Mild reduction with silanes and reductive amination of levulinic acid using a simple manganese catalyst

Article abstract of DOI:10.1016/j.ica.2020.120167

A manganese-based catalytic system using the commercially available complex [Mn(CO)₅Br] was studied for the selective reduction of levulinic acid (LA) to 2-methyl-tetrahydrofuran (MTHF). We further studied the production of pyrrolidines via its reductive amination using silanes (phenylsilane and tetramethyldisiloxane). The results showed high efficiency and selectivity for this reaction leading to high yields using mild reaction conditions.

Full text of DOI:10.1016/j.ica.2020.120167

Inorganica Chimica Acta 516 (2021) 120167
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Inorganica Chimica Acta
journal homepage: www.elsevier.com/locate/ica
Research paper
Mild reduction with silanes and reductive amination of levulinic acid using
a simple manganese catalyst
Diego A. Roa, Juventino J. Garcia*
´
´
Facultad de Química, Universidad Nacional Autonoma de Mexico, Mexico City 04510, Mexico
A R T I C L E I N F O
A B S T R A C T
Keywords:
A manganese-based catalytic system using the commercially available complex [Mn(CO)5Br] was studied for the
selective reduction of levulinic acid (LA) to 2-methyl-tetrahydrofuran (MTHF). We further studied the produc-
tion of pyrrolidines via its reductive amination using silanes (phenylsilane and tetramethyldisiloxane). The re-
sults showed high efficiency and selectivity for this reaction leading to high yields using mild reaction conditions.
Levulinic acid
Manganese
Amination
Reduction
Silanes
2-methyl-tetrahydrofuran
Pyrrolidines
1. Introduction
[7–9]. Recently, the use of earth abundant metal complexes such as [Fe
(CO)4(IMes)] have also been reported via a combination of irradiation
The transformation of biomass-derived molecules into versatile
platform chemicals and potential biofuel candidates has become an area
of current interest. Among these processes, reduction plays a key role in
organic syntheses both in academia and industry [1]. Many efficient and
selective transformations have been discovered leading to significant
developments in the implementation of an emerging biorefinery in-
dustry. Levulinic acid (LA) is one of the most interesting biomass-
derived molecules because it offers two reactive functional groups and
is available at low cost as cellulose waste. LA is a platform chemical and
is used as a fuel additive and serves as a precursor to several high-value
compounds such as γ-valerolactone (GVL) or 2- methyltetrahydrofuran
(MTHF) [2]. The latter offers more value as a fuel additive given its
lower number of oxygen atoms. It is also a solvent of interest given that
its chemical properties are similar to THF but with better physical
properties such as a higher boiling point and lower solubility in water
[3]. Several homogeneous and heterogeneous catalysts have been re-
ported for the hydrogenation of LA to GVL, but there are fewer reports of
direct reduction to MTHF. In homogeneous catalysis, only a few studies
have been reported using noble metals such as ruthenium along with
Bronsted or Lewis acids as additives [4–6].
and thermal conditions [10]. Of note, the previous examples use silanes
as the reducing agents probably because they offer good selectivity and
mild reaction conditions. To the best of our knowledge, no other ex-
amples using a homogeneous catalyst have yet been described for this
process.
Many catalytic systems for LA hydrogenation and reductive amina-
tion processes have been based on the use of noble metals and H2 as a
reducing agent [11]. However, the high cost of noble metals limits their
practical applications and compromises the sustainability of the bio-
refinery concept. As an alternative to noble metal catalysts, non-noble
metal catalysts have gained much attention for use in LA valorization
[12]. Recent reports include the hydrogenation of LA using homoge-
neous iron and cobalt catalysts [13,14].
Recently, several manganese-based catalysts have been reported
showing high activity in a variety of closely related transformations
[15]. Mn is also an abundant metal [16]. However, in most cases, these
catalysts contain a more elaborated ligand [17,18], such as Trovitch’s
catalyst for hydrosilylation of carbonyls [19]. Although this ligand has
great activity (the highest on hydrosilylation in metals of the first
transition series), it contains a pincer ligand [20]. Thus, we disclose here
our findings on the LA hydrogenation to yield 2-methyl-tetrahydrofuran
(MTHF) via a simple manganese pre-catalyst based on [Mn(CO)5Br] and
in the production of pyrrolidines via reductive amination with silanes.
Pyrrolidones are typically produced from the reaction of LA and
primary amines by reductive amination/cyclization using expensive
catalysts such as InI3 or RuCl3 and a variety of reducing reagents;
however, the synthesis of N-substituted pyrrolidines is much more rarer
* Corresponding author.
E-mail address: juvent@unam.mx (J.J. Garcia).
https://doi.org/10.1016/j.ica.2020.120167
Received 20 October 2020; Received in revised form 26 November 2020; Accepted 26 November 2020
Available online 3 December 2020
0020-1693/© 2020 Elsevier B.V. All rights reserved.

