4
Tetrahedron
8
9
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So, we attempted the reaction of aromatic amine with 2
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7315.
equivalents of n-butanal. The reaction proceeded to completion
within 2h at 60 °C to afford 2,3-dialkyl quinolines in good yields
(Scheme 3).
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R1
Yield (%)
5a -CH3
62
5b -OCH3 64
Scheme 3. Zn(OTf)2 catalyzed synthesis of 2,3-dialkyl
quinolines
Multi-component synthesis of structurally diverse quinolines
using aldehydes, amine and alkyne coupling (A3 coupling) has
been achieved using Zn(OTf)2 as a catalyst. This method for the
multi-component synthesis of quinolines maximizes diversity by
the direct use of commercially available starting materials. 2-
Substituted-4-alkyl quinoline was also accessed by using 1-
octyne. Under similar catalytic and reaction condition substituted
aniline and n-butanal produces 2,3-dialkyl quinolines via a
pseudo two-component Povarov reaction. This robust solvent-
free process operates under an ambient atmosphere and avoids
the use of precious metals, hazardous solvents and harsh reaction
conditions. This atom economic process eliminates the waste
generated in the multi-step synthesis. Both electron -rich or -poor
amines and aldehydes participates efficiently in this Zn(OTf)2
catalyzed giving variedly substituted quinolines. Use of
economical and readily available Zn(OTf)2 offers sustainable
alternative to expensive and toxic transition metals. Being three
components reaction, structural decoration of quinoline ring can
be achieved by choosing appropriately substituted starting
aldehyde, amine and alkyne. Variation in the substituent’s
available on quinoline scaffolds open up the gate way to tune its
properties including solubility, luminescence, and biological
activity.
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Supplementary Material
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Electronic Supporting Information (ESI) for this article,
containing detailed procedures and spectral/analytical data for
synthesized compounds is available online at
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