Palladium mediated chemoselective reduction of α,β-unsaturated cyano esters with potassium formate

Article abstract of DOI:10.1081/SCC-120015714

A number of α,Β-unsaturated cyano esters have been chemoselectively reduced with potassium formate as hydrogen donor, and palladium(II) acetate as homogeneous catalyst, in DMF without any concomitant reduction of cyano or carboxylate or halogen groups.

Full text of DOI:10.1081/SCC-120015714

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Palladium Mediated Chemoselective Reduction of α,β-
Unsaturated Cyano Esters with Potassium Formate
Basudeb Basu a b , Md. Hossain Mosharef Bhuiyan a & Satadru Jha a
a Department of Chemistry, University of North Bengal, P.O. North Bengal University,
Darjeeling, India
b Department of Chemistry, University of North Bengal, P.O. North Bengal University,
Darjeeling, 734 430, India
Version of record first published: 21 Aug 2006.
To cite this article: Basudeb Basu, Md. Hossain Mosharef Bhuiyan & Satadru Jha (2003): Palladium Mediated Chemoselective
Reduction of α,β-Unsaturated Cyano Esters with Potassium Formate, Synthetic Communications: An International Journal for
Rapid Communication of Synthetic Organic Chemistry, 33:2, 291-296
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SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 2, pp. 291–296, 2003
Palladium Mediated Chemoselective Reduction
of a,b-Unsaturated Cyano Esters
with Potassium Formate
*
Basudeb Basu, Md. Mosharef Hossain Bhuiyan,
and Satadru Jha
Department of Chemistry, University of North Bengal,
P.O. North Bengal University, Darjeeling, India
ABSTRACT
A number of a,b-unsaturated cyano esters have been chemo-
selectively reduced with potassiumformate as hydrogen donor, and
palladium(II) acetate as homogeneous catalyst, in DMF without any
concomitant reduction of cyano or carboxylate or halogen groups.
Key Words: Hydrogen transfer reduction; a,b-Unsaturated cyano
esters; a,b-Unsaturated tin carboxylate; Palladiumacetate; Potassium
formate.
*Correspondence: Basudeb Basu, Department of Chemistry, University of
North Bengal, P.O. North Bengal University, Darjeeling 734 430, India. Fax:
+91 353 2581546; E-mail: basu_nbu@hotmail.com.
291
DOI: 10.1081/SCC-120015714
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com

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292
Basu, Hossain Bhuiyan, and Jha
Chemoselective reduction of carbon–carbon multiple bond in conju-
gated systems is an important process in organic synthesis.[1] Despite
the bewildering variety of reducing agents available to synthetic chemists,
new and selective reductants are in constant demand. Transition metal-
catalyzed hydrogen transfer reaction with the aid of a hydrogen donor,
such as trialkyl ammonium formate,[2] and other hydrides like n-Bu3SnH,[3]
NaH2PO3/H2O,[4] Ph2SiH2/ZnCl2ꢀH2O,[5] triethoxysilane–water,[6] are
some of the examples employed for selective conjugate reduction. In
most cases, direct source of hydride is used for conjugate addition to
the more nucleophilic b-carbon, whereas formic acid and its salts are
believed to be a source of hydride in situ,[7] which eventually adds to
the b-carbon. Cacchi et al.[8] has recently reported a combination of
Pd(OAc)2/HCOOK as a convenient alternative reductant for conjugate
reduction of a,b-unsaturated carbonyl compounds. On the other hand,
reduction of conjugated nitriles and cyano esters using molecular hydro-
gen or Pd-catalyzed hydride-transfer afforded with reduction of the
cyano group as well.[9] For example, reduction of a,b-unsaturated cyano
esters in presence of Pd/C and p-menthene (as hydrogen donor) led to
reduction of not only the C¼C double bond, but also the nitrile function
to a methyl group.[10] Moreover, reduction of nitrile using a combination
of Pd/C and formic acid seemed to be very variable in many other
examples.[11] Early studies on reduction of alkylidenecyanoacetic esters
using sodiumborohydride at roomtemperature led to reduction of C ¼C
double bond as well as reduction of the ester to alcohol.[12] Sodium
borohydride has however been successfully used for reduction of 1a[13]
and sodiumcyanoborohydride has selectively reduced a,b-unsaturated
esters, nitriles, and nitro compounds.[14] However, metal hydrides are
generally highly reactive and expensive reagents and cyanoborohydride
generates toxic byproducts upon workup. Very recently, Hantzsch
1,4-dihydropyridines (HEH) has been employed for selective reduction
of a,b-unsaturated cyano esters.[15] This procedure, however, involves
specific reagent (Hantzsch 1,4-dihydropyridines) and after the reaction
the redox products require separation. Consequently, it appeared to us
of interest to check the efficacy of Pd(OAc)2/HCOOK combination
in reduction of more functionalized a,b-unsaturated cyano esters.
The study could be of further importance, as the soluble chiral
Pd-catalyzed hydrogen transfer reactions are known to induce asym-
metry in the product.[16] The chiral Pd-complex catalyzed conjugate
reduction without any concomitant reduction of other functional
groups might produce asymmetric compounds for further elaboration
to useful synthetic intermediates. We wish to report that a,b-unsaturated

