Tetrahedron Letters
Bipyridine carbaldehydes as electrophiles in the Morita–Baylis–
Hillman reaction: synthesis of highly functionalized bipyridyl ligands
and a macrocycle
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Siddan Gouthaman, Somasundharam Periyaraja, Ponnusamy Shanmugam
Organic Chemistry Division, Council of Scientific and Industrial Research (CSIR)-Central Leather Research Institute (CLRI), Adyar, Chennai 600020, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A
simple and efficient Morita–Baylis–Hillman (MBH) reaction of bipyridine carbaldehydes and
Received 12 August 2015
Revised 9 September 2015
Accepted 11 September 2015
Available online 11 September 2015
unexplored activated alkenes afforded highly functionalized bipyridyl ligands. Particularly, one-pot
MBH reaction of 2,20-bipyridine-4,40-dicarbaldehyde and 2,20-bipyridine-4-methyl-40-carbaldehyde with
1,6-hexanediol diacrylate afforded a twenty membered bipyridyl macrocycle and bis MBH adducts,
respectively. Synthetic transformations of mono and bis MBH adducts thus obtained have been demon-
strated by preparing bipyridyl N-oxide and [3+2]-cycloadduct of azomethine ylide derived from isatin
and proline.
Keywords:
MBH reaction
Bipyridine
Ó 2015 Elsevier Ltd. All rights reserved.
Electrophile
Pyridine-N-oxide
Spiro pyrrolidine oxindole
Introduction
still in demand. The Morita–Baylis–Hillman (MBH) reaction16 has
been utilized as a synthetic tool in generating complex frameworks
Bipyridine1 derivatives are key synthons in synthetic and mate-
rial chemistry owing to their redox stability.2 Bipyridyl based orga-
nometallics have led to various synthetic methods3 as asymmetric
catalysis.4 Metal complexes with nitrogen ligands offer for the
design of anticancer drugs,5 tissue engineering6 and in drug deliv-
ery.7 In addition, oligopyridine-based heterocycles exhibit a high
chemical stability, long-lived excited-state lifetime, reversible
electrochemical behavior for their optoelectronic property.8 Fur-
thermore, these compounds have also shown potential applica-
tions in bio-sensing, assembly of catenanes and rotaxanes.9 Bis
arm pyridine receptors have been utilized for anion10 and chiral
molecular recognition.11 Bipyridine based polymers could lead to
the electrochromism and electroluminescent display devices.12
Lack of general and efficient methods to manipulate bipyridine
functionalization, most of the existing methods suffer arsenal
strategies such as multi-step and stringent reaction conditions,13
use of expensive and hazardous catalyst/reagents,14 and prolonged
reaction times are generally required.15
and has been used as building blocks in synthetic chemistry and
bioactive molecules.17 The versatility of the reaction has been
demonstrated in the implementation of the MBH adducts.18 We
have studied the synthetic transformation of b-substituted MBH
ester19 derived from electrophiles such as aryl aldehydes, isatin,
ferrocene carboxaldehyde, heteroaldehydes, and ninhydrin. How-
ever, to the best of our knowledge, there is no report on the synthe-
sis of MBH adducts of 2,20-bipyridine with unexplored Micheal
acceptors, thus, functionalization of bipyridine via MBH reaction
has been studied and the preliminary results are presented in this
communication.
Initially, substrate 2,20-bipyridine-4-methyl-40-carbaldehyde 2
was prepared from 4,40-dimethyl-2,20-bipyridine 1 following a lit-
erature procedure,20 while substrate 2,20-bipyridine-4,40-dicar-
baldehyde 321,22 was prepared from the treatment of compound
1 with 2.2 equiv of SeO2 in 1,4-dioxane at reflux afforded dialde-
hyde 3 in 45% yield (Scheme 1). Significantly, the oxidation of 1
has been selectively achieved with SeO2 which avoids the forma-
tion of corresponding bipyridine N-oxides.
Subsequently, MBH reaction of 2 with 1.2 equiv of classical acti-
vated alkene viz. ethyl acrylate 4a and catalytic amount of 1,4-di-
azabicyclo[2.2.2]octane (DABCO) under neat condition at rt for
14 h afforded the MBH adduct 5a in 52% yield. On the other hand,
under similar condition, MBH reaction of 3 with 2.3 equiv of 4a
provided bis MBH adduct 6a in 35% yield (Scheme 1). Thus, to
In view of the difficulty and importance for the functionaliza-
tion of 2,20-bipyridine, development of a simple, efficient, and
expedient method for the functionalization of 2,20-bipyridine is
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Corresponding author. Tel.: +91 44 24437130; fax: +91 44 24911589.
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