D.A. Roa and J.J. Garcia
Inorganica Chimica Acta 516 (2021) 120167
1
monitored by H NMR spectroscopy to understand the reaction mech-
anism of the presented hydrosilylation reaction. Of particular interest
was the high field region of the spectrum because in this area the
presence of hydrides can be assessed, if a monohydride or dihydride type
mechanism may occur [21]. The result of each analysis is shown in
Fig. 1.
Scheme 1. Reduction of levulinic acid with [Mn(CO)5Br].
As seen in Fig. 1, the formation of several signals in the hydride re-
gion was observed in the first hour of heating. Of note, the signal at ꢀ 7.9
ppm has been previously reported as the hydride [Mn(CO)5H]. This was
also detected by GC-MS (S1) and may be a catalytically active complex
[22].
Table 1
Reduction of levulinic acid with different loads of [Mn(CO)5Br].
Entry
% mol [Mn]
t (h)
% Yielda
The signal located at ꢀ 11.05 ppm in the spectrum could be assigned
to the sigma complex with the silane [Mn(CO)5(PhSiH3)]. This is closely
related to other manganese complexes previously assigned in a similar
chemical shift [23]. The signals located at ꢀ 10.75 ppm and ꢀ 16 ppm
can be assigned to hydrides containing a coordinated levulinic acid
molecule by having displaced a carbonyl ligand at the unsaturated hy-
dride [Mn(CO)4H]. The latter is expected to shift to higher fields with
respect to [Mn(CO)5H] as observed in Fig. 1.
1
0
48
48
24
40
48
48
48
0
2
1
74
3
4
~99
~99
~99
~99
95
4
3
5
2.5
2.5
2
6b
7
a
Yields determined by GC-MS, MTHF as internal std.
Mercury drop test.
b
We thus propose a possible reaction pathway in Scheme 4 for the
complete formation of MTHF and a mechanistic proposal for the for-
mation of GVL in Scheme 5. Regarding the reaction pathway, the pro-
posal considers the observed fragments during the reaction monitoring
by GC-MS. Thus, the reaction of LA with hydrosilane (vide infra) is
initially proposed and forms the corresponding silyl ester (Scheme 4,
reaction (1)). This silyl ester is then catalytically reduced to GVL (re-
action 2), and further reduced to 2-methyl-2,3-dihydrofuran (MTDF)
(reaction 3 and 4); finally, it is completely reduced in tandem with a
hydrolysis to produce MTHF (reaction 5 and 6).
Table 2
Temperature assessment.
Entry
T (◦C)
t (h)
% Yielda
1
2
3
80
48
15
24
~99
96
100
100
~99
a
Yields determined by GC-MS.
The mechanistic proposal starts with the formation of [Mn(CO)5H]
via a reaction with the hydrosilane and [Mn(CO)5Br]. This compound
suffers the loss of a carbonyl ligand (complex B) to generate the vacant
site necessary for the coordination of the silyl ester (complex C) (Scheme
5). Here, an end-on type coordination is proposed as in closely related
mechanisms using Mn(I) catalysts [18,24,25]. This step is followed by
an insertion of the hydride in C into the carbonyl moiety at LA to
generate D; intramolecular cyclization of the alkoxy ligand occurs along
with a silanoxide group (complex E) followed by a GVL release to
generate F. Finally, a transmetalation reaction of the silanoxy ligand in
complex F with the incoming hydrosilane regenerates the active species
[Mn(CO)5H] along with the corresponding silanol.
2. Results and discussion
We initially assessed the catalytic activity of complex [Mn(CO)5Br]
with the aim of having a simple and commercially available manganese
complex for the reasons mentioned above. Thus, the key results describe
reactivity optimization regarding catalytic loads of [Mn(CO)5Br] ac-
cording to the reaction depicted in Scheme 1 with details in Table 1.
Consequently, the optimal catalyst load was selected according to
the conditions of entry 5, where we had a higher yield with the lowest
catalyst load. Under these conditions, we assessed the optimum reaction
temperature as shown in Table 2.
To confirm the identity of the signal located at ꢀ 7.9 ppm, complex
[Mn(CO)5H] was synthesized independently according the reported
procedure (see Fig. 2) [22].
With the optimized conditions in hand, the use of a cheaper hydro-
silane was next considered; thus, we turned our attention to the use of
tetramethyldisiloxane (TMDS). Besides the lower cost, this silane is less
susceptible to hydrolysis opening the possibility of using undried sol-
vents and a less risky handling process. Subsequently, the desired
product MTHF could be isolated via simple distillation under reduced
pressure in very good yields (Scheme 2).
A sample of complex [Mn(CO)5H] was independently prepared and
used under the optimized catalytic conditions described above for the
reduction reaction (see Scheme 6). This hydride was able to catalytically
reduce LA. However, a change in selectivity was observed, and this can
Using the optimized conditions described above, the reaction was
studied in the presence of primary amines and phenylsilane in order to
obtain the corresponding pyrrolidines as represented in Scheme 3; the
main experimental results are shown in Table 3.
To quantify and isolate the products listed in Table 3, the corre-
sponding hydrochlorides were prepared instead; the isolated yields are
shown in Table 4.
Scheme 3. Reductive amination of levulinic acid with silanes and pri-
mary amines.
An experiment using stoichiometric amounts of reagents was
Scheme 2. Optimized reduction of LA with silanes.
2

