TBAF-catalyzed hydrosilylation for the reduction of aromatic nitriles

Article abstract of DOI:10.1039/c3nj00171g

The selective catalytic hydrosilylation of functional groups is becoming an interesting tool for organic synthesis. In the present study, fluoride-catalyzed hydrosilylations of aromatic nitriles have been examined in detail. Using catalytic amounts of inexpensive tetra-n-butylammonium fluoride (TBAF) various aromatic nitriles are reduced in good yields under mild conditions.

Full text of DOI:10.1039/c3nj00171g

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TBAF-catalyzed hydrosilylation for the reduction of
aromatic nitriles†
Cite this: NewJ.Chem., 2013,
37, 2061
Christoph Bornschein, Svenja Werkmeister, Kathrin Junge and Matthias Beller*
Received (in Porto Alegre, Brazil)
13th February 2013,
Accepted 3rd April 2013
The selective catalytic hydrosilylation of functional groups is becoming an interesting tool for organic
synthesis. In the present study, fluoride-catalyzed hydrosilylations of aromatic nitriles have been
examined in detail. Using catalytic amounts of inexpensive tetra-n-butylammonium fluoride (TBAF)
various aromatic nitriles are reduced in good yields under mild conditions.
DOI: 10.1039/c3nj00171g
www.rsc.org/njc
Amines represent valuable intermediates for the fine and bulk lower amounts of waste products. However, to date only a few
chemical industries, agrochemicals, dyes as well as pharma- homogeneous catalysts are available for the reduction of
ceuticals.1 Among the various derivatives, primary amines are nitriles to the corresponding primary amines.18–22
by far the synthetically most significant compounds.2,3 The
In particular, the catalytic hydrosilylation is a suitable tool
majority of industrially important primary amines are synthesized for the selective reduction of nitriles.23–26 It exhibits improved
nowadays via amination of alcohols with ammonia or related chemo- and regioselectivity under milder conditions compared
reductive amination of carbonyl compounds (Scheme 1).4 Despite to the conventionally used reducing agents.27
large scale applications, there exists continuing interest in
For the first time, Corriu et al.28 reported transition metal
obtaining these products selectively under milder reaction catalyzed hydrosilylation of nitriles using Wilkinson’s catalyst. In
conditions. Traditionally, on a laboratory scale primary amines the past decades, different transition metals such as Re,21 Ru29
have been prepared by the Gabriel synthesis5 as well as reduc- and Co30 were found to activate the Si–H bond. Unfortunately, all
tive aminations.6,7
these catalysts have drawbacks, for example high costs of the
While the former reaction requires the use of phthalimides catalyst metals and in some cases a large excess of the hydro-
as protecting groups, in reductive aminations sometimes the silanes (up to 10 equiv.) is required. Recently, our group showed
formation of undesired secondary or tertiary amines cannot be the first Fe-catalyzed hydrosilylation of nitriles, using a moderate
avoided.7,8 Notably, in the past decade other selective catalytic excess of the hydrosilane (3.5 equiv.; Scheme 2).24
protocols using ammonia for primary amine synthesis such as
hydroaminomethylations,9,10 alcohol aminations,11,12 and use of fluoride ions as an activator for the hydrosilylation. Again,
Buchwald–Hartwig aminations13–15 have been developed.16
Corriu and co-workers were the first to report alkali fluoride salt
In addition to metal catalysis, a convenient approach is the
In addition to all these methodologies, the catalytic reduction mediated hydrosilylation of carbonyl compounds.31 But since it
of nitriles offers interesting access to primary amines. In general, requires stoichiometric amounts of the fluoride salt to suffi-
nitriles are reduced with stoichiometric amounts of metal ciently activate the hydrosilane, its utility was scarcely explored.
hydrides.17 Advantageously, catalytic hydrogenation leads to The first fluoride-catalyzed hydrosilylation was performed by
Fujita and Hiyama utilizing 2–5 mol% tetra-n-butylammonium
fluoride (TBAF).32 TBAF is a useful catalyst candidate since it
offers a highly nucleophilic fluoride anion as an activator for the
hydrosilylation. To date, fluoride activated hydrosilylations have
been reported in the reduction of carbonyl derivatives like
Scheme 1 Amination of alcohols with ammonia.