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Chemoselective Reduction of a,b-Unsaturated Cyano Esters
293
cyanoesters possessing other sensitive functional groups can be smoothly
converted into the corresponding saturated cyanoacetates according
to Sch. 1. The reduction appeared to be mild and efficient as the
nitrile, ester (alkyl and tri-n-butyl stannyl), and halogen functions
remain unaffected.
A series of a,b-unsaturated cyano esters (1a–i) have been prepared
fromtheir carbonyl substrates condensed with ethyl cyanoacetate under
Knoevenagel condition.[17] The unsaturated cyano ester was dissolved in
DMF and added Pd(OAc)2 (2 mol%), HCOOK (2 equivalent) and stirred
at 45–50ꢁC for 3–4 h in a screw-cap sealed tube under N2. After usual
workup, the product was purified by column chromatography over silica
gel to afford the reduced product in good to excellent yield (Table 1).
Although dehalogenation of halo-aromatics is known under transfer
reduction using heterogeneous catalyst,[18] the present method did not
proceed with cleavage of carbon–halogen bond (Entry 1b). The stannyl
ester (Entry 1h), prepared fromits ethyl ester by transesterification with
bis-tri-n-butyltin oxide,[19] also survived demetallation under the reaction
condition.[20] To observe any effect of ligand participation in the catalytic
process, the reaction was carried out in presence of various ligands, such
as PPh3, P(o-tolyl)3 and TMEDA with the alkylidenecyanoacetic ester
(1i). In all the experiments, a smooth conversion to the reduced product
with excellent yield was obtained. Choice of solvent is an important
factor governing the activity of soluble catalyst in transfer reduction.[11]
As most soluble catalysts are often coordinated to solvent, DMF was
found to be superior in comparison to non-polar solvents like toluene or
carbon tetrachloride.
Thus the present study constitutes a useful condition for selective
reduction of C¼C double bond of a,b-unsaturated cyano esters using
HCOOK/Pd(OAc)2 as simple and inexpensive reductant. The reaction
possibly involves hydride transfer in situ at the b-carbon and proceeds
without any concomitant reduction of cyano, ester, or halogen groups. The
ability of this reductant to performconjugate reduction on functionalized
Scheme 1.

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294
Basu, Hossain Bhuiyan, and Jha
Table 1. Reduction of a,b-unsaturated cyano esters by using HCOOK and
catalytic Pd(OAc)2.
No.
Olefin
Temp./time
45ꢁC/3 h
Product
Yield (%)a
92
1a
1b
1c
1d
1e
45ꢁC/4 h
50ꢁC/4 h
50ꢁC/3 h
45ꢁC/4 h
96
95
87
79
1f
50ꢁC/4 h
45ꢁC/4 h
50ꢁC/3 h
76
95
75
1g
1h
1ib
50ꢁC/3 h
88
aYields refer to single runs and are for pure, isolated products; all compounds
1
were fully characterized by IR, UV, and H- and 13C-NMR spectra.
bThe reaction was also carried out in presence of PPh3, P(o-tolyl)3, and TMEDA.
alkylidenecyanoacetate in a controlled fashion is noteworthy. The
homogeneous catalytic condition offers further use of chiral ligands
to promote asymmetric induction. Future studies will be attempted in
this direction.

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Chemoselective Reduction of a,b-Unsaturated Cyano Esters
295
EXPERIMENTAL
A representative procedure (Table 1, Entry 1e) is as follows: To a
solution of the unsaturated cyano ester (0.50 g, 2.62 mmol) in DMF (5 mL)
was added Pd(OAc)2 (12 mg, 2 mol%), HCOOK (0.44 g, 5.24 mmol) and
stirred the reaction mixture in a sealed tube (screw-cap) under N2 at 45ꢁC
for 4 h. The mixture was cooled, diluted with water and extracted with
ether (3 ꢂ 15 mL). The combined organic layer was washed with brine
solution (10 mL), dried over anhydrous Na2SO4 and concentrated. The
residue was purified by column chromatography over silica gel and elu-
tion with ethyl acetate–light petroleum(1:9) afforded the desired product
1
as colorless oil in 79% yield. IR (neat): ꢀmax 2244, 1747 cmꢃ1; H-NMR
(CDCl3, 300 MHz) ꢁ 1.31 (t, 3H, J ¼ 7.1 Hz), 3.28 (m, 2H), 3.79 (m, 1H),
4.26 (q, 2H, J ¼ 7.1 Hz), 6.23 (s, 1H), 6.30 (s, 1H), 7.34 (s, 1H); 13C-NMR
(CDCl3, 75 MHz) ꢁ 14.3, 36.1, 37.3, 63.3, 108.7, 110.9, 115.9, 142.8,
149.3, 165.4.
ACKNOWLEDGMENTS
We are grateful to the Department of Science and Technology, Govt.
of India, for financial support (No. SP/S1/G-13/97). SJ is a JRF under
the above project.
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Received in the UK October 10, 2001