A novel efficient and chemoselective method for the reduction of nitriles using the system silane/oxo-rhenium complexes

Article abstract of DOI:10.1016/j.tet.2011.08.015

This work reports the reduction of nitriles to the corresponding primary amines with silanes catalyzed by oxo-rhenium complexes. The catalytic system PhSiH₃/ReIO₂(PPh₃)₂ (10 mol %) reduced efficiently a series of nitriles in the presence of a wide range of functional groups such as -Cl, -F, -Br, -I, -CF₃, -OCH₃, -SCH₃, -SO₂CH₃ and -NHTs.

Full text of DOI:10.1016/j.tet.2011.08.015

Tetrahedron 67 (2011) 8183e8186
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A novel efficient and chemoselective method for the reduction of nitriles using
the system silane/oxo-rhenium complexes
ˇ
*
Ivania Cabrita, Ana C. Fernandes
ꢀ
ꢀ
Centro Química Estrutural, Instituto Superior Tecnico, Universidade Tecnica de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 27 May 2011
Received in revised form 29 July 2011
Accepted 6 August 2011
Available online 12 August 2011
This work reports the reduction of nitriles to the corresponding primary amines with silanes catalyzed by
oxo-rhenium complexes. The catalytic system PhSiH3/ReIO2(PPh3)2 (10 mol %) reduced efficiently a series
of nitriles in the presence of a wide range of functional groups such as eCl, eF, eBr, eI, eCF3, eOCH3,
eSCH3, eSO2CH3 and eNHTs.
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Nitriles
Reduction
Primary amines
Silanes
Oxo-rhenium complexes
1. Introduction
Toste and co-workers13,14 havealsostudied the activation of SieH
bond with the high valent oxo-complex ReIO2(PPh3)2. The novel
Amines constitute an important class of compounds in the
manufacture of agrochemicals, dyes, pharmaceutical and other
industrial products. Consequently, the synthesis of amines is an
active field in medicinal chemistry and modern organic synthesis.
The reduction of nitriles is a powerful tool to synthesize primary
amines and it is also a fundamental process in organic chemistry.
Conventional methods for accomplishing this transformation use
catalytic hydrogenation1e7 or strong hydride donors, such as alu-
minium hydrides8 or boranes.9e11 However, these methods suffer
from harsh reaction conditions, such as high temperatures, pres-
sures, use of pyrophoric reducing agents and low functional group
tolerance.
In contrast, silanes or siloxanes are stable to air and moisture
and they are also mild and environmentally benign reducing
agents. However, these reagents are known to be poor reducing
agents, due to their low capacity to donate hydrogen atoms or
hydrides. To overcome this limitation, several combinations of
a silane or a siloxane with transition-metal catalyst have been
studied. For example, Lemaire and co-workers12 have developed
a method for the reduction of nitriles using the system tetrame-
thyldisiloxane/titanium(IV) isopropoxide. Nevertheless, this pro-
cedure requires 100 mol % of titanium complex.
catalytic system silane/ReIO2(PPh3)2 proved to be very efficient for
the hydrosilylation of aldehydes and ketones. We have extended this
result to the activation of SieH,15,16 BeH17 and PeH18 bonds by oxo-
rhenium and oxo-molybdenum complexes. We and other groups
also described the efficient hydrosilylation of aldehydes and
ketones,15,16,19e22 the CeC,23 CeS,23 CeN24 and CeP18,25 bond for-
mation and also the reduction of several functional groups, such as
aromatic nitro compounds,26 imines,21,27,28 amides,29 esters,30
sulfoxides,17,31e35 pyridine N-oxides31 and alkenes36 with the cata-
lytic systems silane/oxo-complexes or borane/oxo-complexes.
The high biological and chemical importance of primary amines,
still justifies the search for novel catalyst systems, leading to effi-
cient and highly chemoselective methods for their synthesis. In
continuation of our interest in developing organic reductions cat-
alyzed by high valent oxo-complexes, herein, we report a novel
method for the reduction of nitriles catalyzed by oxo-rhenium
complexes.
2. Results and discussion
Initially we studied the reduction of the test substrate 4-
chlorobenzonitrile catalyzed by several oxo-rhenium, oxo-molyb-
denum, oxo-tungstenum and oxo-vanadium complexes with dif-
ferent silanes, and using several solvents, in order to assess the best
reaction conditions (Tables 1e3). The progress of the reactions was
monitored by thin layer chromatography or by 1H NMR.
* Corresponding author. Tel.: þ351 218419264; fax: þ351 218464457; e-mail
address: anacristinafernandes@ist.utl.pt (A.C. Fernandes).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.08.015