ketones,32–37 aldehydes,34,36,37 esters,38 and rarely amides.39
¨
¨
Leibniz-Institut fur Katalyse e.V. an der, Universitat Rostock, Albert-Einstein-Straße 29a,
D-18059 Rostock, Germany. E-mail: matthias.beller@catalysis.de;
Fax: +49-381-1281-5000; Tel: +49-381-1281-113
† Electronic supplementary information (ESI) available. See DOI: 10.1039/
c3nj00171g
Scheme 2 Iron-catalyzed hydrosilylation of benzamide.24
c
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(Table 1, entries 4 and 9–11) demonstrates nicely that the
tetra-n-butylammonium (TBA) counter ion is essential for the
catalytic reaction, since it offers a higher nucleophilicity to
the fluoride. Furthermore, TBA is known to have an influence
on the stabilisation of bulky penta-coordinated silicates40
allowing a better fluoride exchange. The importance of fluoride
is proved as no conversion is observed in the presence of the
corresponding bromide (TBAB), chloride (TBAC) or hydrogen
sulfate (TBAHS) as nucleophiles (Table 1, entries 6–8). In
addition, iron(III)fluoride (Table 1, entry 9) gave no conversion
within the observed reaction time. Afterwards, we explored the
catalyst loading for the model reaction (Table 1, entries 2–5).
We obtained the best yield using 5 mol% of the catalyst
(Table 1, entry 4). Lowering the concentration gave worse
conversion, while higher catalyst amounts led to unsatisfactory
product yields, too (Table 1, entry 5). Apparently, selectivity is
decreased using higher catalyst concentration, since secondary
amines were detected in the reaction mixture (GC/MS). Among
the different solvents investigated, toluene gave the best
results. Other selected solvents led to rather low conversion
and yield (Table 1, entries 12–15).
From the results of the hydrosilane screening (Table 2) it
appears that di- and polymeric siloxanes are not useful to
achieve appropriate conversions (Table 2, entries 4, 5, 14 and
15). The best yields were obtained with the initially used
phenylsilane (Table 2, entries 8–12), which is known to be
one of the most reactive hydrosilanes. Exhibiting only one
phenyl residue the silicon atom lacks stabilisation possibilities
and therefore allows a fast reaction using only a slight excess of
the hydrosilane.
Scheme 3 TBAF-catalyzed hydrosilylation of benzonitrile.
In our ongoing research on the development of novel
hydrosilylations, here we report the first convenient fluoride-
catalyzed reduction of different nitriles to primary amines.
More specifically, the combination of a catalytic amount of
TBAF with PhSiH3 (1.3 equiv.) gave rise to a highly active system
which allows the hydrosilylation of C–N-triple bonds to proceed
at room temperature.
Initially, we investigated the reaction of benzonitrile 1a with
hydrosilanes in toluene as a model system (Scheme 3). To gain
insights into factors responsible for the formation of primary
amines we studied the influence of different fluoride sources,
hydrosilanes and solvents. Throughout these studies we found
that the use of only 5 mol% of commercially available TBAF as a
fluoride source gave the desired benzylamine 1b within
60 minutes.
Using PhSiH3, the primary amine was obtained exclusively
without any formation of the undesired secondary amine.
Notably, the small excess of PhSiH3 used allows no quantitative
bissilylation of the product. The resulting amine does not affect
the selectivity of the reaction. Hence, we did not detect any
secondary amine as a by-product.
The results illustrated in Table 1 show that the cheap and
readily available fluoride source, TBAF, gave the best yield
among the different explored fluoride catalysts (Table 1, entry 4).
The obtained reactivity for the different fluoride sources
Next, we optimized the model reaction by varying the
phenylsilane equivalents (Table 2, entries 8–12). Best results
Table 2 Reduction of benzonitrile using different hydrosilanesa
Table 1 Fluoride-catalyzed reduction of benzonitrilea
Hydrosilane Conversionb Yieldb
Entry
Catalyst
Mol%-catalyst
Conversionb,c [%]
Yieldb [%]
Entry Hydrosilane
[equiv.]
