Catalytic transfer reduction of conjugated alkenes and an imine using polymer-supported formates

Article abstract of DOI:10.1016/j.tetlet.2003.10.019

An efficient and mild method for catalytic transfer hydrogenation of C=C and C=N double bonds with the aid of resin-supported formate (PSF) as the hydrogen donor and palladium acetate as the catalyst is reported.

Full text of DOI:10.1016/j.tetlet.2003.10.019

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 8931–8934
Catalytic transfer reduction of conjugated alkenes and an imine
using polymer-supported formates
Basudeb Basu,* Md. Mosharef H. Bhuiyan, Pralay Das and Ismail Hossain
Department of Chemistry, University of North Bengal, Darjeeling 734 430, India
Received 22 August 2003; revised 23 September 2003; accepted 3 October 2003
Abstract—An efficient and mild method for catalytic transfer hydrogenation of CꢀC and CꢀN double bonds with the aid of
resin-supported formate (PSF) as the hydrogen donor and palladium acetate as the catalyst is reported.
©
2003 Elsevier Ltd. All rights reserved.
Catalytic transfer hydrogenation (CTH) with the aid of
a stable hydrogen donor is a useful alternative method
to catalytic hydrogenation by molecular hydrogen. In
used in CTH. Herein we disclose our results illustrating
the synthetic utility of PSF in palladium-catalyzed
transfer hydrogenation of a variety of electron deficient
alkenes and an imine (Scheme 1).
1
transfer hydrogenation, several organic molecules such
2
3
as hydrocarbons, primary and secondary alcohols,
4
and formic acid and its salts have been employed as
the hydrogen source. The use of reagents such as
The PSF was prepared by washing Amberlite resin
−
(
IRA 420, Cl ) packed in a column with 10% aqueous
1
b
hydrazine is less frequent. The use of a hydrogen
donor has some advantages over the use of molecular
hydrogen since it avoids the risks and the constraints
associated with hydrogen gas as well as the necessity for
pressure vessels and other equipment. During the last
decades, asymmetric transfer hydrogenation has been
formic acid solution repeatedly until the washings gave
a negative response for chloride ion (Scheme 2). Finally
the solid was washed with water several times and then
dried under vacuum. The resulting resin formate was
used directly for catalytic reduction. A mixture of
unsaturated compound, palladium acetate (2 mol%)
and resin formate in DMF was stirred at 70–75°C for
5
accomplished using chiral metal complexes.
1
0–16 h (Table 1). After being cooled and diluted with
Functionalized polymers have emerged as potent tools
for solution-phase chemistry and automated parallel
synthesis. Reagents immobilized on solid supports
water the mixture was filtered and extracted with ether,
which on evaporation afforded the desired product.
6
offer advantages in terms of clean and green reactions,
ease of separation of the product and reusability. While
polymeric supports have been used for anchoring sev-
7
eral reducing agents such as borohydrides, tin
8
hydrides etc., solid supported hydrogen donors have
rarely been employed in CTH. Desai and Danks
reported that polymer supported formate (PSF) can be
used in Rh(I)-catalyzed reduction of cinnamic acids,
but their method lacks optimization with substrates
bearing other reducible groups and other multiple
Scheme 1.
9
bonds. In connection with our interest in palladium-
catalyzed transfer hydrogenation of alkenes and imines
10
using potassium formate, we wanted to develop a
stable hydrogen donor anchored to a solid surface to be
Keywords: catalytic transfer hydrogenation; polymer-supported for-
mate; palladium acetate; unsaturated alkenes, imines.
*
Corresponding author: Fax: +91-353-2581546; e-mail: basu nbu@
indiatimes.com
–
Scheme 2.
0
040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2003.10.019

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B. Basu et al. / Tetrahedron Letters 44 (2003) 8931–8934
Table 1. Palladium-catalyzed transfer reduction of alkenes and an imine using PSF

