyst for the chemoselective transfer hydrogenation of aldehydes using an aqueous solution of sodium formate as hydrogen source. A variety of aromatic, heteroaromatic, and aliphatic aldehydes could be reduced to the corresponding alcohols in good to excellent yields with a catalyst loading of 1.0?mol% at 80?°C and 1?h reaction time. If present, C–C double bonds remained unaffected in course of the reaction, even when they are conjugated to the carbonyl group of the aldehyde. The catalyst’s lifetime and activity could be improved when the reactions were conducted in an ionic liquid-based micro emulsion. Graphical abstract: [Figure not available: see fulltext.].

Full text of DOI:10.1007/s00706-018-2279-7

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ORIGINAL PAPER
Chemoselective transfer hydrogenation of aldehydes in aqueous
media catalyzed by a well-defined iron(II) hydride complex
Nikolaus Gorgas1 Aleksandra Ilic1 Karl Kirchner1
•
•
Received: 29 June 2018 / Accepted: 6 August 2018
Ó The Author(s) 2018
Abstract
An iron(II) hydride PNP pincer complex is applied as catalyst for the chemoselective transfer hydrogenation of aldehydes
using an aqueous solution of sodium formate as hydrogen source. A variety of aromatic, heteroaromatic, and aliphatic
aldehydes could be reduced to the corresponding alcohols in good to excellent yields with a catalyst loading of 1.0 mol% at
80 °C and 1 h reaction time. If present, C–C double bonds remained unaffected in course of the reaction, even when they
are conjugated to the carbonyl group of the aldehyde. The catalyst’s lifetime and activity could be improved when the
reactions were conducted in an ionic liquid-based micro emulsion.
Graphical abstract
Keywords Aldehydes Á Transfer hydrogenation Á Chemoselective reduction Á Aqueous media Á Iron catalyst
Introduction
method. The use of hazardous hydrogen gas can be avoided
by employing related transfer hydrogenation reactions that
provide a safe and operationally simple alternative [5]. The
use of formic acid or formate salts as reductant is partic-
ularly attractive since water can be used as reaction med-
ium providing access to a green and sustainable process.
Several iridium- and ruthenium-based catalysts have been
reported to excellently promote the selective transfer
hydrogenation of aldehydes using water as solvent and
formates as hydrogen source [6–9, 10].
The reduction of aldehydes represents an important
industrial process since the respective primary alcohols are
required in large amounts for the production of flavors,
frequencies, and pharmaceuticals [1–4]. As the cleanest
and most atom-economical approach, transition-metal cat-
alyzed hydrogenation is mainly employed for this purpose.
However, the need for high-pressure equipment and con-
cerns about safety issues limit the applicability of this
Within this context, our group developed iron(II) PNP
pincer complexes over the past years that are capable for
the hydrogenation and dehydrogenation of carbonyl com-
pounds [11, 12]. For example, the hydrido carbonyl com-
plex 1 was found to efficiently promote the chemoselective
hydrogenation of aldehydes exhibiting unprecedented
& Karl Kirchner
karl.kirchner@tuwien.ac.at
1
Institute of Applied Synthetic Chemistry, Vienna University
of Technology, Getreidemarkt 9/163-AC, 1060 Vienna,
Austria
123

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N. Gorgas et al.
Scheme 1
activity and productivity under mild conditions (Scheme 1)
[13, 14]. The same catalyst could successfully be employed
in the production of dihydrogen by catalytic decomposition
of formic acid [15]. In both cases, the iron(II) dihydride
species 2 could be identified as the catalytically active
species. Therefore, it appeared obvious to combine these
two processes to reduce carbonyl compounds employing
formic acid (FA) as hydrogen donor. In the present paper,
we now report on the chemoselective reduction of alde-
hydes under transfer hydrogenation conditions using water
as reaction medium.
Table 1 Transfer hydrogenation catalyzed by 1 using NaHCO2/H2O
as reductant
Entry
Cat. loading/mol%
Solvent
Yield/%a
1
1.0
1.0
1.0
1.0
1.0
1.0
0.5
0.25
0.25
1,4-dioxane
Heptane
EtoH
46
33
2
3
46
4
5b
Toluene
Neat
84
56
Results and discussion
6
Neat
[ 99
74
7
Neat
To validate our concept, preliminary experiments were
performed under similar conditions as previously reported
for FA dehydrogenation (THF, 40–60 °C) using 1.0 mol%
of catalyst, 4-fluorobenzaldehyde as substrate (2.0 mmol),
and a 1:1 mixture of FA/NEt3 as reductant (10 mmol).
However, only marginal conversion into the respective
primary alcohol could be detected by 19F{1H} NMR
spectroscopy. Instead, we observed strong gas evolution
and complete consumption of formic acid indicating that
H2 formation takes place much faster than hydrogen
transfer to the substrate, since the intermediately formed
dihydride species presumably gets protonated before it can
react with an aldehyde carbonyl group.
8
9c
Neat
52
Neat
65
Conditions: subst. (2.0 mmol), cat., NaHCO2 (2.5 mmol/2.5 M in
H2O), co-solvent (1.0 cm3); 80 °C, 1 h
aDetermined by 19F{1H}NMR
bPerformed at 60 °C
c17 h reaction time
conducted at 80 °C for 1 h and the outcome of these
reactions is summarized in Table 1. Depending on the co-
solvent, conversions between 33 and 84% were obtained
but best results could be achieved when the aqueous
solution was combined with a neat mixture of the catalyst
and the substrate giving full conversion within 1 h. The
catalytic activity significantly dropped when the reaction
temperature was lowered to 60 °C. Decreasing the catalyst
To circumvent this problem, we envisaged the use of an
aqueous sodium formate solution as reducing agent, which
was added to solutions of the catalyst and the substrate in
different organic solvents. First, the experiments were
123

