Self-encapsulation of homogeneous catalyst species into polymer gel leading to a facile and efficient separation system of amine products in the Ru-catalyzed reduction of carboxamides with polymethylhydrosiloxane (PMHS)

Article abstract of DOI:10.1021/ja054453l

A practical procedure for production of amines is offered by the ruthenium-catalyzed reduction of carboxamides with polymethylhydrosiloxane, in which encapsulation of the catalyst species into the formed insoluble siloxane resins contributes to the separation of both metallic and siloxane residues from the product. Copyright

Full text of DOI:10.1021/ja054453l

Published on Web 09/02/2005
Self-Encapsulation of Homogeneous Catalyst Species into Polymer Gel
Leading to a Facile and Efficient Separation System of Amine Products in the
Ru-Catalyzed Reduction of Carboxamides with Polymethylhydrosiloxane
(PMHS)
Yukihiro Motoyama, Kaoru Mitsui, Toshiki Ishida, and Hideo Nagashima*
Institute for Materials Chemistry and Engineering, Graduate School of Engineering Sciences, Kyushu UniVersity,
Kasuga, Fukuoka 816-8580, Japan
Received July 6, 2005; E-mail: nagasima@cm.kyushu-u.ac.jp
Reduction of carboxamides is a crucially important method in
organic synthesis for the production of amines. Alkali metal
hydrides have long been the reagents of choice for the reaction,
and its utility has been demonstrated innumerable times.1 However,
there still remain drawbacks which should be improved from the
viewpoint of safe and environmentally benign chemical processes:
a stoichiometric quantity of an air- and moisture-sensitive reagent,
which sometimes causes ignition, must be used, and production of
metal hydroxide or oxide wastes makes the isolation of the product
from the reaction mixture difficult. Reduction with air- and
moisture-stable hydrosilanes is one of the solutions;2,3 in particular,
we have recently reported the reduction of amides using trialkyl-
silanes catalyzed by a ruthenium cluster, (µ3,η2,η3,η5-acenaphthylene)-
Ru3(CO)7 (1).4 In this catalytic reaction, the reaction is exothermic
and efficiently proceeds even at room temperature and can be used
for production of a large quantity of amines.4c The siloxane waste
can be removed from the amines by a workup process using strong
acids and bases through the corresponding ammonium salts of the
products formed. In contrast, the acid-base treatment only partially
contributes to removing the ruthenium species (ca. 90%) from the
crude amine product. In other words, removal of metal residues
from the product remains a problem needing improvement, and
for the solution, it is desirable to avoid harsh conditions, such as
strong acids and bases.
to which the catalyst species is effectively self-encapsulated. After
the reaction is complete, the amine product, soluble in appropriate
organic solvents, is facilely separated from the insoluble polymer
gel containing the catalyst species. This idea is actually realized
using a commercially available PMHS. The initial solution contains
an amide, PMHS, ruthenium complex 1, and a small amount of a
solvent in order to make the solution homogeneous (Figure 1, step
A). As the hydride reduction of the amide proceeds, the oxygen
atom originating from the amide contributes to bridging the polymer
chains of the siloxane. This produces a polymer gel with highly
cross-linked siloxane networks (step B).8 After the reaction is
complete, removal of the solvent affords a silicone resin insoluble
in common organic solvents in which the catalyst species is
encapsulated, but the amine product is not (step C).9
As a result,
the product is obtained by washing the silicone resin (solid) with
an appropriate solvent without contamination by the metal residue
as well as silicon waste (step D). In a typical example, reaction of
N,N-dimethyl-3-phenylpropionamide 2a (1 mmol) with PMHS (Mw
) 1500-1900; n ) 25.6 (average); Si-H ) 4.4 equiv to 2a) and
1 (1 mol % based on 2a) was carried out using tetrahydropyran
(THP) as the solvent (0.5 mL) at 30 °C. After 1 h, the homogeneous
solution set to gel (step B). After 15 h, removal of the solvent from
the gel under reduced pressure, a silicone resin, and an amount of
liquid product was obtained (step C). Washing the mixture with
ether gave a clear, colorless solution containing the amine 3a (88%
yield determined by NMR) and a light orange solid (step D).11 It
is important that the orange metal species is only in the silicone
resin (Ru/Si) and not in the amine obtained. In fact, ICP mass
analysis of the amine at step E contained less than 15 ppm of the
ruthenium, which means that >99.95% of the ruthenium species
has been encapsulated by the silicone resin, and does not
contaminate the amine product! Interestingly, the encapsulated
catalyst species is still active in the silicone resin and is reusable;
the recovered ruthenium-containing resin (Ru/Si: 1 mol % of Ru
species) catalyzed the reduction of 2a (1 mmol) with PMHS (Si-H
) 3.3 equiv to 2a) at 30 °C for 15 h to give the amine 3a in 75%
yield.
The reduction of 2a efficiently proceeds in Et2O, THP, dimethoxy-
ethane (DME), cyclopentyl methyl ether (CPME), and toluene.
Washing the resinous materials with ether, hexane, or toluene gave
3a in 82-95% yields with the ruthenium content of 15-43 ppm.
In other words, 99.95-99.85% of the ruthenium was encapsulated
into the silicon resin. The present process can apply to reduction
of various amides 2b-e (5 mmol) using 1 (1 mol % to 2) and
PMHS (Si-H ) 4.4 equiv to 2) in THP (Table 1). The amides
were completely consumed after 15 h, and washing the formed gel
with ether afforded the corresponding amine (NMR analysis showed
the yield to be 93-98%). Subsequent distillation afforded the
As a new concept to resolve these problems, we were interested
in encapsulation of metal species by polymers.5 Elegant work by
Kobayashi and co-workers recently established that encapsulation
of metal species into an organic polymer by “microcapsulation
techniques” led to new types of metal catalysts dispersed on the
polymer supports.6 Our idea is not the usage of polymer-supported
heterogeneous catalysts but that of the microcapsulation technique
itself for removal of the catalyst species from the product. In
the catalytic reduction of amides with polymer-reducing reagents
containing Si-H groups, such as polymethylhydrosiloxane
(PMHS),7 the catalytically active ruthenium species generated by
the reaction of 1 with PMHS contributes to producing the desired
amines. At the same time, the active ruthenium species takes part
in cross-linking the PMHS, resulting in formation of polymer gel,
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10.1021/ja054453l CCC: $30.25 © 2005 American Chemical Society

