Thermal- and microwave-assisted hydrogenation of electron-deficient alkenes using a polymer-supported hydrogen donor

Article abstract of DOI:10.1016/S0040-4039(01)01157-1

Under microwave conditions hydrogenation of olefinic substrates may be achieved in excellent yields using a hydrogen donor supported on an ion-exchange resin and Wilkinson's catalyst.

Full text of DOI:10.1016/S0040-4039(01)01157-1

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 5963–5965
Thermal- and microwave-assisted hydrogenation of
electron-deficient alkenes using a polymer-supported
hydrogen donor
Bimbisar Desai and Timothy N. Danks*
Department of Chemistry, University of Surrey, Guildford, Surrey GU2 7XH, UK
Received 21 May 2001; accepted 28 June 2001
Abstract—Under microwave conditions hydrogenation of olefinic substrates may be achieved in excellent yields using a hydrogen
donor supported on an ion-exchange resin and Wilkinson’s catalyst. © 2001 Elsevier Science Ltd. All rights reserved.
In this paper we wish to report a simple procedure for
catalytic hydrogenation reactions using a recyclable,
polymer-supported transfer hydrogenation source.
nia and, whilst on a small scale this does not create any
serious problems, on a larger scale this release may
become more significant.
Recent environmental constraints have led to the devel-
opment of clean and easily recycled reagents for use in
synthetic chemistry. This need has led to the develop-
ment and use of reagents that are supported on a solid
matrix. Also, because of the development of robotic
systems for chemical synthesis in many industrial sec-
tors, the need for solid-supported reagents has
increased considerably. Such supports facilitate easy
removal of the residues from the reaction mixture with-
out release of the residues into the environment. They
allow work-up procedures to be simplified where simple
filtration rather than extraction, etc., is required.
Reagents supported on organic polymers and within
and/or on the surface of inorganic matrices have all
Microwave-assisted catalytic transfer hydrogenation,
has also been achieved. In most cases, under
4
microwave conditions, Pd/C catalyst, and ammonium
formate as the hydrogen donor are used. Hydrogenoly-
sis has been shown to proceed with a similar level of
5
efficiency under microwave conditions.
During our studies on microwave-assisted hydrogena-
tion reactions we reported how use of the di-formate
salt of tetramethylethylene diamine provided an ideal
alternative to ammonium formate for isotopic labelling
6
of alkenes using Wilkinson’s catalyst.
In this note we wish to report the use of polymer-sup-
ported formates (PSF) for the reduction of alkenes
using Wilkinson’s catalyst. As far as we are aware this
paper represents the first example of a polymer-sup-
ported transfer hydrogenation source for alkenes. The
procedure does not result in sublimation and in princi-
ple, may also be easily adapted for parallel hydrogena-
tion protocols and is also of potential use in robotic
synthesizers.
1
been reported.
Microwave-assisted organic chemistry has also experi-
enced considerable growth over the past decade. Nota-
ble contributions from many groups have been detailed
2
in several recent reviews. Laboratory scale catalytic
3
transfer hydrogenation plays a key role in organic
synthesis. Typically a catalyst (e.g. Pd/C, RhCl(PPh ) ,
3
3
etc.) and a hydrogen source, such as ammonium for-
mate, is used for the hydrogenation reactions. Although
efficient, these reactions are often troublesome since
ammonium formate can sublime and block the reaction
apparatus. Also the reactions lead to release of ammo-
Initially Wilkinson’s catalyst and polymer-supported
formate derived from (aminomethyl)polystyrene (0.6
mmol/g) was used as a hydrogen source in our reac-
tions. Conversion of the resin to the formate form was
achieved by washing with a 20% solution of formic acid
in dichloromethane. After filtration and drying under
vacuum the resulting activated resin was used directly
in a hydrogenation reaction.
Keywords: microwaves; hydrogen donor; hydrogenation; ion-
exchange resin.
*
Corresponding author. E-mail: t.danks@surrey.ac.uk
0
040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01157-1

