Beilstein J. Org. Chem.2018,14, 3078–3087, doi:10.3762/bjoc.14.287
proceeds through a domino Knoevenagel/cyclization/Michael addition/oxidative cyclization reaction sequence.
Keywords: 2-aminochromene; domino reaction; imidazo[1,2-a]pyridine; 2-iminochromene; Michael addition; multicomponent reaction; oxidation; pyridine amination; Introduction
Domino reactions are well
promising anticancer activity [34], thereby showing the importance of this merged heterocyclic skeleton (Figure 1).
The formation of the chromene and imidazole rings in a single-step procedure was independently discovered by us [35][36] and Proença et al. [37][38], who identified 2-iminochromene 3 to be the
, complicated by the need of an oxidant to fulfil the final aromatization. Following our interest in domino [42][43] and MCR chemistry [44][45] and taking an advantage of 2-iminochromene reactivity, herein we report a sequential three-component domino reaction of salicylaldehydes 2 and N-(cyanomethyl)pyridinium
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Graphical Abstract
Figure 1:
Biologically relevant imidazo[1,2-a]pyridines and chromenes.
Beilstein J. Org. Chem.2012,8, 2166–2175, doi:10.3762/bjoc.8.244
used.
Chromane derivatives from the reactions of salicylaldehyde and enolate equivalents derived from malononitrile and its derivatives
The one-pot reaction of salicylaldehyde and malononitrile has proved to be an efficient method for the synthesis of 2-iminochromene derivatives. In general such
synthetic procedures involve a Knoevenagel condensation followed by intramolecular cyclization. In a detailed study directed towards understanding the pathway of the reaction of salicylaldehyde (5) and malononitrile (20), Costa and co-workers reported the efficient synthesis of 2-iminochromene 21 in 90
-diethylamino- and 5-bromo-3-methoxy-substituted salicylaldehydes gave corresponding 2-iminochromene derivatives in 86–100% yields, while the lowest yield of 62% was achieved when 3,4-dihydroxysalicylaldehyde was used.
Further studies by Costa and co-workers revealed that the reaction of salicyldehyde (5) with