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Chemoselective transfer hydrogenation of aldehydes in aqueous media catalyzed by a well-…
loading to 0.5 and 0.25 mol% resulted in 74 and 53% yield,
respectively, which corresponds to TOFs of more than
200 h-1. Only slightly higher conversions were achieved
by extending the reaction time indicating insufficient long
term stability of the catalyst.
Table 2 Substrate screening using pre-catalyst
hydrogenation condition (yields determined by H NMR)
1
under transfer
1
Thus, we investigated the general applicability of this
protocol by testing the reduction of various substrates in
presence of 1.0 mol% of 1 applying a reaction time of 1 h.
Gratifyingly, a variety of aromatic, heteroaromatic, and
aliphatic aldehydes could be reduced giving the corre-
sponding alcohols in good to excellent yields. If present,
C–C double bonds remained unaffected in course of the
reaction, even when they are conjugated to the carbonyl
group of the aldehyde as in the case of some industrial
important substrates such as citral (A8) or cinnamaldehyde
(A9). Moreover, ketones are not reduced by 2 as demon-
strated by a test reaction employing 4-fluoroacetophenone
as substrate (Table 2).
From a mechanistic perspective, the iron dihydride
complex 2 is supposed to represent the catalytically active
species in the reaction. To verify our assumption, an NMR
experiment has been conducted in which a biphasic mix-
ture of 1 in toluene-d8 and an aqueous solution of sodium
formate was heated up to 80 °C for 20 min. NMR analysis
of the toluene phase revealed the formation of the antici-
pated iron(II) dihydride species 2 which is present as a
mixture of a cis and trans isomer [14]. The triplet reso-
nance at - 23.80 ppm shown in Fig. 1 can be assigned to
the hydride formate complex A [16]. The major species,
however, still remains the pre-catalyst 1 pointing towards
incomplete catalyst activation. However, test reactions
using the isolated iron dihydride 2 gave almost equal
results as obtained with pre-catalyst 1.
Fig. 1 1H NMR spectrum (hydride region) recorded during mechanistic studies
123

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N. Gorgas et al.
Scheme 2
Based on our previous studies [13–16] as well as the
observations made in the NMR experiment described
above, a catalytic cycle has been proposed which is
depicted in simplified form in Scheme 2. The pre-catalyst 1
gets activated by replacement of the bromide ligand by the
formate anion. This intermediate is prone to undergo a non-
classical b-hydride elimination resulting in the formation
of the iron(II) dihydride species 2 and liberation of carbon
dioxide. Due to its strong hydridic character [17], trans-2
(B) is capable of a direct nucleophilic attack on the car-
bonyl carbon atom of the aldehyde substrate to form the
alkoxide complex C. This intermediate is then protonated
by H2O to give the final alcohol. Substrate release provides
a vacant coordination site (D) allowing another formate
molecule to bind on to the metal center to close the cat-
alytic cycle.
Since catalyst 1 was recently reported to be highly
compatible with ionic liquids (IL) [18], we tried to improve
the catalyst lifetime and activity by conducting the iron-
catalyzed transfer hydrogenation in ionic liquid-based
micro emulsions. In particular, it appeared promising to
apply a three-phasic system consisting of the aqueous
formate solution, a heptane phase containing the substrate
and the catalyst dissolved in a separate phase of the ionic
123