Dual Si-H effects in platinum-catalyzed silane reduction of carboxamides leading to a practical synthetic process of tertiary-amines involving self-encapsulation of the catalyst species into the insoluble silicone resin formed

Article abstract of DOI:10.1016/j.tetlet.2006.06.165

Combination of commercially available platinum catalysts with siloxanes containing more than two Si-H groups is found to be an efficient catalyst system for the reduction of carboxamides to amines. In particular, facile removal of silicon and platinum residues from the product can be achieved by the use of polymethylhydrosiloxanes as reducing reagents.

Full text of DOI:10.1016/j.tetlet.2006.06.165

Tetrahedron Letters 47 (2006) 6173–6177
Dual Si–H effects in platinum-catalyzed silane reduction of
carboxamides leading to a practical synthetic process of
tertiary-amines involving self-encapsulation of the catalyst
species into the insoluble silicone resin formed
Shiori Hanada, Yukihiro Motoyama and Hideo Nagashima*
Institute for Materials Chemistry and Engineering, Graduate School of Engineering Sciences, Kyushu University,
Kasuga, Fukuoka 816-8580, Japan
Received 26 April 2006; revised 29 June 2006; accepted 30 June 2006
Abstract—Combination of commercially available platinum catalysts with siloxanes containing more than two Si–H groups is found
to be an efficient catalyst system for the reduction of carboxamides to amines. In particular, facile removal of silicon and platinum
residues from the product can be achieved by the use of polymethylhydrosiloxanes as reducing reagents.
Ó 2006 Elsevier Ltd. All rights reserved.
Synthetic procedures using environmentally benign
reagents under mild conditions have lately been receiving
much attention from organic chemists.1 In particular,
easy separation of the products from the reaction mix-
ture is a key point in the production of large quantities
of organic molecules. We have recently reported that a
certain ruthenium cluster catalyzes the reduction of
carboxamides with trialkylsilanes.2 This realizes produc-
tion of gram-quantities of amines with non-pyrophoric
metal hydrides under mild conditions, and the product
can be separated from the siloxane by-products and
most of the ruthenium residues by acid–base treatment
of the reaction mixture.2b Although removal of ruthe-
nium residues from the amine product of this reaction
required further improvement of the process, we have
lately discovered an epoch-making method of the separa-
tion procedure using polymethylhydrosiloxane (PMHS)
as the reducing reagent; the reduction is accompanied
with cross-linking of the silicon-polymer to produce
insoluble silicon resin, to which the ruthenium species
is efficiently soaked up.3 This actually results in facile
separation of the amine product from the by-products,
that is, ruthenium and silicon residues, by simple extrac-
tion and filtration, providing an ideal method of synthe-
sizing silicon- and ruthenium-free amines from amides.
In the course of these studies, we were interested in
the possibility that similar reduction of amides with
PMHS involving self-encapsulation of the metal species
may also take place with other transition metal cata-
lysts. One candidate is H2PtCl6 and other platinum com-
pounds, which are easily available from commercial
sources and widely used for catalytic hydrosilylation of
alkenes in both laboratory and industrial scales.4 How-
ever, the literature suggests that platinum catalysts are
extremely useful for reactions of a wide variety of hydro-
silanes with alkenes and alkynes, but not active for the
reduction of carbonyl compounds. To our best knowl-
edge, the possibility of platinum-catalyzed silane reduc-
tion of amides is only briefly suggested in a paper by
Igarashi and Fuchikami, in which amides were con-
verted to the corresponding amines by hydrosilanes in
the presence of ruthenium and osmium carbonyl com-
plexes.5 In this report, N-acetylpyrrolidine was reduced
to N-ethylpyrrolidine at 100 °C for 16 h in the presence
of PtCl2 (1 mol %) and Et2NH as a cocatalyst (5 mol %);
the reaction giving the product at lower temperature in
short reaction time is apparently desirable for organic
synthesis. In this letter, we wish to report a break-
through on this problem by an interesting ‘dual Si–H
effect’ in the platinum-catalyzed silane reduction of
amides. Platinum catalysts are not active for the reduc-
tion of amides with hydrosilanes containing only one
Keywords: Carboxamide; Dual Si–H effect; Platinum; Reduction; Self-
encapsulation.