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I. Cabrita, A.C. Fernandes / Tetrahedron 67 (2011) 8183e8186
Table 1
proved to be inefficient (Table 1, entries 8e11). Finally, in the absence
of catalyst, the reduction did not occur (Table 1, entry 12).
Reduction of 4-chlorobenzonitrile with PhSiH3 catalyzed by oxo-complexesa
The reduction of 4-chlorobenzonitrile was also studied with the
silanes phenylsilane, dimethylphenylsilane, triethylsilane and pol-
ymethylhydrosiloxane (PMHS). The results obtained show that
PhSiH3 was the most efficient reducing agent tested. Using
300 mol % of PhSiH3, the reduction was complete after 5 h at
refluxing toluene (Table 2, entry 1). Similar reduction with only
200 mol % of PhSiH3 also afforded the amine in 100% conversion,
but the reaction required 24 h (Table 2, entry 2). In contrast, no
reaction was observed using PhMe2SiH, Et3SiH, PMHS or in the
absence of silane (Table 2, entries 3e6).
In Table 3 are summarized the results of the search for the ap-
propriate solvent. We found that toluene was the best solvent for
this reduction at reflux temperature, leading to the complete re-
duction of 4-chlorobenzonitrile in 5 h (Table 3, entry 1). Similar
reduction at room temperature only afforded the amine in 60%
conversion after 24 h (Table 3, entry 2). In benzene, the amine was
also obtained in 100% conversion, but this reduction required 24 h
(Table 3, entry 3). In contrast, tetrahydrofuran, dichloromethane,
chloroform and methanol produced the corresponding amine in
moderate to low yields (Table 3, entries 4e7).
Entry
Catalyst
Catalyst (mol %)
Time
Conversionb (%)
1
2
3
4
5
6
7
8
ReIO2(PPh3)2
ReIO2(PPh3)2
ReOCl3(PPh3)2
ReOCl3(dppm)
Re2O7
MTO
HReO4
MoO2Cl2
MoO2(acac)2
WO2Cl2
10
5
5
24
24
24
24
24
24
24
24
24
24
24
100
40
100
10
10
10
10
10
10
10
10
10
d
No reaction
No reaction
No reaction
No reaction
No reaction
No reaction
No reaction
No reaction
No reaction
9
10
11
12
VO(acac)2
Without catalyst
a
All reactions were carried out with 1.0 mmol of nitrile and 300 mol % of PhSiH3.
Conversion was determined by 1H NMR.
b
Table 2
a
Reduction of 4-chlorobenzonitrile with different silanes catalyzed by ReIO2(PPh3)2
To evaluate the general applicability of the catalytic system
PhSiH3/ReIO2(PPh3)2 (10 mol %), we investigated the reduction of
a series of nitriles at refluxing toluene under air atmosphere (Table 4).
Generally, good to excellent yields of amines were obtained, as hy-
drochloridesalts, including amines bearingelectron-withdrawing- or
electron-donating groups.
Entry
Silane
Silane (mol %)
Time (h)
Conversionb (%)
1
2
3
4
5
6
PhSiH3
PhSiH3
PhMe2SiH
Et3SiH
PMHS
300
200
300
350
400
d
5
24
24
24
24
24
100
100
No reaction
No reaction
No reaction
No reaction
Table 4
a
Reduction of nitriles with the system PhSiH3/ReIO2(PPh3)2
Without silane
a
All reactions were carried out with 1.0 mmol of nitrile and 10 mol % of
ReIO2(PPh3)2.
b
Conversion was determined by 1H NMR.
Entry Substrate
1
Product
Time (h) Yieldb
Table 3
Reduction of 4-chlorobenzonitrile in different solventsa
5
1
92
88
2
Entry
Solvent
Temperature
Time (h)
Conversionb (%)
1
2
3
4
5
6
7
Toluene
Toluene
Benzene
THF
CH2Cl2
CHCl3
Reflux
rt
5
24
24
48
24
23
24
100
60
100
40
47
30
3
4
5
3
83
82
Reflux
Reflux
Reflux
Reflux
Reflux
Methanol
20
a
All reactions were carried out with 1.0 mmol of nitrile and 300 mol % of silane.
Conversion was determined by 1H NMR.
b
In this work, we tested the catalytic activity of the oxo-rhenium
5
6
4
5
84
84
complexes ReIO2(PPh3)2, ReOCl3(PPh3)2, ReOCl3(dppm), Re2O7,
CH3ReO3 (MTO) and HReO4. The best results were obtained with
ReIO2(PPh3)2 (10 mol %) and PhSiH3 (300 mol %) in refluxing tolu-
ene under air atmosphere, affording the complete reduction of 4-
chlorobenzonitrile after 5 h (Table 1, entry 1). Using only 5 mol %
of this catalyst, the corresponding amine was obtained in only 40%
after 24 h (Table 1, entry 2). The complex ReOCl3(PPh3)2 (10 mol %)
was also very efficient, allowing the complete reduction of 4-
chlorobenzonitrile, but this reaction required long reaction time
(24 h) (Table 1, entry 3). In contrast, no reaction was observed in the
presence of 10 mol % of the complexes ReOCl3(dppm), Re2O7, MTO
and HReO4 (Table 1, entries 4e7).
7
8
24
24
91
90
The oxo-complexesMoO2Cl2, MoO2(acac)2, WO2Cl2 andVO(acac)2
were also tested in the reduction of 4-chlorobenzonitrile, but they