D.A. Roa and J.J. Garcia
Inorganica Chimica Acta 516 (2021) 120167
4. Experimental
Table 3
Reductive amination of LA with PhSiH3 catalyzed by [Mn(CO)5Br].
Entry
Amine
%1aa
%1ba
4.1. General considerations
1
94
6
Unless otherwise stated, all processes were performed using standard
Schlenk techniques in an inter-gas/vacuum double manifold or under
argon atmosphere (Praxair 99.998); in a MBraun Unilab SP glovebox
(<1 ppm H2O and O2). All liquid reagents were purchased as reagent
grade and degassed before use. Regular THF (J.T. Baker) was dried and
degassed in a MB-SPS-800. Water was distilled, deionized, and degassed
under an argon flow before use. Levulinic acid (98% purity), phenyl-
silane (reagent grade 97%), tetramethyldisiloxane (reagent grade 97%),
benzylamine (99% purity), n-butylamine (98% purity), sec-butylamine
(98% purity), phenethylamine (99%), ethylenediamine (98% purity),
hexadecylamine (98% purity), phenylamine (99% purity), and bromo-
pentacarbonylmanganese (I) ([Mn(CO)5Br]) (98%) were purchased
from Sigma-Aldrich. Deuterated solvents for NMR experiments were
purchased from Cambridge Isotope Laboratories and were stored under
4 Å molecule sieves for 24 h before use. NMR spectra were recorded at
room temperature on a JEOL 600 MHz. All reagents for the catalytic
reactions were loaded in the indicated glove box. The GC-MS de-
terminations were made using an Agilent 5975C system equipped with a
30-m DB-5MS capillary column (0.25 mm i.d.; 0.25 mm).
2
87
13
3
4
95
95
5
5
5
6
91
48
9
52
4.2. Optimized reaction conditions to yield 2-methyl-tetrahydrofuran
The reactions were performed using a 50 mL-Schlenk flask equipped
with a Rotaflo valve and a magnetic stirring bar. The [Mn(CO)5Br] (2.6
mg, 0.0094 mmol) and LA (43.5 mg, 0.3746 mmol) were dissolved in
1.5 mL of toluene; phenylsilane (81 mg, 0.7493 mmol) was dissolved in
toluene, and both solutions were mixed in a Schlenk flask with stirring.
Upon addition of phenylsilane, the reaction produced gas and was
allowed to react for 5 min. The reaction mixture was then heated at
different temperatures in a silicon oil bath for different periods of time.
All reactions were analyzed by GC/MS.
7
a
90
10
NH2
H2N
Yields determined by GC-MS.
Table 4
Isolated yield of the resulting hydrochlorides.
Entry
Amine
% Yield
1
2
3
4
BuNH2
sBuNH2
BnNH2
PhNH2
88
70
85
40
4.3. Hg drop test
This reaction was performed as described above but with the addi-
tion of 100 mg (0.49 mmol) of Hg (0) followed by heating at 100 ◦C for
24 h. The reaction mixture was filtered with Celite and analyzed by GC/
MS.
be due in one case to the initial formation of the silyl ester (reaction 1,
Scheme 4) right before the formation of [Mn(CO)5H] from [Mn(CO)5Br]
allowing the protection of the carboxylic moiety with a good leaving
group (R(H2)SiOꢀ ) to yield GVL as illustrated in Scheme 5. In the second