*
Corresponding author. Tel./fax: +81 92 583 7819; e-mail: nagasima@
cm.kyushu-u.ac.jp
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.06.165

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S. Hanada et al. / Tetrahedron Letters 47 (2006) 6173–6177
Si–H group in the molecule as the literature suggested;
however, siloxanes containing more than two Si–H
groups facilely reduce the amides under mild conditions.
As an extension of this, use of PMHS having many Si–H
groups in the polymer chain contributes to both facile
reduction of amides and formation of insoluble siloxane
resins to which almost all platinum residues are encapsu-
lated. This discovery provides a practical synthetic
method of silicon and metal-free amines by easily avail-
able platinum catalysts.
the reduction with commercially available PMHS (Az-
max: average n = 25) at 50 °C led to both production
of amines and formation of insoluble silicon resins to
which the platinum species was encapsulated (Fig. 1).
Extraction of the reaction mixture with ether gave the
desired amines (quantitative by NMR and GC analysis)
containing only a tiny amount of silicon residue and
platinum species, which could be removed by passing
the extracts through a short pad of alumina (entry 3).
Other commercially available platinum catalysts,
PtCl2(COD) and ‘Pt[{(CH2@CH)Me2Si}2O]n’ (Kar-
stedt’s catalyst)6 are also useful for this reduction at low-
er than 50 °C (entries 4 and 5). In particular, a xylene
solution of Karstedt’s catalyst (Aldrich) is active enough
to perform the reaction with PMHS even at 0 °C for 3 h
to give the desired amine in 86% isolated yield.7 A nota-
ble side reaction of this process is the formation of
enamine [N,N-dimethyl-(3-phenylpropen-1-yl)amine],
which is typically seen with lower catalyst concentration
We reported earlier that a ruthenium cluster catalyst
reduces the amides to amines with various hydrosilanes
at room temperature to 50 °C. Attempts to replace the
ruthenium catalyst by H2PtCl6Æ6H2O were unsuccessful
as long as we used trialkylsilanes, alkoxysilanes, and
hydrosiloxanes containing only one Si–H group in a
molecule (Scheme 1). For example, no platinum-cata-
lyzed reduction of N,N-dimethyl dihydrocinnamamide
took place at 50 °C with Me2PhSiH, Me2EtSiH, (EtO)3-
SiH, and Me3SiOSiMe2H. In sharp contrast, the reduc-
tion proceeds with HSiMe2OSiMe2H or Me3Si-
(OSiHMe)2OSiMe3 at that temperature to afford the
corresponding amine in 90% or 63% yields, respectively
(Table 1, entries 1 and 2). Dual Si–H groups in HSi-
Me2OSiMe2H or Me3Si(OSiHMe)2OSiMe3 apparently
enhance the reactivity. In contrast to the fact that the
reduction of these two hydrosiloxanes is homogeneous,
Figure 1. Photos of the Pt-catalyzed reaction; A: initial homogeneous
solution, B: after the reaction (gel), C: extraction with ether,
D: insoluble silicone resin containing platinum residue.
Pt catalyst
(0.1–1 mol%)
Ph
NMe2
Ph
NMe2
+
+
"Si2O"
2
"Si–H"
THF
0–50 ºC, 3 h
O
inactive "Si–H"
active "Si–H"
H
H
R2Si
O
SiR2
(R = Me, OSiMe3)
R3SiH
Me
O
H
Me
H
Me Me
Me3Si
Si
Me3Si
Si
Si
O
(RO)3SiH
n OSiMe3
O
mOSiMe3
n
Me3SiOSiMe2H
(PMHS)
(PMHS/PDMS)
Scheme 1. Active vs. inactive hydrosilanes for the platinum-catalyzed reduction of amides.