C O M M U N I C A T I O N S
Figure 1. Photos and images of the reduction of carboxamides with PMHS catalyzed by (µ3,η2,η3,η5-acenaphthylene)Ru3(CO)7 1.
Table 1. Reduction of Various Carboxamidesa
Supporting Information Available: Detailed experimental pro-
cedures and results, characterization data of amides 2a-e and amines
3a-d, photos of Figure 1, IR and 29Si NMR spectra of siloxane gel.
This material is available free of charge via the Internet at http://
pubs.acs.org.
References
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a All reactions were carried out using 5 mmol of 2, 1.5 mL (Si-H ) 22
mmol) of PMHS, 0.05 mmol of 1 in 2.5 mL of THP at 30 °C for 15 h.
b After distillation. c Compound 2a (56 mmol) was used. d At 40 °C for 15
h.
product (>98% purity by GLC analysis) in 74-81% yields. The
present procedure was adaptable to a large quantity of reaction:
6.42 g of 3a was obtained from 10 mL (56 mmol) of 2a (entry 2).
Thus, the present reduction of amides with PMHS offers a
solution as an environmentally benign production of amines,
namely, an efficient catalytic process involving facile separation
of catalyst species and silicone byproducts from the product. The
self-encapsulation of catalyst species into the silicone resin is
considered to be one of the methods for microencapsulation of
molecular catalysts into polymer supports. However, new and
particular features of this process include the following: (1) the
immobilization technique itself is the catalytic process; (2) the active
catalytic species is self-encapsulated into the insoluble polymer
during the reduction; (3) separation of both the catalyst species
and silicone byproducts can facilely be achieved; and (4) recovered
silicone resin can be used as the catalyst for the reduction. This
may be a good entry to a new field of environmentally benign
chemical processes, in which catalytic activation of polymer
reagents leads to both efficient chemical transformation of organic
compounds and removal of catalyst species and polymer byproducts
from the desired products. Work on this line as well as detailed
mechanistic studies on the encapsulation is actively underway.
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(b) Lawrence, N. J.; Drew, M. D.; Bushell, S. M. J. Chem. Soc., Perkin
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2002, 6, 913.
(8) Evidence for the formation of cross-linked silicone was obtained from
the solid-state 29Si NMR. The 29Si CPMAS NMR spectrum showed four
signals at δ 10.4, -35.0, -56.5, and -64.8 ppm assignable to -OSiMe3,
-OSi(H)Me-, Si in the trisiloxane ring, and -OSiMe(O-)2, respectively;
the latter two of which are due to the cross-linked silicones (see Supporting
Information). The integral values of these peaks suggest the proportion
of cross-linked silicone to be ca. 45%. See: (a) Engelhardt, G.; Jancke,
H.; Lippmaa, E.; Samoson, A. J. Organomet. Chem. 1981, 210, 295. (b)
Satyanarayana, N.; Alper, H. Macromolecules 1995, 28, 281 and references
therein.
(9) We have reported that the silane reduction of carbonyl compounds
catalyzed by 1 and its analogue is investigated by the oxidative addition
of the triruthenium species to a Si-H bond. In fact, the oxidative adducts
having a Ru-Si bond were isolated, and their role in catalysis is
investigated (refs 4a and 10). The ruthenium-containing silicone resin (Ru/
Si) showed two characteristic νCO absorptions identical to those seen for
the oxidative adducts (see Supporting Information); these suggest that the
ruthenium species may be immobilized by the Ru-Si bond. In contrast,
there is no chemical interaction between the amine product and the silicone
resin. This provides facile extraction of the amine by ether. For a related
work in which a palladium nanoparticle is stabilized in the cross-linking
PMHS, see: Chauhan, B. P. S.; Rathore, J. S.; Bandoo, T. J. Am. Chem.
Soc. 2004, 126, 8493.
(10) Matsubara, K.; Ryu, K.; Maki, T.; Iura, T.; Nagashima, H. Organometallics
2002, 21, 3023.
(11) The crude amine contains a small amount of oligomeric hydrosiloxanes
and low cross-linking PMHS; the former are generally contained in
commercially purchased PMHS. We believe that contamination of the
siloxane residue can be minimized by using PMHS without containing
hydrosiloxane oligomers and careful control of the charged ratio of PMHS
and the amide.
Acknowledgment. This work was supported by a Grant-in-Aid
for Scientific Research from the Ministry of Education, Culture,
Sports, Science and Technology, Japan. We are grateful to Dr. Thies
Thiemann (Kyushu University) for his helpful discussion.
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