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B. Desai, T. N. Danks / Tetrahedron Letters 42 (2001) 5963–5965
A mixture of formylated (aminomethyl)polystyrene,
Wilkinson’s catalyst and E-3-phenylpropenoic acid in a
minimum quantity of DMSO (0.5 ml) was irradiated at
100 W for 30 s. Filtration and removal of the solvent
led to the isolation of white crystals, which were iden-
tified as the reduction product 3-phenylpropanoic acid
by comparison of spectroscopic data with literature
values. Similarly, when the corresponding methyl and
ethyl esters were used as a substrate, the reaction led to
the formation of the corresponding saturated esters.
Attempts to increase the yield of these reactions by
either increasing the quantity of hydrogen donor or
prolonging the irradiation time led either to degrada-
tion or no significant increase in yield.
®
A mixture of Amberlite IRA 938-supported formate,
Wilkinson’s catalyst and E-3-phenylpropenoic acid in a
minimum quantity of DMSO was irradiated at 100 W
for 30 s. After filtration, extraction and removal of the
solvent, white crystals identified as 3-phenylpropanoic
acid were isolated in excellent yield. When the identical
reaction was performed under thermal conditions
(
70°C, 3 h) the reaction required considerably longer
and resulted in a reduced reaction yield.
It should be noted that after separation of the Amber-
®
lite at the end of the reaction the polymer-supported
formate salt was easily regenerated and could be reused
in further hydrogenation reactions. In total, five reac-
tion/regeneration cycles were possible before there was
an appreciable decrease in the reaction yield.
In view of the relatively low yields of the reduction
products and the relatively high cost of (aminomethyl)-
polystyrene the use of a different support for formate
was investigated. There are several reports of the use of
In order to explore the scope of this reaction, a range of
alkenes were treated with formate and Wilkinson’s
catalyst under identical conditions. The results of these
experiments are presented in Table 1. In each case a
thermal comparison for each reaction is presented. This
allows the influence of the microwave irradiation on the
reaction yield to be better understood.
®
®
relatively inexpensive Amberlite and Amberlyst ion-
1
exchange resins as a support for reagents. In view of
these reports we decided to support formate on these
resins and use the resulting material in catalytic hydro-
genation reactions.
Interestingly for pentenoic acid (Table 1, entry 6) there
is a particularly noticeable improvement by the applica-
tion of microwave irradiation. In all other cases the
reactions show an increase in yield of between 10 and
25% by application of microwave irradiation. The
greatest saving, however, is the dramatically reduced
reaction times and solvent volumes for the microwave-
assisted processes.
The hydrogen donor was prepared by washing Amber-
−
lite (IRA 938 Cl form) resin with formic acid (98%)
and subsequently with water until no further chloride
was eluted. The resulting solid was dried under vacuum
over P O . The resin thus obtained was ready for
2
5
7
further application in hydrogenation reactions.
Table 1. Hydrogenation of alkenes using polymer-supported formate and Wilkinson’s catalyst under microwave and thermal
conditions
Entry
Alkene
R
R%
Producta
Yield (%)
Microwaveb
Thermalc
1
2
3
4
5
6
7
8
1
2
3
4
5
6
7
8
Ph
Ph
Ph
Ph
Ph
Et
CO H
9
10
11
12
13
14
15
16
95
90
80
95
95
95
95
95
80
75
62
70
88
50
95
70
2
CO Me
2
CO Et
2
CHO
COCH3
CO H
2
Ph
Ph
CN
CON(CH3)2
a
All products gave satisfactory spectroscopic data.
All microwave irradiations were carried out at 100 W for 30 s.
All thermal reactions were performed at 70°C for 3 h in DMSO.
b
c
8

B. Desai, T. N. Danks / Tetrahedron Letters 42 (2001) 5963–5965
5965
In conclusion, it has been shown that a formate sup-
ported on an Amberlite resin may be used as a poly-
Loupy, A.; Petit, A.; Hamelin, J.; Texier-Boullet, F.;
Jacquault, P.; Mathe, D. Synthesis 1998, 1213.
®
mer-supported source for transfer hydrogenation
reactions using Wilkinson’s catalyst under thermal and
microwave conditions.
3. (a) Rylander, P. N. Hydrogenation Methods; Academic
Press: Orlando, FL, 1985; (b) James, B. R. Homogenous
Hydrogenation; Wiley: NewYork, 1973.
4
. Banik, B. K.; Barakat, K. J.; Wagle, D. R.; Manhar, M.
S.; Bose, A. K. J. Org. Chem. 1999, 64, 5746.
. (a) Anwer, M. K.; Sherman, D. B.; Roney, J. G.; Spatola,
A. F. J. Org. Chem. 1989, 54, 1284; (b) Anwer, M. K.
Tetrahedron Lett. 1985, 26, 1381; (c) Rajagopal, S.; Spa-
tola, A. F. Appl. Catal. A 1997, 152, 69.
The application of this chemistry for catalytic reduction
of electron-rich alkenes, debenzylations, and asymmet-
ric hydrogenation reactions is currently under investiga-
tion.
5
6
7
8
. Al-Qahtani, M. H.; Cleator, N.; Danks, T. N.; Garman,
R. N.; Jones, J. R.; Stefaniak, S.; Morgan, A. D.; Sim-
monds, A. J. J. Chem. Res. 1998, 26, 400.
. Resin loading was determined as 2.5 mmol g by poten-
tiometric titration after releasing the formate as formic
acid by washing with dil. HCl.
Acknowledgements
−
1
We thank the Personal Chemistry AB for financial
support and provision of
microwave reactor.
a
MW-10 Microwell
. In a typical experiment, E-3-phenylpropenoic acid (0.025
®
g, 0.16 mmol), Amberlite IRA 938-supported formate
(
0.200 g) and Wilkinson’s catalyst (0.04 g, 0.0043 mmol)
References
were suspended in a reaction tube using DMSO (0.5 ml) as
the solvent. The mixture was irradiated with microwaves
at 100 W for 30 s. On cooling the mixture was diluted with
dichloromethane (5 ml) and filtered. The filtrate was
washed with water (2×5 ml). The organic fraction was
1
. (a) Ley, S. V.; Baxendale, I. R.; Bream, R. N.; Jackson, P.
S.; Leach, A. G.; Longbottom, D. A.; Nesi, M.; Scott, J.
S.; Store, R. I.; Taylor, S. J. J. Chem. Soc., Perkin Trans.
1
2000, 3815; (b) Kirschning, A.; Monenschein, H.; Wit-
dried over magnesium sulfate (MgSO ) and the solvent
tenberg, R. Angew. Chem., Int. Ed. 2001, 40, 650.
. (a) Caddick, S. Tetrahedron 1995, 51, 10403; (b) Deshayes,
S.; Liagre, M.; Loupy, A.; Luche, J. L.; Petit, A. Tetra-
hedron 1999, 55, 10851; (c) de la Hoz, A.; D ´ı az-Ortiz, A.;
Moreno, A.; Langa, F. Eur. J. Org. Chem. 2000, 3659; (d)
4
2
removed under reduced pressure to give a reddish-orange
residue which was purified by filtration through a plug of
alumina to give 3-phenylpropanoic acid as white crystals
(0.024 g, 95%).
.