Table 1. Pt-catalyzed reduction of N,N-dimethyl dihydrocinnamamidea
Entry
Catalyst [mol %]
Silane [Si–H: mmol]
Temperature (°C)
Yieldb (%)
1
H2PtCl6Æ6H2O [1]
H2PtCl6Æ6H2O [1]
H2PtCl6Æ6H2O [1]
PtCl2(COD) [1]
Pt[{(CH2@CH)Me2Si}2O]n [1]
H2PtCl6Æ6H2O [0.1]
H2PtCl6Æ6H2O [0.1]
H2PtCl6Æ6H2O [0.1]
HSiMe2OSiMe2H [3.0]
Me3Si(OSiHMe)2OSiMe3 [3.0]
PMHS [3.7]
PMHS [3.7]
PMHS [3.7]
PMHS [3.7]
PMHS/PDMS [2.2]
PMHS [3.7]
50
50
50
40
0
90
90
80
90
63
84
77
2c
3
4
5
6d
7d
8g
86
72e,f
80e
76h
a All reactions were carried out using 1 mmol of amide, 2.2–3.7 mmol of silane, 0.001–0.01 mmol of platinum catalyst in 0.6 mL of THF for 3 h.
b Isolated yield by Al2O3 column.
c For 10 h.
d In heptane.
e Determined by 1H NMR analysis.
f 28% of enamine was formed.
g 5 g (28.2 mmol) of amide was used in dimethoxyethane.
h Isolated by distillation.

S. Hanada et al. / Tetrahedron Letters 47 (2006) 6173–6177
6175
(0.1 mol %) at higher temperature (90 °C) (entry 6). We
found three clues to suppress the enamine formation,
that is, higher catalyst loading (>1 mol %), lower
reaction temperature (<80 °C), and use of poly-
3 revealed that 97.9–98.9% of platinum species was
soaked up to the insoluble silicon resin to give the crude
product, of which purification by a short Al2O3 column
afforded the amine with less than 1 ppm of platinum
content. Furthermore, the platinum-containing silicon
resin is reusable as the catalyst for the silane reduction
of the amide with PMHS to form the desired amines,
though the conversion of amide was somewhat de-
creased (first: 100%, second: 84%, third: 76%). Facile
catalyst recycling and removal of the metallic residue
is an important problem to be solved in the production
of fine chemicals,8 and this process offers a clear solution
to this.
methylhydrosiloxane
(PMHS)/polydimethylsiloxane
(PDMS) copolymer. In fact, use of PMHS/PDMS
copolymer, Me3Si(OSiHMe)n(OSiMe2)mOSiMe3 (n =
13, m = 12), effectively suppress the formation of the en-
amine (entry 7). Careful control of the reaction temper-
ature below 80 °C resulted in successful isolation of a
gram-quantity of the desired amine by 0.1 mol % of
H2PtCl6 as shown in entry 8.
Self-encapsulation of the platinum residue to the insolu-
ble siloxane resin is another important aspect for this
platinum-catalyzed reduction, which takes part in facile
removing the metallic species from the amine product.
In fact, ICP-mass analyses of the product shown in entry
Application of this H2PtCl6Æ6H2O-catalyzed process
with PMHS to the reduction of various tertiary-amides
is summarized in Table 2. All reactions resulted in good
to high yields with both aliphatic and aromatic amides
Table 2. H2PtCl6-catalyzed reduction of various amides with PMHSa
Entry
Amide
Temperature (°C)
Product
Yieldb (%)
84
Ph
NMe2
H
1
50
Ph
NMe2
O
Me
Ph
Ph
Ph
N
2
3
4
5
6
50
25
60
60
60
Ph
Ph
72
92
75
94
88
NMe2
O
N
N
O
NMe
2
Ph
Cl
NMe2
O
Cl
NMe2
NMe2
O
MeO
MeO
NMe2
NMe2
NMe2
O
Me2N
7
8d
60
80
55c
89
Me2N
NMe2
O
Me
N
Me
N
9
50
50
50
95
Bn
Bn
O
Me
N
Me
N
6
6
10
11
80
6
6
Bn
Bn
O
Me
Me
Tracee
8
N
8
Bn
N
Bn
O
a All reactions were carried out using 1 mmol of amide, 250 lL (Si–H = 3.7 mmol) of PMHS, 0.01 mmol of H2PtCl6Æ6H2O in 0.6 mL of THF for 3 h.