I. Cabrita, A.C. Fernandes / Tetrahedron 67 (2011) 8183e8186
8185
Table 4 (continued )
The reduction of nitriles containing the functional groups eCl,
eF, eBr, eI, eCF3 and eSO2CH3 were completed within 1e5 h and
the corresponding amines hydrochloride salts were isolated in high
yields (Table 4, entries 1e6).
Entry Substrate
Product
Time (h) Yieldb
Benzonitrile and 1-naphthonitrile were also successfully re-
duced under the optimized reaction conditions in excellent yields
after 24 h (Table 4, entries 7 and 8). The reduction of aromatic
nitriles containing the electro-donating groups OCH3, SCH3 and
CH3, were also performed in good yields (Table 4, entries 9e11).
However, these reactions required more time than the reduction
of nitriles bearing electron-withdrawing groups (Table 4, entries
1e6). The reduction of the substrate containing the NHTs group
afforded the corresponding amine in moderate yield (Table 4,
entry 12).
9
16
89
10
11
12
15
24
3
91
88
51
Finally, the substrate versatility of this novel method was further
demonstrated by the reduction of phenylacetonitrile in good iso-
lated yield after 24 h (Table 4, entry 13).
The results obtained demonstrate that this novel methodology
for the reduction of nitriles is highly chemoselective, tolerating
several functional groups, such as eCl, eF, eBr, eI, eCF3, eOCH3,
eSCH3, eSO2CH3 and eNHTs (Table 4, entries 1e6, 9e10 and 12).
Mechanistically, we suggest that the reduction of nitriles with the
system silane/oxo-rhenium complexes involves the followed steps:
coordination of two nitriles to the rhenium with liberation of two
phosphines, affording the complex ReIO2(nitrile)2 2; formation of the
hydride species (nitrile)2(O)IRe(H)OSiR30 3 as result of the addition of
13
24
92
a
All reactions were carried out with 1.0 mmol of nitrile and 300 mol % of PhSiH3.
The products were isolated as hydrochloride salt.
b
PPh3
O
Re
PPh3
I
O
1
2 R
C
N
2 PPh3
R
C
N
Re
N
C
R
2
R'3SiH
R
C N
O
O
I
R
C
N
Re
O
7
R
C
N
Re
N
I
O
O
H
I
O
R'3Si
C
R
3
R
R3'Si
N
R'3Si
8
H2O
R
R
C
N
Re
N
R
C
N
Re
N
O
O
H2N
I
O
O
I
9
R'3Si
R
C
R
R'3Si
R'3Si
R
Amine
4
6
N
Re
N
I
O
O
H
R'3Si
R'3SiH
R'3Si
R
5
Scheme 1. Proposed catalytic cycle for the reduction of nitriles with the system silane/ReIO2(PPh3)2.

8186
I. Cabrita, A.C. Fernandes / Tetrahedron 67 (2011) 8183e8186
the SieH bond of the silane to one of the oxo-rhenium bond; dihy-
drosilylation of the nitrile to the corresponding N-disilylamine 8;
formation of amine 9 by hydrolysis of N-disilylamine, probably, due to
the presence of a trace of water in the reaction mixture (Scheme 1).
In comparison with the method using the system tetrame-
thyldisiloxane/titanium(IV) isopropoxide,12 our procedure required
less quantity of catalyst (10 mol %), in contrast to the 100 mol % of
titanium(IV) isopropoxide.
Furthermore, this novel methodology avoid the formation of
secondary amines, by unwanted side-reaction, which is a general
problem observed in the reduction of nitriles by catalytic
hydrogenation.
Another important benefit of this method is that the reduction
can be carried out in simple, readily available laboratory equip-
ment, in contrast to catalytic hydrogenation, which demands
handling of hydrogen gas and often requires rather expensive high-
pressure equipment.
Otheradvantagesof thismethodologyincludehighisolatedyields,
good chemoselectivity, easy work-up and preparation of the cata-
lyst13 and also the stability of the catalyst towards air and moisture,
allowing the reaction to be carried out under air atmosphere.
amine hydrochloride salts. The solids were isolated upon filtration
and then washed with n-hexane to afford the pure amine hydro-
chloride salts, which are all known compounds.
Acknowledgements
This research was supported by FCT through project PTDC/QUI/
71741/2006. I.C. thanks to FCT for a grant (SFRH/BD/74280/2010).
Authors thank to the project PEst-OE/QUI/UI0100/2011 and the
Portuguese NMR Network (IST-UTL Center) for providing access to
the NMR facilities and the Portuguese MS Network (IST Node) for
the ESI measurements.
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In conclusion, we have demonstrated that the catalytic system
PhSiH3/ReIO2(PPh3)2 is very efficient for the reduction of a variety
of nitriles. This novel methodology is highly chemoselective, tol-
erating a large range of functional groups, such as eCl, eF, eBr, eI,
eCF3, eOCH3, eSCH3, eSO2CH3 and eNHTs. We believe that this
procedure will be an alternative to the existing methods for the
reduction of nitriles.
4. Experimental section
4.1. General information
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230e400 mesh. 1H NMR and 13C NMR spectra were measured on
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mixture was stirred at reflux temperature under air atmosphere
and the progress of the reaction was monitored by TLC or 1H NMR.
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~
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