B. Basu et al. / Tetrahedron Letters 44 (2003) 8931–8934
8933
The generality of this methodology has been investi-
gated with different types of electron-deficient alkenes
and an imine (Table 1). We first examined reduction of
alkylidene cyanoacetates (entries 1, 2) using PSF and
palladium acetate (2 mol%) in DMF. The PSF was
employed in excess anticipating that other functional
groups would not react. The reduction of the CꢁC
double bond proceeded smoothly at 70–75°C requiring
only gentle agitation; work-up was then achieved by
simple filtration, extraction with diethyl ether and evap-
oration. The reduced product was purified by column
chromatography over silica gel. Both the cyano and
ester groups remained unaffected under the reaction
conditions. The reduction of a dicyanoalkylidene
derivative (entry 3) was found to occur with similar
efficiency.
In conclusion, we have shown that palladium-catalyzed
transfer hydrogenation can be performed on a variety
of electron-deficient alkenes as well as an imine using
polymer supported formate (PSF) as the source of
hydrogen. The method is operationally simple and
applicable to a variety of unsaturated organic com-
pounds. Other advantages are clean work-up, high
yields and environmentally benign conditions. The use
of a palladium catalyst showed some substrate selectiv-
ity and the transfer hydrogenation appears to proceed
at a slower rate in comparison to that of potassium
formate. Future studies on the mechanistic aspects
including the use of other transition metal complexes
with chelating phosphine ligands are of major interest.
Representative procedure for catalytic transfer hydro-
genation of functionalized alkenes using PSF: To a
solution of methyl 3-(4-acetophenyl)-2-(tert-butoxycar-
bonylamino)-acrylate (entry 9) (321 mg, 1 mmol) in
Based on these encouraging results, the scope and
limitations of this transfer hydrogenation were further
extended. As seen in Table 1, a,b-unsaturated ketones
DMF (3 mL) was added Pd(OAc) (5 mg, 2 mol%). The
2
reaction mixture was flushed with nitrogen and PSF
(
entries 4–7) bearing potentially reducible groups were
(
resin formate, 1 g) was added in one portion. The
hydrogenated efficiently. The reaction, if continued for
a longer period, resulted in partial reduction of the
carbonyl function as well (31%) (entry 4b).
reaction mixture was stirred in a screw-cap sealed tube
at 70°C for 10 h. After cooling, the reaction mixture
was diluted with water and the solid resin was removed
by filtration. The filtrate was extracted with ether (3×15
mL). The combined ethereal layer was washed with
Since dehydroamino acid derivatives are potential pre-
cursors to phenylalanine or alanine based amino acids
11
brine, dried over Na SO and evaporated to dryness
2 4
and their synthesis is one of our major interests, we
attempted reduction of enamides (entries 8, 9) using
PSF and catalytic palladium acetate. Interestingly,
while methyl 2-(tert-butoxycarbonylamino)-acrylate
under reduced pressure. The residue was purified by
column chromatography over silica gel using petroleum
ether:EtOAc (4:1) to furnish methyl 3-(4-acetophenyl)-
2
-(tert-butoxycarbonylamino)propionate 9 as colorless
(
entry 8) was not reducible under the present condi-
crystals (224 mg, 70%); mp 72–73°C; UV (MeOH): umax
tions, the p-acetyl compound (entry 9) underwent
smooth reduction in good yield (70%). Although this
selectivity is difficult to explain without further evi-
dence, the enhanced electrophilicity at the b-carbon of
the alkene and involvement of the ‘hydridic route’
might be the possible reasons.
2
1
7
48 nm; IR (neat): w
516, 1455, 1373 cm ; H NMR (CDCl , 300 MHz): l
.87 (d, 2H, J=8.1 Hz), 7.23 (d, 2H, J=8.1 Hz), 5.05
3360, 2996, 1752, 1670, 1609,
max
−1
1
3
(
d, 2H, J=7.7 Hz), 4.59 (t, 1H, J=7.7 Hz), 3.69 (s,
13
3
H), 2.55 (s, 3H), 1.38 (s, 9H); C-NMR (CDCl , 75
3
MHz): l 197.7, 171.9, 154.9, 141.7, 135.8, 129.5, 128.5,
5
4.1, 52.3, 38.3, 29.6, 28.2, 26.5.
In order to broaden the scope of this study, we carried
out reduction of the CꢀN double bond of an imine. The
Acknowledgements
(
4-methoxybenzylidene)-phenylamine (entry 10) under
similar conditions afforded the secondary amine 10 in
excellent yield (85%). Since the imine was derived from
the corresponding carbonyl compound, this overall
one-pot protocol may be seen as a direct reductive
amination of carbonyl compound using PSF and cata-
lytic palladium acetate. Further studies are in progress
in this direction.
The authors are appreciative of the financial support
provided by The Department of Science & Technology,
Govt. of India (Grant No. SP/S1/G-13/97) and The
Council of Scientific and Industrial Research, New
Delhi (Grant No. 01-1863/03-EMR-II).
Surprisingly, a simple alkyl cinnamate (entry 11) and a
nitro olefin (entry 12) failed to undergo CTH using the
optimized condition. Desai and Danks carried out
reduction of alkyl cinnamates using PSF and
RhCl(PPh3)3 (2.5 mol%) as the catalyst under
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