Transition-metal complex-catalyzed reduction of amides with hydrosilanes: A facile transformation of amides to amines

Article abstract of DOI:10.1016/S0040-4039(01)00039-9

The reaction of amides with hydrosilanes is catalyzed by a variety of transition-metal complexes in the presence or absence of halides and amines as co-catalysts to afford the corresponding amines in good yields.

Full text of DOI:10.1016/S0040-4039(01)00039-9

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 1945–1947
Transition-metal complex-catalyzed reduction of amides with
hydrosilanes: a facile transformation of amides to amines
Mamoru Igarashi and Takamasa Fuchikami*
Sagami Chemical Research Center, 4-4-1 Nishi-Ohnuma, Sagamihara, Kanagawa 229-0012, Japan
Received 11 December 2000; revised 4 January 2001; accepted 5 January 2001
Abstract—The reaction of amides with hydrosilanes is catalyzed by a variety of transition-metal complexes in the presence or
absence of halides and amines as co-catalysts to afford the corresponding amines in good yields. © 2001 Elsevier Science Ltd. All
rights reserved.
The conversion of amides to the corresponding amines
is one of the most important transformations in organic
syntheses. Catalytic hydrogenation of amides usually
required vigorous conditions (high pressures and ele-
vated temperature),1 therefore, the stoichiometric
reduction using metal hydride complexes such as
lithium aluminum hydride2–4 or borane5,6 has been used
in organic syntheses. Recently, Rh complex-catalyzed
reduction of tertiary amides to amines has been
reported using H2SiPh2 or H3SiPh,7 where only one of
HꢀSi bonds can be participated in the reaction, and no
reaction can take place at room temperature with
monohydrosilane, which is more stable and less expen-
sive than polyhydrosilanes. Here, we wish to report the
transition-metal-catalyzed transformation of primary,
secondary and tertiary amides to the corresponding
amines using monohydrosilanes as a reducing agent at
elevated temperature.
Table 1. Reduction of N-acetylpiperidine using triethylsilane catalyzed by Group 7–10 transition-metal complexes
Cat. 1 (1 mol%)
Cat. 2 (5 mol%)
Cat. 3 (5 mol%)
Time (h)
Yield (%)
Mn2(CO)10
Re2(CO)10
Ru3(CO)12
RuCl2(CO)2(PPh3)2
Et2NH
Et2NH
16
16
16
16
16
16
40
16
16
16
16
16
16
40
16
89.3
95.6
88.2
96.1
98.1
94.1
94.4
88.0
99.8
99.3
99.5
94.4
92.6
77.7
78.5
EtI
MeI
I2
EtI
EtI
RuH2(CO)(PPh3)3
Ru(acac)3
Os3(CO)12
Et2NH
Et2NH
Et2NH
Pyridine
Et2NH
RhH(PPh)4
IrCl3
K2IrCl6
Pd(OH)2/C
Pt2Cl
Et2NH
Et2NH
Et2NH
Keywords: transition metals; catalysts; reduction; silicon and compounds; amides; amines.
* Corresponding author. Fax: +81-42-749-7631; e-mail: scrc1@sagami.or.jp
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00039-9

1946
M. Igarashi, T. Fuchikami / Tetrahedron Letters 42 (2001) 1945–1947
cat.
Amide + HSiR3 “ Amine
Optimized conditions are as follows: A mixture of
tertiary amide (1.0 mmol), Et3SiH (3–3.5 mmol), and
transition metal complexes ([Metal]=0.01 mmol), amine
(0.05 mmol), and halide (0.05 mmol) in toluene (1.0 ml)
was heated at 100°C under Ar atmosphere. Product
yields were measured by GLC analysis of the reaction
mixture.
Initially, we surveyed the active catalysts using N-
acetylpiperidine as a substrate and triethylsilane as a
monohydrosilane. Surprisingly, varieties of Group 7–10
transition metals (Mn, Re, Ru, Os, Rh, Ir, Pd and Pt)
complexes have catalytic activities in the presence or
absence of diethyl amine and/or ethyl iodide as co-cata-
lysts to afford N-ethylpiperidine as a sole product
(Table 1). Methyl iodide, or iodine can be used instead
of ethyl iodide, however, bromides such as benzyl bro-
mide were less effective. Pyridine shows the same effect
as diethylamine, but triethylamine and t-butylamine
showed nearly no effect.
Not only triorganohydrosilanes such as triethylsilane,
phenyldimethylsilane, tert-butyldimethylsilane and tri-
isopropylsilane, but also chlorosilane or alkoxysilanes
such as chlorodimethylsilane, ethoxydimethylsilane,
diethoxymethylsilane and triethoxysilane, gave satisfac-
Table 2. Reduction of N-acetylpiperidine using hydrosilanes catalyzed by Ru or Os complexes
HSiR3
Cat. 1 (1 mol%)
Cat. 2 (5 mol%)
Cat. 3 (5 mol%)
Et2NH
Time (h)
Yield (%)
HSiEt3
Os3(CO)12
16
16
16
40
16
16
16
16
99.8
90.2
70.4
50.6
80.1
93.1
90.8
86.1
HSiMe2Ph
HSiMet2Bu
HSiPr3
HSiMe2Cl
HSiMe2(OEt)
HSiMe(OEt)2
HSi(OEt)3
RuCl2(CO)2(PPh3)2
RuCl2(CO)2(PPh3)2
[RuCl2(CO)3]2
EtI
EtI
EtI
Et2NH
Et2NH
Os3(CO)12
RuCl2(CO)2(PPh3)2
RuCl2(CO)2(PPh3)2
[RuCl2(CO)3]2
EtI
EtI
EtI
Et2NH
Figure 1. Reduction of cyclic and acyclic amides using triethylsilane.

M. Igarashi, T. Fuchikami / Tetrahedron Letters 42 (2001) 1945–1947
1947
References
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tert-butyldimethylsilane and triisopropylsilane may be
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attributed to the steric hindrance.
As shown in Fig. 1, a variety of cyclic and acyclic
tertiary amides can be reduced to the corresponding
amines under similar reaction conditions. Excess of
triethylsilane should be required in the reaction with
secondary amides (3–4 equiv.) and primary amides (4–5
equiv.), because dehydrogenative silylation of the NꢀH
bond takes place faster than the reduction (within 30
min under the present reaction conditions). In the
reaction with N-benzylacetamide, N-triethylsilyl-N-
ethylbenzylamine was obtained in 80.3% yield with
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In summary, we have developed facile and efficient
methods for the transformation of amides to amines by
transition-metal complex-catalyzed reduction using
monohydrosilanes. Our method has the following
advantages. A variety of less expensive monohydrosi-
lanes can be used as the reducing agent. Primary,
secondary and tertiary amides can be converted into the
corresponding amines. If desired, silyl-protected amines
can be isolated before hydrolysis in the reaction with
primary or secondary amides.
.
.