[%]
[%]
1
2
3
4
5
6
7
8
/
/
0
52
91
99
100
0
0
0
0
0
30
54
99
55
0
0
0
0
0
0
1
44
23
45
1
2
3
4
5
6
7
8
(EtO)3SiH
Et3SiH
3
3
3
3
3
3
3
1.1
1.2
1.3
1.4
1.5
2
66
9
58
10
0
5
0
91
96
99
99
100
60
25
40
50
0
23
4
0
2
TBAF
TBAF
TBAF
TBAF
TBAB
TBAHS
TBAC
FeF3
NaF
1
3
5
10
5
5
5
5
5
5
5
5
5
5
(EtO)2MeSiH
Pentamethyldisiloxane
Tetramethyldisiloxane
MePh2SiH
Me2PhSiH
PhSiH3
PhSiH3
PhSiH3
PhSiH3
PhSiH3
Ph2SiH2
PMHS
Bis(trimethylsiloxy)-
methylsilane
0
86
83
99
99
92
22
0
9
9
10
11
12
13
14
15
4
3
10
11
12
13
14
15
CsF
TBAF
TBAF
TBAF
TBAF
5 (DCM)
78 (THF)
60 (NMP)
70 (DMSO)
5
3
0
a
Reaction conditions: (i) 1a (1.0 mmol), catalyst (1–10 mol%), phenyl-
a
silane (1.3 equiv.) in toluene (2 mL) at rt for 60 min. (ii) The reaction
mixture is then quenched with 1 M HCl solution for 90 min. Deter- (1.1–5 equiv.) in toluene (2 mL) at rt for 60 min. (ii) The reaction mixture
mined by GC with hexadecane as an internal standard. Solvent in is then quenched with 1 M HCl solution for 90 min. Determined by
Reaction conditions: (i) 1a (1.0 mmol), TBAF (5 mol%), hydrosilane
b
c
b
brackets where no toluene was used.
GC with hexadecane as an internal standard.
c
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Table 3 Scope and limitationsa
Scheme 4 Transarylation of phenylsilane.
Entry
1
Substrate
Time [h]
1
Isolated yield [%]
95
were obtained with an excess of 1.3 to 1.4 equivalents (Table 2,
entries 10 and 11). A larger excess of the hydrosilane again led
to lower yields since side reactions occur.
Interestingly, more than one hydride equivalent is derived
from one molecule of phenylsilane. In order to investigate this
effect, we performed 29Si NMR spectroscopic studies after the
hydrolysis of a typical reaction mixture. Besides Si–O species
resulting from hydrolysis, no phenylsilane was detected.
Instead, to our surprise diphenylsilane was identified as a side
product in this reaction. Additional experiments proved that
the presence of fluoride, nitrile and the counter ion is necessary
for this unusual transarylation of the phenyl group from
PhSiH3 (Scheme 4). We assume that penta-coordinated
[FSiR3H]À (R = Ph, H, N) intermediates offer the additional
hydrides for the quantitative reduction of the different nitrile
substrates. Notably, the nitrile moiety plays a significant role in
this odd transformation, since there is no transarylation
observed in the presence of TBAF alone (GC/MS analysis). To
the best of our knowledge reported transarylations between
silanes do not proceed under such mild conditions.41
It is well known that SiH4 is a dangerous gas, which ignites
when it is exposed to air. Thus, we carefully investigated the
limitations of this formation. Exposing a 20 mmol-scale reac-
tion after one hour to air led to no ignition of the reaction
mixture.
2
3
1.5
1.5
80
79b
4
5
1.5
2
70c
67
6
1.5
73
Using our optimized conditions we studied the scope and
limitations of the TBAF-catalyzed hydrosilylation of nitriles. For
this purpose various aromatic, heteroaromatic and aliphatic
nitriles were examined (Table 3).
7
2
2
2
2
76b
73
In general, aromatic substrates with several electron-donating
substituents were found to be hydrosilylated in good isolated
yields at room temperature (67–80%; Table 3, entries 2–6).
However, ortho-substituted substrates showed no reactivity.
The steric demand of the ortho-substituents seems to hinder the
addition of the active silane species. 3,4-Dimethoxy-benzylamine
(Table 3, entry 4) was obtained in better yields at 60 1C (70%)
compared to the reaction at room temperature (40%). At higher
temperature (110 1C) with this substrate as well as other
aromatic nitriles the reaction gave no conversion. Apart from
electron-rich benzonitriles, some electron-deficient substitu-
ents were also tolerated (Table 3, entries 9–11). Unfortunately,
testing heterocyclic nitriles (3-thiophenecarbonitrile or pico-
linonitrile) as well as hexanenitrile did not show any reactivity
under the described conditions. It is important to note that in
cases where no conversion of the substrate was observed
ignition of the gas phase can occur after exposing the reaction
mixture to air.‡
8
9
62b
79
10
11
12
2
81b
2
1
0
0
13
a
Reaction conditions (i) nitrile (1.0 mmol), TBAF (5–10 mol%),
phenylsilane (1.3 equiv.) in toluene (2 mL) at rt for 1–2 h. (ii) The
reaction mixture is then quenched with 1 M HCl solution for 90 min.
‡ In the reaction of hexanenitrile ignition of the gas phase was observed after
exposing the reaction mixture to air. We assume the formation of significant
amounts of SiH4 to be responsible for this effect.
b
Second catalyst addition (5 mol%) after half of the reaction time.
c
Reaction at 60 1C.
c
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