b Isolated yield by column chromatography.
c Determined by 1H NMR analysis.
d In dimethoxyethane.
e Olefin-isomerized product was obtained.

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S. Hanada et al. / Tetrahedron Letters 47 (2006) 6173–6177
below 60 °C for 3 h, except in the cases of dimethyl-
aminobenzamide and 10-undecenamide. The reaction of
N-benzylpyrrolidinone smoothly proceeds even at 25 °C
to afford the N-benzylpyrrolidine in 92% yield (entry
3). Amides containing a chloride, MeO, or Me2N as
the functional group also underwent the reduction without
problems: although the reactivity of p-Me2NC6H4-
C(O)NMe2 was relatively lower than that of other
amides (60 °C, 3 h: 55% yield), the reaction at 80 °C
gave the product in satisfactory yield (entries 4–8). It
is well known that H2PtCl6Æ6H2O and other platinum
compounds are effective catalysts for the reaction of
Si–H groups in PMHS with olefins.9 The reduction of
amides proceeded with a di- or tri-substituted carbon–
carbon double bond (C@C bond) existing in the same
molecule intact; the desired alkenylamines were formed
in high yields (entries 9 and 10). Only the case where
the hydrosilylation of C@C bonds was competitive with
the reduction of amide was seen in the reduction of
N-benzyl-N-methyl-10-undecenamide (entry 11). Only
a small amount (ꢀ5%) of N-benzyl-N-methylundecen-
amines with internal C@C bond, which could be formed
by isomerization of the terminal C@C bond of the start-
ing material followed by the reduction of the amide
function, was isolated by extraction of the reaction mix-
ture with ether. 29Si CPMAS NMR suggested the immo-
bilization of organic moieties derived from N-benzyl-N-
methyl-10-undecenamide to the silicon resin via the plat-
inum-catalyzed addition of Si–H groups to the C@C
bond.9 Attempted reduction of secondary and primary
amides were not successful.
Acknowledgments
The authors are grateful to Ms. Keiko Ideta (Analytical
Center in Institute for Materials Chemistry and Engi-
neering, Kyushu University) for help with 29Si NMR
analyses. A part of this work was financially supported
by Grant-in-Aid for Scientific Research from the Japan
Society for the Promotion of Science, and the Ministry
of Education, Culture, Sports, Science and Technology,
Japan.
Supplementary data
Detailed experimental procedures and characterization
data. See: http://www.sciencedirect.com/. Supplemen-
tary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2006.06.165.
References and notes
1. Representative reviews: (a) Clark, J. H. Green Chem. 1999,
1, 1; (b) Dioumaev, V. K. Nature 2000, 424, 530, and
references cited therein.
2. (a) Matsubara, K.; Iura, T.; Maki, T.; Nagashima, H. J.
Org. Chem. 2002, 67, 4985; (b) Motoyama, Y.; Itonaga,
C.; Ishida, T.; Takasaki, M.; Nagashima, H. Org. Synth.
2005, 82, 188.
3. Motoyama, Y.; Mitsui, K.; Ishida, T.; Nagashima, H. J.
Am. Chem. Soc. 2005, 127, 13150.
4. (a) Ojima, I. In The Chemistry of Organic Silicon Com-
pounds; Patai, S., Rappoport, Z., Eds.; John Wiley &
Sons: New York, 1989; Part 2, Chapter 25, pp 1479–1526;
(b) Comprehensive Handbook on Hydrosilylation; Marci-
nice, B., Ed.; Pergamon: Oxford, 1992.
