BF₃·OEt₂-Mediated Tandem Annulation: A Strategy To Construct Functionalized Chromeno- and Pyrano-Fused Pyridines

Abstract

A simple and efficient one-pot annulation of arylidenones, alkynes, and nitriles in the presence of BF·OEt is described. A highly functionalized variety of N-substituted pyridine-fused chromeno and pyrano derivatives were obtained with satisfactory yields under mild reaction conditions. The method was proven to be valid for the synthesis of a diverse library of chromeno[3,4-c]pyridines, thiochromeno[3,4-c]pyridines, pyrano[3,4-c]pyridines, and thiopyrano[3,4-c]pyridine derivatives from readily accessible substrates. This experimentally simple protocol provides structurally complex, biologically relevant heterocycles in a one-pot operation.

Recent advances in the transition metal-free synthesis of heterocycles from α,β-unsaturated ketones

“…We were also successful in expanding the scope of this reaction towards the synthesis of chromanone/thiochromanone/pyanone/and thiopyranone fused N-acetylated pyridines. 38 Among different types of pyridine molecules 2,4,6-triarylpyridines, which are known by the name of Krohnke pyridines have gained the attention of scientific community owing to its broad applications in multiple fileds. 39 In 2018, Zhang and co-workers accomplished a metal free synthesis of 2,4,6-triaryl pyridines 69 from chalcones 8 and N-unsubstituted enaminones 68 (Scheme 24).…”

“…We were also successful in expanding the scope of this reaction towards the synthesis of chromanone/thiochromanone/pyanone/and thiopyranone fused N -acetylated pyridines. 38…”

3‐Arylidene‐4‐Chromanones and 3‐Arylidene‐4‐Thiochromanones: Versatile Synthons towards the Synthesis of Complex Heterocycles

“…Ashitha et al (2017) reported a one-pot, multicomponent cascade annulation method for the synthesis of chromenopyridines using arylidenones, alkynes and nitriles, mediated by BF 3 .OEt 2 . [55] Reacting a mixture of (E)-3-benzylidenechroman-4one 1, aryl acetylene 51 and acetonitrile/benzonitrile/acrylonitrile 52 in presence of BF 3 .OEt 2 led to N-acyl substituted pyridine-fused chromans 53 in moderate to good yields (Scheme 18). Similarly, this reaction was also found to afford Nsubstituted chromeno-, thiochromeno-, pyrano-, and thiopyrano[3,4-c]pyridines too in high yields.…”

Discovery of Natural Product Derived Labdane Appended Triazoles as Potent Pancreatic Lipase Inhibitors

“…Therefore, in continuation of our focused ongoing research interest in natural products and natural product based lead molecule − identification for therapeutic applications, in the present work, we have isolated the major compound ( E )-Labda-8­(17),12-diene-15,16-dial. This was synthetically transformed to rationally designed triazole appended analogues and evaluated for their pancreatic lipase inhibitory potential.…”