case, [Mn(CO)5H] reacts directly with the free acid group of LA reducing
it to the corresponding alcohol (5-hydroxy-pentan-2-one).
4.4. Optimization of reaction conditions to obtain 1-butyl-2-
methylpyrrolidine
The reactions were performed using a 50 mL-Schlenk flask equipped
with a Rotaflo valve and a magnetic stirring bar. The [Mn(CO)5Br] (2.6
mg, 0.0094 mmol) and LA (43.5 mg, 0.3746 mmol) and butylamine
(27.4 mg, 0.3746 mmol) were dissolved in 2 mL of toluene and then
phenylsilane (121.5 mg, 1.1228 mmol) dissolved in toluene was added.
The reaction mixture was heated in an oil bath at 100 ◦C for 24 h.
3. Conclusions
Complex [Mn(CO)5Br] is a practical catalytic precursor for the
reduction/cyclization reaction of levulinic acid to produce MTHF with
an excellent yield using hydrosilanes such as phenylsilane or tetrame-
thyldisilane. It offers excellent yields, and tetramethyldisilane can
reduce the costs of the reaction and can use not dried solvents. The 1H
NMR monitoring of a stochiometric reaction allowed to identify the
complex [Mn(CO)5H] formed in-situ as an active catalytic compound,
also independently prepared and assessed as catalyst.
4.5. Reduction reaction of LA monitored by NMR
The [Mn(CO)5Br] (15 mg, 0.055 mmol), levulinic acid (6.4 mg,
0.055 mmol), and phenylsilane (13 mg, 0.11 mmol) were mixed in
toluene‑d8 (1 mL) in a NMR tube (Wilmad with J. Young valve) and
analyzed via a 1H NMR at r.t. The first analysis was 30 min after mixing
with a subsequent analysis 1 h later at 100 ◦C. The sample was finally
heated one more hour at 100 ◦C.
Additionally, the hydroamination reaction was performed using [Mn
(CO)5Br] as a catalytic precursor yielding excellent conversions to pro-
duce pyrrolidines or their hydrochlorides in good isolated yields.
CRediT authorship contribution statement
Diego A. Roa: Data curation, Investigation. Juventino J. Garcia:
Supervision.
3

D.A. Roa and J.J. Garcia
Inorganica Chimica Acta 516 (2021) 120167
Fig. 1. 1H NMR (600 MHz) for the stoichiometric reaction with [Mn(CO)5Br].
Scheme 4. Proposed pathway to MTHF formation.
4

D.A. Roa and J.J. Garcia
Inorganica Chimica Acta 516 (2021) 120167
Scheme 5. Proposed mechanism for the catalytic formation of GVL.
Fig. 2. 1H NMR (600 MHz) of [Mn(CO)5H].
5

D.A. Roa and J.J. Garcia
Inorganica Chimica Acta 516 (2021) 120167
Scheme 6. Reduction reaction with the hydride [Mn(CO)5H].
¨
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The authors declare that they have no known competing financial
interests or personal relationships that could have appeared to influence
the work reported in this paper.
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Acknowledgments
We thank CONACyT (A1-S-7657) and DGAPA-UNAM (IN- 200119)
for financial support. D. A. R. also thanks CONACyT for a Ph.D. grant
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