5. Igarashi, M.; Fuchikami, T. Tetrahedron Lett. 2001, 42,
1945.
6. Hitchcock, P. B.; Lappert, M. F.; Warhurst, J. W. Angew.
Chem., Int. Ed. Engl. 1991, 4, 438.
In summary, we have discovered a practical reduction
procedure for tertiary-amines from carboxamides with
hydrosilanes. This is achieved by catalysis of platinum,
and the catalyst concentration, reaction time, and reac-
tion temperature are apparently lower than the brief re-
port by Igarashi and Fuchikami. The contamination of
platinum residue to the product is minimum, because
the silicon resin formed soaked up the catalyst platinum
species simultaneously. Although these features are also
achieved with the ruthenium catalyst reported earlier,
this platinum catalyzed process has a special advantage
for organic chemists due to the use of commercially
available platinum compounds. The mechanisms of this
remarkable ‘dual Si–H effect’ in the facile reduction of
carboxamides involving efficient removal of silicon and
platinum residues are presumably related to the
RhCl(PPh3)3-catalyzed hydrosilylation of ketones with
HMe2Si(CH2)2SiMe2H previously reported by our
group; there, interaction of two proximate Si–H groups
to the rhodium center dramatically accelerated the reac-
tion.10 Since double oxidative addition of two Si–H
groups to the platinum compounds has been studied
by Shimada and Tanaka,11 the dual Si–H group effect
presented in this paper would be explained by interac-
tion of dual Si–H groups in PMHS and other bi- or
multi-functional siloxanes to platinum species which
accelerate the reduction of amides. Detailed mechanistic
studies on the interaction of platinum species with vari-
ous organosilanes containing dual Si–H groups are now
underway by our research group.12
7. A
typical
example:
To
a
solution
of
PhCH2CH2C(O)NMe2 and PMHS (Si–H = 3.7 equiv to
the amide) in a small amount of THF was added 1 mol %
of Karstedt’s catalyst in xylene (Aldrich) at 0 °C. The
solution rapidly became viscose and set to gel after 5 min.
After 3 h, the mixture was extracted with ether to form
crude dimethyl-3-phenylpropylamine, which was passed
through a short pad of Al2O3 to give the amine (86%).
ICP-mass analyses revealed the platinum content in the
amine to be 36 ppm (crude) and <1 ppm (after
purification).
8. Thayer, A. Chem. Eng. News 2005, 83, 55.
9. Chauhan, B. P. S.; Rathore, J. S. J. Am. Chem. Soc. 2005,
127, 5790.
10. (a) Nagashima, H.; Tatebe, K.; Ishibashi, T.; Nakaoka,
A.; Sakakibara, J.; Itoh, K. Organometallics 1995, 14,
2868; (b) Nagashima, H.; Suzuki, A.; Iura, T.; Ryu, K.;
Matsubara, K. Organometallics 2000, 19, 3579.
11. (a) Corey, J. Y.; Braddock-Wilking, J. Chem. Rev. 1999,
99, 175; (b) Shimada, S.; Rao, M. L. N.; Li, Y.; Tanaka,
M. Organometallics 2005, 24, 6029.
12. The formation of silicon resin containing platinum species
is due to cross-linking of the PMHS chain, in which
platinum catalyzes the reductive deoxygenation of amides
leading to the formation of siloxane networks; this was
clearly evidenced by 29Si CPMAS NMR of the silicon

S. Hanada et al. / Tetrahedron Letters 47 (2006) 6173–6177
6177
resin formed. It is not clear from the TEM analysis of the
silicon resin containing platinum whether the encapsulated
platinum species is molecular or colloidal, which has been
discussed in terms of mechanisms of Pt-catalyzed hydro-
silylation of olefins, see: Lewis, L. N.; Lewis, N. J. Am.
Chem. Soc. 1986, 108, 7228.